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{ "contexts": [ "One hypothesis for thyroid cancer development is its derivation from thyroid cancer stem cells (CSCs). Such cells could arise via different paths including from mutated resident stem cells within the thyroid gland or via epithelial to mesenchymal transition (EMT) from malignant cells since EMT is known to confer stem-like characteristics. Furthermore, EMT is a critical process for epithelial tumor progression, local invasion, and metastasis formation. In addition, stemness provides cells with therapeutic resistance and is the likely cause of tumor recurrence. However, the relevance of EMT and stemness in thyroid cancer progression has not been extensively studied.", "To examine the status of stemness in thyroid papillary cancer, we employed a murine model of thyroid papillary carcinoma and examined the expression of stemness and EMT using qPCR and histochemistry in mice with a thyroid-specific knock-in of oncogenic Braf (LSL-Braf((V600E))/TPO-Cre). This construct is only activated at the time of thyroid peroxidase (TPO) expression in differentiating thyroid cells and cannot be activated by undifferentiated stem cells, which do not express TPO.", "There was decreased expression of thyroid-specific genes such as Tg and NIS and increased expression of stemness markers, such as Oct4, Rex1, CD15, and Sox2 in the thyroid carcinoma tissue from 6-week-old BRAF(V600E) mice indicating the dedifferentiated status of the cells and the fact that stemness was derived in this model from differentiated thyroid cells. The decreased expression of the epithelial marker E-cadherin and increased EMT regulators including Snail, Slug, and TGF-β1 and TGF-β3, and the mesenchymal marker vimentin demonstrated the simultaneous progression of EMT and the CSC-like phenotype. Stemness was also found in a cancer thyroid cell line (named Marca cells) derived from one of the murine tumors. In this cell line, we also found that overexpression of Snail caused up-regulation of vimentin expression and up-regulation of stemness markers Oct4, Rex1, and CD15, with enhanced migration ability of the cells. We also showed that TGF-β1 was able to induce Snail and vimentin expression in the Marca cell thyroid cancer line, indicating the induction of EMT in these cells, and this induction of EMT and stemness was significantly inhibited by celastro a natural inhibitor of neoplastic cells." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [] }

{ "contexts": [ "To retrospectively review the safety and clinical efficacy of bevacizumab concomitant with chemotherapy in Chinese patients with advanced non-squamous non-small cell lung cancer (NSNSCLC).", "Clinical data for 79 patients with NSNSCLC who received bevacizumab concomitant with chemotherapy in Chinese PLA General Hospital from April 28th 2009 to May 5th 2013 were retrospectively reviewed to analyze the clinical efficacy including disease control rate (DCR), overall response rate (ORR), progression-free survival (PFS), overall survival (OS), the Eastern Cooperative Oncology Group (ECOG) score and the safety.", "The Eastern Cooperative Oncology Group (ECOG) score was 0-2. By the final cutoff date (June 9, 2013), 54 (68.4%) patients had disease progression and 37 (46.8%) died. The ORR was 32.9% and the DCR was 83.5%. The ORR of the first-, second-, and third- or later-line treatments were 51.4%, 25.0% and 12.5%, while the DCR were 94.3%, 80.0% and 70.8%, respectively. The median OS (mOS) and PFS (mPFS) were 13.5 and 5.83 months, respectively. The mOS of patients with the first-, second-, and third- or later-line treatments were 16.2, 10.9 and 8.30 months, while the mPFS were 7.27, 5.90 and 5.17 months, respectively. Chemotherapy-related adverse events included myelosuppression, vomiting, hepatic dysfunction and renal dysfunction, while the common serious bevacizumab-related adverse events were thromboembolic problems, gastrointestinal perforation and reversible posterior leukoencephalopathy syndrome, which could be well managed." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Angiogenesis Inhibitors", "Antibodies, Monoclonal, Humanized", "Antineoplastic Combined Chemotherapy Protocols", "Bevacizumab", "Carcinoma, Non-Small-Cell Lung", "China", "Disease-Free Survival", "Female", "Humans", "Lung Neoplasms", "Male", "Middle Aged", "Retrospective Studies", "Treatment Outcome" ] }

{ "contexts": [ "Our study reexamines the prevalence of interval colorectal cancer (I-CRC) by manually reviewing CRC cases at a single institution.", "In 2% to 8% of patients with CRC, diagnosis occurs during the interval 6 to 36 months after a cancer-free colonoscopy. Rates are often determined by linking the date of colonoscopy with cancer registry information.", "We examined all colonoscopies from 1993 to 2011. These examinations were linked with Pennsylvania Cancer Registry data. Matched charts were manually reviewed. We determined whether the CRC was \"prevalent\" or, for patients with a previous colonoscopy, whether they were interval or noninterval based on time from last colonoscopy. For interval cases, we identified \"administrative errors\" that could falsely increase the number of reported I-CRC.", "Over the study period, 43,661 colonoscopies were performed, with 1147 (2.6%) positive for CRC after excluding cases (n=52) in which patients had IBD, previous surgery, or nonadenocarcinoma malignancy. Prevalent CRCs totaled 1062 (92.6%). Noninterval CRCs (diagnosed over 36 mo from index colonoscopy) were present in 40 (3.5%). There remained 45 (3.9%) potential I-CRC cases. However, after manual review, 21 cases were found to be administrative errors. Therefore, the accurate proportion of colonoscopies that found an I-CRC was 2.1% (95% confidence interval, 1.5%-3.2%)." ], "labels": [ "OBJECTIVE", "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Aged", "Aged, 80 and over", "Colonic Neoplasms", "Colonoscopy", "Data Accuracy", "Databases, Factual", "Female", "Humans", "Male", "Middle Aged", "Pennsylvania", "Prevalence", "Registries", "Retrospective Studies", "Time Factors" ] }

{ "contexts": [ "To confirm that the severity of inflammation can promote the colitis-associated colorectal cancer(CAC) and explore the function of STAT3 signal pathway in CAC.", "Mutagenic agent azoxymethane(AOM) and pro-inflammatory agent dextran sodium sulfate salt (DSS) were used to develop a mouse model of CAC. By changing the concentration of DSS (0, 1% and 2% respectively), the mouse model with different extent of severity of inflammation was developed and the risk of carcinogenesis among these groups was compared. The expression of STAT3 signal pathway was detected by immunohistochemistry staining.", "In the evaluation of inflammatory severity, disease activity index, histopathological inflammation scores and the expression of pro-inflammation chemokines such as TNF-α, IL-6 and IL-12 in the higher inflammatory response group were higher than that in the lower inflammatory response group. The incidence of colorectal tumor was 100%(12/12) in the higher inflammatory response group and the incidence of colorectal tumor was 58.3%(7/12) in the lower inflammatory response group, and the difference between these two group was statistically significant (P<0.05). The multiplicity(number of tumors/colon) was 12.5±0.5 in the higher inflammatory response group and the multiplicity was 6.6±1.0 in the lower inflammatory response group, and the difference between these two groups was statistically significant (P<0.001). The tumor load(sum of tumor diameters per mouse) in the higher inflammatory response group was 44.2±2.4 mm and that in the lower inflammatory response group was only 18.7±2.7 mm, and the difference between these two groups was statistically significant (P<0.0001). Moreover, the expression of p-STAT3 (Tyr705) was higher in colitis tissue of the higher inflammatory response group than that of the lower inflammatory response group." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Animals", "Azoxymethane", "Colitis", "Colonic Neoplasms", "Colorectal Neoplasms", "Dextran Sulfate", "Disease Models, Animal", "Immunohistochemistry", "Inflammation", "Interleukin-6", "Mice", "Mice, Inbred C57BL", "STAT3 Transcription Factor", "Signal Transduction", "Tumor Necrosis Factor-alpha" ] }

{ "contexts": [ "One third of non-small cell lung cancer (NSCLC) affects elderly patients in a locally advanced (LA) stage. Induction therapy followed by a curative approach is becoming the standard-of-care for LA-NSCLC.", "We compared the efficacy and tolerance to induction chemotherapy or chemo-radiation followed by surgery or definitive radiotherapy in patients younger (N=64) and older (N=44) than 70 years with LA-NSCLC.", "Elderly patients trended towards having a worse baseline performance status, and presented a higher percentage of IIIB, and squamous tumors. Nevertheless, no significant differences in response rate, operability, or disease-free and overall survival were found between age groups in the whole series, nor in the sub-group of resected patients. Grade 3-4 toxicity tended to be lower in elderly patients." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Age Factors", "Aged", "Aged, 80 and over", "Antineoplastic Combined Chemotherapy Protocols", "Carcinoma, Non-Small-Cell Lung", "Female", "Humans", "Induction Chemotherapy", "Lung Neoplasms", "Male", "Middle Aged" ] }

{ "contexts": [ "Successful cancer treatments still require more compounds to be isolated from natural sources. Thus, we have investigated anti-proliferative/apoptotic effects of methanolic extracts of lichen species Parmelia sulcata Taylor and Usnea filipendula Stirt on human lung cancer (A549, PC3), liver cancer (Hep3B) and rat glioma (C6) cells.", "Anti-proliferative effects were monitored by MTT and adenosine triphosphate viability assays, while genotoxic activity was studied using the comet assay. Additionally, cell death mode and apoptosis assays (fluorescence staining, caspase-cleaved cytokeratin 18, caspase-3 activity and PARP cleavage) were performed.", "Extracts produced anti-population growth effects in a dose-dependent manner (1.56-100 μg/ml) by inducing apoptosis-like cell death. This resulted in the lines having the presence of pyknotic cell nuclei. In addition, significant increase in genetic damage in the cell lines was seen, indicating that DNA damage may have been responsible for apoptotic cell death." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Animals", "Apoptosis", "Ascomycota", "Brain Neoplasms", "Caspase 3", "Cell Line, Tumor", "Cell Proliferation", "DNA Damage", "Enzyme Activation", "Glioma", "Humans", "Keratin-18", "Liver Neoplasms", "Lung Neoplasms", "Neoplasms", "Poly(ADP-ribose) Polymerases", "Rats", "Usnea" ] }

{ "contexts": [ "p16(INK4a) Is overexpressed in almost all precancerous and carcinomatous lesions of the uterine cervix, secondary to interference between high-risk human papillomaviruses (hr-HPVs) and the retinoblastoma gene product. Overexpression of p16(INK4a) has also been identified in patients with high-grade urothelial lesions, both cytologically and histologically. However, the etiological role of HPV has not been documented except in inverted papillomas, low-grade bladder tumors, and younger patients. We therefore attempted to verify if HPV DNA was detectable in p16(INK4a) -positive urothelial tumors.", "A total of 90 urinary cytology samples (33 negative/low-grade cases and 57 high-grade proliferations) were analyzed for p16(INK4a) and HPV DNA. HPV genotyping was performed by polymerase chain reaction using a low-density DNA microarray enabling the detection of 35 HPVs. A reasoned approach combining tissue genotyping and in situ hybridization (ISH) for hr-HPVs was used in patients with urinary HPV.", "Low-risk HPV (HPV-84) and hr-HPVs (HPV-16, -31, and -70) were detected. The prevalence of hr-HPVs in the urine was low: 5 of 82 patients (6.1%) and only 4 of 50 patients (8.0%) with high-grade urothelial malignancy. p16(INK4a) overexpression was noted in 49 high-grade samples (85.9%). In patients with p16(INK4a) -positive tumor cells and hr-HPV in the urine, HPV genotyping and ISH for hr-HPVs were negative in matched tissue sections." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Aged, 80 and over", "Carcinoma, Transitional Cell", "Cohort Studies", "Cyclin-Dependent Kinase Inhibitor p16", "Cystectomy", "Cystoscopy", "DNA, Viral", "Female", "Gene Expression Regulation, Neoplastic", "Genotype", "Humans", "In Situ Hybridization", "Middle Aged", "Neoplasm Invasiveness", "Neoplasm Staging", "Papillomaviridae", "Papillomavirus Infections", "Sensitivity and Specificity", "Tumor Cells, Cultured", "Urinary Bladder Neoplasms" ] }

{ "contexts": [ "The aim of this study was to prospectively evaluate the feasibility and potential advantages of freehand single-photon emission computed tomography (fhSPECT) compared with conventional intraoperative localization techniques for sentinel lymph node biopsy (SLNB) in oral cancer.", "Between November 2012 and February 2014, 23 consecutive patients with clinical T1/T2 oral squamous cell carcinoma and a cN0 neck were recruited. All patients underwent SLNB followed by elective neck dissection (END). All patients received preoperative lymphoscintigraphy. To detect the SLNs intraoperatively, fhSPECT with a combination of conventional acoustic SLN localization and 3-D visual navigation was used.", "All but one of the SLNs detected by preoperative imaging were successfully mapped intraoperatively by fhSPECT (detection rate 98%), including those in six patients with a tumour in the floor of the mouth. A histopathology analysis revealed positive SLNs in 22% of patients. No further metastases were found in LNs resected during END. SLNB correctly predicted the final LN stage in all patients (accuracy 100%). Additional radioactive LNs, which were not present on preoperative lymphoscintigraphy, were observed in three patients." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Aged, 80 and over", "Humans", "Imaging, Three-Dimensional", "Intraoperative Period", "Lymph Nodes", "Middle Aged", "Mouth Neoplasms", "Sentinel Lymph Node Biopsy", "Tomography, Emission-Computed, Single-Photon" ] }

{ "contexts": [ "Salivary gland adenoid cystic carcinoma (ACC) is one of the most common malignant tumours in the oral and maxillofacial region, and has high aggressive potential. Tumour and stroma interactions are critical in determining the biological characteristics of malignancy. The aim of this study was to investigate the presence of myofibroblasts and their roles in the invasive characteristics of ACC.", "Immunohistochemistry was used to detect the expression of vimentin (VIM), α-smooth muscle actin (α-SMA), matrix metalloproteinase 2 (MMP2) and CD34 in ACCs and normal salivary gland controls. A significant difference in α-SMA expression was found between normal controls and ACCs, suggesting the presence of myofibroblasts in ACCs. Immunohistochemical staining also demonstrated higher MMP2 expression in the stroma of ACCs than in the controls (P < 0.001). Primary culture of myofibroblasts from one ACC showed great invasive activity, with high expression of MMP2 and C-X-C motif chemokine 12 (CXCL12) by reverse transcription polymerase chain reaction (RT-PCR) analysis." ], "labels": [ "OBJECTIVE", "RESULTS" ], "meshes": [ "Adult", "Aged", "Aged, 80 and over", "Biomarkers, Tumor", "Carcinoma, Adenoid Cystic", "Chemokine CXCL2", "Female", "Humans", "Immunohistochemistry", "Male", "Matrix Metalloproteinase 2", "Middle Aged", "Myofibroblasts", "Neoplasm Invasiveness", "Reverse Transcriptase Polymerase Chain Reaction", "Salivary Gland Neoplasms" ] }

{ "contexts": [ "Prostate cancer is a common malignancy in men, and inevitably some patients experience biochemical recurrence after radical prostatectomy. To date, there are no reliable predictors for prostate cancer recurrence, and novel predictors are urgently needed. PCDH10 (protocadherin-10) is a novel tumor suppressor gene, which is down-regulated by promoter methylation in prostate cancer. The aim of this study was to evaluate the feasibility of using PCDH10 methylation to predict the biochemical recurrence (BCR) of prostate cancer after radical prostatectomy.", "Fresh tissue samples were obtained from 151 patients with primary prostate cancer, and from 34 patients with benign prostatic hyperplasia (BPH) as control. The methylation status of PCDH10 in prostate cancer tissues and controls were examined using methylation-specific PCR (MSP), and then associated with clinicopathological features and BCR-free survival of patients with prostate cancer.", "We found that PCDH10 methylation was detected in 79 (52.3%) patients with prostate cancer, but no methylation was found in controls (P<0.0001). Moreover, PCDH10 methylation was significantly associated with higher preoperative prostate-specific antigen (PSA) level (P <0.0001), higher Gleason Score (P<0.0001), advanced clinical stage (P=0.0002), lymph node metastasis (P=0.0389), angiolymphatic invasion (P=0.0303), and biochemical recurrence (P=0.0068). Moreover, PCDH10 methylation was associated with poor BCR-free survival (P<0.0001), and may be used as an independent predictor of BCR-free survival (P=0.0046)." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Biomarkers, Tumor", "Cadherins", "DNA Methylation", "DNA Primers", "Disease-Free Survival", "Humans", "Male", "Polymerase Chain Reaction", "Prostatectomy", "Prostatic Neoplasms" ] }

{ "contexts": [ "miRNAs have been implicated in the regulation of key metabolic, inflammatory, and malignant pathways; hence, they might be considered both predictors and players of cancer development.", "Using a case-control study design nested in the ORDET prospective cohort study, we addressed the possibility that specific mRNAs can serve as early predictors of breast cancer incidence in postmenopausal women. We compared leukocyte miRNA profiles of 133 incident postmenopausal breast cancer cases and profiles of 133 women who remained healthy over a follow-up period of 20 years.", "The analysis identified 20 differentially expressed miRNAs, 15 of which were downregulated. Of the 20 miRNAs, miR145-5p and miR145-3p, each derived from another arm of the respective pre-miRNA, were consistently and significantly downregulated in all the databases that we surveyed. For example, analysis of more than 1,500 patients (the UK Metabric cohort) indicated that high abundance of miR145-3p and miR145-5p was associated with longer, and for miR145-3p also statistically significant, survival. The experimental data attributed different roles to the identified miRNAs: Although the 5p isoform was associated with invasion and metastasis, the other isoform seems related to cell proliferation." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Breast Neoplasms", "Case-Control Studies", "Down-Regulation", "Female", "Humans", "MicroRNAs", "Middle Aged", "Postmenopause", "Prospective Studies", "Transfection" ] }

{ "contexts": [ "To determine whether PTEN status in prostate biopsy represents a predictor of intermediate and long-term oncological outcomes after radical prostatectomy, and whether PTEN status predicts response to androgen deprivation therapy.", "In a retrospective analysis of 77 men treated by radical prostatectomy who underwent diagnostic biopsy between 1992-2006, biopsy samples were stained for PTEN expression by the PREZEON assay with >10% staining reported as positive. Cox proportional hazards and log-rank models were used to assess the correlation between PTEN loss and clinical outcomes.", "During a median follow-up period after radical prostatectomy of 8.8 years, 39 men (51%) developed biochemical recurrence, four (5%) had castration-resistant prostate cancer, two (3%) had metastasis and two (3%) died from prostate cancer. PTEN loss was not significantly associated with biochemical recurrence (hazard ratio 2.1, 95% confidence interval 0.9-5.1, P = 0.10), but significantly predicted increased risk of castration-resistant prostate cancer, metastasis and prostate cancer-specific mortality (all log-rank, P < 0.0001), and time from androgen deprivation therapy to castration-resistant prostate cancer (log-rank, P = 0.003). No patient without PTEN loss developed metastases or died from prostate cancer." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Biomarkers, Tumor", "Biopsy", "Follow-Up Studies", "Humans", "Male", "Middle Aged", "North Carolina", "PTEN Phosphohydrolase", "Prognosis", "Prostatic Neoplasms", "Retrospective Studies", "Survival Rate", "Time Factors" ] }

{ "contexts": [ "To assess whether zoledronic acid (ZOL) adds to the effect of combined androgen blockade (CAB) in patients with hormone-naive bone metastatic prostate cancer.", "Patients were treated with either a combination of CAB (luteinizing hormone-releasing hormone agonist and bicalutamide) and ZOL (CAB-Z group) or CAB-alone (historical control patients, CAB-C group). ZOL was injected intravenously at 4 mg every 4 weeks. One hundred and five and 100 patients among 205 enrolled patients were assigned to the CAB-Z group and CAB-C group, respectively. The time to prostate-specific antigen (PSA) failure in patients in the CAB-Z group was compared to that in the CAB-C group. The primary end-point of the study was the time-to-PSA failure.", "PSA and serum N-telopeptide of type I collagen (NTx) levels were examined before treatment and every 3 months after treatment. PSA failure occurred in 42 (40.0%) patients in the CAB-Z group and 48 (48.0%) patients in the CAB-C group. The biochemical recurrence-free rate was significantly lower in patients in the CAB-C group (p=0.004, by log-rank test). The categorical biopsy Gleason score pre-treatment serum NTx and treatment with ZOL were shown to be independent predictors of PSA failure-free survival time (p=0.040, p=0.005 and p=0.026, respectively)." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Aged", "Aged, 80 and over", "Bone Density Conservation Agents", "Bone Neoplasms", "Collagen Type I", "Diphosphonates", "Humans", "Imidazoles", "Male", "Middle Aged", "Peptides", "Prospective Studies", "Prostate-Specific Antigen", "Prostatic Neoplasms", "Zoledronic Acid" ] }

{ "contexts": [ "Residual disease (RD) at definitive resection of incidental gallbladder cancer (IGBCA) influences outcome, but its clinical relevance with respect to anatomic site is incompletely characterized.", "Consecutive patients with IGBCA undergoing re-exploration from 1998 to 2009 were identified; those submitted to a complete resection were analyzed. Demographics and tumor- and treatment-related variables were correlated with RD and survival. Cancer-specific survival was stratified by site of RD (local [gallbladder bed]; regional [bile duct, lymph nodes]; distant [discontiguous liver, port site, peritoneal]).", "Of the 135 patients submitted to re-exploration, RD was found in 82 (61%) overall and in 63 (54%) of 116 patients submitted to resection; the most common site was regional (n = 27, 43%). The T stage of the gallbladder specimen was the only independent predictor of RD (T1b = 35.7%, T2 = 48.3%, T3 = 70%, p = 0.015). The presence of RD at any site dramatically reduced median disease-free survival (DFS) (11.2 vs 93.4 months, p < 0.0001) and disease-specific survival (DSS) (25.2 months vs not reached, p < 0.0001) compared with no RD, respectively. Disease-specific survival did not differ according to RD location, with all anatomic sites being equally poor (p = 0.87). Residual disease at any site predicted DFS (hazard ratio [HR] 3.3, 95% CI 1.9 to 5.7, p = 0.0003) and DSS (HR 2.4, 95% CI 1.2 to 4.6, p = 0.01), independent of all other tumor-related variables." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Aged, 80 and over", "Disease-Free Survival", "Female", "Gallbladder Neoplasms", "Humans", "Incidental Findings", "Male", "Middle Aged", "Neoplasm, Residual", "Prognosis", "Retrospective Studies" ] }

{ "contexts": [ "In breast cancer, distinct expression profiles of microRNAs (miRNAs) have been associated with molecular subgroups and clinicopathological characteristics, implicating a diagnostic and prognostic role of miRNAs. However, the biological functions of deregulated miRNAs in tumor progression are not yet completely defined. In this study, we investigated the function of miR-18a in regulating breast cancer metastasis through the hypoxia-inducible factor 1α (HIF1A)-dependent hypoxic response.", "An orthotopic metastatic breast cancer xenograft model (MDA-MB-231 cells) was used to identify miRNAs associated with spontaneous lung metastasis. The function of miR-18a in regulating HIF1A expression, as well as cellular responses to hypoxia and metastasis, were then studied in vitro and in vivo by assessing ectopic miR-18a expression or miR-18a inhibition. miRNA-mRNA interactions (AGO2 immunoprecipitation and 3' untranslated region Luciferase reporter assays), gene expression (quantitative PCR and microarray), cell migration and invasion, and cell growth were assessed under normoxic or hypoxic conditions, complemented by orthotopic xenograft of tumor cells to the mammary fat pad to investigate the effect of modulating miR-18a expression on primary tumor growth and lung metastasis. Last, clinically relevant correlations between miR-18a, HIF1A, hypoxia-responsive gene expression and distant metastasis-free survival (DMFS) were assessed using published expression array breast tumors data sets.", "miRNAs encoded by the MIR17HG gene were downregulated in lung metastases compared to primary tumors. Ectopic expression of miR-18a, a MIR17HG family member, in a metastatic variant of MDA-MB-231 cells reduced primary tumor growth and lung metastasis, whereas miR-18a inhibition in the parental cells promoted tumor growth and lung metastasis. We identified HIF1A as a direct target of miR-18a. Modulating miR-18a expression significantly affected hypoxic gene expression, cell invasiveness and sensitivity to anoikis and hypoxia in vitro in a HIF1A-dependent manner. Analysis of previously published data revealed that higher expression of HIF1A and a panel of hypoxic genes is associated with shorter DMFS interval in patients with basal-like breast tumors, and that, within this subtype, miR-18a expression is inversely correlated with hypoxic gene expression. Together, these data support a role of miR-18a in repressing distant metastasis through a HIF1A-dependent pathway." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Animals", "Breast Neoplasms", "Cell Hypoxia", "Female", "Gene Expression Regulation, Neoplastic", "Humans", "Hypoxia-Inducible Factor 1, alpha Subunit", "Lung Neoplasms", "MCF-7 Cells", "Mice, Inbred NOD", "Mice, SCID", "MicroRNAs", "Neoplasms, Basal Cell", "RNA Interference" ] }

{ "contexts": [ "Type 1 endometrial cancer (EC) is typically sex hormone sensitive; however, most women diagnosed with EC have already gone through menopause. Several studies have reported that the postmenopausal ovary is hormonally active, and estradiol (E2) production from the ovaries persists for as much as 10 years beyond menopause. The aim of this study was to evaluate whether sex steroid production from the ovaries contributes to the pathogenesis of type 1 EC.", "This was a prospective study of 53 women treated for EC (28 cases of type 1 disease and 25 cases of type 2 disease). Serum specimens were collected from the peripheral and ovarian veins of participants undergoing bilateral oophorectomy. The sex steroid hormone levels and hormonal milieu on cervical cytology were evaluated as maturation value (MV). In addition, the degree of stromal hyperplasia of the ovary was evaluated histologically.", "Although the E2 levels of the peripheral veins did not show any significant differences [8.2 (5.1-12.4) vs 7.4 (5.1-11.7) pg/mL, respectively; P < 0.05], the patients with type 1 EC had a higher E2 level in the ovarian vein than those with type 2 EC [25 (13.8-42.5) vs 15 (10.0-23.0) pg/mL, respectively; P < 0.05]. There were also no significant differences in the rate of moderate to marked hyperplasia of the ovarian stroma between the groups; however, the thickness of the ovarian cortex demonstrated a correlation with the ovarian E2 level. In addition, the MV displayed a strong correlation with the ovarian E2 level, but not the peripheral E2 level." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Aged", "Carcinoma, Endometrioid", "Endometrial Neoplasms", "Estradiol", "Estrone", "Female", "Humans", "Hyperplasia", "Middle Aged", "Ovary", "Postmenopause", "Testosterone", "Up-Regulation", "Veins" ] }

{ "contexts": [ "An oligonucleotide termed 'T-oligo' having sequence homology with telomere overhang has shown cytotoxicity in multiple cancers. We have demonstrated that T-oligo can induce apoptosis in androgen independent prostate cancer cell line DU-145. In this report, we evaluate the use of star-shaped tetraspermine (SSTS) for delivery of T-oligo.", "SSTS was synthesized from spermine and its intrinsic cytotoxicity towards DU-145 cells was compared with spermine and branched polyethyleneimine (bPEI). Atomistic molecular dynamic (MD) simulations were conducted to understand binding and complexation of spermine and SSTS with T-oligo. Complexation was also determined using gel electrophoresis and SYBR gold assay. Complexes were characterized for size, cellular uptake and antiproliferative effect.", "SSTS exhibited significantly lower toxicity than spermine and bPEI. Its affinity towards T-oligo was significantly higher than spermine as determined by experimental studies and confirmed by MD simulations and it formed stable complexes (TONPs) with T-oligo. TONPs facilitated cellular uptake and nuclear accumulation of T-oligo and their cytotoxic potential was observed at concentration several folds lower than that required for T-oligo alone." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Antineoplastic Agents", "Cell Culture Techniques", "Cell Line, Tumor", "Cell Survival", "Drug Carriers", "Edetic Acid", "Flow Cytometry", "Humans", "Male", "Molecular Conformation", "Molecular Dynamics Simulation", "Nanoparticles", "Oligonucleotides", "Prostatic Neoplasms", "Spermine" ] }

{ "contexts": [ "MicroRNA-222 (miR-222) has been shown to play a potential oncogenic role in bladder cancer. The aim of this study was to evaluate the expression of miR-222 in bladder cancer and its potential relevance to clinicopathological characteristics and patient survival.", "Surgical specimens of cancer tissue and adjacent normal tissue were obtained from 97 patients with bladder cancer. The relative expression levels of miR-222 in the cancer and the normal adjacent tissue were measured by quantitative reverse-transcriptase PCR. We analyzed their correlation with clinicopathological parameters and prognostic value.", "The expression level of miR-222 was significantly higher in tumor tissues than in corresponding non-cancerous tissues (5.46 ± 1.45 versus 1.92 ± 0.65, P <  0.0001), and a high expression of miR-222 was found to be significantly associated with tumor grade (P = 0.003) and tumor stage (P = 0.005). The miR-222 expression level was classified as high or low in relation to the median value (cutoff value = 5.15). Kaplan-Meier analysis showed that patients with higher levels of miR-222 had significantly poorer survival than those with lower expression of this miRNA in patients, with a 5-year overall survival of 29.53% and 52.75%, respectively (P = 0.0034). In the multivariate Cox proportional hazards analysis, which included miR-222 level, tumor grade, tumor stage, and tumor number, high miR-222 expression was independently associated with poor survival (P < 0.001; hazard ratio 6.17; 95% CI 2.33 to 10.39)." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Biomarkers, Tumor", "Case-Control Studies", "Cohort Studies", "Female", "Follow-Up Studies", "Gene Expression Regulation, Neoplastic", "Humans", "Male", "MicroRNAs", "Middle Aged", "Neoplasm Grading", "Neoplasm Staging", "Prognosis", "Real-Time Polymerase Chain Reaction", "Reverse Transcriptase Polymerase Chain Reaction", "Survival Rate", "Urinary Bladder", "Urinary Bladder Neoplasms" ] }

{ "contexts": [ "Telomerase, a ribonucleoprotein enzyme mainly consisted of a catalytic protein subunit human telomerase reverse transcriptase (hTERT) and a human telomerase RNA component, is responsible for maintaining telomeres. Telomerase over-expression correlates significantly with tumors and is a prognostic marker. However, telomerase over-expression in breast cancers and the effect of telomerase inhibition as a candidate cancer therapy are unknown.", "We used the dominant-negative mutant of hTERT (DN-hTERT) to inhibit telomerase activity on human breast adenocarcinoma cell line MCF-7 by transfection. Telomeric repeat amplification protocol assays and real-time quantitative RT-PCR were performed to investigate telomerase activity as well as expression of hTERT. Telomere length was measured by the flow-fluorescence in situ hybridization assay. Cell proliferation was assessed by the WST-8 assay, and apoptosis was evaluated by flow cytometry. The tumor formation ability of MCF-7 cells was investigated by transplanting cells subcutaneously into BALB/c nude mice.", "Ectopic expression of DN-hTERT caused dramatically inhibition of telomerase activity and reduction of telomere length. Telomerase inhibition induced growth arrest and apoptosis of MCF7 cells in vitro and loss of tumorigenic properties in vivo." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Animals", "Apoptosis", "Breast Neoplasms", "Cell Proliferation", "Female", "Flow Cytometry", "Genes, Dominant", "Humans", "Mice", "Mice, Inbred BALB C", "Mice, Nude", "RNA, Messenger", "Real-Time Polymerase Chain Reaction", "Reverse Transcriptase Polymerase Chain Reaction", "Telomerase", "Tumor Cells, Cultured", "Xenograft Model Antitumor Assays" ] }

{ "contexts": [ "Ibulocydine (IB), a novel prodrug of CDK inhibitor, has been reported to have anti-cancer effect in human hepatoma cells. In order to address its feasibility as a radiosensitizer to improve radiotherapeutic efficacy for human cancers, this study was designed.", "Human cancer cells of lung and colon were treated with IB and/or radiotherapy (RT). The cellular effects were assessed by CCK-8, clonogenic, flow cytometric, and western blotting assays. In vivo radiotherapeutic efficacy was evaluated using the xenograft mouse model.", "Combined treatment of IB and RT significantly reduced viability and survival fraction of the cells. Apoptotic cell death accompanied with activation of caspases, decrease in Bcl-2/Bax expression, loss of mitochondrial membrane potential (MMP) leading to release of cytochrome c into cytosol was observed. Recovery of Bcl-2 expression level by introducing Bcl-2 expressing plasmid DNA compromised the loss of MMP and apoptosis induced by IB and RT. In vivo therapeutic efficacy of combined treatment was verified in the xenograft mouse model, in which tumor growth was markedly delayed by RT with IB." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Animals", "Apoptosis", "Caspases", "Cell Line, Tumor", "Colonic Neoplasms", "Cytochromes c", "Flow Cytometry", "Humans", "Lung Neoplasms", "Male", "Mice", "Mice, Inbred BALB C", "Mice, Nude", "Mitochondria", "Proto-Oncogene Proteins c-bcl-2", "Pyrimidine Nucleosides", "Radiation-Sensitizing Agents", "Xenograft Model Antitumor Assays" ] }

{ "contexts": [ "Several studies have shown that contralateral prophylactic mastectomy (CPM) provides a disease-free and overall survival (OS) benefit in young women with estrogen receptor (ER)-negative breast cancer. We utilized the National Cancer Data Base to evaluate CPM's survival benefit for young women with early -stage breast cancer in the years that ER status was available.", "We selected 14,627 women ≤45 years of age with American Joint Committee on Cancer stage I-II breast cancer who underwent unilateral mastectomy or CPM from 2004 to 2006. Five-year OS was compared between those who had unilateral mastectomy and CPM using the Kaplan-Meier method and Cox regression analysis.", "A total of 10,289 (70.3 %) women underwent unilateral mastectomy and 4,338 (29.7 %) women underwent CPM. Median follow up was 6.1 years. After adjusting for patient age, race, insurance status, co-morbidities, year of diagnosis, ER status, tumor size, nodal status, grade, histology, facility type, facility location, use of adjuvant radiation and chemohormonal therapy, there was no difference in OS in women <45 years of age who underwent CPM compared towith those who underwent unilateral mastectomy (hazard ratio [HR] = 0.93; p = 0.39). In addition, Tthere was no improvement in OS in women <45 years of age with T1N0 tumors who underwent CPM versus unilateral mastectomy (HR = 0.85; p = 0.37) after adjusting for the aforementioned factors. Among women ≤45 years of age with ER-negative tumors who underwent CPM, there was no improvement in OS compared with women who underwent unilateral mastectomy (HR = 1.12; p = 0.32) after adjusting for the same aforementioned factors." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Adolescent", "Adult", "Breast Neoplasms", "Carcinoma, Ductal, Breast", "Carcinoma, Lobular", "Confounding Factors (Epidemiology)", "Female", "Follow-Up Studies", "Humans", "Mastectomy", "Middle Aged", "Neoplasm Grading", "Neoplasm Invasiveness", "Neoplasm Staging", "Prognosis", "Receptors, Estrogen", "SEER Program", "Selection Bias", "Survival Rate", "Young Adult" ] }

{ "contexts": [ "BRAF mutations occur in 5% to 10% of metastatic colorectal cancers and are biomarkers associated with a poor prognosis. However, the outcomes with standard chemotherapy over sequential lines of therapy in a large cohort of patients with BRAF-mutant tumors have not been described.", "We searched the M.D. Anderson Cancer Center databases for patients with colorectal cancer and identified BRAF mutations between December 2003 and May 2012. Patients were analyzed for clinical characteristics, PFS, overall survival, and chemotherapeutic agents used. Survival was estimated according to the Kaplan-Meier method.", "Among the 1567 patients tested for BRAF mutations at our institution, 127 (8.1%) had tumors with BRAF mutations. The 71 patients who presented with metastatic disease received a median of 2 lines of chemotherapy. For the first 3 lines of chemotherapy, median PFS was 6.3 months (n = 69 patients; 95% confidence interval [CI], 4.9-7.7 months), 2.5 months (n = 58 patients; 95% CI, 1.8-3.0 months), and 2.6 months (n = 31 patients; 95% CI, 1.0-4.2 months), respectively. Median PFS was not affected by the backbone chemotherapeutic agent in the first-line setting, whether oxaliplatin-based or irinotecan-based (6.4 months vs. 5.4 months, respectively; P = .99)." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Antibodies, Monoclonal", "Antibodies, Monoclonal, Humanized", "Antineoplastic Combined Chemotherapy Protocols", "Biomarkers, Tumor", "Camptothecin", "Cetuximab", "Colorectal Neoplasms", "Disease-Free Survival", "Female", "Humans", "Irinotecan", "Liver Neoplasms", "Lung Neoplasms", "Lymphatic Metastasis", "Male", "Metastasectomy", "Microsatellite Instability", "Middle Aged", "Mutation", "Neoplasm Staging", "Organoplatinum Compounds", "Oxaliplatin", "Panitumumab", "Peritoneal Neoplasms", "Proto-Oncogene Proteins B-raf", "Survival Rate" ] }

{ "contexts": [ "Long-term results of a study investigating potential prognostic factors for treatment outcomes in patients with stage III esophageal cancer are presented.", "In 64 patients, the impact of tumor cell expression of erythropoietin (EPO) and erythropoietin-receptor (EPO-R) and ten additional factors (age, gender, performance status, tumor length, tumor stage (T-stage), nodes (N-stage), histology/grading, hemoglobin levels during radiotherapy, surgery) on survival and loco-regional control was evaluated up to 10 years following radio-chemotherapy.", "On multivariate analysis, improved survival was associated with low EPO-R expression (p=0.034) and hemoglobin levels during radiotherapy ≥ 12 g/dl (p=0.026). Low EPO expression was associated with survival on univariate (p=0.010) but not on multivariate analysis (p=0.42). On multivariate analysis, improved loco-regional control was significantly associated with hemoglobin levels during radiotherapy ≥ 12 g/dl (p<0.001)." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Erythropoietin", "Esophageal Neoplasms", "Female", "Hemoglobins", "Humans", "Male", "Middle Aged", "Neoplasm Staging", "Oxygen", "Prognosis", "Receptors, Erythropoietin", "Time Factors" ] }

{ "contexts": [ "Consumption of lycopene through tomato products has been suggested to reduce the risk of prostate cancer. Cellular adhesion and migration are important features of cancer progression and therefore a potential target for cancer interception. In the present study we have examined the in vitro effect of lycopene on these processes.", "Prostate cancer cell lines PC3, DU145 and immortalised normal prostate cell line PNT-2 were used. The adhesion assay consisted of seeding pre-treated cells onto Matrigel™, gently removing non-adherent cells and quantitating the adherent fraction using WST-1. Migratory potential was assessed using ibidi™ migration chamber inserts, in which a cell-free zone between two confluent areas was allowed to populate over time and the migration measured.", "24 hour incubation of prostate cell lines with 1.15µmol/l lycopene showed a 40% reduction of cellular motility in case of PC3 cells, 58% in DU145 cells and no effect was observed for PNT2 cells. A dose related inhibition of cell adhesion to a basement membrane in the form of Matrigel™ was observed in all three cell lines and it reached statistical significance for PC3 and PNT2 cells at lycopene concentrations ≥1.15µmol/l. However, in case of DU145, only a concentration of 2.3µmol/l showed a significant reduction." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Apoptosis", "Carotenoids", "Cell Adhesion", "Cell Movement", "Humans", "Lycopene", "Lycopersicon esculentum", "Male", "Prostatic Neoplasms" ] }

{ "contexts": [ "Prostate cancer is the second most common form of cancer in males, affecting one in eight men by the time they reach the age of 70 years. Current diagnostic tests for prostate cancer have significant problems with both false negatives and false positives, necessitating the search for new molecular markers. A recent investigation of endosomal and lysosomal proteins revealed that the critical process of endosomal biogenesis might be altered in prostate cancer. Here, a panel of endosomal markers was evaluated in prostate cancer and nonmalignant cells and a significant increase in gene and protein expression was found for early, but not late endosomal proteins. There was also a differential distribution of early endosomes, and altered endosomal traffic and signaling of the transferrin receptors (TFRC and TFR2) in prostate cancer cells. These findings support the concept that endosome biogenesis and function are altered in prostate cancer. Microarray analysis of a clinical cohort confirmed the altered endosomal gene expression observed in cultured prostate cancer cells. Furthermore, in prostate cancer patient tissue specimens, the early endosomal marker and adaptor protein APPL1 showed consistently altered basement membrane histology in the vicinity of tumors and concentrated staining within tumor masses. These novel observations on altered early endosome biogenesis provide a new avenue for prostate cancer biomarker investigation and suggest new methods for the early diagnosis and accurate prognosis of prostate cancer." ], "labels": [ "UNLABELLED" ], "meshes": [ "Adaptor Proteins, Signal Transducing", "Antigens, CD", "Biomarkers, Tumor", "Cell Line, Tumor", "Endosomes", "Gene Expression Regulation, Neoplastic", "Humans", "Male", "Prostatic Neoplasms", "Receptors, Transferrin", "Signal Transduction" ] }

{ "contexts": [ "SOX18 is a transcription factor known to be involved in blood and lymphatic vessel, hair follicle development, and wound healing processes. In addition, it has been reported that SOX18 may influence cancer growth. The role of SOX18 expression in ovarian cancer (OC) has not been determined.", "SOX18 expression was assessed in 85 OC cases using immunohistochemical methods and in ovarian cancer cell lines on the mRNA and protein level.", "SOX18 was expressed in cancer cell nuclei as well as the cytoplasm. Higher nuclear SOX18 expression was associated with presence of residual disease following surgical treatment (p=0.0158) and advanced disease stage (p=0.0056). Univariate survival analysis revealed that high SOX18 (p=0.0125) expression, presence of residual disease (p<0.0001) and advanced disease stage (p<0.0324) predicted poor patient outcome." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Cell Line, Tumor", "Female", "Humans", "Immunohistochemistry", "Ovarian Neoplasms", "Platinum", "SOXF Transcription Factors" ] }

{ "contexts": [ "Arsenic trioxide (ATO) strongly induces apoptosis and differentiation in acute promyelocytic leukemia, and induces cell cycle arrest in most solid tumors. Although many signaling pathways are involved in its antitumor mechanism, a detailed investigation of the transforming growth factor beta-bone morphogenetic protein signaling pathway has not been performed.", "A microarray containing 113 genes associated with the pathway was used to screen important molecules that participate in the antitumor effects of ATO. The expression levels of the inhibitors of DNA binding-2 (ID2) in 4 different types of cancer cells were determined by quantitative reverse transcription PCR and Western blotting. Human esophageal squamous cell carcinoma cell line Eca109 and pancreatic carcinoma cell line BxPC3 cells were transfected with siRNAs targeting ID2 and scrambled control siRNA. Cell proliferation was evaluated by methyl thiazolyl tetrazolium assay.", "Eighteen upregulated and 12 downregulated genes were identified. After verification at the transcriptional and translational levels in 4 different cancer cells, ID2 was identified as an ATO antitumor-associated protein. In addition, specific silencing of ID2 could enhance ATO-induced cell proliferation inhibition in cancer cells." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Antineoplastic Agents", "Arsenic Trioxide", "Arsenicals", "Base Sequence", "Blotting, Western", "Bone Morphogenetic Proteins", "Carcinoma", "Cell Line, Tumor", "Colorectal Neoplasms", "Esophageal Neoplasms", "Gene Expression Regulation, Neoplastic", "Humans", "Inhibitor of Differentiation Protein 2", "Molecular Sequence Data", "Neoplasms", "Oxides", "Pancreatic Neoplasms", "Protein Biosynthesis", "Reverse Transcriptase Polymerase Chain Reaction", "Signal Transduction", "Stomach Neoplasms", "Transcription, Genetic", "Transforming Growth Factor beta", "Up-Regulation" ] }

{ "contexts": [ "Profilins are actin-modulating proteins regulating many intracellular functions based on their multiple and diverse ligand interactions. They have been implicated to play a role in many pathological conditions such as allergies, cardiovascular diseases, muscular atrophy, diabetes, dementia and cancer. Post-translational modifications of profilin 1 can alter its properties and subsequently its function in a cell. In the present study, we identify the importance of phosphorylation of profilin 1 at serine 137 (S137) residue in breast cancer progression.", "We found elevated profilin 1 (PFN) in human breast cancer tissues when compared to adjacent normal tissues. Overexpression of wild-type profilin 1 (PFN-WT) in breast cancer MCF7 cells made them more migratory, invasive and adherent independent in comparison to empty vector transfected cells. Mutation in serine phosphorylation site (S137) of profilin 1 (PFN-S137A) significantly abrogated these properties. Mutation affecting actin-binding ability (PFN-R74E) of profilin 1 enhanced its tumorigenic function whereas mutation affecting its poly-L-proline binding function (PFN-H133S) alleviated these mechanisms in breast cancer cells. PFN-WT was found to activate matrix metalloproteinases by zymography, MMP2 and MMP9 in presence of PDBu (phorbol 12, 13 dibutyrate, PI3K agonist) to enhance migration and invasion in MCF7 cells while PFN-S137A did not. Phosphorylation increased migration and invasion in other mutants of profilin 1. Nuclear profilin levels also increased in the presence of PDBu." ], "labels": [ "BACKGROUND", "RESULTS" ], "meshes": [ "Blotting, Western", "Breast Neoplasms", "Cell Line, Tumor", "Electrophoresis, Polyacrylamide Gel", "Female", "Flow Cytometry", "Humans", "In Vitro Techniques", "Phosphorylation", "Profilins", "Wound Healing" ] }

{ "contexts": [ "Colorectal cancer (CRC) screening is effective but underutilized. Although physician recommendation is an important predictor of screening, considerable variation in CRC screening completion remains.", "To characterize the influence of patient trust in care providers on CRC screening behavior.", "Data were collected as part of a cluster-randomized CRC screening intervention trial performed in the San Francisco Community Health Network from March 2007 to January 2012 (analysis, Spring 2012). All study participants received a recommendation to complete CRC screening from their primary care provider (PCP). Included participants were aged 50-79 years, not current with screening, and completed the Wake Forest Trust Scale (WFTS) measuring trust in PCPs and doctors in general. Primary outcome was CRC screening completion (colonoscopy or fecal occult blood testing) within 12 months following enrollment. Multivariable association adjusted for race/ethnicity, language, and other sociodemographics was estimated using generalized estimating equations with logit link and binomial distribution.", "WFTS response was 70.3% (701). Most participants (83%) were Latino, Asian, or black. Most had income <$30,000 (96%) and public health insurance (86%). Higher trust in PCP was associated with screening completion (OR=1.11, 95% CI=1.03, 1.17), but trust in doctors was not (OR=1.02, 95% CI=0.82, 1.28). Race, language, and other sociodemographic factors were not significant in multivariable analysis." ], "labels": [ "BACKGROUND", "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Aged", "Colonoscopy", "Colorectal Neoplasms", "Female", "Humans", "Male", "Mass Screening", "Middle Aged", "Occult Blood", "Patient Acceptance of Health Care", "Physician-Patient Relations", "Poverty", "San Francisco", "Trust" ] }

{ "contexts": [ "Rectal cancer has a higher risk of developing lung metastasis compared with colon cancer. It is unclear whether the prognosis after pulmonary metastasectomy for these distinct tumors is different.", "Patients who underwent pulmonary metastasectomy for colorectal carcinoma were analyzed for survival and patterns of recurrence depending on the location of the primary colorectal cancer. Multivariate regression analysis was performed to identify clinical variables predictive of survival after pulmonary metastasectomy.", "Between 1985 and 2012, 698 patients underwent pulmonary metastasectomy for metastatic colorectal cancer. Complete information was available in 626 patients. These patients were divided into groups based on whether the primary tumor was colon or rectal in origin. Median follow-up was 45.5 months (range, 23 to 287 months). There were no statistical differences between the two groups in terms of number of lung metastases, tumor size, or lymph node involvement. There was no difference in overall survival (p = 0.545). Five-year disease-free survival for colon cancer patients was 67.2% compared with 60.1% for rectal cancer (p = 0.004). The most common sites of recurrence after pulmonary metastasectomy were liver in colon cancer and lung in rectal cancer. Multivariate Cox proportional hazards analysis indicated that rectal cancer (hazard ratio, 1.39; 95% confidence interval, 1.07 to 1.83; p = 0.015) and multiple metastases (>3; hazard ratio, 1.41; 95% confidence interval, 1.04 to 1.89; p = 0.027) were independent adverse risk factors affecting disease-free survival after pulmonary metastasectomy." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Aged, 80 and over", "Colorectal Neoplasms", "Female", "Humans", "Lung Neoplasms", "Male", "Metastasectomy", "Middle Aged", "Neoplasm Recurrence, Local", "Prognosis", "Proportional Hazards Models" ] }

{ "contexts": [ "We have previously reported the crucial roles of oncogenic Kirsten rat sarcoma viral oncogene homolog (KRAS) in inhibiting apoptosis and disrupting cell polarity via the regulation of phosphodiesterase 4 (PDE4) expression in human colorectal cancer HCT116 cells in three-dimensional cultures (3DC). Herein we evaluated the effects of resveratrol, a PDE4 inhibitor, on the luminal cavity formation and the induction of apoptosis in HCT116 cells.", "Apoptosis was detected by immunofluorescence using confocal laser scanning microscopy with an antibody against cleaved caspase-3 in HCT116 cells treated with or without resveratrol in a two-dimensional culture (2DC) or 3DC.", "Resveratrol did not induce apoptosis of HCT116 cells in 2DC, whereas the number of apoptotic HCT116 cells increased after resveratrol treatment in 3DC, leading to formation of a luminal cavity." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Apoptosis", "HCT116 Cells", "Humans", "Phosphodiesterase 4 Inhibitors", "Resveratrol", "Stilbenes" ] }

{ "contexts": [ "To investigate the influence of clinical characteristics including nutritional markers on postoperative survival in patients undergoing total gastrectomy (TG) for gastric cancer (GC).", "One hundred fifty-four patients were enrolled. Uni- and multivariate analyses using the Cox proportional hazard model were performed to explore the most valuable clinical characteristic that was associated with postoperative survival.", "Multivariate analysis using twelve clinical characteristics selected from univariate analyses revealed that age (≤ 72/>72), carcinoembryonic antigen (≤ 20/>20) (ng/ml), white blood cell count (≤ 9.5/>9.5) (× 10(3)/mm(3)), prognostic nutritional index (PNI) (≤ 45/>45) and lymph node metastasis (negative/positive) were associated with postoperative survival. Kaplan-Meier analysis and log-rank test showed that patients with higher PNI (>45) had a higher postoperative survival rate than those with lower PNI (≤ 45) (p<0.001)." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Female", "Gastrectomy", "Humans", "Male", "Middle Aged", "Nutritional Status", "Prognosis", "Proportional Hazards Models", "Retrospective Studies", "Stomach Neoplasms" ] }

{ "contexts": [ "Tumor-derived matricellular proteins such as osteopontin (OPN) and tenascin-C (TN-C) have been implicated in tumor growth and metastasis. However, the molecular basis of how these proteins contribute to tumor progression remains to be elucidated. Importantly, these matricellular proteins are known to interact with α9β1 integrin. Therefore, we hypothesized that tumor-derived α9β1 integrin may contribute to tumor progression. To clarify the roles of α9β1 integrin in tumor growth and lymphatic metastasis, we used an inhibitory anti-human α9β1 integrin antibody (anti-hα9β1 antibody) and a α9β1 integrin-positive human breast cancer cell line, MDA-MB-231 luc-D3H2LN (D3H2LN), in vitro functional assays, and an in vivo orthotopic xenotransplantation model. In this study, we demonstrated that tumor, but not host α9β1 integrin, contributes to tumor growth, lymphatic metastasis, recruitment of cancer-associated fibroblasts (CAFs), and host-derived OPN production. We also found that CAFs contributed to tumor growth, lymphatic metastasis, and host-derived OPN levels. Consistent with those findings, tumor volume was well-correlated with numbers of CAFs and levels of host-derived OPN. Furthermore, it was shown that the inoculation of D3H2LN cells into mammary fat pads with mouse embryonic fibroblasts (MEFs), obtained from wild type, but not OPN knock-out mice, resulted in enhancement of tumor growth, thus indicating that CAF-derived OPN enhanced tumor growth. These results suggested that tumor α9β1-mediated signaling plays a pivotal role in generating unique primary tumor tissue microenvironments, which favor lymphatic metastasis and tumor growth." ], "labels": [ "UNLABELLED" ], "meshes": [ "Animals", "Breast Neoplasms", "Cell Line, Tumor", "Cell Proliferation", "Female", "Fibroblasts", "Humans", "Integrins", "Lymphatic Metastasis", "Mice", "Mice, Knockout", "Neoplasm Invasiveness", "Osteopontin", "Signal Transduction" ] }

{ "contexts": [ "It has been hypothesized that minichromosome maintenance (MCM) proteins, which are replicative control factors, can be used to detect tumor proliferation. The aim of the present study was to investigate the expression of MCM in colorectal cancer tissues and correlate it to clinical outcomes.", "The study included 145 patients with colorectal cancer who underwent curative surgery, from January 2002 until December 2004, at the Kurume University Hospital in Fukuoka, Japan. The median follow-up duration was 87 months. The expression of MCM7 in tissues was studied by immuno-histochemical staining. The labeling index (LI) of MCM7 was calculated by dividing the number of positively-stained cells by the total number of cells counted. We divided samples into two groups: positive (MCM7 LI 76% or higher) and negative (MCM7 LI less than 76%).", "In patients with Dukes A and B, there were no significant differences in either overall survival (OS) or recurrence-free survival (RFS) between patents with MCM7-positive and those with MCM7-negative disease. On the other hand, in patients with Dukes C, there was significantly worse OS and RFS for patients with MCM7-positive compared to those with MCM7-negative disease." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Aged, 80 and over", "Colorectal Neoplasms", "Female", "Humans", "Immunohistochemistry", "Ki-67 Antigen", "Male", "Middle Aged", "Minichromosome Maintenance Complex Component 7", "Neoplasm Recurrence, Local", "Proportional Hazards Models", "Risk Factors" ] }

{ "contexts": [ "Whether moderate to severe obesity (body mass index (BMI)≥30 to <40kg/m(2)) contributes to breast cancer recurrence and mortality remains uncertain.", "1199 women, recruited within 12 months of their diagnosis of hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) invasive breast cancer completed an enrolment questionnaire and an annual follow-up questionnaire every 12 months for another 5 years. The impact of obesity on time to either local or distant recurrence or new breast cancer, or death due to breast cancer was determined by Cox regression. Women in the most extreme categories of BMI (<18.5 and ≥40) were excluded from the analysis.", "Of the 1155 included women, mean age, 58.4±11.6 years, 53.8% had Stage 1 disease and 88.9% received oral adjuvant endocrine therapy (OAET) within 2 years of diagnosis. The likelihood of an event was significantly associated with moderate to severe obesity (HR=1.71, 95%CI, 1.12-2.62, p=0.014), disease beyond Stage 1 (HR=2.87, 95% CI 1.73-4.75, p<0.001), OAET (HR=0.26, 95%CI 0.14-0.46, p<0.001), mastectomy (HR=3.28, 95%CI 1.98-5.44, p<0.001) and radiotherapy (HR=2.12, 95%CI 1.24-3.63, p=0.006). For Stage 1 disease, only moderate to severe obesity (HR 3.23, 95%CI 1.48-7.03, p=0.003) and OAET use (HR 0.41, 95%CI 0.17-0.98, p=0.046) were significantly associated with an event." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Aged", "Body Mass Index", "Breast Neoplasms", "Carcinoma, Ductal, Breast", "Carcinoma, Lobular", "Cause of Death", "Chemotherapy, Adjuvant", "Cohort Studies", "Disease-Free Survival", "Female", "Follow-Up Studies", "Humans", "Mastectomy", "Mastectomy, Segmental", "Middle Aged", "Neoadjuvant Therapy", "Neoplasm Recurrence, Local", "Neoplasm Staging", "Obesity", "Prognosis", "Radiotherapy, Adjuvant", "Receptor, ErbB-2", "Receptors, Estrogen", "Receptors, Progesterone", "Risk Factors", "Survival Rate" ] }

{ "contexts": [ "Prostate cancer is one of the most common complex diseases with high leading cause of death in men. Identifications of prostate cancer associated genes and biomarkers are thus essential as they can gain insights into the mechanisms underlying disease progression and advancing for early diagnosis and developing effective therapies.", "In this study, we presented an integrative analysis of gene expression profiling and protein interaction network at a systematic level to reveal candidate disease-associated genes and biomarkers for prostate cancer progression. At first, we reconstructed the human prostate cancer protein-protein interaction network (HPC-PPIN) and the network was then integrated with the prostate cancer gene expression data to identify modules related to different phases in prostate cancer. At last, the candidate module biomarkers were validated by its predictive ability of prostate cancer progression.", "Different phases-specific modules were identified for prostate cancer. Among these modules, transcription Androgen Receptor (AR) nuclear signaling and Epidermal Growth Factor Receptor (EGFR) signalling pathway were shown to be the pathway targets for prostate cancer progression. The identified candidate disease-associated genes showed better predictive ability of prostate cancer progression than those of published biomarkers. In context of functional enrichment analysis, interestingly candidate disease-associated genes were enriched in the nucleus and different functions were encoded for potential transcription factors, for examples key players as AR, Myc, ESR1 and hidden player as Sp1 which was considered as a potential novel biomarker for prostate cancer." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Biomarkers, Tumor", "Computational Biology", "Disease Progression", "Gene Expression Profiling", "Genes, Neoplasm", "Humans", "Male", "Molecular Sequence Annotation", "Prostatic Neoplasms", "Protein Interaction Mapping", "Sp1 Transcription Factor" ] }

{ "contexts": [ "Prognosis and treatment of patients with breast carcinoma of no special type (NST) is dependent on a few established parameters, such as tumor size, histological grade, lymph node stage, expression of estrogen receptor, progesterone receptor, and HER-2/neu, and proliferation index. The original Nottingham Prognostic Index (NPI) employs a three-tiered classification system that stratifies patients with breast cancer into good, moderate, and poor prognostic groups. The aim of our study was to use robust immunohistochemical methodology for determination of ER, PR, HER-2/neu, Ki-67, p53, and Bcl-2, and to observe differences in the expression of these markers when patients are stratified according to the original, three-tiered Nottingham Prognostic Index.", "Paraffin blocks from 120 patients diagnosed with breast carcinoma, NST, were retrieved from our archive. Cases included in the study were female patients previously treated with modified radical mastectomy and axillary dissection.", "Our study demonstrates that expression of markers of good prognosis, such as ER, PR, and Bcl-2, is seen with higher frequency in good and moderate NPI groups. In contrast, overexpression of HER-2/neu, a marker of adverse prognosis, is more frequent in moderate and poor NPI groups. High proliferation index, as measured by Ki-67, is seen in moderate and poor NPI groups, whereas low proliferation index is seen in good NPI groups." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Biomarkers, Tumor", "Breast Neoplasms", "Female", "Humans", "Immunoenzyme Techniques", "Prognosis", "Proto-Oncogene Proteins c-bcl-2", "Receptor, ErbB-2", "Receptors, Estrogen", "Receptors, Progesterone", "Severity of Illness Index", "Tumor Suppressor Protein p53" ] }

{ "contexts": [ "Lung cancer is the most important cause of cancer mortality worldwide, but the underlying mechanisms of this disease are not fully understood. Copy number variations (CNVs) are promising genetic variations to study because of their potential effects on cancer.", "Here we conducted a pilot study in which we systematically analyzed the association of CNVs in two lung cancer datasets: the Environment And Genetics in Lung cancer Etiology (EAGLE) and the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial datasets. We used a preestablished association method to test the datasets separately and conducted a combined analysis to test the association accordance between the two datasets. Finally, we identified 167 risk SNP loci and 22 CNVs associated with lung cancer and linked them with recombination hotspots. Functional annotation and biological relevance analyses implied that some of our predicted risk loci were supported by other studies and might be potential candidate loci for lung cancer studies." ], "labels": [ "BACKGROUND", "RESULTS" ], "meshes": [ "DNA Copy Number Variations", "Genome-Wide Association Study", "Humans", "Lung Neoplasms", "Polymorphism, Single Nucleotide", "Risk" ] }

{ "contexts": [ "Is weight-training exercise intervention harmful to women with or at risk of breast cancer-related lymphoedema?", "Systematic review with meta-analysis of randomised trials.", "Women with or at risk of breast cancer-related lymphoedema.", "Progressive weight-training exercise.", "The primary outcomes were severity (volume difference) and incidence of arm lymphoedema. Secondary outcomes included muscle strength of the upper and lower limbs, quality of life and body mass index.", "Eleven studies from eight trials involving 1091 women were included. Weight-training exercise of low to moderate intensity with relatively slow progression significantly improved the upper limb strength (SMD 0.93, 95% CI 0.73 to 1.12) and lower limb strength (SMD 0.75, 95% CI 0.47 to 1.04) without increasing the arm volume (SMD -0.09, 95% CI -0.23 to 0.05) or incidence of breast cancer-related lymphoedema (RR 0.77, 95% CI 0.52 to 1.15). No significant effects were noted for body mass index (SMD -0.10, 95% -0.31 to 0.11). Some aspects of quality of life may improve with weight training. PARTICIPANTS in all trials used pressure garments and received supervision; no trials used high-intensity weight training." ], "labels": [ "OBJECTIVE", "METHODS", "METHODS", "METHODS", "METHODS", "RESULTS" ], "meshes": [] }

{ "contexts": [ "B7-H1, a co-inhibitory molecule of the B7 family, is found aberrantly expressed in ovarian cancer cells and infiltrating macrophage/dendritic-like cells, and plays a critical role in immune evasion by ovarian cancer. IL-12, an inducer of Th1 cell development, exerts immunomodulatory effects on ovarian cancer. However, whether IL-12 regulates B7-H1 expression in human ovarian cancer associated-macrophages has not been clarified. Therefore, we investigated the effects of IL-12 on the expression of B7-H1 in ovarian cancer-associated macrophages and possible mechanisms.", "PMA induced THP-1-derived macrophages or human monocyte-derived macrophages were treated with recombinant IL-12 (rIL-12) or infected with adenovirus carrying human IL-12 gene (Ad-IL-12-GFP) for 24 h, then cocultured with the SKOV3 ovarian cancer cell line for another 24 h. Macrophages were collected for real-time PCR and Western blot to detect the expression of B7-H1, and activation of the NF-κB signaling pathway. Moreover, supernatants were collected to assay for IL-12, IFN-γ and IL-10 by ELISA. In addition, monocyte-derived macrophages treated with IFN-γ were cocultured with SKOV3 and determined for the expression of B7-H1. Furthermore, the expression of B7-H1 in monocyte-derived macrophages was also evaluated after blocking NF-κB signaling.", "The expression of B7-H1 was significantly upregulated in monocyte-derived macrophages treated with rIL-12 or Ad-IL-12-GFP compared with the control groups (p<0.05), accompanied by a remarkable upregulation of IFN-γ (p<0.05), a marked downregulation of IL-10 (p<0.05) and activation of NF-κB signaling. However, the upregulation of B7- H1 was inhibited by blocking the NF-κB signaling pathway (p<0.05). Expression of B7-H1 was also increased (p<0.05) in monocyte-derived macrophages treated with IFN-γ and cocultured with SKOV3. By contrast, the expression of B7-H1 in THP-1-derived macrophages was significantly decreased when treated in the same way as monocyte-derived macrophages (p<0.05), and IL-10 was also significantly decreased but IFN-γ was almost absent." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "B7-H1 Antigen", "Cell Line, Tumor", "Enzyme Activation", "Female", "Humans", "Interferon-gamma", "Interleukin-10", "Interleukin-12", "Macrophages", "Ovarian Neoplasms", "Transcription Factor RelA", "Tumor Escape" ] }

{ "contexts": [ "Stathmin is a ubiquitous cytosolic regulatory phosphoprotein and is overexpressed in different human malignancies. The main physiological function of stathmin is to interfere with microtubule dynamics by promoting depolymerization of microtubules or by preventing polymerization of tubulin heterodimers. Stathmin plays important roles in regulating many cellular functions as a result of its microtubule-destabilizing activity. Currently, the critical roles of stathmin in cancer cells, as well as in lymphocytes have been valued. This review discusses stathmin and microtubule dynamics in cancer development, and hypothesizes their possible relationship with epithelial-mesenchymal transition (EMT).", "A PubMed search using such terms as \"stathmin\", \"microtubule dynamics\", \"epithelial-mesenchymal transition\", \"EMT\", \"malignant potential\" and \"cancer\" was performed to identify relevant studies published in English. More than 100 related articles were reviewed.", "The literature clearly documented the relationship between stathmin and its microtubule-destabilizing activity of cancer development. However, the particular mechanism is poorly understood. Microtubule disruption is essential for EMT, which is a crucial process during cancer development. As a microtubule-destabilizing protein, stathmin may promote malignant potential in cancer cells by initiating EMT." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [] }

{ "contexts": [ "Adjuvant chemotherapy improves survival in patients with gastric cancer. However, the relationship between the timing of adjuvant chemotherapy and survival has not been investigated.", "Patients with D2-resected stage 2 and 3 gastric cancer that received adjuvant chemotherapy from 2005 to 2011 at Yonsei University Health System were included. The patients were grouped according to intervals between surgery and adjuvant chemotherapy.", "Among 840 patients, the interval from surgery to the start of adjuvant therapy was less than 4 weeks in 337 (40.1 %) patients (early group), 4-8 weeks in 467 (55.6 %) patients (intermediate group), and more than 8 weeks in 36 (4.3 %) patients (late group). The 5-year RFS was 55.7 % in the early group, 54.4 % in the intermediate group, and 43.6 % in the late group (p = 0.076). The corresponding 5-year OS rates were 63.4, 62.8, and 51.7 % (p = 0.037)." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Adenocarcinoma, Mucinous", "Aged", "Antineoplastic Combined Chemotherapy Protocols", "Carcinoma, Signet Ring Cell", "Chemotherapy, Adjuvant", "Female", "Follow-Up Studies", "Humans", "Male", "Neoplasm Recurrence, Local", "Neoplasm Staging", "Prognosis", "Stomach Neoplasms", "Survival Rate", "Time Factors" ] }

{ "contexts": [ "Androgen receptor (AR) plays an important role in male breast cancer (MBC). Additionally, endocrine therapy is the most important treatment in oestrogen receptor (ER)-positive advanced breast cancer. This study was aimed to investigate the role of AR in MBC treatment and prognosis and to analyse the relationship between AR and the effect of tamoxifen treatment in MBC patients.", "AR protein levels and other tumour characteristics (e.g. expression of ER (ESR1), PR (PGR), AR, HER2 (ERBB2) and Ki-67 (MKI67)) in breast cancer tissue from 102 MBC patients were determined using immunohistochemical analysis. Additionally, the relationship between AR status and clinicopathological features was analysed using the χ(2)-test. Association with survival was initially analysed using the Kaplan-Meier method and the log-rank test, and Cox regression analysis was used to adjust for other prognostic indicators.", "High expression of AR was not correlated with T-stage, histological grade, HER2 status and the status of other sex hormone receptors, but was associated with lymph node metastases (P=0.032). AR-positive patients showed significantly shorter 5-year overall survival (OS) rates (P=0.045) and 5-year disease-free survival (DFS) rates (P=0.026) than AR-negative patients. By contrast, for patients who received tamoxifen therapy, AR-negative patients showed a higher clinical benefit rate than AR-positive patients (P=0.025). Additionally, the median TTP and OS were significantly different (P=0.02 for TTP; P=0.029 for OS)." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Antineoplastic Agents, Hormonal", "Biomarkers, Tumor", "Breast Neoplasms, Male", "Chemotherapy, Adjuvant", "Disease-Free Survival", "Estrogen Antagonists", "Gene Expression Regulation, Neoplastic", "Humans", "Immunohistochemistry", "Kaplan-Meier Estimate", "Ki-67 Antigen", "Male", "Middle Aged", "Neoplasm Staging", "Predictive Value of Tests", "Receptor, ErbB-2", "Receptors, Androgen", "Receptors, Estrogen", "Receptors, Progesterone", "Tamoxifen", "Treatment Outcome" ] }

{ "contexts": [ "Oncolytic viruses represent a promising therapy against cancers with acquired drug resistance. However, low efficacy limits its clinical application. The objective of this study is to investigate whether pharmacologically modulating autophagy could enhance oncolytic Newcastle disease virus (NDV) strain NDV/FMW virotherapy of drug-resistant lung cancer cells.", "The effect of NDV/FMW infection on autophagy machinery in A549 lung cancer cell lines resistant to cisplatin (A549/DDP) or paclitaxel (A549/PTX) was investigated by detection of GFP-microtubule-associated protein 1 light chain 3 (GFP-LC3) puncta, formation of double-membrane vesicles and conversion of the nonlipidated form of LC3 (LC3-I) to the phosphatidylethanolamine-conjugated form (LC3-II). The effects of autophagy inhibitor chloroquine (CQ) and autophagy inducer rapamycin on NDV/FMW-mediated antitumor activity were evaluated both in culture cells and in mice bearing drug-resistant lung cancer cells.", "We show that NDV/FMW triggers autophagy in A549/PTX cells via dampening the class I PI3K/Akt/mTOR/p70S6K pathway, which inhibits autophagy. On the contrary, NDV/FMW infection attenuates the autophagic process in A549/DDP cells through the activation of the negative regulatory pathway. Furthermore, combination with CQ or knockdown of ATG5 significantly enhances NDV/FMW-mediated antitumor effects on A549/DDP cells, while the oncolytic efficacy of NDV/FMW in A549/PTX cells is significantly improved by rapamycin. Interestingly, autophagy modulation does not increase virus progeny in these drug resistant cells. Importantly, CQ or rapamycin significantly potentiates NDV/FMW oncolytic activity in mice bearing A549/DDP or A549/PTX cells respectively." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Animals", "Autophagy", "Cell Line, Tumor", "Chick Embryo", "Chloroquine", "Drug Resistance, Neoplasm", "Gene Knockdown Techniques", "Humans", "Lung Neoplasms", "Mice", "Mice, Nude", "Microtubule-Associated Proteins", "Neoplasm Transplantation", "Newcastle disease virus", "Oncolytic Virotherapy", "Oncolytic Viruses", "Sirolimus", "Xenograft Model Antitumor Assays" ] }

{ "contexts": [ "The aim of this study was to investigate the smoking status of lung cancer patients and to confirm the risk of smoking for patients undergoing lung cancer surgery.", "We conducted a retrospective study of patients undergoing lung cancer surgery. Between May 2004 and March 2013, 716 patients underwent lung cancer surgery at our institution. Based on smoking status, the patients were classified into 3 groups: nonsmoker, past smoker, and current smoker. Based on exclusion criteria, a final total of 670 patients were investigated for the association between smoking status and postoperative complications. In addition, we explored the effect of smoking on survival after surgery.", "There were 254 non-smokers, 246 past smokers, and 170 current smokers. The percent of female patients, adenocarcinoma, and stage IA cancer was highest in the nonsmokers. Respiratory function was significantly impaired in past and current smokers. Respiratory and cardiac complications were found less frequently in non-smokers (11.4%) followed by 17.1% of past smokers and 21.2% of current smokers (p = 0.0226). Univariate analysis showed that smoking was a significantly poor prognostic factor for overall survival. The 5-year survival rates for non-smokers, past, and current smokers were 81.4, 65.4, and 68.8%, respectively (p = 0.0003)." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adenocarcinoma", "Adult", "Aged", "Aged, 80 and over", "Carcinoma, Squamous Cell", "Female", "Humans", "Lung Neoplasms", "Male", "Middle Aged", "Multivariate Analysis", "Neoplasm Staging", "Prognosis", "Pulmonary Surgical Procedures", "Retrospective Studies", "Risk Factors", "Smoking" ] }

{ "contexts": [ "We evaluated whether detecting prostate cancer cells by the nested reverse transcriptase-polymerase chain reaction (RT-PCR) in lymph nodes has predictive value for serum prostate specific antigen (PSA) recurrence in patients undergoing radical prostatectomy.", "We assessed the presence of prostate cancer cells by RT-PCR for prostate specific membrane antigen and PSA assay in lymph nodes dissected from 38 patients with localized prostate cancer treated with radical prostatectomy. The results of nested RT-PCR assay were compared with biochemical recurrence.", "Nested RT-PCR was positive in the lymph nodes of 2 of 18 patients (11%) with stage pT2a and 5 of 20 (25%) with stage pT2b disease. All 7 patients had biochemical recurrence. We noted a significant difference in the Kaplan-Meier recurrence-free actuarial probability curve in those with positive and negative nested RT-PCR results for prostate specific membrane antigen, PSA and prostate specific membrane antigen-PSA in the lymph nodes (p = 3.02x10(-7), 2.23x10(-7) and 3.02x10(-7), respectively). Multivariate analysis of serum PSA, Gleason score and preoperative RT-PCR assay in peripheral blood showed that nested RT-PCR for prostate specific membrane antigen, PSA and prostate specific membrane antigen-PSA in the lymph nodes were independent predictors of recurrence (p = 0.0089, 0.0075 and 0.0089, respectively)." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Aged", "Humans", "Lymph Nodes", "Lymphatic Metastasis", "Male", "Middle Aged", "Neoplasm Recurrence, Local", "Neoplasm Staging", "Predictive Value of Tests", "Prognosis", "Prostate-Specific Antigen", "Prostatectomy", "Prostatic Neoplasms", "Reverse Transcriptase Polymerase Chain Reaction" ] }

{ "contexts": [ "To determine the efficacy of screening women under age 50 with a significant family history of breast cancer.", "Results from 22 Breast Units in the UK identified as being able to provide data were surveyed and pooled through regional data managers or consultant breast specialists.", "Data relating to 8783 women screened and 9075 woman years of follow-up was analysed. Cancer incidence was 11.3/1000/year. The rate of cancer detection was 4. 78/1000 at prevalent screening and 4.52/1000 at incident screening. Median age at diagnosis was 43 years. Interval cancers presented at a rate of 2.45/1000. Comparison with the National Health Service Breast Screening Programme for women aged 50-64 revealed a similar rate of cancer detection and a similar incidence of ductal carcinoma in situ. The pathological features of screen-detected cancers in this study strongly suggest that prognosis for these women is more favourable than if they had presented symptomatically." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Breast Neoplasms", "Female", "Humans", "Incidence", "Middle Aged", "Prevalence", "United Kingdom" ] }

{ "contexts": [ "The number of positive axillary lymph nodes predicts prognosis and is often important in determining adjuvant chemotherapy in breast cancer patients. This study was undertaken to determine if differences in the extent of axillary node dissection would alter the number of reported positive nodes.", "The study population consisted of 302 patients with invasive breast cancer who underwent complete (level I/II/III) axillary lymph node dissection. Assuming that all patients had undergone a level I/II dissection, it was determined how frequently a patient's nodal category (0, 1-3, 4-9, >10 positive nodes) would have been altered if a level I or level I/II/III dissection were performed.", "Assuming that all 302 patients had undergone a level I/II dissection, performing only level I dissection would have resulted in a change in nodal category in 15.9% of all patients and 36.1% of patients with positive nodes. The corresponding changes for a level I/II/III dissection would have been 4.3% and 9.5%, respectively." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Axilla", "Bias", "Breast Neoplasms", "Female", "Humans", "Lymph Node Excision", "Lymph Nodes", "Lymphatic Metastasis", "Neoplasm Staging", "Prognosis" ] }

{ "contexts": [ "An intact and fully functional multiprotein DNA replication complex (DNA synthesome) from human as well as from murine mammary carcinoma cells was first isolated and characterized in our laboratory. The human cell synthesome supports the in vitro origin-specific simian virus 40 (SV40) DNA replication reaction in the presence of the viral large T-antigen using a semiconservative mechanism and has been shown to contain all the proteins and enzymes required to support DNA synthesis. We are currently using the DNA synthesome as a unique model for analyzing the mechanism of action of anticancer drugs affecting DNA replication. The purpose of this study was to further investigate the mechanism of action of ara-C using the DNA synthesome isolated from the human breast cancer cell line MDA MB-468.", "Synthesome-mediated SV40 DNA replication was performed in the presence of various concentrations of ara-CTP (the active metabolite of ara-C) and the types of daughter DNA molecules produced were analyzed lusing neutral and alkaline gel electrophoresis. We also examined the effect of ara-C on intact MDA MB-468 cell DNA synthesis and on cell proliferation. In addition, we studied the effect of ara-CTP on the activity of some of the synthesome target proteins (the DNA polymerases alpha and delta).", "Full-length daughter DNA molecules were obtained in the presence of low concentrations of ara-CTP while at higher concentrations, there was an inhibition of full-length daughter DNA synthesis. The findings suggest that specifically the initiation phase of DNA synthesis was inhibited by ara-CTP since the production of the short Okazaki fragments was suppressed at all concentrations of the drug above 10 microM. In addition, it was found that the IC50 of ara-CTP for inhibition of synthesome-mediated in vitro DNA replication was comparable to that required to inhibit intact cell DNA synthesis. Further experimentation has shown that ara-CTP preferentially inhibits the activity of the synthesome-associated DNA polymerase alpha enzyme while the DNA polymerase delta seems to be resistant to the inhibitory effect of that drug." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Antigens, Polyomavirus Transforming", "Antimetabolites, Antineoplastic", "Arabinofuranosylcytosine Triphosphate", "Breast Neoplasms", "Cell Division", "Cytarabine", "DNA Polymerase I", "DNA Polymerase III", "DNA Replication", "DNA, Neoplasm", "Humans", "Replicon", "Tumor Cells, Cultured" ] }

{ "contexts": [ "Our objective was to determine whether paclitaxel-induced apoptosis in human lung cancer cells is Fas dependent.", "Human lung cancer cell lines were evaluated for morphologic evidence of apoptosis, DNA fragmentation (TUNEL positivity), and caspase-3 activation after paclitaxel treatment. Human lung adenocarcinoma, squamous cell carcinoma, undifferentiated lung carcinoma, and bronchoalveolar carcinoma cell lines were each cultured in 10 micromol/L paclitaxel.", "After 24 hours of culture in paclitaxel, a 22% to 69% increase in the number of apoptotic cells was evident by means of methylene blue-azure A-eosin staining with characteristic blebbing and nuclear condensation. TUNEL assay also confirmed an increase of 19.9% to 73.0% of cells with nuclear fragmentation. Caspase-3 activity, assayed by Z-DEVD cleavage, increased from 20% to 215% (P <.05). ZB4, an antagonistic anti-Fas antibody, did not block paclitaxel induction of caspase-3 activity (155.8 vs 165.8 U, not significant). Apoptotic morphologic changes were inhibited in cells cultured in the presence of paclitaxel and Ac-DEVD-CHO, a caspase-3 inhibitor." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Antineoplastic Agents, Phytogenic", "Apoptosis", "Carcinoma, Non-Small-Cell Lung", "Caspase 3", "Caspase Inhibitors", "Caspases", "DNA Fragmentation", "Humans", "In Situ Nick-End Labeling", "Lung Neoplasms", "Oligopeptides", "Paclitaxel", "Tumor Cells, Cultured", "fas Receptor" ] }

{ "contexts": [ "Increased concentrations of metalloproteinases are associated with the invasive and metastatic behavior of several human malignant tumors. Normally, enzymatic activity is tightly regulated by nonspecific mechanisms and specific inhibitors. The aim of the study was to determine the potential of a synthetic metalloproteinase inhibitor, batimastat, to show its in vitro effect on MatLyLu cancer cells and its in vivo effect on tumor growth in orthotopic cancer (R3327 Dunning tumor) in rats.", "In vitro, a dose response curve of batimastat was generated over 4 days using the MTT assay. Prostate cancer was injected in vivo in male Copenhagen rats by inoculating R3327 Dunning tumor cells (MatLyLu) into the ventral prostatic lobe of 30 rats. Each of 10 rats received batimastat (30 mg/kg body weight) or vehicle administered once a day by i.p. application beginning the day of cell inoculation. Ten rats remained untreated. The effect on local tumor growth was evaluated by measuring tumor weights 20 days after tumor cell inoculation.", "Significant inhibition of tumor cell proliferation in vitro occurred at 400 and 4,000 ng/ml batimastat. After orthotopic cell inoculation, tumors grew to mean weights of 18.9 g in the control group without treatment, to 22.3 g in the vehicle group, and to 11.1 g in the treated group. In comparison to the control group and to the vehicle group, tumor weights increased significantly less under treatment with batimastat." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Animals", "Antineoplastic Agents", "Cell Division", "Dose-Response Relationship, Drug", "Male", "Neoplasm Transplantation", "Phenylalanine", "Prostatic Neoplasms", "Rats", "Thiophenes", "Tumor Cells, Cultured" ] }

{ "contexts": [ "The aim of this study was to investigate the value of p53 and cyclin D1 gene expression in predicting the risk of occult lymph node metastases in patients with head and neck squamous cell carcinoma (HNSCC).", "The expression of cyclin D1 and p53 was evaluated by means of immunohistochemical analysis in 32 HNSCC patients with clinically and radiologically negative lymph nodes in whom metastatic involvement was subsequently demonstrated at histologic examination (pN+). A group of 64 head and neck cancer patients with histologically negative laterocervical lymph nodes (pN0) was used as a control.", "Cyclin D1 and p53 expression were observed respectively in 42 (43.7%) and 48 cases (50%). Cyclin D1 expression significantly correlated with tumor extension and advanced clinical stage (p =.002 and p =.001, respectively). At univariate regression analysis, cyclin D1 expression significantly correlated with the presence of occult lymph node metastases (p =. 0007), and it remained an independent predictor at multivariate regression analysis (p =.0059)." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Analysis of Variance", "Biomarkers, Tumor", "Biopsy, Needle", "Carcinoma, Squamous Cell", "Cyclin D1", "Female", "Head and Neck Neoplasms", "Humans", "Immunohistochemistry", "Logistic Models", "Lymph Node Excision", "Lymph Nodes", "Lymphatic Metastasis", "Male", "Middle Aged", "Multivariate Analysis", "Neoplasm Staging", "Predictive Value of Tests", "Sensitivity and Specificity", "Survival Rate", "Tumor Suppressor Protein p53" ] }

{ "contexts": [ "Little is known about the role of the CO2 pneumoperitoneum on tumor cells that spread from the portal system into the liver during laparoscopic surgery for gastrointestinal malignancies. Therefore, we designed a study to investigate the effect of CO2 pneumoperitoneum on cancer cells implanted in the portal vein in a rabbit model.", "Immediately after intraportal inoculation of 2.5x10(5) cells of VX2 cancer, the rabbits received either CO2 pneumoperitoneum at a pressure of 10 mm Hg for 30 min (pneumoperitoneum group, n = 14) or laparotomy alone for 30 min (laparotomy group, n = 14).", "The number (p<0.01) and area of cancer nodules (p = 0.045) on the liver surface on day 17 were greater in the pneumoperitoneum group than in the laparotomy group. The frequency of cancer nodules >3.0 mm in diameter was higher in the pneumoperitoneum group than in the laparotomy group (p<0.001)." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Animals", "Carbon Dioxide", "Disease Progression", "Gastrointestinal Neoplasms", "Laparoscopy", "Liver Neoplasms, Experimental", "Male", "Neoplasm Seeding", "Neoplasm Transplantation", "Pneumoperitoneum, Artificial", "Portal Vein", "Rabbits" ] }

{ "contexts": [ "Sentinel lymph node biopsy (SLNB) before mastectomy and immediate breast reconstruction (IBR) may help to avoid the negative cosmetic effects of radiotherapy on reconstructed breasts in lymph node-positive patients. Concerns have been raised regarding possible delays whilst awaiting the SLNB result prior to definitive surgery, which needs to be performed within 31 days of cancer diagnosis. The aim was to investigate whether initial SLNB delays mastectomy and IBR.", "All patients who had IBR between January 2005 and 2007 were reviewed retrospectively. Before October 2005 axillary staging was performed simultaneously with mastectomy and IBR (Group I). After October 2005, SLNB was performed as an initial procedure and patients with positive SLNB were only offered a temporary tissue expander to be replaced by autogenous reconstruction after completing the cancer treatment (Group II). Date of diagnosis and waiting times were recorded and the two groups were compared. Different reasons for delays in treatment were studied.", "One hundred and thirty-nine IBR (123 patients) were included in the statistical analysis (67 IBR in Group I and 72 IBR in Group II). Seventy-one patients (57.7%) had no delay (mean waiting time of 23 days). Fifty-two patients (42.3%) had delay longer than 31 days (mean waiting time of 66 days). Group I patients had a mean waiting time (standard deviation) of 38.8 (38) days and Group II patients 42.7 (24) days (p = 0.51)." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Breast Neoplasms", "Carcinoma, Ductal, Breast", "Carcinoma, Intraductal, Noninfiltrating", "Female", "Humans", "Mammaplasty", "Mastectomy", "Middle Aged", "Preoperative Care", "Retrospective Studies", "Sentinel Lymph Node Biopsy", "Time Factors" ] }

{ "contexts": [ "Chronic inflammation is hypothesized to influence prostate cancer development, although a definitive link has not been established.", "Prostate cancer cases (N = 191) detected on a for-cause (clinically indicated) or end-of-study (protocol directed) biopsy, and frequency-matched controls (N = 209), defined as negative for cancer on an end-of-study biopsy, were sampled from the placebo arm of the Prostate Cancer Prevention Trial. Inflammation prevalence and extent in benign areas of biopsy cores were visually assessed using digital images of hematoxylin and eosin-stained sections. Logistic regression was used to estimate associations.", "Of note, 86.2% of cases and 78.2% of controls had at least one biopsy core (of three assessed) with inflammation in benign areas, most of which was chronic. Men who had at least one biopsy core with inflammation had 1.78 [95% confidence interval (CI), 1.04-3.06] times the odds of prostate cancer compared with men who had zero cores with inflammation. The association was stronger for high-grade disease (Gleason sum 7-10, N = 94; OR, 2.24; 95% CI, 1.06-4.71). These patterns were present when restricting to cases and controls in whom intraprostatic inflammation was the least likely to have influenced biopsy recommendation because their prostate-specific antigen (PSA) was low (<2 ng/mL at biopsy)." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Case-Control Studies", "Chronic Disease", "Follow-Up Studies", "Humans", "Inflammation", "Male", "Middle Aged", "Neoplasm Grading", "Neoplasm Staging", "Prognosis", "Prostate", "Prostate-Specific Antigen", "Prostatic Neoplasms", "Survival Rate" ] }

{ "contexts": [ "Distant prostate cancers are commonly hormone refractory and exhibit increased growth no longer inhibited by androgen deprivation therapy. Understanding all molecular mechanisms contributing to uncontrolled growth is important to obtain effective treatment strategies for hormone refractory prostate cancers (HRPC). The aryl hydrocarbon receptor (AhR) affects a number of biological processes including cell growth and differentiation. Several studies have revealed that exogenous AhR ligands inhibit cellular proliferation but recent evidence suggests AhR may possess intrinsic functions that promote cellular proliferation in the absence of exogenous ligands.", "qRT-PCR and western blot analysis was used to determine AhR mRNA and protein expression in hormone sensitive LNCaP cells as well as hormone refractory DU145, PC3 and PC3M prostate cancer cell lines. LNCaP cells express AhR mRNA and protein at a much lower level than the hormone refractory cell models. Cellular fractionation and immunocytochemistry revealed nuclear localization of AhR in the established hormone refractory cell lines while LNCaP cells are devoid of nuclear AhR protein. qRT-PCR analysis used to assess basal CYP1B1 levels and a xenobiotic responsive element binding assay confirmed ligand independent transcriptional activity of AhR in DU145, PC3 and PC3M cells. Basal CYP1B1 levels were decreased by treatment with specific AhR inhibitor, CH223191. An in vitro growth assay revealed that CH223191 inhibited growth of DU145, PC3 and PC3M cells in an androgen depleted environment. Immunohistochemical staining of prostate cancer tissues revealed increased nuclear localization of AhR in grade 2 and grade 3 cancers compared to the well differentiated grade 1 cancers." ], "labels": [ "BACKGROUND", "RESULTS" ], "meshes": [ "Androgens", "Basic Helix-Loop-Helix Transcription Factors", "Cell Line, Tumor", "Cell Nucleus", "Cell Proliferation", "Gene Expression Regulation, Neoplastic", "Humans", "Ligands", "Male", "Neoplasm Staging", "Prostatic Neoplasms", "Protein Transport", "RNA, Messenger", "Receptors, Aryl Hydrocarbon", "Signal Transduction", "Subcellular Fractions", "Transcription, Genetic" ] }

{ "contexts": [ "The risk of breast cancer in carriers of BRCA1 and BRCA2 mutations is influenced by factors other than the genetic mutation itself. Modifying factors include a woman's reproductive history and family history of cancer. Risk factors are more likely to be present in women with breast cancer than in women without breast cancer, and therefore the risk of cancer in the two breasts should not be independent. It is not clear to what extent modifying factors influence the risk of a first primary or a contralateral breast cancer in BRCA carriers.", "We conducted a matched case-control study of breast cancer among 3920 BRCA1 or BRCA2 mutation carriers. We asked whether a past history of breast cancer in the contralateral breast was a risk factor for breast cancer.", "After adjustment for age, country of residence, and cancer treatment, a previous cancer of the right breast was found to be a significant risk factor for cancer of the left breast among BRCA1 or BRCA2 carriers (relative risk: 2.1; 95% confidence interval: 1.4 to 3.0; p < 0.0001)." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [] }

{ "contexts": [ "To identify molecular features associated with clinico-pathological parameters in renal cell cancer.", "Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging was employed for a kidney cancer tissue microarray containing tissue samples from 789 patients for which clinical follow-up data were available.", "A comparison of mass spectrometric signals with clinico-pathological features revealed significant differences between papillary and clear cell renal cell cancer. Within the subgroup of clear cell RCC, statistical associations with tumor stage (seven signals, p<0.01 each), Fuhrman grade (seven signals, p<0.0001 each), and presence of lymph node metastases (10 signals, p<0.01 each) were found. In addition, the presence of one signal was significantly linked to shortened patient survival (p=0.0198)." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Aged", "Carcinoma, Renal Cell", "Female", "Humans", "Kidney Neoplasms", "Male", "Middle Aged", "Neoplasm Grading", "Neoplasm Staging", "Phenotype", "Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization", "Tissue Array Analysis" ] }

{ "contexts": [ "Formyl peptide receptor 1 (FPR1) as a regulator of innate inflammatory response has been implicated in tumor progression of gliomas. The purpose of the present study was to evaluate the prognostic significance and the ligand-receptor interaction of FPR1 in gastric cancer (GC).", "FPR1 was immunohistochemically-analyzed in tissue sections originating from 116 GC patients. Reverse transcription-polymerase chain reaction (RT-PCR) was used for the assessment of interaction between FPR1 and the FPR1 ligand annexin A1 (AnxA1) in GC cells.", "High FPR1 expression was significantly associated with stage IV disease, submucosal invasion, serosal invasion, and clinical outcome of GC. Multivariate analysis showed that high FPR1 expression was an independent risk factor of poor overall survival in GC patients. FPR1 expression increased significantly when AnxA1 overexpression was present in GC cells. A positive feedback regulation of FPR1 was involved in the AnxA1-FPR1 signal transduction." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Aged, 80 and over", "Biomarkers, Tumor", "Disease Progression", "Female", "Gastrectomy", "Humans", "Immunohistochemistry", "Kaplan-Meier Estimate", "Male", "Middle Aged", "Prognosis", "Proportional Hazards Models", "Receptors, Formyl Peptide", "Reverse Transcriptase Polymerase Chain Reaction", "Risk Factors", "Stomach Neoplasms" ] }

{ "contexts": [ "The purpose of this study was to compare the in vivo anti-tumor efficacy of a mucoadhesive, lipid-based, oral paclitaxel formulation (DHP107) with traditional, intraperitoneal (IP) paclitaxel using an orthotopic mouse model of chemotherapy-sensitive SKOV3ip1 ovarian cancer.", "To determine the optimal therapeutic dose of oral paclitaxel, DHP107 was administered per os to female athymic nude mice at 0, 25, or 50 mg/kg twice per week. Control mice received 100 µL saline once per week. IP injections of paclitaxel at 5 mg/kg once per week were used for comparison. To evaluate the potential therapeutic effect of metronomic DHP107 chemotherapy, mice received DHP107 50 mg/kg once per week per os, which was compared with 25 mg/kg twice per week and with vehicle-treated controls.", "Low-dose DHP107 (25 mg/kg) twice per week was as effective as IP paclitaxel (5 mg/kg once a week) but high-dose DHP107 (50 mg/kg once per week) was less effective at inhibiting tumor growth in an orthotopic mouse model (88%, 82%, and 36% decrease in tumor weight, respectively). Mice that received 25 mg/kg DHP107 twice per week or 50 mg/kg DHP107 once per week per os had a significant decrease in tumor weight compared with vehicle-treated controls (p<0.01, both doses)." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [] }

{ "contexts": [ "The development of reliable gene expression profiling technology increasingly impacts our understanding of lung cancer biology. Here, we used RNA sequencing (RNA-Seq) to compare the transcriptomes of non-small cell lung cancer (NSCLC) and normal lung tissues and to investigate expression in lung cancer tissues.", "We enrolled 88 male patients (mean age, 61.2 years) with NSCLC. RNA-Seq was performed on 88 pairs of NSCLC tumor tissue and non-tumor tissue from 54 patients with adenocarcinoma and 34 patients with squamous cell carcinoma. Immunohistochemistry was performed to validate differential candidate gene expression in a different NSCLC group.", "RNA-Seq produced 25.41 × 10(6) (± 8.90 × 10(6)) reads in NSCLC tissues and 24.70×10(6) (± 4.70 × 10(6)) reads in normal lung tissues [mean (± standard deviation)]. Among the genes expressed in both tissues, 335 were upregulated and 728 were downregulated ≥ 2-fold (p < 0.001). Four upregulated genes - CBX3, GJB2, CRABP2, and DSP - not previously reported in lung cancer were studied further. Their altered expression was verified by immunohistochemistry in a different set of NSCLC tissues (n = 154). CBX3 was positive in 90.3% (139 cases) of the samples; GJB2, in 22.7% (35 cases); CRABP2, in 72.1% (111 cases); and DSP, in 17.5% (27 cases). The positive rate of CRABP2 was higher in adenocarcinoma than squamous cell carcinoma (p < 0.01)." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Aged", "Biomarkers, Tumor", "Carcinoma, Non-Small-Cell Lung", "Chromosomal Proteins, Non-Histone", "Connexins", "High-Throughput Nucleotide Sequencing", "Humans", "Immunohistochemistry", "Lung Neoplasms", "Male", "Middle Aged", "Real-Time Polymerase Chain Reaction", "Receptors, Retinoic Acid", "Sequence Analysis, RNA", "Tissue Array Analysis", "Transcriptome", "Up-Regulation" ] }

{ "contexts": [ "Shaoyao decoction (SYD) is a traditional Chinese medicine prescription formulated by Liu Wan-Su, a master of traditional Chinese medicine in Jin-Yuan Dynasty. SYD is effective in treating ulcerative colitis. Paeonol, a component of SYD, inhibits colorectal cancer (CRC) cell proliferation and induces CRC cell apoptosis. In this study, azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colitis-associated CRC (caCRC) model and CRC cell lines were used to examine the effects of SYD on CRC in vivo and in vitro.", "A translational medicine strategy based on phytomics quality control was adopted. Liquid chromatography was employed for the chemical characterization and chemical fingerprinting of SYD. Protein expression and macrophage existence were determined by immunohistochemistry and western blot. Serum cytokines were quantified by Luminex assay.", "AOM/DSS-induced caCRC phenotypically resembled human caCRC. SYD significantly increased the survival rate of the mice, ameliorated the general well-being of the mice, and reduced the incidence and multiplicity of colonic neoplasms. SYD inhibited epithelial-mesenchymal transition (EMT), as indicated by upregulated epithelia cadherin and downregulated neuronal cadherin, fibronectin, vimentin, and transcription factor Snail. SYD reduced the expression levels of serum interleukin 1β, interleukin-6, tumor necrosis factor α, tumor-associated macrophages, and p65. These results showed that SYD can attenuate proinflammatory cytokines and inhibit EMT." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Acetophenones", "Animals", "Blotting, Western", "Colitis", "Colorectal Neoplasms", "Cytokines", "Down-Regulation", "Drugs, Chinese Herbal", "Epithelial-Mesenchymal Transition", "Inflammation Mediators", "Male", "Mice", "Mice, Inbred C57BL" ] }

{ "contexts": [ "Given the emerging role of microRNA in tumor disease progression, we investigated the association between microRNA expression, liver metastasis and prognosis of colorectal cancer.", "Colorectal cancer tissues from patients with or without liver metastases were profiled to identify differentially expressed microRNA. Expression profile was further assessed using quantitative reverse transcription PCR and in situ hybridization. Correlation between miR-181a expression, the most differentially expressed microRNA, between patients with and without liver metastasis, and its downstream target genes were investigated using qRT-PCR. Luciferase reporter assay was conducted to establish functional association between miR-181a and its target genes. Manipulation of miR-181a expression and its consequences in tumor growth and metastasis were demonstrated in various in vitro and in vivo models.", "miR-181a was revealed being the most elevated in CRC with liver metastases. miR-181a expression correlated with advanced stage, distant metastasis, and served as an independent prognostic factor of poor overall survival. Stable transfection of CRC cell lines with miR-181a promoted cell motility and invasion, as well as tumor growth and liver metastasis,while silencing its expression resulted in reduced migration and invasion. Additionally, we identified WIF-1 as direct and functional targets of miR-181a. Ectopic expression of miR-181a suppressed the epithelial markers E-cadherin and β-catenin, while enhanced the mesenchymal markers vimentin." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Adaptor Proteins, Signal Transducing", "Adenocarcinoma", "Aged", "Biomarkers", "Cadherins", "Cell Proliferation", "Colorectal Neoplasms", "Epigenesis, Genetic", "Epithelial-Mesenchymal Transition", "Female", "Gene Expression Profiling", "Gene Expression Regulation, Neoplastic", "Humans", "Liver Neoplasms", "Male", "MicroRNAs", "Middle Aged", "Neoplasm Invasiveness", "Prognosis", "RNA, Small Interfering", "Repressor Proteins", "Signal Transduction", "Survival Analysis", "Tumor Cells, Cultured", "Vimentin", "beta Catenin" ] }

{ "contexts": [ "MicroRNA-26b (miR-26b) has been reported to be down-regulated in a wide range of malignant tumors, However, the mechanism by which miR-26b is implicated in breast cancer tumorigenesis is incompletely understood. This study was undertaken to evaluate the expression pattern of miR-26b and characterize its biological role in human breast cancer.", "Reverse transcription-polymerase chain reaction (RT-PCR) was used to quantify the expression levels of miR-26b in breast cancer and adjacent non-cancerous breast tissues. MTT, colony formation assay and cell cycle assay were carried out to characterize the miR-26b function. Finally, to validate the target gene of miR-26b, luciferase reporter assay was employed, followed by RT-PCR and Western blot confirmation.", "Here, we found that miR-26b expression was relatively downregulated in breast cancer specimens (P<0.01). Overexpression of miR-26b dramatically suppressed cell proliferation, colony formation and induced G0/G1 cell cycle arrest of MDA-MB-231 and Mcf-7 cells. Luciferase assays revealed that miR-26b directly targeted the 3'UTR of CDK8. Overexpression of miR-26b led to the downregulation of CDK8 and β-catenin expression. Similarly, CDK8 knockdown by siRNA suppressed cell growth and subsequent β-catenin expression." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [] }

{ "contexts": [ "Acute pain can lead to immune dysfunction, which can be partly ameliorated by successful pain management. Opioids, which are widely used for analgesia, can result in the deterioration of immune function. This study aimed to investigate the influence of morphine with or without flurbiprofen as post-operative analgesics on the immune systems of patients undergoing gastric cancer surgery.", "60 patients undergoing gastric cancer surgery were equally randomized into two groups. They received post-operative patient-controlled intravenous (IV) analgesia using morphine either with or without flurbiprofen. Visual analogue scale (VAS) scores, Bruggemann comfort scale (BCS) scores, morphine consumption, time of first flatus, incidence of nausea/vomiting, and T-lymphocyte subsets (CD3⁺, CD4⁺, and CD8⁺) and natural killer cells (CD3⁻CD16⁺CD56⁺) were evaluated.", "No significant difference was observed in the VAS scores, BCS scores, and nausea/vomiting incidence between groups. Less morphine was consumed and the time of first flatus was earlier in patients receiving morphine with flurbiprofen than morphine alone. The expression of CD3⁺, CD4⁺, CD4⁺/CD8⁺, and CD3⁻CD16⁺CD56⁺ decreased at 2 hours after incision and, except for CD3⁻CD16⁺CD56⁺, returned to baseline at 120 hours after surgery. Moreover, the expression of CD3⁻CD16⁺CD56⁺ at 2 hours after incision and the expression of CD3⁺, CD4⁺, CD4⁺/CD8⁺, and CD3⁻CD16⁺CD56⁺ at 24 hours after surgery were higher in patients receiving morphine with flurbiprofen than morphine alone." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Analgesia, Patient-Controlled", "Analgesics, Opioid", "Anti-Inflammatory Agents, Non-Steroidal", "Double-Blind Method", "Female", "Flurbiprofen", "Humans", "Killer Cells, Natural", "Male", "Middle Aged", "Morphine", "Pain Measurement", "Pain, Postoperative", "Stomach Neoplasms", "T-Lymphocyte Subsets" ] }

{ "contexts": [ "Hepatocyte nuclear factor 4α (HNF4α) is a liver enriched transcription factor and is indispensable for liver development. However, the role of HNF4α in hepatocellular carcinoma (HCC) progression remains to be elucidated. We report that reduced HNF4α expression correlated well with the aggressive clinicopathological characteristics of HCC and predicted poor prognosis of patients. HNF4α levels were even lower in metastatic HCCs, and ectopic HNF4α expression suppressed the metastasis of hepatoma cells both in vitro and in vivo. Forced HNF4α expression attenuated the expression and nuclear translocation of RelA (p65) and impaired NF-κB activation through an IKK-independent mechanism. Blockage of RelA robustly attenuated the suppressive effect of HNF4α on hepatoma cell metastasis. MicroRNA (miR)-7 and miR-124 were transcriptionally up-regulated by HNF4α, which repressed RelA expression by way of interaction with RelA-3' untranslated region (UTR). In addition, nuclear factor kappa B (NF-κB) up-regulated the expression of miR-21 in hepatoma cells, resulting in decreased HNF4α levels through down-regulating HNF4α-3'UTR activity." ], "labels": [ "UNLABELLED" ], "meshes": [ "Adult", "Aged", "Aged, 80 and over", "Animals", "Carcinoma, Hepatocellular", "Cells, Cultured", "China", "Disease Progression", "Epithelial-Mesenchymal Transition", "Feedback, Physiological", "Female", "Hepatocyte Nuclear Factor 4", "Humans", "Liver Neoplasms", "Male", "MicroRNAs", "Middle Aged", "NF-kappa B", "Rats, Wistar", "Transcription Factor RelA", "Young Adult" ] }

{ "contexts": [ "The observed association between pioglitazone and bladder cancer could be causal or because of bias in the design of prior studies. We hypothesize that proteinuria testing may lead to detection bias if routine test results for proteinuria lead to a full urinalysis.", "We reanalyzed patients with diabetes mellitus within Kaiser Permanente Northern California. Logistic and Cox regression adjusted for age, sex, race, and smoking were used to assess the association of proteinuria testing with pioglitazone use, subsequent full urinalysis, and diagnosis with bladder cancer.", "Patients treated with pioglitazone were more likely than others with diabetes to undergo testing for proteinuria (p < 0.001). The odds of positive tests for proteinuria were higher among pioglitazone-treated patients (OR = 1.41, 95%CI 1.36-1.46). A positive proteinuria test was associated with increased odds of completing a urinalysis in the following 6 months (OR = 1.78, 95%CI 1.73-1.85). Negative and positive proteinuria test results were inversely (hazard ratio (HR) 0.63, 95%CI 0.52-0.75) and positively associated (HR 2.45, 95%CI 2.12-2.82) with bladder cancer risk, respectively. Adjustment for negative and positive proteinuria testing reduced the magnitude of association between pioglitazone and bladder cancer by only 5 to 10% (ever-exposed HR: from 1.06 to 1.01 and >4 years exposure HR: from 1.38 to 1.28)." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Aged, 80 and over", "California", "Cohort Studies", "Confounding Factors (Epidemiology)", "Diabetes Mellitus, Type 2", "Female", "Follow-Up Studies", "Humans", "Hypoglycemic Agents", "Male", "Middle Aged", "Pioglitazone", "Proteinuria", "Thiazolidinediones", "Urinary Bladder Neoplasms" ] }

{ "contexts": [ "Tumour cells alter the characteristics of the adjacent stroma to create a supportive microenvironment during cancer progression. In vitro and in vivo experiments were carried out to verify the role of stromal TGF-β1 in reinforcing of the invasive potential in low invasive cancer.", "Isolated NF or CAF was co-cultured with low invasive HSC-2 cells to evaluate whether stromal TGF-β1 induced PDPN expression by Transwell invasion and influenced tumour growth in orthotopic xenografts.", "Stimulation by TGF-β1 promoted PDPN expression and Transwell invasion through SMAD signalling as well as activation of Src, P38 mitogen activated protein kinase and extracellular regulated kinase 1/2. PDPN induction was TβRII-dependent. Tumour growth of HSC-2 OSCC in a mouse xenograft was intensified in the tumour CAF microenvironment." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Animals", "Blotting, Western", "Carcinoma, Squamous Cell", "Coculture Techniques", "Disease Progression", "Enzyme-Linked Immunosorbent Assay", "Fibroblasts", "Heterografts", "Immunohistochemistry", "Male", "Membrane Glycoproteins", "Mice", "Mice, Inbred BALB C", "Mice, Nude", "Mouth Neoplasms", "Neoplasm Invasiveness", "Phenotype", "Signal Transduction", "Transforming Growth Factor beta1", "Tumor Microenvironment" ] }

{ "contexts": [ "We hypothesized that miR-194 may control Forkhead box protein M1 (FoxM1) expression in gastric cancer cells and therefore may have therapeutic potential in gastric cancer.", "The expression level of miR-194 was examined using real-time PCR in human gastric cancer and noncancerous gastric tissues, gastric cancer cell and normal gastric mucosal epithelial cell. We examined whether the miR-194 regulates cell migration and invasion, and the epithelial-mesenchymal transition Phenotype by inhibiting FoxM1 in gastric cancer cells.", "The expression of miR-194 was significantly lower in gastric cancer compared with non-cancerous gastric tissues and cells. Exogenous expression of miR-194 inhibited cell migration, invasion, and the epithelial-mesenchymal transition phenotype in gastric cancer cells. Moreover, we discovered a novel post-transcriptional regulatory mechanism of FoxM1 expression that is mediated by miR-194." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Cell Line, Tumor", "Cell Movement", "Epithelial Cells", "Epithelial-Mesenchymal Transition", "Forkhead Box Protein M1", "Forkhead Transcription Factors", "Gastric Mucosa", "Gene Expression Regulation, Neoplastic", "Humans", "MicroRNAs", "Phenotype", "RNA Interference", "Stomach Neoplasms", "Up-Regulation" ] }

{ "contexts": [ "HAGE protein is a known immunogenic cancer-specific antigen.", "The biological, prognostic and predictive values of HAGE expression was studied using immunohistochemistry in three cohorts of patients with BC (n=2147): early primary (EP-BC; n=1676); primary oestrogen receptor-negative (PER-BC; n=275) treated with adjuvant anthracycline-combination therapies (Adjuvant-ACT); and primary locally advanced disease (PLA-BC) who received neo-adjuvant anthracycline-combination therapies (Neo-adjuvant-ACT; n=196). The relationship between HAGE expression and the tumour-infiltrating lymphocytes (TILs) in matched prechemotherapy and postchemotherapy samples were investigated.", "Eight percent of patients with EP-BC exhibited high HAGE expression (HAGE+) and was associated with aggressive clinico-pathological features (Ps<0.01). Furthermore, HAGE+expression was associated with poor prognosis in both univariate and multivariate analysis (Ps<0.001). Patients with HAGE+did not benefit from hormonal therapy in high-risk ER-positive disease. HAGE+and TILs were found to be independent predictors for pathological complete response to neoadjuvant-ACT; P<0.001. A statistically significant loss of HAGE expression following neoadjuvant-ACT was found (P=0.000001), and progression-free survival was worse in those patients who had HAGE+residual disease (P=0.0003)." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Antineoplastic Agents, Hormonal", "Antineoplastic Combined Chemotherapy Protocols", "Biomarkers, Tumor", "Breast Neoplasms", "Carcinoma", "Combined Modality Therapy", "Cyclophosphamide", "DEAD-box RNA Helicases", "Drug Resistance, Neoplasm", "Female", "Fluorouracil", "Humans", "Kaplan-Meier Estimate", "Lymphocytes, Tumor-Infiltrating", "Mastectomy", "Menopause", "Methotrexate", "Mitotic Index", "Neoplasm Invasiveness", "Neoplasm Proteins", "Neoplasms, Hormone-Dependent", "Prognosis", "Proportional Hazards Models", "Receptor, ErbB-2", "Receptors, Estrogen", "Receptors, Progesterone", "Tamoxifen", "Treatment Outcome" ] }

{ "contexts": [ "Three-dimensional (3D) surface matching is a novel method to administer deep inspiration breath-hold (DIBH) radiation therapy for left-sided breast cancer to reduce cardiac exposure. We analyzed port (x-ray) films to assess patient setup accuracy and treatment times to assess the practical workflow of this system.", "The data from 50 left-sided breast cancer patients treated with DIBH were studied. AlignRT (London, UK) was used. The distance between the field edge and the anterior pericardial shadow as seen on the routine port films (dPORT), and the corresponding distance seen on the digitally reconstructed radiographs (DRR) from the planning (dDRR) were compared as a quantitative measure of setup accuracy. Variations of dPORT - dDRR over the treatment course were assessed. In a subset of 21 patients treated with tangential beams alone, the daily treatment durations were analyzed to assess the practical workflow of this system.", "Considering all 50 patients, the mean absolute systematic uncertainty between dPORT and dDRR was 0.20 cm (range, 0 to 1.22 cm), the mean systematic uncertainty was -0.07 cm (range, -1.22 to 0.67 cm), and their mean random uncertainty was 0.19 cm (range, 0 to 0.84 cm). There was no significant change in dPORT - dDRR during the course of treatment. The mean patient treatment duration for the 21 patients studied was 11 minutes 48 seconds. On intrapatient assessments, 15/21 had nonsignificant trends toward reduced treatment durations during their course of therapy. On interpatient comparisons, the mean treatment times declined as we gained more experience with this technique." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Breast Neoplasms", "Breath Holding", "Female", "Humans", "Imaging, Three-Dimensional", "Inhalation", "Lung", "Radiotherapy Planning, Computer-Assisted", "Reproducibility of Results", "Tomography, X-Ray Computed" ] }

{ "contexts": [ "To examine relationships among demographic variables, healthcare system distrust, lung cancer stigma, smoking status, and timing of medical help-seeking behavior in individuals with symptoms suggestive of lung cancer after controlling for ethnicity, socioeconomic status, and social desirability.", "Descriptive, cross-sectional, correlational study.", "Outpatient oncology clinics in Louisville, KY.", "94 patients diagnosed in the past three weeks to six years with all stages of lung cancer.", "Self-report, written survey packets were administered in person followed by a semistructured interview to assess symptoms and timing characteristics of practice-identified patients with lung cancer.", "Timing of medical help-seeking behavior, healthcare system distrust, lung cancer stigma, and smoking status.", "Lung cancer stigma was independently associated with timing of medical help-seeking behavior in patients with lung cancer. Healthcare system distrust and smoking status were not independently associated with timing of medical help-seeking behavior." ], "labels": [ "OBJECTIVE", "METHODS", "METHODS", "METHODS", "METHODS", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Aged, 80 and over", "Attitude to Health", "Cross-Sectional Studies", "Decision Making", "Female", "Humans", "Kentucky", "Lung Neoplasms", "Male", "Middle Aged", "Oncology Service, Hospital", "Patient Acceptance of Health Care", "Smoking", "Social Stigma", "Socioeconomic Factors", "Statistics as Topic", "Time Factors" ] }

{ "contexts": [ "Recurrent prostate cancer remains a major problem. Staging, grading and prostate specific antigen level at surgery are helpful but still imperfect predictors of recurrence. For this reason there is an imperative need for additional biomarkers that add to the prediction of currently used prognostic factors.", "We evaluated the extent of promoter methylation of genes previously reported as aberrantly methylated in prostate cancer (AIM1, APC, CCND2, GPX3, GSTP1, MCAM, RARβ2, SSBP2 and TIMP3) by quantitative fluorogenic methylation-specific polymerase chain reaction. We used cancer tissue from a nested case-control study of 452 patients surgically treated for prostate cancer. Recurrence cases and controls were compared and the association between methylation extent and recurrence risk was estimated by logistic regression adjusting for patient age at prostatectomy, prostatectomy year, stage, grade, surgical margins and preprostatectomy prostate specific antigen. All statistical tests were 2-sided with p ≤0.05 considered statistically significant.", "The extent of GSTP1 methylation was higher in patients with recurrence than in controls (p = 0.01), especially patients with early disease, ie organ confined or limited extraprostatic extension (p = 0.001). After multivariate adjustment GSTP1 promoter methylation at or above the median was associated with an increased risk of recurrence, including in men with early disease (each p = 0.05)." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "DNA Methylation", "DNA, Neoplasm", "Follow-Up Studies", "Glutathione S-Transferase pi", "Humans", "Incidence", "Male", "Maryland", "Middle Aged", "Neoplasm Recurrence, Local", "Prognosis", "Promoter Regions, Genetic", "Prostatectomy", "Prostatic Neoplasms", "Retrospective Studies" ] }

{ "contexts": [ "Neoadjuvant chemotherapy (NACT) improves the prognosis of patients with esophageal cancer who respond, but it is not effective in nonresponders. Therefore, it is crucial to establish a reliable method of predicting response before initiation of chemotherapy. Hypercoagulability, which is thought to be because of upregulation of tissue factor (TF) in cancer cells, was reported to be associated with chemoresistance. The aim of this study was to investigate the association between TF expression and response to NACT in esophageal cancer.", "In 67 patients with advanced esophageal cancer, TF expression in pretreatment biopsy samples was evaluated immunohistochemically and correlated with clinicopathologic factors and response to chemotherapy.", "TF was expressed by 43.3% of the tumors, but there were no correlations observed with any clinicopathologic parameters examined. Clinical and histologic responses to chemotherapy were significantly worse in TF-positive patients compared with TF-negative patients. Multivariate analysis revealed that TF expression was significantly associated with a poor clinical response (P = 0.0431). TF expression was also independently associated with poor progression-free survival (P = 0.0353)." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Aged", "Biopsy", "Carcinoma, Squamous Cell", "Disease Progression", "Disease-Free Survival", "Drug Resistance, Neoplasm", "Esophageal Neoplasms", "Esophagus", "Female", "Humans", "Male", "Middle Aged", "Neoadjuvant Therapy", "Neoplasm Grading", "Predictive Value of Tests", "Prognosis", "Thrombophilia", "Thromboplastin" ] }

{ "contexts": [ "This study was to investigate whether the expression of a disintegrin and metalloproteinase-9 (ADAM9) is correlated with the expression of hepatoma-derived growth factor (HDGF) in surgically resected non-small cell lung cancer (NSCLC), to evaluate the significance of HDGF and ADAM9 as novel molecular staging biomarkers, prognostic biomarkers and predictive biomarkers for postoperative adjuvant chemotherapy in surgically resected stage I NSCLC, to provide essential consistence proof to the possible novel pathway of HDGF-ADAM9 pathway.", "Sixty-three cases of resected stage I NSCLC with mediastinal N2 lymph node dissection were immunohistochemically analyzed for HDGF and ADAM9 protein expression. Multivariate analysis and survival analysis were conducted.", "HDGF and ADAM9 were observed highly expressed in NSCLC compared with normal control lung tissues (P < 0.05). HDGF high expression cases showed significantly lower survival rate (55.6 vs. 84.7 %, P = 0.009). HDGF high expression was an independent factor of shortened survival time in resected stage I NSCLC (P = 0.015). ADAM9 high expression cases showed significantly lower survival rate (56.9 vs. 88.7 %, P = 0.015). ADAM9 high expression was an independent factor of shortened survival time in resected stage I NSCLC (P = 0.021). Pearson's correlation analysis revealed that ADAM9 expression was correlated positively and significantly with HDGF expression in 63 cases of stage I NSCLC (r = 0.547, P = 0.000)." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "ADAM Proteins", "Adenocarcinoma", "Adult", "Aged", "Biomarkers, Tumor", "Carcinoma, Non-Small-Cell Lung", "Chemotherapy, Adjuvant", "Female", "Humans", "Intercellular Signaling Peptides and Proteins", "Kaplan-Meier Estimate", "Lung Neoplasms", "Lymphatic Metastasis", "Male", "Membrane Proteins", "Middle Aged", "Neoplasm Staging", "Prognosis", "Proportional Hazards Models" ] }

{ "contexts": [ "Endometrial cancers (ECs) are the most common form of gynecologic malignancy. Recent studies have reported that ECs reveal distinct markers for molecular pathogenesis, which in turn is linked to the various histological types of ECs. To understand further the molecular events contributing to ECs and endometrial tumorigenesis in general, a more precise identification of cancer-associated molecules and signaling networks would be useful for the detection and monitoring of malignancy, improving clinical cancer therapy, and personalization of treatments.", "ECs-specific gene co-expression networks were constructed by differential expression analysis and weighted gene co-expression network analysis (WGCNA). Important pathways and putative cancer hub genes contribution to tumorigenesis of ECs were identified. An elastic-net regularized classification model was built using the cancer hub gene signatures to predict the phenotypic characteristics of ECs. The 19 cancer hub gene signatures had high predictive power to distinguish among three key principal features of ECs: grade, type, and stage. Intriguingly, these hub gene networks seem to contribute to ECs progression and malignancy via cell-cycle regulation, antigen processing and the citric acid (TCA) cycle." ], "labels": [ "BACKGROUND", "RESULTS" ], "meshes": [ "Citric Acid Cycle", "Endometrial Neoplasms", "Female", "Gene Regulatory Networks", "Humans" ] }

{ "contexts": [ "Angiogenin undergoes nuclear translocation and stimulates ribosomal RNA transcription in both endothelial and cancer cells. Consequently, angiogenin has a dual effect on cancer progression by inducing both angiogenesis and cancer cell proliferation. The aim of this study was to assess whether neamine, a blocker of nuclear translocation of angiogenin, possesses antitumor activity toward oral cancer.", "The antitumor effect of neamine on oral cancer cells was examined both in vitro and in vivo.", "Neamine inhibited the proliferation of HSC-2, but not that of SAS oral cancer cells in vitro. Treatment with neamine effectively inhibited growth of HSC-2 and SAS cell xenografts in athymic mice. Neamine treatment resulted in a significant decrease in tumor angiogenesis, accompanied by a decrease in angiogenin- and proliferating cell nuclear antigen-positive cancer cells, especially of HSC-2 tumors." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Angiogenesis Inducing Agents", "Animals", "Cell Line, Tumor", "Cell Proliferation", "Disease Progression", "Framycetin", "Humans", "Immunohistochemistry", "In Situ Nick-End Labeling", "Mice", "Mice, Nude", "Mouth Neoplasms", "Neovascularization, Pathologic", "Protein Transport", "Ribonuclease, Pancreatic", "Xenograft Model Antitumor Assays" ] }

{ "contexts": [ "NOTCH-regulated ankyrin repeat protein (NRARP) has been implicated in crosstalk between NOTCH and wingless-type mouse mammary tumor virus integration site (WNT) signals during development. Our study aimed to clarify its role in breast cancer cells.", "Public microarray data were used to analyze gene expression in human and rat breast cancer. A short interfering RNA was introduced into MCF7 and T47D human breast cancer cells for NRARP silencing. Gene expression was analyzed by quantitative polymerase chain reaction.", "The NRARP transcript was commonly overexpressed in various rat mammary cancer models. In addition, a subset of human breast cancer also expressed high levels of NRARP transcript, which correlated positively with up-regulation of cell proliferation-related genes. Silencing of NRARP suppressed the growth of MCF7 and T47D cells and lowered the expression of cell cycle-related genes in MCF7 cells." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Animals", "Ankyrin Repeat", "Breast Neoplasms", "Cell Line, Tumor", "Cell Proliferation", "Female", "Gene Knockdown Techniques", "Humans", "Neoplasm Proteins", "Oligonucleotide Array Sequence Analysis", "Polymerase Chain Reaction", "Rats", "Rats, Sprague-Dawley", "Receptors, Notch", "Transcriptome", "Up-Regulation" ] }

{ "contexts": [ "Although previous studies have demonstrated the prognostic value of positron emission tomography (PET) parameters in other malignancies, the role of PET in pancreatic cancer has yet to be well established. We analyzed the prognostic utility of PET for patients with locally advanced pancreatic cancer (LAPC) undergoing fractionated stereotactic body radiation therapy (SBRT).", "Thirty-two patients with LAPC in a prospective clinical trial received up to 3 doses of gemcitabine, followed by 33 Gy in 5 fractions of 6.6 Gy, using SBRT. All patients received a baseline PET scan prior to SBRT (pre-SBRT PET). Metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum and peak standardized uptake values (SUVmax and SUVpeak) on pre-SBRT PET scans were calculated using custom-designed software. Disease was measured at a threshold based on the liver SUV, using the equation Livermean + [2 × Liversd]. Median values of PET parameters were used as cutoffs when assessing their prognostic potential through Cox regression analyses.", "Of the 32 patients, the majority were male (n=19, 59%), 65 years or older (n=21, 66%), and had tumors located in the pancreatic head (n=27, 84%). Twenty-seven patients (84%) received induction gemcitabine prior to SBRT. Median overall survival for the entire cohort was 18.8 months (95% confidence interval [CI], 15.7-22.0). An MTV of 26.8 cm(3) or greater (hazard ratio [HR] 4.46, 95% CI 1.64-5.88, P<.003) and TLG of 70.9 or greater (HR 3.08, 95% CI 1.18-8.02, P<.021) on pre-SBRT PET scan were associated with inferior overall survival on univariate analysis. Both pre-SBRT MTV (HR 5.13, 95% CI 1.19-22.21, P=.029) and TLG (HR 3.34, 95% CI 1.07-10.48, P=.038) remained independently associated with overall survival in separate multivariate analyses." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Aged", "Antimetabolites, Antineoplastic", "Blood Glucose", "Carcinoma, Pancreatic Ductal", "Deoxycytidine", "Dose Fractionation, Radiation", "Drug Administration Schedule", "Female", "Fluorodeoxyglucose F18", "Glycolysis", "Humans", "Induction Chemotherapy", "Liver", "Male", "Middle Aged", "Multimodal Imaging", "Pancreatic Neoplasms", "Positron-Emission Tomography", "Prognosis", "Prospective Studies", "Radiopharmaceuticals", "Radiosurgery", "Regression Analysis", "Tomography, X-Ray Computed", "Tumor Burden" ] }

{ "contexts": [ "Mitochondrial DNA (mtDNA) copy number correlates with tumor pathology in some cancers.", "To investigate mtDNA copy number in head and neck cancer (HNC).", "mtDNA copy number was determined and compared between HNC patients and malignancy-free controls.", "The mtDNA copy number was significantly higher in HNC patients, increased with cancer progression and correlated negatively with patient survival." ], "labels": [ "BACKGROUND", "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Base Sequence", "DNA Copy Number Variations", "DNA Primers", "DNA, Mitochondrial", "Female", "Head and Neck Neoplasms", "Humans", "Male", "Middle Aged", "Prognosis", "Real-Time Polymerase Chain Reaction", "Survival Rate" ] }

{ "contexts": [ "The long noncoding RNA HOTAIR has been reported to be a good biomarker for poor prognosis in a variety of human cancers. However, whether HOTAIR could serve as novel biomarker to predict prognosis in cervical cancer or not is unknown. The aim of the present study was to examine the expression of HOTAIR in cervical cancers and to investigate the relationship between this lncRNA expression levels and existing clinicopathological factors and patient survival.", "We examined the expression of HOTAIR in 218 cervical cancer tissues and matched 218 adjacent normal tissues using quantitative real-time RT-PCR and analyzed its correlation with the clinical parameters.", "The results showed that HOTAIR expression in cervical cancer tissues was significantly upregulated compared with the matched nontumorous tissues (P < 0.0001). Increased HOTAIR expression was significantly correlated with FIGO stage (P < 0.0001), lymph node metastasis (P < 0.0001), depth of cervical invasion (P < 0.0001), tumor size (P = 0.006) and age (P = 0.020), but not other clinical characteristics. Moreover, cervical cancer patients with HOTAIR higher expression have shown significantly poorer overall survival (P < 0.0001) and disease-free survival (P < 0.0001) than those with lower HOTAIR expression. Univariate (P < 0.0001, HR = 4.566, 95 % CI 2.122-9.825) and multivariate (P = 0.012, HR = 2.863, 95 % CI 1.263-76.490). Cox regression analyses showed that HOTAIR expression served as an independent predictor for overall survival." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adenocarcinoma", "Adult", "Age Factors", "Aged", "Carcinoma, Squamous Cell", "Disease Progression", "Disease-Free Survival", "Female", "Gene Expression", "Genetic Markers", "Humans", "Lymphatic Metastasis", "Middle Aged", "Neoplasm Invasiveness", "Prognosis", "RNA, Long Noncoding", "ROC Curve", "Real-Time Polymerase Chain Reaction", "Up-Regulation", "Uterine Cervical Neoplasms" ] }

{ "contexts": [ "Chemoradiation (CRT) has been shown to lead to downsizing of an important portion of rectal cancers. In order to tailor treatment at an earlier stage during treatment, predictive models are being developed. Adding blood biomarkers may be attractive for prediction, as they can be collected very easily and determined with excellent reproducibility in clinical practice. The hypothesis of this study was that blood biomarkers related to tumor load, hypoxia and inflammation can help to predict response to CRT in rectal cancer.", "295 patients with locally advanced rectal cancer who were planned to undergo CRT were prospectively entered into a biobank protocol (NCT01067872). Blood samples were drawn before start of CRT. Nine biomarkers were selected, based on a previously defined hypothesis, and measured in a standardized way by a certified lab: CEA, CA19-9, LDH, CRP, IL-6, IL-8, CA IX, osteopontin and 25-OH-vitamin D. Outcome was analyzed in two ways: pCR vs. non-pCR and responders (defined as ypT0-2N0) vs. non-responders (all other ypTN stages).", "276 patients could be analyzed. 20.7% developed a pCR and 47.1% were classified as responders. In univariate analysis CEA (p=0.001) and osteopontin (p=0.012) were significant predictors for pCR. Taking response as outcome CEA (p<0.001), IL-8 (p<0.001) and osteopontin (p=0.004) were significant predictors. In multivariate analysis CEA was the strongest predictor for pCR (OR 0.92, p=0.019) and CEA and IL-8 predicted for response (OR 0.97, p=0.029 and OR 0.94, p=0.036). The model based on biomarkers only had an AUC of 0.65 for pCR and 0.68 for response; the strongest model included clinical data, PET-data and biomarkers and had an AUC of 0.81 for pCR and 0.78 for response." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Aged, 80 and over", "Biomarkers, Tumor", "Carcinoembryonic Antigen", "Chemoradiotherapy", "Female", "Humans", "Interleukin-8", "Male", "Middle Aged", "Multivariate Analysis", "Neoplasm Staging", "Osteopontin", "Predictive Value of Tests", "Prognosis", "Prospective Studies", "Rectal Neoplasms", "Reproducibility of Results", "Young Adult" ] }

{ "contexts": [ "Nitric oxide (NO), mainly synthesized by inducible nitric oxide synthase (NOS2) in pathological conditions, plays an important role in cytotoxicity, inflammation and fibrosis. Elevations in exhaled NO after thoracic radiation have been reported to predict radiation-induced lung injury (RILI). This study examined whether genetic variations in NOS2 gene is associated with the risk of RILI.", "A cohort of 301 patients between 2009 and 2011 were genotyped for 21 single nucleotide polymorphisms (SNPs) in the NOS2 gene by the Sequenom MassArray system. Kaplan-Meier cumulative probability was used to assess RILI risk and Cox proportional hazards analyses were performed to evaluate the effect of NOS2 genotypes on RILI.", "Multivariate analysis found that three SNPs (rs2297518, rs1137933 and rs16949) in NOS2 were significantly associated with risk of RILI⩾2 (P value=0.001, 0.000092, 0.001, respectively) after adjusting for other covariates. Their associations were independent of radiation dose and mean lung dose. Further haplotype analysis indicated that the ATC haplotype of three SNPs is associated with reducing the risk of developing RILI." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Aged, 80 and over", "Female", "Genetic Predisposition to Disease", "Genetic Variation", "Haplotypes", "Humans", "Kaplan-Meier Estimate", "Lung", "Lung Injury", "Lung Neoplasms", "Male", "Middle Aged", "Nitric Oxide Synthase Type II", "Polymorphism, Single Nucleotide", "Proportional Hazards Models", "Radiation Injuries", "Radiotherapy, Intensity-Modulated" ] }

{ "contexts": [ "This study is to investigate the role of miR-143 expression in cervical squamous cell carcinoma (SCC).", "The expression level of miR-143 was examined by quantitative real-time PCR. Human papillomavirus (HPV) genotype was detected by HPV genotype detection kit. The expression level of bcl-2 was detected by immunohistochemistry.", "The positive rate of HPV was 78% in the patients of cervical SCC. The most prevalent genotype was HPV16, with a positive rate of 42%. The expression level of miR-143 was significantly lower in the cervical SCC tissues than that in the normal cervical tissues (Z=-2.180, P=0.029). Down-regulated miR-143 expression was associated with tumor size, lymph node metastasis and HPV16 infection in cervical cancer patients. No significant associations were found between the expression levels of miR-143 and age, clinical stage, differentiation or lymph vascular space invasion. And, in cervical SCC patients after treatment with Taxol chemotherapy, the expression level of miR-143 was higher and the positive expression of bcl-2 protein was lower. However, the differences in expression changes of miR-143 and bcl-2 were not statistically significant (miR-143, Z=-0.763, P=0.446; bcl-2 protein, χ2=2.277, P=0.131)." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Aged, 80 and over", "Antineoplastic Agents, Phytogenic", "Biomarkers, Tumor", "Carcinoma, Squamous Cell", "Chemotherapy, Adjuvant", "Chi-Square Distribution", "China", "DNA, Viral", "Down-Regulation", "Female", "Gene Expression Regulation, Neoplastic", "Genotype", "Human Papillomavirus DNA Tests", "Human papillomavirus 16", "Humans", "Lymphatic Metastasis", "MicroRNAs", "Middle Aged", "Neoadjuvant Therapy", "Paclitaxel", "Papillomavirus Infections", "Real-Time Polymerase Chain Reaction", "Treatment Outcome", "Tumor Burden", "Uterine Cervical Neoplasms" ] }

{ "contexts": [ "Epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs) are considered to be crucial for cancer biology. The purpose of this study was to determine whether EMT directly led to the acquisition of tumour-initiating capacity in breast cancer cell lines.", "Epithelial-mesenchymal transition was induced in five breast cancer cell lines and one normal breast cell line by EMT-related cytokine stimulation. Mesenchymal-epithelial transition (MET) was induced by stably overexpressing miR-200c in three mesenchymal-like breast cancer cell lines. Molecular expression and cell function analysis were performed to evaluate the effect of EMT or MET on tumour-initiating capacity and other biological characteristics.", "The induction of EMT did not enhance tumour-initiating capacity but, instead, conferred a CD44(+)/CD24(-/low) phenotype as well as cell proliferation, migration, and resistance to doxorubicin and radiation on breast cancer cell lines. Furthermore, MET did not lead to inhibition or loss of the tumour-initiating capacity in mesenchymal-like breast cancer cell lines, but it markedly attenuated other malignant properties, including proliferation, invasion, and resistance to therapy." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Animals", "Antibiotics, Antineoplastic", "Antigens, Neoplasm", "Breast Neoplasms", "Cell Division", "Cell Line, Tumor", "Cell Movement", "Cholera Toxin", "Cytokines", "Doxorubicin", "Drug Resistance, Neoplasm", "Epithelial-Mesenchymal Transition", "Female", "Humans", "Hyaluronan Receptors", "Hydrocortisone", "Immunophenotyping", "Insulin", "Mice", "Mice, Inbred NOD", "Mice, SCID", "MicroRNAs", "Neoplasm Transplantation", "Neoplastic Stem Cells", "Radiation Tolerance" ] }

{ "contexts": [ "The role of peritoneal washing cytology in determining further treatment strategies after surgery for gastric cancer remains unclear. One reason for this is the fact that optimal procedures to increase the accuracy of predicting peritoneal metastasis have not been established. The aim of this study was to evaluate the efficacy of cytology using samples harvested from two different abdominal cavity sites during gastric cancer surgery.", "We prospectively recruited 108 patients who were clinically diagnosed with locally advanced gastric cancer (higher than cT1 stage disease). Peritoneal washing fluids were collected from the pouch of Douglas and the subphrenic area. Patients were prospectively followed up for 2 years to determine the recurrence and survival rates.", "Thirty-three patients dropped out of the study for various reasons, so 75 patients were included in the final analysis. Seven patients (9.3%) showed positive cytology findings, of whom, three showed peritoneal recurrence. Tumor size was the only factor associated with positive cytology findings (P=0.037). The accuracy and specificity of cytology for predicting peritoneal recurrence were 90.1% and 94.2%, respectively, whereas the sensitivity was 50.0%. The survival rate did not differ between patients with positive cytology findings and those with negative cytology findings (P=0.081)." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [] }

{ "contexts": [ "Cytokeratin 19 is significant for indicating cancer cells, and Cyfra 21-1 is a fragment of cytokeratin 19. This retrospective study was designed to define the prognostic value of serum Cyfra 21-1 in epithelial ovarian cancers (EOC).", "Serum Cyfra 21-1 concentration was obtained from 42 patients with EOC prior to treatment. Various prognostic aspects were examined using univariable and multivariable analyses. The standard serum marker cancer antigen 125 was measured simultaneously and compared in this analysis.", "Serum levels of both Cyfra 21-1 and cancer antigen 125 were associated with positive retroperitoneal lymph nodes and platinum resistance; higher levels of Cyfra 21-1 (3.0 ng/mL as the cut-off) were associated with shorter disease-free survival (16 months vs. 28 months, p = 0.001) and overall survival (29 months vs. 41 months, p = 0.007) than lower levels. Further univariable analysis showed that Cyfra 21-1, poor differentiation, and retroperitoneal lymph node metastasis were related to platinum resistance and mortality. Multivariable analysis indicated retroperitoneal lymph node metastasis and serum Cyfra 21-1 were independent risk factors for both disease-free survival and overall survival." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Antigens, Neoplasm", "Antineoplastic Agents", "Biomarkers, Tumor", "CA-125 Antigen", "Carcinoma, Ovarian Epithelial", "Disease-Free Survival", "Drug Resistance, Neoplasm", "Female", "Humans", "Kaplan-Meier Estimate", "Keratin-19", "Lymph Nodes", "Lymphatic Metastasis", "Membrane Proteins", "Middle Aged", "Multivariate Analysis", "Neoplasms, Glandular and Epithelial", "Ovarian Neoplasms", "Platinum Compounds", "Prognosis", "Retrospective Studies", "Risk Factors" ] }

{ "contexts": [ "We utilized whole-genome mapping of promoters that are activated by DNA hypomethylation in hepatocellular carcinoma (HCC) clinical samples to shortlist novel targets for anticancer therapeutics. We provide a proof of principle of this approach by testing six genes short-listed in our screen for their essential role in cancer growth and invasiveness.", "We used siRNA- or shRNA-mediated depletion to determine whether inhibition of these genes would reduce human tumor xenograft growth in mice as well as cell viability, anchorage-independent growth, invasive capacities, and state of activity of nodal signaling pathways in liver, breast, and bladder cancer cell lines.", "Depletion of EXOSC4, RNMT, SENP6, WBSCR22, RASAL2, and NENF effectively and specifically inhibits cancer cell growth and cell invasive capacities in different types of cancer, but, remarkably, there is no effect on normal cell growth, suggesting a ubiquitous causal role for these genes in driving cancer growth and metastasis. Depletion of RASAL2 and NENF in vitro reduces their growth as explants in vivo in mice. RASAL2 and NENF depletion interferes with AKT, WNT, and MAPK signaling pathways as well as regulation of epigenetic proteins that were previously demonstrated to drive cancer growth and metastasis." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Animals", "Biomarkers, Tumor", "Carcinoma, Hepatocellular", "Carrier Proteins", "Cell Movement", "Cell Proliferation", "Cysteine Endopeptidases", "DNA Methylation", "Exosome Multienzyme Ribonuclease Complex", "Gene Expression Regulation, Neoplastic", "Genome-Wide Association Study", "Humans", "Intercellular Signaling Peptides and Proteins", "Liver Neoplasms", "Male", "Methyltransferases", "Mice", "Mice, Inbred NOD", "Mice, SCID", "Nerve Tissue Proteins", "Promoter Regions, Genetic", "RNA, Small Interfering", "RNA-Binding Proteins", "Signal Transduction" ] }

{ "contexts": [ "Primary androgen deprivation therapy (PADT) is the most effective systemic therapy for patients with metastatic prostate cancer. Nevertheless, once PSA progression develops, the prognosis is serious and mortal. We sought to identify factors that predicted the prognosis in a series of patients with metastatic prostate cancer.", "Two-hundred eighty-six metastatic prostate cancer patients who received PADT from 1998 to 2005 in Nara Uro-Oncology Research Group were enrolled. The log-rank test and Cox's proportional hazards model were used to determine the predictive factors for prognosis; rate of castration-resistant prostate cancer (CRPC) and overall survival.", "The median age, follow-up period and PSA level at diagnosis were 73 years, 47 months and 174 ng/mL, respectively. The 5-year overall survival rate was 63.0%. The multivariable analysis showed that Gleason score (Hazard ratio [HR]:1.362; 95% confidence interval [C.I.], 1.023-1.813), nadir PSA (HR:6.332; 95% C.I., 4.006-9.861) and time from PADT to nadir (HR:4.408; 95% C.I., 3.099-6.271) were independent prognostic factors of the incidence of CRPC. The independent parameters in the multivariate analysis that predicted overall survival were nadir PSA (HR:5.221; 95% C.I., 2.757-9.889) and time from PADT to nadir (HR:4.008; 95% C.I., 2.137-7.517)." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Aged", "Aged, 80 and over", "Androgen Antagonists", "Biomarkers, Tumor", "Carcinoma", "Humans", "Male", "Middle Aged", "Prognosis", "Prostate-Specific Antigen", "Prostatic Neoplasms", "Reproducibility of Results", "Sensitivity and Specificity", "Survival Analysis", "Treatment Outcome" ] }

{ "contexts": [ "It has been recognized for almost a decade that concentrations of signaling androgens sufficient to activate the androgen receptor are present in castration-resistant prostate cancer tissue. The source of these androgens is highly controversial, with three competing models proposed. We, therefore, wished to determine the androgenic potential of human benign and malignant (hormone-naïve and treated) prostate tissue when incubated with various precursors and examine concomitant changes in enzyme expression.", "Freshly harvested prostate tissue [benign, hormone-naïve, and hormone-refractory prostate cancer (HRPC)] was incubated in excess concentrations of cholesterol, progesterone, DHEA, androstenedione, or testosterone for 96 hours, and steroid concentrations in the conditioned media measured by gas chromatography-mass spectroscopy. Changes in the expression of androgen synthetic and/or degradative enzymes were determined by expression microarray and qPCR. Significant changes were confirmed in an independent dataset.", "Of the precursor molecules tested, only incubation with androstenedione gave rise to significant concentrations of signaling androgens. Although this was observed in all tissue types, it occurred to a significantly greater degree in hormone-refractory compared with hormone-naïve cancer. Consistent with this, gene set enrichment analysis of the expression microarray data revealed significant upregulation of 17HSD17B activity, with overexpression of the canonical enzyme AKR1C3 confirmed by qPCR in the same samples and in a publicly available expression dataset. Importantly, we found no evidence to support a significant contribution from either the \"backdoor\" or \"5-α dione\" pathway." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "3-Hydroxysteroid Dehydrogenases", "Aged", "Aged, 80 and over", "Aldo-Keto Reductase Family 1 Member C3", "Androgens", "Androstenedione", "Estradiol Dehydrogenases", "Humans", "Hydroxyprostaglandin Dehydrogenases", "Male", "Middle Aged", "Prostate", "Prostatic Neoplasms", "Receptors, Androgen", "Signal Transduction", "Up-Regulation" ] }

{ "contexts": [ "To identify microRNAs (miRNA) that predict response to anti-EGFR antibodies in patients with wild-type KRAS metastatic colorectal cancer (mCRC).", "miRNA profiling was performed in a training set of 87 patients with mCRC refractory to chemotherapy treated with anti-EGFR antibodies. This included 33 fresh-frozen (FF) and 35 formalin-fixed paraffin-embedded (FFPE) samples retrospectively collected and 19 prospectively collected FF samples. An independent validation cohort consisting of 19 FF and 26 FFPE prospectively collected samples from patients with mCRC treated with anti-EGFR antibodies was used to confirm our findings.", "After screening the expression of 1,145 miRNAs in FF samples from the training set, we identified that hsa-miR-31-3p expression level was significantly associated with progression-free survival (PFS). Statistical models based on miRNA expression discriminated between high and low risk of progression for both FF and FFPE samples. These models were confirmed in the validation cohort for both FF [HR, 4.1; 95% confidence interval (CI), 1.1-15.3; P < 0.04] and FFPE samples (HR, 2.44; 95% CI, 1.1-5.4; P = 0.028). The percentage of variation of RECIST criteria in the validation series was significantly associated with the expression level of hsa-miR-31-3p (r(2) = 0.49; P = 0.0035) and risk status determined by hsa-miR-31-3p expression level (P = 0.02, Kruskal-Wallis rank test). Nomograms were built and validated to predict PFS-depending on hsa-miR-31-3p expression level. Following in vitro studies, we identified 47 genes regulated by hsa-miR-31-3p." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Aged, 80 and over", "Antineoplastic Combined Chemotherapy Protocols", "Biomarkers, Tumor", "Colorectal Neoplasms", "ErbB Receptors", "Female", "Follow-Up Studies", "Humans", "Liver Neoplasms", "Male", "MicroRNAs", "Middle Aged", "Mutation", "Neoplasm Staging", "Paraffin Embedding", "Prognosis", "Prospective Studies", "Proto-Oncogene Proteins", "Proto-Oncogene Proteins p21(ras)", "Retrospective Studies", "Survival Rate", "Young Adult", "ras Proteins" ] }

{ "contexts": [ "The study's aim was to assess the internal reliability for the nine domains of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) to evaluate homogeneity across clinical studies and whether sample characteristics predict coefficient heterogeneity.", "A systematic literature review was undertaken. Internal reliability was assessed against Cronbach α coefficient >0.70. Reliability generalization was undertaken using fixed- and random-effects models. A weighted least squares regression model was applied to determine whether baseline sample characteristics (language, percentage of women, sample size, sample means and standard deviations, and cancer type) predicted variation in α coefficients.", "A total of 33 studies were identified. Eight domains demonstrated good internal reliability (unweighted/weighted by sample variance). One domain, Cognitive Functioning, consistently performed poorly. In terms of moderating variables, none of the sample characteristic variables explained sample variance for the Physical or Role Functioning domains. For the other domains, language, percentage of women, and sample means and variances accounted for some of the heterogeneity observed." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Activities of Daily Living", "Adult", "Aged", "Female", "Humans", "Language", "Least-Squares Analysis", "Male", "Middle Aged", "Neoplasms", "Psychometrics", "Quality of Life", "Reproducibility of Results", "Surveys and Questionnaires" ] }

{ "contexts": [ "To determine the expression of proteasome aotivator gamma (REGgamma) in human lung cancer tissues and cell lines and its association with malignant biological behaviors.", "Immunohistochemistry (IHC) was used to detect the expression of REGgamma in lung cancer and normal lung tissues. The expressions of REGgamma in lung cancer cells and normal epithelial cells were determined by Western blot. The H1975 lung cancer stable cell lines with different levels of REGgamma expression were constructed and their proliferations were evaluated by MTT assay. PI staining was used to assess the influence of REGgamma on cell growth cycle. The effect of REGgamma on the migration of lung cancer cells were observed with the cell scratch experiment.", "Lung cancer tissues had significantly higher levels of REGgamma expression than normal tissues. Similarly, lung cancer cell lines showed higher levels of REGgamma expression than the normal epithelial cell line. The overexpression of REGgamma enhanced cancer cell proliferations (P < 0.05), promoted more cells into the S+G2/M phase (P < 0.05) and promoted the migration of cancer cells (P < 0.05). All of these effects were reversed after suppression of REGgamma." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Autoantigens", "Blotting, Western", "Cell Cycle", "Cell Line, Tumor", "Cell Proliferation", "Humans", "Immunohistochemistry", "Lung Neoplasms", "Proteasome Endopeptidase Complex" ] }

{ "contexts": [ "Although neoadjuvant chemotherapy (NAC) for locally advanced breast cancer can improve operability and local disease control, there is a lack of reliable biomarkers that predict response to chemotherapy or long-term survival. Since expression of aldehyde dehydrogenase-1 (ALDH1) is associated with the stem-like properties of self-renewal and innate chemoresistance in breast cancer, we asked whether expression in serial tumor samples treated with NAC could identify women more likely to benefit from this therapy.", "Women with locally advanced breast cancer were randomly assigned to receive four cycles of anthracycline-based chemotherapy, followed by four cycles of taxane therapy (Arm A), or the same regimen in reverse order (Arm B). Tumor specimens were collected at baseline, after four cycles, and then at surgical resection. ALDH1 expression was determined by immunohistochemistry and correlated with tumor response using Fisher's exact test while Kaplan-Meier method was used to calculate survival.", "A hundred and nineteen women were enrolled into the study. Fifty seven (48%) were randomized to Arm A and 62 (52%) to Arm B. Most of the women (90%) had ductal carcinoma and 10% had lobular carcinoma. Of these, 26 (22%) achieved a pathological complete response (pCR) after NAC. There was no correlation between baseline ALDH1 expression and tumor grade, stage, hormone receptor, human epidermal growth factor receptor 2 (HER2) status and Ki67 index. ALDH1 negativity at baseline was significantly associated with pCR (P = 0.004). The presence of ALDH1(+) cells in the residual tumor cells in non-responding women was strongly predictive of worse overall survival (P = 0.024). Moreover, serial analysis of specimens from non-responders showed a marked increase in tumor-specific ALDH1 expression (P = 0.028). Overall, there was no survival difference according to the chemotherapy sequence. However, poorly responding tumours from women receiving docetaxel chemotherapy showed an unexpected significant increase in ALDH1 expression." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Antineoplastic Combined Chemotherapy Protocols", "Breast Neoplasms", "Cyclophosphamide", "Docetaxel", "Drug Administration Schedule", "Epirubicin", "Female", "Fluorouracil", "Humans", "Immunohistochemistry", "Isoenzymes", "Kaplan-Meier Estimate", "Ki-67 Antigen", "Middle Aged", "Multivariate Analysis", "Neoadjuvant Therapy", "Neoplasm Staging", "Prognosis", "Receptor, ErbB-2", "Retinal Dehydrogenase", "Taxoids", "Treatment Outcome" ] }

{ "contexts": [ "Development of novel strategies in the treatment of advanced thyroid cancer are needed. Our laboratory has previously identified a role for nuclear factor κB (NF-κB) signaling in human thyroid cancer cell growth, survival, and invasion.", "Our goal was to establish the role of NF-κB signaling on thyroid cancer growth and metastases in vivo and to begin to dissect mechanisms regulating this effect.", "We examined tumor formation of five thyroid cancer cell lines in an in vivo model of thyroid cancer and observed tumor establishment in two of the cell lines (8505C and BCPAP).", "Inhibition of NF-κB signaling by overexpression of a dominant-negative IκBα (mIκBα) significantly inhibited thyroid tumor growth in tumors derived from both cell lines. Further studies in an experimental metastasis model demonstrated that NF-κB inhibition impaired growth of tumor metastasis and prolonged mouse survival. Proliferation (mitotic index) was decreased in 8505C tumors, but not in BCPAP tumors, while in vitro angiogenesis and in vivo tumor vascularity were significantly inhibited by mIkBα only in the BCPAP cells. Cytokine antibody array analysis demonstrated that IL-8 secretion was blocked by mIκBα expression. Interestingly, basal NF-κB activity and IL-8 levels were significantly higher in the two tumorigenic cell lines compared with the nontumorigenic lines. Furthermore, IL-8 transcript levels were elevated in high-risk human tumors, suggesting that NF-κB and IL-8 are associated with more aggressive tumor behavior." ], "labels": [ "BACKGROUND", "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Animals", "Cells, Cultured", "Gene Expression Regulation, Neoplastic", "Human Umbilical Vein Endothelial Cells", "Humans", "I-kappa B Proteins", "Interleukin-8", "Male", "Mice", "Mice, Nude", "NF-KappaB Inhibitor alpha", "NF-kappa B", "Neoplasm Metastasis", "Neoplasm Transplantation", "Neovascularization, Pathologic", "Thyroid Neoplasms" ] }

{ "contexts": [ "Although obesity is associated with gonadal dysfunction in the general population, gonadotoxic treatment might diminish the impact of obesity in childhood cancer survivors (CCS). The aim was to evaluate whether altered body composition is associated with gonadal dysfunction in male CCS, independent of gonadotoxic cancer treatment.", "Three hundred fifty-one male CCS were included. Median age at diagnosis was 5.9 years (0-17.8) and median age at follow-up 25.6 years (18.0-45.8). Total and non-SHBG-bound testosterone, sex hormone-binding globulin, inhibin B, and follicle-stimulating hormone (FSH) were studied. Potential determinants were BMI, waist circumference, waist-hip ratio, and body composition measures (dual energy X-ray absorptiometry).", "Non-SHBG-bound testosterone was significantly decreased in survivors with BMI ≥ 30 kg/m(2) (adjusted mean 9.1 nmol/L vs. 10.2 nmol/L, P = 0.015), high fat percentage (10.0 vs. 11.2, P = 0.004), and high waist circumference (>102 cm) (9.0 vs. 11.0, P = 0.020). Survivors with high fat percentage (≥25%) had significantly lower inhibin B/FSH ratios (inhibin B/FSH ratio: β -34%, P = 0.041)." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adolescent", "Adult", "Body Composition", "Body Mass Index", "Case-Control Studies", "Child", "Child, Preschool", "Follicle Stimulating Hormone", "Humans", "Infant", "Inhibins", "Male", "Middle Aged", "Neoplasms", "Obesity", "Retrospective Studies", "Sex Hormone-Binding Globulin", "Survivors", "Testis", "Testosterone", "Waist Circumference", "Waist-Hip Ratio", "Young Adult" ] }

{ "contexts": [ "PA-MSHA, a genetically engineered Pseudomonas aeruginosa (PA) strain, is currently under investigation as a new anti-cancer drug. It can induce cell cycle arrest and apoptosis in different human cancer cells, including hormone receptor negative breast cancer cells. However, the underlying mechanism of tumor lethality mediated by PA-MSHA remains to be fully investigated.", "The effect of PA-MSHA on human hormone receptor negative breast cancer cells was analyzed by morphological measurement, western blot, cell proliferation assay and mouse xenograft model.", "PA-MSHA was found to induce endoplasmic reticulum (ER) stress in breast cancer cell lines through the IRE1 signaling pathway. Inhibiting autophagy potentiated the cytotoxic effect of PA-MSHA while treating breast cancer cell lines. In mouse xenograft model, PA-MSHA produced more pronounced tumor suppression in mice inoculated with IRE1 gene knockdown. MDA-MB-231HM cells." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Animals", "Apoptosis", "Autophagy", "Breast Neoplasms", "Cell Line, Tumor", "Cell Proliferation", "Endoplasmic Reticulum Stress", "Endoribonucleases", "Female", "Gene Knockdown Techniques", "Hemagglutinins", "Humans", "Mice", "Protein-Serine-Threonine Kinases", "Pseudomonas aeruginosa", "Signal Transduction", "Xenograft Model Antitumor Assays" ] }

{ "contexts": [ "Genome-wide association studies (GWAS) have demonstrated that the single nucleotide polymorphism (SNP) MAP3K1 rs889312 is a genetic susceptibility marker significantly associated with a risk of hormone-related tumors such as breast cancer. Considering steroid hormone-mediated signaling pathways have an important role in the progression of gastric cancer, we hypothesized that MAP3K1 rs889312 may be associated with survival outcomes in gastric cancer. The purpose of this study was to test this hypothesis.", "We genotyped MAP3K1 rs889312 using TaqMan in 884 gastric cancer patients who received subtotal or total gastrectomy. Kaplan-Meier survival analysis and Cox proportional hazard regression were used to analyze the association between MAP3K1 rs889312 genotypes and survival outcomes of gastric cancer.", "Our findings reveal that the rs889312 heterozygous AC genotype was significantly associated with an increased rate of mortality among patients with diffuse-type gastric cancer (log-rank P = 0.028 for AC versus AA/CC, hazard ratio [HR] = 1.32, 95% confidence interval [CI] = 1.03-1.69), compared to those carrying the homozygous variant genotypes (AA/CC). Additionally, univariate and multivariate Cox regression analysis demonstrate that rs889312 polymorphism was an independent risk factor for poor survival in these patients." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Adult", "Aged", "Aged, 80 and over", "Asian Continental Ancestry Group", "China", "Female", "Gastrectomy", "Genome-Wide Association Study", "Humans", "MAP Kinase Kinase Kinase 1", "Male", "Middle Aged", "Polymorphism, Single Nucleotide", "Prognosis", "Risk Factors", "Stomach Neoplasms", "Survival Analysis" ] }

{ "contexts": [ "The incidence of gastric cancer after successful Helicobacter pylori eradication has been increasing. We previously reported that epithelium with low-grade atypia (ELA) appeared on the surface of gastric cancer after H. pylori eradication. Here, we investigate the clinical and biological characteristics of such ELA.", "We studied 27 cases of gastric cancer detected after successful H. pylori eradication therapy. We examined the prevalence of ELA among these cases and its significance for endoscopic discovery after H. pylori eradication. We additionally investigated the mucus, p53 and Ki67 expressions in ELA.", "Epithelium with low-grade atypia that continuous with the gastric tumor was detected in 22 of 27 cases (81%), a significantly greater percentage than that for controls (p < 0.01). We found that gastric-type mucin was frequently expressed in this epithelium. Neither p53- nor Ki67-positive cells were found in ELA, irrespective of their expression in tumor tissue. The presence of ELA was positively correlated with the clinical interval between H. pylori eradication and gastric cancer detection." ], "labels": [ "BACKGROUND", "METHODS", "RESULTS" ], "meshes": [ "Aged", "Endoscopy, Gastrointestinal", "Epithelium", "Female", "Gastric Mucosa", "Helicobacter Infections", "Humans", "Ki-67 Antigen", "Male", "Middle Aged", "Mucus", "Stomach Neoplasms", "Tumor Suppressor Protein p53" ] }

{ "contexts": [ "To evaluate the expression of CXCR4, its ligand SDF-1, β-catenin and E-cadherin throughout the local tumor microenvironment of prostate cancer.", "A total of 64 prostate cancer specimens, 24 frozen and 40 paraffin-embedded sections, were obtained from patients treated with radical prostatectomy for clinically localized cancer. Real-time RT-PCR was used for mRNA quantification of CXCR4 and SDF-1 in the tumor center (T), tumor front (F) and distant peritumoral tissue (D). Immunohistochemical analysis was used to investigate the expression patterns of CXCR4, E-cadherin and β-catenin. Clinical records of these patients were studied for follow-up data, and the prognostic value of these molecules' expression was statistically assessed.", "CXCR4 mRNA and protein were significantly increased at the tumor front as compared to distant tissue or tumor center. In comparison, SDF-1 mRNA level gradually increased from the tumor center to the distant peritumoral tissue. High CXCR4 at the tumor front was associated with high Gleason score. Low SDF-1 at the tumor front was associated with locally advanced cancer and disease recurrence. Moreover, high CXCR4 staining at the tumor front and increased cytosolic E-cadherin expression in the same location was associated with locally advanced disease." ], "labels": [ "OBJECTIVE", "METHODS", "RESULTS" ], "meshes": [ "Aged", "Biomarkers, Tumor", "Cadherins", "Cell Movement", "Chemokine CXCL12", "Humans", "Male", "Middle Aged", "Prognosis", "Prostatectomy", "Prostatic Neoplasms", "RNA, Messenger", "Receptors, CXCR4", "beta Catenin" ] }