Relationship between co-stimulatory molecule B7-H3 expression and gastric carcinoma histology and prognosis

AIM:To investigate the expression of co-stimulatorymolecule B7-H3 in gastric carcinoma and adenomatissue as well as normal gastric tissue and to explore therelationship between B7-H3 expression and pathologicalfeatures and prognosis of gastric carcinoma.METHODS:B7-H3 expression was detected in 102samples of human gastric carcinoma and 10 samples ofgastric adenoma and 10 samples of normal gastric tissueby immunohistochemical assay.Correlation betweenthe expression of B7-H3 and the patients'age,sex,gastric carcinoma locus,tumor size,tissue type,tumorinfiltration depth,differentiation degree,lymph nodemetastasis,and survival time was analyzed.RESULTS:B7-H3 was expressed in all gastric adenomasamples and in 58.8% samples of gastric carcinoma.B7-H3 expression in gastric carcinoma samples wasnot related with the patients'age,sex,lymph nodemetastasis,and tumor size(P>0.05),but with thesurvival time,infiltration depth of tumor and tissue type.CONCLUSION:Detection of B7-H3 expression in gastriccarcinoma tissue is beneficial to the judgment of theprognosis of gastric carcinoma patients and the choice oftreatment.

High expression of CD11c indicates favorable prognosis in patients with gastric cancer

AIM: To determine the relationship between CD11 c expression level and prognosis in patients with gastric cancer(GC).METHODS: This retrospective survival study was performed from July 31,2008 to June 30,2014. Our study inclusion criteria included all the patients with GC who underwent surgical resection between January 1998 and December 2009 in the Third Affiliated Hospital of Soochow University. CD11 c expression levels in 140 patients with GC at different UICC stages were evaluated using immunohistochemistry,and GC tissues from 16 cases were further verified by q RTPCR. The χ2 test was used to compare the patientand disease-related factors between the low CD11 c expression group and the high expression group. Univariate probabilities of overall survival(OS) and disease-free survival(DFS) were assessed using the Kaplan-Meier method. The log rank test was used to compare survival curves. Different multivariate COX models were used to estimate the association between CD11 c expression and both death and recurrence riskin GC patients.RESULTS: The average CD11 c expression level was 5.1 ± 1.8/high power field(HPF) in 10 gastritis samples,4.5 ± 2.3/HPF in 10 gastric polyp samples and 9.7 ± 6.3/HPF in 140 gastric cancer samples,respectively. The CD11 c expression level was significantly decreased from UICC stage Ⅰ to stage Ⅳ(stage Ⅰ: 16.0 ± 7.4,stage Ⅱ: 10.4 ± 5.5,stage Ⅲ: 9.4 ± 6.1,stage Ⅳ: 5.3 ± 3.2,P < 0.001). Patients in the high CD11 c expression group had a greater 3- and 5-year OS probability and longer median survival time compared with the low CD11 c expression group,(67.7% vs 39.2%; 51.4% vs 29.0%; 67.0 mo vs 28.0 mo; χ2 = 6.80,P = 0.009),and had a greater 3- and 5-year DFS probability and longer median DFS time(63.7% vs 24.0%; 49.1% vs 11.9%; 64.0 mo vs 18.0 mo; χ2 = 15.39,P < 0.001). Patients with high CD11 c high expression had a reduced risk of death(HR = 0.56,95%CI: 0.33-0.98,P < 0.05) and relapse(HR = 0.39,95%CI: 0.23-0.67,P < 0.01) compared with patients with low CD11 c expression after adjustment of potential confounders,with the exception of tumor size. However,the protective effect related to death(HR = 0.90,95%CI: 0.49-1.67,P = 0.749) and relapse(HR = 0.65,95%CI: 0.36-1.19,P = 0.160) disappeared when tumor size was incorporated into the model.CONCLUSION: High expression of CD11 c decreased the risk of death and relapse,and may be regarded as an alternative indicator of favorable prognosis in patients with GC.

Paclitaxel based vs oxaliplatin based regimens for advanced gastric cancer

AIM:To compare the efficacy and safety of paclitaxel combined with fluorouracil plus cisplatin(PCF),and oxaliplatin combined with fluorouracil plus leucovorin(FOLFOX-4) regimens for advanced gastric cancer(AGC).METHODS:Ninety-four patients with AGC were randomly assigned to receive paclitaxel(50 mg/m2 iv) on days 1,8 and 15,cisplatin(20 mg/m2 iv) and ? uorouracil(750 mg/m2 iv) on days 1-5,or oxaliplatin(85 mg/m2 iv) and leucovorin(200 mg/m2 iv) on day 1,followed by bolus fluorouracil(400 mg/m2 iv) and fluorouracil(600 mg/m2 iv) on days 1 and 2.The primary end point was the 1-year survival time.RESULTS:The overall response rate(ORR) of the pa-tients was 48.0% and 45.5% to PCF and FOLFOX-4,respectively.The disease control rate(DCR) of PCF and FOLFOX-4 was 82.0% and 81.8%,respectively.The median survival times(MSTs) of the patients were 10.8 and 9.9 mo,respectively,after treatment with PCF and FOLFOX-4.The 1-year survival rate of the patients was 36.0% and 34.1%,respectively,after treatment with PCF and FOLFOX-4.No significant difference was observed in ORR,DCR,MST or 1-year survival rate between the two groups.The most common adverse events were anemia,nausea and vomiting,and grade 3/4 alopecia in PCF treatment group,and anemia,grade 1/2 neurotoxic effect and grade 3/4 neutropenia in FOLFOX-4 treatment group.CONCLUSION:Patients with AGC have a similar response rate to PCF and FOLFOX-4 regimens with a similar survival rate.The PCF and FOLFOX-4 regimens are efficacious and tolerable as a promising therapy for AGC.

Famitinib versus placebo in the treatment of refractory metastatic colorectal cancer:a multicenter,randomized,double-blinded,placebo-controlled,phaseⅡclinical trial

Background: Metastatic colorectal cancer(mCRC) patients with progressive disease after all available standard therapies need new medication for further treatment. Famitinib is a small-molecule multikinase inhibitor, with promising anticancer activities. This multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial was designed to evaluate the safety and efficacy of famitinib in mCRC.Methods: Famitinib or placebo was administered orally once daily. The primary endpoint was progression-free survival(PFS). Secondary endpoints included objective response rate(ORR), disease control rate(DCR), overall survival(OS), quality-of-life(QoL), and safety.Results: Between July 18,2012 and Jan 22,2014, a total of 167 patients were screened, and 154 patients were randomized in a 2:1 ratio to receive either famitinib(n = 99) or placebo(n = 55). The median PFS was 2.8 and 1.5 months in the famitinib and placebo groups(hazard ratio = 0.60,95% confidence interval = 0.41-0.86, P = 0.004). The DCR was 59.8% and 31.4%(P = 0.002) and the ORR was 2.2% and 0.0%(P = 0.540) in the famitinib and placebo groups,respectively. The most frequent grade 3-4 adverse events were hypertension(11.1%), hand-foot syndrome(10.1%),thrombocytopenia(10.1%) and neutropenia(9.1%). Serious adverse events occurred in 11(11.1%) patients in the famitinib group and 5(9.1%) in the placebo group(P = 0.788). The median OS of the famitinib and placebo groups was 7.4 and 7.2 months(P = 0.657).Conclusion: Famitinib prolonged PFS in refractory mCRC patients with acceptable tolerability.Trial registration This study was registered on ClinicalTrials.gov(NCT01762293) and was orally presented in the 2015 ASCO-Gastrointestinal

Mechanism of T cell regulation by microRNAs

MicroRNAs （miRNAs） are small, non-coding single-stranded RNAs that can modulate target gene expression at post- transcriptional level and participate in cell proliferation, differentiation, and apoptosis. T cells have important functions in acquired immune response; miRNAs regulate this immune response by targeting the mRNAs of genes involved in T cell developmentp proliferationj differentiationp and function. For instancep miR-181 family members function in progression by targeting Bcl2 and CD69, among others. MiR-17 to miR-92 clusters function by binding to CREB 1, PTEN, and Bim. Considering that the suppression ofT cell-mediated immune responses against tumor cells is involved in cancer progression, we should investigate the mechanism by which miRNA regulates T cells to develop new approaches for cancer treatment.

Metabolism of high density lipoproteins in liver cancer

Liver plays a vital role in the production and catabolism of plasma lipoproteins. It depends on the integrity of cellular function of liver, which ensures homeostasis of lipid and lipoprotein metabolism. When liver cancer occurs these processes are impaired and high-density lipoproteins are changed.

Combined Therapy against Recurrent Hemangiopericytoma:A Case Report

A patient with a seven-year history of recurrent metastatic hemangiopericytoma(HPC) was admitted.During his treatment,he received surgical resection,radiotherapy,radiofrequency hyperthermia and chemotherapy using combined doxorubicin,dacarbazin, vincristine,ginsenoside Rg3,and recombinant human endostatin.This synergistic method provides an encouraging model for treating HPC.

B7-H4 Expression and Increased Death Risk of Cancer Patients： A Meta-Analysis

OBJECTIVE The relationship between higher levels of B7-H4 expression and death risk of cancer patients remains to be clarified. In the current study, information from an ordinary scale and those from several outcome scales were combined to make a single estimate. PubMed databases were searched for survival studies on the hazard ratios （HR） of malignant tumors associated with higher B7-H4 expression from 1999 to 2010. METHODS The fixed effect model was used to estimate the combined HRs of six studies. Sensitivity analysis was performed to assess the stability. Publication bias was also estimated. Six studies that meet the inclusion criteria were identified; these studies reported the associations between the higher B7-H4 expression and death risk of cancer patients. RESULTS A 42% increase in death risk was observed in patients with higher B7-H4 expression （HR = 1.42; 95% confidence interval： 1.16-1.72）. Sensitivity analyses found the results robust. The analysis shows that higher levels of B7-H4 expression are associated with the death risk of patients suffering from various cancers. CONCLUSION B7-H4 may be a negative regulatory molecule for antitumor immune responses and a molecular target for tumor immunotherapy.

Three-year Follow-up on the Safety and Effectiveness of Rituximab Plus Chemotherapy as First-Line Treatment of Diffuse Large B-Cell Lymphoma and Follicular Lymphoma in Real-World Clinical Settings in China： A Prospective, Multicenter, Noninterventional Study

Background： Prospective real-life data on the safety and effectiveness of rituximab in Chinese patients with diffuse large B-cell lymphoma （DLBCL） or follicular lymphoma （FL） are limited. This real-world study aimed to evaluate long-term safety and effectiveness outcomes ofrituximab plus chemotherapy （R-chemo） as first-line treatment in Chinese patients with DLBCL or FL. Hepatitis B virus （HBV） reactivation management was also investigated. Methods： A prospective, multicenter, single-arm, noninterventional study of previously untreated CD20-positive DLBCL or FL patients receiving first-line R-chemo treatment at 24 centers in China was conducted between January 17, 2011 and October 31, 2016. Enrolled patients underwent safety and effectiveness assessments after the last rituximab dose and were followed up for 3 years. Effectiveness endpoints included progression-free survival （PFS） and overall survival （OS）. Safety endpoints were adverse events （AEs）, serious AEs, drug-related AEs, and AEs of special interest. We also reported data on the incidence of HBV reactivation. Results： In total, 283 previously untreated CD20-positive DLBCL and 31 FL patients from 24 centers were enrolled. Three-year PFS was 59% （95% confidence interval [CI]： 50-67%） for DLBCL patients and 46% （95% CI： 20-69%） for FL patients. For DLBCL patients, multivariate analyses showed that PFS was not associated with international prognostic index, tumor maximum diameter, HBV infection status, or number ofrituximab treatment cycles, and OS was only associated with age 〉60 years （P 〈 0.05）. R-chemo was well tolerated. The incidence of HBV reactivation in hepatitis B surface antigen （HBsAg）-positive and HBsAg-negative/hepatitis B core antibody-positive patients was 13% （3/24） and 4% （3/69）, respectively. Conclusions： R-chemo is effective and safe in real-world clinical practice as first-line treatment for DLBCL and FL in China, and that HBV reactivation during R-chemo is manageable with preventive measures and treatment.