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25,445,714
Does psammaplin A induce Sirtuin 1-dependent autophagic cell death in doxorubicin-resistant MCF-7/adr human breast cancer cells and xenografts?
{ "contexts": [ "Psammaplin A (PsA) is a natural product isolated from marine sponges, which has been demonstrated to have anticancer activity against several human cancer cell lines via the induction of cell cycle arrest and apoptosis. New drugs that are less toxic and more effective against multidrug-resistant cancers are urgently needed.", "We tested cell proliferation, cell cycle progression and autophagic cell death pathway in doxorubicin-resistant MCF-7 (MCF-7/adr) human breast cancer cells. The potency of PsA was further determined using an in vivo xenograft model." ], "labels": [ "BACKGROUND", "METHODS" ], "meshes": [ "Acetylation", "Animals", "Antibiotics, Antineoplastic", "Autophagy", "Breast Neoplasms", "Cell Division", "Cell Line, Tumor", "Disulfides", "Doxorubicin", "Drug Resistance, Neoplasm", "Female", "G2 Phase", "Gene Expression Regulation, Neoplastic", "Heterografts", "Humans", "Membrane Proteins", "Mice", "Mice, Nude", "Neoplasm Transplantation", "Sirtuin 1", "Tumor Suppressor Protein p53", "Tyrosine", "Xenograft Model Antitumor Assays" ] }
PsA significantly inhibited MCF-7/adr cells proliferation in a concentration-dependent manner, with accumulation of cells in G2/M phase of the cell cycle. PsA significantly decreased SIRT1 enzyme activity and reduced expression of SIRT1 protein in the cultured cells with greater potency than sirtinol or salermide. Acetylation of p53, a putative target of SIRT1, increased significantly following PsA treatment. In addition, PsA markedly increased the expression levels of autophagy-related proteins. In support of this, it was found that PsA significantly increased the expression of damage-regulated autophagy modulator (DRAM), a p53-induced protein.
yes
25,432,519
Do tumor-infiltrating immune cell profiles and their change after neoadjuvant chemotherapy predict response and prognosis of breast cancer?
{ "contexts": [ "Tumor microenvironment immunity is associated with breast cancer outcome. A high lymphocytic infiltration has been associated with response to neoadjuvant chemotherapy, but the contribution to response and prognosis of immune cell subpopulations profiles in both pre-treated and post-treatment residual tumor is still unclear.", "We analyzed pre- and post-treatment tumor-infiltrating immune cells (CD3, CD4, CD8, CD20, CD68, Foxp3) by immunohistochemistry in a series of 121 breast cancer patients homogeneously treated with neoadjuvant chemotherapy. Immune cell profiles were analyzed and correlated with response and survival.", "We identified three tumor-infiltrating immune cell profiles, which were able to predict pathological complete response (pCR) to neoadjuvant chemotherapy (cluster B: 58%, versus clusters A and C: 7%). A higher infiltration by CD4 lymphocytes was the main factor explaining the occurrence of pCR, and this association was validated in six public genomic datasets. A higher chemotherapy effect on lymphocytic infiltration, including an inversion of CD4/CD8 ratio, was associated with pCR and with better prognosis. Analysis of the immune infiltrate in post-chemotherapy residual tumor identified a profile (cluster Y), mainly characterized by high CD3 and CD68 infiltration, with a worse disease free survival." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Anthracyclines", "Antibodies, Monoclonal, Humanized", "Antigens, CD", "Antigens, CD20", "Antigens, Differentiation, Myelomonocytic", "Antineoplastic Agents", "Breast Neoplasms", "CD3 Complex", "CD4 Antigens", "CD8 Antigens", "Carcinoma, Ductal, Breast", "Female", "Forkhead Transcription Factors", "Humans", "Lymphocytes, Tumor-Infiltrating", "Middle Aged", "Neoadjuvant Therapy", "Prognosis", "Taxoids", "Trastuzumab", "Tumor Microenvironment", "Young Adult" ] }
Breast cancer immune cell subpopulation profiles, determined by immunohistochemistry-based computerized analysis, identify groups of patients characterized by high response (in the pre-treatment setting) and poor prognosis (in the post-treatment setting). Further understanding of the mechanisms underlying the distribution of immune cells and their changes after chemotherapy may contribute to the development of new immune-targeted therapies for breast cancer.
yes
25,448,648
Are routine preoperative restaging CTs after neoadjuvant chemoradiation for locally advanced rectal cancer low yield : a retrospective case study?
{ "contexts": [ "Pre-operative restaging CT scans are often performed routinely following neoadjuvant chemoradiotherapy for locally advanced rectal cancer. There is a paucity of data on the utility of this common practice. We sought to determine how often restaging CTs identified disease progression or regression that altered management.", "We performed a single-institution retrospective study. From 2007 to 2011, 182 patients had newly-diagnosed, non-metastatic rectal adenocarcinoma, of which 96 were surgical candidates with clinical stage II/III disease. Ninety-one of these patients (95%) completed neoadjuvant chemoradiation.", "Eighty-three out of 91 patients (91%) had restaging CTs. Four patients (5%) had new lesions suspicious for distant metastasis (2 lung, 2 liver) on restaging CT scan reports (1 of these was present on initial staging CT but not reported). All 4 patients had node-positive disease. In no case did restaging CT result in a change in surgical management." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Adenocarcinoma", "Aged", "Chemoradiotherapy, Adjuvant", "Female", "Humans", "Male", "Middle Aged", "Neoadjuvant Therapy", "Neoplasm Staging", "Rectal Neoplasms", "Retrospective Studies", "Tomography, X-Ray Computed" ] }
Because of the financial costs and established risks of intravenous contrast and cumulative radiation exposure, it may be advisable to take a more selective approach to preoperative imaging. Larger, prospective studies may enable identification of an at-risk cohort who would benefit most from restaging CT.
yes
25,440,267
Is increased time from neoadjuvant chemoradiation to surgery associated with higher pathologic complete response rates in esophageal cancer?
{ "contexts": [ "The interval between neoadjuvant chemoradiation treatment and surgery has been described as an important predictor of pathologic response to therapy in nonesophageal cancer sites. We retrospectively reviewed our experience with patients who underwent neoadjuvant chemoradiation and esophagectomy to better understand the impact of the timing of surgery on pathologic complete response rates in esophageal cancer.", "Two hundred thirty-one sequentially treated patients from 2000 to 2011 were identified for this study; 88 of these patients completed neoadjuvant chemoradiation followed by esophagectomy at our institution. The interval between completion of chemoradiation and surgery was calculated for each patient. The patients were categorized into quartiles and also into 3-week interval groups. Treatment factors and surgical morbidity data, including the estimated blood loss and length of operative stay, were also assessed.", "Quartiles for the neoadjuvant chemoradiation to surgery interval were less than 45 days, 46 to 50 days, 51 to 63 days, and 64+ days. Corresponding pathologic complete response rates were 12.5%, 20.0%, 22.7%, and 40.9% (p = 0.03). Results for 3-week intervals were similar (p = 0.02). There was no association between increasing time interval between the ending of neoadjuvant chemoradiation to surgery and length of stay longer than 2 weeks." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Aged, 80 and over", "Chemoradiotherapy, Adjuvant", "Esophageal Neoplasms", "Esophagectomy", "Female", "Humans", "Male", "Middle Aged", "Neoadjuvant Therapy", "Retrospective Studies", "Time Factors" ] }
A longer interval between completion of neoadjuvant chemoradiation and surgery was associated with higher pathologic complete response rates without an impact on surgical morbidity.
yes
25,444,981
Is δNp63 expression a protective factor of progression in clinical high grade T1 bladder cancer?
{ "contexts": [ "Several risk factors have been claimed to predict the progression of clinically high grade T1 bladder tumors. However, these factors are not specific enough to define which patients should be treated immediately with radical cystectomy. Therefore, it is critical to identify molecular markers that can help provide individualized, risk stratified decision making. Our main goal was to evaluate the role of total p63, p53 and ΔNp63 expression in cases of clinically high grade T1 bladder cancer progression.", "Total p63, p53 and ΔNp63 expression was analyzed by immunohistochemistry in 134 clinically high grade T1 tumors. We assessed clinical progression to muscle invasive disease or radical cystectomy as a patient outcome end point. Survival analysis was done for recurrence-free, progression-free, disease specific and overall survival.", "A total of 132 patients (98.5%) underwent repeat transurethral resection. Cases of early progression (less than 3 months) were excluded from study to avoid under staging. Of the tumors 90 (67.2%) showed ΔNp63 expression loss. During a median followup of 62.1 months 19 patients (14.2%) progressed to muscle invasive disease. The progression rate was 21.1% in patients with tumors characterized by ΔNp63 loss but no progression was observed in those with tumors with ΔNp63 expression (p <0.001). There was no difference in the number of patients who underwent repeat transurethral resection, had associated carcinoma in situ, showed lymphovascular invasion or received followup intravesical bacillus Calmette-Guérin courses." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Biomarkers, Tumor", "Disease Progression", "Female", "Humans", "Immunohistochemistry", "Male", "Neoplasm Grading", "Protective Factors", "Transcription Factors", "Tumor Suppressor Proteins", "Urinary Bladder Neoplasms" ] }
ΔNp63 expression is a favorable prognostic factor in clinically high grade T1 bladder cancer. This marker identifies patients at low risk for progression who could benefit from conservative therapy with transurethral bladder tumor resection and bacillus Calmette-Guérin, avoiding over treatment with immediate radical cystectomy.
yes
25,429,340
Is p63 more sensitive and specific than 34βE12 to differentiate adenocarcinoma of prostate from cancer mimickers?
{ "contexts": [ "Prostate cancer is the world's leading cause of cancer and the second cause of cancer-related death in men after lung cancer. Differentiation of prostate adenocarcinoma from benign prostate lesions and hyperplasia sometimes cannot be done on the basis of morphologic findings. Considering the fact that in the prostate adenocarcinoma there is no basal cell layer, basal cell markers can help to differentiate prostate adenocarcinoma from cancer mimickers.", "We studied 98 prostate biopsy blocks (40 adenocarcinoma and 58 benign lesions) for basal cell marker expression.", "p63 and 34βE12 were negative in all prostate adenocarcinoma specimens, but all benign prostate hyperplasia and high grade intraepithelial neoplasia cases expressed them." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [] }
Basal cell markers can help to distinguish prostate adenocarcinoma from cancer mimickers.
yes
25,434,319
Are phospholipase C epsilon 1 ( PLCE1 ) haplotypes associated with increased risk of gastric cancer in Kashmir Valley?
{ "contexts": [ "Phospholipase C epsilon 1 (PLCE1) plays a crucial role in carcinogenesis and progression of several types of cancers. A single nucleotide polymorphism (SNP, rs2274223) in PLCE1 has been identified as a novel susceptibility locus. The aim of the present study was to investigate the role of three potentially functional SNPs (rs2274223A > G, rs3765524C > T, and rs7922612C > T) of PLCE1 in gastric cancer patients from Kashmir Valley.", "The study was conducted in 108 GC cases and 195 healthy controls from Kashmir Valley. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism method. Data were statistically analyzed using c2 test and logistic regression models. A P value of less than 0.05 was regarded as statistically significant.", "The frequency of PLCE1 A2274223C3765524T7922612, G2274223C3765524T7922612 , and G2274223T3765524C7922612 haplotypes were higher in patients compared with controls, conferred high risk for GC [odds ratio (OR) =6.29; P = 0.001; Pcorr = 0.003], (OR = 3.23; P = 0.011; Pcorr = 0.033), and (OR = 5.14; P = 0.011; Pcorr = 0.033), respectively. Smoking and salted tea are independent risk factors for GC, but we did not find any significant modulation of cancer risk by PLCE1 variants with smoking or excessive consumption of salted tea." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "DNA, Neoplasm", "Female", "Follow-Up Studies", "Genetic Predisposition to Disease", "Genotype", "Haplotypes", "Humans", "India", "Male", "Middle Aged", "Phosphoinositide Phospholipase C", "Polymerase Chain Reaction", "Polymorphism, Genetic", "Prevalence", "Retrospective Studies", "Risk Factors", "Stomach Neoplasms" ] }
These results suggest that variation in PLCE1 may be associated with GC risk in Kashmir Valley.
yes
25,448,803
Is tGFBI Expression in Cancer Stromal Cells Associated with Poor Prognosis and Hematogenous Recurrence in Esophageal Squamous Cell Carcinoma?
{ "contexts": [ "Esophageal squamous cell carcinoma (ESCC) is an important cause of cancer-related death worldwide. To improve prognoses in patients with ESCC, we evaluated the potential of transforming growth factor-beta-induced protein (TGFBI), which is overexpressed in ESCC, as a therapeutic candidate.", "We examined the clinical significance of TBFBI in 102 ESCC samples using real-time RT-PCR. Immunohistochemical studies were conducted to examine the localization of TGFBI. Knockdown of TGFBI in cocultured fibroblasts was performed to determine the roles of TGFBI in migration and invasion.", "The level of TGFBI in ESCC tissues was higher than that in normal tissues. The high TGFBI expression group (n = 16) had higher TGFB1 expression and more frequent hematogenous recurrence than the low-expression group (n = 86). High TGFBI expression was an independent prognostic factor in patients with ESCC. TGFBI was mainly localized in stromal cells of ESCC. Moreover, suppression of TGFBI in fibroblasts inhibited the migration and invasion capacity of TE8 ESCC cells." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Aged", "Apoptosis", "Biomarkers, Tumor", "Blotting, Western", "Carcinoma, Squamous Cell", "Cell Movement", "Cell Proliferation", "Esophageal Neoplasms", "Extracellular Matrix Proteins", "Female", "Follow-Up Studies", "Gene Expression Regulation, Neoplastic", "Hematologic Neoplasms", "Humans", "Immunoenzyme Techniques", "Lymphatic Metastasis", "Male", "Middle Aged", "Neoplasm Invasiveness", "Neoplasm Recurrence, Local", "Neoplasm Staging", "Prognosis", "RNA, Messenger", "RNA, Small Interfering", "Real-Time Polymerase Chain Reaction", "Reverse Transcriptase Polymerase Chain Reaction", "Stromal Cells", "Survival Rate", "Transforming Growth Factor beta", "Tumor Cells, Cultured", "Wound Healing" ] }
High TGFBI expression in ESCC tissues could be a powerful biomarker of poor prognosis and hematogenous recurrence. TGFBI in stromal cells might be a promising molecular target for ESCC treatment.
yes
25,437,683
Is delayed duodenal stump blow-out following total gastrectomy for cancer : Heightened awareness for the continued presence of the surgical past in the present the key to a successful duodenal stump disruption management . A case report?
{ "contexts": [ "Duodenal stump disruption remains one of the most dreadful postgastrectomy complications, posing an overwhelming therapeutic challenge.", "The present report describes the extremely rare occurrence of a delayed duodenal stump disruption following total gastrectomy with Roux-en-Y esophagojejunostomy for cancer, because of mechanical obstruction of the distal jejunum resulting in increased backpressure on afferent limp and duodenal stump. Surgical management included repair of distal jejunum obstruction, mobilization and re-stapling of the duodenum at the level of its intact second part and retrograde decompressing tube duodenostomy through the proximal jejunum." ], "labels": [ "BACKGROUND", "METHODS" ], "meshes": [] }
Several strategies have been proposed for the successful management post-gastrectomy duodenal stump disruption however; its treatment planning is absolutely determined by the presence or not of generalized peritonitis and hemodynamic instability with hostile abdomen. In such scenario, urgent reoperation is mandatory and the damage control principle should govern the operative treatment.
yes
25,436,124
Is cD133-positive tumor cell content a predictor of early recurrence in colorectal cancer?
{ "contexts": [ "The aims of this study were to demonstrate the tumorigenicity of CD133+ colon cancer cells in vitro, analyze the correlations between spheroid formation and clinicopathologic variables, and screen for overexpressed genes in CD133+ colon cancer stem cells. Moreover, the aim of this study was to establish a living tumor tissue bank using surgically resected specimens.", "Using LoVo cell line, we isolated CD133+ cells and performed clonogenic assay and animal experiment to test tumorigenicity of CD133+ cells. Twenty-nine surgical samples were freshly collected from 27 patients who received curative or palliative surgery, and the samples were mechanically and enzymatically dissociated into single cells.", "We confirmed the enhanced tumorigenicity of CD133+ cells isolated from LoVo cell line both in vitro and in vivo. Of these 29 samples, 8 (28%) contained >3% CD133+ cells. Sphere formation was significantly higher in samples from patients with lymphatic invasion than in those without lymphatic invasion [54.5% (6/11) vs. 12.5% (2/16); P=0.033] and in samples containing >3% of CD133+ cells than in those containing ≤3% of CD133+ cells [36.4% (4/11) vs. 0% (0/16); P=0.019]." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [] }
These findings indicate that CD133 is a valid marker for identifying cancer stem cells from fresh surgically resected colorectal cancer tissues. Furthermore, we successfully established a living tumor tissue bank using surgically resected colorectal tissues with a viability of >70%.
yes
25,436,452
Does resveratrol enhance palmitate-induced ER stress and apoptosis in cancer cells?
{ "contexts": [ "Palmitate, a saturated fatty acid (FA), is known to induce toxicity and cell death in various types of cells. Resveratrol (RSV) is able to prevent pathogenesis and/or decelerate the progression of a variety of diseases. Several in vitro and in vivo studies have also shown a protective effect of RSV on fat accumulation induced by FAs. Additionally, endoplasmic reticulum (ER) stress has recently been linked to cellular adipogenic responses. To address the hypothesis that the RSV effect on excessive fat accumulation promoted by elevated saturated FAs could be partially mediated by a reduction of ER stress, we studied the RSV action on experimentally induced ER stress using palmitate in several cancer cell lines.", "We show that, unexpectedly, RSV promotes an amplification of palmitate toxicity and cell death and that this mechanism is likely due to a perturbation of palmitate accumulation in the triglyceride form and to a less important membrane fluidity variation. Additionally, RSV decreases radical oxygen species (ROS) generation in palmitate-treated cells but leads to enhanced X-box binding protein-1 (XBP1) splicing and C/EBP homologous protein (CHOP) expression. These molecular effects are induced simultaneously to caspase-3 cleavage, suggesting that RSV promotes palmitate lipoapoptosis primarily through an ER stress-dependent mechanism. Moreover, the lipotoxicity reversion induced by eicosapentaenoic acid (EPA) or by a liver X receptor (LXR) agonist reinforces the hypothesis that RSV-mediated inhibition of palmitate channeling into triglyceride pools could be a key factor in the aggravation of palmitate-induced cytotoxicity." ], "labels": [ "BACKGROUND", "RESULTS" ], "meshes": [ "Antineoplastic Agents, Phytogenic", "Apoptosis", "Cell Line, Tumor", "DNA-Binding Proteins", "Endoplasmic Reticulum", "Endoplasmic Reticulum Stress", "Hep G2 Cells", "Humans", "Neoplasms", "Palmitates", "Reactive Oxygen Species", "Regulatory Factor X Transcription Factors", "Resveratrol", "Stearoyl-CoA Desaturase", "Stilbenes", "Transcription Factor CHOP", "Transcription Factors", "Triglycerides", "X-Box Binding Protein 1" ] }
Our results suggest that RSV exerts its cytotoxic role in cancer cells exposed to a saturated FA context primarily by triglyceride accumulation inhibition, probably leading to an intracellular palmitate accumulation that triggers a lipid-mediated cell death. Additionally, this cell death is promoted by ER stress through a CHOP-mediated apoptotic process and may represent a potential anticancer strategy.
yes
25,426,294
Does iNKT/CD1d-antitumor immunotherapy significantly increase the efficacy of therapeutic CpG/peptide-based cancer vaccine?
{ "contexts": [ "Therapeutic cancer vaccines aim to boost the natural immunity against transformed cancer cells, and a series of adjuvants and co-stimulatory molecules have been proposed to enhance the immune response against weak self-antigens expressed on cancer cells. For instance, a peptide/CpG-based cancer vaccine has been evaluated in several clinical trials and was shown in pre-clinical studies to favor the expansion of effector T versus Tregs cells, resulting in a potent antitumor activity, as compared to other TLR ligands. Alternatively, the adjuvant activity of CD1d-restricted invariant NKT cells (iNKT) on the innate and adaptive immunity is well demonstrated, and several CD1d glycolipid ligands are under pre-clinical and clinical evaluation. Importantly, additive or even synergistic effects have been shown upon combined CD1d/NKT agonists and TLR ligands. The aim of the present study is to combine the activation and tumor targeting of activated iNKT, NK and T cells.", "Activation and tumor targeting of iNKT cells via recombinant α-galactosylceramide (αGC)-loaded CD1d-anti-HER2 fusion protein (CD1d-antitumor) is combined or not with OVA peptide/CpG vaccine. Circulating and intratumoral NK and H-2Kb/OVA-specific CD8 responses are monitored, as well as the state of activation of dendritic cells (DC) with regard to activation markers and IL-12 secretion. The resulting antitumor therapy is tested against established tumor grafts of B16 melanoma cells expressing human HER2 and ovalbumin.", "The combined CD1d/iNKT antitumor therapy and CpG/peptide-based immunization leads to optimized expansion of NK and OVA-specific CD8 T cells (CTLs), likely resulting from the maturation of highly pro-inflammatory DCs as seen by a synergistic increase in serum IL-12. The enhanced innate and adaptive immune responses result in higher tumor inhibition that correlates with increased numbers of OVA-specific CTLs at the tumor site. Antibody-mediated depletion experiments further demonstrate that in this context, CTLs rather than NK cells are essential for the enhanced tumor inhibition." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [] }
Altogether, our study in mice demonstrates that αGC/CD1d-antitumor fusion protein greatly increases the efficacy of a therapeutic CpG-based cancer vaccine, first as an adjuvant during T cell priming and second, as a therapeutic agent to redirect immune responses to the tumor site.
yes
25,436,328
Is increased expression of pleiotrophin a prognostic marker for patients with gastric cancer?
{ "contexts": [ "BACKGROUND/AIMs: Pleiotrophin (PTN) have been demonstrated to play an important role in the development of human gastric cancer. However, the prognostic value remains unclear. The aim of this study was to investigate whether expression of PTN has prognostic relevance in human gastric cancer.", "Immunohistochemistry was used to investigate the expression of PTN proteins in 178 patients with gastric cancer. The level of PTN mRNA in gastric cancer tissues and paratumor tissues were evaluated in 52 paired cases by quantitative real-time polymerase chainreaction(qRT-PCR). Survival analysis by the Kaplan-Meier method was performed to assess prognostic significance.", "The expression level of PTN in gastric cancer tissues was significantly higher (P<0.001) than those in paratumor tissues according to the immunohistochemistry analysis, which was confirmed by qRT-PCR analysis. Additionally, the overexpression of PTN was significantly associated with the tumor site (P=0.001), Lauren’s classification (P<0.001),histologic differentiation(P=0.014),depth of invasion(P<0.001), TNM stage (P=0.003),and lymph node metastasis (P=0.002). Moreover, the Cox proportional- hazards regression analysis revealed that the increased expression of PTN was an independent prognostic factor for poor recurrence-free survival(RFS) and overall survival(OS)(both P<0.001)." ], "labels": [ "UNLABELLED", "METHODS", "RESULTS" ], "meshes": [ "Adolescent", "Adult", "Aged", "Aged, 80 and over", "Biomarkers, Tumor", "Carrier Proteins", "Cytokines", "Disease-Free Survival", "Female", "Gastrectomy", "Humans", "Immunohistochemistry", "Kaplan-Meier Estimate", "Male", "Middle Aged", "Neoplasm Staging", "Proportional Hazards Models", "RNA, Messenger", "Real-Time Polymerase Chain Reaction", "Risk Factors", "Stomach Neoplasms", "Time Factors", "Treatment Outcome", "Up-Regulation", "Young Adult" ] }
These findings indicated that the expression of PTN is significantly correlated with prognosis in gastric cancer patients, suggesting that the expression of PTN may be used as an independent prognostic marker.
yes
25,432,142
Does nAIF1 inhibit gastric cancer cells migration and invasion via the MAPK pathways?
{ "contexts": [ "Nuclear apoptosis-inducing factor 1 (NAIF1) could induce apoptosis in gastric cancer cells. Previously, we have reported that the expression of NAIF1 protein is down-regulated in gastric cancer tissues compared with the adjacent normal tissues. However, the role of NAIF1 in gastric cancer cells is not fully understood.", "The effects of NAIF1 on cell viability were evaluated by MTT and colony formation assays. The ability of cellular migration and invasion were analyzed by transwell assays. The expression levels of targeted proteins were determined by western blot. The relative RNA expression levels were analyzed using quantitative polymerase chain reaction assays. Xenograft experiment was employed to determine the anti-tumor ability of NAIF1 in vivo.", "The study demonstrates that transient transfection of NAIF1 in gastric cancer cells BGC823 and MKN45 could inhibit the cell proliferation, migration, and invasion of the two gastric cancer cell lines. The tumor size is smaller in NAIF1-overexpressed MKN45 cell xenograft mice than in unexpressed group. Further in-depth analysis reveals that NAIF1 reduces the expression of MMP2 as well as MMP9, and inhibits the activation of FAK, all of which are key molecules involved in regulating cell migration and invasion. In addition, NAIF1 inhibits the expression of c-Jun N-terminal kinase (JNK) by accelerating its degradation through ubiquitin-proteasome pathway. Meanwhile, NAIF1 reduces the mRNA and protein expression of ERK1/2." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Actins", "Animals", "Apoptosis Regulatory Proteins", "Blotting, Western", "Cell Line, Tumor", "Cell Movement", "Disease Progression", "Focal Adhesion Kinase 1", "Gene Expression Regulation, Neoplastic", "Humans", "JNK Mitogen-Activated Protein Kinases", "MAP Kinase Signaling System", "Matrix Metalloproteinase 2", "Matrix Metalloproteinase 9", "Mice", "Neoplasm Invasiveness", "Nuclear Proteins", "Phosphorylation", "Proteasome Endopeptidase Complex", "Real-Time Polymerase Chain Reaction", "Signal Transduction", "Stomach Neoplasms", "Ubiquitin" ] }
Our study revealed that NAIF1 plays a role in regulating cellular migration and invasion through the MAPK pathways. It could be a therapeutic target for gastric cancer.
yes
25,434,636
Is invasion of uterine cervical squamous cell carcinoma cells facilitated by locoregional interaction with cancer-associated fibroblasts via activating transforming growth factor-beta?
{ "contexts": [ "Local invasion is a common pattern of spread in uterine cervical squamous cell carcinoma (CSCC). Although transforming growth factor-beta (TGF-β) facilitates invasion of various types of cancer cells, the role of the TGF-β pathway in CSCC is unclear. In this study, we analyzed the role of TGF-β signaling in the progression of CSCC.", "Immunohistochemistry was used to examine the expression of TGF-β pathway molecules in 67 CSCC samples with clinicopathological data. Activation of the TGF-β pathway was investigated following co-culture of CSCC cells and cervical cancer-associated fibroblasts (CCAFs).", "Clinicopathological analysis of CSCC samples revealed that prominent expression of TGF-β receptor-2 was more frequent in CSCC with lymphovascular space invasion (LVSI) than without LVSI (p < 0.01). Lymph node metastasis was more frequent in cases in which phosphorylated SMAD3 (pSMAD3) was localized exclusively at the boundary of tumor clusters (n = 9, p < 0.05). Recombinant TGF-β1 increased pSMAD3 expression and enhanced cellular invasion (p < 0.005) in CSCC cells, which was attenuated by an inhibitor of the TGF-β receptor (p < 0.005). Enhanced pSMAD3 expression and invasion was also observed when conditioned media from CSCC cells co-cultured with CCAFs were administered. Luciferase assays showed that this medium contained a large amount of active TGF-β. Along with TGF-β activation, thrombospondin-1 was upregulated in both CSCC cells and CCAFs, while thrombospondin-1 silencing in either CSCC cells or CCAFs repressed the activity of TGF-β. Thrombospondin-1 was prominently expressed in cases with pSMAD3 boundary staining (p < 0.05)." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Carcinoma, Squamous Cell", "Cell Communication", "Female", "Fibroblasts", "Humans", "Middle Aged", "Neoplasm Invasiveness", "Neoplasm Staging", "Signal Transduction", "Transforming Growth Factor beta", "Uterine Cervical Neoplasms" ] }
These results suggest that interaction between CSCC cells and surrounding CCAFs activates TGF-β via thrombospondin-1 secretion to facilitate CSCC invasion.
yes
25,446,542
Is increased serum cancer antigen-125 a marker for severity of deep endometriosis?
{ "contexts": [ "To determine whether cancer antigen-125 (CA-125) levels are increased in women with endometriosis, especially in those with endometriomas (OMAs), deep infiltrating lesions (DIE), and superficial endometriosis (SUP) compared with controls without endometriosis in a large cohort of operated women.", "Cross-sectional study (Canadian Task Force classification II-2).", "Tertiary-care university hospital.", "Four hundred six women with histologically proven endometriosis and 279 women without endometriosis.", "Surgical examination of the abdomino-pelvic cavity.", "Preoperative serum CA-125 antigen levels were evaluated by electrochemoluminescence immunoassay in women with endometriosis and controls. Correlations between serum CA-125 levels and clinical and anatomical characteristics of disease severity were examined. Women with endometriosis displayed higher mean serum CA-125 levels compared with disease-free controls (50.1 ± 62.4 U/mL vs 22.5 ± 25.2 U/mL; p ≤ .001). CA-125 levels were significantly increased in women with OMA (60.8 ± 63.5 U/mL) and DIE (55.2 ± 68.7 U/mL) compared with women with SUP (23.2 ± 24.5 U/mL) and controls (22.5 ± 25.2 U/mL). There was no difference in CA-125 levels between patients with SUP and controls and between patients with OMA and DIE. CA-125 serum levels were correlated with DIE severity: the mean number of DIE lesions and worst DIE lesion." ], "labels": [ "OBJECTIVE", "METHODS", "METHODS", "METHODS", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Biomarkers", "CA-125 Antigen", "Cross-Sectional Studies", "Endometriosis", "Female", "France", "Humans", "Middle Aged", "Peritoneum", "Severity of Illness Index", "Young Adult" ] }
Serum CA-125 levels were significantly increased in women with severe forms of endometriosis, OMA, and DIE lesions. In addition, elevated serum Ca-125 levels were associated with more severe and extended DIE lesions. In women with superficial peritoneal lesions, CA-125 levels were not different from women without endometriosis.
yes
25,450,878
Do long-term lung cancer survivors have permanently decreased quality of life after surgery?
{ "contexts": [ "Retrospective evaluation of the long-term health-related quality of life (HRQoL) among survivors after non-small-cell lung cancer (NSCLC) surgery.", "A total of 586 patients underwent surgery for NSCLC in Helsinki University Central Hospital between January 2000 and June 2009. Two validated quality-of-life questionnaires, the 15D and the EORTC QLQ-C30 with its lung cancer-specific module, QLQ-LC13, were sent to the 276 patients alive in June 2011. Response rate was 83.3%. Results of the 15D were compared with those of an age- and gender-standardized general population.", "Median follow-up was 5 years. Compared with a general population, our patients had a significantly lower 15D total score, representing their total HRQoL and scores for dimensions of mobility, breathing, usual activities, depression, distress, and vitality. The patients, however, scored significantly higher on vision, hearing, and mental function." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Aged", "Carcinoma, Non-Small-Cell Lung", "Depression", "Female", "Finland", "Follow-Up Studies", "Humans", "Lung Neoplasms", "Male", "Middle Aged", "Neoplasm Staging", "Quality of Life", "Retrospective Studies", "Surveys and Questionnaires", "Survival Analysis", "Survivors", "Thoracic Surgical Procedures" ] }
NSCLC survivors may suffer postoperatively from permanently reduced long-term HRQoL compared to an age- and gender-matched general population. This is essential patient information as more patients are surviving longer.
yes
25,445,226
Does corn silk maysin induce apoptotic cell death in PC-3 prostate cancer cells via mitochondria-dependent pathway?
{ "contexts": [ "Despite recent advances in prostate cancer diagnostics and therapeutics, the overall survival rate still remains low. This study was aimed to assess potential anti-cancer activity of maysin, a major flavonoid of corn silk (CS, Zea mays L.), in androgen-independent human prostate cancer cells (PC-3).", "Maysin was isolated from CS of Kwangpyeongok, a Korean hybrid corn, via methanol extraction and preparative C18 reverse phase column chromatography. Maysin cytotoxicity was determined by either monitoring cell viability in various cancer cell lines by MTT assay or morphological changes. Apoptotic cell death was assessed by annexin V-FITC/PI double staining, depolarization of mitochondrial membrane potential (MMP), expression levels of Bcl-2 and pro-caspase-3 and by terminal transferase mediated dUTP-fluorescein nick end labeling (TUNEL) staining. Underlying mechanism in maysin-induced apoptosis of PC-3 cells was explored by evaluating its effects on Akt and ERK pathway.", "Maysin dose-dependently reduced the PC-3 cell viability, with an 87% reduction at 200 μg/ml. Maysin treatment significantly induced apoptotic cell death, DNA fragmentation, depolarization of MMP, and reduction in Bcl-2 and pro-caspase-3 expression levels. Maysin also significantly attenuated phosphorylation of Akt and ERK. A combined treatment with maysin and other known anti-cancer agents, including 5-FU, etoposide, cisplatin, or camptothecin, synergistically enhanced PC-3 cell death." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Antineoplastic Agents, Phytogenic", "Apoptosis", "Caspase 3", "Cell Line, Tumor", "Flavonoids", "Glucosides", "Humans", "MAP Kinase Signaling System", "Male", "Membrane Potential, Mitochondrial", "Mitochondria", "Prostate", "Prostatic Neoplasms", "Proto-Oncogene Proteins c-akt", "Signal Transduction", "Zea mays" ] }
These results suggested for the first time that maysin inhibits the PC-3 cancer cell growth via stimulation of mitochondria-dependent apoptotic cell death and may have a strong therapeutic potential for the treatment of either chemo-resistant or androgen-independent human prostate cancer.
yes
25,451,672
Does intensity-modulated whole pelvic radiotherapy provide effective dosimetric outcomes for cervical cancer treatment with lower toxicities?
{ "contexts": [ "To compare the efficacy of intensity-modulated radiotherapy, three-dimensional conformal radiotherapy, and conventional radiotherapy for cervical cancer treatment.", "Whole pelvis intensity-modulated radiotherapy, three-dimensional conformal radiotherapy, and conventional radiotherapy plans were designed for 16 patients with stage IIB cervical cancer, each using the prescribed dose of 50.4 Gy/28 fractions. Dose-volume histograms of the target volume and organs at risk were evaluated.", "Compared to the 3D conformal and conventional radiotherapy plans, the intensity-modulated radiotherapy plan demonstrated superior conformal treatment. The mean planning target volume dose of all three plans reached the target effective therapeutic dose. The planning target volume dose of the intensity-modulated radiotherapy plan was significantly higher than that of either the three-dimensional conformal radiotherapy or conventional radiotherapy plan (P<0.05). When more than 30 Gy was administered in intensity-modulated radiotherapy, organs at risk including the small intestine, rectum, bladder, and bone marrow received a significantly reduced volume of radiation. In comparison of the average planning target volume doses, significant volume reductions in irradiation of organs at risk were obtained with full bladders." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Female", "Humans", "Middle Aged", "Pelvis", "Radiotherapy Dosage", "Radiotherapy, Conformal", "Radiotherapy, Intensity-Modulated", "Treatment Outcome", "Uterine Cervical Neoplasms" ] }
An intensity-modulated radiotherapy plan with appropriate margins encompassing the primary tumour and potential microscopic pelvic disease reduces the dose to organs at risk without compromising target coverage. Intensity-modulated radiotherapy is an appropriate definitive treatment for patients with cervical cancer.
yes
25,436,609
Is tP53 Pro72 allele enriched in oral tongue cancer and frequently mutated in esophageal cancer in India?
{ "contexts": [ "The tumor suppressor p53 is known to be inactivated frequently in various cancers. In addition, germline polymorphisms in TP53 are known to affect protein function and influence risk of developing different types of cancers. In this study, we analyzed the association of TP53 Pro72Arg polymorphism with squamous cell carcinoma of oral tongue (SCCOT) and esophagus (ESCC) in India.", "We assessed the distribution of TP53 Pro72Arg polymorphism in one hundred and fifteen and eighty two SCCOT and ESCC patients, respectively, with respect to one hundred and ten healthy controls from the same population. In addition, we analyzed association of the polymorphism with several clinico-pathological and molecular parameters.", "Pro72 allele was significantly enriched in SCCOT patients compared to the healthy control group but neither allele was enriched in ESCC. Interestingly, Pro72 allele was preferentially mutated in ESCC which was confirmed by analysis of samples heterozygous for Pro72Arg." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Base Sequence", "Carcinoma, Squamous Cell", "Esophageal Neoplasms", "Esophageal Squamous Cell Carcinoma", "Esophagus", "Female", "Humans", "India", "Male", "Middle Aged", "Molecular Sequence Data", "Mutation", "Polymorphism, Genetic", "Tongue", "Tongue Neoplasms", "Tumor Suppressor Protein p53" ] }
Our study revealed the association of Pro72 allele with SCCOT suggesting the effect of this polymorphism on SCCOT risk. Preferential mutation of Pro72 allele exclusively in ESCC indicates the need for further studies to understand the tissue specific effect of p53 polymorphism.
yes
25,443,923
Is low percentage of free prostate-specific antigen ( PSA ) a strong predictor of later detection of prostate cancer among Japanese men with serum levels of total PSA of 4.0 ng/mL or less?
{ "contexts": [ "To investigate the effect of the percentage of free prostate-specific antigen (%fPSA) on future prostate cancer risk.", "We examined serum total PSA (tPSA) and %fPSA annually in a prostate cancer-screening cohort between July 2001 and June 2011. Men with tPSA >4.0 ng/mL or tPSA of 2.0-4.0 ng/mL with %fPSA ≤12% were screened as positive and were recommended to undergo a biopsy. The study population consisted of 6368 men, aged 40-79 years, who had tPSA ≤4.0 ng/mL at initial screening and who subsequently underwent 1 or more screenings. We calculated the cumulative risk and hazard ratio of prostate cancer stratified by the initial %fPSA groups as quartiles of prostate cancer patients.", "During a median follow-up of 36 months, 119 men were diagnosed with prostate cancer. The lowest quartile of %fPSA (<13.3%) was associated with a 21.2-fold higher risk of having prostate cancer compared with the highest quartile (>22.2%). For the subset with an initial tPSA ≤1.0 ng/mL, all men diagnosed with cancer had an initial %fPSA ≤33.3% (median). For the subset with tPSA >1.0 ng/mL, men with %fPSA ≤23.0% (median) had significantly higher risk for cancer than those with %fPSA >23.0% (P <.0001). Of the 114 men with prostate cancer in whom pathologic findings were available, 79 (69.3%) had a Gleason score ≥3 + 4 = 7." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Asian Continental Ancestry Group", "Biopsy", "Early Detection of Cancer", "Humans", "Japan", "Male", "Middle Aged", "Proportional Hazards Models", "Prostate-Specific Antigen", "Prostatic Neoplasms", "Treatment Outcome" ] }
A low %fPSA is a strong predictor of a subsequent diagnosis of prostate cancer among men with tPSA levels ≤4.0 ng/mL. Measurement of %fPSA might enhance the detection of high-grade cancer that warrants aggressive treatment.
yes
25,442,486
Is vitamin D deficiency in mycosis fungoides and Sézary syndrome patients similar to other cancer patients?
{ "contexts": [ "The purpose of this study was to determine the prevalence of vitamin D deficiency in CTCL patients and whether supplementation corrects vitamin D deficiency or treatment outcome.", "Three hundred eleven CTCL patients including 27/311 (8.7%) with Sézary syndrome (SS), 169 cancer controls, and 69 normal controls from the M.D. Anderson clinics had 25(OH)D3 levels determined and categorized as deficient (< 20 ng/mL),insufficient (20-29 ng/mL), or sufficient (≥ 30 ng/mL). Clinical response was determined according to a change in percent body surface area involvement.", "Low 25(OH)D3 (< 30 ng/mL) levels were present in 76.9% of mycosis fungoides/SS patients, 75.2% of cancer controls, and 66.7% of healthy controls (P ¼ .05, .07) and in 30% to 39% of historical normal controls. Correction of deficiency was successful in 35% or 55 of 156 patients who were given dealer's choice of either vitamin D2 at 50,000 IU orally (p.o.) biweekly or D3 1000 IU p.o. daily. Correction of vitamin D levels was noted in 27 of 100 (27%) patients given D3 and 28 of 56 (50%) given D2. Responses to standard CTCL therapy was similar among patients with corrected and persistently low levels (P ¼ .51)." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Case-Control Studies", "Dietary Supplements", "Female", "Humans", "Male", "Middle Aged", "Mycosis Fungoides", "Neoplasm Staging", "Neoplasms", "Sezary Syndrome", "Treatment Outcome", "Vitamin D", "Vitamin D Deficiency", "Young Adult" ] }
To our knowledge,this is the first study of vitamin D status in CTCL patients. Vitamin D deficiency was present in CTCL and other cancer patients compared with normal and historical controls. Correction of vitamin D deficiency and type of vitamin D supplementation used did not affect the overall clinical disease response.
yes
25,430,449
Does over-expression of small ubiquitin-like modifier proteases 1 predict chemo-sensitivity and poor survival in non-small cell lung cancer?
{ "contexts": [ "Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors. Despite the advances in therapy over the years, its mortality remains high. The aim of this study was to evaluate the expression of small ubiquitin-like modifier (SUMO) proteases 1 (SENP1) in NSCLC tissues and its role in the regulation of vascular endothelial growth factor (VEGF) expression. We also investigated the association between the expression level of SENP1 and the clinicopathological features and survival of the patients.", "A SENP1 small interfering RNA (siRNA) was constructed and transfected into the NSCLC cells. VEGF gene expression was analyzed by real-time polymerase chain reaction (RT-PCR). Immunohistochemistry staining was used to assess the expression of SENP1 in 100 NSCLC patients and its association with the clinicopathological features and survival was analyzed.", "VEGF expression was significantly higher in NSCLC tissues than in normal lung tissues. Inhibition of SENP1 by siRNA was associated with decreased VEGF expression. SENP1 was over-expressed in 55 of the 100 NSCLC samples (55%) and was associated with a moderate and low histological tumor grade (3.6%, 38.2%, and 58.2% in high, moderate and low differentiated tumors, respectively, P = 0.046), higher T stage (10.9% in T1, and 89.1% in T2 and T3 tumor samples, P < 0.001) and TNM stage (10.9% in stage I, and 89.1% in stages II and III tumor samples, P < 0.001). The rate of lymph node metastasis was significantly higher in the SENP1 over-expression group (76.4%) than that in the SENP1 low expression group (33.3%, P < 0.001). Sixty three patients received postoperative chemotherapy, including 34 with SENP1 over-expression and 29 with SENP1 low expression. Among the 34 patients with SENP1 over-expression, 22 (64.7%) patients developed recurrence or metastasis, significantly higher than those in the low expression group 27.6% (8/29) (P = 0.005). Multivariate Cox regression analysis showed that lymph node metastasis (P = 0.015), TNM stage (P = 0.001), and SENP1 expression level (P = 0.002) were independent prognostic factors for the survival of NSCLC patients." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Antineoplastic Agents", "Blotting, Western", "Carcinoma, Non-Small-Cell Lung", "Cell Line, Tumor", "Cysteine Endopeptidases", "Endopeptidases", "Female", "Humans", "Immunohistochemistry", "In Vitro Techniques", "Lung Neoplasms", "Male", "Reverse Transcriptase Polymerase Chain Reaction" ] }
SENP1 may be a promising predictor of survival, a predictive factor of chemo-sensitivity for NSCLC patients, and potentially a desirable drug target for lung carcinoma target therapy.
yes
25,428,807
Does exosome-mediated transfer of miR-10b promote cell invasion in breast cancer?
{ "contexts": [ "Exosomes are 30-100 nm membrane vesicles of endocytic origin, mediating diverse biological functions including tumor cell invasion, cell-cell communication and antigen presentation through transfer of proteins, mRNAs and microRNAs. Recent evidence suggests that microRNAs can be released through ceramide-dependent secretory machinery regulated by neutral sphingomyelinase 2 (nSMase2) enzyme encoded by the smpd3 gene that triggers exosome secretion. However, whether exosome-mediated microRNA transfer plays any role in cell invasion remains poorly understood. Thus, the aim of this study was to identify the exosomal microRNAs involved in breast cancer invasion.", "The expression level of endogenous and exosomal miRNAs were examined by real time PCR and the expression level of target proteins were detected by western blot. Scanning electron and confocal microscopy were used to characterize exosomes and to study its uptake and transfer. Luciferase reporter plasmids and its mutant were used to confirm direct targeting. Furthermore, the functional significance of exosomal miR-10b was estimated by invasion assay.", "In this study, we demonstrate that microRNA carrying exosomes can be transferred among different cell lines through direct uptake. miR-10b is highly expressed in metastatic breast cancer MDA-MB-231 cells as compared to non-metastatic breast cancer cells or non-malignant breast cells; it is actively secreted into medium via exosomes. In particular, nSMase2 or ceramide promotes the exosome-mediated miR-10b secretion whereas ceramide inhibitor suppresses this secretion. Moreover, upon uptake, miR-10b can suppress the protein level of its target genes such as HOXD10 and KLF4, indicating its functional significance. Finally, treatment with exosomes derived from MDA-MB-231 cells could induce the invasion ability of non-malignant HMLE cells." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Breast Neoplasms", "Cell Line, Tumor", "Cell Movement", "Exosomes", "Female", "Homeodomain Proteins", "Humans", "Kruppel-Like Transcription Factors", "MicroRNAs", "Neoplasm Invasiveness", "Transcription Factors" ] }
Together, our results suggest that a set of specific microRNAs may play an important role in modulating tumor microenvironment through exosomes. Thus, a better understanding of this process may aid in the development of novel therapeutic agents.
yes
25,443,649
Are aerobic capacity and upper limb strength reduced in women diagnosed with breast cancer : a systematic review?
{ "contexts": [ "What are typical values of physical function for women diagnosed with breast cancer and how do these compare to normative data?", "Systematic review with meta-analysis.", "Women diagnosed with breast cancer who were before, during or after treatment.", "Physical function was divided into three categories: aerobic capacity, upper and lower extremity muscular fitness, and mobility. Measures of aerobic capacity included field tests (6-minute walk test, 12-minute walk tests, Rockport 1-mile test, and 2-km walk time) and submaximal/maximal exercise tests on a treadmill or cycle ergometer. Measures of upper and lower extremity muscular fitness included grip strength, one repetition maximum (bench, chest or leg press), muscle endurance tests, and chair stands. The only measure of mobility was the Timed Up and Go test.", "Of the 1978 studies identified, 85 were eligible for inclusion. Wide ranges of values were reported, reflecting the range of ages, disease severity, treatment type and time since treatment of participants. Aerobic fitness values were generally below average, although 6-minute walk time was closer to population norms. Upper and lower extremity strength was lower than population norms for women who were currently receiving cancer treatment. Lower extremity strength was above population norms for women who had completed treatment." ], "labels": [ "OBJECTIVE", "METHODS", "METHODS", "METHODS", "RESULTS" ], "meshes": [] }
Aerobic capacity and upper extremity strength in women diagnosed with breast cancer are generally lower than population norms. Assessment of values for lower extremity strength is less conclusive. As more research is published, expected values for sub-groups by age, treatment, and co-morbidities should be developed. [Neil-Sztramko SE, Kirkham AA, Hung SH, Niksirat N, Nishikawa K Campbell KL (2014) Aerobic capacity and upper limb strength are reduced in women diagnosed with breast cancer: a systematic review.Journal of Physiotherapy60: 189-200].
yes
25,436,461
Is coexpression of IQ-domain GTPase-activating protein 1 ( IQGAP1 ) and Dishevelled ( Dvl ) correlated with poor prognosis in non-small cell lung cancer?
{ "contexts": [ "IQ-domain GTPase-activating protein 1 (IQGAP1) binds to Dishevelled (Dvl) and functions as a modulator of Dvl nuclear localization in Xenopus embryos. However, the relationship between IQGAP1 and Dvl in tumor tissues is unclear.", "We used immunohistochemistry to assess the expressions of IQGAP1 and Dvl in a cohort of 111 non-small cell lung cancer (NSCLC) patients. Association of their localization expressions with clinicopathological factors was also analyzed.", "The positive rate of IQGAP1 in primary tumors was 48.6% (54/111) for its cytoplamic expression, 9.0% (10/111) for nuclear expression and 31.5% (35/111) for membranous expression; the positive rate of Dvl was 65.8% (73/111) for cytoplamic expression, 9.9% (11/111) for nuclear expression and 10.8% (12/111) for membranous expression. Coexpression rate of IQGAP1 and Dvl was 77.8% (42/54) in the cytoplasm, 80.0% (8/10) in the nucleus and 8.6% (3/35) in the membrane. Coexpression of IQGAP1 and Dvl in the cytoplasm and nucleus were significantly correlated (P<0.05), but not in the membrane (P>0.05). The positive expression rates of cyclin D1 and c-myc were significantly higher in the group of IQGAP1 and Dvl coexpression in the nucleus than that in the cytoplasm. Coexpression rate of IQGAP1 and Dvl in the cytoplasm and nucleus was significantly higher in lymph nodal metastases (63.3%, 19/30) than in primary growths (38.3%, 31/81), correlating with poor prognosis. Five-year survival time after resection in the group with their coexpression in the cytoplasm and nucleus was significantly lower than that with no coexpression (44.705±3.355 vs 58.403±2.543 months, p<0.05)." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Adaptor Proteins, Signal Transducing", "Carcinoma, Non-Small-Cell Lung", "Cell Nucleus", "Cytoplasm", "Dishevelled Proteins", "Female", "Humans", "Lung Neoplasms", "Lymphatic Metastasis", "Male", "Middle Aged", "Phosphoproteins", "Prognosis", "Survival Analysis", "Wnt Signaling Pathway", "Xenopus Proteins", "ras GTPase-Activating Proteins" ] }
Coexpression of IQGAP1 and Dvl in the cytoplasm and nucleus was correlated with the lymph nodal metastase and poor prognosis of NSCLC, and coexpression in nucleus might play a critical role in the activation of canonical Wnt pathway.
yes
25,436,343
Is cD133 expression correlated with poor prognosis in colorectal cancer?
{ "contexts": [ "Cancer stem cells (CSC) was reported to play an important role in various kinds of cancer. CD133 is one of the cancer stem cell markers in solid cancers. However, the correlation between CD133 expression and the clinicopathological factors in colorectal cancer (CRC) remains unclear.", "Forty patients with CRC who underwent operations were enrolled. Expression of CD133 was investigated by immunohistochemistry (IHC). The staining was observed in the cytoplasm of cancer cells and the patients who have the staining were defined as CD133-positive cases. The patients were divided into two groups: the CD133-positive group (n = 22) and negative group (n = 18). Clinicopathological factors were compared between the two groups. The prognostic factors were investigated by multivariate analysis.", "In the CD133-positive group, the incidence of lymph node and liver metastasis, lymphatic and venous invasion, as well as the progression of stage of cancer were higher than that in the CD133-negative group. The 5-year survival rate and the disease-free survival rate in the CD133-positive group were lower than that in the CD133-negative group. The multivariate analysis revealed that CD133 expression tended to be an independent prognostic factor." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "AC133 Antigen", "Aged", "Antigens, CD", "Biomarkers, Tumor", "Chi-Square Distribution", "Colectomy", "Colorectal Neoplasms", "Disease-Free Survival", "Female", "Glycoproteins", "Humans", "Immunohistochemistry", "Kaplan-Meier Estimate", "Male", "Multivariate Analysis", "Neoplasm Staging", "Peptides", "Proportional Hazards Models", "Risk Factors", "Time Factors", "Treatment Outcome" ] }
CD133 expression is correlated with poor prognosis in CRC.
yes
25,422,241
Is structural maintenance of chromosomes 4 a predictor of survival and a novel therapeutic target in colorectal cancer?
{ "contexts": [ "Structural maintenance of chromosomes 4 (SMC-4) is a chromosomal ATPase which plays an important role in regulate chromosome assembly and segregation. However, the role of SMC-4 in the incidence of malignancies, especially colorectal cancer is still poorly understood.", "We here used quantitative PCR and Western blot analysis to examine SMC-4 mRNA and protein levels in primary colorectal cancer and paired normal colonic mucosa. SMC-4 clinicopathological significance was assessed by immunohistochemical staining in a tissue microarray (TMA) in which 118 cases of primary colorectal cancer were paired with noncancerous tissue. The biological function of SMC-4 knockdown was measured by CCK8 and plate colony formation assays. Fluorescence detection has been used to detect cell cycling and apoptosis.", "SMC-4 expression was significantly higher in colorectal cancer and associated with T stage, N stage, AJCC stage and differentiation. Knockdown of SMC-4 expression significantly suppressed the proliferation of cancer cells and degraded its malignant degree." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Adenosine Triphosphatases", "Adult", "Aged", "Aged, 80 and over", "Apoptosis", "Biomarkers, Tumor", "Cell Cycle", "Cell Differentiation", "Cell Proliferation", "Chromosomal Proteins, Non-Histone", "Chromosomes, Human", "Colorectal Neoplasms", "Disease Progression", "Female", "Gene Expression Regulation, Neoplastic", "Humans", "Intestinal Mucosa", "Male", "Middle Aged", "Neoplasm Staging", "RNA, Messenger" ] }
Our clinical and experimental data suggest that SMC-4 may contribute to the progression of colorectal carcinogenesis. Our study provides a new therapeutic target for colorectal cancer treatment.
yes
25,442,336
Is epidermal growth factor receptor mutation associated with longer local control after definitive chemoradiotherapy in patients with stage III nonsquamous non-small-cell lung cancer?
{ "contexts": [ "To determine the frequency and clinical significance of epidermal growth factor receptor (EGFR) mutations in patients with potentially curable stage III non-small-cell lung cancer (NSCLC) who are eligible for definitive chemoradiotherapy (CRT).", "Between January 2001 and December 2010, we analyzed the EGFR mutational status in consecutive NSCLC patients who were treated by CRT. The response rate, relapse-free survival, 2-year relapse-free rate, initial relapse sites, and overall survival of the patients were investigated.", "A total of 528 patients received CRT at our hospital during the study period. Of these, 274 were diagnosed as having nonsquamous NSCLC. Sufficient specimens for mutational analyses could be obtained from 198 of these patients. The proportion of patients with EGFR activating mutations was 17%. In addition to the well-known characteristics of patients carrying EGFR mutations (female, adenocarcinoma, and never/light smoker), the proportion of cases with smaller primary lesions (T1/2) was found to be higher in patients with EGFR mutations than in those with wild-type EGFR. Patients with EGFR mutations showed similar response rate, relapse-free survival, and 2-year relapse-free rates as compared to patients with wild-type EGFR. Local relapses as the site of initial relapse occurred significantly less frequently in patients with EGFR mutation (4% vs 21%; P=.045). Patients with EGFR mutations showed longer local control (adjusted hazard ratio 0.49; P=.043). After disease progression, a majority of the patients with EGFR mutations received EGFR tyrosine kinase inhibitors (62%), and these patients showed longer postprogression survival than those with wild-type EGFR." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adenocarcinoma", "Adult", "Aged", "Antineoplastic Combined Chemotherapy Protocols", "Carboplatin", "Carcinoma, Non-Small-Cell Lung", "Chemoradiotherapy", "Cisplatin", "ErbB Receptors", "Female", "Humans", "Lung Neoplasms", "Male", "Middle Aged", "Mutation", "Neoplasm Recurrence, Local", "Paclitaxel", "Protein Kinase Inhibitors", "Radiation Tolerance", "Radiotherapy Dosage", "Sex Factors", "Vinblastine", "Vinorelbine" ] }
Our study is the first to show radiosensitive biology of EGFR-mutated tumors in definitive CRT with curative intent. This finding could serve as a credible baseline estimate of EGFR-mutated population in stage III nonsquamous NSCLC.
yes
25,451,952
Do elevated levels of preoperative circulating CD44⁺ lymphocytes and neutrophils predict poor survival for non-small cell lung cancer patients?
{ "contexts": [ "Certain circulating cells have been shown to predict the clinical outcome of several cancers. The objective of this study was to identify clinical, hematological and immunological predictors of prognosis in non-small cell lung cancer (NSCLC) patients.", "A retrospective study on a prevalent cohort of 225 NSCLC patients hospitalized at the Zhejiang Province Cancer Hospital (ZPCH) was conducted from August 1, 2006 to April 15, 2008. Circulating lymphocytes were measured by flow cytometry. WBC count and classification in peripheral blood were measured with a Coulter counter. We calculated the proportion of patients surviving after first hospital admission and hazard ratios (HR) using the Cox proportional hazards model.", "Elevated levels of preoperative circulating CD44(+) lymphocytes, WBCs and neutrophils indicated low cumulative survival. Clinical stage (HR: 2.292; 95% confidence interval (CI): 1.34-3.91, P=0.002), neutrophils (HR: 1.877; 95% CI: 1.34-2.62, P<0.001) and CD44(+) lymphocytes (HR: 1.018; 95% CI: 1.00-1.03, P=0.002) are independent predictors of survival in NSCLC patients, respectively. Elevated levels of CD44(+) lymphocytes and neutrophils correlated with distant metastasis and prognosis in NSCLC patients with stage III/IV, respectively." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Carcinoma, Non-Small-Cell Lung", "Cohort Studies", "Female", "Humans", "Hyaluronan Receptors", "Lung Neoplasms", "Lymphocytes", "Male", "Middle Aged", "Neutrophils", "Prognosis", "Retrospective Studies", "Survival Analysis" ] }
CD44(+) lymphocytes along with neutrophils could serve as an independent prognostic marker for NSCLC patients.
yes
25,453,049
Does imaging DNA damage allow detection of preneoplasia in the BALB-neuT model of breast cancer?
{ "contexts": [ "A prominent feature of many human cancers is oncogene-driven activation of the DNA damage response (DDR) during early tumorigenesis. It has been shown previously that noninvasive imaging of the phosphorylated histone H2A variant H2AX, γH2AX, a DNA damage signaling protein, is possible using (111)In-labeled anti-γH2AX antibody conjugated to the cell-penetrating peptide transactivator of transcription (TAT). The purpose of this study was to investigate whether (111)In-anti-γH2AX-TAT detects the DDR during mammary oncogenesis in BALB-neuT mice.", "Mammary fat pads from BALB-neuT and wild-type mice (age, 40-106 d) were immunostained for γH2AX. (111)In-anti-γH2AX-TAT or a control probe was administered intravenously to BALB-neuT mice. SPECT was performed weekly and compared with tumor detection using palpation and dynamic contrast-enhanced MR imaging.", "γH2AX expression was elevated in hyperplastic lesions in the mammary fat pads of BALB-neuT mice aged 76-106 d, compared with normal fat pads from younger mice and carcinomas from older mice (13.5 ± 1.2 γH2AX foci/cell vs. 5.2 ± 1.5 [P < 0.05] and 3.4 ± 1.1 [P < 0.001], respectively). Serial SPECT imaging revealed a 2.5-fold increase in (111)In-anti-γH2AX-TAT accumulation in the mammary fat pads of mice aged 76-106 d, compared with control probe (P = 0.01). The median time to detection of neoplastic lesions by (111)In-anti-γH2AX-TAT (defined as >5% injected dose per gram of tissue) was 96 d, compared with 120 and 131 d for dynamic contrast-enhanced MR imaging and palpation, respectively (P < 0.001)." ], "labels": [ "UNLABELLED", "METHODS", "RESULTS" ], "meshes": [ "Animals", "DNA Damage", "Disease Progression", "Female", "Image Processing, Computer-Assisted", "Immunoconjugates", "Magnetic Resonance Imaging", "Mammary Neoplasms, Experimental", "Mice", "Mice, Inbred BALB C", "Precancerous Conditions", "Radiopharmaceuticals", "Tissue Distribution", "Tomography, Emission-Computed, Single-Photon" ] }
DDR imaging using (111)In-anti-γH2AX-TAT identified mammary tumors significantly earlier than MR imaging. Imaging the DDR holds promise for the detection of preneoplasia and as a technique for screening cancer-prone individuals.
yes
25,427,922
Is uRG4 overexpression correlated with cervical cancer progression and poor prognosis in patients with early-stage cervical cancer?
{ "contexts": [ "Upregulator of cell proliferation 4 (URG4) has been implicated in the oncogenesis of certain cancers. However, the correlation between URG4 expression and clinicopathological significance in human cancer remains unclear. Therefore, this study investigated its expression and clinicopathological significance in cervical cancer patients.", "URG4 expression was examined using quantitative PCR (qPCR) and western blotting in normal cervical epithelial cells, cervical cancer cells, and eight matched pairs of cervical cancer tissues and adjacent noncancerous tissues from the same patient. In addition, immunohistochemistry (IHC) was used to examine URG4 expression in paraffin-embedded tissues from 167 cervical cancer patients (FIGO stages Ib1-IIa2). Statistical analyses were performed to evaluate associations between URG4 expression and prognostic and diagnostic factors.", "URG4 was significantly upregulated in the cervical cancer cell lines and tissues compared with the normal cells and adjacent noncancerous cervical tissues. IHC revealed high URG4 expression in 59 out of the 167 (35.13%) cervical cancer specimens. Its expression was significantly correlated with clinical stage (P < 0.0001), tumour size (P = 0.012), T classification (P = 0.023), lymph node metastasis (P = 0.001) and vaginal involvement (P = 0.002). Patients with high URG4 expression, particularly those who received concurrent chemotherapy and radiotherapy (P < 0.0001), showed a shorter overall survival (OS) and disease-free survival (DFS) compared to those with the low expression of this protein. Multivariate analysis revealed that URG4 expression is an independent prognostic factor for cervical cancer patients." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Cell Line, Tumor", "Disease Progression", "Female", "Gene Expression", "Humans", "Lymphatic Metastasis", "Middle Aged", "Neoplasm Proteins", "Neoplasm Staging", "Prognosis", "Tumor Burden", "Uterine Cervical Neoplasms", "Young Adult" ] }
Our results demonstrated that elevated URG4 protein expression is associated with a poor outcome in patients with early-stage cervical cancer. URG4 may be a novel prognostic marker and therapeutic target for the treatment of cervical cancer.
yes
25,436,802
Does multicenter immunohistochemical ALK-testing of non-small-cell lung cancer show high concordance after harmonization of techniques and interpretation criteria?
{ "contexts": [ "Detection of anaplastic lymphoma kinase (ALK)-gene rearrangements in non-small-cell lung cancer (NSCLC) is mainly performed by fluorescence in-situ hybridization (FISH). The question was raised if FISH might be replaced by immunohistochemistry (IHC) in a reliable and reproducible manner across different laboratories.", "After calibration of the staining instruments and training of the observers to binary interpretation (positive versus negative), 15 NSCLC were independently tested for ALK protein expression by IHC only in a multicenter setting (16 institutes). Each laboratory utilized the VENTANA ALK-D5F3 IHC assay. As demonstrated by FISH the samples displayed unequivocal ALK break-positivity (6×) and negativity (7×), as well as ALK positive-\"borderline\" character (2×), which is challenging for FISH diagnosis and thus was RT-PCR-confirmed.", "All seven ALK FISH-negative cases were homogenously scored as ALK-IHC negative. All 16 participants scored the two ALK positive-\"borderline\" samples as unequivocally positive according to their protein expression. Concordant IHC interpretation was also noticed in four of six unequivocal ALK break positive cases. In two of six some observers described a weak/heterogeneous ALK-IHC staining. This would have resulted in a subsequent ALK-testing (FISH/PCR) in a routine diagnostic setting." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Anaplastic Lymphoma Kinase", "Carcinoma, Non-Small-Cell Lung", "Gene Rearrangement", "Humans", "Immunohistochemistry", "In Situ Hybridization, Fluorescence", "Lung Neoplasms", "Receptor Protein-Tyrosine Kinases" ] }
This so-called "ALK-Harmonization-Study" shows for the first time that predictive semiquantitative IHC reveals reliable and reproducible results across several labs when methodology and interpretation are strictly defined and the pathologists are uniquely trained. The application of validated ALK IHC assays and its comparison to ALK-FISH is highly needed in future clinical trials. This might answer the question if ALK-IHC cannot only serve as a prescreening tool, but as a stand-alone test at least in cases displaying an unequivocally staining pattern as well as an alternative predictive test in samples with reduced FISH interpretability.
yes
25,442,987
Is hospital readmission associated with poor survival after esophagectomy for esophageal cancer?
{ "contexts": [ "Hospital readmissions are costly and associated with inferior patient outcomes. There is limited knowledge related to readmissions after esophagectomy for malignancy. Our aim was to determine the impact on survival of readmission after esophagectomy.", "This cohort study utilizes Surveillance, Epidemiology, and End Results-Medicare data (2002 to 2009). Survival, length of stay, 30-day readmissions, and discharge disposition were determined. Multivariate logistic regression models were created to examine risk factors associated with readmission.", "In all, 1,744 patients with esophageal cancer underwent esophagectomy: 80% of patients (1,390) were male, and mean age was 73 years; 71.8% of tumors (1,251) were adenocarcinomas, and 72.5% (1,265) were distal esophageal tumors; 38% of patients (667) received induction therapy. Operative approach was transthoracic in 52.6% of patients (918) and transhiatal in 37.4% (653), and required complex reconstruction (intestinal interposition) in 9.9% (173). Stage distribution was as follows: stage I, 35.3% (616); stage II, 32.5% (566); stage III, 27.9% (487); and stage IV, 2.3% (40). Median length of stay was 13 days, hospital mortality was 9.3% (158 patients), and 30-day readmission rate was 18.6% (212 of 1,139 home discharges); 25.4% of patients (443) were discharged to institutional care facilities. Overall survival was significantly worse for patients who were readmitted (p < 0.0001, log rank test). Risk factors for readmission were comorbidity score of 3+, urgent admission, and urban residence." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Aged", "Cohort Studies", "Esophageal Neoplasms", "Esophagectomy", "Female", "Humans", "Male", "Patient Readmission", "Retrospective Studies", "Risk Factors", "Survival Rate" ] }
Hospital readmissions after esophagectomy for cancer occur frequently and are associated with worse survival. Improved identification of patients at risk for readmission after esophagectomy can inform patient selection, discharge planning, and outpatient monitoring. Optimization of such practices may lead to improved outcomes at reduced cost.
yes
25,440,618
Does dexmedetomidine reduce atrial fibrillation after lung cancer surgery?
{ "contexts": [ "To evaluate whether the use of intraoperative dexmedetomidine (DEX) during lung cancer surgery may reduce the incidence of postoperative atrial fibrillation (POAF).", "A retrospective study.", "Academic hospital.", "Seven hundred three adult patients with non-small-cell lung cancer.", "Patients younger than 18 years of age with a history of atrial fibrillation were excluded. Episodes of atrial fibrillation were identified from electronic medical records and consisted of cardiology consultations, electrocardiogram records, and use of anti-arrhythmic medications within the postoperative admission time. The Wilcoxon rank sum test was used to evaluate the difference in a continuous variable between patient groups. Fisher's exact test or the chi-square test was used to evaluate the association between 2 categorical variables. Logistic regression models were used for multivariate analysis. Overall POAF incidence was 136 of 703 (19.35%), with a mean onset of 3.01±2.03 days after surgery. Among patients, 204 (29.02%) received DEX intraoperatively. Male gender and age were strong predictors of POAF. POAF incidence was comparable between patients who were (n=93, 21.1%) and were not (n=43, 18.6%) treated with DEX (p=0.46). The mean onset time of arrhythmia was similar in both groups (DEX users: 2.93±2.49 days; non-DEX users: 3.05±1.79 days; p=0.146)." ], "labels": [ "OBJECTIVE", "METHODS", "METHODS", "METHODS", "RESULTS" ], "meshes": [ "Adrenergic alpha-2 Receptor Agonists", "Aged", "Atrial Fibrillation", "Carcinoma, Non-Small-Cell Lung", "Dexmedetomidine", "Female", "Humans", "Intraoperative Care", "Lung Neoplasms", "Male", "Middle Aged", "Postoperative Complications", "Pulmonary Surgical Procedures", "Retrospective Studies", "Treatment Outcome" ] }
These results were similar to those published elsewhere on POAF incidence and risk factors. This study could not confirm the hypothesis that the intraoperative use of DEX is associated with a reduced rate of POAF after thoracic surgery for lung cancer.
no
25,445,419
Does bRCAness predict resistance to taxane-containing regimens in triple negative breast cancer during neoadjuvant chemotherapy?
{ "contexts": [ "To provide optimal treatment of heterogeneous triple negative breast cancer (TNBC), we need biomarkers that can predict the chemotherapy response.", "We retrospectively investigated BRCAness in 73 patients with breast cancer who had been treated with taxane- and/or anthracycline-based neoadjuvant chemotherapy (NAC). Using multiplex, ligation-dependent probe amplification on formalin-fixed core needle biopsy (CNB) specimens before NAC and surgical specimens after NAC. BRCAness status was assessed with the assessor unaware of the clinical information.", "We obtained 45 CNB and 60 surgical specimens from the 73 patients. Of the 45 CNB specimens, 17 had BRCAness (38.6% of all subtypes). Of the 23 TNBC CNB specimens, 14 had BRCAness (61% of TNBC cases). The clinical response rates were significantly lower for BRCAness than for non-BRCAness tumors, both for all tumors (58.8% vs. 89.3%, P = .03) and for TNBC (50% vs. 100%, P = .02). All tumors that progressed with taxane therapy had BRCAness. Of the patients with TNBC, those with non-BRCAness cancer had pathologic complete responses significantly more often than did those with BRCAness tumors (77.8% vs. 14.3%, P = .007). After NAC, the clinical response rates were significant lower for BRCAness than for non-BRCAness tumors in all subtypes (P = .002) and in TNBC cases (P = .008). After a median follow-up of 26.4 months, 6 patients-all with BRCAness-had developed recurrence. Patients with BRCAness had shorter progression-free survival than did those with non- BRCAness (P = .049)." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Antineoplastic Combined Chemotherapy Protocols", "Carcinoma, Ductal, Breast", "Drug Resistance, Neoplasm", "Female", "Genes, BRCA1", "Genes, BRCA2", "Heterozygote", "Humans", "Middle Aged", "Mutation", "Neoadjuvant Therapy", "Prognosis", "Retrospective Studies", "Taxoids", "Triple Negative Breast Neoplasms" ] }
Identifying BRCAness can help predict the response to taxane, and changing regimens for BRCAness TNBC might improve patient survival. A larger prospective study is needed to further clarify this issue.
yes
25,440,089
Does e2F4 regulatory program predict patient survival prognosis in breast cancer?
{ "contexts": [ "Genetic and molecular signatures have been incorporated into cancer prognosis prediction and treatment decisions with good success over the past decade. Clinically, these signatures are usually used in early-stage cancers to evaluate whether they require adjuvant therapy following surgical resection. A molecular signature that is prognostic across more clinical contexts would be a useful addition to current signatures.", "We defined a signature for the ubiquitous tissue factor, E2F4, based on its shared target genes in multiple tissues. These target genes were identified by chromatin immunoprecipitation sequencing (ChIP-seq) experiments using a probabilistic method. We then computationally calculated the regulatory activity score (RAS) of E2F4 in cancer tissues, and examined how E2F4 RAS correlates with patient survival.", "Genes in our E2F4 signature were 21-fold more likely to be correlated with breast cancer patient survival time compared to randomly selected genes. Using eight independent breast cancer datasets containing over 1,900 unique samples, we stratified patients into low and high E2F4 RAS groups. E2F4 activity stratification was highly predictive of patient outcome, and our results remained robust even when controlling for many factors including patient age, tumor size, grade, estrogen receptor (ER) status, lymph node (LN) status, whether the patient received adjuvant therapy, and the patient's other prognostic indices such as Adjuvant! and the Nottingham Prognostic Index scores. Furthermore, the fractions of samples with positive E2F4 RAS vary in different intrinsic breast cancer subtypes, consistent with the different survival profiles of these subtypes." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Breast Neoplasms", "Carcinoma", "Chromatin Immunoprecipitation", "E2F4 Transcription Factor", "Female", "Gene Expression Profiling", "Gene Expression Regulation, Neoplastic", "Humans", "Prognosis", "Proportional Hazards Models", "Survival Rate", "Transcriptome" ] }
We defined a prognostic signature, the E2F4 regulatory activity score, and showed it to be significantly predictive of patient outcome in breast cancer regardless of treatment status and the states of many other clinicopathological variables. It can be used in conjunction with other breast cancer classification methods such as Oncotype DX to improve clinical outcome prediction.
yes
25,440,760
Does s100A3 suppression inhibit in vitro and in vivo tumor growth and invasion of human castration-resistant prostate cancer cells?
{ "contexts": [ "To investigate the role of S100A3 and the effect of S100A3 inhibition on human castration-resistant prostate cancer (CRPC) cells by using in vitro and in vivo functional assays.", "Using human CRPC cells (PC3 and DU145), S100A3 expression levels were assessed by reverse transcription-polymerase chain reaction and Western blot analysis. After S100A3-specific small interfering ribonucleic acid (RNA) treatment, cell viability was determined by Cell Counting Kit-8 assay, and apoptotic cell fractions were evaluated by flow cytometry. The invasive properties of these cells and the expression pattern of matrix metalloproteinases (MMPs) were assessed using transwell migration assays, reverse transcription-polymerase chain reaction, and gelatin zymography. Finally, the in vivo efficacy of S100A3 inhibition on human CRPC cells was investigated using human tumor xenograft models in nude mice.", "Human CRPC cells showed overexpression of S100A3, and its suppression reduced cell viability owing to apoptotic cell death. Additionally, S100A3 inhibition decreased the invasiveness of human CRPC cells. Moreover, MMP-2 and MMP-9 were downregulated in PC3, whereas only MMP-9 was downregulated in D145 after S100A3 inhibition. In human CRPC xenograft models, we noted a marked reduction in tumor growth in mice injected with S100A3 short hairpin RNA-transfected PC3 and DU145 cells." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Animals", "Humans", "In Vitro Techniques", "Male", "Mice, Nude", "Neoplasm Invasiveness", "Prostatic Neoplasms, Castration-Resistant", "S100 Proteins", "Tumor Cells, Cultured" ] }
Human CRPC cells showed upregulation of S100A3 expression, and S100A3 inhibition reduced tumor cell viability. S100A3 inhibition reduced invasion capability with downregulation of MMP expression. More importantly, S100A3 inhibition resulted in tumor growth suppression in human CRPC xenograft models, suggesting S100A3 could serve as a novel therapeutic target for the treatment of human CRPC.
yes
25,428,458
Is a high body mass index in esophageal cancer patients associated with adverse outcomes following esophagectomy?
{ "contexts": [ "There is no consensus about the impact of a high BMI on postoperative morbidity and survival after esophagectomy. The aim of this study was to determine the influence of a high BMI on postoperative complications and survival in a large cohort of esophageal cancer patients.", "From January 2006 to December 2012, 1,342 consecutive esophageal cancer patients who underwent esophagectomy were included in this study. Patients were divided into three groups: 950 patients were classified as normal BMI (BMI 18.5-24.9 kg/m(2)), 279 were classified as high BMI (BMI ≥ 25 kg/m(2)), and 113 as low BMI (BMI < 18.5 kg/m(2)). Multivariate logistic regression models were used to identify confounding factors associated with postoperative complications. The impact of BMI on overall survival (OS) was estimated by the Kaplan-Meier method and Cox proportional hazard models.", "The predominance of pathological type was esophageal squamous cell carcinoma (n = 1,280, 95.4 %). Overall morbidity, mortality, and hospital stay did not differ among groups. The incidence of pneumonia was higher in patients with high BMI compared with those with normal BMI (14.7 vs. 9.9 %, P = 0.025). However, chylothorax was less frequent in high-BMI group (0.4 % in high-BMI group, 3.1 % in normal group, and 3.5 % in low group, P = 0.011). Logistic regression analysis revealed high BMI was independently associated with decreased incidence of chylothorax [HR 0.86; 95 % confidence interval 0.76-0.97]. Overweight and obese patients had significantly better overall survival than underweight patients (median OS 55.6 vs. 32.5 months, P = 0.013), while the pathological stage was significantly higher in underweight patients (P = 0.001). In multivariate analysis, T status, N status, differentiation grade, and tumor length were identified as independent prognostic factors." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Body Mass Index", "Carcinoma, Squamous Cell", "Esophageal Neoplasms", "Esophageal Squamous Cell Carcinoma", "Esophagectomy", "Female", "Humans", "Incidence", "Kaplan-Meier Estimate", "Male", "Middle Aged", "Obesity", "Postoperative Complications", "Proportional Hazards Models", "Treatment Outcome" ] }
A high BMI is not associated with increased overall morbidity following esophagectomy; moreover, it is associated with decreased incidence of chylothorax. The better overall survival in patients with high BMI compared with those with low BMI might be due to a relatively low pathological stage. A high BMI should therefore not be a relative contraindication for esophagectomy.
no
25,436,375
Is pattern of first recurrent lesions in pancreatic cancer : hepatic relapse associated with dismal prognosis and portal vein invasion?
{ "contexts": [ "The aim of this study was to evaluate patterns of the initial recurrence after pancreatectomy for pancreatic cancer and risk factors in each pattern.", "This study included 209 pancreatic cancer patients who underwent pancreatectomy and of whom the detailed information on the first recurrent lesions detected by imaging during postoperative followup were available. Relapse patterns were classified into 4 groups: liver, peritoneal, local and extra-abdominal recurrences. We evaluated their associations with prognosis and various clinicopathological factors to identify relevant risk factors.", "Cumulative numbers of patients with liver, peritoneal, local, and extra-abdominal recurrences were 81, 70, 98 and 22, respectively, for the first recurrences. Hepatic relapse was associated with significantly shorter overall survival than other sites (p<0.001) and was an independent prognostic factor in multivariate analysis (p<0.001). Pathological portal vein invasion was the only independent risk factor for hepatic relapse (p=0.045). There was no significant correlation between the depth of invasion and prevalence of hepatic relapse." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Aged, 80 and over", "Chi-Square Distribution", "Female", "Humans", "Kaplan-Meier Estimate", "Liver Neoplasms", "Logistic Models", "Male", "Middle Aged", "Multivariate Analysis", "Neoplasm Invasiveness", "Neoplasm Recurrence, Local", "Pancreatectomy", "Pancreatic Neoplasms", "Pancreaticoduodenectomy", "Portal Vein", "Proportional Hazards Models", "Risk Factors", "Time Factors", "Treatment Outcome" ] }
Hepatic relapse was associated with a dismal prognosis and with pathological portal vein invasion. Novel therapeutic strategies are therefore required to reduce the incidence of hepatic relapse, especially in patients with portal vein invasion.
yes
25,428,515
Does preoperative neutrophil-to-lymphocyte ratio predict response to first-line platinum-based chemotherapy and prognosis in serous ovarian cancer?
{ "contexts": [ "To investigate the role of preoperative neutrophil-to-lymphocyte ratio (NLR) in prediction of response to first-line platinum-based chemotherapy and survival outcome in serous ovarian cancer (SOC) patients.", "Clinicopathologic data were reviewed for patients with SOC treated with primary cytoreduction followed by platinum-based chemotherapy. The correlations of NLR value with clinicopathological features, clinical response to chemotherapy, and survival outcome were further explored.", "High preoperative NLR was significantly associated with advanced FIGO stage, histological grade, increased serum CA-125 level, and positive lymph node metastasis (P < 0.05, respectively). SOC patients in the third and fourth NLR quartile had significantly lower complete response rates compared to those in the first NLR quartile. In addition, survival analysis identified NLR as an independent prognostic factor for both PFS (HR 2.262, 95% CI 1.342-3.811; P = 0.002) and OS (HR 3.254, 95% CI 1.741-6.084; P < 0.001) in SOC patients." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Antineoplastic Agents", "Disease-Free Survival", "Female", "Follow-Up Studies", "Humans", "Lymphocyte Count", "Middle Aged", "Neutrophils", "Organoplatinum Compounds", "Ovarian Neoplasms", "Predictive Value of Tests", "Preoperative Period", "Prognosis", "Survival Analysis", "Treatment Outcome" ] }
Our findings indicated that high levels of preoperative NLR might be a potential biomarker of worse response to first-line platinum-based chemotherapy and poor clinical outcomes in patients with SOC. Further validation of this easily available parameter as a potential stratification tool in prospective studies should be encouraged.
yes
25,426,613
Does peroxiredoxin 1 promote pancreatic cancer cell invasion by modulating p38 MAPK activity?
{ "contexts": [ "The aim of this study was to investigate the role of peroxiredoxin 1 (Prdx1) in the invasiveness of pancreatic ductal adenocarcinoma (PDAC) cells.", "Immunohistochemistry was used to determine overexpression of Prdx1 in human PDAC tissues. Immunoprecipitation and immunocytochemistry were used to determine the interaction and intracellular distribution of Prdx1 and a member of the mitogen-activated protein kinase (MAPK) family protein, p38 MAPK, in PDAC cells. Finally, immunocytochemistry and Matrigel invasion assay were used to examine the effects of Prdx1 and p38 MAPK on the formation of cell protrusions and PDAC cell invasion.", "Prdx1 is overexpressed in human PDAC tissues. Peroxiredoxin 1 interacts with active forms of p38 MAPK, and complexes of Prdx1 and phosphorylated p38 MAPK localize at the leading edges of migrating PDAC cells. Suppression of Prdx1 decreases active p38 MAPK localized in cell protrusions and inhibits the invasiveness of PDAC cells. Consequently, suppression of Prdx1 inhibits membrane ruffling and protrusions. The p38 MAPK inhibitor SB203580 also decreases the formation of membrane protrusions and inhibits invasiveness." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Carcinoma, Pancreatic Ductal", "Cell Line, Tumor", "Cell Movement", "Cell Surface Extensions", "Gene Expression Regulation, Enzymologic", "Gene Expression Regulation, Neoplastic", "Humans", "Neoplasm Invasiveness", "Pancreatic Neoplasms", "Peroxiredoxins", "Phosphorylation", "Protein Binding", "Protein Kinase Inhibitors", "RNA Interference", "Signal Transduction", "Transfection", "p38 Mitogen-Activated Protein Kinases" ] }
Prdx1 associates with the formation of membrane protrusions through modulation of the activity of p38 MAPK, which in turn promotes PDAC cell invasion.
yes
25,445,501
Is long noncoding RNA PCA3 gene promoter region related to the risk of prostate cancer on Chinese males?
{ "contexts": [ "Long noncoding RNA prostate cancer gene antigen 3 (PCA3) is one of the most prostate cancer-specific genes at present. Consequently, the prostate-specific expression and the sharp up-regulation of PCA3 RNA in prostate cancer suggest a unique transcriptional regulation, which possibly can be attributed to promoter polymorphism. In this study, we investigated a short tandem repeat (STR) polymorphism of TAAA in the promoter region of PCA3 gene found in our previous study in prostate cancer (PCa) patients and benign prostatic hypertrophy (BPH) patients, aiming to evaluate the association between the STR and increased risk for PCa.", "120 PCa cases and 120 benign prostatic hypertrophy (BPH) cases were identified among participants. The region encompassing the TAAA repeat was amplified with a specific primer set we designed and screened by PCR-based cloning and sequencing in paired peripheral blood leukocytes and prostate tissues. Genotype-specific risks were estimated as odds ratios (ORs) associated with 95% confidence intervals (CIs) and adjusted for age by means of unconditional logistic regression.", "5 PCA3 TAAA STR polymorphisms and 8 genotypes were found in both peripheral blood leukocytes and prostate tissues, the carriers with more TAAA repeats were associated with increased risk for PCa than individuals having less TAAA repeats. Interestingly, 18 (15.0%) of 120 PCa patients had more (TAAA)n repeats in prostate tissues than that in peripheral blood leukocytes, and 3 (2.5%) of 120 had less (TAAA)n repeats in prostate tissues." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Aged", "Aged, 80 and over", "Antigens, Neoplasm", "Asian Continental Ancestry Group", "Base Sequence", "Genetic Predisposition to Disease", "Genotype", "Humans", "Male", "Microsatellite Repeats", "Middle Aged", "Odds Ratio", "Promoter Regions, Genetic", "Prostatic Hyperplasia", "Prostatic Neoplasms", "RNA, Long Noncoding", "Reverse Transcriptase Polymerase Chain Reaction" ] }
The results of this study suggest that short tandem repeat polymorphism of TAAA in the promoter region of PCA3 gene is a risk-increasing factor for prostate cancer in the Chinese population. In addition to the hereditary factor, the insertion mutation of (TAAA)n in a local tissue maybe another mechanism of the onset of PCa.
yes
25,435,904
Is perfusion CT a valuable diagnostic method for prostate cancer : a prospective study of 94 patients?
{ "contexts": [ "The aim of this study is to assess the usefulness of perfusion computer tomography (pCT) in prostate cancer (PCa) diagnostics.", "94 patients with biopsy-proven PCa were enrolled in the study. Dynamic pCT of the prostate gland was performed for 50 seconds after an intravenous injection of contrast medium. Blood flow (BF), blood volume (BV), mean transit time (MTT) and permeability surface area product (PS) were computed in the suspected PCa area and in normal prostatic tissue.", "PCa was visible in pCT in 90 of the 94 examined patients as a focal peripheral CT enhancement. When PCa was located in the peripheral zone (PZ), it was visible on perfusion maps, mostly showing an early peak followed by wash-out. The average values of all perfusion parameters were higher for tumour than for normal prostate tissue (p < 0.000). BV and BF were dependent on tumour grade expressed by the Gleason score (GS). All PCa cases were divided into groups, according to histological grade, as low (GS ≤ 6), medium (GS = 7), and high (GS > 7). In high-grade PCa, the mean BF value was significantly higher (p = 0.001) than the mean value of BF low- and medium-grade PCa (p = 0.011). Similar results were obtained regarding the mean values of BV; the more aggressive the cancer grade, the higher the mean BV value (p = 0.04)." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [] }
CT quantitative perfusion imaging allows PCa to be distinguished from normal prostate tissue. The highest values for BF and BV were observed in the most aggressive PCa grade.
yes
25,431,127
Do a phase II study of sulforaphane-rich broccoli sprout extracts in men with recurrent prostate cancer?
{ "contexts": [ "Diets high in cruciferous vegetables are associated with lower risk of incidence of prostate cancer, including aggressive forms of this disease. Human intervention studies with cruciferous vegetable-rich diets also demonstrate modulation of gene expression in important pathways in prostate cells.", "Sulforaphane is a constituent of these foods postulated to harbor the anti-neoplastic activity based on multiple tumor models. Our own work demonstrates that sulforaphane inhibits AR signaling in prostate cancer cells. Here, we report results from the first clinical trial of sulforaphane-rich extracts in men with prostate cancer.", "We treated 20 patients who had recurrent prostate cancer with 200 μmoles/day of sulforaphane-rich extracts for a maximum period of 20 weeks and determined the proportion of patients with ≥50% PSA declines, the primary endpoint. Only one subject experienced a ≥50% PSA decline. Thus, the primary endpoint was not achieved. Seven patients experienced smaller PSA declines (<50%). There was also a significant lengthening of the on-treatment PSA doubling time (PSADT) compared with the pre-treatment PSADT [6.1 months pre-treatment vs. 9.6 months on-treatment (p = 0.044)]. Finally, treatment with sulforaphane-rich extracts was safe with no Grade 3 adverse events." ], "labels": [ "BACKGROUND", "OBJECTIVE", "METHODS" ], "meshes": [ "Area Under Curve", "Brassica", "Chromatography, Liquid", "Dose-Response Relationship, Drug", "Glutathione Transferase", "Half-Life", "Humans", "Isothiocyanates", "Male", "Metabolic Clearance Rate", "Neoplasm Recurrence, Local", "Plant Extracts", "Prostate-Specific Antigen", "Prostatic Neoplasms", "Tandem Mass Spectrometry" ] }
Treatment with 200 μmoles/day of sulforaphane-rich extracts did not lead to ≥50% PSA declines in the majority of patients. However, because of the safety of treatment and the effects on PSADT modulation, further studies, including those with higher doses, may be warranted to clarify the role of sulforaphane as a prevention agent or treatment agent.
yes
25,452,543
Is digital rectal examination in primary care important for early detection of prostate cancer : a retrospective cohort analysis study?
{ "contexts": [ "Currently, there is no standardised screening for prostate cancer in Europe. Assessment of risk is opportunistically undertaken in consultation with the GP or urologist. Evaluation of the prostate gland consists of a prostate-specific antigen (PSA) serum level and a digital rectal examination (DRE) of the gland. DRE is an essential part of the assessment that can independently predict prostate cancer in the setting of a normal PSA level.", "To evaluate the clinical usefulness of the DRE in general practice and urology clinics, and to ascertain its positive predictive value and sensitivity.", "A retrospective analysis study of a cohort of Irish men who underwent TRUS guided biopsy of the prostate in a single Irish tertiary referral centre, despite a normal PSA level. Patients were identified from a Rapid Access Prostate Clinic patient database. Pathological biopsy results were correlated with clinical DRE findings.", "Patient demographics, PSA levels, and DRE findings from a prospectively established database and hospital data systems from May 2009 to October 2013 were analysed.", "Of 103 men referred over a 53-month period with a normal age-adjusted PSA level, 67% were referred on the basis of an abnormal DRE alone. Thirty-five per cent of males with a normal PSA had prostate cancer. DRE alone had a sensitivity and specificity of 81% and 40% respectively in diagnosing prostate cancer, with a positive predictive value of 42%. Seventy-six per cent of these men had high-grade disease." ], "labels": [ "BACKGROUND", "OBJECTIVE", "METHODS", "METHODS", "RESULTS" ], "meshes": [ "Aged", "Digital Rectal Examination", "Early Detection of Cancer", "Humans", "Ireland", "Male", "Middle Aged", "Physical Examination", "Practice Guidelines as Topic", "Predictive Value of Tests", "Primary Health Care", "Prostate-Specific Antigen", "Prostatic Neoplasms", "Referral and Consultation", "Retrospective Studies", "Sensitivity and Specificity" ] }
DRE is a key part of the assessment for prostate cancer. It can independently identify patients at risk of prostate cancer, with a substantial proportion of these having clinically significant disease requiring treatment. This study reinforces the importance of DRE in the primary care setting in the assessment for prostate cancer. An abnormal DRE, even in the setting of a normal PSA level, necessitates referral.
yes
25,424,898
Does celecoxib induce epithelial-mesenchymal transition in epithelial ovarian cancer cells via regulating ZEB1 expression?
{ "contexts": [ "The purpose of our study was to investigate the therapeutic potential of Celecoxib for epithelial ovarian cancer, especially on cellular morphological changes, proliferation invasion and epithelial-mesenchymal transition (EMT).", "The MTT and transwell assays were performed to evaluate the effect of Celecoxib on proliferation and invasion ability of ovarian cancer cell lines, respectively. Western blot was carried out to detect the expression of epithelial phenotypes, E-cadherin and Keratin, and mesenchymal phenotypes, N-cadherin and Vimentin, as well as p-AKT, p-ERK and ZEB1. ZEB1 small-interfering RNA (siRNA) was used to downregulate the expression of ZEB1 to further inquiring into the downstream of Celecoxib-induced EMT.", "Cellular morphological assessment revealed that both A2780 and SKOV3 cells gradually appeared in the morphology of mesenchymal cells after Celecoxib treatment. The MTT assay demonstrated that celecoxib had no effect on cell proliferation. Transwell assay showed that Celecoxib significantly increased the cell invasion ability. Western blot data proved that the expression of E-cadherin and keratin was elevated, whereas the expression of N-cadherin and Vimentin was decreased in a dose-dependent manner compared with the untreated cells, the expression of p-AKT, p-ERK and ZEB1 was also obviously elevated. However, ZEB1 siRNA reversed Celecoxib-induced E-cadherin expression and N-cadherin expression, as well as cellular invasiveness." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Cadherins", "Carcinoma, Ovarian Epithelial", "Celecoxib", "Cell Line, Tumor", "Cell Proliferation", "Down-Regulation", "Epithelial-Mesenchymal Transition", "Female", "Homeodomain Proteins", "Humans", "Neoplasms, Glandular and Epithelial", "Ovarian Neoplasms", "Pyrazoles", "RNA, Small Interfering", "Sulfonamides", "Transcription Factors", "Zinc Finger E-box-Binding Homeobox 1" ] }
Our results indicated that Celecoxib might induce EMT and increase cellular invasiveness in ovarian cancer cells in vitro, which also implied that it needed a comprehensive evaluation in preclinical researches before introducing Celecoxib into the clinical regimen.
yes
25,425,969
Does core needle biopsy of breast cancer tumors increase distant metastases in a mouse model?
{ "contexts": [ "Incisional biopsies, including the diagnostic core needle biopsy (CNB), routinely performed before surgical excision of breast cancer tumors are hypothesized to increase the risk of metastatic disease. In this study, we experimentally determined whether CNB of breast cancer tumors results in increased distant metastases and examine important resultant changes in the primary tumor and tumor microenvironment associated with this outcome.", "To evaluate the effect of CNB on metastasis development, we implanted murine mammary 4T1 tumor cells in BALB/c mice and performed CNB on palpable tumors in half the mice. Subsequently, emulating the human scenario, all mice underwent complete tumor excision and were allowed to recover, with attendant metastasis development. Tumor growth, lung metastasis, circulating tumor cell (CTC) levels, variation in gene expression, composition of the tumor microenvironment, and changes in immunologic markers were compared in biopsied and non-biopsied mice.", "Mice with biopsied tumors developed significantly more lung metastases compared to non-biopsied mice. Tumors from biopsied mice contained a higher frequency of myeloid-derived suppressor cells (MDSCs) accompanied by reduced CD4 + T cells, CD8 + T cells, and macrophages, suggesting biopsy-mediated development of an increasingly immunosuppressive tumor microenvironment. We also observed a CNB-dependent up-regulation in the expression of SOX4, Ezh2, and other key epithelial-mesenchymal transition (EMT) genes, as well as increased CTC levels among the biopsy group." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Animals", "Biopsy, Large-Core Needle", "Breast", "Breast Neoplasms", "Cell Line, Tumor", "Cytokines", "Disease Models, Animal", "Enhancer of Zeste Homolog 2 Protein", "Epithelial-Mesenchymal Transition", "Female", "Flow Cytometry", "Gene Expression Regulation, Neoplastic", "Humans", "Lung Neoplasms", "Lymphocytes", "Macrophages", "Mammary Glands, Animal", "Mammary Neoplasms, Experimental", "Mice, Inbred BALB C", "Neoplastic Cells, Circulating", "Polycomb Repressive Complex 2", "Reverse Transcriptase Polymerase Chain Reaction", "SOXC Transcription Factors", "Tumor Microenvironment" ] }
CNB creates an immunosuppressive tumor microenvironment, increases EMT, and facilitates release of CTCs, all of which likely contribute to the observed increase in development of distant metastases.
yes
25,446,120
Is hAP1 gene expression associated with radiosensitivity in breast cancer cells?
{ "contexts": [ "The purpose of this study was to investigate the relationship between huntingtin-associated protein1 (HAP1) gene and radiation therapy of breast cancer cells.", "HAP1 gene was transfected into breast cancer MCF-7 cells, which was confirmed by quantitative reverse transcription-polymerase chain reaction analysis (qRT-PCR) and Western blot in vitro. The changes of cell radiosensitivity were assessed by colony formation assay. Apoptosis were examined by flow cytometry. The expressions of two radiation-induced genes were evaluated by Western blot. Tumor growth was investigated in nude mice xenograft models in vivo.", "Our data showed that HAP1 gene expression was significantly increased in HAP1-transfected MCF-7 cells in comparison with the parental cells or negative control cells. The survival rate in MCF-7/HAP1 cells was significantly decreased after irradiation (0, 2, 4, 6, 8Gy), compared to cells in MCF-7 and MCF-7/Pb groups in vitro. HAP1 gene increased apoptosis in MCF-7 cells after irradiation. Additionally, the tumor volume and weight in MCF-7/HAP1+RT group were observably lower than in MCF-7/HAP1 group and MCF-7/Pb+RT group." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Animals", "Apoptosis", "Breast Neoplasms", "Female", "Flow Cytometry", "Gene Expression Regulation, Neoplastic", "Humans", "MCF-7 Cells", "Mice", "Mice, Nude", "Neoplasm Transplantation", "Nerve Tissue Proteins", "Radiation Tolerance", "Reverse Transcriptase Polymerase Chain Reaction", "Stem Cells" ] }
The present study indicated that HAP1 gene expression was related to the radiosensitivity of breast cancer cells and may play an important role in the regulation of cellular radiosensitivity.
yes
25,451,483
Does pulmonary rehabilitation during induction chemoradiotherapy for lung cancer improve pulmonary function?
{ "contexts": [ "Chemoradiotherapy for non-small cell lung cancer can impair pulmonary function, particularly when it is followed by surgery. This study aimed to document the changes in respiratory function as a result of a perioperative intensive pulmonary rehabilitation program in patients with non-small cell lung cancer who underwent induction chemoradiotherapy.", "A total of 82 consecutive patients underwent pulmonary resection after undergoing induction chemoradiotherapy. A pulmonary rehabilitation program was started at the same time as the induction chemoradiotherapy. Standard respiratory function tests were performed before and after induction chemoradiotherapy. Treatment-related mortality and the incidence of postoperative respiratory complications were investigated. The Wilcoxon signed-rank test was used to analyze the differences in spirometric changes.", "All patients underwent a pulmonary rehabilitation program for an average of 10 weeks. Significant increases were observed in forced vital capacity (+6.4%, P = .0096) and forced expiratory volume in 1 second (+10.4%, P < .0001). Diffusing capacity of the lung for carbon monoxide decreased (-14.0%, P < .0001). Patients with respiratory impairment (forced vital capacity <80% predicted or forced expiratory volume in 1 second/forced vital capacity <70%) showed significant improvements in forced vital capacity (+13.9%, P = .0025) and forced expiratory volume in 1 second (+22.5%, P < .0001). Significant increases were observed in forced vital capacity (+7.0%, P = .0042) and forced expiratory volume in 1 second (+10.8%, P = .0001) in patients with a smoking history. There was no mortality, and postoperative respiratory morbidity was 6.1%." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Carcinoma, Non-Small-Cell Lung", "Chemoradiotherapy", "Combined Modality Therapy", "Female", "Humans", "Lung Neoplasms", "Male", "Middle Aged", "Pneumonectomy", "Postoperative Complications", "Respiratory Function Tests", "Retrospective Studies" ] }
A pulmonary rehabilitation program for patients with non-small cell lung cancer undergoing induction chemoradiotherapy seems to improve respiratory function. It is particularly recommended for smokers and patients with respiratory impairment.
yes
25,424,877
Is the level of RECQL1 expression a prognostic factor for epithelial ovarian cancer?
{ "contexts": [ "The human RECQ DNA helicase family is involved in genomic stability. Gene mutations of RECQL2, RECQL3, and RECQL4 are associated with genetic disorders and induce early aging and carcinogenesis. Although previous studies have reported that the level of RECQL1 expression is correlated with the prognosis of some of malignancies, the function of RECQL1 is not yet clarified. The present study aimed to examine the relationship between prognosis and the level of RECQL1 expression in epithelial ovarian cancer (EOC), and to identify the role of RECQL1 in EOC cells.", "The level of RECQL1 expression was determined immunohistochemically in 111 patients with EOC who received initial treatment at Hirosaki University hospital between 2006 and 2011. Effects of RECQL1 on cell growth or apoptosis were examined in vitro using wild-type and OVCAR-3 cells (RECQL1(+) cells) and similar cells transfected with RECQL1 siRNA transfected (RECQL1(-) cells).", "The level of RECQL1 expression was not related to histological type, clinical stage, or retroperitoneal lymph node metastasis, but the expression level was significantly higher (P = 0.002) in patients with recurrence than those without recurrence, and progression-free survival and complete response rate to chemotherapy were also improved in patients with RECQL1-low expression (n = 39) stage III/IV EOC (P = 0.02 and P <0.05 vs RECQL1-high expression patients (n = ), respectively). A cell proliferation and colony formation assays revealed significantly less growth of RECQL1(-) cells compared to RECQL1(+) cells. A flow cytometry using annexin V -FITC and propidium iodide (PI) staining revealed a significant increase in apoptotic RECQL1(-) cells. Cell cycle analysis showed a significantly greater distribution in subG1 phase indicating apoptotic cells in RECQL1(-) cells than in RECQL1(+) cells." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Aged, 80 and over", "Antineoplastic Agents", "Apoptosis", "Biomarkers, Tumor", "Carcinoma, Ovarian Epithelial", "Cell Line, Tumor", "Cell Nucleus", "Disease-Free Survival", "Drug Resistance, Neoplasm", "Female", "Gene Expression", "Humans", "Kaplan-Meier Estimate", "Middle Aged", "Neoplasms, Glandular and Epithelial", "Ovarian Neoplasms", "Prognosis", "RecQ Helicases", "Young Adult" ] }
These results suggest that RECQL1 is a prognostic factor for EOC and that RECQL1 contributes to potential malignancy by inhibiting apoptosis.
yes
25,449,207
Are bone-related Parameters the Main Prognostic Factors for Overall Survival in Men with Bone Metastases from Castration-resistant Prostate Cancer?
{ "contexts": [ "Previous studies have reported on prognostic factors for castration-resistant prostate cancer (CRPC); however, most of these studies were conducted before docetaxel chemotherapy was approved for CRPC.", "To evaluate the prognostic value of multiple parameters in men with bone metastases due to CRPC using a contemporary dataset.", "The analysis included 1901 patients with metastatic CRPC enrolled in an international, multicenter, randomized, double-blind phase 3 trial conducted between May 2006 and October 2009.", "We developed multivariate validated Cox proportional hazards models and nomograms to estimate 12-mo and 24-mo survival probabilities and median survival time." ], "labels": [ "BACKGROUND", "OBJECTIVE", "METHODS", "UNASSIGNED" ], "meshes": [ "Adult", "Age Factors", "Aged", "Aged, 80 and over", "Alkaline Phosphatase", "Bone Density Conservation Agents", "Bone Neoplasms", "Collagen Type I", "Denosumab", "Diphosphonates", "Double-Blind Method", "Hemoglobins", "Humans", "Imidazoles", "Kallikreins", "Male", "Middle Aged", "Multivariate Analysis", "Peptides", "Prognosis", "Proportional Hazards Models", "Prostate-Specific Antigen", "Prostatic Neoplasms, Castration-Resistant", "Zoledronic Acid" ] }
The median (95% confidence interval) overall survival was 20 (18, 21) mo. The final model included 12 of the 15 potential prognostic variables evaluated (concordance index 0.72). Seven bone-related variables were associated with longer survival in the final model: alkaline phosphatase ≤143 U/l (p<0.0001); bone-specific alkaline phosphatase (BSAP) <146 U/l (p<0.0001); corrected urinary N-telopeptide (uNTx) ≤50 nmol/mmol (p=0.0008); mild or no pain (Brief Pain Inventory-Short Form [BPI-SF] score ≤4) (p<0.0001); no previous skeletal-related event (SRE; p=0.0002); longer time from initial diagnosis to first bone metastasis (p<0.0001); and longer time from first bone metastasis to randomization (p<0.0001). Other significant predictors of improved survival included prostate-specific antigen (PSA) level <10 ng/ml (p<0.0001), hemoglobin >128g/l (p<0.0001), absence of visceral metastases (p<0.0001), Eastern Co-operative Oncology Group (ECOG) score ≤1 (p=0.017), and younger age (p=0.008). Nomograms were generated based on the parameters included in the final validated models (with/without uNTx and BSAP). One limitation was that lactate dehydrogenase (LDH) levels, a known prognostic factor, were not available in this study.
yes
25,439,319
Is persistent arm pain distinct from persistent breast pain following breast cancer surgery?
{ "contexts": [ "Persistent pain following breast cancer surgery is well documented. However, it is not well characterized in terms of the anatomic site affected (ie, breast, arm). In 2 separate growth mixture modeling analyses, we identified subgroups of women (N = 398) with distinct breast pain and arm pain trajectories. The fact that these latent classes differed by anatomic site, types of tissue affected, and neural innervation patterns suggests the need for separate evaluations of these distinct persistent pain conditions. The purposes of this companion study were to identify demographic and clinical characteristics that differed between the 2 arm pain classes and determine if differences existed over time in sensitivity in the upper inner arm and axillary lymph node dissection sites, pain qualities, pain interference, and hand and arm function, as well as to compare findings with persistent breast pain. Higher occurrence rates for depression and lymphedema were found in the moderate arm pain class. Regardless of pain group membership, sensory loss was observed in the upper inner arm and axillary lymph node dissection site. Arm pain was described similarly to neuropathic pain and interfered with daily functioning. Persistent arm pain was associated with sustained impairments in shoulder mobility." ], "labels": [ "UNLABELLED" ], "meshes": [ "Arm", "Breast", "Breast Neoplasms", "Female", "Hand Strength", "Humans", "Middle Aged", "Motor Activity", "Pain Measurement", "Pain, Postoperative", "Range of Motion, Articular", "Shoulder", "Time Factors" ] }
For persistent breast and arm pain, changes in sensation following breast cancer surgery were notable. Persistent arm pain was associated with sustained interference with daily functioning and upper body mobility impairments. Long-term management of persistent pain following breast cancer surgery is warranted to improve the quality of survivorship for these women.
yes
25,439,318
Is persistent breast pain following breast cancer surgery associated with persistent sensory changes , pain interference , and functional impairments?
{ "contexts": [ "Interindividual variability exists in persistent breast pain following breast cancer surgery. Recently, we used growth mixture modeling to identify 3 subgroups of women (N = 398) with distinct persistent breast pain trajectories (ie, mild, moderate, severe) over 6 months following surgery. The purposes of this study were to identify demographic and clinical characteristics that differed among the breast pain classes and, using linear mixed effects modeling, to examine how changes over time and in sensitivity in the breast scar area, pain qualities, pain interference, and hand and arm function differed among these classes. Several demographic and clinical characteristics differentiated the breast pain classes. Of note, 60 to 80% of breast scar sites tested were much less sensitive than the unaffected breast. Significant group effects were observed for pain qualities and interference scores, such that, on average, women in the severe pain class reported higher scores than women in the moderate pain class. In addition, women in the moderate pain class reported higher scores than women in the mild pain class. Compared to women in the mild pain class, women in the severe pain class had significantly impaired grip strength, and women in the moderate and severe pain classes had impaired flexion and abduction." ], "labels": [ "UNLABELLED" ], "meshes": [ "Arm", "Breast", "Breast Neoplasms", "Cicatrix", "Female", "Humans", "Middle Aged", "Motor Activity", "Pain Measurement", "Pain, Postoperative" ] }
Subgroups of women with persistent postsurgical breast pain differed primarily with respect to the severity rather than the nature or underlying mechanisms of breast pain. Pervasive sensory loss and the association between persistent breast pain and sustained interference with function suggest the need for long-term clinical follow-up.
yes
27,512,947
Do patient-oncologist alliance and psychosocial well-being in Chinese society strongly affect cancer management adherence with cancer of unknown primary?
{ "contexts": [ "Patient-oncologist alliance and psychosocial well-being have strong associations with adherence to cancer management. For patients with cancer of unknown primary (CUP), adherence is crucial to treatment or occult primary screening plans. There has been no study investigating the relationship between alliance, psychosocial factors, and adherence in such patients or in Chinese sociocultural settings.", "The measures of alliance, psychosocial well-being, and adherence willingness were administered to patients with CUP, with a mean age of 58.33 ± 11.24 years. Multiple linear regression models were applied to investigate the independent relationship between alliance and adherence by controlling for socioeconomic and psychosocial confounders.", "Alliance was found to be independently and positively associated with greater adherence willingness and adherence to treatment and follow-up screening after controlling for significant confounders, including medical conditions, psychosocial well-being variables, and socioeconomic factors." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Aged", "China", "Female", "Humans", "Male", "Middle Aged", "Neoplasms, Unknown Primary", "Physician-Patient Relations", "Treatment Adherence and Compliance" ] }
Stronger patient-oncologist alliance may foster enhanced adherence to treatment and follow-up screening in patients with CUP. Patient-oncologist alliance seems affected by socioeconomic factors and psychosocial well-being in the Chinese sociocultural settings.
yes
27,513,268
Does paCaHa inhibit proliferation of human cancer cells in vitro?
{ "contexts": [ "The aim of this study was to investigate the antiproliferative and cytotoxic effects of a newly synthesized molecule named paracetamol acetohydroxamic acid (PaCaHa) on human neoplastic cell lines.", "A549, CRL 2923, HeLa, and ARPE were treated with various concentrations of PaCaHa and DMSO (vehicle control). The cytotoxic/cytostatic effects of PaCaHa were determined after a 24-h incubation period and compared to the DMSO control. The cytotoxic and antiproliferative effects were determined by the trypan blue dye exclusion and MTT methods.", "A higher susceptibility to PaCaHA was found in CRL 2923 and HeLa cells, while A549 and ARPE cells were less responsive to PaCaHa. The percent of cytotoxicity resulting from 400 µg/mL of PaCaHa were >90 for CRL-2923 and HeLa, 68 for A549, and 64 for ARPE cells. The cytotoxic difference between CRL-2923/HeLa and ARPE/A549 cells was significant (P < 0.05)." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Acetaminophen", "Cell Line, Tumor", "Cell Proliferation", "Humans", "Neoplasms" ] }
PaCaHa showed dose dependent cytotoxic and antiproliferative effects on three distinct human cancer cell lines. The differential effect of PaCaHa on different cancer cell lines suggests that PaCaHa could have a potential antitumor effect on specific cancer types. These results support further comprehensive studies on PaCaHa and its derivatives.
yes
27,519,527
Is which better for gastric cancer patients , perioperative or adjuvant chemotherapy : a meta-analysis?
{ "contexts": [ "The preferred chemotherapy method for gastric cancer continues to be matter of debate. We performed a meta-analysis to comparing prognosis and safety between perioperative chemotherapy and adjuvant chemotherapy to identify the better chemotherapy option for gastric cancer.", "We searched the PubMed, EMBASE, Cochrane Library, and Ovid databases for eligible studies until February 2016. The main endpoints were prognostic value (hazard ratio [HR] for overall survival [OS] and 1-, 2-, 3-, and 5-year survival rate), response rate of chemotherapy, radical resection rate, post-operative complication rate, and adverse effects of chemotherapy.", "Five randomized controlled trials and six clinical controlled trials involving 1,240 patients were eligible for analysis. Compared with the adjuvant chemotherapy group, the perioperative chemotherapy group had significantly better prognosis (HR, 0.74; 95 % CI, 0.61 to 0.89; P < 0.01). The difference between the two groups remained significant in the studies that used combination chemotherapy as the neoadjuvant chemotherapy regimen (HR, 0.59; 95 % CI, 0.46 to 0.76; P < 0.01) but were not significant in the studies that used fluoropyrimidine monotherapy (HR, 0.93; 95 % CI, 0.56 to 1.55; P = 0.84). Furthermore, the two groups showed no significant differences in the post-operative complication rates (relative risk, 0.98; 95 % CI, 0.63 to 1.51; P = 0.91) or adverse effects of chemotherapy (P > 0.05 for all adverse effects)." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Antineoplastic Agents", "Female", "Humans", "Male", "Middle Aged", "Neoadjuvant Therapy", "Perioperative Care", "Prognosis", "Randomized Controlled Trials as Topic", "Stomach Neoplasms", "Survival Analysis", "Treatment Outcome", "Young Adult" ] }
Perioperative chemotherapy showed improved survival compared to adjuvant chemotherapy for gastric cancer. In addition, combination chemotherapy resulted in better survival compared to monotherapy in the neoadjuvant chemotherapy regimens.
yes
27,493,887
Does obesity Modify the Risk of Differentiated Thyroid Cancer in a Cytological Series of Thyroid Nodules?
{ "contexts": [ "A possible impact of obesity on the risk of thyroid cancer has been postulated in some studies, but it remains controversial.", "To investigate the association between obesity and differentiated thyroid carcinoma in a population of unselected patients subjected to fine-needle aspiration cytology (FNAC) for thyroid nodules.", "We retrospectively evaluated the results of FNAC of thyroid nodules in 4,849 patients (3,809 females and 1,040 males; mean age 55.9 ± 14.1 years). Patients were stratified according to their body mass index (BMI). There were 1,876 (38.7%) normal-weight patients (BMI 18-24.9), 1,758 (36.2%) overweight (BMI 25-29.9), 662 (13.7%) grade 1 obese (BMI 30-34.9), 310 (6.4%) grade 2 obese (BMI 35-39.9) and 243 (5.0%) grade 3 obese (BMI >40).", "The prevalence of suspicious or malignant nodules (Thy4/Thy5) did not differ across the 5 BMI groups, i.e. it was 6.8% in normal-weight patients, 6.3% in overweight patients, 6.3% in grade 1 obese patients, 4.0% in grade 2 obese patients and 4.2% in grade 3 obese patients (p = 0.29). The prevalence of Thy4/Thy5 nodules did not differ when males and females were evaluated separately (p = 0.22 and p = 0.12, respectively). A significant, lower rate of Thy4/5 cytology was observed in female patients with grade 2-3 obesity (odds ratio 0.51; 95% confidence interval 0.284-0.920; p = 0.009)." ], "labels": [ "BACKGROUND", "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [] }
The results of this study, in a retrospective series of patients with thyroid nodules, do not confirm previous findings reporting an association between obesity and differentiated thyroid carcinoma. Thus, obese patients with nodular thyroid disease should be managed the same as normal-weight patients.
no
27,519,795
Does tumor suppressor miRNA-204-5p promote apoptosis by targeting BCL2 in prostate cancer cells?
{ "contexts": [ "Prostate cancer (PCa) is a leading cause of cancer-related death in men, which emphasizes the need for novel therapeutic approaches. Targeting microRNA (miRNA) has been considered as a therapeutic strategy against cancers. Human miR-204-5p potentially targeting BCL2 has been reported to be downregulated in various cancers. We hypothesized that miR-204-5p overexpression induces cancer cell apoptosis by repressing BCL2 expression.", "A vector harboring mature miR-204-5p was constructed and delivered into human PCa cells. The expression level of miR-204-5p was determined by miRNA quantitative polymerase chain reaction (QPCR). Luciferase reporter assays were performed to verify the function of mature miR-204-5p and its direct binding to BCL2 transcripts. The expression levels of BCL-2 messenger RNA (mRNA) and protein samples were measured by QPCR and Western blot, respectively. Cell viability was detected by WST-1 assays. Induction of apoptosis was determined by increased levels of cleavage caspase 3 and caspase 3/7 activity.", "The expression levels of miR-204-5p were downregulated in PCa cells compared with normal prostate epithelial cells. Transfection of pSM-204 resulted in up to 6.2-fold higher expression of miR-204-5p when compared with pSM control. The mRNA levels of several potential target genes of miR-204-5p were decreased in pSM-204-transfected PC3 and Rv1 cells. BCL2 mRNA and protein expression decreased in miR-204-5p-transfected cells, which led to cytochrome C release from mitochondria. It subsequently increased cleaved caspase 3 and caspase 3/7 activities and reduced cell viability. Cotransfection of a reporter vector harboring the BCL2 3'-untranslated region to compete with endogenous transcripts partially rescued miR-204-5p-induced apoptosis." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Apoptosis", "Blotting, Western", "Cell Line, Tumor", "Down-Regulation", "Gene Expression Regulation, Neoplastic", "Humans", "Male", "MicroRNAs", "Prostatic Neoplasms", "Proto-Oncogene Proteins c-bcl-2", "Real-Time Polymerase Chain Reaction", "Up-Regulation" ] }
Human miR-204-5p targets BCL2 in PCa cells. Restoration of miR-204-5p in PCa could therefore be considered as a novel strategy by targeting antiapoptotic BCL2.
yes
27,512,995
Does thrombomodulin influence the Survival of Patients with Non-Metastatic Colorectal Cancer through Epithelial-To-Mesenchymal Transition ( EMT )?
{ "contexts": [ "Treatment resistance and metastasis are the major causes of death among patients with colorectal cancer (CRC). Approximately 20% of surgically treated patients ultimately develop metastases during the follow-up period. Currently, the TNM system is the only available prognostic test. Therefore, the identification of new markers for CRC remains important. Thrombomodulin (TM), a glycoprotein, is involved in angiogenesis and has been linked to many malignant diseases. However, the function of TM in CRC remains unclear.", "A total of 170 patients with CRC participated in this study. TM expression was analyzed via immunohistochemistry. Univariate (Kaplan-Meier) analysis was used to analyze patient outcomes, including overall survival (OS) and disease-free survival (DFS). TM expression was manipulated using shRNA or an overexpression system. Transwell migration assays, wound healing migration assays, and the xCELLigence biosensor system were used to detect cell proliferative and migratory capacities.", "TM expression in the tumor tissues significantly and positively correlated with the DFS and OS of non-metastatic patients with CRC (ps = 0.036 and 0.0218, respectively). Suppression of TM expression increased the proliferation and migration of DLD-1 cells. TM overexpression reduced the cells' proliferative and migratory capacities. Cyclooxygenase (COX)-2 expression was up-regulated following TM silencing. Furthermore, the association between the migration of colon cancer cells and the levels of TM and epithelial-to-mesenchymal transition (EMT) markers (fibronectin, vimentin and ezrin) was confirmed in HT29 and DLD-1 cells." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Biomarkers, Tumor", "Cell Movement", "Cell Proliferation", "Colorectal Neoplasms", "Cyclooxygenase 2", "Disease-Free Survival", "Epithelial-Mesenchymal Transition", "Humans", "Prognosis", "Survival Analysis", "Thrombomodulin", "Tumor Cells, Cultured", "Up-Regulation" ] }
Our study demonstrates that patients with non-metastatic CRC display low TM expression in their tumors and exhibit reduced DFS and OS. The enhanced expression of mesenchymal markers and COX-2 may be involved in the mechanisms that underlie recurrence in patients with cancer displaying low TM expression.
yes
27,502,717
Is tumor-related leukocytosis associated with poor radiation response and clinical outcome in uterine cervical cancer patients?
{ "contexts": [ "To evaluate response to radiation and clinical outcome of uterine cervical cancer patients with tumor-related leukocytosis (TRL) at initial diagnosis and during definitive radiotherapy.", "We retrospectively analyzed 2456 patients with stage IA-IVA uterine cervical cancer who received definitive radiotherapy with (37.4%) or without (62.6%) platinum-based chemotherapy between 1986 and 2012. TRL was defined as two or more occurrences of leukocytosis over 9000/μl at the time of diagnosis and during the course of treatment. Locoregional failure-free survival (LFFS) and overall survival (OS) were compared between patients with or without TRL.", "The median age of all patients was 55 years, and the median follow-up time was 65.1 months. TRL was observed in 398 patients (16%) at initial diagnosis; TRL (+) patients were younger and had larger tumors, advanced stage, and more frequent lymph node metastases (all P < 0.05). TRL (+) patients showed a significantly lower rate of complete remission than TRL (-) patients (89.9% versus 96.3%, respectively, P = 0.042). Ten-year LFFS and OS for all patients were 84% and 78%, respectively. LFFS and OS were significantly lower in TRL (+) patients than TRL (-) patients (10-year LFFS: 69% versus 87% respectively, P < 0.001; 10-year OS: 63% versus 81% respectively P < 0.001). After propensity score matching, LFFS and OS rates in TRL (+) patients remained significantly lower than for TRL (-) patients; this significant difference was also observed on multivariate analysis. Twenty-six percent of patients with locoregional failure (n = 345) were TRL (+) and had significantly poorer median OS (6 versus 12 months, P = 0.001)." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Cisplatin", "Disease-Free Survival", "Female", "Humans", "Leukocytosis", "Lymphatic Metastasis", "Middle Aged", "Neoplasm Recurrence, Local", "Neoplasm Staging", "Neoplasms, Second Primary", "Prognosis", "Radiation Tolerance", "Radiotherapy", "Treatment Failure", "Uterine Cervical Neoplasms" ] }
This study reveals the aggressive nature of cervical cancer with TRL and its poor response to radiation therapy. Given the unfavorable prognosis and higher probability of treatment failure, optimal diagnostic and therapeutic approaches and careful monitoring for early detection of recurrence should be considered for these patients.
yes
27,502,396
Does uPAR enhance malignant potential of triple-negative breast cancer by directly interacting with uPA and IGF1R?
{ "contexts": [ "Due to lack of a targeted therapy for the triple-negative breast cancer (TNBC) patients, it is important to explore this aggressive breast cancer type in more detail and to establish novel therapeutic approaches. TNBC is defined negative for the protein expression of oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). One prominent feature of this cancer type is the frequent overexpression of major components of the urokinase-type plasminogen activator system (uPAS) including uPA, its receptor uPAR and the inhibitor PAI-1, which may be valuable as therapeutic targets.", "Direct interactions of uPAR with interactors were demonstrated by immunoprecipitations and proximity ligation assays. For stable knockdowns of target proteins, lentiviral vectors were used and the effects were analysed by immunoblottings and using in vitro cell viability, migration and invasion assays. Immunohistochemical and statistical analyses of biomarkers and clinical parameters were conducted in a TNBC cohort (n = 174).", "Direct tumour-promoting interactions of uPAR with uPA and the insulin-like growth factor receptor 1 (IGF1R) were shown in TNBC cells and these interactions were significantly reduced (p = 0.001) when uPAR was downregulated. The combined knockdown of uPAR and uPA or IGF1R additively and significantly reduced cell viability, migration and invasion of the model cell lines. In TNBC tissue, the complexes formed by uPAR with uPA or with IGF1R significantly correlated with the histological grade (p = 0.0019) as well as with cathepsin B and D (p ≤ 0.0001) that are implicated in cell invasion and metastasis." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Cell Line, Tumor", "Cell Movement", "Cell Proliferation", "Cell Survival", "Female", "Gene Expression Regulation, Neoplastic", "Humans", "MCF-7 Cells", "Neoplasm Grading", "Receptors, Somatomedin", "Receptors, Urokinase Plasminogen Activator", "Triple Negative Breast Neoplasms", "Urokinase-Type Plasminogen Activator" ] }
Our outcomes show that not only overexpressed biomarkers promote tumourigenesis, but rather their interactions further potentiate tumour progression. This study emphasises the potential of combined approaches targeting uPAR and its interactors with regard to an improved therapy of TNBC.
yes
27,499,968
Does positive expression of miR-361-5p indicate better prognosis for breast cancer patients?
{ "contexts": [ "MicroRNA-361-5p (miR-361-5p) has been reported to be tumor suppressor in colorectal, gastric and prostate cancer, but as an oncogene in cervical cancer. No previous research has focused on the expression of miR-361-5p and its exact prognostic role in breast cancer (BC).", "In this study, a tissue microarray (TMA)-based miRNA detection in situ hybridization (ISH) with LNA probe was used to detect miR-361-5p expression in 375 BC tissue. The expression level of miR-361-5p in BC and its potential prognostic value was investigated.", "Positive miR-361-5p staining was observed in 78.7% (N=295; 78.7% positive, 21.3% negative) in the 375 cases. The clinical outcome of patients with positive miR-361-5p expression [median disease-free survival (DFS) time 95.52 months] was significantly better than that of patients (median DFS time 82.33 months) with negative miR-361-5p expression (P=0.002). Moreover, the prognostic value of miR-361-5p was most significant among patients with triple-negative breast cancer (TNBC) for DFS (P=0.004)." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [] }
These results indicated that miR-361-5p expression is an independent predictive factor for better prognosis in BC.
yes
27,495,308
Does sMARCE1 regulate metastatic potential of breast cancer cells through the HIF1A/PTK2 pathway?
{ "contexts": [ "While aberrant activation of the chromatin-remodeling SWI/SNF complexes has been associated with cancer development and progression, the role of each subunit in tumor cells is poorly defined. This study is aimed to characterize the role of SMARCE1/BAF57 in regulating metastasis of breast cancer cells.", "Genetic approaches and chemical inhibitors were used to manipulate the activities of SMARCE1 and its downstream targets in multiple breast cancer cell lines. Xenograft mouse models were used to analyze the role of SMARCE1 in lung metastasis in vivo. Nonadherent culture conditions were used to elucidate the role of SMARCE1 in regulating anoikis. Chromatin immunoprecipitation (ChIP), immunoprecipitation, and immunoblotting assays were designed to dissect the mechanism of action of SMARCE1. Public databases were used to investigate the relationship between SMARCE1 deregulation and breast cancer prognosis.", "SMARCE1 knockdown reduced lung metastasis of breast cancer cells and sensitized tumor cells to anoikis. In response to loss of attachment, SMARCE1 interacted with and potentiated transcriptional activity of HIF1A, resulting in rapid PTK2 activation. Both HIF1A and PTK2 were indispensable for SMARCE1-mediated protection against anoikis by promoting activation of ERK and AKT pathways while suppressing the expression of pro-apoptotic BIM protein. Expression data analysis of a large cohort of human breast tumors revealed that high expression of SMARCE1 or PTK2 is associated with poor prognosis and tumor relapse, and PTK2 expression is positively correlated with SMARCE1 expression in basal-like and luminal B subtypes of breast tumors." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Animals", "Anoikis", "Base Sequence", "Binding Sites", "Breast Neoplasms", "Carcinogenesis", "Cell Line, Tumor", "Chromatin Assembly and Disassembly", "Chromosomal Proteins, Non-Histone", "DNA-Binding Proteins", "Female", "Focal Adhesion Kinase 1", "Gene Expression", "Gene Expression Regulation, Neoplastic", "Gene Knockdown Techniques", "Humans", "Hypoxia-Inducible Factor 1, alpha Subunit", "Kaplan-Meier Estimate", "Lung Neoplasms", "Mice, Inbred NOD", "Mice, SCID", "Neoplasm Transplantation", "Promoter Regions, Genetic", "Signal Transduction", "Transcriptional Activation" ] }
SMARCE1 plays an essential role in breast cancer metastasis by protecting cells against anoikis through the HIF1A/PTK2 pathway. SMARCE1-mediated PTK2 activation likely plays a key role in promoting metastasis of basal-like and luminal B subtype of breast tumors.
yes
27,507,616
Does integrated Epigenomics Analysis reveal a DNA Methylation Panel for Endometrial Cancer Detection Using Cervical Scrapings?
{ "contexts": [ "Endometrial cancer is a common gynecologic cancer whose incidence is increasing annually worldwide. Current methods to detect endometrial cancer are unreliable and biomarkers are unsatisfactory for screening. Cervical scrapings were reported as a potential source of material for molecular testing. DNA methylation is a promising cancer biomarker, but limited use for detecting endometrial cancer.", "We analyzed two methylomics databases of endometrioid-type endometrial cancer. Using nonnegative matrix factorization algorithm clustered the methylation pattern and reduced the candidate genes. We verified in pools DNA from endometrial cancer tissues and cervical scrapings, and validated in 146 cervical scrapings from patients with endometrioid-type endometrial cancer (n = 50), uterine myoma (n = 40), and healthy controls (n = 56) using quantitative methylation-specific PCR (QMSP). The logistic regression was used to evaluate the performance of methylation signal and gene combination.", "We filtered out 180 methylated genes, which constituted four consensus clusters. Serial testing of tissues and cervical scrapings detected 14 genes that are hypermethylated in endometrial cancer. Three genes, BHLHE22, CDO1, and CELF4, had the best performance. Individual genes were sensitivity of 83.7%-96.0% and specificity of 78.7%-96.0%. A panel comprising any two of the three hypermethylated genes reached a sensitivity of 91.8%, specificity of 95.5%, and odds ratio of 236.3 (95% confidence interval, 56.4-989.6). These markers were also applied to cervical scrapings of type II endometrial cancer patients, and detected in 13 of 14 patients." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Biomarkers, Tumor", "Case-Control Studies", "Cluster Analysis", "CpG Islands", "DNA Methylation", "Endometrial Neoplasms", "Epigenomics", "Female", "Gene Expression Profiling", "Gene Expression Regulation, Neoplastic", "Humans", "Middle Aged", "Mutation", "Neoplasm Grading", "Neoplasm Staging", "ROC Curve", "Reproducibility of Results" ] }
This study demonstrates the potential use of methylated BHLHE22/CDO1/CELF4 panel for endometrial cancer screening of cervical scrapings. Clin Cancer Res; 1-10. ©2016 AACR.
yes
27,506,388
Do grape compounds suppress colon cancer stem cells in vitro and in a rodent model of colon carcinogenesis?
{ "contexts": [ "We have previously shown that the grape bioactive compound resveratrol (RSV) potentiates grape seed extract (GSE)-induced colon cancer cell apoptosis at physiologically relevant concentrations. However, RSV-GSE combination efficacy against colon cancer stem cells (CSCs), which play a key role in chemotherapy and radiation resistance, is not known.", "We tested the anti-cancer efficacy of the RSV-GSE against colon CSCs using isolated human colon CSCs in vitro and an azoxymethane-induced mouse model of colon carcinogenesis in vivo.", "RSV-GSE suppressed tumor incidence similar to sulindac, without any gastrointestinal toxicity. Additionally, RSV-GSE treatment reduced the number of crypts containing cells with nuclear β-catenin (an indicator of colon CSCs) via induction of apoptosis. In vitro, RSV-GSE suppressed - proliferation, sphere formation, nuclear translocation of β-catenin (a critical regulator of CSC proliferation) similar to sulindac in isolated human colon CSCs. RSV-GSE, but not sulindac, suppressed downstream protein levels of Wnt/β-catenin pathway, c-Myc and cyclin D1. RSV-GSE also induced mitochondrial-mediated apoptosis in colon CSCs characterized by elevated p53, Bax/Bcl-2 ratio and cleaved PARP. Furthermore, shRNA-mediated knockdown of p53, a tumor suppressor gene, in colon CSCs did not alter efficacy of RSV-GSE." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Animals", "Antineoplastic Agents, Phytogenic", "Apoptosis", "Cell Proliferation", "Colonic Neoplasms", "Disease Models, Animal", "Grape Seed Extract", "Male", "Mice", "Neoplastic Stem Cells", "Resveratrol", "Signal Transduction", "Stilbenes", "Vitis", "beta Catenin" ] }
The suppression of Wnt/β-catenin signaling and elevated mitochondrial-mediated apoptosis in colon CSCs support potential clinical testing/application of grape bioactives for colon cancer prevention and/or therapy.
yes
27,489,286
Is aDAM17 a Tumor Promoter and Therapeutic Target in Western Diet-associated Colon Cancer?
{ "contexts": [ "Epidermal growth factor receptors (EGFR) are required for tumor promotion by Western diet. The metalloprotease, ADAM17 activates EGFR by releasing pro-EGFR ligands. ADAM17 is regulated by G-protein-coupled receptors, including CXCR4. Here we investigated CXCR4-ADAM17 crosstalk and examined the role of ADAM17 in tumorigenesis.", "We used CXCR4 inhibitor, AMD3100 and ADAM17 inhibitor, BMS566394 to assess CXCR4-ADAM17 crosstalk in colon cancer cells. We compared the expression of CXCR4 ligand, CXCL2, and ADAM17 in mice fed Western diet versus standard diet. Separately, mice were treated with marimastat, a broad-spectrum ADAM17 inhibitor, or AMD3100 to assess EGFR activation by ADAM17 and CXCR4. Using Apc-mutant Min mice, we investigated the effects of ADAM17/10 inhibitor INCB3619 on tumorigenesis. To assess the effects of colonocyte ADAM17, mice with ADAM17 conditional deletion were treated with azoxymethane (AOM). ADAM17 expression was also compared in colonocytes from primary human colon cancers and adjacent mucosa.", "CXCL12 treatment activated colon cancer cell EGFR signals, and CXCR4 or ADAM17 blockade reduced this activation. In vivo, Western diet increased CXCL12 in stromal cells and TGFα in colonocytes. Marimastat or AMD3100 caused >50% reduction in EGFR signals (P < 0.05). In Min mice, INCB3619 reduced EGFR signals in adenomas and inhibited intestinal tumor multiplicity (P < 0.05). In the AOM model, colonocyte ADAM17 deletion reduced EGFR signals and colonic tumor development (P < 0.05). Finally, ADAM17 was upregulated >2.5-fold in human malignant colonocytes." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "ADAM17 Protein", "Animals", "Carcinogenesis", "Cell Line, Tumor", "Chemokine CXCL2", "Colonic Neoplasms", "Diet, Western", "ErbB Receptors", "Humans", "Ligands", "Mice", "Piperidines", "Receptors, CXCR4", "Signal Transduction", "Spiro Compounds", "Transforming Growth Factor alpha" ] }
ADAM17 is a Western diet-inducible enzyme activated by CXCL12-CXCR4 signaling, suggesting the pathway: Western diet→CXCL12→CXCR4→ADAM17→TGFα→EGFR. ADAM17 might serve as a druggable target in chemoprevention strategies. Clin Cancer Res; 1-13. ©2016 AACR.
yes
27,508,043
Does human papillomavirus infection correlate with inflammatory Stat3 signaling activity and IL-17 expression in patients with breast cancer?
{ "contexts": [ "Microbiota has been suggested in promoting chronic inflammation in human tissues which, in turn, promotes tumor development. This study tests a hypothesis that high-risk human papillomavirus (HR-HPV) infection may correlate with proinflammatory Stat3 signaling activities and IL-17 levels in breast cancer (BC) patients.", "This study examined HPV infection by GenChip technology, constitutively active Stat3 (p-Stat3) and IL-17 levels by immunohistochemistry (IHC) using specific antibodies in 379 BC patients, together with 245 paired adjacent breast adenosis (ABA) tissues and 100 unrelated breast adenosis (BA) tissues.", "We obtained four major findings: (1) HR-HPV16/18 infections existed in 10.5% (34/325) of BC issues, higher than control BA tissues (4%, 4/100, P = 0.047). (2) Using IHC methodology, BC tissues showed more overactive p-Stat3 (2+/3+, 38.5%, 146/379) than ABA tissues (27.3%, 67/245, P < 0.001); similarly, BC also had more tissues overexpressing IL-17 (2+/3+, 61.5%, 233/379) than ABA tissues (51.8%, 127/245, P < 0.001). (3) High levels (2+/3+) of both active p-Stat3 and IL-17 correlated with poor differentiation and lymph nodal metastasis in BC (both with P < 0.05), but not with patients' prognosis. (4) HR-HPV infections correlated with both active p-Stat3 (P = 0.018) and its downstream IL-17 levels (P = 0.021) in BC tissues." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [] }
There may be a possible tri-lateral relationship among HPV infection, constitutive Stat3 activity and IL-17 level, whose collaborations could orchestrate a proinflammatory microenvironment in breast tissues by which promote carcinogenesis and/or facilitate progression of breast cancer.
yes
27,519,926
Do manual Lymphatic Drainage and Active Exercise Effects on Lymphatic Function Translate Into Morbidities in Women Who Underwent Breast Cancer Surgery?
{ "contexts": [ "To evaluate manual lymphatic drainage (MLD) and active exercise effects on lymphatic alterations of the upper limb (UL), range of motion (ROM) of shoulder, and scar complications after breast cancer surgery.", "Clinical trial.", "Health care center.", "Women (N=105) undergoing radical breast cancer surgery who were matched for staging, age, and body mass index.", "Women (n=52) were submitted to MLD and 53 to active exercises for UL for 1 month and followed up.", "Shoulder ROM, surgical wound inspection and palpation, UL circumference measurements, and lymphoscintigraphy were performed in preoperative and postoperative periods.", "There was no significant difference between groups with regard to wound healing complications, ROM, and UL circumferences. After surgery, 25 (48.1%) of the MLD group and 19 (35.8%) of the active exercise group showed worsening in radiopharmaceutical uptake velocity, whereas 9 (17.3%) of the MLD group and 11 (20.8%) of the active exercise group showed improved velocity (P=.445). With regard to uptake intensity, 27 (51.9%) of the MLD group and 21 (39.6%) of the active exercise group showed worsening whereas 7 (13.5%) of the MLD group and 7 (13.2%) of the active exercise group showed some improvement (P=.391). The presence of collateral circulation was similar in both groups at both time points evaluated. The active exercise group had a significant increase in postoperative liver absorption (P=.005), and the MLD group had a significant increase in postoperative dermal backflow (P=.024)." ], "labels": [ "OBJECTIVE", "METHODS", "METHODS", "METHODS", "METHODS", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Breast Cancer Lymphedema", "Breast Neoplasms", "Exercise Therapy", "Female", "Humans", "Massage", "Mastectomy", "Middle Aged", "Physical Therapy Modalities", "Range of Motion, Articular", "Upper Extremity" ] }
MLD and active exercise effects are equivalent with regard to morbidity. Minor changes in lymphatic function associated with either MLD or active exercises were not related to patients' symptoms or signs.
no
27,498,128
Does iHC4 score plus clinical treatment score predict locoregional recurrence in early breast cancer?
{ "contexts": [ "Immunohistochemical 4 (IHC4) score plus Clinical Treatment Score (CTS) is an inexpensive tool predicting risk of distant recurrence in women with early breast cancer (EBC). IHC4 score is based on ER, PR, HER2 and Ki67 index. This study explores the role of the combined score (IHC4 + CTS) in predicting risk of locoregional recurrence (LRR) in women with EBC who had breast conservation surgery (BCS) without adjuvant radiotherapy (study group). The secondary objective was to evaluate the clinicopathological differences between our study group and women who had adjuvant radiation following BCS (control group).", "Patients were selected from the local database over a 13-year period. IHC testing was done where results were missing. Combined scores were calculated using the appropriate formulae.", "Patients in the study group (81 patients) had favorable clinicopathological features compared to the control group (1406 patients). The Cox regression indicated a statistically significant association between the combined score and the risk of LRR (p = 0.03). The incidence of LRR was zero, 20% and 33.3% in the low, intermediate and high risk groups respectively (p = 0.007). Margin status was the only variable not included in the combined score. The Cox regression analysis demonstrated that the combined score (p = 0.02) and the ordinal measure of margins (p = 0.03) were significant independent predictors of LRR." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Aged, 80 and over", "Australia", "Case-Control Studies", "Female", "Health Status Indicators", "Humans", "Immunohistochemistry", "Incidence", "Ki-67 Antigen", "Mastectomy, Segmental", "Middle Aged", "Neoplasm Invasiveness", "Neoplasm Recurrence, Local", "Predictive Value of Tests", "Prognosis", "Proportional Hazards Models", "Prospective Studies", "Radiotherapy, Adjuvant", "Receptor, ErbB-2", "Receptors, Estrogen", "Receptors, Progesterone", "Regression Analysis", "Risk Assessment", "Risk Factors", "Treatment Outcome", "Unilateral Breast Neoplasms" ] }
This is the first study of its kind. The IHC4 score + CTS can be used to identify low risk women who can potentially avoid adjuvant radiotherapy.
yes
27,506,777
Is the transposable element environment of human genes associated with histone and expression changes in cancer?
{ "contexts": [ "Only 2 % of the human genome code for proteins. Among the remaining 98 %, transposable elements (TEs) represent millions of sequences. TEs have an impact on genome evolution by promoting mutations. Especially, TEs possess their own regulatory sequences and can alter the expression pattern of neighboring genes. Since they can potentially be harmful, TE activity is regulated by epigenetic mechanisms. These mechanisms participate in the modulation of gene expression and can be associated with some human diseases resulting from gene expression deregulation. The fact that the TE silencing can be removed in cancer could explain a part of the changes in gene expression. Indeed, epigenetic modifications associated locally with TE sequences could impact neighboring genes since these modifications can spread to adjacent sequences.", "We compared the histone enrichment, TE neighborhood, and expression divergence of human genes between a normal and a cancer conditions. We show that the presence of TEs near genes is associated with greater changes in histone enrichment and that differentially expressed genes harbor larger histone enrichment variation related to the presence of particular TEs." ], "labels": [ "BACKGROUND", "RESULTS" ], "meshes": [ "Algorithms", "Cell Line, Tumor", "Cell Transformation, Neoplastic", "Chromatin Assembly and Disassembly", "Chromosome Mapping", "Chromosomes, Human", "Cluster Analysis", "Computational Biology", "DNA Transposable Elements", "Databases, Genetic", "Epigenesis, Genetic", "Gene Expression Regulation, Neoplastic", "Gene Ontology", "Genetic Variation", "Histones", "Humans", "Models, Statistical", "Neoplasms" ] }
Taken together, these results suggest that the presence of TEs near genes could favor important variation in gene expression when the cell environment is modified.
yes
27,501,501
Does the Urtica dioica extract enhance sensitivity of paclitaxel drug to MDA-MB-468 breast cancer cells?
{ "contexts": [ "Due to the chemo resistant nature of cancer cells and adverse effects of current therapies, researchers are looking for the most efficient therapeutic approach which has the lowest side effects and the highest toxicity on cancer cells. The aim of the present study was to investigate the synergic effect of Urtica dioica extract in combination with paclitaxel on cell death and invasion of human breast cancer MDA-MB-468 cell line.", "To determine the cytotoxic effects of Urtica dioica extract with paclitaxel, MTT assay was performed. The scratch test was exploited to assess the effects of Urtica dioica, Paclitaxel alone and combination on migration of cancer cells. The expression levels of snail-1, ZEB1, ZEB2, twist, Cdc2, cyclin B1 and Wee1 genes were quantified using qRT-PCR and western blot performed for snail-1expression. The effects of plant extract, Paclitaxel alone and combination on different phases of cell cycle was analyzed using flow cytometry.", "Results of MTT assay showed that Urtica dioica significantly destroyed cancer cells. Interestingly, Concurrent use of Urtica dioica extract with paclitaxel resulted in decreased IC50 dose of paclitaxel. Moreover, findings of scratch assay exhibited the inhibitory effects of Urtica dioica, Paclitaxel alone and combination on migration of MDA-MB-468 cell line. Our findings also demonstrated that the extract substantially decreased the Snail-1 and related gene expression. Ultimately, Cell cycle arrest occurred at G2/M phase post-treatment by deregulating Cdc2 and wee1." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Breast Neoplasms", "CDC2 Protein Kinase", "Cell Cycle Checkpoints", "Cell Cycle Proteins", "Cell Death", "Cell Line, Tumor", "Cell Movement", "Cyclin-Dependent Kinases", "Drug Synergism", "Gene Expression Regulation, Neoplastic", "Humans", "Inhibitory Concentration 50", "Nuclear Proteins", "Paclitaxel", "Plant Extracts", "Protein-Tyrosine Kinases", "RNA, Messenger", "Snail Family Transcription Factors", "Urtica dioica", "Wound Healing" ] }
Our results demonstrated that the dichloromethane extract of Urtica dioica inhibit cell growth and migration. Also, Urtica dioica extract substantially increased sensitivity of breast cancer cells to paclitaxel. Therefore, it can be used as a potential candidate for treatment of breast cancer with paclitaxel.
yes
27,497,986
Does a Blockade of IGF Signaling sensitize Human Ovarian Cancer Cells to the Anthelmintic Niclosamide-Induced Anti-Proliferative and Anticancer Activities?
{ "contexts": [ "Ovarian cancer is the most lethal gynecologic malignancy, and there is an unmet clinical need to develop new therapies. Although showing promising anticancer activity, Niclosamide may not be used as a monotherapy. We seek to investigate whether inhibiting IGF signaling potentiates Niclosamide's anticancer efficacy in human ovarian cancer cells.", "Cell proliferation and migration are assessed. Cell cycle progression and apoptosis are analyzed by flow cytometry. Inhibition of IGF signaling is accomplished by adenovirus-mediated expression of siRNAs targeting IGF-1R. Cancer-associated pathways are assessed using pathway-specific reporters. Subcutaneous xenograft model is used to determine anticancer activity.", "We find that Niclosamide is highly effective on inhibiting cell proliferation, cell migration, and cell cycle progression, and inducing apoptosis in human ovarian cancer cells, possibly by targeting multiple signaling pathways involved in ELK1/SRF, AP-1, MYC/MAX and NFkB. Silencing IGF-1R exert a similar but weaker effect than that of Niclosamide's. However, silencing IGF-1R significantly sensitizes ovarian cancer cells to Niclosamide-induced anti-proliferative and anticancer activities both in vitro and in vivo." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Animals", "Antineoplastic Agents", "Antineoplastic Combined Chemotherapy Protocols", "Antiparasitic Agents", "Apoptosis", "Basic Helix-Loop-Helix Leucine Zipper Transcription Factors", "Cell Cycle", "Cell Line, Tumor", "Cell Movement", "Cell Proliferation", "Drug Repositioning", "Female", "Gene Expression Regulation, Neoplastic", "HEK293 Cells", "Humans", "Insulin-Like Growth Factor I", "Mice", "NF-kappa B", "Niclosamide", "Ovarian Neoplasms", "RNA, Small Interfering", "Receptor, IGF Type 1", "Repressor Proteins", "Signal Transduction", "Transcription Factor AP-1", "Xenograft Model Antitumor Assays", "ets-Domain Protein Elk-1" ] }
Niclosamide as a repurposed anticancer agent may be more efficacious when combined with agents that target other signaling pathways such as IGF signaling in the treatment of human cancers including ovarian cancer.
yes
27,502,058
Do anthracycline-Associated T1 Mapping Characteristics Are Elevated Independent of the Presence of Cardiovascular Comorbidities in Cancer Survivors?
{ "contexts": [ "Cardiovascular magnetic resonance T1 mapping characteristics are elevated in adult cancer survivors; however, it remains unknown whether these elevations are related to age or presence of coincident cardiovascular comorbidities.", "We performed blinded cardiovascular magnetic resonance analyses of left ventricular T1 and extracellular volume (ECV) fraction in 327 individuals (65% women, aged 64±12 years). Thirty-seven individuals had breast cancer or a hematologic malignancy but had not yet initiated their treatment, and 54 cancer survivors who received either anthracycline-based (n=37) or nonanthracycline-based (n=17) chemotherapy 2.8±1.3 years earlier were compared with 236 cancer-free participants. Multivariable analyses were performed to determine the association between T1/ECV measures and variables associated with myocardial fibrosis. Age-adjusted native T1 was elevated pre- (1058±7 ms) and post- (1040±7 ms) receipt of anthracycline chemotherapy versus comparators (965±3 ms; P<0.0001 for both). Age-adjusted ECV, a marker of myocardial fibrosis, was elevated in anthracycline-treated cancer participants (30.4±0.7%) compared with either pretreatment cancer (27.8±0.7%; P<0.01) or cancer-free comparators (26.9±0.2%; P<0.0001). T1 and ECV of nonanthracycline survivors were no different than pretreatment survivors (P=0.17 and P=0.16, respectively). Native T1 and ECV remained elevated in cancer survivors after accounting for demographics (including age), myocardial fibrosis risk factors, and left ventricular ejection fraction or myocardial mass index (P<0.0001 for all)." ], "labels": [ "BACKGROUND", "RESULTS" ], "meshes": [ "Aged", "Anthracyclines", "Antineoplastic Agents", "Cardiomyopathies", "Cardiotoxicity", "Comorbidity", "Cross-Sectional Studies", "Edema, Cardiac", "Female", "Fibrosis", "Humans", "Least-Squares Analysis", "Magnetic Resonance Imaging, Cine", "Male", "Middle Aged", "Multivariate Analysis", "Myocardium", "Predictive Value of Tests", "Prognosis", "Risk Factors", "Stroke Volume", "Survivors", "Time Factors", "United States", "Ventricular Function, Left" ] }
Three years after anthracycline-based chemotherapy, elevations in myocardial T1 and ECV occur independent of underlying cancer or cardiovascular comorbidities, suggesting that imaging biomarkers of interstitial fibrosis in cancer survivors are related to prior receipt of a potentially cardiotoxic cancer treatment regimen.
yes
27,507,635
Is palliative homecare associated with reduced high- and low-acuity emergency department visits at the end of life : A population-based cohort study of cancer decedents?
{ "contexts": [ "Prior work shows that palliative homecare services reduce the subsequent need for hospitalizations and emergency services; however, no study has investigated whether this association is present for emergency department visits of high acuity or whether it only applies to low-acuity emergency department visits.", "To examine the association between palliative versus standard homecare nursing and the rate of high-acuity and low-acuity emergency department visits among cancer decedents during their last 6 months of life.", "This is a retrospective cohort study of end-of-life homecare patients in Ontario, Canada, who had confirmed cancer cause of death from 2004 to 2009. A multivariable Poisson regression analysis was implemented to examine the association between the receipt of palliative homecare nursing (vs standard homecare nursing) and the rate of high- and low-acuity emergency department visits, separately.", "There were 54,743 decedents who received homecare nursing in the last 6 months of life. The receipt of palliative homecare nursing decreased the rate of low-acuity emergency department visits (relative rate = 0.53, 95% confidence interval = 0.50-0.56) and was significantly associated with a larger decrease in the rate of high-acuity emergency department visits (relative rate = 0.37, 95% confidence interval = 0.35-0.38)." ], "labels": [ "BACKGROUND", "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Aged, 80 and over", "Cohort Studies", "Emergency Service, Hospital", "Female", "Home Care Services", "Hospitalization", "Humans", "Male", "Middle Aged", "Neoplasms", "Ontario", "Palliative Care", "Regression Analysis", "Retrospective Studies", "Terminal Care" ] }
Receiving homecare nursing with palliative intent may decrease the need for dying cancer patients to visit the emergency department, for both high and low-acuity visits, compared to receiving general homecare nursing. Policy implications include building support for additional training in palliative care to generalist homecare nurses and increasing access to palliative homecare nursing.
yes
27,520,310
Is dCLK1 up-regulated and associated with metastasis and prognosis in colorectal cancer?
{ "contexts": [ "Metastasis is a primary cause of colorectal cancer (CRC)-related death, and cancer stem cells (CSCs) are thought to be majorly responsible for initiating metastatic behaviors. Doublecortin-like kinase 1 (DCLK1) was recently discovered to be a marker for gastrointestinal CSCs. Here, we aimed to explore whether DCLK1 is associated with CRC metastasis through clinical and in vitro investigations.", "The expression levels of DCLK1 mRNA and protein in human CRC tissues were analyzed through quantitative RT-PCR and immunohistochemistry staining, respectively. Human CRC cell line SW480 was selected to explore the effect of DCLK1 overexpression on cell migration and invasion. Besides, the associations between DCLK1 and epithelial-mesenchymal transition (EMT) were determined.", "Compared to normal colorectal tissues, DCLK1 expression was significantly up-regulated in human CRC tissues and correlated well with high lymphatic metastasis and poor prognosis in patients. DCLK1 expression was inversely associated with overall survival in CRC patients. Overexpression of DCLK1 in SW480 cells markedly promoted cell migration and invasion. Furthermore, we validated that DCLK1 could facilitate EMT in cancer cells by up-regulation of the mesenchymal markers Vimentin and ZEB1 and down-regulation of the epithelial marker E-cadherin in SW480 cells." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Biomarkers, Tumor", "Case-Control Studies", "Cell Line, Tumor", "Colorectal Neoplasms", "Epithelial-Mesenchymal Transition", "Female", "Humans", "Immunohistochemistry", "Intracellular Signaling Peptides and Proteins", "Male", "Middle Aged", "Neoplasm Metastasis", "Paraffin Embedding", "Prognosis", "Protein-Serine-Threonine Kinases", "RNA, Messenger", "Up-Regulation" ] }
DCLK1 up-regulation may play a contributory role in CRC metastasis and poor prognosis via activation of EMT. DCLK1 may serve as an independent predictor for CRC prognosis.
yes
27,514,530
Does over-expression of long noncoding RNA BANCR inhibit malignant phenotypes of human bladder cancer?
{ "contexts": [ "Accumulating evidences indicated that lncRNAs play crucial regulatory roles in oncogenesis and progression of cancers. BRAF activated non-coding RNA (BANCR) has been identified to contribute to the progression of some human cancers. However, the relationship between BANCR and bladder cancer (BC) is largely unclear.", "BANCR expression levels in BC, paired non-cancer tissues and BC cell lines were detected by real-time quantitative RT-PCR (qRT-PCR). The relationships between BANCR expression levels and the clinical characteristics were evaluated. BANCR expression was enhanced by transfecting a pcDNA-BANCR vector. We used both CCK-8 assay and Edu assay to detect cell proliferation. We also detect cell apoptosis and migration by using ELISA assay, Flow cytometry and transwell assay, respectively. All statistical analyses were executed by using the SPSS 20.0 software.", "BANCR expression levels were remarkably decreased in BC tissues compared with adjacent noncancerous tissues. BANCR expression levels in two BC cell lines were also significantly down-regulated. Clinicopathologic analysis revealed that low BANCR expression was positively correlated with TNM stage, but not associated with other clinicopathological characteristics. BANCR has been successfully overexpressed in BC cell lines (T24 and SW780) by transfecting a pcDNA-BANCR vector. Cell proliferation inhibition, apoptosis induction and migration suppression were also observed in pCDNA-BANCR-transfected T24 and SW780 cells." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Apoptosis", "Carcinoma, Transitional Cell", "Cell Line, Tumor", "Cell Movement", "Cell Proliferation", "Down-Regulation", "Female", "Gene Expression Regulation, Neoplastic", "Humans", "Male", "Neoplasm Staging", "RNA, Long Noncoding", "Urinary Bladder Neoplasms" ] }
These data suggested that BANCR represents a tumor suppressor player in bladder cancer, contributes to tumor proliferation, apoptosis and migration, and may serve as a new candidate biomarker and a potential therapeutic target for patients with BC.
yes
27,493,875
Does salidroside alleviate cachexia symptoms in mouse models of cancer cachexia via activating mTOR signalling?
{ "contexts": [ "Cachexia has a devastating impact on survival and quality of life for many cancer patients and contributes to nearly one-third of all cancer deaths; also, it is associated with poor responses to chemotherapy and survival. A better understanding of the underlying mechanisms of cancer-associated cachexia (CAC), coupled with effective therapeutic approaches, will improve management of progressive functional impairment in cancer patients. Salidroside, a phenylpropanoid glycoside in Rhodiola rosea L, has been reported to possess potential anti-fatigue, anti-ageing, and anti-Alzheimer's disease properties. It is widely consumed as a nutritional supplement, but its effects on CAC and the possible mechanism remain a mystery.", "In the murine models of cachexia induced by CT-26 and Lewis lung carcinoma (LLC) tumour, respectively, main features of CAC were determined after treatment of salidroside or chemotherapy. In vitro experiments were performed using murine C2C12 myotubes, which were treated by tumour necrosis factor-α. Levels of several critical muscle-related signal proteins such as mammalian target of rapamycin (mTOR), p-mTOR, and myosin heavy chain (MyHC) were examined using western blot both in vitro and in vivo.", "In the present study, we showed the exciting effect of salidroside on the treatment of CAC. In CT-26 and LLC models, respectively, salidroside treatment could effectively preserve the tumour-free body weight, decrease loss of adipose and gastrocnemius muscles, alleviate tumour burden, and prolong their survival time. Additionally, in combined chemotherapy, salidroside could synergistically enhance the anti-tumour activity of cisplatin, especially decreased or eliminated chemotherapy-induced cachexia. Further analysis demonstrated that salidroside could significantly increase expression of mTOR, p-mTOR, and MyHC in gastrocnemius muscle. Also, results in vitro showed that salidroside could not only obviously increase mTOR, p-mTOR, and MyHC expression in C2C12 myotubes but also effectively rescue their down-regulation induced by tumour necrosis factor-α." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [] }
In the current study, the exciting effect of salidroside on CAC suggested that salidroside supplementation might be a promising approach for a multi-targeted therapy for the treatment of CAC.
yes
27,494,037
Is methadone superior to fentanyl in treating neuropathic pain in patients with head-and-neck cancer?
{ "contexts": [ "Cancer pain is still inadequately treated in up to 60% of cancer patients. Based on the additional effect on the N-Methyl-d-Aspartate receptor, we expected that methadone (Met) could provide better pain relief than fentanyl (Fen) in cancer pain with a neuropathic pain component.", "A randomised controlled trial was performed with 52 strong opioids naive patients with head-and-neck cancer with substantial pain (pain Numerical Rating Scale [NRS] > 4) and a neuropathic pain component (Douleur Neuropathique [DN4] > 4). Twenty-six patients were treated with Met and 26 with Fen. Patients were evaluated at 1, 3 and 5 weeks. The primary outcomes were reduction in average pain, clinical success (defined as 50% average pain decrease) and reduction in pain interference. Secondary outcomes were global perceived effect (GPE) and side-effects.", "Reduction in NRS was higher with the use of Met at 1, 3 and 5 weeks (pain change 2.9, 3.1 and 3.1) compared to Fen (1.4, 1.7 and 2.0). This difference was significant at 1 (p = 0.011) and at 3 weeks (p = 0.03). Clinical success (>50% improvement) was higher with Met at 1 week (15% versus 50%, p = 0.012). The change in pain interference, the GPE and side-effect profile were not significantly different between the groups." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Analgesics, Opioid", "Cancer Pain", "Female", "Fentanyl", "Head and Neck Neoplasms", "Humans", "Male", "Methadone", "Middle Aged", "Neuralgia", "Pain Measurement", "Patient Satisfaction", "Prospective Studies", "Quality of Life" ] }
This is the first study to compare the effects of Met to Fen in cancer patients with a neuropathic pain component. Based on the results of this study, Met should be considered in the treatment of oncological pain with a neuropathic component.
yes
27,493,271
Does tERT promoter mutation predict radioiodine refractory in distant metastatic differentiated thyroid cancer?
{ "contexts": [ "Telomerase Reverse Transcriptase (TERT) promoter mutation has been reported to be associated with aggressive characteristics in differentiated thyroid cancer (DTC). This study examined the status of TERT promoter mutation in distant metastatic DTC (DM-DTC), and evaluated the correlation between TERT mutation and radioactive iodine-131(RAI) uptake, as well as that between TERT mutation and therapy response.", "TERT promoter and B-Raf proto-oncogene (BRAF) V600E mutation were retrospectively examined in primary tumors of 66 DM-DTC patients. Stimulated thyroglobulin (sTg) changes, RAI uptake status (avid or non-avid), and other imaging evidence were analyzed to evaluate therapy response. After a median follow-up of 46.5 months (interquartile range, 29.0 to 70.5 months), therapy response was classified as disease control and refractory.", "The prevalence of TERT mutations was 22.73% (15/66), of which C228T mutation was more prevalent (13/15) than C250T mutation (2/15). Rising sTg was noticed in 93.33% (14/15) of TERT mutation group. While in cases with both mutations negative, 78.12 % (25/32) presented with decreased sTg. TERT mutation closely correlated with poor RAI therapy response (p<0.001), and all 15 patients were classified as refractory to RAI with a positive predictive value of 100% at the end point of follow-up. TERT mutation was associated with older mean age at diagnosis (p<0.001), larger mean tumor diameter (P = 0.013), and more likelihood of both BRAF mutation coexistence (P = 0.044) and refractory to RAI (p<0.001). In the 36 cases received imaging semi-quantitative analysis, it was found that TERT mutation significantly correlated with non-RAI-avidity, with a much lower mean tumor/background (T/B) ratio (obtained from post RAI therapy whole-body scanning) than TERT wild-type (p<0.001). And DM-DTC patients with TERT mutation were more likely to lose RAI-avidity at initial RAI therapy than those with only BRAF mutation (8/8 vs 5/11, Fisher's exact test, P = 0.018)." ], "labels": [ "UNASSIGNED", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Biomarkers, Tumor", "Carcinoma", "China", "Female", "Genetic Markers", "Genetic Predisposition to Disease", "Humans", "Iodine Radioisotopes", "Male", "Middle Aged", "Neoplasm Metastasis", "Prevalence", "Promoter Regions, Genetic", "Radiation Tolerance", "Retrospective Studies", "Telomerase", "Thyroid Neoplasms", "Treatment Failure", "Treatment Outcome" ] }
TERT promoter mutation closely associates with non-RAI-avidity in DM-DTC, and when comparing with BRAF mutation, TERT mutation manifested a worse negative influence on RAI uptake. It could also be used as a predictive marker to early identify refractory to RAI.
yes
27,514,407
Does transcription Factor KLF5 bound a Cyclin E1 Polymorphic Intronic Enhancer to Confer Increased Bladder Cancer Risk?
{ "contexts": [ "It is well established that environmental toxins, such as exposure to arsenic, are risk factors in the development of urinary bladder cancer, yet recent genome-wide association studies (GWAS) provide compelling evidence that there is a strong genetic component associated with disease predisposition. A single-nucleotide polymorphism (SNP), rs8102137, was identified on chromosome 19q12, residing 6 kb upstream of the important cell-cycle regulator and proto-oncogene, Cyclin E1 (CCNE1). However, the functional role of this variant in bladder cancer predisposition has been unclear because it lies within a non-coding region of the genome. Here, it is demonstrated that bladder cancer cells heterozygous for this SNP exhibit biased allelic expression of CCNE1 with 1.5-fold more transcription occurring from the risk allele. Furthermore, using chromatin immunoprecipitation assays, a novel enhancer element was identified within the first intron of CCNE1 that binds Kruppel-like Factor 5 (KLF5), a known transcriptional activator in bladder cancer. Moreover, the data reveal that the presence of rs200996365, a SNP in high-linkage disequilibrium with rs8102137 residing in the center of a KLF5 motif, alters KLF5 binding to this genomic region. Through luciferase assays and CRISPR-Cas9 genome editing, a novel polymorphic intronic regulatory element controlling CCNE1 transcription is characterized. These studies uncover how a cancer-associated polymorphism mechanistically contributes to an increased predisposition for bladder cancer development." ], "labels": [ "UNASSIGNED" ], "meshes": [ "Cell Line, Tumor", "Cyclin E", "Enhancer Elements, Genetic", "Gene Expression Regulation, Neoplastic", "Genetic Predisposition to Disease", "Genome-Wide Association Study", "Humans", "Kruppel-Like Transcription Factors", "Oncogene Proteins", "Polymorphism, Single Nucleotide", "Urinary Bladder Neoplasms" ] }
A polymorphic KLF5 binding site near the CCNE1 gene explains genetic risk identified through GWAS. Mol Cancer Res; 14(11); 1078-86. ©2016 AACR.
yes
27,505,202
Are self-reported and automatic cognitions associated with exercise behavior in cancer survivors?
{ "contexts": [ "Physical activity is beneficial for cancer survivors, but exercise participation is low in this population. It is therefore important to understand the psychological factors underlying exercise uptake so that more effective interventions can be developed. Social-cognitive theory constructs such as outcome expectancies predict exercise behavior, but self-report measures have several limitations. We examined the associations between implicit (automatic) cognitions and exercise behavior and self-efficacy in endometrial cancer survivors.", "This was a longitudinal study to examine predictors of exercise behavior in female endometrial cancer survivors who all received an exercise intervention. Participants (N = 100, mean age of 57.0) completed questionnaires to assess self-report exercise-related measures (outcome expectancy and attitudes about and identification with exercise) and reaction time (RT) tasks to assess implicit exercise cognitions (expectancy accessibility, implicit attitudes about exercise, and implicit self-identification with exercise) at baseline and at 2, 4, and 6 months at follow-up. Exercise behavior was measured using accelerometers and self-report. Data were analyzed using linear mixed models.", "Expectancy accessibility was associated with exercise duration independent of the corresponding self-report measure. Exercise implicit attitudes and self-identification were prospectively associated with exercise self-efficacy only after adjustment for the corresponding self-report measures and baseline self-efficacy. Self-report measures were also associated with study outcomes." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Culture", "Endometrial Neoplasms", "Exercise", "Female", "Home Care Services", "Humans", "Longitudinal Studies", "Middle Aged", "Neoplasm Staging", "Reaction Time", "Self Efficacy", "Self Report", "Survivors" ] }
Both self-reported cognitions and implicit cognitions may be useful to identify individuals at risk of failing to exercise. Individuals so identified might be provided with a different or more intensive intervention. The data also suggest cognitive targets for intervention. (PsycINFO Database Record
yes
27,498,289
Is overexpression of β-Catenin and Cyclin D1 Associated with Poor Overall Survival in Patients with Stage IA-IIA Squamous Cell Lung Cancer Irrespective of Adjuvant Chemotherapy?
{ "contexts": [ "This study was aimed at understanding the effect of β-catenin and cyclin D1 on overall survival in patients with early-stage NSCLC and at evaluating if the prognostic effect can be modified by adjuvant chemotherapy.", "We retrospectively analyzed the expression of β-catenin and cyclin D1 using immunohistochemistry in formalin-fixed paraffin-embedded tissues from 576 patients with early-stage NSCLC.", "The median duration of follow-up was 5.1 years. Overexpression of β-catenin and cyclin D1 was found in 56% and 50% of 576 cases, respectively. Overexpression of β-catenin and cyclin D1 was significantly associated with poor overall survival (p = 0.003 and p = 0.0009, respectively; log rank test) in squamous cell carcinomas, not in adenocarcinomas. The prognostic significance of each protein in the squamous cell carcinomas was limited to stages IA, IB, and IIA. In addition, simultaneous overexpression of β-catenin and cyclin D1 in the squamous cell carcinomas synergistically increased hazard ratios (HRs) 15.79 (95% confidence interval [CI] = 1.09-51.23; p =0.04) for stage IA, 10.30 (95% CI = 2.29-46.41; p = 0.002) for stage 1B, and 3.55 (95% CI = 1.22-10.36; p = 0.02) times for stage 2A compared to those without overexpression of the two proteins, after adjusting for confounding factors. In addition, the effect was not dependent on adjuvant chemotherapy." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Biomarkers, Tumor", "Carcinoma, Non-Small-Cell Lung", "Carcinoma, Squamous Cell", "Chemotherapy, Adjuvant", "Cyclin D1", "Female", "Humans", "Immunohistochemistry", "Male", "Middle Aged", "Neoplasm Staging", "Retrospective Studies", "Survival Rate", "beta Catenin" ] }
The present study suggests that simultaneous overexpression of β-catenin and cyclin D1 may be associated with poor overall survival irrespective of platinum-based adjuvant chemotherapy in stage IA-IIA squamous cell carcinoma of the lung.
yes
27,505,036
Does race predict the development of metastases in men with nonmetastatic castration-resistant prostate cancer?
{ "contexts": [ "Although race is associated with prostate cancer progression in early stage disease, once men have advanced disease, it is unclear whether race continues to predict a poor outcome. The authors hypothesized that, in an equal-access setting among patients with castration-resistant prostate cancer (CRPC) and no known metastases (M0/Mx), black men would receive imaging tests at similar rates as nonblack men (ie, there would be an equal opportunity to detect metastases) but would have a higher risk of metastatic disease.", "In total, 837 men who were diagnosed with M0/Mx CRPC during 2000 through 2014 from 5 Veterans Affairs hospitals in the SEARCH (Shared Equal Access Regional Cancer Hospital) database were analyzed. Data on all imaging tests after CRPC diagnosis were collected, including date, type, and outcome. Multivariable Cox models were used to test associations between race and the time to first metastasis, first bone metastasis, first bone scan, second bone scan among men who had a negative first bone scan, and overall survival.", "Black men (n = 306) were equally as likely as nonblack men (n = 531) to receive a first and second bone scan after a diagnosis of CRPC. There were no significant differences in the risk of developing any metastases, bone metastases, time to bone scans, or overall survival between black men and nonblack men (all P > .2)." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Aged", "Aged, 80 and over", "Bone Neoplasms", "Bone and Bones", "Continental Population Groups", "Disease Progression", "Humans", "Male", "Proportional Hazards Models", "Prostate", "Prostatic Neoplasms, Castration-Resistant" ] }
The lack of racial differences in the development of metastases and scanning practices observed in this study suggests that, once men have a diagnosis of M0/Mx CRPC, race may not be a prognostic factor. Efforts to understand prostate cancer racial disparities may derive greater benefit by focusing on the risk of developing prostate cancer and on the outcomes of men who have early stage disease. Cancer 2016;122:3848-3855. © 2016 American Cancer Society.
no
27,506,669
Is pretreatment quality-of-life score a better discriminator of oesophageal cancer survival than performance status?
{ "contexts": [ "Performance status [Eastern Cooperative Oncology Group (ECOG)] is a physician-assigned score indicating a patient's fitness for treatment. Functional assessment of cancer therapy-esophagus (FACT-E) is a patient-reported, health-related quality-of-life (HRQOL) instrument containing an oesophageal cancer subscale (ECS). Our objective was to assess the discriminative ability of pretreatment FACT-E and ECS when compared with performance status in predicting survival in patients with Stage II-III oesophageal cancer.", "Patient data from four prospective studies were pooled together. These four studies included oesophageal patients who received chemoradiation either as neoadjuvant therapy or as definitive therapy. Three separate Cox regressions were performed considering FACT-E, ECS and ECOG as the main predictors, respectively. Receiver-operating characteristics analyses were performed.", "Of the 120 curative intent patients, 39.8% (n = 51), 58.6% (n = 75) and 1.6% (n = 2) had ECOG 0, 1 and 2, respectively. On Cox regression analysis, pretreatment FACT-E (P = 0.04) and ECS (P = 0.004) but not ECOG (P = 0.27) were independently associated with overall survival. ECOG could not discriminate between survivors and non-survivors (P = 0.28) with an area under the curve (AUC) of 0.56 [95% confidence interval (CI): 0.45-0.66], whereas FACT-E (P = 0.02) and ECS (P < 0.001) were discriminative with AUC = 0.63 (95% CI: 0.52-0.73) and AUC = 0.69 (95% CI: 0.60-0.79), respectively." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Activities of Daily Living", "Adenocarcinoma", "Chemoradiotherapy", "Combined Modality Therapy", "Esophageal Neoplasms", "Humans", "Middle Aged", "Neoplasm Staging", "Proportional Hazards Models", "Prospective Studies", "Quality of Life", "ROC Curve", "Treatment Outcome" ] }
In patients with Stage II-III oesophageal cancer being considered for curative therapy, pretreatment FACT-E and ECS have better discrimination for survival than does ECOG. The majority of patients were ECOG 0/1. Thus, these patient-derived scores were able to discriminate survivors from non-survivors even within this constrained range of clinician-assigned performance status. This highlights the potential utility of FACT-E and ECS as prognostic tools.
yes
27,495,815
Is survival associated with complete response on MRI after neoadjuvant chemotherapy in ER-positive HER2-negative breast cancer?
{ "contexts": [ "Pathological complete remission (pCR) of estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer is rarely achieved after neoadjuvant chemotherapy (NAC). In addition, the prognostic value of pCR for this breast cancer subtype is limited. We explored whether response evaluation by magnetic resonance imaging (MRI) is associated with recurrence-free survival after NAC in ER-positive/HER2-negative breast cancer.", "MRI examinations were performed in 272 women with ER-positive/HER2-negative breast cancer before, during and after NAC. MRI interpretation included lesion morphology at baseline, changes in morphology and size, and contrast uptake kinetics. These MRI features, clinical characteristics and final pathology were correlated with recurrence-free survival.", "The median follow up time was 41 months. There were 35 women with events, including 19 breast-cancer-related deaths. On multivariable analysis, age younger than 50 years (hazard ratio (HR) = 2.55, 95 % confidence interval (CI) 1.3, 5.02, p = 0.007), radiological complete response after NAC (HR = 14.11, CI 1.81, 1818; p = 0.006) and smaller diameters of washout/plateau enhancement at MRI after NAC (HR = 1.02, CI 1.00, 1.04, p = 0.036) were independently associated with best recurrence-free survival. Pathological response was not significant; HR = 2.12, CI 0.86, 4.64, p = 0.096." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Antineoplastic Combined Chemotherapy Protocols", "Breast Neoplasms", "Carcinoma, Ductal, Breast", "Chemotherapy, Adjuvant", "Disease-Free Survival", "Female", "Humans", "Kaplan-Meier Estimate", "Magnetic Resonance Imaging", "Middle Aged", "Multivariate Analysis", "Neoadjuvant Therapy", "Proportional Hazards Models", "Receptor, ErbB-2", "Receptors, Estrogen", "Treatment Outcome", "Young Adult" ] }
MRI after NAC in ER-positive/HER2-negative tumors may be predictive of recurrence-free survival. A radiological complete response at MRI after NAC is associated with an excellent prognosis.
yes
27,495,988
Does next-generation sequencing survey of biliary tract cancer reveal the association between tumor somatic variants and chemotherapy resistance?
{ "contexts": [ "Biliary tract cancers (BTCs) are uncommon and are associated with a dismal prognosis. Combinations of gemcitabine and platinum chemotherapy (gemcitabine and platinum-based therapy [GP]) form the standard approach for treating advanced BTC. To characterize the spectrum of mutations and to identify potential biomarkers for a GP response in BTC, this study evaluated the genomic landscape and assessed whether mutations affecting DNA repair were associated with GP resistance.", "Pretreatment, formalin-fixed, paraffin-embedded samples from 183 BTC patients treated with GP were analyzed. Cox regression models were used to determine the association between mutations, progression-free survival (PFS), and overall survival (OS).", "When genes with an incidence > 10% were considered, no individual gene was independently predictive of a GP response. In patients with unresectable BTC who received GP as their first-line therapy, the joint status of cyclin-dependent kinase inhibitor 2A (CDKN2A), tumor protein 53 (TP53), and AT-rich interaction domain 1A (ARID1A) was associated with PFS (P = .0004) and OS (P ≤ .0001). Patients with mutations in CDKN2A and TP53 were identified as a poor-prognosis cohort with a median PFS of 2.63 months and a median OS of 5.22 months. Patients with mutant ARID1A, regardless of the single-mutation status of TP53 or CDKN2A, had similar outcomes. A patient who exhibited mutations in all 3 genes had a median PFS of 20.37 months, and OS was not reached." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Aged, 80 and over", "Antineoplastic Combined Chemotherapy Protocols", "Biliary Tract Neoplasms", "Cyclin-Dependent Kinases", "Deoxycytidine", "Disease-Free Survival", "Drug Resistance, Neoplasm", "Female", "Humans", "Male", "Middle Aged", "Mutation", "Organoplatinum Compounds", "Prognosis", "Surveys and Questionnaires", "Treatment Outcome", "Young Adult" ] }
In the largest exploratory analysis of this kind for BTC, 3 prevalent, mutually exclusive mutations represent distinct patient cohorts. These mutations are prognostic and may represent a predictive biomarker for a GP response. Prospective studies to validate these findings are needed, and they should include the incorporation of therapies that exploit the genomic instability observed with these mutations in BTC. Cancer 2016;122:3657-66. © 2016 American Cancer Society.
yes
27,507,052
Does long non-coding RNA ANRIL promote the invasion and metastasis of thyroid cancer cells through TGF-β/Smad signaling pathway?
{ "contexts": [ "To investigate the effect of antisense non-coding RNA in the INK4 locus (ANRIL) on invasion and metastasis of thyroid cancer (TC).", "ANRIL expression was significantly up-regulated in TC tissues and cells (P < 0.001), and ANRIL expression was significantly different regarding histological grade and LNM (both P < 0.01). The siRNA-mediated ANRIL silencing inhibits proliferation, invasion, and metastasis of TPC-1 and SW579 cells, and lung metastasis, which can be reversed by TGF-β1 siRNA. The mRNA levels of p15INK4b, p14ARF and p16INK4a in TPC-1 and SW579 cells increased significantly after silencing ANRIL (all P < 0.001), and TGF-β1 siRNA could reverse the ANRIL siRNA induced increase of p15INK4b; expressions of TGF-β1 and p-Smad2/3 were increased after silencing ANRIL (both P < 0.05).", "TC and adjacent normal tissues were collected from 105 TC patients. LncRNA ANRIL expressions were detected by qRT-PCR. The siRNA ANRIL and siRNA TGF-β1 were constructed for TPC-1 and SW579 cell line transfection: si-ANRIL group, si-TGF-β1 group, si-ANRIL + si-TGF-β1 group, negative control group and blank group. Effects of ANRIL silencing on proliferation, invasion and metastasis of TC cells was detected by MTT assay, Transwell assay and tail vein injection of nude mice in vitro and in vivo. TGF-β1 and p-Smad2/3 expressions in TGF-β/Smad signaling pathway were detected by western blot." ], "labels": [ "OBJECTIVE", "RESULTS", "METHODS" ], "meshes": [ "Adult", "Aged", "Aged, 80 and over", "Cell Line, Tumor", "Cyclin-Dependent Kinase Inhibitor p15", "Female", "Gene Silencing", "Humans", "Male", "Middle Aged", "Neoplasm Invasiveness", "Neoplasm Metastasis", "RNA, Long Noncoding", "RNA, Small Interfering", "Signal Transduction", "Thyroid Neoplasms", "Transforming Growth Factor beta1" ] }
ANRIL may reduce p15INK4B expression through inhibiting TGF-β/Smad signaling pathway, promoting invasion and metastasis of TC cells, and the silencing of ANRIL inhibits the invasion and metastasis of TPC-1 cells.
yes
27,510,332
Is intensity-Modulated Radiation Therapy Associated with Perioperative or Survival Benefit over 3D-Conformal Radiotherapy for Rectal Cancer?
{ "contexts": [ "The use of intensity-modulated radiation therapy (IMRT) in rectal cancer has steadily increased over traditional 3D conformal radiotherapy (3D-CRT) due to perceived benefit of delivering higher treatment doses while minimizing exposure to surrounding tissues. However, IMRT is technically challenging and costly, and its effects on rectal cancer outcomes remain unclear.", "Adults with clinical stage II and III rectal adenocarcinoma who underwent neoadjuvant chemoradiotherapy with 45-54 Gy of radiation and surgery were included from the 2006-2013 National Cancer Data Base. Patients were grouped based the modality of radiation received: IMRT or 3D-CRT. Multivariable regression modeling adjusting for demographic, clinical, and treatment characteristics was used to examine the impact of IMRT vs. 3D-CRT on pathologic downstaging, resection margin positivity, sphincter loss surgery, 30-day unplanned readmission and mortality after surgery, and overall survival.", "Among 7386 patients included, 3330 (45 %) received IMRT and 4056 (55 %) received 3D-CRT. While the mean radiation dose delivered was higher with IMRT (4735 vs. 4608 cGy, p < 0.001), it was associated with higher risks of positive margins (adjusted odds ratio (OR) 1.57; p < 0.001) and sphincter loss surgery (OR 1.32; p < 0.001). There were no differences between IMRT and 3D-CRT in the likelihood of pathologic downstaging (OR 0.89, p = 0.051), unplanned readmission (OR 0.79; p = 0.07), or 30-day mortality (OR 0.61; p = 0.31) after surgery. Additionally, there were no differences in overall survival at 8 years (IMRT vs. 3D-CRT: 64 vs. 64 %; adjusted hazard ratio 1.06, p = 0.47)." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Adenocarcinoma", "Chemoradiotherapy", "Female", "Humans", "Male", "Middle Aged", "Neoadjuvant Therapy", "Neoplasm Staging", "Patient Readmission", "Proportional Hazards Models", "Radiotherapy Dosage", "Radiotherapy, Conformal", "Radiotherapy, Intensity-Modulated", "Rectal Neoplasms" ] }
IMRT is associated with worse local tumor control without any long-term survival benefit for patients with locally advanced rectal cancer. Given the lack of significant advantage and the higher cost of IMRT, caution should be exercised when using IMRT instead of traditional 3D-CRT for rectal cancer.
no
27,491,499
Is renal assessment using CKD-EPI equation useful as an early predictor of contrast- induced nephropathy in elderly patients with cancer?
{ "contexts": [ "To assess respective roles of serum creatinine (SCr) alone and estimated glomerular filtration rate (eGFR) as an early predictor for contrast-induced nephropathy (CIN) in elderly patients with cancer.", "eGFR of 348 patients at 65years or older with malignancy who underwent contrast-enhanced computed tomography (CECT) were calculated. eGFR was calculated based on the following three equations: Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI); Modification of Diet in Renal Disease Study (MDRD); Cockcroft-Gault (CG). CIN was subdivided into two groups: CIN", "After CECT, CIN occurred in 50 (14.4%) patients, including 33 CIN" ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Acute Kidney Injury", "Aged", "Algorithms", "Contrast Media", "Creatinine", "Female", "Glomerular Filtration Rate", "Hospital Mortality", "Humans", "Length of Stay", "Logistic Models", "Male", "Neoplasms", "Prognosis", "Proportional Hazards Models", "Tomography, X-Ray Computed" ] }
In elderly patients with cancer who visit the emergency department, renal assessment before CECT using CKD-EPI equation was superior to SCr alone, MDRD equation, or CG formula in predicting the occurrence of CIN related CECT.
yes
27,509,986
Do cancer Patients Are at High Risk of Mortality if Presenting with Sepsis at an Emergency Department?
{ "contexts": [ "Sepsis is an emergency condition with high mortality and morbidity rate. There are limited data on the association of cancer as a risk factor for mortality in sepsis patients in the emergency department (ED).", "This retrospective study was conducted at the ED, Faculty of Medicine, Ramathibodi Hospital, Bangkok, Thailand. The study period was between January 1st and December 31st, 2014. The inclusion criteria were as follows: adult patients over 15 years of age who presented at the ED with suspicion of sepsis, received treatment at the ED, and whose blood culture was found to be positive. Clinical data were recorded from medical records including the Mortality in Emergency Department Sepsis score (MEDS score). The primary outcome of this study was mortality at one month. Multivariate logistic regression analysis was used to identify independent factors associated with death.", "During the study period, there were 775 eligible patients. The two most common pathogens identified from blood cultures were Staphylococcus aureus (193 patients; 24.9%) and Escherichia coli (158 patients; 20.4%). At one month after presenting at the ED, 110 patients (14.2%) had died. There were four significant factors for death, having cancer, being on an endotracheal tube, initial diagnosis of bacteremia, and high MED scores. Having cancer had an adjusted OR of 2.12 (95% CI of 1.29, 3.47)." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Aged", "Emergency Service, Hospital", "Escherichia coli", "Female", "Hospital Mortality", "Humans", "Male", "Neoplasms", "Retrospective Studies", "Risk Factors", "Sepsis", "Staphylococcus aureus", "Thailand" ] }
Cancer patients have double the risk of mortality if presenting with sepsis at the ED.
yes
27,491,861
Does lRG1 mRNA expression in breast cancer associate with PIK3CA genotype and with aromatase inhibitor therapy outcome?
{ "contexts": [ "PIK3CA is the most frequent somatic mutated oncogene in estrogen receptor (ER) positive breast cancer. We previously observed an association between PIK3CA genotype and aromatase inhibitors (AI) treatment outcome. This study now evaluates whether expression of mRNAs and miRs are linked to PIK3CA genotype and are independently related to AI therapy response in order to define potential expressed biomarkers for treatment outcome.", "The miR and mRNA expression levels were evaluated for their relationship with the PIK3CA genotype in two breast tumor datasets, i.e. 286 luminal cancers from the TCGA consortium and our set of 84 ER positive primary tumors of metastatic breast cancer patients who received first line AI. BRB Array tools class comparison was performed to define miRs and mRNAs whose expression associate with PIK3CA exon 9 and 20 status. Spearman correlations established miR-mRNA pairs and mRNAs with related expression. Next, a third dataset of 25 breast cancer patients receiving neo-adjuvant letrozole was evaluated, to compare expression levels of identified miRs and mRNAs in biopsies before and after treatment. Finally, to identify potential biomarkers miR and mRNA levels were related with overall survival (OS) and progression free survival (PFS) after first-line AI therapy.", "Expression of 3 miRs (miR-449a, miR-205-5p, miR-301a-3p) and 9 mRNAs (CCNO, FAM81B, LRG1, NEK10, PLCL1, PGR, SERPINA3, SORBS2, VTCN1) was related to the PIK3CA status in both datasets. All except miR-301a-3p had an increased expression in tumors with PIK3CA mutations. Validation in a publicly available dataset showed that LRG1, PGR, and SERPINA3 levels were decreased after neo-adjuvant AI-treatment. Six miR-mRNA pairs correlated significantly and stepdown analysis of all 12 factors revealed 3 mRNAs (PLCL1, LRG1, FAM81B) related to PFS. Further analyses showed LRG1 and PLCL1 expression to be unrelated with luminal subtype and to associate with OS and with PFS, the latter independent from traditional predictive factors." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Aromatase Inhibitors", "Biomarkers, Tumor", "Breast Neoplasms", "Class I Phosphatidylinositol 3-Kinases", "Disease-Free Survival", "Female", "Gene Expression Profiling", "Gene Expression Regulation, Neoplastic", "Genotype", "Glycoproteins", "Humans", "MicroRNAs", "Mutation", "RNA, Messenger", "Transcriptome", "Treatment Outcome" ] }
We showed in two datasets of ER positive and luminal breast tumors that the expression of 3 miRs and 9 mRNAs associate with the PIK3CA status. Expression of LRG1 is independent of luminal (A or B) subtype, decreased after neo-adjuvant AI-treatment, and is proposed as potential biomarker for AI therapy outcome.
yes
25,075,018
Is nuclear expression of phosphorylated focal adhesion kinase associated with poor prognosis in human colorectal cancer?
{ "contexts": [ "To determine whether phosphorylated focal adhesion kinase (P-FAK) has prognostic value in colorectal cancer (CRC) and to test whether it has any association with Tensin 4 (TNS4) expression.", "P-FAK expression was assessed using immunohistochemistry in 462 CRC cases arrayed on a tissue microarray. P-FAK and TNS4 expression were assessed by immunohistochemistry in 40 cases of paired primary colorectal cancer and corresponding hepatic metastases.", "Nuclear P-FAK expression was observed in 44% of studied cases. Positive nuclear P-FAK expression was associated with shorter disease-specific survival in univariate (p=0.005) and multivariate analysis (p=0.016). P-FAK expression was greater in metastases than the primary tumours (p<0.001) and showed significant association with nuclear TNS4 (p<0.001) in metastases." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Aged", "Aged, 80 and over", "Cell Nucleus", "Colorectal Neoplasms", "Female", "Focal Adhesion Protein-Tyrosine Kinases", "Humans", "Male", "Microfilament Proteins", "Middle Aged", "Neoplasm Metastasis", "Phosphorylation", "Prognosis", "Tensins", "Tissue Array Analysis" ] }
P-FAK expression is an independent prognostic marker in CRC. The present data suggest that the FAK signalling pathway may interact with TNS4, a known oncogene in CRC.
yes
25,096,191
Is sIRT1 required for oncogenic transformation of neural stem cells and for the survival of `` cancer cells with neural stemness '' in a p53-dependent manner?
{ "contexts": [ "Cancer stemness, observed in several types of glioma stem cells (GSCs), has been demonstrated to be an important barrier for efficient cancer therapy. We have previously reported that cancerous neural stem cells (F3.Ras.CNSCs), derived from immortalized human neural stem cells by a single oncogenic stimulation, form glial tumors in vivo.", "We searched for a commonly expressed stress modulator in both F3.Ras.CNSCs and GSCs and identified silent mating type information regulation 2, homolog (SIRT1) as a key factor in maintaining cancer stemness.", "We demonstrate that the expression of SIRT1, expressed in \"cancer cells with neural stemness,\" is critical not only for the maintenance of stem cells, but also for oncogenic transformation. Interestingly, SIRT1 is essential for the survival and tumorigenicity of F3.Ras.CNSCs and GSCs but not for the U87 glioma cell line." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Animals", "Brain Neoplasms", "Cell Line, Tumor", "Cell Survival", "Cell Transformation, Neoplastic", "Glioblastoma", "Humans", "Male", "Mice, Nude", "Neoplastic Stem Cells", "Neural Stem Cells", "Sirtuin 1", "Tumor Suppressor Protein p53" ] }
These results indicate that expression of SIRT1 in cancer cells with neural stemness plays an important role in suppressing p53-dependent tumor surveillance, the abrogation of which may be responsible not only for inducing oncogenic transformation but also for retaining the neural cancer stemness of the cells, suggesting that SIRT1 may be a putative therapeutic target in GSCs.
yes
25,070,070
Is apoptosis inhibitor-5 overexpression associated with tumor progression and poor prognosis in patients with cervical cancer?
{ "contexts": [ "The apoptosis inhibitor-5 (API5), anti-apoptosis protein, is considered a key molecule in the tumor progression and malignant phenotype of tumor cells. Here, we investigated API5 expression in cervical cancer, its clinical significance, and its relationship with phosphorylated extracellular signal-regulated kinase 1 and 2 (pERK1/2) in development and progression of cervical cancer.", "API5 effects on cell growth were assessed in cervical cancer cell lines. API5 and pERK1/2 immunohistochemical staining were performed on a cervical cancer tissue microarray consisting of 173 primary cervical cancers, 306 cervical intraepithelial neoplasias (CINs), and 429 matched normal tissues.", "API5 overexpression promoted cell proliferation and colony formation in CaSki cells, whereas API5 knockdown inhibited the both properties in HeLa cells. Immunohistochemical staining showed that API5 expression increased during the normal to tumor transition of cervical carcinoma (P < 0.001), and this increased expression was significantly associated with tumor stage (P = 0.004), tumor grade (P < 0.001), and chemo-radiation response (P = 0.004). API5 expression levels were positively associated with pERK1/2 in cervical cancer (P < 0.001) and high grade CIN (P = 0.031). In multivariate analysis, API5+ (P = 0.039) and combined API5+/pERK1/2+ (P = 0.032) were independent prognostic factors for overall survival." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Apoptosis Regulatory Proteins", "Cell Line, Tumor", "Disease Progression", "Female", "Gene Expression Regulation, Neoplastic", "HeLa Cells", "Humans", "Mitogen-Activated Protein Kinase 1", "Mitogen-Activated Protein Kinase 3", "Nuclear Proteins", "Phosphorylation", "Prognosis", "Survival Analysis", "Tissue Array Analysis", "Uterine Cervical Neoplasms" ] }
API5 expression is associated with pERK1/2 in a subset of cervical cancer patients and its expression predicts poor overall survival, supporting that API5 may be a promising novel target for therapeutic interventions.
yes
25,088,804
Does neighborhood influence on recreational physical activity and survival after breast cancer?
{ "contexts": [ "Higher levels of physical activity have been associated with improved survival after breast cancer diagnosis. However, no previous studies have considered the influence of the social and built environment on physical activity and survival among breast cancer patients.", "Our study included 4,345 women diagnosed with breast cancer (1995-2008) from two population-based studies conducted in the San Francisco Bay Area. We examined questionnaire-based moderate/strenuous recreational physical activity during the 3 years before diagnosis. Neighborhood characteristics were based on data from the 2000 US Census, business listings, parks, farmers' markets, and Department of Transportation. Survival was evaluated using multivariable Cox proportional hazards models, with follow-up through 2009.", "Women residing in neighborhoods with no fast-food restaurants (vs. fewer fast-food restaurants) to other restaurants, high traffic density, and a high percentage of foreign-born residents were less likely to meet physical activity recommendations set by the American Cancer Society. Women who were not recreationally physically active had a 22% higher risk of death from any cause than women that were the most active. Poorer overall survival was associated with lower neighborhood socioeconomic status (SES) (p(trend) = 0.02), whereas better breast cancer-specific survival was associated with a lack of parks, especially among women in high-SES neighborhoods." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Breast Neoplasms", "Exercise", "Female", "Humans", "Middle Aged", "Population Density", "Proportional Hazards Models", "Recreation", "Residence Characteristics", "Risk Reduction Behavior", "San Francisco", "Social Class", "Social Environment", "Surveys and Questionnaires", "Survivors", "Transportation", "United States" ] }
Certain aspects of the neighborhood have independent associations with recreational physical activity among breast cancer patients and their survival. Considering neighborhood factors may aide in the design of more effective, tailored physical activity programs for breast cancer survivors.
yes
25,092,163
Do lymph node metastases impact survival in follicular variant papillary thyroid cancer?
{ "contexts": [ "Follicular variant of papillary thyroid cancer (FVPTC) is the most common and fastest growing subtype of papillary thyroid cancer (PTC) with features of both PTC and follicular thyroid cancer (FTC). The purpose of this study was to determine the patient and tumor features associated with lymph node metastases (LNM) in FVPTC.", "This was a retrospective review of adult (≥18) patients with histologically confirmed diagnoses of FVPTC within the SEER database between 1988 and 2009. LNM were defined by at least two lymph nodes with metastatic disease. To determine factors associated with LNM, we constructed a multivariate logistic regression model from significant variables (p < 0.05) identified on univariate analysis. Similarly, we used a Cox proportional hazards model to understand the relative importance of LNM in determining disease-specific mortality (DSM).", "Of the 20,357 cases of FVPTC with lymph node data available, 1,761 (8.7%) had LNM; 61.1% of these LNM were located in the central neck and 38.9% were in the lateral neck. Extrathyroidal extension (odds ratio [OR] 2.6, 95% confidence interval [CI] 2.2-3.0, p < 0.01) and multifocality (OR 3.0, 95% CI 2.5-3.6, p < 0.01) were the strongest predictors of LNM. Importantly, LNM did not independently predict DSM (p = 0.52). Tumor size >4 cm (hazards ratio [HR] 5.3, 95% CI 2.2-12.8, p < 0.01) and extrathyroidal extension (HR 8.2, 95% CI 3.0-22.0, p < 0.01) were the strongest predictors of DSM." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Adenocarcinoma, Follicular", "Adult", "Carcinoma, Papillary", "Female", "Follow-Up Studies", "Humans", "Lymphatic Metastasis", "Male", "Middle Aged", "Neoplasm Staging", "Prognosis", "Retrospective Studies", "SEER Program", "Survival Rate", "Thyroid Neoplasms" ] }
LNM occur in less than 10% of patients with FVPTC but do not impact DSM. Instead, DSM in FVPTC is related to size and local invasion.
no
25,081,667
Does short-hairpin RNA-mediated MTA2 silencing inhibit human breast cancer cell line MDA-MB231 proliferation and metastasis?
{ "contexts": [ "To observe the effects of metastasis-associated tumor gene family 2 (MTA2) depletion on human breast cancer cell proliferation and metastasis.", "A short-hairpin RNA targeting MTA2 was chemically synthesized and transfected into a lentivirus to construct Lv-shMTA2 for infection into the MDA-MB231 human breast cancer cell line. At 48 hours after infection cells were harvested and mRNA and protein levels of MTA2 were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting, respectively. Cell viability and metastasis were assessed by CCK-8, wound-healing assay and Transwell assay, respectively. In addition, a xenograft model of human breast cancer was constructed to investigate cancerous cell growth and capacity for metastasis.", "After infection with Lv-shMTA2, mRNA and protein levels of MTA2 was significantly reduced (p<0.05) and MDA-MB231 cell proliferation and metastasis were inhibited (p<0.05). In addition, mean tumor size was smaller than that in control group nude mice (p<0.05) and numbers of metastatic deposits in lung were lower than in control group mice (p<0.05). Depletion of MTA2 affected MMP-2 and apoptosis-related protein expression." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Animals", "Breast Neoplasms", "Cell Line, Tumor", "Cell Movement", "Cell Proliferation", "Cell Survival", "Female", "Histone Deacetylases", "Humans", "Lung Neoplasms", "Matrix Metalloproteinase 2", "Mice", "Mice, Inbred BALB C", "Mice, Nude", "RNA Interference", "RNA, Messenger", "RNA, Small Interfering", "Repressor Proteins", "Wound Healing" ] }
For the first time to our knowledge we showed that MTA2 depletion could significantly inhibit human breast cancer cell growth and metastasis, implying that MTA2 might be involved in the progression of breast cancer. The role of MTA2 in breast cancer growth and metastasis might be linked with regulation of matrix metalloproteinase and apoptosis.
yes
25,098,630
Is expression of A disintegrin and metalloprotease 8 associated with cell growth and poor survival in colorectal cancer?
{ "contexts": [ "A disintegrin and metalloprotease 8 (ADAM8) has been reported to be associated with various malignancies. However, no studies have examined ADAM8 association in colorectal cancer (CRC). The aim of this study was to investigate the expression and function of ADAM8 in CRC.", "Expression level of ADAM8 in CRC was evaluated by quantitative RT-PCR, western blot and immunohistochemical staining analysis. The role of ADAM8 in colorectal carcinogenesis was evaluated by in vitro assays. The correlations between ADAM8 status and clinicopathological features including survival were analyzed.", "ADAM8 was highly expressed in CRC tissues compared with adjacent normal tissues. Knockdown of ADAM8 in two CRC cell lines resulted in reduced cellular growth and proliferation, and increased apoptosis. Immunohistochemistry analysis showed no significant correlations of ADAM8 protein expression with clinicopathologic features. Survival analysis indicated that patients with ADAM8-positive tumors had worse 5-year overall survival (OS, p = 0.037) and 5-year disease free survival (DFS, p = 0.014) compared with those with ADAM8-negative tumors. Multivariate analysis indicated ADAM8 expression was an independent prognostic factor for both OS and DFS (both p< 0.001). Subgroup analysis showed that 5-year OS of colon cancer, T3-T4 stage and N0 stage was worse for patients with ADAM8-positive tumors than those with ADAM8-negative tumors (p < 0.05). The 5-year DFS in colon cancer, T3-T4 stage, N0 stage, TNM stage II, adenocarcinoma, moderate differentiation and male patient subgroups was also worse for patients with ADAM8-positive tumors than those with ADAM8-negative tumors (p < 0.05)." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "ADAM Proteins", "Aged", "Cell Line, Tumor", "Cell Proliferation", "Colorectal Neoplasms", "Female", "Gene Knockdown Techniques", "HT29 Cells", "Humans", "Male", "Membrane Proteins", "Middle Aged", "Neoplasm Staging", "Risk Factors", "Survival Analysis" ] }
Our results show that ADAM8 is overexpressed in CRC, promotes cell growth and correlates with worse OS and DFS, and thus could serve as a biomarker for individual CRC patient therapy.
yes
25,075,066
Does silibinin administration improve hepatic failure due to extensive liver infiltration in a breast cancer patient?
{ "contexts": [ "Silibinin exerts hepatoprotective, anti-inflammatory and anti-fibrotic effects. Several pre-clinical studies have shown anti-tumoral activity of silibinin in breast cancer cell lines.", "We present the case of a heavily pre-treated breast cancer patient with extensive liver infiltration. The patient presented with progressive liver failure despite several chemotherapy treatments, including paclitaxel, capecitabine and vinorelbine. After four cycles of a fourth-line chemotherapy treatment consisting of carboplatin and gemcitabine, the patient's liver blood test results deteriorated to life-threatening levels. The compassionate use of Legasil®, a new commercially available nutraceutical product containing a new silibinin formulation, was offered to the patient according to article 37 of the 2013 Declaration of Helsinki. After treatment initiation, the patient presented clinical and liver improvement, which permitted the patient to continue palliative chemotherapy." ], "labels": [ "BACKGROUND", "METHODS" ], "meshes": [ "Adult", "Breast Neoplasms", "Female", "Humans", "Liver", "Liver Failure", "Silybin", "Silymarin", "Vitamin E" ] }
This is the first case report of a clinical benefit of silibinin administration in a breast cancer patient.
yes