Autophagy Inhibition Stimulates Apoptosis in Oesophageal Squamous Cell Carcinoma Treated with Fasudil.

Fasudil has been proven to be a promising chemotherapeutic drug for various malignancies. However, the potential anticancer effects of fasudil in oesophageal squamous cell carcinoma (ESCC) remain to be established. We confirmed the RhoA activity is inhibited by fasudil in ESCC cells. Then measured the effects of fasudil on apoptosis and autophagy in ESCC. Our study showed fasudil could both induce ESCCs apoptosis and autophagy, and when fasudil-induced autophagy was inhibited by knockdown of the essential autophagy genes (Beclin 1 or ATG7), and pharmacologic agent (chloroquine) treatment, both treatments also significantly sensitized ESCC to fasudil-induced apoptosis, reducing cell viability in vitro. Our study showed autophagy inhibitors combined with fasudil could significantly induce ESCC apoptosis, which may provide a novel therapeutic strategy for ESCC.

The clinical pathological characteristics and prognosis of FGFR1 gene amplification in non-small-cell lung cancer: a meta-analysis.

FGFR1 amplification is recognized as a novel therapy target for non-small-cell lung cancer (NSCLC), especially in squamous cell carcinoma (SCC). However, the association between FGFR1 amplification and the clinicopathological characteristics of NSCLC remains controversial. We performed a meta-analysis of 17 eligible studies to examine the correlation between FGFR1 gene amplification and clinicopathological characteristics. FGFR1 amplification was closely related to these clinicopathological features, including sex (odds ratio [OR] 2.05, 95% confidence interval [CI] 1.50-2.80), smoking (OR 3.31, 95% CI 2.02-5.44), and histology (OR 3.60, 95% CI 2.82-4.59). FGFR1 amplification was associated with shorter overall survival, and no significant heterogeneity existed between studies (I (2)=3.8%). We should note that publication bias may partly account for these results, but our findings remained significant after the trim-and-fill method (hazard ratio 1.22, 95% CI 1.06-1.40). However, no significant correlation was found with poor disease-free survival (hazard ratio 1.43, 95% CI 0.96-2.12). In conclusion, this study showed that FGFR1 amplification was significantly associated with sex, smoking, and histology. FGFR1 amplification could be a marker of poor prognosis in NSCLC patients, especially in SCC patients.

Helicobacter pylori infection and esophageal cancer risk: an updated meta-analysis.

AIM: To clarify the association between Helicobacter pylori (H. pylori) infection and the risk of esophageal carcinoma through a meta-analysis of published data. METHODS: Studies which reported the association between H. pylori infection and esophageal cancer published up to June 2013 were included. The odds ratios (ORs) and corresponding 95%CIs of H. pylori infection on esophageal cancer with respect to health control groups were evaluated. Data were extracted independently by two investigators and discrepancies were resolved by discussion with a third investigator. The statistical software, STATA (version 12.0), was applied to investigate heterogeneity among individual studies and to summarize the studies. A meta-analysis was performed using a fixed-effect or random-effect method, depending on the absence or presence of significant heterogeneity. RESULTS: No significant association between H. pylori infection and esophageal squamous cell carcinoma (ESCC) risk was found in the pooled overall population (OR = 0.97, 95%CI: 0.76-1.24). However, significant associations between H. pylori infection and ESCC risk were found in Eastern subjects (OR = 0.66, 95%CI: 0.43-0.89). Similarly, cytotoxin-associated gene-A (CagA) positive strains of infection may decrease the risk of ESCC in Eastern subjects (OR = 0.77, 95%CI: 0.65-0.92), however, these associations were not statistically significant in Western subjects (OR = 1.26, 95%CI: 0.97-1.63). For esophageal adenocarcinoma (EAC) the summary OR for H. pylori infection and CagA positive strains of infection were 0.59 (95%CI: 0.51-0.68) and 0.56 (95%CI: 0.45-0.70), respectively. CONCLUSION: H. pylori infection is associated with a decreased risk of ESCC in Eastern populations and a decreased risk of EAC in the overall population.

Adenovirus-mediated interferon-γ gene therapy induced human pancreatic carcinoma Capan-2 cell apoptosis in vitro and in vivo.

Pancreatic cancer is one of the most lethal human malignancies with a very low 5-year survival rate, which highlights urgent needs for more effective therapeutic strategies. In this study, we examined the potential therapeutic effects of an adenovirus encoding human interferon gamma (Ad-IFNγ) on pancreatic carcinoma cells Capan-2 in vitro and in vivo. The results indicated that Ad-IFNγ could significantly inhibit tumor cell growth via inducing cell apoptosis. After infection, IFNγ expressed durably and stably in xenografts, predominantly in tumor tissue, while much less in blood and liver. Thus, adenovirus-mediated intratumoral injection of human IFNγ gene could be an effective gene therapeutic system for the treatment of pancreatic carcinoma.

Hypermethylation-modulated downregulation of RASSF1A expression is associated with the progression of esophageal cancer.

BACKGROUND AND AIMS: Chromosome 3p21 is an important locus harboring critical tumor suppressor genes (TSGs) implicated in the pathogenesis of multiple tumors including esophageal carcinoma (EC). Aberrant promoter methylation is a fundamental mechanism of inactivation of TSGs in cancer. RASSF1A, a candidate tumor suppressor gene, recently cloned from the lung tumor locus at 3p21.3, is frequently inactivated by hypermethylation of its promoter region in a number of malignancies. We undertook this study to investigate the methylation status of RASSF1A and its significance in esophageal squamous cell carcinoma (ESCC). METHODS: Real-time RT-PCR and real-time methylation-specific PCR (real-time MSP) were used to detect RASSF1A expression and the methylation status of the RASSF1A promoter, respectively, in 124 primary ESCC tissues. RESULTS: Hypermethylation, partial methylation and unmethylation of the promoter region of RASSF1A were detected in 56 (45.2%), 23 (18.6%) and 45 (36.2%) of 124 ESCC samples, respectively. Unmethylation of the promoter region of RASSF1A was detected in 119 (96%) of the 124 corresponding noncancerous tissues. Five (4.0%) of 124 noncancerous tissues showed partial methylation. The presence of hypermethylation was statistically associated with loss of RASSF1A mRNA expression in primary ESCC (p <0.05). There were statistically significant correlations between the presence of hypermethylation and regional lymph node involvement (p=0.000), histological differentiation (p=0.009) and tumor stage (p=0.000). CONCLUSIONS: Our results suggest that RASSF1A may be one of the ESCC-related TSGs located at 3p21, and hypermethylation of the CpG island promoter of the RASSF1A is associated with the progression of ESCC.