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Background Pancreatic cancer is one of the most common malignant tumors of the digestive tract, and it has a poor prognosis. Traditional methods are not effective to accurately assess the prognosis of patients with pancreatic cancer. Immunotherapy is a new promising approach for the treatment of pancreatic cancer; however, some patients do not respond well to immunotherapy, which may be related to tumor microenvironment regulation. In this study, we use gene expression database to mine important immune genes and establish a prognostic prediction model for pancreatic cancer patients. We hope to provide a feasible method to evaluate the prognosis of pancreatic cancer and provide valuable targets for pancreatic cancer immunotherapy. Results We used univariate COX proportional hazard regression analysis, the least absolute shrinkage and selection operator, and multivariate COX regression analysis to screen 8 genes related to prognosis from the 314 immune-related genes, and used them to construct a new clinical prediction model in the TCGA pancreatic cancer cohort. Subsequently, we evaluated the prognostic value of the model. The Kaplan–Meier cumulative curve showed that patients with low risk scores survived significantly longer than patients with high risk scores. The area under the ROC curve (AUC value) of the risk score was 0.755. The univariate COX analysis showed that the risk score was significantly related to overall survival (HR 1.406, 95% CI 1.237–1.598, P Conclusions Based on the TCGA-PAAD cohort, we identified immune-related markers with independent prognostic significance, validated, and analyzed their biological functions, to provide a feasible method for the prognosis of pancreatic cancer and provide potentially valuable targets for pancreatic cancer immunotherapy.

// Dongfang Tang 1 , Lu Yue 2 , Ruyong Yao 3 , Lin Zhou 4 , Yuqin Yang 4 , Liming Lu 4 and Wen Gao 1 1 Department of Thoracic Surgery, Huadong Hospital Affiliated to FuDan University, Huadong, China 2 Department of Oncology of the Qingdao Municipal Hospital, Qingdao, China 3 Central Laboratory of the Affiliated Hospital of Medical College Qingdao University, Qingdao, China 4 Central Laboratory of Shanghai Chest Hospital Affiliated to Shanghai Jiaotong University, China Correspondence to: Wen Gao, email: gaowenchest@163.com Keywords: lung cancer, IDO signaling, p53, metastasis Received: February 10, 2017 Accepted: March 29, 2017 Published: April 25, 2017 ABSTRACT In present study, we are to clear demonstrate the genetic evidence of IDO signaling’s impact on invasion and metastasis in lung cancer. Here we examined IDO1 expression levels in non-small cell lung cancer (NSCLC) patients (64) tumor/normal pairs underwent RT-PCR and comprehensive histological, immunohistochemica and clinical analysis. The NSCLC cells stably expressing IDO1 was analyzed for migration and invasion assays and the regulatory mechanism in vitro and metastasis assays in vivo . As results, we reported that IDO1 expression increased by more than 3.2-fold in lung cancer compared with their corresponding non-tumor tissues, and the up-regulation of IDO1 is significantly correlated to TNM stage and lymph node-metastasis. The over-expression of IDO1 significantly encouraged the metastasis and invasion of lung cancer cells, and IDO1 could promote metastasis formation in vivo . Furthermore, we further found that p53 could attenuate IDO signaling in lung cancer cell migration partly. In conclusion, these results demonstrate that the IDO signaling’s impact on invasion and metastasis and the suppressive effect of p53 on IDO1 in lung cancer, present one novel therapeutic strategy for early metastatic lung cancer in clinical.

Insulin-like growth factor (IGF) signaling plays an important role in tumorigenesis and metastasis. Here, we analyzed insulin-like growth factor (IGF) binding protein-2 (IGFBP2) expression in 81 lung cancer patients and 36 controls consisting of healthy and benign pulmonary lesion participants for comparison, then validated the IGFBP2 expression in additional 84 lung cancer patients, and evaluated the prognostic and chemoresistant significance of IGFBP2 in two cohorts respectively. Next we detected the reversal effect of trichostatin A (TSA) on chemoresistance in cell lines with high IGFBP2 expression. As a result, the mean expression of IGFBP2 in lung cancer patients was significantly higher than that in controls and increased with lung cancer progressed to advanced stage. In addition, high IGFBP2 expression was independently predictive for chemoresistance; over-expressed IGFBP2 enhances cell activity and TSA can reverse the chemoresistance induced by high IGFBP2 expression through enhancing autophagy. Furthermore, multivariate analysis showed that lung cancer patients whose blood IGFBP2 was higher had a poor survival outcome, with a hazard ratio of 8.22 (95%CI 1.78–37.92, P = 0.007) after adjustment for stage, histopathology, EGFR mutation, age, smoking and surgery.

Background The brain is a frequent site of metastases from non-small cell lung cancer (NSCLC). The purpose of this study was to detect the expression of CUG-binding protein 1 (CUGBP1) messenger ribonucleic acid (mRNA) and Ki-67 in metastasized brain tissue from NSCLC and determine the relationship between CUGBP1 and brain metastases. Methods The expression of CUGBP1 mRNA and Ki-67 in metastasized brain tissue from NSCLC was investigated by semiquantitative polymerase chain reaction and immunohistochemistry, respectively. The expression of CUGBP1 and Ki-67 in metastasized brain tissue from NSCLC was related to clinical characteristics, as assessed using the chi-square test. The prognostic significance was assessed by univariate and multivariate analyses using the Cox hazard model. Results The expression of CUGBP1 mRNA and Ki-67 was overexpressed in metastasized brain tissue from NSCLC and was correlated with differentiation. In addition, by both univariate and multivariate survival analyses, CUGBP1 expression, Ki-67 expression, and age were noted to be independent indicators of a shorter postsurgical survival. Conclusion The expression of CUGBP1 is an important factor in the development of brain metastases from NSCLC.

Background At present, the expression of MOR1 and its function in gastric cancer remains unclear with evidence suggesting that it is to be involved in tumor progression and metastasis. The study was to assess the clinicopathologic relevance and prognostic value of MOR1 expression in gastric cancer. Methods Real-time quantitative RT-PCR and immunohistochemical staining were used to detect MOR1 expression in primary gastric cancerous surgical specimens and adjacent nontumorous tissues. Results High MOR1 expression was detected in cancerous tumor compared with their adjacent nontumorous tissues. In addition, the chi-square test revealed that high MOR1 expression was significantly correlated with depth of invasion (p = 0.006), lymph node metastasis (p = 0.001), distant metastasis (p = 0.017), and TNM staging (p = 0.027). Moreover, Kaplan–Meier analysis revealed a significant association between MOR1 expression and overall survival. High expression of MOR1 was identified as an independent and significant predictor gene of reduced postoperative survival. Conclusion We conclude that MOR1 expression may be a useful biomarker for better prediction of the clinical outcome and management of gastric cancer patients.

Objective To evaluate the effect of semiconductor laser irradiation on root canal sealing after routine root canal therapy (RCT). Methods Sixty freshly extracted single-rooted human teeth were randomly divided into six groups (n = 10). The anatomic crowns were sectioned at the cementoenamel junction and the remaining roots were prepared endodontically with conventional RCT methods. Groups A and B were irradiated with semiconductor laser at 1W for 20 seconds; Groups C and D were ultrasonically rinsed for 60 seconds as positive control groups; Groups E and F without treatment of root canal prior to RCT as negative control groups. Root canal sealing of Groups A, C and E were evaluated by measurements of apical microleakage. The teeth from Groups B, D and F were sectioned, and the micro-structures were examined with scanning electron microscopy (SEM). One way ANOVA and LSD-t test were used for statistical analysis (α = .05). Results The apical sealing of both the laser irradiated group and the ultrasonic irrigated group were significantly different from the control group (p0.5). SEM observation showed that most of the dentinal tubules in the laser irradiation group melted, narrowed or closed, while most of the dentinal tubules in the ultrasonic irrigation group were filled with tooth paste. Conclusion The application of semiconductor laser prior to root canal obturation increases the apical sealing of the roots treated.

It is known that mitochondrial ATP-sensitive potassium channels (mitoKATP) play a significant role in protecting cerebral function from ischemia-reperfusion injury, which is related with a decrease in the mitochondrial matrix calcium. However, the effect of mitochondrial calcium uniporter (MCU) on diazoxide-induced cerebral protection is still indistinct. The purpose of the present paper is to further observe the relationship between mitoKATP and MCU, and to probe the mechanism. Adult male Wistar rats were randomly divided into five groups: the Sham group, the I-R group, the Dzx+I-R group, the Dzx+Sper+I-R group, and the Sper+I-R group. Rats not in the Sham group were exposed to 2-hour ischemia followed by 24-hour reperfusion. Diazoxide and spermine were administrated 30 minutes before ischemia or 10 minutes before reperfusion, respectively. After 24-hour reperfusion, animals were given neurological performance tests, overdosed with general anesthesia, and then their brains were excised for infarct volume, pathological changes, and apoptosis analysis. The beneficial effects of diazoxide (improved neurological deficits, decreased infarct volume, and apoptosis, evidenced by the decreased expression of cytochrome c and Bax) were significantly neutralized by spermine. The results of the present work suggest that diazoxide-induced cerebral protection against ischemia-reperfusion injury is mediated by spermine through apoptotic pathway.

In the present study, we intend to detect the expression of Forkhead box transcription (FOXM1) in gastric cancer tissues and cell lines, and analyze the correlation between FOXM1 expression and clinic-pathological features as well as their association with clinic outcomes in patients with resectable gastric cancers.We examined the expression of FOXM1 in 103 cancer tissues from patients who underwent gastrectomy during Jan 2007 to Nov 2007 and 68 randomly selected para-cancer tissues by immunohistochemistry. The expression of FOXM1 protein in the benign and malignant human gastric cell lines was simultaneously detected using Western blot analysis. Data on clinic-pathological features and relevant prognostic factors in these patients were then analyzed.FOXM1 expression was absolutely higher in gastric cancer than para-cancer tissues (P 0.001) and normal gastric epithelium cell lines (P = 0.022). No significant association was found between FOXM1 expression and any clinic-pathological parameters (P 0.1). FOXM1 amplification was showed to be independently associated with prognosis in gastric cancer patients (P = 0.001), and its affection is more significant in patients with tumor size larger than 5 cm (P = 0.004), pT3-4 (P = 0.003) or pIII-IV (P = 0.001) as a result of stage-stratified analysis.Overexpressed FOXM1 is a potential diagnostic and poor prognostic biomarker in postoperational gastric cancer patients.

Objective To investigate the effects of small interfering RNA (siRNA)-mediated silencing of the ribonucleotide reductase M2 subunit (RRM2) on the apoptosis and the drug sensitivity of cisplatin-resistant SKOV3/DDP cells. Methods Small interfering RNA transfection was mediated by lipofectamine 2000 to silence RRM2 gene. Messenger RNA (mRNA), and protein expression levels of RRM2 were evaluated by real-time polymerase chain reaction and Western blot after transfection. The cell growth inhibition rate was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. The cellular apoptosis and cycling was identified by flow cytometry (FCM). Results The messenger RNA and protein expression levels of RRM2 markedly decreased after the RRM2 siRNA transfection. The half inhibition concentration of cisplatin in RRM2-RNA interference cells (interference group) was lower than that in RRM2-negative cells (noninterference group) and the SKOV3/DDP cells (blank control group) (P = 0.032). Small interfering RNA–mediated inhibition of RRM2 effectively induced G1/S-phase cell cycle arrest and increased drug (gemcitabine and cisplatin)-induced apoptotic fraction at 72 hours ( (96% ± 3.0)%) after transfection (P Conclusion Small interfering RNA–mediated RRM2 knockdown significantly reversed SKOV3/DDP cell resistance to cisplatin. RNA interference technology combined with gemcitabine and cisplatin can effectively improve the apoptosis rate of the cisplatin-resistant ovarian cancer cell, which is expected to become the first-line treatment options for the cisplatin-resistant ovarian cancer.

The ability of differentiated thyroid cancer and adjacent thyroid cells to concentrate iodine is dependent on their expression of a functional NA(+)/I(-) symporter (NIS). Thyroid cancer is insensitive to (131)I treatment if the thyroid cells lack the ability to concentrate iodide. Thus, in this study, we aimed to determine whether the NIS protein was differentially expressed in thyroid cancer and various surrounding tissues. We recruited 114 cases of papillary thyroid carcinoma (PTC) and divided them into two groups: 60 patients of 9 males and 51 females with a mean age of 49.55 years who had PTC with surrounding nodular goiter tissue (simplified as G(NG)), and 54 patients of 8 males and 46 females with a mean age of 45.78 years who had PTC with surrounding normal tissue (G(normal)) after total or near total thyroidectomy. Formalin-fixed and paraffin-embedded tissue sections were prepared for immunohistochemical staining of the NIS protein and semi-quantitative analysis. The NIS protein was expressed in the basolateral membrane of the normal epithelium, while PTC and nodular goiter cells expressed NIS in the cytoplasm and basolateral membrane. The expression levels of the NIS protein were higher in the adjacent normal tissues compared with those of the surrounding nodular goiter tissues (P=0.002) and expression levels of the NIS protein were higher in PTC tissues compared with the surrounding nodular goiter tissues (P=0.008). The data from this study indicate that cancer-surrounding tissues may play a significant role in mediating the sensitivity of PTC patients to radioactive iodine treatment.

To evaluate the effect of excision repair cross-complementing group 1 (ERCC1) and X-ray cross-complementing group 1 (XRCC1) gene polymorphisms on treatment outcome in patients receiving oxaliplatin-based regimens for metastatic colorectal cancer.Hundred and thirteen patients with a diagnosis of metastatic colorectal cancer were treated with oxaliplatin-based chemotherapy. ERCC1 codon 118C/T and XRCC1 codon 399A/G polymorphisms were tested by real-time polymerase chain reaction (RT-PCR) method in peripheral blood lymphocytes of these patients. Disease control rates and survivals were compared by types of genotypes.Analyses of the patterns of the polymorphism located at ERCC1 codon 118 showed that 55 (48.67%) patients were homozygous for C/C genotype, 15 (13.27%) were homozygous for the T/T genotype, and 43 (38.06%) were heterozygous for C/T genotype. Analyses of the polymorphism located at XRCC1 codon 399 showed that 61 (53.98%) patients were homozygous for A/A genotype, 13 (11.50%) were homozygous for the G/G genotype, and 39 (34.52%) were heterozygous for A/G genotype. After two cycles of chemotherapy, there was complete response (CR) in 1 patient, partial response (PR) in 24 patients, and stable disease (SD) in 56 patients. Altogether in 81 (71.68%) patients the disease was controlled after chemotherapy. Thirty-two (28.32%) patients showed disease progression. After adjusting for some clinical factors, both the ERCC1 polymorphism and the XRCC1 polymorphism lost their roles in predicting DCR (P = 0.662, P = 0.631) and MST (P = 0.692, P = 0.572). But the combination of ERCC1 and XRCC1 polymorphisms was significantly associated with DCR (P = 0.01) and MST (P = 0.000) independently.This is the first study which showed that polymorphisms of ERCC1 and XRCC1, in combination not individually, were independent predictors for DCR and OS. This may contribute to the selection of patients who would benefit from oxaliplatin-based chemotherapy for metastatic colorectal cancer.

To assess whether the polymorphism of ERCC1 Asn118Asn (C → T) had effects on cancer response to chemotherapy and outcome in Chinese patients treated with oxaliplatin as first-line chemotherapy regimen for advanced colorectal cancer. ERCC1 Asn118Asn polymorphism was analyzed in 99 patients with stages III and IV advanced colorectal cancer treated with oxaliplatin-based chemotherapy. For all of the patients, ERCC1 Asn118Asn genotype was analyzed for associations with treatment response and time to disease progress (TTP). The allele frequencies of the ERCC1 gene codon 118 were C/C 50.51% (50/99), C/T 41.41% (41/99), T/T 8.08% (8/99), respectively. Patients with C/C genotype showed higher response rate than those with C/T + T/T (OR = 3.764, 95% CI: 1.310–10.813). The median TTP of all patients was 7 months (95% CI: 5.569–8.431). Patients with C/C genotype showed a median TTP of 10 months (95% CI: 8.924–11.076), which was longer than 5 months (95% CI: 4.424–5.576) in patients with C/T + T/T genotypes. Our results showed a link between ERCC1 Asn118Asn genetic polymorphism and cancer response to oxaliplatin-based chemotherapy and time to disease progress in Chinese patients with advanced colorectal cancer. ERCC1 Asn118Asn genotyping may be of predictive benefit in selecting treatment regimen for advanced colorectal cancer.

The mechanism of action of oncogenic or tumor suppressor microRNAs is not well understood. We examined the microRNA expression profile in completely resected lung adenocarcinoma and examined the associated response to erlotinib. The lung adenocarcinoma tissue and adjacent normal lung parenchyma of 226 stage IIB and IIIA patients who underwent complete resection were obtained for two separate retrospective cohorts. In cohort 1 (119 patients; 80 with epidermal growth factor receptor (EGFR) mutations and 39 without), miRNA microarrays were used to identify EGFR-related miRNAs and their association with survival. In cohort 2 (107 patients with EGFR mutations), the miRNAs and their association with survival and response to erlotinib were analyzed by qRT-PCR. Cox proportional hazards regression was used to evaluate the effect of treatment on survival. As a result, erlotinib is associated with a significant improvement in overall survival (P = 0.0075, cohort 1; P = 0.0372, cohort 2) and disease progression (P = 0.6929, cohort 1; P = 0.3347, cohort 2) in patients with reduced miRNA-21 expression. Additionally, miRNA-145 is strongly associated with overall survival (P = 0.0008, cohort 1; P = 0.0131, cohort 2) and progression-free survival (P = 0.0198, cohort 1; P = 0.0269, cohort 2). Understanding the response rate to erlotinib relative to miRNA-21 (77.3 vs. 41.7 %, P

Although a number of studies have indicated that the positive expression of nucleophosmin (NPM) and trefoil factor 3 (TFF3) is associated with oncogenesis and poor prognosis in several tumor types, the prognostic value of the co-expression of NPM and TFF3 in gastric cancer (GC) has not been fully elucidated. Therefore, in this study, we aimed to investigate the role of NPM and TFF3 in GC and determine their prognostic value. We retrospectively reviewed 108 patients who had undergone radical gastric tumor resection. The expression of NPM and TFF3 was detected by immunohistochemistry and the association of NPM and TFF3 with clinicopathological characteristics was investigated using the Chi-square test. Furthermore, univariate and multivariate analyses were conducted to determine the prognostic value of these markers. Of the 108 samples, NPM was positive in 57 (53%) and TFF3 was positive in 54 samples (50%). The positive expression of NPM was correlated with advanced tumor stage and recurrence (P=0.0333 and P

microRNAs have been implicated in regulating diverse cellular pathways. Although there is emerging evidence that some microRNAs can function as oncogenes or tumor suppressors, the role of microRNAs in mediating cancer progression remains unexplored. And whether expression levels of a panel of biologically relevant microRNAs can be used as prognostic or predictive biomarkers in radically resected non-small-cell lung carcinoma (NSCLC) patients still needs to be further validated. Our analyses involved two separated, retrospective cohorts. Firstly, microRNA expression profile was performed in a cohort consisted of 128 radically resected NSCLC patients [60 were positive to epidermal growth factor receptor (EGFR) mutation and 68 were negative] and 32 healthy providers to identify EGFR mutation-related microRNAs and to determine their association with survival. In addition, to validate our findings, we used quantitative reverse transcriptase polymerase chain reaction assays to measure microRNAs and assess their association with disease progression, survival, and response to gefitinib in an independent cohort of 201 patients with EGRF mutation. In radically resected NSCLC patients, the expression levels of miR-21, 10b in patients with EGFR mutation were much higher than those without mutation. We used Cox proportional-hazards regression to evaluate the effect of treatment on survival. In both univariate and multivariate analyses, gefitinib was associated with a significant improvement in overall survival in patients with reduced miR-21 expression. Thus, miR-21 expression emerged as an independent predictor of the response to gefitinib. Additionally, miR-10b is highly expressed in progressive disease compared with complete remission or stable disease (P < 0.001). However, miR-21 expression has no significant prognosis for disease progression (P = 0.720). Meanwhile, when overall survival was considered as the end point, miR-10b did not have a significant difference between different subgroups (P = 0.634). The expression patterns of microRNAs differ significantly between patients with positive and negative EGFR mutation. And the expression status of miR-21 and 10b in such patients is associated with disease progression, survival, and response to adjuvant therapy with gefitinib.

Gastric cancer (GC) is a highly aggressive malignant tumor. Its high mortality rate prompts the urgent need for novel therapeutic agents. The aim of this study is to detect the expression of CRM1 in GC, which has not been reported to date. The expression of CRM1 in GC and adjacent noncancerous tissues (ANCT) of gastrectomy specimens from 120 GC patients was measured by immunohistochemistry. In addition, correlations between the CRM1 staining and the clinicopathologic features as well as survival were analyzed. Positive expression rates of CRM1 in GC and ANCT were 57.8 and 6.7 %, respectively. High expression of CRM1 was significantly associated with increased serum level of carcinoma embryonic antigen (CEA, P = 0.02) but not associated with that of carbohydrate antigen 19–9 (P = 0.38). CRM1 levels were correlated with more advanced tumor stages (P = 0.01), positive Her2 status (P = 0.01), and distant metastasis (P = 0.02). Univariate analysis showed that CEA (P = 0.0076), TNM stage (P = 0.0001), metastasis (P = 0.027), and CRM1 expression (P = 0.0019) were significant risk factors affecting overall survival of GC patients. The multivariate analysis indicated that the CRM1 was an independent indicator for GC survival (P = 0.0048). The current results indicated that CRM1 expressed in a subpopulation of GC with aggressive behavior and could serve as a prognosis marker for poor outcome.

Cytokeratin 19 (CK-19) is a prognostic indicator of recurrence and metastasis of hepatocellular carcinoma (HCC) following radical resection. To investigate the role of CK-19 in assessment of early recurrence and prognosis in patients with hepatitis B virus (HBV)-related HCC following radical resection. In total, 235 patients with HBV-related HCC (age, 15–82 years; mean age, 54 ± 10 years) undergoing radical resection were screened for inclusion from January 2005 to December 2010. Malignant tissues and adjacent non-malignant tissues were sampled during surgery, and CK-19 and Ki-67 expression was determined by tissue microarray and immunohistochemistry. CK-19 mRNA levels in 30 randomly selected frozen HCC specimens were examined by reverse transcription polymerase chain reaction from January 2011 to June 2011. Correlations of CK-19 and Ki-67 expression with tumor recurrence, metastasis, disease-free survival (DFS), and overall survival (OS) were analyzed. Elevated CK-19 expression was correlated with early recurrence (P = 0.001), shorter DFS (P = 0.001), and reduced OS (P = 0.010). CK-19 expression was correlated with the Ki-67 index (P = 0.037), histological differentiation (P = 0.016), focal number (P = 0.044), and blood vessel tumor embolism (P = 0.002). Patients with metastasis within 1 year exhibited stronger CK-19 expression than did patients without metastasis (P < 0.05). Furthermore, early recurrence was associated with elevated CK-19 mRNA levels (χ2 = 5.761, P = 0.016).When confirmed by a low alpha-fetoprotein concentration (

Summary PRINCIPLES: Platinum agents cause DNA cross-linking and oxidative damage. Genetic polymorphisms of GSTP1 and XRCC1 involved in glutathione metabolic and DNA repair pathways may explain inter individual differences in chemosensitivity and clinical outcome in NSCLC patients treated with platinum-based regimens. METHODS: We used DNA sequencing methods to evaluate genetic polymorphisms of the GSTP1A313G and XRCC1G28152A in 111 patients with stage IV NSCLC treated with platinum-based chemotherapy. Clinical response was evaluated according to RECIST criteria after 2–3 cycles of chemotherapy and time to progression (TTP) was calculated from the time of initial treatment to disease progression. RESULTS: GSTP1A313G and XRCC1G28152A polymorphisms, both alone and in combination, were significantly associated with response to treatment and clinical outcome (p

e12007 Background: Resistance to docetaxel, a chemotherapy drug for breast cancer treatment, occurs in about 50% of patients, and the underlying molecular mechanisms of drug resistance are not fully understood. Gene regulation through miR-141 has been shown to play an important role in cancer drug resistance. This study investigated the role of miR-141 expression in breast cancer cells of acquired docetaxel resistance. Methods: We detected miR-141 expression in docetaxel-resistant (MCF-7/DTX, MDA-MB-231/DTX) and docetaxel-sensitive (MCF-7, MDA-MB-231) breast cancer cells and then focused on its roles in regulation of docetaxel chemoresistance. We also identified EIF4E as a novel target of miR-141 by luciferase assay. Results: Inhibition of miR-141 enhanced response to docetaxel in MCF-7/DTX and MDA-MB-231/DTX cells, respectively; whereas overexpression of miR-141 confered the resistance in MCF-7, MDA-MB-231 cells, respectively. By directly targeting EIF4E mRNA, miR-141 acts on genes that are necessary for...

The aim of this study was to evaluate the predictive value of the polymorphism Glutathione S-transferase P1 (GSTP1) Ile(105)Val on oxaliplatin/5-FU-based chemotherapy in advanced gastric cancer. Patients with advanced gastric cancer accepted oxaliplatin/5-FU-based chemotherapy as first-line chemotherapy were investigated. GSTP1 Ile(105)Val polymorphism was detected by TaqMan-MGB probe allelic discrimination method. Response to treatment was assessed by disease controlled rate. Time to progression, overall survival and toxicities were recorded. Final patient outcomes were as follows: the allele frequencies of GSTP1 were (105)Ile/(105)Ile 52%, (105)Ile/(105)Val 41% and (105)Val/(105)Val 7%. For patients with (105)Ile/(105)Ile and those with at least one (105)Val allele, disease control rate was 39% and 71% (P=0.026), respectively; median time to progression was 4.0 and 7.0 months (P=0.002); median overall survival time was 7.0 and 9.5 months (P=0.002). Neurological toxicity was more frequently occurred in patients with two (105)Ile alleles (P=0.005). In conclusion, patients with at least one (105)Val allele have better prognosis and response to oxaliplatin/5-FU-based regimen as first-line treatment for patients with advanced gastric cancer.