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22,805,864 | Is collapsin response mediator protein 4 expression associated with liver metastasis and poor survival in pancreatic cancer? | {
"contexts": [
"Pancreatic cancer is an aggressive malignancy with one of the worst mortality rates of all cancers. Recently, collapsin response mediator proteins (CRMPs) were reported to be associated with proliferation, apoptosis, differentiation, and invasion in several cancers. However, CRMP expression and their role in pancreatic cancer have not been investigated. This study aimed to clarify the clinical significance of CRMPs in pancreatic cancer.",
"Expression of crmp genes in 11 pairs of pancreatic cancer and corresponding noncancerous pancreas tissues were examined by real-time RT-PCR. Knockdown of CRMP4 expression using siRNA was examined in pancreatic cancer cell lines to determine whether CRMP4 regulates cell proliferation and invasion in vitro. Furthermore, CRMP4 protein levels in primary tumors of pancreatic cancer (n = 53) were examined by immunohistochemistry and compared with the clinicopathological features of the tumors.",
"Of all the CRMPs, only CRMP4 was differentially expressed in pancreatic cancer tissues (p = 0.008). CRMP4 knockdown using siRNA reduced cellular invasion, but did not affect proliferation. The expression of CRMP4 was detected immunohistochemically in 34 (64.2 %) of the 53 pancreatic cancer samples, and CRMP4 expression was correlated with severe venous invasion (p = 0.044), stage (p = 0.019), and liver metastasis (p = 0.021). Multivariate analyses suggested that venous invasion and CRMP4 overexpression were prognostic factors for survival."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adenocarcinoma",
"Adult",
"Aged",
"Apoptosis",
"Biomarkers, Tumor",
"Blotting, Western",
"Cell Differentiation",
"Cell Proliferation",
"Female",
"Humans",
"Immunoenzyme Techniques",
"Liver Neoplasms",
"Lymphatic Metastasis",
"Male",
"Middle Aged",
"Muscle Proteins",
"Neoplasm Invasiveness",
"Neoplasm Staging",
"Pancreas",
"Pancreatic Neoplasms",
"Prognosis",
"RNA, Messenger",
"RNA, Small Interfering",
"Real-Time Polymerase Chain Reaction",
"Reverse Transcriptase Polymerase Chain Reaction",
"Survival Rate",
"Tumor Cells, Cultured"
]
} | Our results suggested that CRMP4 is significantly associated with poor prognosis by promoting liver metastasis and can serve as a novel therapeutic target for pancreatic cancer. | yes |
22,829,558 | Is deleted in Colorectal Cancer ( DCC ) gene polymorphism associated with H. pylori infection among susceptible Malays from the north-eastern region of Peninsular Malaysia? | {
"contexts": [
"Using genome-wide case-control association approach, the current study aimed to determine whether genetic polymorphism(s) is/are associated with H. pylori infection among ethnic Malays from the north-eastern region of Peninsular Malaysia, a region with an exceptionally low prevalence for H. pylori infection and gastric cancer.",
"Twenty-three Malay subjects positive for H. pylori confirmed with urease test and histology were enrolled as \"cases\" and 37 subjects negative for H. pylori were \"controls\". Both groups were matched for age and environmental risks. Extracted DNA samples (QIAGEN, Germany) from the venous blood of study subjects were genotyped using the Human Mapping 50k xbal array (Affymetrix, USA). High throughput downstream analyses were then used to determine the significant SNP(s) associated with H. pylori infection.",
"Out of 20,361 SNPs filtered using the genotype association test, the top 1% (203) significant SNPs were selected for functional enrichment analysis. Of the 15 \"enriched\" SNPs, the rs10502974 which was located within the intronic region of Deleted in Colorectal Cancer (DCC) gene was the SNP most significantly associated with H. pylori infection (p=0.00549)."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Aged",
"Aged, 80 and over",
"Genes, DCC",
"Genetic Predisposition to Disease",
"Helicobacter Infections",
"Helicobacter pylori",
"Humans",
"Malaysia",
"Middle Aged",
"Polymorphism, Single Nucleotide"
]
} | Ethnic Malays is genetically susceptible to H. pylori infection and is possibly mediated through a genetic variation in the DCC gene. | yes |
22,805,008 | Is wRAP53 an independent prognostic factor in rectal cancer- a study of Swedish clinical trial of preoperative radiotherapy in rectal cancer patients? | {
"contexts": [
"Expression of WRAP53 protein has oncogenic properties and it is up regulated in several types of tumors.",
"We examined expression of WRAP53 protein in rectal cancers and analyzed its relationship to the response to preoperative radiotherapy and patient survival. The WRAP53 protein was examined by immunohistochemistry in normal mucosa, primary tumors and lymph node metastases from 143 rectal cancer patients participated in a Swedish clinical trial of preoperative radiotherapy.",
"Frequency of WRAP53 protein expression was increased in primary rectal cancer compared to the normal mucosa (p<0.05). In non-radiotherapy group positive WRAP53 in primary tumors (p=0.03, RR, 3.73, 95% CI, 1.13-11.89) or metastases (p=0.01, RR, 4.11, 95% CI, 1.25-13.14), was associated with poor prognosis independently of stages and differentiations. In radiotherapy group, positive WRAP53 in the metastasis correlated with better survival (p=0.04). An interaction analysis showed that the correlations of WRAP53 with the prognostic significance with and without radiotherapy in the metastasis differed (p=0.01). In the radiotherapy group, expression of WRAP53 in metastases gave a better outcome (p=0.02, RR, 0.32, 95% CI, 0.13-0.84), and an interaction analysis showed significance between the two groups (p=0.01)."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Aged",
"Aged, 80 and over",
"Apoptosis",
"Biomarkers, Tumor",
"Female",
"Humans",
"Immunohistochemistry",
"Kaplan-Meier Estimate",
"Male",
"Middle Aged",
"Neoplasm Metastasis",
"Prognosis",
"Rectal Neoplasms",
"Sweden",
"Telomerase"
]
} | WRAP53 may be a new biomarker used to predict prognosis and to select suitable patients for preoperative radiotherapy. | yes |
22,836,512 | Is βV-tubulin expression associated with outcome following taxane-based chemotherapy in non-small cell lung cancer? | {
"contexts": [
"Tubulin-binding agents (TBAs) are effective in non-small cell lung cancer (NSCLC) treatment. Both βIII- and βV-tubulins are expressed by cancer cells and may lead to resistance against TBAs.",
"Pre-treatment samples from 65 locally advanced or oligometastatic NSCLC patients, who underwent uniform induction chemotherapy with paclitaxel and platinum followed by radiochemotherapy with vinorelbine and platinum were retrospectively analysed by immunohistochemistry. Protein expression of βIII- and βV-tubulin was morphometrically quantified.",
"Median pre-treatment H-score for βIII-tubulin was 110 (range: 0-290), and 160 for βV-tubulin (range: 0-290). Low βIII-tubulin expression was associated with improved overall survival (OS) (P=0.0127, hazard ratio (HR): 0.328). An association between high βV-tubulin expression and prolonged progression-free survival (PFS, median 19.2 vs 9.4 months in high vs low expressors; P=0.0315, HR: 1.899) was found. Further, high βV-tubulin expression was associated with objective response (median H-score 172.5 for CR+PR vs 120 for SD+PD patients, P=0.0104) or disease control following induction chemotherapy (170 for CR+PR+SD vs 100 for PD patients, P=0.0081), but not radiochemotherapy."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Aged",
"Antineoplastic Combined Chemotherapy Protocols",
"Bridged-Ring Compounds",
"Carcinoma, Non-Small-Cell Lung",
"Cohort Studies",
"Disease-Free Survival",
"Female",
"Humans",
"Immunohistochemistry",
"Lung Neoplasms",
"Male",
"Middle Aged",
"Retrospective Studies",
"Taxoids",
"Transfection",
"Treatment Outcome",
"Tubulin"
]
} | Expression of βV-tubulin was associated with treatment response and PFS following paclitaxel-based chemotherapy of locally advanced and oligometastatic NSCLC patients. Prolonged OS was associated with low levels of βIII-tubulin. Prospective evaluation of βIII/βV-tubulin expression in NSCLC is warranted. | yes |
22,812,913 | Is the Renalase Asp37Glu polymorphism associated with hypertension and cardiovascular events in an urban-based prospective cohort : the Malmö Diet and cancer study? | {
"contexts": [
"Renalase (gene name RNLS), a recently discovered enzyme with monoamine oxidase activity, is implicated in the degradation of catecholamines. Recent studies delineate a possible role of this enzyme in blood pressure (BP) maintenance and cardiac protection and two single nucleotide polymorphisms, RNLS rs2576178 A > G and rs2296545 C > G have been associated with hypertension. The latter SNP leads to a non synonymous Asp to Glu substitution deleting a flavin adenine dinucleotide (FAD) binding site with possible impaired functionality. We tested the hypothesis that these polymorphisms could affect BP levels, hypertension prevalence, and risk of incident cardiovascular events in middle-aged Swedes.",
"The polymorphisms were genotyped in 5696 participants of the population-based Cardiovascular Cohort of the \"Malmö Diet and Cancer\" (MDC-CC). The incidence of cardiovascular events (coronary events [n = 408], strokes [n = 330], heart failure [n = 190] and atrial fibrillation/flutter [n = 406]) was monitored for an average of approximately 15 years of follow-up.",
"Both before and after adjustment for sex, age and BMI the polymorphisms did not show any effect on BP level and hypertension prevalence. Before and after adjustment for major cardiovascular risk factors, the hazard ratio for cardiac and cerebrovascular events was not significantly different in carriers of different genotypes. A significant interaction was found between the rs2296545 C > G and age with respect to BP/hypertension."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Age Factors",
"Aged",
"Cardiovascular Diseases",
"Female",
"Health Surveys",
"Humans",
"Hypertension",
"Incidence",
"Male",
"Middle Aged",
"Monoamine Oxidase",
"Neoplasms",
"Polymorphism, Genetic",
"Prevalence",
"Prospective Studies",
"Risk",
"Stroke"
]
} | Our data do not support a major role for these RNLS polymorphisms in determining BP level and incident events at population level. The positive interaction with age suggest that the effect of the rs2296545 C > G polymorphism, if any, could vary between different ages. | no |
22,840,462 | Is microvessel proliferation by co-expression of endothelial nestin and Ki-67 associated with a basal-like phenotype and aggressive features in breast cancer? | {
"contexts": [
"To quantify tumour angiogenesis, microvessel density (MVD) has been widely used. We here present a novel angiogenesis marker, microvessel proliferation (MVP), based on dual immunohistochemical staining of nestin and Ki-67. Immature endothelial cells express nestin, and when co-expressed with the proliferation marker Ki-67, the number of proliferating immature blood vessels can be measured.",
"Microvessel proliferation was evaluated in 178 breast cancer samples and estimated by vascular proliferation index (VPI), the ratio between the number of vessels containing proliferating endothelial cells and the total number of immature vessels.",
"High VPI was strongly associated with several markers of aggressive breast cancer, such as negative oestrogen receptor (ER) status (p = 0.003), high tumour cell proliferation by Ki-67 (p = 0.004), high p53 expression (p = 0.001), and five profiles for the basal-like phenotype (odds ratios (OR); range 3.4-6.3). Also, high VPI was significantly associated with interval detected breast cancer compared with screening detected lesions (p < 0.0005), and adverse outcome in univariate and multivariate survival analysis (p = 0.034 and p = 0.022, respectively)."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Aged",
"Breast Neoplasms",
"Carcinoma",
"Cell Proliferation",
"Endothelium",
"Female",
"Humans",
"Ki-67 Antigen",
"Microvessels",
"Middle Aged",
"Neoplasm Grading",
"Neovascularization, Pathologic",
"Nestin",
"Prognosis",
"Receptors, Estrogen",
"Receptors, Progesterone",
"Tumor Suppressor Protein p53"
]
} | Microvessel proliferation is a novel marker of ongoing angiogenesis and was associated with aggressive tumour features, basal-like phenotypes, interval presentation, and prognosis in this series of breast cancer. | yes |
22,806,547 | Does inhibition of nuclear factor-κB enhance the antitumor effect of paclitaxel against gastric cancer with peritoneal dissemination in mice? | {
"contexts": [
"Intraperitoneal (i.p.) administration of paclitaxel is useful for treating malignant tumors with peritoneal dissemination, but the therapeutic efficacy is limited. Chemoresistance due to paclitaxel-induced nuclear factor-kappa B (NF-κB) activation is an important cause of suboptimal therapeutic efficacy.",
"The purpose of this study was to prove that addition of nafamostat mesilate (FUT-175), a synthetic serine protease inhibitor and an NF-κB inhibitor, to i.p. paclitaxel enhances antitumor effects of paclitaxel against gastric cancer with peritoneal dissemination.",
"In vitro, we assessed NF-κB activity and apoptosis in response to treatment with FUT-175 alone, paclitaxel alone, or a combination of FUT-175 and paclitaxel in a human gastric cancer cell line (MKN-45). In vivo, we established peritoneal dissemination in nude mice by i.p. injection of MKN-45 cells. The animals received i.p. injections of FUT-175 alone three times a week (FUT-175 group), of paclitaxel alone once a week (paclitaxel group), or a combination of FUT-175 and paclitaxel (combination group) three times and once a week, respectively.",
"In the combination group, paclitaxel-induced NF-κB activation was inhibited and apoptosis was enhanced in comparison with those in the other groups both in vitro and in vivo. In the combination group, number and weight of peritoneal nodules were significantly lower than those in the paclitaxel group (p = 0.0009 and p = 0.0417, respectively). In the survival analysis, the combination group had a significantly better survival than the paclitaxel group (p = 0.0048)."
],
"labels": [
"BACKGROUND",
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Antineoplastic Agents",
"Caspase 3",
"Caspase 8",
"Cell Cycle",
"Cell Line, Tumor",
"Cell Proliferation",
"Gene Expression Regulation",
"Guanidines",
"Humans",
"I-kappa B Proteins",
"Male",
"Mice",
"Mice, Nude",
"NF-KappaB Inhibitor alpha",
"NF-kappa B",
"Neoplasms, Experimental",
"Paclitaxel",
"Peritoneal Neoplasms",
"Poly(ADP-ribose) Polymerases",
"Stomach Neoplasms"
]
} | FUT-175 enhances the antitumor effect of i.p. paclitaxel against gastric cancer with peritoneal dissemination by inhibiting NF-κB activation in mice. | yes |
22,806,544 | Is neuronal pentraxin II ( NPTX2 ) frequently down-regulated by promoter hypermethylation in pancreatic cancers? | {
"contexts": [
"Gene silencing via promoter hypermethylation plays a crucial role in the pathogenesis of cancers. Neuronal pentraxin II (NPTX2) has been observed to be hypermethylated in pancreatic cancers. Methylation of NPTX2 might provide a novel diagnostic marker for pancreatic cancers.",
"The objective of this study is to investigate the abnormal patterns of DNA methylation of NPTX2 in pancreatic cancers, and its role in the transcriptional silencing of NPTX2.",
"NPTX2 expression was detected by reverse-transcription polymerase chain reaction (RT-PCR), and the methylation status of NPTX2 was assessed by methylation-specific polymerase chain reaction (MSP). Immunohistochemistry was used to examine the NPTX2 protein expression. The pancreatic cancer cell lines were treated with the DNA methyltransferase inhibitor, histone deacetylase inhibitors, either alone or in combination.",
"The MSP analysis revealed that the promoter region of NPTX2 gene was largely unmethylated in normal pancreatic tissues, while NPTX2 was frequently hypermethylated in pancreatic cancer cells and in primary pancreatic carcinomas. Quantitative RT-PCR revealed that the mean mRNA expression level of NPTX2 in the pancreatic cancer tissues was significantly lower than that in the paired adjacent normal tissues (0.96 ± 0.91 vs. 2.78 ± 1.42, P < 0.001). Consistent with RT-PCR detection, treatment with 5Aza-dC resulted in different degrees of induction of NPTX2 protein in the various cancer cell lines."
],
"labels": [
"BACKGROUND",
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adenocarcinoma",
"Biomarkers, Tumor",
"C-Reactive Protein",
"Cell Line, Tumor",
"DNA Methylation",
"Down-Regulation",
"Gene Expression Regulation, Neoplastic",
"Gene Silencing",
"Humans",
"Methyltransferases",
"Nerve Tissue Proteins",
"Pancreatic Neoplasms",
"Polymerase Chain Reaction",
"Promoter Regions, Genetic",
"RNA, Messenger"
]
} | We demonstrate that the NPTX2 protein is down-regulated in human primary pancreatic cancers and in pancreatic cancer cell lines. This study provides the first evidence that the down-regulation of NPTX2 tightly correlates with its promoter hypermethylation. | yes |
22,819,108 | Are inducible nitric oxide synthase and PPARγ involved in bladder cancer progression? | {
"contexts": [
"We evaluated the role of inducible nitric oxide synthase and PPARγ as prognostic factors for bladder cancer.",
"Inducible nitric oxide synthase and PPARγ were evaluated by Western blot and immunohistochemistry in a mouse bladder cancer model of nonmuscle invasive and invasive MB49-I tumor cells, and in human bladder cancer samples.",
"Inducible nitric oxide synthase expression was negative in mouse normal urothelium and higher in invasive than in noninvasive MB49 tumors. In vitro inducible nitric oxide synthase activity, determined as nitrite, was higher in MB49-I than in MB49 cells (p <0.001). In human samples expression was also associated with tumor invasion. Nuclear PPARγ expression was negative in normal mouse urothelium but higher in nonmuscle invasive MB49 than in MB49-I tumors. Similarly in human tumors low PPARγ was associated with poor prognosis factors, such as high histological grade (p = 0.0160) and invasion status (p = 0.0352). A positive correlation was noted between inducible nitric oxide synthase and PPARγ in low histological grade and nonmuscle invasive tumors (Pearson correlation index 0.6368, p = 0.0351, 0.4438 and 0.0168, respectively). As determined by gene reporter assay, PPARγ activity was induced by nitric oxide only in nonmuscle invasive MB49 cells (p <0.001)."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Disease Progression",
"Humans",
"Mice",
"Mice, Inbred C57BL",
"Nitric Oxide Synthase Type II",
"PPAR gamma",
"Prognosis",
"Urinary Bladder Neoplasms"
]
} | Results suggest that increased PPARγ controls inducible nitric oxide synthase expression at early tumor stages. However, regulation is lost at advanced tumor stages, when the increase in inducible nitric oxide synthase and the decrease in PPARγ seem to be associated with bladder cancer progression. | yes |
22,821,767 | Are urine TMPRSS2 : ERG fusion transcript integrated with PCA3 score , genotyping , and biological features correlated to the results of prostatic biopsies in men at risk of prostate cancer? | {
"contexts": [
"Detection of fusion gene TMPRSS2:ERG transcripts in urine have been recently described in order to refine urine-based detection of prostate cancer (PCa), but data its clinical impact remain scarce. We aimed at investigating the correlation of TMPRSS2:ERG, prostate cancer antigen 3 (PCA3), prostate specific antigen (PSA) density, genetic variants, and androgenic status with outcome and pathological findings at prostatic biopsy.",
"Between 2007 and 2011, 291 patients at risk of PCa because of PSA > 3.0 ng/ml (55%) or candidate to active surveillance protocol justifying restaging biopsy management (45%) were recruited. TMPRSS2:ERG was detected by urine assay (Progensa™). PCA3-score, PSA level, bioavailable testosterone level, prostate volume, rs1447295 and rs6983267 genotypes were prospectively assessed. Univariate and multivariate analysis by logistic regression model (logit) were conducted to study the correlation of TMPRSS2:ERG status, PCA3, and PSA density with biopsy results, and Gleason score.",
"Of 291 patients, 173 had PCa and 118 had negative biopsy. PCA3 score, PSA density and TMPRSS2:ERG-score were correlated with presence of PCa (P < 0.0001, P = 0.046, and P < 0.0001, respectively). This correlation remained strong on multivariable analysis model (area under curve 0.743). PCA3 score and PSA density were significantly associated with presence of Grade 4 through multivariable analysis. PCA3 score was also correlated to the percentage of positive cores at biopsy (P = 0.008)."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Aged",
"Antigens, Neoplasm",
"Biomarkers, Tumor",
"Biopsy",
"Gene Fusion",
"Genotype",
"Humans",
"Logistic Models",
"Male",
"Middle Aged",
"Multivariate Analysis",
"Prospective Studies",
"Prostate",
"Prostatic Neoplasms",
"Retrospective Studies",
"Risk Factors",
"Sensitivity and Specificity",
"Serine Endopeptidases",
"Trans-Activators",
"Transcription, Genetic",
"Transcriptional Regulator ERG"
]
} | Integration of levels TMPRSS2:ERG transcripts in urine, with PCA3-score, androgenic status, genetic status and traditional clinical variables could significantly increase detection of high risk localized PCa. | yes |
22,832,328 | Are metabolism-related proteins differentially expressed according to the molecular subtype of invasive breast cancer defined by surrogate immunohistochemistry? | {
"contexts": [
"The purpose of this study was to investigate the expression of metabolism-related proteins such as Glut-1 and carbonic anhydrase IX (CAIX) according to breast cancer molecular subtype.",
"We generated a tissue microarray of 276 breast cancer patients and performed immunohistochemical staining for known metabolism-related proteins, which were evaluated according to the molecular subtype.",
"The expression of IGF-1, MIF, and HIF-1α was correlated with the HER-2 type (p < 0.05). Glut-1 overexpression and CAIX expression were associated with TNBC type, especially with basal-like type, high histologic grade, estrogen receptor negativity, and progesterone receptor negativity (p < 0.05). The expression of Glut-1 and CAIX was correlated with statistical significance (p < 0.001)."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Antigens, Neoplasm",
"Biomarkers, Tumor",
"Breast Neoplasms",
"Carbonic Anhydrase IX",
"Carbonic Anhydrases",
"Carcinoma, Ductal, Breast",
"Female",
"Gene Expression Regulation, Neoplastic",
"Glucose Transporter Type 1",
"Glycolysis",
"Humans",
"Hypoxia-Inducible Factor 1, alpha Subunit",
"Immunohistochemistry",
"Immunophenotyping",
"Intramolecular Oxidoreductases",
"Macrophage Migration-Inhibitory Factors",
"Middle Aged",
"Neoplasm Grading",
"Neoplasm Staging",
"Prognosis",
"Protein-Serine-Threonine Kinases",
"Receptor, ErbB-2",
"Survival Rate",
"Tissue Array Analysis"
]
} | We identified different patterns of expression of metabolism-related proteins according to the molecular subtypes of breast cancer defined by surrogate immunohistochemistry. Increased expression of HIF-1α, IGF-1, and MIF was noted in HER-2 type breast cancer and increased expression of Glut-1 and CAIX was noted in TNBC type breast cancer, especially in the basal-like subtype, which exhibited a glycolytic and acid-resistant tumor phenotype. | yes |
22,821,802 | Is use of β-blockers associated with prostate cancer-specific survival in prostate cancer patients on androgen deprivation therapy? | {
"contexts": [
"Experimental evidence suggests a role for the β(2) -adrenergic receptor pathway in prostate cancer (PCa). We have investigated the association of β-blocker use with PCa incidence and survival in a Norwegian cohort.",
"Data from the Oslo II study in 2000 (n = 6515) were linked with information from the Cancer Registry of Norway and Statistics Norway. PCa risk and overall- and PCa-specific mortality were analyzed using uni- and multi-variable Cox- and competing risk regression models.",
"At baseline, 776 men (11.9%) reported using a β-blocker. 212 men (3.3%) were diagnosed with PCa before the survey, leaving 6,303 eligible for incidence analysis. During a median follow-up of 122 months, 448 (7.1%) men were diagnosed with PCa. β-blocker use was not associated with PCa risk [hazard ratio (HR): 1.05, 95% CI: 0.79-1.40]. For all patients (n = 655; including med diagnosed before the survey), β-blocker use was not associated with PCa-specific mortality (HR: 0.55, 95% CI 0.24-1.26, P = 0.16). However, in the subgroup of men planned to receive androgen deprivation therapy (ADT), as reported to the Cancer Registry (n = 263), β-blocker use was associated with reduced PCa-specific mortality (HR: 0.14, 95% CI 0.02-0.85, P = 0.032). No effect on overall mortality was seen (HR, all patients: 0.88, 95% CI 0.56-1.38, P = 0.57). β-blocker use did not appear to affect PSA level, Gleason score, or T-stage at diagnosis; however, these variables were missing for many cases."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adrenergic beta-Antagonists",
"Aged",
"Androgen Antagonists",
"Cohort Studies",
"Follow-Up Studies",
"Humans",
"Incidence",
"Kaplan-Meier Estimate",
"Male",
"Middle Aged",
"Norway",
"Prostatic Neoplasms",
"Registries",
"Regression Analysis",
"Survival Rate",
"Treatment Outcome"
]
} | Our findings demonstrate a possible benefit of β-blocker use for men treated with ADT, suggesting the need for investigation in larger cohorts. | yes |
22,836,510 | Does downregulation of miR-126 induce angiogenesis and lymphangiogenesis by activation of VEGF-A in oral cancer? | {
"contexts": [
"MicroRNA (miRNA)-126 (miR-126) is an endothelial-specific miRNA located within intron 7 of epidermal growth factor-like domain 7 (EGFL7). However, the role of miR-126 in cancer is controversial.",
"We examined the function of miR-126 in oral squamous cell carcinoma (OSCC) cells. Furthermore, a series of 118 cases with OSCC were evaluated for the expression levels of miR-126.",
"MicroRNA-126 (miR-126) was associated with cell growth and regulation of vascular endothelial growth factor-A activity, and demethylation treatment increased expression levels of miR-126 and EGFL7 in OSCC cells. A significant association was found between miR-126 expression and tumour progression, nodal metastasis, vessel density, or poor prognosis in OSCC cases. In the multivariate analysis, decreased miR-126 expression was strongly correlated with disease-free survival."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Aged",
"Aged, 80 and over",
"Carcinoma, Squamous Cell",
"Cell Line, Tumor",
"Disease-Free Survival",
"Down-Regulation",
"Endothelial Growth Factors",
"Female",
"Humans",
"Lymphangiogenesis",
"Male",
"MicroRNAs",
"Middle Aged",
"Mouth Neoplasms",
"Neovascularization, Pathologic",
"Transcriptional Activation",
"Vascular Endothelial Growth Factor A"
]
} | The present results suggest that miR-126 might be a useful diagnostic and therapeutic target in OSCC. | yes |
22,821,394 | Does aDC map in the prediction of pelvic lymph nodal metastatic regions in endometrial cancer? | {
"contexts": [
"To evaluate the usefulness of apparent diffusion coefficient (ADC) in discriminating metastatic from non-metastatic pelvic lymph nodal sites in endometrial cancer.",
"This retrospective study included 40 patients with endometrial cancer who underwent MRI [T2-weighted, dynamic T1-weighted images and diffusion-weighted images with body background suppression (DWIBS), b-values 0 and 1,000 s/mm(2)], total hysterectomy and pelvic lymphadenectomy. Lymph nodes identifiable on DWIBS were evaluated, classified into six nodal regions, and for each node ADC values, short- and long-axis diameters were measured by two readers. Histopathological findings and follow-up information served as the reference standard.",
"Average (± standard deviation) mean and minimum ADC region value (0.87 ± 0.15 and 0.74 ± 0.07 × 10(-3) mm(2)/s) of metastatic sites (n = 7) were significantly lower than those of non-metastatic ones (n = 89; 1.07 ± 0.20 and 1.02 ± 0.20; p-value = 0.010 and 0.0004). Mean short-axis and short-to-long axis ratios of metastatic nodes were 7.47 mm and 0.68. Using the minimum ADC region value with threshold 0.807 × 10(-3) mm(2)/s, sensitivity, specificity, positive and negative predictive value and accuracy were 100 %, 98.3 %, 63.6 %, 100 % and 98.3 %, respectively (reader 1)."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adenocarcinoma",
"Aged",
"Contrast Media",
"Diffusion Magnetic Resonance Imaging",
"Endometrial Neoplasms",
"Female",
"Gadolinium DTPA",
"Humans",
"Hysterectomy",
"Lymph Node Excision",
"Lymph Nodes",
"Lymphatic Metastasis",
"Middle Aged",
"Neoplasm Grading",
"Neoplasm Invasiveness",
"Pelvis",
"Predictive Value of Tests",
"ROC Curve",
"Retrospective Studies",
"Sensitivity and Specificity"
]
} | In endometrial cancer, mean and minimum ADC region values of metastatic nodal sites are significantly lower than those found at normal sites. | yes |
16,846,534 | Does mUC1 alter oncogenic events and transcription in human breast cancer cells? | {
"contexts": [
"MUC1 is an oncoprotein whose overexpression correlates with aggressiveness of tumors and poor survival of cancer patients. Many of the oncogenic effects of MUC1 are believed to occur through interaction of its cytoplasmic tail with signaling molecules. As expected for a protein with oncogenic functions, MUC1 is linked to regulation of proliferation, apoptosis, invasion, and transcription.",
"To clarify the role of MUC1 in cancer, we transfected two breast cancer cell lines (MDA-MB-468 and BT-20) with small interfering (si)RNA directed against MUC1 and analyzed transcriptional responses and oncogenic events (proliferation, apoptosis and invasion).",
"Transcription of several genes was altered after transfection of MUC1 siRNA, including decreased MAP2K1 (MEK1), JUN, PDGFA, CDC25A, VEGF and ITGAV (integrin alphav), and increased TNF, RAF1, and MMP2. Additional changes were seen at the protein level, such as increased expression of c-Myc, heightened phosphorylation of AKT, and decreased activation of MEK1/2 and ERK1/2. These were correlated with cellular events, as MUC1 siRNA in the MDA-MB-468 line decreased proliferation and invasion, and increased stress-induced apoptosis. Intriguingly, BT-20 cells displayed similar levels of apoptosis regardless of siRNA, and actually increased proliferation after MUC1 siRNA."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Antigens, Neoplasm",
"Apoptosis",
"Breast Neoplasms",
"Cell Line, Tumor",
"Cell Proliferation",
"Female",
"Humans",
"Mucin-1",
"Mucins",
"Neoplasm Invasiveness",
"RNA, Small Interfering",
"Transcription, Genetic"
]
} | These results further the growing knowledge of the role of MUC1 in transcription, and suggest that the regulation of MUC1 in breast cancer may be more complex than previously appreciated. The differences between these two cell lines emphasize the importance of understanding the context of cell-specific signaling events when analyzing the oncogenic functions of MUC1, and caution against generalizing the results of individual cell lines without adequate confirmation in intact biological systems. | yes |
16,846,533 | Is central nervous system relapse in patients with breast cancer associated with advanced stages , with the presence of circulating occult tumor cells and with the HER2/neu status? | {
"contexts": [
"To evaluate the incidence of central nervous system (CNS) involvement in patients with breast cancer treated with a taxane-based chemotherapy regimen and to determine predictive factors for CNS relapse.",
"The medical files of patients with early breast cancer (n = 253) or advanced stage breast cancer (n = 239) as well of those with other solid tumors (n = 336) treated with or without a taxane-based chemotherapy regimen during a 42-month period were reviewed. HER2/neu overexpression was identified by immunohistochemistry, whereas cytokeratin 19 (CK-19) mRNA-positive circulating tumor cells (CTCs) in the peripheral blood were identified by real-time PCR.",
"The incidence of CNS relapse was similar in patients suffering from breast cancer or other solid tumors (10.4% and 11.4%, respectively; P = 0.517). The incidence of CNS relapse was significantly higher in breast cancer patients with advanced disease (P = 0.041), visceral disease and bone disease (P = 0.036), in those who were treated with a taxane-containing regimen (P = 0.024), in those with HER2/neu-overexpressing tumors (P = 0.022) and, finally, in those with detectable CK-19 mRNA-positive CTCs (P = 0.008). Multivariate analysis revealed that the stage of disease (odds ratio, 0.23; 95% confidence interval, 0.007-0.23; P = 0.0001), the HER2/neu status (odds ratio, 29.4; 95% confidence interval, 7.51-101.21; P = 0.0001) and the presence of CK-19 mRNA-positive CTCs (odds ratio, 8.31; 95% confidence interval, 3.97-12.84; P = 0.001) were independent predictive factors for CNS relapse."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Aged",
"Aged, 80 and over",
"Antineoplastic Agents",
"Breast Neoplasms",
"Central Nervous System Neoplasms",
"Female",
"Humans",
"Keratin-19",
"Middle Aged",
"Neoplasm Staging",
"Neoplastic Cells, Circulating",
"Predictive Value of Tests",
"RNA, Messenger",
"Receptor, ErbB-2",
"Taxoids"
]
} | CNS relapses are common among breast cancer patients treated with a taxane-based chemotherapy regimen, patients with HER2/neu-positive tumor and patients with CK-19 mRNA-positive CTCs. | yes |
16,817,912 | Is prior chemoradiotherapy associated with a higher life-threatening complication rate after palliative insertion of metal stents in patients with oesophageal cancer? | {
"contexts": [
"Self-expanding metal stents are used routinely to palliate dysphagia due to oesophageal cancer.",
"To compare the frequency of life-threatening complications after self-expanding metal stent insertion, depending on whether patients received prior chemoradiotherapy or no treatment.",
"During 7 years, 116 consecutive patients were treated at a single centre in a palliative intent by insertion of self-expanding metal stent for dysphagia due to an oesophageal cancer. Patients were retrospectively separated into two groups: patients with chemoradiotherapy before self-expanding metal stent insertion (group 1, n = 56) and patients with no treatment before or after self-expanding metal stent insertion (group 2, n = 60). Life-threatening complications were compared and predictive risk factors of postprocedure complications were identified.",
"Median dysphagia was significantly improved during the first month (grade 3 to grade 1 in the two groups). Early and late major complications occurred more frequently in group 1 (23.2% vs. 3.3%; P < 0.002 and 21.6% vs. 5.1%; P < 0.02 respectively). Prior chemoradiotherapy was the only independent predictive factor of postprocedure major complications, with an odds ratio of 5.59 (CI 95% 1.7-18.1)."
],
"labels": [
"BACKGROUND",
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Aged",
"Antineoplastic Agents",
"Combined Modality Therapy",
"Deglutition Disorders",
"Esophageal Neoplasms",
"Female",
"Humans",
"Male",
"Middle Aged",
"Postoperative Complications",
"Radiotherapy",
"Retrospective Studies",
"Risk Factors",
"Stents"
]
} | Life-threatening complications after palliative self-expanding metal stent placement seem to occur more frequently in patients with prior chemoradiotherapy. Prevention of these severe complications should be considered before stenting. | yes |
16,827,122 | Does pARP regulate TGF-beta receptor type II expression in estrogen receptor-positive breast cancer cell lines? | {
"contexts": [
"Expression of the tumor suppressor gene, transforming growth factor beta receptor type II (TbetaRII) is often reduced in estrogen receptor-positive breast cancer cells leading to uninhibited tumor cell growth. A clear understanding of its regulation is necessary to identify potential mechanisms to re-express this tumor suppressor gene.",
"The regulation of TbetaRII expression was studied by utilizing 5'promoter deletion constructs, followed by EMSA analyses. The resulting binding protein was affinity purified and identified by mass spectrophotometry.",
"An inverted CCAAT box centered at -79 was found to be essential for TbetaRII promoter activity. Purification of the protein binding to this region and subsequent mass spectrophotometric analysis identified the binding protein as poly(ADP-ribose)polymerase I (PARP). ChIP assays verified that PARP interacted with the TbetaRII promoter in vivo."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Breast Neoplasms",
"CCAAT-Binding Factor",
"Cell Line, Tumor",
"Gene Expression Regulation, Neoplastic",
"Humans",
"Poly (ADP-Ribose) Polymerase-1",
"Poly(ADP-ribose) Polymerases",
"Promoter Regions, Genetic",
"Protein-Serine-Threonine Kinases",
"Receptor, Transforming Growth Factor-beta Type II",
"Receptors, Estrogen",
"Receptors, Transforming Growth Factor beta",
"Transcription Factors",
"Transfection"
]
} | The present study demonstrated that PARP is important for TbetaRII expression in estrogen receptor-positive breast cancer cell lines. | yes |
16,832,786 | Are [ Triiodothyronine receptors ( TR ) present in breast cancer tissues ]? | {
"contexts": [
"Possible relationships between breast cancer and thyroid hormones have been suggested for many years. The aim of this study was qualitative examination of triiodothyronine receptors (TR) in breast cancer tissues and in non cancerous breast tissue taken from the opposite side to the localization of the tumor.",
"The material consisted of 15 breast cancer tissues of grades G1 to G3 and the same number of control tissues obtained during radical mastectomy or local tumor resection. Tissues were homogenized. Protein fraction was isolated. Protein for TR was assessed in Western Blot reaction.",
"Protein fraction for TR was present in all cancer tissues and 6 healthy controls."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Aged",
"Blotting, Western",
"Breast Neoplasms",
"Female",
"Humans",
"Mastectomy, Radical",
"Mastectomy, Segmental",
"Receptors, Thyroid Hormone"
]
} | Obtained data may suggest so far unknown role of thyroid hormones and their nuclear receptors in the generation and development of breast cancer. | yes |
16,824,932 | Is delta mtDNA4977 more common in non-tumoral cells from gastric cancer sample? | {
"contexts": [
"The aim of this study was to determine the frequency of delta mtDNA4977 in tumoral cells as compared with adjacent normal cells in gastric cancer.",
"In order to investigate whether a high incidence of mutation exists in mitochondrial DNA of gastric cancer tissues, we screened one of common region of the mitochondrial genome by PCR amplification and Southern blot followed by DNA sequence analysis. DNA isolated from these cells was used to amplify hypervariable regions ATPase8/6, COXIII, ND3, ND4 and ND5 of delta mtDNA4977.",
"In 107 cancer patients, delta mtDNA4977 was detected in 6 cases (5.60%) of the tumoral tissues and 18 cases (16.82%) of the non-tumoral tissues that were adjacent to the tumors. Levels of delta mtDNA4977 deletions were found to be more in non-tumoral tissues than in adjacent tumoral tissues. There was no correlation of patients with certain clinical parameters like age, sex, tumor location and tumor size; however, there was an obvious relationship with intestinal-type of gastric cancer."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"DNA, Mitochondrial",
"Female",
"Gene Deletion",
"Humans",
"Iran",
"Male",
"Sequence Analysis, DNA",
"Stomach",
"Stomach Neoplasms"
]
} | Unknown genetic aspects, ambiguous environmental factors and reactive oxygen species (ROS) can cause the delta mtDNA4977 mutation rate to be increased in gastric cancer. The results suggest that percentage level of delta mtDNA4977 is less common and intolerable in tumoral tissue, probably because of high metabolism and ROS generation. We supposed that the cells initially had delta mtDNA4977 transform to tumoral cells and the existed deletion conferred metabolic disadvantage; thus, cells containing such a mtDNA deletion would be overgrown by other cancer cells without this mtDNA deletion. As a result, the presence of delta mtDNA4977 will be low in tumoral cells. | yes |
16,831,167 | Is aberrant expression of cystatin C in prostate cancer associated with neuroendocrine differentiation? | {
"contexts": [
"To investigate the expression of cystatin C and the relationship with neuroendocrine differentiation and proliferation in benign and malignant prostatic tissues, as cystatin C, the most important inhibitor of human lysosomal cysteine proteases, is considered to be a major regulator of pathological protein degradation in inflammatory and neoplastic diseases.",
"Immunoreactivity for cystatin C, prostate-specific antigen, Ki-67 and the neuroendocrine marker chromogranin A was examined in whole-mount radical prostatectomy specimens and using tissue microarrays. Cystatin C in tissue homogenates was analysed by Western blotting and enzyme-linked immunosorbent assay (ELISA). The expression and relative levels of cystatin C mRNA were assessed by in situ hybridization and quantitative real-time polymerase chain reaction (QRT-PCR).",
"The intensity of cystatin C immunostaining in Gleason grade 2 and 3 prostate cancer was significantly higher than in benign prostatic tissues, but decreased significantly with increasing Gleason grades. There was strong expression of cystatin C in neuroendocrine-like cells, which increased significantly with increasing Gleason grades. The Ki-67 immunoreactivity also increased significantly during de-differentiation. In situ hybridization showed staining patterns in concordance with the immunohistochemical results. ELISA showed high concentrations of cystatin C in benign and malignant tissue extracts and QRT-PCR further corroborated that the cystatin C gene is highly expressed in both benign and malignant prostatic tissues."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Aged",
"Cell Transformation, Neoplastic",
"Chromogranin A",
"Chromogranins",
"Cystatin C",
"Cystatins",
"Disease Progression",
"Humans",
"Ki-67 Antigen",
"Male",
"Middle Aged",
"Neuroendocrine Tumors",
"Prostatic Neoplasms"
]
} | There was a significant decrease in the immunohistochemical expression of cystatin C in non-neuroendocrine prostate cancer cells, concomitant with increasing Gleason grades. That there were more strongly cystatin C-positive neuroendocrine-like cells in prostate cancer than in benign prostatic tissue suggests a connection between cystatin C and neuroendocrine differentiation in prostate cancer progression. | yes |
16,831,168 | Do high-grade and hormone-treated prostate cancer express high levels of thymidylate synthase? | {
"contexts": [
"To evaluate the expression of thymidylate synthase and dihydropyrimidine dehydrogenase in prostate tissue.",
"Tissue from 79 patients with localized prostate cancer was used. Thymidylate synthase and dihydropyrimidine dehydrogenase expression were determined semiquantitatively by immunohistochemistry.",
"Thymidylate synthase and dihydropyrimidine dehydrogenase immunostaining grades of benign tissue were significantly higher than those of cancer tissue (both P < 0.01). Cancer tissue with a primary Gleason grade of > or = 4 expressed a higher thymidylate synthase staining grade than those with a primary Gleason grade of <4 (P < 0.01). Cancer tissue spots from patients treated with neoadjuvant therapy revealed significantly higher thymidylate synthase and dihydropyrimidine dehydrogenase grades than those with no neoadjuvant therapy (P < 0.01)."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Aged",
"Antineoplastic Agents, Hormonal",
"Chemotherapy, Adjuvant",
"Cohort Studies",
"Dihydrouracil Dehydrogenase (NADP)",
"Humans",
"Immunohistochemistry",
"Male",
"Middle Aged",
"Prostatic Neoplasms",
"Retrospective Studies",
"Thymidylate Synthase"
]
} | High thymidylate synthase expression in localized prostate cancer might reflect an aggressive status. High expression in high-grade prostate cancers and prostate cancers after hormonal therapy suggest that thymidylate synthase could be a new therapeutic target for advanced prostate cancer. | yes |
16,845,800 | Does knockdown of survivin expression by small interfering RNA suppress proliferation of two human cancer cell lines? | {
"contexts": [
"To construct an expression vector of small interfering RNA (siRNA) against survivin and observe its effects on survivin expression and proliferation of human pancreatic cancer cell line PC-2 and breast cancer cell line MCF-7.",
"Constructed an expression vector of siRNA against survivin and transfected it into PC-2 and MCF-7 cells using lipofectamine 2000. The expression of survivin was detected by semi-quantitive RT-PCR and immunohistochemistry, and its effects on proliferation of PC-2 and MCF-7 cells were detected by MTT assay.",
"The introduction of sequence-specific siRNA could efficiently suppress survivin expression at both mRNA and protein levels in the two cancer cell lines. In PC-2 cells, the expression inhibition rates were 81.25% at mRNA level and 74.24% at protein level. In MCF-7 cells, the expression inhibition rates were 64.91% at mRNA level and 79.72% at protein level. The proliferation of PC-2 and MCF-7 cells was also suppressed, and 24 and 48 hours after the cells were reseeded, the proliferation inhibition rates of PC-2 cells were 28.00% and 33.38%, and that of MCF-7 cells were 31.58% and 33.02%, respectively."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Base Sequence",
"Breast Neoplasms",
"Cell Line, Tumor",
"Cell Proliferation",
"Female",
"Gene Expression",
"Humans",
"Inhibitor of Apoptosis Proteins",
"Microtubule-Associated Proteins",
"Pancreatic Neoplasms",
"Plasmids",
"RNA, Messenger",
"RNA, Neoplasm",
"RNA, Small Interfering",
"Survivin",
"Transfection"
]
} | The expression vector of siRNA against survivin can block survivin expression in PC-2 and MCF-7 cells efficiently and specifically. Down regulation of survivin expression can suppress proliferation of PC-2 and MCF-7 cells. Survivin RNAi may have potential value in gene therapy of human cancers. | yes |
16,847,925 | Is high Pin1 expression associated with tumor progression in colorectal cancer? | {
"contexts": [
"Peptidyl prolyl cis-trans isomerase (Pin1) isomerizes only phosphorylated serine or threonine residues preceding proline in certain proteins and affects the protein function. Pin1 interacts with many signaling pathways, including Wnt signaling pathway that is crucial for colorectal tumorigenesis. Pin1 promotes cyclin D1 over-expression directly or through the stabilization of beta-catenin. Pin1 is over-expressed in some cancers such as prostate and breast cancers. This study aimed to determine whether Pin1 plays a role in colorectal tumorigenesis through the upregulation of beta-catenin and cyclin D1.",
"Immunohistochemical analyses were performed on 105 colorectal cancer tissue samples using anti-Pin1, anti-beta-catenin, and anti-cyclin D1 antibodies. We examined the relationships between Pin1 expression and clinicopathological factors, prognosis, and beta-catenin/cyclin D1 expression.",
"High Pin1 expression was observed in 40 cases (38%) and positively correlated with histological type (P=0.0240), depth of invasion (P=0.0051), and staging (P=0.0027) of colorectal tumors. High Pin1 expression was also correlated with the over-expressions of both beta-catenin (P=0.0225) and cyclin D1 (P=0.0137)."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Aged",
"Colorectal Neoplasms",
"Cyclin D1",
"Disease Progression",
"Female",
"Gene Expression Regulation, Enzymologic",
"Gene Expression Regulation, Neoplastic",
"Humans",
"Immunohistochemistry",
"Lymphatic Metastasis",
"Male",
"Neoplasm Invasiveness",
"Peptidylprolyl Isomerase",
"Signal Transduction",
"Survival Rate",
"beta Catenin"
]
} | These results suggest that Pin1 plays an important role in colorectal tumorigenesis, presumably by increasing beta-catenin and cyclin D1 expressions. | yes |
16,844,458 | Does granulocyte colony-stimulating receptor promote beta1-integrin-mediated adhesion and invasion of bladder cancer cells? | {
"contexts": [
"To determine whether granulocyte colony-stimulating factor receptor (G-CSFR) autocrine signaling promotes endothelial cell adhesion and invasion of bladder cancer cells through a beta1-integrin-mediated pathway. A significant fraction of invasive bladder carcinomas express both G-CSF and G-CSFR. Bladder carcinoma cell line 5637 constitutively secretes G-CSF but lacks G-CSFR expression. Thus, we studied the effects of G-CSFR expression on cell adhesion and invasion in this unique model system.",
"Flow cytometry and adhesion assay were performed to detect expression of beta1-integrin in G-CSFR-expressing 5637 cells and adhesion of these cells to human umbilical vein endothelial cell, respectively. Furthermore, an invasion chamber assay was done with the 5637 cells. Next, we used the G-CSF-specific antibody, siRNA, and a truncated version of G-CSFR (GR19) to block G-CSFR autocrine loop in these cells. We also used a beta1-integrin-specific neutralizing antibody in the adhesion and invasion assays with the 5637 cells.",
"G-CSFR-mediated increased expression (approximately threefold) of beta1-integrin is significantly abrogated by G-CSF specific antibody or siRNA in 5637 cells. GR19 also completely blocked beta1-integrin expression. G-CSFR signaling increased adhesion (approximately 2.5-fold) of 5637 cells to human umbilical vein endothelial cells, which are potently blocked by beta1-integrin-specific antibody. G-CSF/G-CSFR autocrine signaling significantly increased the invasiveness of 5637 cells (approximately 10-fold), which was reduced by either attenuating G-CSF production (G-CSF-specific antibody and siRNA) or interfering with G-CSFR signaling (GR19). Furthermore, beta1-integrin-specific antibody completely blocked G-CSFR-mediated invasion of 5637 cells."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adhesiveness",
"Autocrine Communication",
"Cell Line, Tumor",
"Endothelium, Vascular",
"Flow Cytometry",
"Granulocyte Colony-Stimulating Factor",
"Humans",
"Integrin beta1",
"Neoplasm Invasiveness",
"Receptors, Granulocyte Colony-Stimulating Factor",
"Signal Transduction",
"Urinary Bladder Neoplasms"
]
} | Autocrine G-CSF/G-CSFR signaling in bladder cancer can significantly contribute to cancer cell adhesion and invasion in a beta1-integrin-dependent manner. | yes |
16,827,106 | Does keratinocyte growth factor ( KGF ) induce tamoxifen ( Tam ) resistance in human breast cancer MCF-7 cells? | {
"contexts": [
"Both estrogen receptor-alpha (ER-alpha) and progesterone receptor (PR) are good prognostic factors and indicators of benefit from endocrine therapy in breast cancer patients. The relationship of the ER-alpha and PR status and the difference in clinical benefit from endocrine therapy in breast cancer is currently unclear. It has been suggested that keratinocyte growth factors (KGFs) are important regulatory factors in breast cancer. Our laboratory has demonstrated that KGF can act as an estromedin for the stimulation of breast cancer cell growth. Also, KGF stimulates aromatase activity in primary cultured human breast cells. This enzyme is a key to the conversion of androgens to estrogens. In the present study, ER-alpha, two estrogen-regulated genes, PR and PTPgamma, KGF and their relationship with endocrine resistance in human breast cancer cells were investigated.",
"MCF-7 cells were treated with KGF (1, 5, 10, 20 ng/ml), KGF-13 (0.1, 1, 10 microM) or vehicles as control for 24 hours. KGF-13 is a potential receptor-binding pentapeptide constructed using the KGF peptide residues 101-105 (RTVAV) as a template, located within the beta 4--beta 5 loop. Total RNA were isolated and real-time PCR was employed to identify ER-alpha, PR and PTPgamma gene expressions in response to KGF and KGF-13. Western blot analysis was used to verify the levels of ER-alpha and PR protein, whereas immunohistochemical staining was used to detect PTPgamma expression in MCF-7 cells. To determine the response of MCF-7 cells to endocrine therapy, MCF-7 was treated with either 20 ng/ml KGF or 10 microM KGF-13 combined with 1, 3 and 5 microM of 4-hydroxytamoxifen (4OH-Tam). A non-radioactive cell proliferation assay was applied to determine the growth rate of MCF-7 cells. The results of real-time PCR and the cell proliferation assay were analyzed by Student's t-test and p-values of less than 0.05 were considered statistically significant.",
"Our data showed that KGF significantly suppressed ER-alpha, PR and PTPgamma expression in MCF-7 cells. KGF suppressed ER-alpha, PR and PTPgamma mRNA to a maximal inhibition at 20 ng/ml by 88%, 57% and 61%, respectively. Western blot analysis and immunohistochemical staining confirmed the down-regulation of ER-alpha, PR and PTPgamma by KGF in protein levels. Ten microM KGF-13 also decreased ER-alpha expression. Ten microM KGF-13 significantly decreased ER-alpha, PR and PTPgamma mRNA expressions by 51%, 57% and 67%, respectively. These KGF-13-mediated mRNA down-regulations were also observed in protein levels. In a cell proliferation assay, 4OH-Tam (3, 5 microM) induced MCF-7 cell death. KGF and KGF-13 alone did not stimulate MCF-7 cell growth. KGF significantly disrupted 4OH-Tam cell killing effects by 1.2- and 1.3-fold at 4OH-Tam concentrations of 3 microM and 5 microM, respectively. KGF-13 significantly disrupted 4OH-Tam cell killing effects by 1.2- and 1.7-fold at 4OH-Tam concentrations of 3 microM and 5 microM, respectively."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Antineoplastic Agents, Hormonal",
"Breast Neoplasms",
"Cell Line, Tumor",
"Cell Survival",
"Down-Regulation",
"Drug Resistance, Neoplasm",
"Estrogen Receptor alpha",
"Fibroblast Growth Factor 7",
"Humans",
"Nerve Tissue Proteins",
"Protein Tyrosine Phosphatases",
"RNA, Messenger",
"Receptor-Like Protein Tyrosine Phosphatases, Class 5",
"Receptors, Progesterone",
"Signal Transduction",
"Tamoxifen"
]
} | Our results suggested that not only ER-alpha and PR but also PTPgamma could be potential bio-makers for growth factor-induced endocrine resistant in breast cancer. KGF might increase the endocrine resistance via decreasing ER-alpha, PR and PTPgamma as well. Moreover, the functional analysis of KGF-13 implied possible applications of using short receptor-binding peptides derived from intact KGF as breast cancer therapeutic agents. Thus, our experimental data provided evidence of KGF-induced anti-hormone resistance in human breast cancer and suggested novel strategies for breast cancer via interference with KGF signaling. | yes |
16,827,104 | Does antibody-dependent cell cytotoxicity to breast cancer target despite inhibitory KIR signaling? | {
"contexts": [
"Natural killer (NK) cells express killer immunoglobulin-like (KIR) inhibitory receptors, which recognize certain HLA class I molecules (KIR ligands), and stimulatory receptors such as FcgammaRIII. The purpose of this study was to test the possible influence of inhibitory KIR signaling on antibody-dependent cell cytotoxicity (ADCC) mediated by allogeneic NK cells against breast cancer targets.",
"The cytotoxic activity of volunteer donor NK cells against the cell lines SKBR-3, T47D and MCF-7, which have high, low and no HER2 gene amplification, respectively, were studied. Both cell lines and donors were assigned to the C1 or C2 superfamily, defined by the structure of the HLA-Cw molecule.",
"It was found that ADCC mediated by allogeneic NK cells occurred despite combinations of NK cells and breast cancer targets predicted to trigger inhibitory KIR signaling."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Antibodies, Monoclonal",
"Antibodies, Monoclonal, Humanized",
"Antibody-Dependent Cell Cytotoxicity",
"Breast Neoplasms",
"Cell Line, Tumor",
"Gene Amplification",
"HLA-C Antigens",
"Humans",
"Immunotherapy, Adoptive",
"Killer Cells, Natural",
"Monomeric GTP-Binding Proteins",
"Polymerase Chain Reaction",
"Receptor, ErbB-2",
"Signal Transduction",
"Trastuzumab"
]
} | We suggest that adoptive immunotherapy with allogeneic NK cells and trastuzumab may be an effective combination against breast cancer targets. | yes |
16,827,102 | Does targeting a methioninase-containing fusion protein to breast cancer urokinase receptors inhibit growth and migration? | {
"contexts": [
"We previously reported that a novel fusion protein (consisting of an amino-terminal fragment of urokinase which binds to the urokinase receptor, and L-methioninase which depletes methionine and arrests the growth of methionine-dependent tumors) inhibited MCF-7 breast cancer cells in vitro.",
"We produced this fusion protein, L-methioninase, and a mutated fusion protein without L-methioninase activity by recombinant methods. MCF-7 cell proliferation and mobility were measured in vitro in a culture wounding assay. Protein binding to MCF-7 cells was measured by immunocytochemical localization. MCF-7 tumor xenograft growth was measured in nude mice.",
"The fusion protein was significantly more effective than L-methioninase in either the in vitro or in vivo assays. The binding assay showed that the unmutated and mutated fusion protein bound to the cells, but L-methioninase did not."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Breast Neoplasms",
"Carbon-Sulfur Lyases",
"Cell Growth Processes",
"Cell Line, Tumor",
"Cell Movement",
"Humans",
"Injections, Intralesional",
"Mice",
"Mice, Nude",
"Mutagenesis, Site-Directed",
"Receptors, Cell Surface",
"Receptors, Urokinase Plasminogen Activator",
"Recombinant Fusion Proteins",
"Xenograft Model Antitumor Assays"
]
} | Our results suggest that this fusion protein has potential as a therapeutic agent for cancer treatment. | yes |
16,825,816 | Do serum hemoglobin levels predict response to strontium-89 and rhenium-186-HEDP radionuclide treatment for painful osseous metastases in prostate cancer? | {
"contexts": [
"Retrospective comparative analysis of strontium-89 chloride (Sr89) and rhenium-186-hydroxyethylidene diphosphonate (Re186-HEDP) radionuclide treatment to find predictors of response in patients with painful metastases from hormone refractory prostate cancer.",
"Clinical data from 60 hormone refractory PCA patients (i.e. rising PSA at castrate testosterone serum levels) was obtained. Twenty-nine were treated with Sr89, 31 were treated with Re186-HEDP for painful osseous metastasis. Response was defined as a patient-reported decrease in pain and/or reduction in pain medication with stable pain level. Hematological parameters and serum levels of PSA, alkaline phosphatase, and lactate dehydrogenase were assessed prior to and at 4-week intervals after treatment.",
"Median survival of all patients was 7 months (95% CI: 6-9 months). Overall, 33/60 (55%) patients reported a decrease in pain after the first radionuclide treatment. This percentage was similar for patients treated with Re168-HEDP and Sr89. Mean duration of reported pain response was 75 days (+/- 68 days) for Sr89 and 61 days (+/- 56 days) for Re186-HEDP, which was not significantly different. A lower blood hemoglobin concentration was associated with a lower pain response rate. In a multivariate Cox regression analysis, pain response to radionuclide treatment predicted longer survival after treatment."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Aged",
"Bone Neoplasms",
"Etidronic Acid",
"Hemoglobins",
"Humans",
"Male",
"Organometallic Compounds",
"Pain",
"Predictive Value of Tests",
"Prostatic Neoplasms",
"Radioisotopes",
"Retrospective Studies",
"Strontium Radioisotopes"
]
} | Pain response was present in 55% of patients. Serum hemoglobin concentration prior to radionuclide treatment predicted pain response for both Re186-HEDP and Sr89. A reduction in pain upon radionuclide treatment was associated with a longer survival after treatment. | yes |
16,821,618 | Is low pre-radiotherapy prostate-specific antigen level a significant predictor of treatment success for postoperative radiotherapy in patients with prostate cancer? | {
"contexts": [
"The optimal role of postoperative radiotherapy for patients with prostate cancer remains undefined.",
"The medical records of 70 patients (median age: 66 years), who had received radical radiotherapy (RT) between the years 1996 and 2004 after radical prostatectomy (RP), were analyzed. Fifteen patients had received immediate adjuvant RT, while the other 55 patients had received salvage therapy. Hormonal therapy had been performed in 28 patients before RT and continued in two of them concurrently with RT. A median dose of 60 Gy was delivered to the prostate bed. Pelvic node irradiation was performed in all patients.",
"After a median follow-up period of 23 months, 21 patients had experienced biochemical failure. Actuarial 3- and 5-year biochemical relapse-free survival estimates were 67.4%. No patient had local failure, although distant metastases with biochemical failure were found in five patients. On univariate analysis, the following were significant for biochemical failures: seminar vesicle involvement, serum PSA level >1 ng/ml before RT, pathological pelvic node involvement, RT indication (adjuvant vs. salvage) and Gleason score. However, only the serum PSA level before RT was significant on multivariate analysis."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Aged",
"Aged, 80 and over",
"Disease-Free Survival",
"Humans",
"Male",
"Middle Aged",
"Neoplasm Staging",
"Predictive Value of Tests",
"Prostate-Specific Antigen",
"Prostatectomy",
"Prostatic Neoplasms",
"Radiotherapy, Adjuvant",
"Retrospective Studies",
"Salvage Therapy"
]
} | Postoperative RT with a pre-RT PSA level <0.1 ng/ml seemed to be effective in patients with prostate cancer. | yes |
16,822,847 | Is fGFR4 Arg388 allele associated with resistance to adjuvant therapy in primary breast cancer? | {
"contexts": [
"A recent study presented first evidence that a single nucleotide polymorphism (SNP) at codon 388 of fibroblast growth factor receptor 4 (FGFR4) gene, causing a transmembrane domain missense mutation (Gly388Arg), is associated with disease outcome in node-positive breast cancer. This article addresses the clinical relevance of this SNP, FGFR4 genotype, phenotype, and HER2 regarding patient outcome and influence of adjuvant systemic therapy in a substantial primary breast cancer collective (n = 372; median follow-up, 94.5 months).",
"Polymerase chain reaction restriction fragment length polymorphism analysis of germ-line polymorphism was performed in uninvolved lymph nodes; FGFR4 and HER2 expression were assessed immunohistochemically in tissue microarrays.",
"In 51% of patients, homo- or heterozygous Arg388 allele was present. No correlation existed between FGFR4 genotype and expression or HER2 status. In node-negative patients, FGFR4 genotype was not correlated with disease outcome. In node-positive patients, however, FGFR4 Arg388 was significantly associated with poor disease-free survival (DFS; P = .02) and overall survival (OS; P = .04). Notably, this association seems to be attributable to relatively poor therapy response in Arg388 carriers, reflected in their significantly shorter DFS (P = .02) and OS (P = .045) among patients receiving adjuvant systemic therapy. It is also seen as a significant interaction term in a multivariate proportional hazards model with Arg388 carriers having only about half as much benefit from adjuvant systemic therapy as wild-type carriers."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Aged",
"Alleles",
"Antineoplastic Combined Chemotherapy Protocols",
"Arginine",
"Biomarkers, Tumor",
"Breast Neoplasms",
"Chemotherapy, Adjuvant",
"Disease Progression",
"Drug Resistance, Neoplasm",
"Female",
"Genetic Markers",
"Genotype",
"Glycine",
"Humans",
"Immunohistochemistry",
"Middle Aged",
"Multivariate Analysis",
"Mutation, Missense",
"Phenotype",
"Polymorphism, Single Nucleotide",
"Predictive Value of Tests",
"Prognosis",
"Proportional Hazards Models",
"Receptor, Fibroblast Growth Factor, Type 4"
]
} | According to this study, FGFR4 Arg388 genotype is a marker for breast cancer progression in patients with adjuvant systemic therapy, particularly chemotherapy, and thus may indicate therapy resistance. | yes |
16,830,214 | Does preoperative enteral immunonutrition improve postoperative outcome in patients with gastrointestinal cancer? | {
"contexts": [
"The purpose of this study was to evaluate the effect of preoperative immunonutrition pharmaceutics (IMPACT) diet versus standard enteral nutrition (EN) on the nutritional status and immunity of patients with colorectal or gastrointestinal (GI) cancer and to evaluate whether it influences the incidence of postoperative complication.",
"Sixty patients with GI cancer were randomly divided into 2 groups, immunonutrition (IM) and control diet (CT), each of which was fed with IMPACT and conventional diet, respectively, for 7 days before surgical procedures. Variables of nutritional status and immunity, postoperative complications, infections, and the days of postoperative hospitalization were measured.",
"There were no significant differences in the immunological and nutritional variables between the 2 groups preoperatively. The incidence of postoperative complications was significantly lower and the days of postoperative hospitalization were significantly decreased in the IM group. Serum concentrations of both prealbumin (PALB) and transferrin (TRF) were lower in the IM than in the CT group on postoperative day 3 (P<0.01). TRF continued to be significantly lower in the CT group than in the IM group between day 4 and day 7. However, PALB was significantly lower than before operation in the IM group on postoperative day 3 and TRF was significantly higher in the IM than the CT group on postoperative day 3 (P<0.05). Both PALB and TRF were significantly higher in the IM than the CT group on postoperative day 7 (P<0.05). Postoperative immunoglobulin G (IgG) level in the IM group was higher than that in the CT group (13.35+/-2.06 g/l vs. 9.59+/-2.23 g/l, P<0.05). CD4/CD8 ratio was significantly higher in the IM group (2.10+/-0.51 vs. 1.62+/-0.52, P<0.05)."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Chi-Square Distribution",
"Enteral Nutrition",
"Female",
"Gastrointestinal Neoplasms",
"Humans",
"Immunity",
"Incidence",
"Male",
"Middle Aged",
"Nutritional Status",
"Postoperative Complications",
"Preoperative Care",
"Serum Albumin",
"Statistics, Nonparametric",
"Transferrin",
"Treatment Outcome"
]
} | Preoperative enteral IM in patients with GI cancer improves nutritional status and immunity and decreases the incidence of postoperative complications and infections. | yes |
16,837,820 | Does expression of the high-affinity fluoropyrimidine-preferring nucleoside transporter hCNT1 correlate with decreased disease-free survival in breast cancer? | {
"contexts": [
"Nucleoside and nucleobase derivatives are currently used in the treatment of a variety of solid tumors; however, the role of plasma membrane transporters as biomarkers of drug metabolism has not been fully addressed. Thus, the purpose of this study was to determine whether the concentrative nucleoside transporter hCNT1 is a predictive marker of therapeutic response.",
"We studied a cohort of 90 breast cancer patients who were treated with cyclophosphamide-methotrexate-5-fluorouracil after surgery and then monitored for up to 108 months. hCNT1 and enzymes associated with nucleotide metabolism (thymidine phosphorylase, dihydropyrimidine dehydrogenase and thymidylate synthase) were assessed immunohistochemically in tissue samples.",
"Human CNT1 presence was mostly cytoplasmic, with some nuclear staining. The percentage of hCNT1-positive cells correlated positively with the expression of thymidine phosphorylase and dihydropyrimidine dehydrogenase. Nuclear staining correlated negatively with decreased disease-free survival, whereas the percentage of hCNT1-positive cells correlated positively with reduced long-term survival, with the hCNT1-positive index (>80%) being indicative of poor prognosis. A relative risk of relapse was associated with high hCNT1-positive indexes, whereas when this parameter was combined with the nodal status (positive), a high risk of relapse was found, suggesting that both parameters may reflect a poor prognosis."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Aged",
"Antineoplastic Combined Chemotherapy Protocols",
"Biomarkers, Tumor",
"Breast Neoplasms",
"Chemotherapy, Adjuvant",
"Cyclophosphamide",
"Disease-Free Survival",
"Female",
"Fluorouracil",
"Gene Expression Regulation, Neoplastic",
"Humans",
"Immunohistochemistry",
"Membrane Transport Proteins",
"Methotrexate",
"Middle Aged",
"Predictive Value of Tests",
"Prognosis"
]
} | These results indicate that the expression of the high-affinity concentrative nucleoside transporter hCNT1 has a prognostic value in determining disease-free survival and risk of relapse in breast cancer patients undergoing surgery followed by cyclophosphamide-methotrexate-5-fluorouracil chemotherapy. | yes |
16,818,693 | Is 8q gain an independent predictor of poor survival in diagnostic needle biopsies from prostate cancer suspects? | {
"contexts": [
"The main procedure to confirm a suspected diagnosis of prostate cancer is histologic analysis of ultrasound-guided sextant prostate biopsies. As it is difficult to reliably assess tumor stage and grade in such minute samples, the clinical significance of some tumor foci remains unclear. Genetic markers that could augment pretreatment prognostic information would improve the clinical management of the disease.",
"We have analyzed by comparative genomic hybridization a consecutive series of prostate needle biopsies obtained prospectively from 100 prostate cancer suspects. For 25 of these patients, a second independent biopsy core was analyzed to assess possible tumor heterogeneity. Additionally, a three-color fluorescent in situ hybridization assay was done in paraffin-embedded biopsy cores to validate the comparative genomic hybridization findings and to confirm their prognostic value.",
"Sixty-one of 100 biopsy samples had morphologic evidence of prostate cancer and 41 (67%) of these displayed genomic copy number changes as opposed to none of the morphologically normal biopsies. The presence of losses, amplifications, and the total number of genomic imbalances were significantly associated with poorly differentiated tumors. Kaplan-Meier curves with log-rank test showed that patients whose tumors displayed 8q gains had a significantly worse survival even when tumor grade was taken into account (P = 0.008). Restricting the analysis to cases with Gleason score 7, the most troublesome category in terms of prognostic information, gains at 8q were still significantly associated with poor survival (P = 0.011), something that was confirmed by fluorescent in situ hybridization in an independent series of biopsies with much longer follow-up time (P = 0.023)."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Aged",
"Aged, 80 and over",
"Biopsy, Needle",
"Chromosomes, Human, Pair 8",
"Follow-Up Studies",
"Humans",
"In Situ Hybridization, Fluorescence",
"Kaplan-Meier Estimate",
"Male",
"Middle Aged",
"Neoplasm Staging",
"Predictive Value of Tests",
"Prognosis",
"Prostatic Neoplasms",
"Survival Rate"
]
} | We show that whole genomic information can be obtained from minute needle biopsies of prostate cancer suspects and that genetic data can provide additional prognostic information before a therapeutic decision is taken. | yes |
16,818,686 | Are exon 19 deletion mutations of epidermal growth factor receptor associated with prolonged survival in non-small cell lung cancer patients treated with gefitinib or erlotinib? | {
"contexts": [
"Somatic mutations in the epidermal growth factor receptor (EGFR) have been detected in patients with non-small cell lung cancer (NSCLC) and are associated with sensitivity to treatment with gefitinib or erlotinib. Our study explored the relationship between the two most common types of somatic EGFR mutations, exon 19 deletions and the L858R point mutation, and outcomes of patients following treatment with gefitinib or erlotinib.",
"Tumor specimens obtained before treatment with gefitinib or erlotinib were analyzed for EGFR mutations. Patients with exon 19 deletion or L858R mutations were identified. The response rate, time to progression, and overall survival were determined for the two groups.",
"We identified 36 patients with NSCLC and an EGFR mutation who were treated with gefitinib or erlotinib. Patients with an exon 19 deletion had a significantly longer overall survival compared with patients with an L858R mutation (38 versus 17 months; P = 0.04). There were also trends toward higher response rate (73% versus 50%) and improved time to progression (24 versus 10 months) for the patients with an exon 19 deletion, although these were not independently significant in a multivariate analysis. A difference in response rate for patients treated with gefitinib compared with erlotinib was also noted [18 of 23 (78%) versus 3 of 9 (33%); P = 0.04]. No obvious difference in time to progression or overall survival was noted between gefitinib- and erlotinib-treated patients."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Aged",
"Aged, 80 and over",
"Carcinoma, Non-Small-Cell Lung",
"DNA Mutational Analysis",
"DNA, Neoplasm",
"Disease Progression",
"ErbB Receptors",
"Erlotinib Hydrochloride",
"Exons",
"Female",
"Follow-Up Studies",
"Gefitinib",
"Genotype",
"Humans",
"Lung Neoplasms",
"Male",
"Middle Aged",
"Neoplasm Staging",
"Point Mutation",
"Quinazolines",
"Retrospective Studies",
"Sequence Deletion",
"Survival Rate",
"Treatment Outcome"
]
} | Patients with NSCLC and EGFR exon 19 deletions have a longer survival following treatment with gefitinib or erlotinib compared with those with the L858R mutation. Pooling of greater numbers of patients and completion of prospective trials are needed to further define the predictive and prognostic roles of different EGFR mutations with respect to treatment with gefitinib, erlotinib, and other EGFR inhibitors. | yes |
16,835,067 | Do potential residential exposure to toxics release inventory chemicals during pregnancy and childhood brain cancer? | {
"contexts": [
"Although the susceptibility of the developing fetus to various chemical exposures is well documented, the role of environmental chemicals in childhood brain cancer etiology is not well understood.",
"We aimed to evaluate whether mothers of childhood brain cancer cases had greater potential residential exposure to Toxics Release Inventory (TRI) chemicals than control mothers during pregnancy.",
"We included 382 brain cancer cases diagnosed at < 10 years of age from 1993 through 1997 who were identified from four statewide cancer registries. One-to-one matched controls were selected by random-digit dialing. Computer-assisted telephone interviews were conducted. Using residential history of mothers during pregnancy, we measured proximity to TRI facilities and exposure index, including mass and chemicals released. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using conditional logistic regression to estimate brain cancer risk associated with TRI chemicals.",
"Increased risk was observed for mothers living within 1 mi of a TRI facility (OR = 1.66 ; 95% CI, 1.11-2.48) and living within 1 mi of a facility releasing carcinogens (OR = 1.72 ; 95% CI, 1.05-2.82) for having children diagnosed with brain cancer before 5 years of age, compared to living > 1 mi from a facility. Taking into account the mass and toxicity of chemical releases, we found a nonsignificant increase in risk (OR = 1.25 ; 95% CI, 0.67-2.34) comparing those with the lowest versus highest exposure index."
],
"labels": [
"BACKGROUND",
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Brain Neoplasms",
"Child",
"Child, Preschool",
"Environmental Exposure",
"Environmental Pollutants",
"Female",
"Humans",
"Male",
"Pregnancy",
"Time Factors"
]
} | Risk of childhood brain cancers may be associated with living near a TRI facility ; however, this is an exploratory study and further studies are needed. | yes |
16,839,413 | Is bcl-2 protein expression associated with p27 and p53 protein expressions and MIB-1 counts in breast cancer? | {
"contexts": [
"Recent experimental studies have shown that Bcl-2, which has been established as a key player in the control of apoptosis, plays a role in regulating the cell cycle and proliferation. The aim of this study was to investigate the relationship between Bcl-2 and p27 protein expression, p53 protein expression and the proliferation activity as defined by the MIB-1 counts. The prognostic implication of Bcl-2 protein expression in relation to p27 and p53 protein expressions and MIB-1 counts for breast cancer was also evaluated.",
"The immunohistochemical expression of Bcl-2 protein was evaluated in a series of 249 invasive ductal carcinomas of the breast, in which p27 and p53 protein expressions and MIB-1 counts had been determined previously.",
"The Bcl-2 protein expression was found to be decreased in 105 (42%) cases. A decreased Bcl-2 protein expression was significantly correlated with a nuclear grade of III, a negative estrogen receptor, a decreased p27 protein expression, a positive p53 protein expression, positive MIB-1 counts and a positive HER2 protein expression. The incidence of a nuclear grade of III and positive MIB-1 counts increased as the number of abnormal findings of Bcl-2, p27 and p53 protein expressions increased. A univariate analysis indicated a decreased Bcl-2 protein expression to be significantly (p = 0.0089) associated with a worse disease free survival (DFS), while a multivariate analysis indicated the lymph node status and MIB-1 counts to be independently significant prognostic factors for the DFS."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Aged",
"Aged, 80 and over",
"Breast Neoplasms",
"Cyclin-Dependent Kinase Inhibitor p27",
"Disease-Free Survival",
"Female",
"Gene Expression Regulation, Neoplastic",
"Humans",
"Immunohistochemistry",
"Ki-67 Antigen",
"Lymphatic Metastasis",
"Middle Aged",
"Proto-Oncogene Proteins c-bcl-2",
"Receptor, ErbB-2",
"Tumor Suppressor Protein p53"
]
} | The Bcl-2 protein expression has a close correlation with p27 and p53 protein expressions and the proliferation activity determined by MIB-1 counts in invasive ductal carcinoma of the breast. The prognostic value of Bcl-2 as well as p27 and p53 protein expressions was dependent on the proliferation activity in breast cancer. | yes |
16,837,800 | Is chromoendoscopy a valuable tool for screening of high-risk patients with head and neck cancer for early detection of esophageal cancer? | {
"contexts": [
"The incidence of esophageal cancer is markedly increased in patients with head and neck cancer, and the presence of esophageal cancer is associated with reduced survival rates.",
"We investigated whether the results of screening for esophageal cancer in patients with head and neck cancer using chromoendoscopy would change the treatment of such patients.",
"87 patients with head and neck cancer and known alcohol or nicotine abuse were screened for esophageal cancer.",
"The patients underwent esophagogastroduodenoscopy and staining of the esophagus with 2% Lugol's solution. Biopsies were taken from unstained areas for histopathological assessment.",
"Esophageal cancer was newly diagnosed in 10 patients (11.5%), including 2 with carcinoma in situ. There were dysplastic changes in 6 patients (7%) and an unknown Barrett esophagus in 4 patients (5%). In 36 patients (41%) unstained areas were associated with esophagitis. While unstained areas could not be detected in 17 patients, the histology was normal in 14 patients with unstained areas. In all the patients with newly detected invasive esophageal cancer, the treatment had to be changed from a curative neoadjuvant approach to palliative treatment. In 2 patients with carcinoma in situ mucosectomy was performed. In the cases with dysplastic areas and newly detected Barrett epithelium a careful follow-up regime was arranged."
],
"labels": [
"BACKGROUND",
"OBJECTIVE",
"METHODS",
"METHODS",
"RESULTS"
],
"meshes": [
"Biopsy",
"Carcinoma in Situ",
"Carcinoma, Squamous Cell",
"Diagnosis, Differential",
"Early Diagnosis",
"Esophageal Neoplasms",
"Esophagoscopy",
"Female",
"Head and Neck Neoplasms",
"Humans",
"Iodides",
"Male",
"Middle Aged",
"Neoplasm Staging",
"Neoplasms, Multiple Primary",
"Risk Factors",
"Staining and Labeling"
]
} | The staging of patients with head and neck cancer, and the risk factors for esophageal cancer should include chromoendoscopy of the esophagus as a standard procedure. Extended staging provides critical additional information, which helps to more safely distinguish future candidates for curative and palliative treatment. | yes |
16,832,552 | Do tumor-infiltrating CD4+ T lymphocytes in early breast cancer reflect lymph node involvement? | {
"contexts": [
"The role of immune system in the pathogenesis and progression of breast cancer is a subject of controversy, and this stimulated us to investigate the association of the immunophenotype of tumor-infiltrating lymphocytes in early breast cancer with the spread of tumor cells to axillary lymph nodes.",
"Tumor samples from 23 patients with early breast cancer from the Department of Gynecology and Obstetrics of Ribeirão Preto Medical School (USP) were obtained at the time of biopsy and submitted to an enzyme-digestion procedure for the extraction of tumor-infiltrating lymphocytes. The lymphocytes extracted were analyzed by dual-color flow cytometry with monoclonal antibodies in these combinations: CD3 FITC/CD19 PE, CD3 FITC/CD4 PE, CD3 FITC/CD8 PE, and CD16/56 PerCP, which are specific for immunophenotyping of T and B lymphocytes, helper and cytotoxic T lymphocytes, and natural killer (NK) cells. The mean percentage of these cells was used for comparing groups of patients with or without lymph node metastasis.",
"The mean value for T-lymphocyte infiltration was 24.72 +/- 17.37%; for B-lymphocyte infiltration, 4.22 +/- 6.27%; for NK-cell infiltration, 4.41 +/- 5.22%, and for CD4(+) and CD8(+) T-lymphocyte infiltration, 12.43 +/- 10.12% and 11.30 +/- 15.09%, respectively. Only mean values of T- and CD4(+) T-lymphocyte infiltration were higher in the group of patients with lymph node metastasis, while no differences were noted in the other lymphocyte subpopulations."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Aged",
"Aged, 80 and over",
"Antibodies, Monoclonal",
"Axilla",
"Breast Neoplasms",
"CD4-Positive T-Lymphocytes",
"Female",
"Flow Cytometry",
"Humans",
"Immunophenotyping",
"Lymph Nodes",
"Lymphatic Metastasis",
"Lymphocyte Subsets",
"Lymphocytes, Tumor-Infiltrating",
"Middle Aged",
"Neoplasm Invasiveness",
"Neoplasm Staging"
]
} | The association of tumor-infiltrating CD4(+) T lymphocytes with lymph node metastasis suggests a role for these cells in the spread of neoplasia to lymph nodes in patients with early breast cancer. | yes |
16,827,157 | Is down-regulation of Gadd45 expression associated with tumor differentiation in non-small cell lung cancer? | {
"contexts": [
"Evidence suggests that the growth arrest and DNA damage-inducible gene 45 (Gadd45) is an effective indicator of poor prognosis or malignant potential in solid tumors. The purpose of this study was to determine the gene expression patterns and clinical relevance of Gadd45 in tumor specimens of non-small cell lung cancer (NSCLC) patients.",
"Using a quantitative real-time RT-PCR method, the mRNA expression of Gadd45 was analyzed in tumor and paired normal-appearing tissues of 66 patients with NSCLC. The gene expression data for each patient were matched to the clinicopathological parameters.",
"Gadd45 mRNA expression was detectable in all (100%) specimens analyzed. The overall median mRNA expression level of Gadd45 was approximately 10-fold lower in tumor tissues than in matching normal lung tissues (p < 0.001). High intratumoral Gadd45 expression was significantly associated with a poorer histological grading (p = 0.041)."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Aged",
"Aged, 80 and over",
"Carcinoma, Non-Small-Cell Lung",
"Cell Cycle Proteins",
"Cell Differentiation",
"Down-Regulation",
"Female",
"Gene Expression Regulation, Neoplastic",
"Humans",
"Lung Neoplasms",
"Male",
"Middle Aged",
"Nuclear Proteins",
"Polymerase Chain Reaction",
"RNA, Messenger"
]
} | The significant decrease in Gadd45 expression in tumors compared with normal tissue and its association with histological grading suggest a role for Gadd45 in the differentiation pathway of NSCLC. | yes |
16,823,510 | Is breast cancer risk associated with polymorphic forms of xeroderma pigmentosum genes in a cohort of women from Washington County , Maryland? | {
"contexts": [
"The genes mutated in the cancer-prone syndrome, xeroderma pigmentosum (XP genes), have been well studied both biochemically and mechanistically. These genes are important components of the DNA nucleotide excision repair (NER) pathway, which protects against environmentally-induced cancers. XP genes are also downstream of the hereditary breast cancer syndrome gene, BRCA1, suggesting that XP genes may be important to hereditary forms of breast cancer as well. Although mutated XP genes are rare, polymorphic forms with potential functional deficiencies are common, and could pose a significant cancer risk in the general population.",
"This study tested the hypothesis that common polymorphic variants of XP genes were associated with the risk of breast cancer among a population of women in Washington County, Maryland.",
"Five single nucleotide polymorphisms (SNPs) among four XP genes (XPC, XPD, XPF and XPG) were genotyped from DNA samples collected at baseline, and then analyzed by conditional logistic regression for association with the incidence of breast cancer. 321 cases were individually matched to 321 controls, by age and menopausal status.",
"No significant associations were found between breast cancer risk and any of the XP genotypes. Odds ratios for all genotypes ranged from 0.61 to 1.14, and none were statistically significant. Adjustment and stratification for family history of breast cancer did not alter the findings."
],
"labels": [
"BACKGROUND",
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Breast Neoplasms",
"Cohort Studies",
"DNA Repair",
"Female",
"Gene Frequency",
"Genetic Predisposition to Disease",
"Genotype",
"Humans",
"Maryland",
"Middle Aged",
"Multivariate Analysis",
"Polymorphism, Single Nucleotide",
"Risk Factors",
"Xeroderma Pigmentosum"
]
} | These results suggest that polymorphisms of XP genes are not likely to be significant risk factors for women within the general population. This study did not address, however, risks for subpopulations of women with high exposures to DNA damaging agents. | no |
16,830,385 | Is genetic instability of BRCA1 gene at locus D17S855 related to clinicopathological behaviors of gastric cancer from Chinese population? | {
"contexts": [
"To investigate genetic instability of gene BRCA1 at locus D17S855, and their relationship with clinicopathological characteristics of gastric cancer in Chinese population.",
"Microsatellite instability (MSI) and loss of heterozygosity (LOH) of gene BRCA1 at locus D17S855 were compared between 37 samples of gastric cancer and corresponding non-cancerous gastric tissue.",
"MSI at locus D17S855 was positive in 7 of 37 samples of gastric cancer (18.95%). MSI had a close relationship with TNM staging but no relation with lymph node metastasis, histological type or tumor differentiation. MSI positive frequency in TNM I + II (31.58%, 6/19) was much higher than that in TNM III + IV (5.56%, 1/18), (P < 0.05). LOH positive rate was 18.92% (7/37). LOH had no relationship to histological type, tumor differentiation or lymph node metastasis, but LOH positive rate in TNM III + IV was 33.33% (6/18), much higher than that in TNM I + II ( 5.26%, 1/19), (P < 0.05). BRCA1 protein was expressed in 14 of 37 samples of gastric cancer. The positive rates of BRCA1 protein in TNM I + II and TNM III + IV were 57.89% and 16.67%, respectively, (P < 0.05). The positive rate of BRCA1 protein was 77.78% in high differentiation samples, 30.77% in middle differentiation and 12.50% in lower differentiation samples, (P < 0.05)."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Asian Continental Ancestry Group",
"BRCA1 Protein",
"China",
"DNA, Neoplasm",
"Disease Progression",
"Genes, BRCA1",
"Genes, Neoplasm",
"Genomic Instability",
"Humans",
"Loss of Heterozygosity",
"Lymphatic Metastasis",
"Microsatellite Repeats",
"Neoplasm Staging",
"Polymorphism, Single-Stranded Conformational",
"Prognosis",
"Stomach Neoplasms"
]
} | MSI of BRCA1 gene could be used as a molecular marker in early phases of sporadic gastric cancer in Chinese population. LOH occurs at later period of gastric cancer, therefore, it could be used as prognostic factor. | yes |
16,822,880 | Does low meprin alpha expression differentiate primary ovarian mucinous carcinoma from gastrointestinal cancers that commonly metastasise to the ovaries? | {
"contexts": [
"Currently, no specific immunohistochemical markers are available to differentiate primary mucinous epithelial ovarian cancer (MOC) from adenocarcinomas originating at other sites that have metastasised to the ovary, which may have an impact on patient management and prognosis.",
"To investigate the expression of two intestinal markers, galectin 4 and meprin alpha, in mucinous carcinomas of the ovary and gastrointestinal tract.",
"Using immunohistochemical analysis, the expression of galectin 4 and meprin alpha was investigated in 10 MOCs and in 38 mucinous adenocarcinomas of colon, pancreas, stomach and appendix, the most common sites of origin of ovarian metastases.",
"Total cytoplasmic galectin 4 expression was relatively consistent between the different carcinomas. Membranous meprin alpha expression was significantly lower in MOCs compared with gastrointestinal carcinomas. Moreover, meprin alpha expression showed greater discrimination between the ovarian and gastrointestinal carcinomas than the cytokeratins CK7 and CK20, the current standard immunohistochemical markers used to determine the tissue origin of mucinous carcinomas involving the ovaries."
],
"labels": [
"BACKGROUND",
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adenocarcinoma",
"Adenocarcinoma, Mucinous",
"Biomarkers, Tumor",
"Diagnosis, Differential",
"Female",
"Galectin 4",
"Gastrointestinal Neoplasms",
"Humans",
"Immunoenzyme Techniques",
"Keratin-20",
"Keratin-7",
"Metalloendopeptidases",
"Neoplasm Proteins",
"Ovarian Neoplasms"
]
} | Meprin alpha is a useful additional marker in differentiating primary from secondary mucinous adenocarcinomas of the ovary. | yes |
16,823,179 | Is the prognostic value and overexpression of cyclin A correlated with gene amplification of both cyclin A and cyclin E in breast cancer patient? | {
"contexts": [
"Deregulation of cell cycle control is a hallmark of cancer. The primary cyclins (A, B1, D1, D3 and E) are crucial for cell cycle progression. Secondary cyclins (C and H) have putative indirect effects on cell cycle propulsion and are not previously evaluated in breast cancer. We have examined protein expression and gene amplification of cyclins in breast carcinomas and correlated the findings with clinical follow-up data. We have previously demonstrated that over-expression of cyclin A is associated with poor prognosis in breast cancer patients. In this study we wanted to evaluate the mechanisms behind overexpression of cyclin A, as well as the impact of other cyclins, both at the gene level and at the protein level, on prognosis of breast cancer patients. The impact of TP53 gene mutations on gene amplification of cyclins was also evaluated.",
"Real-Time Quantitative PCR was used to detect gene amplification of cyclins in tumour tissue from 86 patients operated for invasive breast carcinomas, while immunohistochemistry was applied to detect protein expression of the same cyclins.",
"Of the 80-breast tumour samples available for cyclin A gene amplification analyses, 26.7% (23/80) was defined to have cyclin A gene amplification. 37.2% (32/79) had cyclin B1 gene amplification, 82.6% (71/82) of the samples harboured amplification of cyclin C gene, 74.4% (64/82) had cyclin D1 gene amplification, 41.9% (36/86) had cyclin D3 gene amplification, 29.1% (25/81) of the patients had cyclin E gene amplification and 9.3% (8/86) of the samples showed amplification of the cyclin H gene. When correlation between gene amplification and protein expression was evaluated, we observed a statistical significant correlation between gene amplification and protein expression of cyclin A (p=0.009) and cyclin D3 (p<0.001). However, the correlation between gene amplification and protein expression of cyclin A, as well as the prognostic value of cyclin A overexpression, was affected by gene amplification of cyclin E. Gene amplification of none of the other cyclins was associated with patient prognosis. There was a statistical significant correlation between TP53 gene mutations and gene amplification of cyclins A, D3 and B1. No correlation was observed between gene amplification of secondary cyclins (H and C) and TP53 gene mutations."
],
"labels": [
"UNLABELLED",
"METHODS",
"RESULTS"
],
"meshes": [
"Breast Neoplasms",
"Cyclin A",
"Cyclin E",
"DNA Mutational Analysis",
"DNA, Neoplasm",
"Female",
"Gene Amplification",
"Gene Expression Regulation, Neoplastic",
"Genes, p53",
"Humans",
"Immunohistochemistry",
"Middle Aged",
"Multivariate Analysis",
"Mutation",
"Neoplasm Staging",
"Polymerase Chain Reaction",
"Prognosis"
]
} | The overexpression of cyclin A is correlated to gene amplification of both cyclin A and cyclin E. Over-expression of cyclin A is associated with poor prognosis in breast cancer patients. When analysed in a multivariate analyses model, gene amplification as well as protein expression of none of the other cyclins than cyclin A are associated with patient prognosis in breast carcinomas. TP53 gene mutation seems to correlate with gene amplification of primary, but not secondary cyclins. | yes |
16,837,520 | Is uptake of cervical cancer screening in The Netherlands mainly influenced by women 's beliefs about the screening and by the inviting organization? | {
"contexts": [
"This study aims to examine the impact of women's characteristics (demographics, risk behaviour, and beliefs) on the uptake of cervical cancer screening, taking practice characteristics (demographic and organizational) into account.",
"Routinely collected data of screening status were sampled from electronic medical records of 32 Dutch general practices. Additionally, a questionnaire was sent to a sample of 2224 listed women-1204 screened, 1020 unscreened. We used a step-by-step, logistic, multilevel approach to examine determinants of the screening uptake.",
"Analyses of data for 1392 women (968 screened and 424 unscreened) showed that women's beliefs about cervical screening and attendance are the best predictors of screening uptake, even when demographic and organizational aspects are taken into account. Women aged 40-50 years who felt high personal moral obligation, who had only one sexual partner ever, and who were invited and reminded by their own general practice had the greatest likelihood of screening uptake. A non-response study was performed; the non-responders to the questionnaire (mainly unscreened) thought they had less risk of cervical cancer, were less motivated, less often intended to get future screening, and were more convinced that cervical cancer cannot be cured."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Family Practice",
"Female",
"Health Knowledge, Attitudes, Practice",
"Humans",
"Logistic Models",
"Mass Screening",
"Middle Aged",
"Moral Obligations",
"Motivation",
"Netherlands",
"Patient Acceptance of Health Care",
"Risk-Taking",
"Surveys and Questionnaires",
"Uterine Cervical Neoplasms",
"Vaginal Smears",
"Women's Health"
]
} | To improve the uptake rate, we should focus on the personal moral obligation of eligible women, beliefs about the risks of cervical cancer, and available cures. Invitations and reminders within general practices enhance the uptake rate. | yes |
8,053,078 | Does ondansetron stimulate prolactin release in breast cancer patients? | {
"contexts": [
"Prolactin (PRL) may be a tumor growth factor, mainly for breast cancer. The antidopaminergic drugs commonly used in the treatment of chemotherapy-induced vomiting stimulate PRL release, and this finding could represent a potentially negative biologic event for cancer patients. This study was performed to analyze PRL response to the serotonin-type 3 receptor antagonist ondansetron, a new active drug in the treatment of vomiting due to chemotherapy, in cancer patients.",
"The study included 8 premenopausal breast cancer patients undergoing adjuvant chemotherapy. Ondansetron was given intravenously at a dose of 8 mg, and venous blood samples were drawn at 0, 20, 60 and 120 min. The result were compared to those seen in 10 breast cancer patients treated with metoclopramide (10 mg. i.v.).",
"PRL mean levels significantly increased in response to metoclopramide. In contrast, no significant changes in PRL mean values occurred after ondansetron injection."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Breast Neoplasms",
"Female",
"Humans",
"Middle Aged",
"Ondansetron",
"Prolactin"
]
} | The study showed that ondansetron, whose efficacy in the treatment of chemotherapy-induced vomiting is well known, does not stimulate the tumor growth factor PRL in cancer patients, in contrast the the action of the most commonly used antidopaminergic drugs. | no |
12,378,342 | Is mGr1-Ag associated with multidrug-resistant phenotype of gastric cancer cells? | {
"contexts": [
"MGr1-antigen (Ag) was previously reported as an upregulated protein in multidrug-resistant (MDR) gastric cancer cells. The aim of this study was to characterize the role of MGr1-Ag in the multidrug resistance of gastric cancer cells.",
"Laser scanning confocal microscopy (LSCM), two-dimensional electrophoresis, and Western blot were used to detect MGr1-Ag in gastric cancer cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay was used to determine the sensitivity of the MDR gastric cancer cells, SGC7901/VCR, to chemotherapeutic drugs. Adriamycin accumulation and retention in SGC7901/VCR cells were analyzed using flow cytometry.",
"LSCM showed that MGr1-Ag localized mainly on the membrane and partly in the cytoplasm of SGC7901/VCR cells. Western blot showed that the expression level of MGr1-Ag in SGC7901/VCR cells was higher than that in its parental cells, SGC7901, and that the apparent molecular weight and isoelectric point of MGr1-Ag were 42 kDa and pH 4.8, respectively. After incubation with MGr1 antibody, SGC7901/VCR cells showed significantly decreased IC(50) values for adriamycin (from 0.887 +/- 0.081 mg/l to 0.607 +/- 0.084 mg/l; P, 0.05), vincristine (from 0.707 +/- 0.055 mg/l to 0.557 +/- 0.042 mg/l; P, 0.05), and 5-fluorouracil (from 4.367 +/- 0.407 mg/l to 2.630 +/- 0.644 mg/l; P, 0.05), as well as slightly increased IC(50) values for mitomycin (from 0.183 +/- 0.045 mg/l to 0.198 +/- 0.048 mg/l; P. 0.05). In addition, incubation with MGr1 significantly enhanced adriamycin accumulation and retention in SGC7901/VCR cells."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Antibodies, Monoclonal",
"Antigens",
"Antigens, Neoplasm",
"Antineoplastic Agents",
"Blotting, Western",
"Doxorubicin",
"Drug Resistance, Multiple",
"Drug Resistance, Neoplasm",
"Electrophoresis, Gel, Two-Dimensional",
"Electrophoresis, Polyacrylamide Gel",
"Fluorescence",
"Humans",
"Microbial Sensitivity Tests",
"Microscopy, Confocal",
"Phenotype",
"Stomach Neoplasms",
"Survival Rate",
"Tumor Cells, Cultured"
]
} | Overexpression of MGr1-Ag is associated with the MDR phenotype of gastric cancer cells. | yes |
12,374,693 | Does antibody to vascular endothelial growth factor slow growth of an androgen-independent xenograft model of prostate cancer? | {
"contexts": [
"Human tumors are dependent on angiogenesis for growth, and vascular endothelial growth factor (VEGF) is a major regulator of this process. We aimed to study clinical utility of a recombinant humanized monoclonal anti-VEGF antibody (rhu alpha VEGF) in the treatment of the CWR22R androgen-independent xenograft model of prostate cancer.",
"rhu alpha VEGF has previously shown clinical activity in several xenograft cancer models. We administered 5 mg/kg rhu alpha VEGF i.p. twice weekly as a single agent and together with paclitaxel to established CWR22R xenografts.",
"rhu alphaVEGF inhibited established tumor growth by 85% (P < 0.01 for trajectories of the average tumor volumes of the groups) at 3 weeks, but after cessation of rhu alpha VEGF treatment, tumor regrowth ensued. A paclitaxel dosage of 6.25 mg/kg s.c. five times/week slowed tumor growth (72% compared with controls at 3 weeks, P = 0.02). The combination of paclitaxel and rhu alpha VEGF resulted in greater inhibition of tumor growth than that observed with either agent alone (98% growth inhibition, P = 0.024 versus rhualpha VEGF alone and P = 0.02 versus paclitaxel alone). Paclitaxel alone had no antiangiogenic effects at the dosage studied, whereas rhu alpha VEGF had significant inhibition of angiogenesis, noted by microvessel density and CD34 staining."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Androgens",
"Animals",
"Antibodies, Monoclonal",
"Antineoplastic Agents, Phytogenic",
"Apoptosis",
"Blotting, Western",
"Disease Models, Animal",
"Drug Therapy, Combination",
"Endothelial Growth Factors",
"Humans",
"Immunoenzyme Techniques",
"In Situ Nick-End Labeling",
"Intercellular Signaling Peptides and Proteins",
"Lymphokines",
"Male",
"Mice",
"Mice, Inbred BALB C",
"Mice, Nude",
"Neoplasms, Hormone-Dependent",
"Neovascularization, Pathologic",
"Paclitaxel",
"Prostatic Neoplasms",
"Vascular Endothelial Growth Factor A",
"Vascular Endothelial Growth Factors"
]
} | rhu alpha VEGF has cytostatic clinical activity in this androgen-independent prostate cancer xenograft model, and the addition of paclitaxel demonstrates increased clinical activity. | yes |
12,386,916 | Are sequence variants in the human 25-hydroxyvitamin D3 1-alpha-hydroxylase ( CYP27B1 ) gene associated with prostate cancer risk? | {
"contexts": [
"1,25-dihydroxyvitamin D(3) has been shown to have antiproliferative properties on normal and neoplastic prostatic cells. 25-hydroxyvitamin D(3) 1-alpha-hydroxylase, the enzyme that catalyzes the final step of vitamin D synthesis, converting 25-hydroxyvitamin D(3) to 1,25-dihydroxyvitamin D(3), is expressed in the prostate.",
"The human 25-hydroxyvitamin D(3) 1-alpha-hydroxylase gene (CYP27B1) was resequenced in a case/control panel consisting of 64 individuals (48 Caucasians and 16 African Americans), with equal numbers of hereditary prostate cancer cases, sporadic cases, and unaffected controls. Three frequent single nucleotide polymorphisms (SNPs) were genotyped in 245 prostate cancer cases and 222 controls.",
"Six noncoding SNPs were identified in the CYP27B1 gene. No significant difference was found in allele and genotype frequencies between sporadic cases and unaffected controls for the three genotyped SNPs."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"25-Hydroxyvitamin D3 1-alpha-Hydroxylase",
"Alleles",
"Case-Control Studies",
"DNA, Neoplasm",
"Genetic Predisposition to Disease",
"Humans",
"Male",
"Middle Aged",
"Polymerase Chain Reaction",
"Polymorphism, Single Nucleotide",
"Prostatic Neoplasms",
"Sequence Analysis, DNA"
]
} | This study suggests that the CYP27B1 gene does not play a major role as a prostate cancer susceptibility gene. | no |
12,378,339 | Does surgery for gastric cancer increase plasma levels of vascular endothelial growth factor and von Willebrand factor? | {
"contexts": [
"Angiogenesis and hemostatic activation are important factors in tumor progression and metastasis. Because surgical intervention induces tissue hypoxia and hemostatic activation, we analyzed the effect of gastric surgery on the plasma concentrations of vascular endothelial growth factor (VEGF), soluble P-selectin (sP-selectin), and von Willebrand factor (vWf).",
"Plasma VEGF, sP-selectin, and vWf concentrations were measured in 14 patients with gastric cancer before operation and on postoperative day 1 (POD 1). Correlations between disease stage and the effect of surgical intervention were analyzed.",
"The plasma concentrations of these three factors did not correlate with the disease stage. Plasma levels of sP-selectin did not change after operation (before surgery, 87.6 +/- 34.1 ng/ml; on POD 1, 101.1 +/- 48.1 ng/ml; P = 0.123). Plasma VEGF and vWf concentrations were significantly elevated on POD 1 (VEGF, 33.3 +/- 20.5 pg/ml before surgery and 61.9 +/- 35.6 pg/ml on POD 1; P = 0.0013; vWf, 164 +/- 31.1% before surgery and 211.1 +/- 66.1% on POD 1; P = 0.027)."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Aged",
"Biomarkers, Tumor",
"Endothelial Growth Factors",
"Female",
"Gastrectomy",
"Humans",
"Intercellular Signaling Peptides and Proteins",
"Japan",
"Lymphokines",
"Male",
"Middle Aged",
"Neoplasm Recurrence, Local",
"Neoplasm Staging",
"P-Selectin",
"Statistics as Topic",
"Stomach Neoplasms",
"Survival Analysis",
"Treatment Outcome",
"Vascular Endothelial Growth Factor A",
"Vascular Endothelial Growth Factors",
"von Willebrand Factor"
]
} | Because VEGF and vWf are involved in angiogenesis, tumor-platelet adhesion, and tumor-endothelial cell adhesion, surgical intervention could influence tumor growth and metastasis. | yes |
12,374,685 | Does coexpression of parathyroid hormone related protein and its receptor in early breast cancer predict poor patient survival? | {
"contexts": [
"Parathyroid hormone-related protein (PTHRP) is in part responsible for the clinical syndrome of hypercalcaemia of malignancy and has been implicated as an important factor in the development of bone metastases. The aim of this study was to determine the coexpression of PTHRP and its receptor in early breast cancer (EBC) and bone metastases (BM), and correlate these findings to clinical outcome.",
"Samples of surgically excised EBC (n = 176) and BM (n = 43) were collected and stored in liquid nitrogen. PTHRP protein was determined using immunohistochemistry and receptor mRNA using in situ hybridization (n = 107) or semiquantitative reverse transcription-PCR (n = 69).",
"PTHRP protein was expressed in 115 of 170 (68%) EBC compared with 100% of BM (P < 0.001), whereas its receptor mRNA was expressed in 88 of 176 (50%) EBC compared with 35 of 43 (81%) BM (P < 0.001). Coexpression of both PTHRP and its receptor was present in 62 EBC samples (37%) and in 35 BM samples (81%; P < 0.001). The PTHRP receptor correlated well with increasing patient age, but not with tumor size, grade, estrogen receptor, progesterone receptor, or lymph node status. Individually PTHRP and PTHRP receptor both correlated well with a reduced disease-free survival (P < 0.004) and receptor alone with reduced overall survival (P < 0.003). Coexpression of both PTHRP and receptor predicted the worst clinical outcome at 5 years, with a mortality rate of 20 of 62 (32%) compared with the ligand and receptor-negative group with 2 of 32 (6%; P < 0.004)."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Aged",
"Bone Neoplasms",
"Breast Neoplasms",
"DNA Primers",
"DNA Probes",
"DNA, Complementary",
"Female",
"Gene Expression Regulation, Neoplastic",
"Humans",
"Immunoenzyme Techniques",
"In Situ Hybridization",
"Ki-67 Antigen",
"Middle Aged",
"Parathyroid Hormone-Related Protein",
"Peptide Hormones",
"Polymerase Chain Reaction",
"RNA, Messenger",
"Receptor, Parathyroid Hormone, Type 1",
"Receptors, Estrogen",
"Receptors, Parathyroid Hormone",
"Receptors, Progesterone",
"Reverse Transcriptase Polymerase Chain Reaction"
]
} | Overall these results show that the PTHRP receptor is expressed more frequently in BM than EBC, and is associated with poor clinical outcome and survival. | yes |
12,377,958 | Is time to progression in metastatic breast cancer patients treated with epirubicin improved by the addition of either cisplatin or lonidamine : final results of a phase III study with a factorial design? | {
"contexts": [
"To investigate the value of the addition of either cisplatin (CDDP) or lonidamine (LND) to epirubicin (EPI) in the first-line treatment of advanced breast cancer.",
"Three hundred seventy-one metastatic breast cancer patients with no prior systemic chemotherapy for advanced disease were randomized to receive either EPI alone (60 mg/m(2) on days 1 and 2 every 21 days), EPI and CDDP (30 mg/m(2) on days 1 and 2 every 21 days), EPI and LND (450 mg orally daily, given continuously), or EPI, CDDP, and LND. Time to progression, response rates, side effects, and survival were compared according to the 2 x 2 factorial design of this study.",
"The groups were well balanced with respect to prognostic factors. Time to progression did not differ in the comparison between CDDP arms and non-CDDP arms (median, 10.9 months v 9.4 months, respectively; P =.10) or between that of LND arms and non-LND arms (median, 10.8 months v 9.9 months, respectively; P =.47), nor did overall survival. The response rate did not significantly differ in the comparison between LND arms and non-LND arms (62.9% v 54.0%, P =.08). No difference in treatment activity was observed between CDDP arms and non-CDDP arms. Toxicity was significantly higher in the CDDP arms, leading to CDDP dose adjustment in 40% of cases. The most frequent side effects were of a hematologic and gastrointestinal nature. The addition of LND produced more myalgias and fatigue."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Aged",
"Antineoplastic Combined Chemotherapy Protocols",
"Breast Neoplasms",
"Cisplatin",
"Disease Progression",
"Epirubicin",
"Female",
"Humans",
"Indazoles",
"Logistic Models",
"Middle Aged",
"Survival Analysis"
]
} | Neither CDDP nor LND was able to significantly improve the time to progression obtained by EPI. CDDP, however, significantly worsened the drug's tolerability. | no |
12,374,690 | Is overexpression of the peripheral benzodiazepine receptor a relevant prognostic factor in stage III colorectal cancer? | {
"contexts": [
"The peripheral benzodiazepine receptor (PBR) has been implicated in the growth control of colorectal cancer, where PBR-specific ligand-binding is increased 3-4-fold. However, the prognostic relevance of PBR (over) expression has not yet been evaluated in colorectal cancer.",
"A 5-year follow-up was performed in 116 consecutive patients undergoing surgery for colorectal cancer with regional or distant metastases [Union International Contre le Cancer (UICC) stage III, 59 patients; UICC stage IV, 57 patients]. The monoclonal anti-PBR antibody 8 D7 was used for immunohistochemical examination of paraffin-embedded sections. PBR-specific staining was compared in cancer tissues and normal mucosa. Kaplan-Meier survival curves were calculated.",
"Twenty-eight % of the colorectal cancers strongly overexpressed PBR. The mean survival of patients with stage III cancer was 56.2 +/- 9.2 months with and 86.8 +/- 6.6 months without high overexpression of PBR (P = 0.006). Univariate and multivariate analyses revealed that high PBR overexpression is an independent unfavorable prognostic factor in stage III colorectal cancer. In stage IV, however, the PBR status did not correlate with different survival times."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adenocarcinoma",
"Adult",
"Aged",
"Aged, 80 and over",
"Case-Control Studies",
"Colorectal Neoplasms",
"Disease-Free Survival",
"Female",
"Follow-Up Studies",
"Humans",
"Immunoenzyme Techniques",
"Intestinal Mucosa",
"Male",
"Middle Aged",
"Neoplasm Staging",
"Prognosis",
"Receptors, GABA-A",
"Survival Rate"
]
} | Strong PBR overexpression is a new independent prognostic marker in stage III colorectal cancer. Evaluating PBR overexpression may be useful for stratifying risk and developing risk-adapted strategies of adjuvant therapy. | yes |
12,374,697 | Does blockade of insulin-like growth factor I receptor function inhibit growth and angiogenesis of colon cancer? | {
"contexts": [
"Insulin-like growth factors (IGFs) I and II and their principle receptor, IGF-I receptor (IGF-IR), are frequently expressed in human colon cancers and play a role in preventing apoptosis, enhancing cell proliferation, and inducing expression of vascular endothelial growth factor (VEGF). To elucidate the in vitro and in vivo effects of IGF-IR in human colon cancer growth and angiogenesis, HT29 cells were transfected with a truncated dominant-negative (DN) form of IGF-IR or vector alone.",
"IGF-I increased VEGF expression in parental and vector-transfected cells, whereas IGF-I induction of VEGF mRNA and protein was abrogated in IGF-IR DN cells. The IGF-IR DN cells demonstrated inhibited growth in both monolayer culture and soft agar (P < 0.05). s.c. injections of IGF-IR DN cells in nude mice led to significantly decreased tumor growth (P < 0.05). Immunohistochemical analyses revealed that IGF-I DN tumors demonstrated decreased tumor cell proliferation, VEGF expression, and vessel count and increased tumor cell apoptosis (P < 0.05 for all parameters compared with controls). Furthermore, IGF-IR DN-transfected cells yielded significantly decreased tumorigenicity and growth in the liver."
],
"labels": [
"OBJECTIVE",
"RESULTS"
],
"meshes": [
"Animals",
"Apoptosis",
"Cell Division",
"Colonic Neoplasms",
"Endothelial Growth Factors",
"Genes, Dominant",
"Humans",
"Immunoenzyme Techniques",
"In Situ Nick-End Labeling",
"In Vitro Techniques",
"Injections, Subcutaneous",
"Insulin-Like Growth Factor I",
"Intercellular Signaling Peptides and Proteins",
"Liver Neoplasms",
"Lymphokines",
"Male",
"Mice",
"Mice, Nude",
"Mitogen-Activated Protein Kinase 1",
"Mitogen-Activated Protein Kinase 3",
"Mitogen-Activated Protein Kinases",
"Neovascularization, Pathologic",
"Phosphorylation",
"Platelet Endothelial Cell Adhesion Molecule-1",
"Proliferating Cell Nuclear Antigen",
"RNA, Messenger",
"Receptor, IGF Type 1",
"Transfection",
"Tumor Cells, Cultured",
"Vascular Endothelial Growth Factor A",
"Vascular Endothelial Growth Factors"
]
} | These studies demonstrate that the IGF ligand-receptor system plays an important role in multiple mechanisms that mediate human colon cancer growth including regulation of VEGF and angiogenesis. | yes |
12,378,629 | Does angiogenesis inhibitor TNP-470 suppress growth of peritoneal disseminating foci of human colon cancer line Lovo? | {
"contexts": [
"To study the effect of angiogenesis inhibitor TNP-470 on peritoneal dissemination of colon cancer in nude mice.",
"The MTT assay was used to evaluate the inhibitory effect of TNP-470 on human colon cancer cell line Lovo. Lovo cells were injected into the peritoneal cavity of BABL/C nu/nu mice and the models of peritoneal dissemination were developed. Thirty nude mice were randomly divided into control and TNP-470-treated group. In TNP-470-treated group, TNP-470 was injected subcutaneously every other day from day 1 until sacrifice or death (30 mg x kg(-1)). The control group received a sham injection of the same volume saline solution.",
"In vitro, TNP-470 inhibited the growth of Lovo cells, with its IC50 at 2.14 X 10(2) microg x L(-1). In vitro, TNP-470 demonstrated growth inhibition of tumors. Mice body weight and abdominal circumferences were significantly different between TNP-470-treated group (24.5+/-3.2 g, 7.0+/-1.1 cm) and control group (29.5+/-2.1 g, 10.3+/-1.5 cm), P=0.005 and P=0.001. The number of disseminated foci was significantly different between the control group (92.1+/-20.6) and the TNP-470-treated group (40.3+/-12.3), P<0.001. The maximal size of foci was significantly smaller in TNP-470-treated group (3.3+/-0.7 mm) than that of control (7.3+/-2.3 mm), P=0.004. Mean survival time was significantly longer in TNP-470-treated group(98.00+/-12.06 d) than that in control group (41.86+/-9.51 d), P<0.001."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adenocarcinoma",
"Angiogenesis Inhibitors",
"Animals",
"Cell Division",
"Colonic Neoplasms",
"Cyclohexanes",
"Female",
"Humans",
"In Vitro Techniques",
"Mice",
"Mice, Inbred BALB C",
"Mice, Nude",
"O-(Chloroacetylcarbamoyl)fumagillol",
"Peritoneum",
"Sesquiterpenes",
"Tumor Cells, Cultured"
]
} | Angiogenesis inhibitor TNP-470 might be effective in treating peritoneal dissemination of colon cancer and improve the survival rate of nude mice. | yes |
12,394,766 | Is lactobacillus species more cytotoxic to human bladder cancer cells than Mycobacterium Bovis ( bacillus Calmette-Guerin )? | {
"contexts": [
"We determined if Lactobacillus species has growth inhibitory effects in human bladder cancer cell lines and how this effect compares with the known effects of Mycobacterium bovis, that is bacillus Calmette-Guerin (BCG).",
"The growth of MGH and RT112 cells were determined by cell counts after 24, 48 and 72 hours of exposure to L. casei strain Shirota (Yakult, Singapore) or L. rhamnosus strain GG (National Collection of Industrial and Marine Bacteria, Ltd., Aberdeen, Scotland) (1 x 10 and 1 x 10 cfu) or BCG (1 x 10 cfu) in the presence and absence of streptomycin. Annexin-V was used to monitor the presence of pre-apoptotic cells.",
"L. rhamnosus GG inhibited MGH proliferation and it was cytotoxic to RT112 cells (p <0.05). L. casei Shirota was cytotoxic to the 2 cell lines (p <0.05). BCG had a similar cytotoxic effect in MGH cells as Lactobacillus species but was not as effective in RT112 cells. Streptomycin abrogated the cytotoxic effect of Lactobacillus species but not that of BCG. Cytotoxic activity was not found in Lactobacilli culture supernates but it was induced in the presence of mammalian cells. L. rhamnosus GG induced apoptosis in RT112 but not in MGH cells. No apoptotic cells were detected after treatment with L. casei Shirota."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"BCG Vaccine",
"Cell Division",
"Cell Survival",
"Cytotoxicity Tests, Immunologic",
"Humans",
"Lactobacillus casei",
"Tumor Cells, Cultured",
"Urinary Bladder Neoplasms"
]
} | Lactobacillus species induced cytotoxic effects in bladder cancer cells. Unlike BCG, it requires bacterial protein synthesis. Like BCG, L. casei Shirota induces cell death primarily via necrosis. The cytoxicity of these lactobacilli in bladder cancer cells raises the possibility of using this species of bacteria as intravesical agents for treating bladder cancer. | yes |
12,378,118 | Does resection of pancreatic cancer normalize the preoperative increase of tumor necrosis factor alpha gene expression? | {
"contexts": [
"Tumor necrosis factor alpha (TNF-alpha) appears to play a role in the cachexia and diabetes seen in patients with cancers. However, increased TNF-alpha is seen in some, but not all, of the cancer patients.",
"The mRNA transcripts of TNF-alpha and its receptors (TNF-RI and TNF-RII) were quantified in blood cells of pancreatic cancer patients, using competitive quantitative reverse transcriptase-polymerase chain reaction. Plasma TNF-alpha was also quantified in these patients by enzyme-linked immunosorbent assay. Control blood came from healthy subjects.",
"The TNF-alpha mRNA transcripts (per microgram of total RNA) were increased in pancreatic cancer patients (6.8 +/- 2.1 x 10(6), n = 10), compared to control (1.2 +/- 0.2 x 10(6), n = 9, p < 0.05). After the tumour was removed, the TNF-alpha mRNA transcripts were reduced to a level (2.1 +/- 0.8 x 10(6)) similar to the control. In the cancer patients, no significant changes were found in TNF-RI and TNF-RII gene transcription, compared to the controls."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Aged",
"Base Sequence",
"DNA Primers",
"Enzyme-Linked Immunosorbent Assay",
"Female",
"Gene Expression Regulation, Neoplastic",
"Humans",
"Male",
"Middle Aged",
"Molecular Sequence Data",
"Pancreatic Neoplasms",
"RNA, Messenger",
"Reference Values",
"Reverse Transcriptase Polymerase Chain Reaction",
"Transcription, Genetic",
"Tumor Necrosis Factor-alpha"
]
} | The expression of the TNF-alpha gene is upregulated in patients with pancreatic cancer and normalized after the pancreatic tumor is removed. These results are consistent with the concept that TNF-alpha is involved in metabolic disorders associated with pancreatic cancer. | yes |
12,374,237 | Does carbon dioxide insufflation reduce discomfort due to flexible sigmoidoscopy in colorectal cancer screening? | {
"contexts": [
"Flexible sigmoidoscopy is currently recommended as a screening modality for colorectal cancer. However, a substantial number of patients experience discomfort because of the procedure. possibly limiting compliance and thus screening success. During endoscopy, air is commonly used to insufflate the bowel. Carbon dioxide rather than air insufflation has been shown to reduce procedure-related pain and discomfort in colonoscopy. The aim of the present study was to evaluate whether carbon dioxide insufflation reduces discomfort during and after flexible sigmoidoscopy for colorectal cancer screening.",
"In a randomized, double-blinded design, 230 consecutive participants in a population-based flexible sigmoidoscopy colorectal cancer screening trial were assigned to have their examination performed with either carbon dioxide or air insufflation. Patients were asked to grade discomfort experienced both during and in the hours after the procedure on a visual analogue scale.",
"Carbon dioxide insufflation significantly reduced the amount of discomfort at 1, 3 and 6 h after the sigmoidoscopy. One hour after the examination. 84% of patients in the CO2 group reported no discomfort, compared to 64% in the air group (P = 0.006). No differences between the groups were observed during the examination."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Carbon Dioxide",
"Colorectal Neoplasms",
"Double-Blind Method",
"Female",
"Humans",
"Insufflation",
"Male",
"Mass Screening",
"Middle Aged",
"Pain",
"Pain Measurement",
"Patient Satisfaction",
"Sigmoidoscopy",
"Surveys and Questionnaires"
]
} | Carbon dioxide insufflation significantly reduced post-examination discomfort. The use of carbon dioxide rather than air insufflation may contribute to better public acceptance for flexible sigmoidoscopy screening. | yes |
12,394,763 | Do beta-catenin mutations correlate with over expression of C-myc and cyclin D1 Genes in bladder cancer? | {
"contexts": [
"We hypothesized that over expression of c-myc and cyclin D1 genes is transcriptionally activated by beta-catenin mutation independent of gene amplification in bladder cancer. To test this hypothesis we investigated the relationship of beta-catenin mutation to c-myc and cyclin D1 mRNA with special reference to the changes in copy number of the 2 genes.",
"Genomic DNA and total RNA were extracted from 59 bladder cancer specimens and from 31 histologically normal specimens of bladder mucosa. We performed beta-catenin deletion screening by polymerase chain reaction (PCR) using primers spanning exons 3 (including the glycogen synthase kinase-3beta consensus motif), 5 and 6. Mutational changes in beta-catenin in exons 3, 5 and 6 were detected by each PCR-single strand conformational polymorphism analysis followed by direct DNA sequencing. mRNA expression and copy numbers of c-myc and cyclin D1 were determined by semiquantitative reverse transcriptase-PCR and competitive genomic PCR.",
"Missense mutations of beta-catenin found in grade 3 bladder cancer were involved in the consensus motif of glycogen synthase kinase-3beta in exon 3. These cancers showed strong intracellular accumulation of beta-catenin and intense expression of c-myc and cyclin D1 mRNA compared with samples lacking the beta-catenin mutation. When grade 3 cancers were compared, expression levels of c-myc and cyclin D1 mRNA were still higher in those with versus without the beta-catenin mutation. In bladder cancers with beta-catenin mutations copy numbers of the c-myc and cyclin D1 genes did not amplify."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Carcinoma, Transitional Cell",
"Cyclin D1",
"Cytoskeletal Proteins",
"DNA Mutational Analysis",
"Gene Expression Regulation, Neoplastic",
"Humans",
"Mutation, Missense",
"Neoplasm Staging",
"Proto-Oncogene Proteins c-myc",
"RNA, Messenger",
"Reverse Transcriptase Polymerase Chain Reaction",
"Trans-Activators",
"Urinary Bladder",
"Urinary Bladder Neoplasms",
"beta Catenin"
]
} | Bladder cancer harboring a beta-catenin mutation may represent aggressive biological behavior with enhanced proliferating activity. These findings are important for understanding the role of beta-catenin mutation in the pathogenesis of bladder cancer. | yes |
12,384,067 | Do cytokeratin deposits in lymph nodes show distinct clinical significance from lymph node micrometastasis in human esophageal cancers? | {
"contexts": [
"Cytokeratin immunostaining is the most common method used to identify micrometastatic cancer cells from the lymph nodes. However, contamination with hyalinized cytokeratin particles, frequently observed in the lymph nodes of esophageal cancer patients, can lead to misinterpretation of cytokeratin immunostaining.",
"Cytokeratin immunostaining (AE1/AE3) of surgically removed lymph nodes was performed for 41 cases of node-negative, but locally advanced (T3, T4), esophageal cancer patients. Cytokeratin immunoreactivity (CK) was classified as micrometastasis (MM) or cytokeratin deposit (CD) by the presence or absence of tumor nuclei in serial sections given hematoxylin-eosin staining.",
"CK (+) was observed in 18 patients (44%), including 11 with MM (+) (27%) and 10 with CD (+) (24%). There was no correlation between MM and CD, and neither was associated with clinicopathological factors, except for a high incidence of preoperative chemotherapy in CD (+) patients. The presence of CK did not affect postoperative survival of esophageal cancer patients at this limited stage, showing a 5-year survival rate of 57% for CK (+) and 64% for CK (-) (P = 0.6064). Interestingly, patients with MM (+) showed poorer prognosis than MM (-) (5-year survival: 28% vs 79%, P = 0.0188), while CD (+) patients tended to display better prognosis than CD (-) ones (5-year survival: 78% vs 56%, P = 0.1860)."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Esophageal Neoplasms",
"Humans",
"Immunohistochemistry",
"Keratins",
"Lymph Nodes",
"Lymphatic Metastasis",
"Prognosis"
]
} | Evaluation by cytokeratin immunostaining of lymph nodes requires careful discrimination of CD from MM, in order to allow MM to be used as a prognostic factor for esophageal cancer patients. | yes |
12,390,391 | Is early postoperative compensatory anti-inflammatory response syndrome associated with septic complications after major surgical trauma in patients with cancer? | {
"contexts": [
"Patients who undergo major surgery for cancer are at high risk of postoperative infection. Postoperative immunosuppression may be due to dysregulation of cytokine production. The aim of this study was to investigate the association between changes in serum proinflammatory and anti-inflammatory cytokine concentrations and postoperative septic complications after major surgery.",
"Serial blood samples were collected from 30 consecutive patients for determination of serum cytokine levels. Healthy volunteers were used as the control group.",
"Eleven patients developed no complications (group 1), 14 developed sepsis or severe sepsis (group 2), and five developed septic shock (group 3). On day 1 the patients in groups 2 and 3 had significantly higher levels of interleukin (IL) 6 than those in group 1. IL-6 levels remained high until day 5. Tumour necrosis factor (TNF), IL-1, interferon (IFN) gamma and IL-12 levels were not affected by surgical trauma or by the occurrence of septic complications. After operation the circulating IL-1 receptor antagonist (IL-1ra) concentration was increased in all groups, but patients in group 3 had significantly higher levels of IL-1ra than those in group 1. IL-1ra levels correlated with IL-6 levels. The pattern of IL-10 levels was similar to that of IL-1ra levels."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Cytokines",
"Female",
"Humans",
"Interleukin-10",
"Interleukin-6",
"Male",
"Middle Aged",
"Neoplasms",
"Postoperative Period",
"Prospective Studies",
"Receptors, Interleukin-1",
"Systemic Inflammatory Response Syndrome",
"Tumor Necrosis Factor-alpha"
]
} | Serum concentrations of proinflammatory cytokines (TNF, IL-1, IFN-gamma and IL-12) were not affected by operation or the occurrence of septic complications. The postoperative increase in IL-6 concentration was associated with septic morbidity, while raised IL-1ra concentration was associated with postoperative septic shock. | yes |
12,386,920 | Does inhibition of human chorionic gonadotropin beta-subunit modulate the mitogenic effect of c-myc in human prostate cancer cells? | {
"contexts": [
"Amplification of the proto-oncogene c-myc has been identified as one of the most common genetic alterations in prostate cancer, thus making it an attractive therapeutic target. However, certain prostate cancer cells are unresponsive to c-Myc inhibition. The purpose of this study was to test the hypothesis that effective growth inhibition in the refractory cancer cells can be achieved by blocking c-myc along with a growth factor using a novel phosphorodiamidate morpholino antisense oligomer-based approach. Human chorionic gonadotropin, a growth factor implicated in neoplasm, causes activation of c-myc through a G-protein-coupled pathway of signal transduction.",
"In this study, the effect of inhibition of beta-hCG and c-myc singly or in combination was evaluated in DU145 (RB -/-, p53-/-, androgen-independent) and LNCaP (Rb+/+, p53 +/+, androgen-sensitive) human prostate cancer cell lines and in a DU145 subcutaneous xenograft murine model.",
"Antisense phosphorodiamidate morpholino oligomers directed against beta-hCG and c-myc caused a specific decrease of the target protein levels. Unlike LNCaP cells, DU145 cell growth was refractory to c-Myc inhibition. Unresponsiveness to c-myc inhibition in DU145 cells was overcome by targeting both beta-hCG and c-myc genes, resulting in potentiation of the antiproliferative effect seen with inhibition of beta-hCG alone."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Biological Availability",
"Chorionic Gonadotropin, beta Subunit, Human",
"Gene Expression Regulation, Neoplastic",
"Humans",
"Male",
"Mice",
"Mice, Nude",
"Morpholines",
"Oligonucleotides, Antisense",
"Phosphorus Compounds",
"Prostatic Neoplasms",
"Proto-Oncogene Proteins c-myc",
"Random Allocation",
"Specific Pathogen-Free Organisms",
"Tumor Cells, Cultured"
]
} | The inhibition of beta-hCG sensitizes prostate cancer cells to the antiproliferative effects of c-Myc inhibition, including tumors that are refractory to c-Myc decrease alone. | yes |
12,377,807 | Is gastroprotective peptide trefoil factor family 2 gene activated by upstream stimulating factor but not by c-Myc in gastrointestinal cancer cells? | {
"contexts": [
"Damage to the gastrointestinal mucosa results in the acute up-regulation of the trefoil factor family peptides TFF1, TFF2, and TFF3. They possess protective, healing, and tumour suppressive functions. Little is known about the regulation of TFF gene expression. The promoters of all three TFF genes contain binding sites (E box) for upstream stimulating factor (USF) and Myc/Max/Mad network proteins.",
"To determine the nature and function of transcription factors that bind to these E boxes and to understand their role for TFF gene expression.",
"TFF promoter activities were determined by reporter gene assays. DNA binding was monitored by electromobility shift assays and by chromatin immunoprecipitation analyses. Expression of endogenous TFF was determined by multiplex RT-PCR.",
"It was observed that the TFF2 promoter is specifically and efficiently activated by USF transcription factors but not by c-Myc. USF displayed comparable binding to a high affinity Myc/Max binding site compared with the three TFF E boxes, while c-Myc exhibited lower affinity to the TFF E boxes. In contrast, pronounced binding differences were observed in cells with a strong preference for USF to interact specifically with the TFF2 E box, while Myc was not above background. Exogenous expression of USF was sufficient to activate the chromosomal TFF2 and to a lesser extent, the TFF1 gene."
],
"labels": [
"BACKGROUND",
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Binding Sites",
"DNA-Binding Proteins",
"Electrophoretic Mobility Shift Assay",
"Gastrointestinal Neoplasms",
"Gene Expression Regulation",
"Growth Substances",
"Humans",
"Mucins",
"Muscle Proteins",
"Neuropeptides",
"Peptides",
"Precipitin Tests",
"Promoter Regions, Genetic",
"Proto-Oncogene Proteins c-myc",
"Reverse Transcriptase Polymerase Chain Reaction",
"Transcription Factors",
"Transcriptional Activation",
"Trefoil Factor-2",
"Trefoil Factor-3",
"Tumor Cells, Cultured",
"Upstream Stimulatory Factors"
]
} | These findings define USF factors as regulators of the TFF2 gene and suggest that promoter specific effects are important for a pronounced gene activation of this cytoprotective peptide. | yes |
11,454,877 | Is ovarian failure after adjuvant chemotherapy associated with rapid bone loss in women with early-stage breast cancer? | {
"contexts": [
"We sought to evaluate the effects of chemotherapy-induced ovarian failure on bone loss and markers of skeletal turnover in a prospective longitudinal study of young women with breast cancer receiving adjuvant chemotherapy.",
"Forty-nine premenopausal women with stage I/II breast cancers receiving adjuvant chemotherapy were evaluated within 4 weeks of starting chemotherapy (baseline), and 6 and 12 months after starting chemotherapy with dual-energy absorptiometry and markers of skeletal turnover osteocalcin and bone-specific alkaline phosphatase. Chemotherapy-induced ovarian failure was defined as a negative pregnancy test, greater than 3 months of amenorrhea, and a follicle-stimulating hormone > or = 30 MIU/mL at the 12-month evaluation.",
"Among the 35 women who were defined as having ovarian failure, highly significant bone loss was observed in the lumbar spine by 6 months and increased further at 12 months. The median percentage decrease of bone mineral density in the spine from 0 to 6 months and 6 to 12 months was -4.0 (range, -10.4 to +1.0; P =.0001) and -3.7 (range, -10.1 to 9.2; P =.0001), respectively. In contrast, there were no significant decreases in bone mineral density in the 14 patients who retained ovarian function. Serum osteocalcin and bone specific alkaline phosphatase, markers of skeletal turnover, increased significantly in the women who developed ovarian failure."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Alkaline Phosphatase",
"Amenorrhea",
"Antineoplastic Agents",
"Antineoplastic Combined Chemotherapy Protocols",
"Bone Density",
"Bone Resorption",
"Breast Neoplasms",
"Chemotherapy, Adjuvant",
"Female",
"Follicle Stimulating Hormone",
"Humans",
"Longitudinal Studies",
"Middle Aged",
"Osteocalcin",
"Premenopause"
]
} | Chemotherapy-induced ovarian failure causes rapid and highly significant bone loss in the spine. This may have implications for long-term breast cancer survivors who may be at higher risk for osteopenia, and subsequently osteoporosis. Women with breast cancer who develop chemotherapy-induced ovarian failure should have their bone density monitored and treatments to attenuate bone loss should be evaluated. | yes |
11,458,119 | Is inhibition of telomerase related to the life span and tumorigenicity of human prostate cancer cells? | {
"contexts": [
"Telomerase, the enzyme that catalyzes the elongation of telomeres, is illegitimately activated in the majority of cancers, including that of the prostate, where it may greatly extend the life span of malignant cells. The inhibition of telomerase by molecular intervention has been shown to lead eventually to cell death in several tumor or in vitro immortalized cell lines and in 1 case prevent tumor growth in vivo. Therefore, we tested whether a similar strategy may be used to limit the tumorigenic potential of late stage prostate cancer cells.",
"PC-3, LNCaP and DU-145 human prostate cancer cells were infected with a retrovirus encoding a dominant-negative version of the catalytic subunit of telomerase (DN-hTERT). Subclones or polyclonal populations were assayed for DN-hTERT expression, telomerase activity, telomere length, cell life span and in most cases tumorigenicity in nude mice.",
"DN-hTERT expression levels directly correlated with cell life span and tumorigenic growth. PC-3 cells expressing high levels of DN-hTERT died rapidly and failed to form tumors in nude mice, whereas cells expressing the lowest levels proliferated the longest and generated tumors that later spontaneously regressed. Similarly the inhibition of telomerase activity in LNCaP cells was greater than in DU-145 cells and correspondingly LNCaP cells had a shorter life span."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Animals",
"Cell Death",
"Humans",
"Male",
"Mice",
"Mice, Inbred BALB C",
"Mice, Nude",
"Neoplasm Transplantation",
"Prostatic Neoplasms",
"Telomerase",
"Tumor Cells, Cultured"
]
} | DN-hTERT expression limits the life span and tumorigenic potential of human prostate cancer cells, although the onset of these effects appears to be dictated by the expression level of DN-hTERT. Therefore, telomerase represents an attractive target for potentially managing prostate cancer. Nevertheless, effective means of inhibiting the enzyme may be required for a therapeutically useful outcome. | yes |
11,454,999 | Is loss of expression of the PTEN gene protein product associated with poor outcome in breast cancer? | {
"contexts": [
"The PTEN gene, a candidate tumor suppressor, is localized to chromosome 10q23 and shares extensive homology with cytoskeletal proteins auxilin and tensin. A high frequency of mutations at the PTEN locus has been described in a variety of neoplasms including breast cancer. However, the role of PTEN alternations and its association with outcome variables in breast neoplasia is not well established.",
"Formalin-fixed paraffin embedded tissues from 151 women (mean age 62 years, range 26-98) with primary diagnosis of invasive breast cancer were evaluated for PTEN protein expression by automated immunohistochemical methods. Slides were scored semi-quantitatively based on staining intensity and distribution, and results were compared with clinical pathologic parameters. The mean follow-up was 56 months (range 1-169).",
"Seventy-three (48%) of 151 breast tumors had loss of PTEN protein expression. On univariate analysis, loss of PTEN expression (P =.034), stage (P <.0001), node positive (P <.0001), and tumor grade (P =.002) were associated with disease-related death. Loss of PTEN expression also predicted lymph node metastasis (P <.0001), and correlated with loss of estrogen receptor staining (P =.040). Loss of PTEN did not correlate with stage, tumor grade, disease recurrence, or loss of progesterone receptor [although a trend was seen (P =.092). On multivariate analysis, stage (P <.0001), lymph node metastasis (P <.0001), and tumor grade (P =.002) correlated with survival."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Aged",
"Aged, 80 and over",
"Breast Neoplasms",
"Female",
"Humans",
"Immunohistochemistry",
"Middle Aged",
"PTEN Phosphohydrolase",
"Phosphoric Monoester Hydrolases",
"Prognosis",
"Survival Analysis",
"Tumor Suppressor Proteins"
]
} | Loss of PTEN protein expression occurs commonly in breast cancer and correlates with disease related death, lymph node metastasis, and loss of estrogen receptor staining. Our results support the proposed role of PTEN as a candidate tumor suppressor in breast cancer and suggest a need for further study of this marker. | yes |
11,442,533 | Are patterns of pelvic invasion prognostic in the treatment of locally recurrent rectal cancer? | {
"contexts": [
"Local recurrence of rectal cancer after curative resection remains a difficult clinical problem. The aim of this study was to elucidate prognostic risk factors after resection of recurrent cancer.",
"Between January 1983 and December 1999, 83 patients with locally recurrent rectal cancer were studied retrospectively for survival benefit by re-resection. Sixty patients underwent resection for recurrent cancer, including total pelvic exenteration in 30 patients and sacrectomy in 23 patients. The extent of locally recurrent tumour was classified by the pattern of pelvic invasion as follows: localized, sacral invasion and lateral invasion.",
"Multivariate analysis showed that the pattern of pelvic invasion was a significant prognostic factor which independently influenced survival after resection of recurrent cancer (P < 0.001). The 5-year survival rates were 38 per cent in the localized type (n = 27), 10 per cent in the sacral invasive type (n = 16) and zero in the lateral invasive type (n = 17)."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Aged",
"Female",
"Humans",
"Male",
"Middle Aged",
"Multivariate Analysis",
"Neoplasm Invasiveness",
"Neoplasm Recurrence, Local",
"Pelvic Exenteration",
"Pelvic Neoplasms",
"Prognosis",
"Proportional Hazards Models",
"Rectal Neoplasms",
"Retrospective Studies",
"Risk Factors",
"Survival Analysis",
"Time Factors"
]
} | Resection for locally recurrent rectal cancer is potentially curative in patients with localized or sacral invasive patterns of recurrence. Alternatives should be explored in patients with recurrence involving the lateral pelvic wall. | yes |
11,467,626 | Is gastroesophageal reflux disease a risk factor for laryngeal and pharyngeal cancer? | {
"contexts": [
"Gastroesophageal reflux disease (GERD) is a proposed risk factor for developing laryngeal and pharyngeal cancers. No controlled study has examined this association.",
"A case-control-study was performed using the computerized hospitalization and outpatient databases of the US Department of Veterans Affairs. All patients, who were veterans, had been identified as being hospitalized with laryngeal or pharyngeal during 1991 to 1997. In addition, all persons diagnosed with laryngeal or pharyngeal cancer in 1999 in the outpatient files were identified. From the same patient populations, four nonmatched control subjects were randomly assigned for each case. The medical history for cases and controls was retrospectively searched for GERD diagnoses, tobacco use, and alcohol dependence. Multivariable logistic regression analyses were performed to assess the risk factors for laryngeal and pharyngeal cancers.",
"A total of 8,228 hospitalized patients with laryngeal cancers and 1,912 with pharyngeal cancers were compared to 32,912 and 7,648 hospitalized controls, while 9,292 outpatients with laryngeal cancer and 2,769 outpatients with pharyngeal cancer were compared with 37,168 and 11,076 outpatient controls without cancer. Among hospitalized persons, the prevalence of GERD was higher among patients with laryngeal cancer (8.9 vs 4.0%, p < 0.0001) and pharyngeal cancer (6.2 vs 3.8%, p < 0.0001). In a multivariable logistic regression analysis that was controlled for age, gender, ethnicity, smoking, and alcohol, GERD was associated with an adjusted odds ratio (OR) of 2.40 for laryngeal cancer among hospitalized patients (95% CI 2.15-2.69, p < 0.0001) and an adjusted OR of 2.38 (95% CI 1.87-3.02, p < 0.0001) for pharyngeal cancer. For outpatients, GERD was associated with an adjusted OR = 2.31 (95% CI 2.10-2.53) for laryngeal cancer and adjusted OR = 1.92 (95% CI 1.72-2.15)."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Aged",
"Case-Control Studies",
"Female",
"Gastroesophageal Reflux",
"Humans",
"Laryngeal Neoplasms",
"Logistic Models",
"Male",
"Middle Aged",
"Pharyngeal Neoplasms",
"Retrospective Studies",
"Risk Factors",
"Veterans"
]
} | Among US veterans, the risk for laryngeal or pharyngeal cancers is modestly increased in the presence of GERD. This effect seems to be independent of age, gender, smoking, and alcohol intake. | yes |
11,458,121 | Does methylation of the E-cadherin gene promoter correlate with progression of prostate cancer? | {
"contexts": [
"We studied the methylation status of E-cadherin gene promoter in prostate cancer and its relationship with E-cadherin inactivation in prostate cancer.",
"Seven human prostate cell lines and 35 microdissected prostate cancer specimens were analyzed for E-cadherin promoter methylation using the bisulfite genome sequencing technique. E-cadherin messenger (m)RNA expression and protein expression were also studied in prostate cell lines by reverse transcriptase-polymerase chain reaction and in prostate cancer specimens by immunostaining, respectively.",
"The overall methylation of E-cadherin promoter was evident in 14 of 20 grades III to V (70%) and in 5 of 15 grades I to II (33%) prostate cancer samples. It correlated with absent or reduced E-cadherin immunostaining. Methylation in low grade tumors was present mainly in the exon region, whereas in high grade tumors methylation was also present in the promoter region. Methylation was noted in 2 of 6 prostate cancer cell lines (33%) and correlated well with decreased E-cadherin mRNA in these cell lines. Treatment with the demethylating agent 5-aza-2'-deoxycytidine restored E-cadherin mRNA levels in the E-cadherin negative prostate cancer cell lines TSUPr1 and DuPro."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Cadherins",
"Humans",
"Immunohistochemistry",
"Male",
"Methylation",
"Polymerase Chain Reaction",
"Promoter Regions, Genetic",
"Prostatic Neoplasms",
"Tumor Cells, Cultured"
]
} | Methylation of the E-cadherin gene is common in prostate cancer and the severity of E-cadherin methylation correlates with tumor progression. This study implies that the invasion and metastasis suppressor function of E-cadherin may often be compromised in human prostate cancer by epigenetic rather than by mutational events. | yes |
11,459,200 | Do arsenic compounds induce cytotoxicity and apoptosis in cisplatin-sensitive and -resistant gynecological cancer cell lines? | {
"contexts": [
"Arsenic compounds have been found to be effective in the treatment of acute promyelocytic leukemia through the downregulation of bcl-2 expression. Resistant ovarian cancer cells often overexpress bcl-2 or p53 proteins or both. We hypothesized that arsenic compounds, such as As2O3 and As2S3, could also be active against gynecological cancers resistant to conventional chemotherapy.",
"We investigated the effects of these two arsenic compounds in vitro on ovarian cancer cell lines sensitive (OVCAR, GG, JAM) and resistant (CI80-13S) to cisplatin (CDDP) and on human cervical cancer cell lines (HeLa) in comparison with their effects on human fibroblasts (HF). A fluorometric assay based on measurements of fluorescein diacetate (FDA) in cells was used to determine cell viability. Apoptosis was assessed in terms of cell morphology, by flow cytometry and by a DNA fragmentation assay.",
"Treatment of each cell line with the As2O3 or As2S3 led to a marked dose-dependent decrease in cell growth. The IC50 of the two compounds indicated a significantly greater cytotoxic effect against all the cancer cells tested than against the normal HF. At a clinically achievable concentration (2 microM), As2O3 selectively inhibited the growth and induced apoptosis in CI80-13S, OVCAR and HeLa cells but had no significant apoptotic effect on GG or JAM cells or HF. Following treatment with 5 microM As2S3, the CI80-13S, OVCAR and HeLa cells also exhibited growth inhibition and induction of apoptosis."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Antineoplastic Agents",
"Apoptosis",
"Arsenic Trioxide",
"Arsenicals",
"Cell Size",
"Cisplatin",
"Dose-Response Relationship, Drug",
"Drug Resistance, Neoplasm",
"Drug Screening Assays, Antitumor",
"Female",
"HeLa Cells",
"Humans",
"Ovarian Neoplasms",
"Oxides",
"Sulfides",
"Time Factors",
"Tumor Cells, Cultured",
"Uterine Cervical Neoplasms"
]
} | Arsenic compounds (As2O3 and As2S3) can inhibit growth and induce apoptosis in human ovarian and cervical cancer cells at clinically achievable concentrations, indicating that As2O3 and As2S3 could be effective in the treatment of gynecological cancer. | yes |
11,456,056 | Is mRI phenotype associated with response to doxorubicin and cyclophosphamide neoadjuvant chemotherapy in stage III breast cancer? | {
"contexts": [
"The preferred management for women with stage II or locally advanced breast cancer (LABC) is neoadjuvant chemotherapy. Pathologic response to chemotherapy has been shown to be an excellent predictor of outcome. Surrogates that can predict pathologic response and outcome will fuel future changes in management. Magnetic resonance imaging (MRI) demonstrates that patients with LABC have distinct tumor patterns. We investigated whether or not these patterns predict response to therapy.",
"Thirty-three women who received neoadjuvant doxorubicin and cyclophosphamide chemotherapy for 4 cycles and serial breast MRI scans before and after therapy were evaluated for this study. Response to therapy was measured by change in the longest diameter on the MRI.",
"Five distinct imaging patterns were identified: circumscribed mass, nodular tissue infiltration diffuse tissue infiltration, patchy enhancement, and septal spread. The likelihood of a partial or complete response as measured by change in longest diameter was 77%, 37.5%, 20%, and 25%, respectively."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Aged",
"Antineoplastic Agents",
"Breast Neoplasms",
"Chemotherapy, Adjuvant",
"Cyclophosphamide",
"Doxorubicin",
"Female",
"Humans",
"Magnetic Resonance Imaging",
"Middle Aged",
"Neoadjuvant Therapy",
"Neoplasm Staging",
"Patient Selection",
"Phenotype",
"Predictive Value of Tests",
"Treatment Outcome"
]
} | MRI affords three-dimensional characterization of tumors and has revealed distinct patterns of tumor presentation that predict response. A multisite trial is being planned to combine imaging and genetic information in an effort to better understand and predict response and, ultimately, to tailor therapy and direct the use of novel agents. | yes |
11,456,053 | Is bcl-2 a useful prognostic marker in Dukes ' B colon cancer? | {
"contexts": [
"Currently, the use of adjuvant therapy specifically in Dukes' B colon cancers is controversial, emphasizing the importance of identifying prognostic markers to select patients for such therapy. Bcl-2 plays an important role in apoptosis regulation of solid tumors, such as colon and breast cancer, and is normally expressed in the base of the colonic crypts. The purpose of this study is to determine whether or not bcl-2 expression can be used to predict survival in Dukes' B colon cancer patients.",
"Charts of 76 patients operated on at the Royal Victoria Hospital from 1986 to 1992 were reviewed. Bcl-2 staining was done with the avidin-biotin-peroxidase complex method using commercially available monoclonal bcl-2 antibodies. Two pathologists graded the intensity of bcl-2 staining on a scale of 0-3 and estimated the percentage of tumor cells staining positively (T-percent). Univariate and multiple regression of factors on overall survival (OS) and disease-free survival (DFS) was done with a Cox proportional hazards model and Kaplan-Meier survival curves.",
"The mean age was 71.2 years, with 41 female and 35 male patients. Mean tumor size was 5.4 cm with tumor grades of 19 well, 52 moderate, and 5 poorly differentiated. Tumors expressing bcl-2 had a similar DFS (P = .14) but a significantly improved OS (P = .04) compared with the bcl-2 negative tumors. The risk ratio for DFS was 0.49 (95% CI, 0.19-1.26) and for OS was 0.35 (95% CI, 0.13-0.94)."
],
"labels": [
"BACKGROUND",
"METHODS",
"RESULTS"
],
"meshes": [
"Adult",
"Aged",
"Apoptosis",
"Biomarkers, Tumor",
"Colonic Neoplasms",
"Female",
"Humans",
"Immunoenzyme Techniques",
"Male",
"Middle Aged",
"Proto-Oncogene Proteins c-bcl-2",
"Statistics as Topic",
"Survival Analysis"
]
} | These data indicate that enhanced bcl-2 expression, specifically in Dukes' B colon carcinomas, is associated with improved survival. Thus, patients whose tumors do not express bcl-2 should be considered for adjuvant therapy. | yes |
11,446,858 | Is castration-induced reduction of vascular endothelial growth factor expression in benign human prostate tissue lost in advanced prostate cancer? | {
"contexts": [
"To determine the role of vascular response in the castration-induced regression of benign and malignant human prostate tissue, as recent studies show that castration rapidly decreases blood flow and induces endothelial cell death, which may be important for subsequent epithelial cell death and involution of the glandular tissue of the prostate.",
"The expression of vascular endothelial growth factor (VEGF) and its receptors was analysed using the quantitative reverse transcriptase-polymerase chain reaction, in benign and tumour areas of core biopsies taken before, and approximately 1 week after castration therapy. The castration-induced VEGF response was related to therapy-induced changes in tumour cell apoptotic index and subsequent response in serum prostate-specific antigen (PSA). In another set of patients, serum VEGF was quantified by enzyme-linked immunosorbent assay before, and at 3--6 months after castration therapy.",
"VEGF mRNA was down-regulated after castration in benign prostate tissue (P < or = 0.05), whereas in tumour tissue, VEGF levels were reduced in some of the patients but unchanged or increased in others. In most patients whose tumour tissue responded with VEGF reduction, there was a corresponding increase in tumour cell apoptosis. Serum VEGF levels were not significantly changed after castration. Almost all patients responded with a substantial reduction in serum PSA after castration."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Apoptosis",
"Biopsy",
"Castration",
"Endothelial Growth Factors",
"Humans",
"Lymphokines",
"Male",
"Prostatic Neoplasms",
"RNA, Messenger",
"Reverse Transcriptase Polymerase Chain Reaction",
"Vascular Endothelial Growth Factor A",
"Vascular Endothelial Growth Factors"
]
} | Castration reduces VEGF mRNA expression in benign prostate tissue and generally in those prostate tumours where castration also induces tumour cell apoptosis. This suggests that a therapy-induced down-regulation of VEGF could be important for tumour cell death. | yes |
11,469,074 | Does repetitive mucosal trauma promote colon cancer in experimental rat model? | {
"contexts": [
"To investigate the effect of repetitive mucosal trauma, anastomosis and intestinal content on experimental colonic carcinogenesis as there is the possibility than non-specific colon lesions can promote cancer.",
"We performed to sixty female Sprague-Dawley rats a 4 cm colon loop defunctionalization with double colostomy (traumatic site). Intestinal continuity was restored with an end-to-end colo-colic silk anastomosis. The surviving 47 rats were divided in 3 groups: Group A: 27 rats treated with DMH. Group B: 10 rats treated with EDTA and Group C: Control of 10 rats. Animals were sacrificed 31-32 weeks after surgery for macro and micropathological studies.",
"In group A appeared 60 tumours: 44 in the functional colon, 20 of them in the anastomotic site; 8 in the non traumatised defunctionalized segment and 18 in the traumatised segment (p < 0.05)."
],
"labels": [
"OBJECTIVE",
"METHODS",
"RESULTS"
],
"meshes": [
"Anastomosis, Surgical",
"Animals",
"Colonic Neoplasms",
"Female",
"Intestinal Mucosa",
"Rats",
"Rats, Sprague-Dawley"
]
} | a) Continuous microtraumas on colonic mucosa in rats are cancer promotional factors; b) silk suture in anastomosis promotes cancer. | yes |
8,204,036 | Does gastric remnant cancer have a better prognosis than primary gastric cancer? | {
"contexts": [
"To study the prognosis of gastric remnant cancer following radical resection (group 1) compared with that of primary gastric cancer of the upper third of the stomach following radical resection (group 2).",
"Cohort study with a 5-year follow-up.",
"A university hospital in Austria.",
"Group 1 consisted of 43 patients, and group 2, of 61. Postoperative deaths and deaths during the follow-up period that were not related to gastric cancer were excluded. Fifteen patients in group 1 (34.9%) presented with stage I cancer; 10 (23.3%), stage II; 13 (30.2%), stage III; and five (11.6%), stage IV. Twenty patients in group 2 (32.8%) presented with stage I cancer; 12 (19.7%), stage II; 15 (24.6%), stage III; and 14 (22.9%), stage IV (Union Internationale Contre le Cancer staging classification, 1987).",
"Overall and stage-related 5-year survival rates.",
"The overall 5-year survival rate was 53.5% in group 1 and 32.8% in group 2 (P < .05). The stage-related 5-year survival rate in group 1 was 100% for stage I and 80% for stage II. In group 2, the stage-related 5-year survival rate was 65% for stage I and 25% for stage II (both, P < .01). No significant difference was noted for stages III and IV."
],
"labels": [
"OBJECTIVE",
"METHODS",
"METHODS",
"METHODS",
"METHODS",
"RESULTS"
],
"meshes": [
"Adolescent",
"Adult",
"Aged",
"Female",
"Follow-Up Studies",
"Gastrectomy",
"Humans",
"Lymph Node Excision",
"Male",
"Middle Aged",
"Neoplasm Recurrence, Local",
"Neoplasm Staging",
"Prognosis",
"Stomach Neoplasms",
"Survival Rate",
"Time Factors"
]
} | The prognosis of cancer of the gastric remnant presenting as stage I or II is good and is significantly better than that of the equivalent stages of primary cancer of the upper third of the stomach. | yes |