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High preoperative plasma fibrinogen levels are associated with distant metastases and impaired prognosis after curative resection in patients with colorectal cancer.

Resveratrol, a plant-derived polyphenolic compound and a phytoestrogen, was shown to possess multiple protective effects including anti-inflammatory response and anti-oxidative stress. Hypoxic pulmonary hypertension (HPH) is a progressive disease characterized by sustained vascular resistance and marked pulmonary vascular remodeling. The exact mechanisms of HPH are still unclear, but inflammatory response and oxidative stress was demonstrated to participate in the progression of HPH. The present study was designed to investigate the effects of resveratrol on HPH development. Sprague-Dawley rats were challenged by hypoxia exposure for 28 days to mimic hypoxic pulmonary hypertension along with treating resveratrol (40 mg/kg/day). Hemodynamic and pulmonary pathomorphology data were then obtained, and the anti-proliferation effect of resveratrol was determined by in vitro assays. The anti-inflammation and anti-oxidative effects of resveratrol were investigated in vivo and in vitro. The present study showed that resveratrol treatment alleviated right ventricular systolic pressure and pulmonary arterial remodeling induced by hypoxia. In vitro experiments showed that resveratrol notably inhibited proliferation of pulmonary arterial smooth muscle cells in an ER-independent manner. Data showed that resveratrol administration inhibited HIF-1 α expression in vivo and in vitro, suppressed inflammatory cells infiltration around the pulmonary arteries, and decreased ROS production induced by hypoxia in PAMSCs. The inflammatory cytokines' mRNA levels of tumor necrosis factor α, interleukin 6, and interleukin 1β were all suppressed by resveratrol treatment. The in vitro assays showed that resveratrol inhibited the expression of HIF-1 α via suppressing the MAPK/ERK1 and PI3K/AKT pathways. The antioxidant axis of Nuclear factor erythroid-2 related factor 2/ Thioredoxin 1 (Nrf-2/Trx-1) was up-regulated both in lung tissues and in cultured PASMCs. In general, the current study demonstrated that resveratrol may prevent pulmonary hypertension through its anti-proliferation, anti-inflammation and antioxidant effects. Hence, the present data may offer novel targets and promising pharmacological perspective for treating hypoxic pulmonary hypertension.

Background Gastric carcinoma (GC) has one of the highest mortality rates of cancer diseases and has a high incidence rate in China. Palliative chemotherapy is the main treatment for advanced gastric cancer. It is necessary to compare the effectiveness and toxicities of different regimens. This study explores the possibility of methylation of DNA damage repair genes serving as a prognostic and chemo-sensitive marker in human gastric cancer. Methods The methylation status of five DNA damage repair genes (CHFR, FANCF, MGMT, MLH1, and RASSF1A) was detected by nested methylation-specific PCR in 102 paraffin-embedded gastric cancer samples. Chi-square or Fisher's exact tests were used to evaluate the association of methylation status and clinic-pathological factors. The Kaplan–Meier method and Cox proportional hazards models were employed to analyze the association of methylation status and chemo-sensitivity. Results The results indicate that CHFR, MLH1, RASSF1A, MGMT, and FANCF were methylated in 34.3 % (35/102), 21.6 % (22/102), 12.7 % (13/102), 9.8 % (10/102), and 0 % (0/102) of samples, respectively. No association was found between methylation of CHFR, MLH1, RASSF1A, MGMT, or FANCF with gender, age, tumor size, tumor differentiation, lymph node metastasis, and TNM stage. In docetaxel-treated gastric cancer patients, resistance to docetaxel was found in CHFR unmethylated patients by Cox proportional hazards model (HR 0.243, 95 % CI, 0.069–0.859, p = 0.028), and overall survival is longer in the CHFR methylated group compared with the CHFR unmethylated group (log-rank, p = 0.036). In oxaliplatin-treated gastric cancer patients, resistance to oxaliplatin was found in MLH1 methylated patients (HR 2.988, 95 % CI, 1.064–8.394, p = 0.038), and overall survival was longer in the MLH1 unmethylated group compared with the MLH1 methylated group (log-rank, p = 0.046). Conclusions CHFR is frequently methylated in human gastric cancer, and CHFR methylation may serve as a docetaxel-sensitive marker. MLH1 methylation was related to oxaliplatin resistance in gastric cancer patients.

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These results support the experimental evidence that interaction of expression of p16 and CDK4 may play an important role in the Rb/p16 pathway, and the expression patterns of CDK4 and p16 may be imperative in the development of colorectal carcinoma, thus becoming a new prognostic marker in colorectal cancer.

Hypoxia-inducible factor-1 (HIF-1) is a major determinant of invasion and metastasis in several tumor types. We previously reported that HIF-1α contributed to multidrug resistance in gastric cancer. However, the role of HIF-2α on the progression of gastric cancer is seldom reported. In this study, we first examined the possible role of HIF-1α and HIF-2α in the process of invasiveness and metastasis of gastric cancer, using immunohistochemistry of 80 gastric cancer tissues, western blot and real-time PCR of 8 fresh gastric cancer tissues. The results showed that HIF-1α and HIF-2α were significantly correlated with the clinical stage and were highly expressed in metastatic gastric cancers compared to nonmetastatic ones. Western blot analysis revealed that hypoxia (1% O₂, 8 h) induced HIF-1α and HIF-2α expression in different gastric cancer cell lines, including SGC7901, AGS, MGC803 and MKN45. Adhesion and invasion assays found that hypoxia caused an increase in adhesive and invasive abilities of gastric cancer cells. Small interfering (si) RNA against HIF-1α and HIF-2α in SGC7901 cells significantly inhibited hypoxia-induced adhesive and invasive abilities. Finally, the JNK inhibitor SP 600125 abolished hypoxia-induced HIF-1α and HIF-2α expression, and inhibited the adhesive and invasive abilities of gastric cancer cells exposed to hypoxia in a dose-dependent manner. Taken together, the present work suggested that HIF-1α and HIF-2α were involved in metastasis and invasion of gastric cancer cells under hypoxia, with the involvement of JNK signal pathway.

The balance between MMP-2 and TIMP-2 plays a crucial role in the process of colorectal carcinoma invasion and metastasis.