Predictable factors for lymph node metastasis in early gastric cancer analysis of clinicopathologic factors and biological markers.

Predicting lymph node metastasis (LNM) accurately is very important to decide treatment strategies preoperatively. The aim of this study was to explore risk factors that predict the presence of LNM in early gastric cancer (EGC). A total of 230 patients with EGC who underwent curative gastrectomy with lymph adenectomy at Xinhua Hospital from January 2006 to July 2014 were retrospectively reviewed. We studied the relationship between clinicopathological factors, biological markers (p53, ki67, nm23, vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), E-cadherin (E-cad), beta-catenin (b-catenin), glutathione S-transferase (GST), and topoisomerase II (Topo II)), and LNM of EGC patients by chi-square test and logistic regression analysis. Meta-analyses were further conducted to review the effects of the proteins (P53, ki67, E-cad, and b-catenin) on LNM in ECG patients. LNM was detected in 42 (18.3 %) of 230 patients. Incidences of LNM was distinct in different tumor size (p = 0.044), depth of submucosal invasion (p < 0.0001), and P53 overexpression (p = 0.004). Multivariate analysis further indentified that large tumor size (≥20 mm, odds ratio (OR) = 2.168, p = 0.041), submucosa (OR = 4.000, p = 0.0005), and P53 overexpression (OR = 3.010, p = 0.022) were independent risk factors of LNM in EGC patients. The meta-analysis revealed a significantly statistical association of P53, ki67, and b-catenin with an increased risk of LNM in EGC patients (P53, OR = 1.81, p = 0.017; ki67, OR = 2.53, p = 0.0003; b-catenin, OR = 0.53, p = 0.01). Tumor size (≥20 mm), the depth of invasion (submucosa), and P53 overexpression may be helpful predictors of LNM in EGC patients. Furthermore, the results of meta-analysis revealed that P53, ki67 overexpression, and abnormal expression of b-catenin may be associated with LNM in EGC. The results need further validation in single large studies.

SHMT1 C1420T polymorphism contributes to the risk of non-Hodgkin lymphoma: evidence from 7309 patients.

BACKGROUND: Serine hydroxymethyltransferase 1 (SHMT1) is a key enzyme in the folate metabolic pathway that plays an important role in biosynthesis by providing one carbon unit. SHMT1 C1420T may lead to the abnormal biosynthesis involved in DNA synthesis and methylation, and it may eventually increase cancer susceptibility. Many epidemiologic studies have explored the association between C1420T polymorphism and the risk of non-Hodgkin lymphoma (NHL), but the results have been contradictory. Therefore, we performed this meta-analysis to evaluate the relationship. METHODS: The meta-analyses were conducted to evaluate the effect of SHMT1 C1420T polymorphism on NHL risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to measure the strength of the association. RESULTS: Eight studies encompassing 3232 cases and 4077 controls were included. A statistically significant association was found between SHMT1 C1420T polymorphism and NHL risk under the allelic comparison (T vs. C: OR = 1.09, 95% CI 1.01-1.17); a borderline association was found between SHMT1 C1420T polymorphism and NHL risk under the homozygote model (TT vs. CC: OR = 1.18, 95% CI 1.00-1.39) and the dominant model (CT+TT vs. CC: OR = 1.10, 95% CI 1.00-1.21). CONCLUSION: SHMT1 C1420T polymorphism may be associated with NHL risk, which needs to be validated in large, prospective studies.

[Trastuzumab in combination with chemotherapy versus chemotherapy alone for first-line treatment of HER2-positive advanced gastric or gastroesophageal junction cancer: a Phase III, multi-center, randomized controlled trial, Chinese subreport].

OBJECTIVE: To evaluate the efficacy and safety of trastuzumab in combination with chemotherapy versus chemotherapy alone in the first-line treatment of HER-2-positive advanced gastric or gastro-oesophageal junction cancer. METHODS: Fifteen Chinese research centers are involved in the BO18255 (ToGA) study. Patients with gastric or gastro-oesophageal junction cancer were eligible for inclusion if their tumor showed overexpression of HER-2 protein by immunohistochemistry +++ or FISH-positive. Patients were randomly assigned in a 1:1 ratio to receive a chemotherapy regimen consisting of capecitabine or 5-FU plus cisplatin or chemotherapy in combination with intravenous trastuzumab. The primary endpoint was overall survival. RESULTS: Eighty-five Chinese patients were enrolled in this study, of whom 84 were included in the primary analysis: trastuzumab plus chemotherapy (FP/H) (n = 36) and chemotherapy alone (FP)(n = 48). The median follow-up was 15.2 months in the FP/H group and 14.2 months in the FP group. The median survival time was 12.6 months in the FP/H group compared with 9.7 months in the FP group [hazard ratio 0.72, 95%CI (0.40; 1.29)]. Grade 3/4 adverse events were higher in the FP/H(63.9%)than FP (47.9%) groups, including neutropenia, vomiting and nausea. Two mild cardiac adverse events occurred in the FP/H group. Severe adverse events occurred in 3 cases of both two groups, respectively. CONCLUSIONS: Addition of trastuzumab to chemotherapy is well tolerated and shows improved survival in Chinese patients with advanced gastric or gastro-oesophageal junction cancer. These results are consistent with the results of ToGA whole population trial. Trastuzumab in combination with chemotherapy can be considered as a new option for patients with HER-2-positive advanced gastric or gastro-oesophageal junction cancer.

A Retrospective Case Series Of High-Intensity Focused Ultrasound (HIFU) In Combination With Gemcitabine And Oxaliplatin (Gemox) On Treating Elderly Middle And Advanced Pancreatic Cancer.

PURPOSE: This retrospective study was conducted to evaluate the safety and efficacy of high-intensity focused ultrasound (HIFU) ablation combined with Gemcitabine and Oxaliplatin (Gemox) for the treatment of middle and advanced pancreatic cancer in elderly patients. METHODS: Forty-seven patients with pancreatic cancer treated with HIFU and Gemox were evaluated for inclusion, and 38 cases were finally included. The primary endpoint was safety. Secondary endpoints included the response rate, the clinical benefit response (CBR), overall survival (OS), progression-free survival (PFS). RESULTS: After combination therapy of HIFU and Gemox, severe complications were rarely reported, and no treatment-related death occurred. The rate of three or four-degree myelosuppression was low, and no obvious impairment of hepatorenal function was observed. Pancreatitis and gastrointestinal injury did not occurred. The disease control rate (DCR) was estimated to be 76.3%, including complete remission (CR), partial remission (PR), stable disease (SD) in 1, 6, 22 cases, respectively. And the objective response rate (ORR) was 18.4%. The clinical benefit rate (CBR) was 68.4%, with the pain significantly relieved (P<0.01). The serum level of CA19-9 showed significant changes after HIFU treatment. The median overall survival (OS) was 12.5 months, with a 6-month and 12-month OS rate of 82.13% and 59.34%, respectively. Stratified analyses did not reveal any significant difference between patients in different stages. CONCLUSION: Elderly patients (≥ 60 years old) with pancreatic cancer would experience tolerable toxicity and obtain good clinical benefits from the combination therapy of HIFU ablation and Gemox.

A case report of targeted therapy with apatinib in a patient with advanced gastric cancer and high serum level of alpha-fetoprotein.

BACKGROUND: Alpha-fetoprotein (AFP) is an important marker for hepatocellular carcinoma, and the detection of serum AFP is currently the principle method for the diagnosis of hepatocellular carcinoma. The prevalence of gastric cancer (GC) with high level of serum AFP is extremely rare, but has unique clinical features. CASE SUMMARY: We herein present a rare case with GC and high level of serum AFP. A 64-year-old Chinese female underwent gastrectomy was diagnosed as gastric adenocarcinoma and the pathological stage was T1bN0M0, IA. With the progression of disease, the tumor widely metastasized and the serum AFP level increased progressively with the highest level of 3396 ng/mL. She successively entered into 3 lines palliative systematic chemotherapy and fourth-line targeted therapy of apatinib, a small molecule tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2. Although previous studies suggested that the prognosis of this special type of GC was poor, this patient lived for 22 months after tumor transfer. Apatinib kept her progression-free survival for 5 months, and the overall survival was 4.5 years. CONCLUSION: So, we speculate that maybe we can focus apatinib on serum AFP elevated GC patients.

Expression of CD44 in pancreatic cancer and its significance.

BACKGROUND: CD44 is a potentially interesting prognostic marker and therapeutic target in pancreatic cancer. The expression of CD44 has been reported to correlate with poor prognosis of pancreatic cancer in most literatures. The purpose of this study is to investigate the roles of CD44 in pancreatic caner, and their correlation with the prognosis of pancreatic cancer patients. METHODS: 67 pancreatic cancer samples were collected in Xinhua hospital affiliated to Shanghai Jiaotong University dating from Jan 2010 to Dec 2012. Immunohistochemistry was applied to test the expression of CD44 in pancreatic cancer. The clinical data of the patients were collected including their gender, age, the histology and location, lymph node metastasis and so on. The correlation between the CD44 expression and the clinicopathological factors of patients with pancreatic cancer was analyzed by the software SPSS 13.0. We devise and synthesis of effectively interference of shRNA sequence of CD44, which was transefected to the pancreatic cancer cells PANC-1. Colony formation assay, cell migration assays and western blot were performed. RESULTS: The positive rates of CD44 expression in pancreatic samples were 73.1% (49/67). Univariate analysis showed that there were a significant differences between the CD44 expression and the pancreatic cancer' T staging, TNM staging, lymph node metastasis, the differentiation degree, tumor location (P < 0.05). The Cox proportional hazards model showed that differentiation, CD44 expression and nerve invasion were independent prognostic factors. Knockdown of CD44 expression in pancreatic cancer cells led to decreased cellular proliferation and migration ability, accompanied by downregulation of p-ERK and p-AKT. CONCLUSION: CD44 were related to the distant metastasis and aggressive malignant behaviors of pancreatic cancer. CD44 may regulate tumorigenesis and cancer metastasis partially via PI3K/AKT or MAPK/ERK regulatory pathway.

Oncogenic role of the chromobox protein CBX7 in gastric cancer.

BACKGROUND: Chromobox 7 (CBX7) is a Polycomb family protein that extends the lifespan of normal human cells via downregulating the expression of INK4a/ARF tumor suppressor locus. It was found that CBX7 expression was upregulated in lymphoma, but downregulated in some other human malignancies. The role of CBX7 in most types of cancer is still not clear. The purpose of this study is to investigate the role of CBX7 in gastric cancer. METHODS: The expression of CBX7 and its potential target protein p16(INK4a) in gastric cancer cell lines and gastric tumors was assayed by Western blot analysis and immunohistochemistry(IHC). The correlations between CBX7 expression and p16(INK4a), clinicopathological characteristics, and prognosis were analyzed. Gastric cancer cell line SGC-7901 was transfected with CBX7 siRNA expressing plasmids, and the expression of various proteins was analyzed by Western blot analysis. Cellular senescence, anchorage independent growth, and cell migration assays were performed to determine the functional role of CBX7 in gastric cancer cells. RESULTS: CBX7 was found to be overexpressed in gastric cancer cell lines and gastric tumors. Overexpression of CBX7 in gastric cancer tissues correlated with patients' age, clinical stage and lymph node metastasis. Knockdown of CBX7 expression in gastric cancer cells led to increased cellular senescence, decreased cellular proliferation and migration ability, accompanied by upregulation of p16(INK4a). CONCLUSIONS: CBX7 acts as an oncogene in the carcinogenesis and progression of gastric cancer, and it may regulate tumorigenesis, cell migration and cancer metastasis partially via p16(INK4a) regulatory pathway.