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Background: The prognosis of patients with advanced gastric cancer (AGC) remains poor, and no single chemotherapy regimen is recognized as a global standard. A phase II trial was conducted to determine the efficacy and tolerability of capecitabine and oxaliplatin (XELOX) given every 3 weeks in combination in patients with AGC. Methods: Patients with previously untreated AGC received intravenous oxaliplatin 130 mg/m2 over 2 h on day 1 plus oral capecitabine 1,000 mg/m2 twice daily on days 1–14, every 3 weeks. Treatment was continued for 8 cycles or until disease progression or intolerable toxicity. Results: Fifty patients were enrolled. In total, 210 cycles of XELOX were delivered. The OVERALL response rate was 42% (95% CI 28.6–56.7), with 2 complete and 19 partial responses. At 15.2 months of median follow-up, median time to progression and overall survival were 5.8 (95% CI 3.4–8.2) and 11.1 (95% CI 5.6–16.5) months, respectively. The most common hematological adverse event was neutropenia (56% of patients); grade 3–4 neutropenia was observed in 6 patients, with neutropenic fever in only 2 patients. The most common non-hematological toxicities were vomiting (34%), hand-foot syndrome (26%), diarrhea (24%) and neurosensory toxicity (22%). There were no treatment-related deaths. Conclusions: XELOX is active for the first-line treatment of AGC with a manageable tolerability profile. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The aim of this study is to evaluate the safety and efficacy of the combination of capecitabine and oxaliplatin (XELOX) as first-line treatment in Chinese patients with metastatic colorectal carcinoma (mCRC). Furthermore, we aimed to explore whether a maintenance therapy with oral capecitabine in patients who were non-progression to the XELOX regimen was able to improve the duration of disease control (DDC). One hundred twenty-four patients with mCRC received a 3-weekly regimen of oxaliplatin plus capecitabine (XELOX) as first-line treatment. Patients without progressive disease after six cycles of XELOX could stop treatment or continue to receive oral capecitabine until disease progression or unacceptable toxicity. A total of 637 cycles (median 6 cycles) of XELOX were given to 124 patients (males 58.1%, median age 52 years). The response rate was 49.1% (complete response in 11 patients and partial response in 50 patients). The median overall survival and progression-free survival were 20.0 and 8.0 months, respectively. Main drug-related grade 3–4 toxicities included neutrapenia (5.6%), nausea/vomiting (4%), thrombocytopenia (2.4%), diarrhea (2.4%) and hand–foot syndrome (2.4%). Among 62 patients achieving objective response or stable disease after at least 6 cycles of XELOX, there were 22 patients received oral capecitabine as maintenance therapy. The median DDC was significantly longer for maintenance therapy group than those of no maintenance group (14 vs. 9 months; P = 0.041). XELOX is a highly effective first-line treatment for Chinese mCRC patients. The response rate, TTP, and overall survival of patients treated with this regimen are similar to those treated with FU/leucovorin/oxaliplatin. Furthermore, our preliminary data show maintenance therapy with capecitabine for those patients without progressive disease after at least six cycles of XELOX can significantly improve DDC; and further prospective randomized control trial is warranted. [ABSTRACT FROM AUTHOR]

Background: To evaluate the efficacy and toxicity of an oxaliplatin, fluorouracil (5-FU), and folinic acid (FOLFOX-6) combination therapy in patients with advanced or recurrent gastric cancer. Methods: Patients with previously untreated advanced or recurrent gastric cancer received oxaliplatin 100 mg/m2 and leucovorin 400 mg/m2 (2-hour intravenous infusion) followed by a 5-FU bolus of 400 mg/m2 (10-min infusion) and then 5-FU 2,600–3,000 mg/m2 (46-hour continuous infusion). The chemotherapy was repeated every 14 days. Results: Fifty-one patients were enrolled in this study. Of these, 46 were assessable for efficacy, and all patients were assessable for toxicity. Three of 51 patients achieved a complete response, and 18 had partial responses, giving an overall response rate of 41.2%. Stable disease was observed in 11 (21.6%) patients and progressive disease in 14 (27.5%). The median time to progression was 5.4 months, and the median overall survival was 12.1 months. NCI-CTC grade 3/4 hematological toxicities were neutropenia and anemia in 9.8 and 7.8% of the patients, respectively. Grade 3 peripheral neuropathy was recorded in 3 (5.9%) patients. Other NCI-CTC grade 3 or 4 toxicities included diarrhea in 3 patients (5.9%) and vomiting in 5 (9.8%). There were no treatment-related deaths. Conclusions: This oxaliplatin/5-FU/folinic acid regimen shows good efficacy and an acceptable toxicity profile in advanced or recurrent gastric cancer patients; further clinical trials are warranted. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Metabolic inhibition via PFKFB3 inhibition has demonstrated considerable tumor inhibitory effects in various studies; however, PFKFB3 inhibition did not show satisfactory tumor inhibition when used in clinical trials. PFKFB3 is a crucial metabolic enzyme that is highly upregulated in cancer cells and directly affects tumor glycolysis. Here, we showed that PFKFB3 inhibition suppresses tumors in vitro and in vivo in immune-deficient xenografts. However, this inhibition induces the upregulation of PD-L1 levels, which inactivated cocultured T-cells in vitro, compromises anti-tumor immunity in vivo, and reduced anti-tumor efficacy in an immune-competent mouse model. Functionally, PD-1 mAb treatment enhances the efficacy of PFKFB3 inhibition in immunocompetent and hu-PBMC NOG mouse models. Mechanistically, PFKFB3 inhibition increases phosphorylation of PFKFB3 at residue Ser461, which increases interaction with HIF-1a, and their colocalization into the nucleus, where HIF-1a transcriptionally upregulate PD-L1 expression and causes subsequent tumor immune evasion. Higher phos-PFKFB3 correlated with higher PD-L1 expression, lower CD8 and GRZMB levels, and shorter survival time in ESCC patients. [ABSTRACT FROM AUTHOR]

Background: Long non-coding RNAs (lncRNAs) have emerged as critical regulators of tumor progression. However, the role and molecular mechanism of lncRNA XIST in gastric cancer is still unknown. Methods: Real-time PCR analysis was performed to measure the expression levels of lncRNA XIST in gastric cancer tissues and cell lines, the correlation between lncRNA XIST expression and clinicopathological characteristics and prognosis was analyzed in gastric cancer patients. The biological function of lncRNA XIST on gastric cancer cells were determined both in vitro and in vivo. The regulating relationship between lncRNA XIST and miR-101 was investigated in gastric cancer cells. Results: lncRNA XIST was significantly up-regulated in gastric cancer tissues and cell lines. Overexpression of lncRNA XIST was markedly associated with larger tumor size, lymph node invasion, distant metastasis and TNM stage in gastric cancer patients. Functionally, knockdown of lncRNA XIST exerted tumor-suppressive effects by inhibiting cell proliferation, migration and invasion in vitro and tumor growth and metastasis in vivo. Furthermore, an inverse relationship between lncRNA XIST and miR-101 was found. Polycomb group protein enhancer of zeste homolog 2 (EZH2), a direct target of miR-101, could mediated the biological effects that lncRNA XIST exerted. Conclusions: lncRNA XIST is up-regulated and is associated with aggressive tumor phenotypes and patient survival in gastric cancer, and the newly identified lncRNA XIST/miR-101/EZH2 axis could be a potential biomarkers or therapeutic targets for gastric cancer patients. [ABSTRACT FROM AUTHOR]

Background: Plenty of studies have demonstrated the prognostic value of various inflammation-based indexes in cancer. This study was designed to investigate the prognostic value of the C-reactive protein/albumin (CRP/Alb) ratio in esophageal squamous cell carcinoma. Methods: A retrospective study of 423 cases with newly diagnosed esophageal squamous cell carcinoma was conducted. We analyzed the association of the CRP/Alb ratio with clinicopathologic characteristics. The prognostic value was explored by univariate and multivariate survival analysis. In addition, we compared the discriminatory ability of the CRP/Alb ratio with other inflammation-based prognostic scores by evaluating the area under the receiver operating characteristics curves (AUC), including the modified Glasgow Prognostic Score (mGPS), neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR). Results: The optimal cut-off value was identified to be 0.095 for the CRP/Alb ratio. A higher level of the CRP/Alb ratio was associated with larger tumor size (P < 0.001), poorer differentiation (P = 0.019), deeper tumor invasion (P = 0.003), more lymph node metastasis (P = 0.015), more distant metastasis (P < 0.001) and later TNM stage (P < 0.001). The CRP/Alb ratio was identified to be the only inflammation-based prognostic score with independent association with overall survival by multivariate analysis (P = 0.031). The AUC value of the CRP/Alb ratio was higher compared with the NLR and PLR, but not mGPS at 6, 12 and 24 months of follow-up. In addition, the CRP/Alb ratio could identify a group of patients with mGPS score of 0 who had comparable overall survival with those with mGPS score of 1. Conclusions: The CRP/Alb ratio is a novel but promising inflammation-based prognostic score in esophageal squamous cell carcinoma. It is a valuable coadjutant for the mGPS to further identify patients' survival differences. [ABSTRACT FROM AUTHOR]

Background: Primary small cell carcinoma of the esophagus (SCCE) is a highly aggressive disease characterized by early dissemination and poor prognosis. Because of the rarity of this disease, few previous studies have investigated the biomarkers associated with its prognosis. Leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) is a stem cell marker and a member of the canonical Wnt-signaling cascade. However, the clinical role of Lgr5 in SCCE remains unknown. Methods: Tissue sections were obtained from 44 patients diagnosed with SCCE and expression of Lgr5 was examined by immunohistochemistry. The correlations between Lgr5 expression, and clinical parameters and prognostic significance were evaluated. Results: Lgr5 was expressed in SCCE cancer tissues. High Lgr5 expression was significantly correlated with lymph node metastasis (p = 0.003), late stage (p = 0.003) and unfavorable response to chemotherapy (p = 0.013) according to RECIST 1.0 criteria. Patients with higher Lgr5 expression levels had shorter overall survival times than those with lower expression levels. Conclusions: These results demonstrated that overexpression of Lgr5 was significantly correlated with lymph node metastasis, tumor stage, and response to chemotherapy. Furthermore, high levels of Lgr5 expression appeared to be associated with poorer survival in patients with SCCE. [ABSTRACT FROM AUTHOR]

Background Paxillin (PXN) has been found to be aberrantly regulated in various malignancies and involved in tumor growth and invasion. The clinicopathological and prognostic significance of PXN in gastric cancer is still unclear. Methods The expression of PXN was determined in paired gastric cancer tissues and adjacent normal tissues by Western blotting and real-time PCR. Immunohistochemistry was performed to detect the expression of PXN in 239 gastric cancer patients. Statistical analysis was applied to investigate the correlation between PXN expression and clinicopathological characteristics and prognosis in patients. Additionally, the effects of PXN on gastric cancer cell proliferation and migration were also evaluated. Results PXN was up-regulated in gastric cancer tissues and cell lines as compared with adjacent normal tissues and normal gastric epithelial cell line GES-1. Overexpression of PXN was correlated with distant metastasis (P = 0.001) and advanced tumor stage (P = 0.021) in gastric cancer patients. Patients with high PXN expression tended to have poor prognosis compared with patients with low PXN expression (P < 0.001). Multivariate analysis demonstrated that PXN expression was an independent prognostic factor (P = 0.020). Moreover, ectopic expression of PXN promotes cell proliferation and migration in AGS cells whereas knockdown of PXN inhibits cell proliferation and migration in SGC7901 cells. Conclusions PXN plays an important role in tumor progression and may be used as a potential prognostic indicator in gastric cancer. [ABSTRACT FROM AUTHOR]

Background: A phase III clinical trial has already shown the survival benefits of postoperative chemotherapy in gastric cancer. However, there are limited published data concerning the elderly. This study aims to investigate the use of adjuvant chemotherapy for gastric cancer after D2 gastrectomy among the elderly and identify its impact on survival. Methods:We retrospectively reviewed 360 patients who had undergone D2 gastrectomy, aged 65 years or older, with non-metastatic gastric cancer in a single institution. We analyzed the predictors and survival benefits of adjuvant chemotherapy use in the elderly. Further, we analyzed the survival benefits of adjuvant chemotherapy by dividing the patients into groups according to disease stages and chemotherapeutic regimens. Results: Among the 360 patients, only 34.7% of patients received adjuvant chemotherapy. Age, tumor location, lymph node involvement and tumor invasion were associated with the receipt of adjuvant chemotherapy. Adjuvant chemotherapy improved the overall survival for non-metastatic elderly patients (HR 0.60, 95%CI 0.42-0.83, P = 0.003). Significant survival benefits were found with adjuvant chemotherapy in stage III patients (HR 0.67, 95%CI 0.47-0.97, P = 0.033), but not in stage I patients or in stage II patients (HR 0.52, 95%CI 0.21-1.30 P = 0.161). Compared to adjuvant chemotherapy without platinum, no significant survival benefits were observed with platinum-containing chemotherapy (HR 0.84, 95%CI 0.49-1.45, P = 0.530). Besides adjuvant chemotherapy, other independent prognostic factors of survival included tumor location, tumor size, histologic grade, depth of tumor invasion, and lymph node status. Conclusions: This study demonstrated the survival benefits of adjuvant fluoropyrimidine-based chemotherapy among the elderly patients with non-metastatic gastric cancer after D2 gastrectomy. However, due to the limitations of this study, further well-designed prospective studies with large populations are needed to confirm these findings and identify the patients that can tolerate and benefit from adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Background: The development of pancreatic cancer is a process in which genes interact with environmental factors. We performed this study to determine the effects of the ABO blood group, obesity, diabetes mellitus, metabolic syndrome (MetS), smoking, alcohol consumption and hepatitis B viral (HBV) infection on patient survival. Methods: A total of 488 patients with pancreatic cancer were evaluated. Result: Patients who presented as chronic carriers of HBV infection were younger at disease onset (p=0.001) and more predominantly male (p=0.020) than those never exposed to HBV. Patients with MetS had later disease staging (p=0.000) and a lower degree of pathological differentiation (p=0.008) than those without MetS. In a univariate analysis, the ABO blood group, smoking and alcohol consumption were not associated with overall survival. HBsAg-positivity and elevated fasting plasma glucose were significantly associated with unfavorable survival though not in the multivariate analysis. The presence of MetS (HR: 1.541, 95% CI: 1.095-2.169, p=0.013), age ≥65, an elevated CA19-9 baseline level, TNM staging, the type of surgery, the degree of differentiation and chemotherapy were independently associated with overall survival. Conclusion: We report, for the first time, that patients with chronic HBV infection may represent a special subtype of pancreatic cancer, who have a younger age of disease onset and male dominancy. Patients with MetS had later disease staging and a poorer histological grade. Patients with MetS demonstrated significantly poorer survival. [ABSTRACT FROM AUTHOR]

Background: In this study, we established a hypothetical tumor-lodds-metastasis (TLM) and tumor-ratio-metastasis (TRM) staging system. Moreover, we compared them with the 7th edition of American Joint Committee on Cancer tumor-nodes-metastasis (AJCC TNM) staging system in gastric cancer patients after D2 resection. Methods: A total of 1000 gastric carcinoma patients receiving treatment in our center were selected for the analysis. Finally, 730 patients who received D2 resection were retrospectively studied. Patients were staged using the TLM, TRM and the 7th edition AJCC TNM system. Survival analysis was performed with a Cox regression model. We used two parameters to compare the TNM, TRM and TLM staging system, the -2log likelihood and the hazard ratio. Results: The cut points of lymph node ratio (LNR) were set as 0, 0-0.3, 0.3-0.6, 0.6-1.0. And for the log odds of positive lymph nodes (LODDS), the cut points were established as ≤-0.5, -0.5-0, 0-0.5, >0.5. There were significant differences in survival among patients in different LODDS classifications for each pN or LNR groups. When stratified by the LODDS classifications, the prognosis was highly homologous between those in the according pN or LNR classifications. Multivariate analysis showed that TLM staging system was better than the TRM or TNM system for the prognostic evaluation. Conclusions: The TLM system was superior to the TRM or TNM system for prognostic assessment of gastric adenocarcinoma patients after D2 resection. [ABSTRACT FROM AUTHOR]

Background: Melanoma antigen D1 (MAGED1) is a member of the type II melanoma antigen (MAGE) family. The down-regulation of MAGED1 expression has been shown in breast carcinoma cell lines and in glioma stem cells and may play an important role in apoptosis and anti-tumorigenesis. However, there is no report on its clinical role in colorectal cancer (CRC). Methods: We examined the expression of MAGED1 by qPCR in colorectal cancer tissues and their adjacent nontumorous tissues taken from 6 cases and performed Western blotting and IHC analyses. In addition, we analyzed MAGED1 expression in 285 clinicopathologically characterized colorectal cancer patients. Results: MAGED1 expression was significantly down-regulated in colorectal cancer tissues compared with adjacent non-tumorous tissues and was associated with clinical stage (p < 0.001), T classification (p = 0.001), N classification (p < 0.001), M classification (p < 0.001) and pathologic differentiation (p = 0.002). Patients with lower MAGED1 expression had a shorter survival time than those with higher MAGED1 expression. Univariate and multivariate analyses indicated that MAGED1 expression was an independent prognostic factors (p < 0.001). Conclusions: MAGED1 may serve as a novel prognostic biomarker of human colorectal cancer. [ABSTRACT FROM AUTHOR]

Background: DNA polymerase η (pol η) is capable of bypassing DNA adducts produced by cisplatin or oxaliplatin and is associated with cellular tolerance to platinum. Previous studies showed that defective pol η resulted in enhanced cisplatin or oxaliplatin sensitivity in some cell lines. The purpose of the present study was to investigate the role of pol η protein expression in metastatic gastric adenocarcinoma. Methods: Four gastric adenocarcinoma cell lines were chosen to explore the relationship between pol η protein expression and oxaliplatin sensitivity by western blotting and MTT assay. Eighty metastatic gastric adenocarcinoma patients treated with FOLFOX or XELOX regimen as first-line chemotherapy were analyzed, corresponding pretreatment formalin-fixed paraffin-embedded tumor tissues were used to detect pol η protein expression by immunohistochemistry. Relationship between pol η protein expression and clinical features and outcome of these patients was analyzed. Results: A positive linear relationship between pol η protein expression and 48 h IC50 values of oxaliplatin in four gastric cancer cell lines was observed. Positivity of pol η protein expression was strongly associated with poor treatment response, as well as shorter survival at both univariate (8 versus 14 months; P < 0.001) and multivariate (hazard ratio, 4.555; 95% confidence interval, 2.461-8.429; P < 0.001) analysis in eighty metastatic gastric adenocarcinoma patients. Conclusions: Our study indicates that polη is a predictive factor of treatment response and survival of metastatic gastric adenocarcinoma patients treated with FOLFOX or XELOX as first-line chemotherapy. Therefore confirming the value of polη in studies with prospective design is mandatory. [ABSTRACT FROM AUTHOR]

The authors investigated the prevalence of hepatitis B virus (HBV) infection by using serologic markers in non‐Hodgkin lymphoma (NHL) compared with other types of cancers in Chinese patients.In this case‐control study, HBV and other hepatitis markers were compared between a study group and a control group. The study group included 587 patients with NHL (age range, 16–86 years), and the control group included 1237 patients (age range, 16–89 years) who were diagnosed with other cancers except liver cancer. An enzyme‐linked immunosorbent assay was used to test serum samples from both groups for HBV markers and other hepatitis markers.Logistic regression analysis showed that there was a higher prevalence of HBV infection in patients with the B‐cell subtype of NHL (30.2%) than in patients with other cancers (14.8%; odds ratio [OR], 2.6; 95% confidence interval [95% CI], 2.0–3.4); however, in patients with the T‐cell subtype of NHL, the HBV infection rate (19.8%) was similar to that among patients with other cancers (OR, 1.2; 95% CI, 0.8–1.8). A significant difference in HBV prevalence was found between B‐cell and T‐cell NHL (OR, 2.3; 95% CI, 1.4–3.6). In the patients with B‐cell NHL, those who were infected with HBV had a significantly earlier disease onset (9.5 years) than those who were not infected with HBV.The current results demonstrated that patients with B‐cell NHL, but not patients with T‐cell NHL, had a higher prevalence of HBV infection. HBV infection was associated with a significantly earlier disease onset (P < .001), a finding that suggested the possibility that HBV may play an etiologic role in the induction of B‐cell NHL. Cancer 2007. © 2007 American Cancer Society. [ABSTRACT FROM AUTHOR]