Jiuda Zhao

Associations between interleukin-1 polymorphisms and gastric cancers among three ethnicities

AIM To investigate the associations between interleukin (IL)-1B and IL-1RN polymorphisms and gastric cancers among the Tibet, Hui and Han ethnicities. METHODS Genomic DNA was extracted from peripheral blood of 210, 205, and 202 healthy volunteers and from 155, 158, and 197 gastric cancer patients from the Tibet, Hui, and Han populations, respectively. Polymorphisms in IL-1B and IL-1RN were analyzed by denaturing high-performance liquid chromatography. RESULTS Carriers of the IL-1B-31 CC genotype had an increased risk of intestinal type gastric cancer [odds ratio (OR) = 2.17, P = 0.037] in the Tibet ethnicity. Carriers of the IL-1B 2/L genotype had an increased risk of both intestinal and diffuse types of gastric cancer (OR = 2.08, 2.31, P = 0.007, 0.016, respectively) in the Hui ethnicity. In the Han population, carriers of the IL-1B-31 CC, IL-1B-511CT, TT genotypes had increased risk of intestinal type gastric cancer (OR = 2.51, 2.74, 5.66, P = 0.005, 0.002, 0.000, respectively). CONCLUSION IL-1B and IL-RN genotypes may differentially contribute to gastric cancer among the Tibet, Hui, and Han ethnicities in the Qinghai area of China.

Association of HER2 status with prognosis in gastric cancer patients undergoing R0 resection: A large-scale multicenter study in China

AIM To determine whether the positive status of human epidermal growth receptor 2 (HER2) can be regarded as an effective prognostic factor for patients with gastric cancer (GC) undergoing R0 resection. METHODS A total of 1562 GC patients treated by R0 resection were recruited. HER2 status was evaluated in surgically resected samples of all the patients using immunohistochemical (IHC) staining. Correlations between HER2 status and clinicopathological characteristics were retrospective analyzed. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard model, stratified by age, gender, tumor location and tumor-node-metastasis (TNM) stage, with additional adjustment for potential prognostic factors. RESULTS Among 1562 patients, 548 (positive rate = 35.08%, 95%CI: 32.72%-37.45%) were HER2 positive. Positive status of HER2 was significantly correlated with gender (P = 0.004), minority (P < 0.001), tumor location (P = 0.001), pathological grade (P < 0.001), TNM stage (P < 0.001) and adjuvant radiotherapy (74.67% vs 23.53%, P = 0.011). No significant associations were observed between HER2 status and disease free survival (HR = 0.19, 95%CI: 0.96-1.46, P = 0.105) or overall survival (HR = 1.19, 95%CI: 0.96-1.48, P = 0.118) using multivariate analysis, although stratified analyses showed marginally statistically significant associations both in disease free survival and overall survival, especially among patients aged < 60 years or with early TNM stages (I and II). Categorical age, TNM stage, neural invasion, and adjuvant chemotherapy were, as expected, independent prognostic factors for both disease free survival and overall survival. CONCLUSION The positive status of HER2 based on IHC staining was not related to the survival in patients with GC among the Chinese population.

Adjuvant chemotherapy with S-1 plus oxaliplatin improves survival of patients with gastric cancer after D2 gastrectomy: A multicenter propensity score-matched study

AIM To investigate the safety and efficacy of S-1 plus oxaliplatin (SOX) as an adjuvant chemotherapy regimen in gastric cancer (GC) after D2 dissection. METHODS GC Patients who underwent D2 gastrectomy from September 2009 to December 2011 in four Chinese institutions were enrolled. Patients with stage IB-IIIC GC, who received adjuvant SOX treatment were matched by propensity scores with those who underwent surgery alone and those who conducted capecitabine plus oxaliplatin (XELOX) regimen. Disease-free survival (DFS) and overall survival (OS) were compared among the groups. In addition, adverse events in SOX patients were analyzed. RESULTS Of 1944 GC patients who underwent D2 dissection, 867 were included for analysis. One hundred and seventeen patients treated with SOX were matched to 234 patients who conducted surgery alone. Fifty-seven patients treated with SOX were matched to 57 patients who received XELOX. The estimated five-year DFS was 57.5% in the adjuvant SOX group which was higher than that (44.6%) in the surgery alone group (P = 0.001); and the estimated five-year OS was 68.3% which was higher than that (45.8%) of surgery alone group (P < 0.001). Survival benefit was also revealed in stage III and > 60 years old subgroups (P < 0.001 and P = 0.015, respectively). Compared with XELOX regimen, SOX showed no significant difference in DFS (P = 0.340) and OS (P = 0.361). The most common ≥ 3 grade adverse events of SOX regimen were neutropenia (22.6%), leukopenia (8.9%) and thrombocytopenia (5.6%). CONCLUSION Compared with surgery alone, SOX regimen significantly improves the long-term survival and has acceptable toxicity in patients with stage IB-IIIC GC after D2 dissection. It may be a novel adjuvant chemotherapy regimen in GC patients.

Anlotinib: a novel multi-targeting tyrosine kinase inhibitor in clinical development

Anlotinib is a new, orally administered tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptors (PDGFR), and c-kit. Compared to the effect of placebo, it improved both progression-free survival (PFS) and overall survival (OS) in a phase III trial in patients with advanced non-small-cell lung cancer (NSCLC), despite progression of the cancer after two lines of prior treatments. Recently, the China Food and Drug Administration (CFDA) approved single agent anlotinib as a third-line treatment for patients with advanced NSCLC. Moreover, a randomized phase IIB trial demonstrated that anlotinib significantly prolonged the median PFS in patients with advanced soft tissue sarcoma (STS). Anlotinib also showed promising efficacy in patients with advanced medullary thyroid carcinoma and metastatic renal cell carcinoma (mRCC). The tolerability profile of anlotinib is similar to that of other tyrosine kinase inhibitors that target VEGFR and other tyrosine kinase-mediated pathways; however, anlotinib has a significantly lower incidence of grade 3 or higher side effects compared to that of sunitinib. We review the rationale, clinical evidence, and future perspectives of anlotinib for the treatment of multiple cancers.

Novel fluoropyrimidine-based chemotherapy for advanced well-differentiated neuroendocrine tumors: a clinical update

ABSTRACT Introduction: Patients with advanced well-differentiated neuroendocrine tumors (NETs) who have bulky and/or symptomatic and/or rapidly progressive disease require chemotherapy treatment. Areas covered: This review summarizes the accumulating evidence for treatment with fluorouracil-based chemotherapy in well-differentiated NETs. The main clinical studies, toxicity and predictors of fluorouracil- based chemotherapy regimens in well-differentiated NETs are discussed, along with the current issues, future research directions and therapeutic prospects. Expert opinion: Somatostatin analogs may control symptoms of hormone excess and tumor growth in patients with well-differentiated metastatic NETs, and biological therapies may improve progression-free survival for these patients. However, chemotherapy leads to higher objective response rates and symptom control by reducing tumor bulk. The low response rate and significant toxicities of conventional chemotherapy regimens limit their widespread use. Fortunately, some novel fluoropyrimidine-based treatment including fluorouracil, capecitabine, or S-1 based chemotherapy with or without antiangiogenic agents have been investigated in recent years. These treatments showed significant efficacy and less toxicity in pancreatic and non-pancreatic metastatic well-differentiated NETs. Additionally, non-pancreatic well-differentiated NETs have also achieved similar tumor response or survival comparable to pancreatic NETs. Moreover, some predictors of response to these treatment regimens have been evaluated.

Is it a protective factor of Helicobacter pylori infection in prognosis of all gastric cancer

Purpose - We aimed to assess whether Helicobacter pylori infection influences prognosis in gastric cancer patients (GC). Methods - We systematically searched MEDLINE, PubMed, EBSCO, EMBASE, and the Cochrane Library (CENTRAL) Register from inception to June 1, 2017. Overall survival (mean OS) or disease-free survival (mean DFS) in GC patients were calculated using the hazard ratio (HR) and 95% confidence intervals (95% CIs). Results - In total, 19 articles with 4,321 GC patients were enrolled. Helicobacter pylori infection is associated with longer OS (HR 0.73; 95% CI 0.60-0.89; P < 0.001) and DFS (HR 0.75; 95% CI 0.53-1.07; P = 0.002) in GC patients overall. For our subgroup analysis, the pooled HRs and 95% CIs were as follows: China (OS: HR 0.95; 95% CI 0.63-1.42; P = 0.804 and DFS: HR 0.88; 95% CI 0.50-1.56; P = 0.658), Europe (OS: HR 0.69; 95% CI 0.52-0.92; P = 0.010 and DFS: HR 0.62; 95% CI 0.32-1.17; P = 0.141), United States (OS: HR 0.77: 95% CI 0.56-1.06; P = 0.105), Korea (OS: HR 0.45; 95% CI 0.27-0.75; P = 0.002 and DFS: HR 0.45; 95% CI 0.24-0.83, P = 0.011), and Turkey (OS: HR 0.94; 95% CI 0.52-1.70; P = 0.839 and DFS: HR 0.95; 95% CI 0.53-1.71, P = 0.864). Moreover, for R0 or M0 patients, H. pylori infection is associated with better OS and DFS (P all values < 0.05). Conclusions - Helicobacter pylori infection has a better prognosis in GC patients from Korea and Europe. Helicobacter pylori infection has no association with prognosis for China, the United States, or Turkey. Also, H. pylori infection has a better prognosis in R0 resection or M0 GC patients.

Impact of High Altitude on Clinicopathological Features and Prognosis after R0 Resection for Gastric Cancer: A Population-Based Multicenter Study

Geographic variation has an important role in both carcinogenesis and prognosis of gastric cancer (GC). High altitude is a special hypoxic environment that is also correlated with the occurrence of GC. Different onset features and prognoses of GC in high altitude with respect to plains are rarely reported and remain unknown. This multicenter study compared different clinicopathological characteristics and prognoses of patients with resected GC who were from locations of both high altitudes and plains in China. From December 2009 to December 2011, patients with resected GC were retrospectively recruited at four centers located at high altitudes and the plains. Clinicopathological data were analyzed to explore the differences between the two groups. The Cox proportional-hazards model was used to investigate the prognostic factors for GC and estimate the independent impact of altitude on long-term survival after adjusting for covariates. Noncardia GC, from a moderate to well tumor grade, was more common in patients from high altitudes. Moreover, a higher proportion of moderate to well and moderate tumor grade and younger age of onset was found in patients with noncardia GC coming from high altitudes. Different overall survival (OS) presented in noncardia GC rather than cardia GC, with 69.94% GC-related 3-yr OS in high altitude versus 75.23% in the plains. High altitude was confirmed as a significant prognostic factor for noncardia GC (the hazard ratio for high altitude vs. plains was 1:50, with a 95% confidence interval; 1.06-1.82, p = 0.018) through a multivariate Cox proportional-hazards model analysis. This prognostic value was independent of all other factors. High altitude has an important role in clinicopathological features and prognosis of GC. Improvements in GC diagnosis and management at high altitudes are urgently needed.