Yi Liao

Neoadjuvant chemotherapy for gastric cancer: A meta‐analysis of randomized, controlled trials

Although the effect of neoadjuvant chemotherapy in gastric cancer has been extensively studied, the data of survival benefit are still controversial. The purpose of this work was to assess the effectiveness of neoadjuvant chemotherapy followed by surgery in patients with gastric cancer.

Levels of human replication factor C4, a clamp loader, correlate with tumor progression and predict the prognosis for colorectal cancer

BackgroundHuman replication factor C4 (RFC4) is involved in DNA replication as a clamp loader and is aberrantly regulated across a range of cancers. The current study aimed to investigate the function of RFC4 in colorectal cancer (CRC).MethodsThe mRNA levels of RFC4 were assessed in 30 paired primary CRC tissues and matched normal colonic tissues by quantitative PCR. The protein expression levels of RFC4 were evaluated by western blotting (n = 16) and immunohistochemistry (IHC; n = 49), respectively. Clinicopathological features and survival data were correlated with the expression of RFC4 by IHC analysis in a tissue microarray comprising 331 surgically resected CRC. The impact of RFC4 on cell proliferation and the cell cycle was assessed using CRC cell lines.ResultsRFC4 expression was significantly increased in CRC specimens as compared to adjacent normal colonic tissues (P <0.05). High levels of RFC4, determined on a tissue microarray, were significantly associated with differentiation, an advanced stage by the Tumor-Node-Metastasis (TNM) staging system, and a poor prognosis, as compared to low levels of expression (P <0.05). However, in multivariate analysis, RFC4 was not an independent predictor of poor survival for CRC. In vitro studies, the loss of RFC4 suppressed CRC cell proliferation and induced S-phase cell cycle arrest.ConclusionRFC4 is frequently overexpressed in CRC, and is associated with tumor progression and worse survival outcome. This might be attributed to the regulation of CRC cell proliferation and cell cycle arrest by RFC4.

CISD2 enhances the chemosensitivity of gastric cancer through the enhancement of 5-FU-induced apoptosis and the inhibition of autophagy by AKT/mTOR pathway

Gastric cancer (GC) is a prevalent upper gastrointestinal tumor characterized by high morbidity and mortality due to imperfect screening systems and the rapid development of resistance to 5‐fluorouracil (5‐FU). CDGSH iron sulfur domain 2 (CISD2) has been recently regarded as a candidate oncogene in several types of tumors. It is, therefore, necessary to investigate its biological function and clinical significance in gastric cancer. In this study, the down‐regulated expression level of CISD2 in GC compared with adjacent normal tissues was evaluated by quantitative RT‐PCR and Western blotting. An immunohistochemical analysis indicated that CISD2 expression in GC was significantly correlated with age (P = 0.002), Laurens classification (P = 0.001), and differentiation (P = 0.049). Two cell lines, MKN1 and BGC823, were used to analyze the role of CISD2 in gastric carcinogenesis and response to 5‐FU through CCK‐8 assays, the RT‐CES system, Transwell assays, flow cytometry, and confocal fluorescence microscopy. The overexpression of CISD2 resulted in reduced cellular growth and proliferation, inhibition of metastatic ability, and increased apoptosis. 5‐FU treatment increased endogenous as well as exogenous overexpression of CISD2 in GC cells. Further investigation revealed that CISD2 enhanced sensitivity to 5‐FU via an increase in apoptosis and inhibition of protective autophagy through the activation of the AKT/mTOR pathway. In conclusion, CISD2 is down‐regulated in gastric cancer, and its effects on the inhibition of cellular proliferation, metastatic ability, and increased chemotherapy sensitivity are mediated by antagonism to 5‐FU‐induced autophagy through the AKT/mTOR pathway.

Screening for colorectal cancer in Tianhe, Guangzhou: results of combining fecal immunochemical tests and risk factors for selecting patients requiring colonoscopy

Abstract Objective To explore the performance of a protocol combining fecal immunochemical test (FIT) and a high-risk factor questionnaire (HRFQ) for selecting patients requiring colonoscopy as part of a population-based colorectal cancer (CRC) screening program in China. Methods From 2015 to 2016, we conducted a CRC screening program for all residents aged 45 years or older in Tianhe District, Guangzhou City, China. Participants underwent an FIT and received an HRFQ as part of primary screening. Those with positive FIT and/or HRFQ results were considered to be at high risk and were recommended to undergo colonoscopy. Results A total of 10 074 subjects were recruited and enrolled in the screening program. In the enrolled population, 17.5% had positive FIT results and 19.4% had positive HRFQ results. Of those recommended to undergo diagnostic colonoscopy, 773 did so. The screening method’s overall positive predictive value (PPV) was 4.9% for non-adenomatous polyps, 11.4% for low-risk adenomas (LRAs), 15.9% for high-risk adenomas (HRAs) and 1.6% for CRC. The PPVs of positive FIT results for non-adenomatous polyps, LRAs, HRAs and CRC were 5.2%, 15.9%, 22.5% and 2.5%, respectively. The PPVs of positive HRFQ results for non-adenomatous polyps, LRA, HRA and CRC were 4.1%, 10.2%, 14.3% and 1.4%, respectively. The PPVs associated with combined positive FIT and HRFQ results for non-adenomatous polyps, LRAs, HRAs and CRC were 4.5%, 16.4%, 23.7% and 2.8%, respectively. Conclusion Our results suggest that this two-step CRC screening strategy, involving a combination of FIT and HRFQ followed by colonoscopy, is useful to identify early-stage CRC. The high detection rates and PPVs for CRC and adenomas encourage this strategy’s use in ongoing screening programs.

ADAMTS5 acts as a tumor suppressor by inhibiting migration, invasion and angiogenesis in human gastric cancer

BackgroundADAMTS5 has been reported to be involved in the progression of several human tumors. Nevertheless, the role of ADAMTS5 in gastric cancer (GC) remains poorly defined.MethodsADAMTS5 expression levels were analyzed by quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC) in GC cell lines and tissues, and the correlations between ADAMTS5 expression and clinicopathological features and survival were also examined. In vitro assays, including transwell assays, wound healing assays and cell adhesion assays, were employed to further explore the biological functions of ADAMTS5. A MAP kinase pathway microarray was used to identify the underlying mechanisms. The expression of ADAMTS5 and ETS1 and the microvessel density (MVD) were also analyzed using IHC to determine correlations with angiogenesis in GC.ResultsADAMTS5 expression was downregulated in gastric cancer tissues. Low expression of ADAMTS5 was associated with gender, histological type, degree of differentiation, M stage, TNM stage and vascular invasion, and was also an independent indicator of a poor prognosis for patients with GC. ADAMTS5 overexpression markedly inhibited GC cell migration and invasion and enhanced cell adhesion to the extracellular matrix (ECM), whereas knockdown of ADAMTS5 exerted the opposite effects. Furthermore, the ADAMTS5 expression status was negatively correlated with ETS1 expression and MVD.ConclusionADAMTS5 is downregulated in GC and suppresses tumor metastasis and angiogenesis by inhibiting ETS1-mediated changes in MVD and potentially acts as a novel prognostic marker and a potential therapeutic target in human GC.

Nuclear receptor binding protein 1 correlates with better prognosis and induces caspase-dependent intrinsic apoptosis through the JNK signalling pathway in colorectal cancer

Nuclear receptor binding protein 1 (NRBP1) is a ubiquitously expressed and highly conserved pseudokinase that has important roles in cellular homoeostasis. Despite recent advances in understanding the biology of NRBP1, the role of NRBP1 and its underlying mechanism in colorectal cancer (CRC) have not been fully elucidated. In the present study, we observed that NRBP1 expression levels were significantly reduced in CRC tissues compared with corresponding adjacent normal tissues, and high NRBP1 expression correlated with better prognosis in CRC. Overexpression of NRBP1 inhibited CRC cell proliferation and promoted apoptosis in vitro and in vivo. In contrast, knockdown of NRBP1 expression increased cell proliferation and decreased the percentage of apoptotic cells. Moreover, overexpression of NRBP1 activated caspase-dependent intrinsic apoptosis. In addition, we further discovered that NRBP1 regulated the apoptotic pathway through interaction with JNK. Finally, NRBP1 overexpression led to attenuated CRC growth in a xenograft mouse model. Our study illustrates the suppressor role of NRBP1 in CRC and provides a potential therapeutic target.

Epigenetic silencing of ADAMTS5 is associated with increased invasiveness and poor survival in patients with colorectal cancer

PurposeA disintegrin and metalloprotease with motif 5(ADAMTS5) has been involved in colorectal cancer (CRC) with hypermethylation in the promoter. However, its role in CRC remains unclear. The aim of this study was to explore the clinical significance and biological effect of ADAMTS5 on colorectal carcinogenesis. Through MSP, qRT-PCR, WB and IHC analysis, followed by a variety of in vitro assays, we report the function of ADAMTS5 in CRC. ADAMTS5 was markedly hypermethylaed and downregulated in tumor tissues compared with non-tumor tissues (p < 0.001). Negative expression of ADAMTS5 was much more common in tumor tissues than that in normal tissues (p < 0.001) and correlated with histologic types (p = 0.002), poor OS (p = 0.029) and DFS (p = 0.018). In vitro assay revealed that overexpression of ADAMTS5 inhibited the capabilities of migration and invasion of CRC cells, and no effect on cell growth, cell cycle and apoptosis. ADAMTS5 is hypermethylated and inhibits cancer cells invasion and migration in colorectal cancer, and correlates with OS and DFS, indicating that ADAMTS5 might be a useful biomarker in colorectal cancer therapy.

Risk factors of gastric remnant cancer: a meta-analysis and systematic review

Aim: To investigate the risk factors of gastric remnant cancer. Methods: A search on PubMed, Embase, ISI Web of SCIENCE, Cochrane Library, CNKI, and Wanfang was performed to identify relevant literature published from January 1990 to May 2014. The effect of gastric remnant cancer was estimated by risk ratio (RRs) with 95% confidence intervals (CIs) for each study using a fixed effects or random effects model. Results: 28 studies with a total of 1132 patients met the inclusion criteria in our study. The risk for gastric remnant cancer was positively associated with a male gender, an initial ulcerative disease, a previous Billroth II anastomosis. Gastric remnant cancer was also more likely to be located at the site of initial anastomosis and was associated with a poorly differentiated and/or undifferentiated histology. However no significance was observed between the TNM stage and the gastric remnant cancer. Conclusion: Meta-analysis found that gastric remnant cancer is associated with gender, reason for initial surgery, type of initial surgery performed, location, histology.

Current Concepts in Gastric Signet Ring Cell Carcinoma

Background: Classified as “diffuse” by the Lauren’s classification gastric signet ring cell carcinoma is an adenocarcinoma with distinct features which separates it from other types of gastric cancer. Affecting mainly young female patients, gastric SRC is mainly due to the loss of E-cadherin and CDH1+. In this review we look into the pathogenesis, clinical features, diagnosis, treatment, and prognosis of gastric SRC. Materials and Methods: We reviewed the literature published until September 2014 to identify studies of gastric SRC. Studies were identified by using the Medline and PubMed databases using the terms “gastric signet ring cell carcinoma”, “gastric signet ring cell cancer”, “signet ring cell cancer”, “signet ring cell carcinoma”. Researches on esophageal SRC, intestinal SRC were excluded in our study. Results: A down-regulation of epithelial cadherin is essential for the initiation, and progression of gastric signet ring cell cancer cells. Once gastric cells lose E-cadherin, they have an increase in motility due to epithelial-mesenchymal transition. A strong correlation in the mutation of Snail, Slug, and Twist as well as an activation of the phosphatidylinositol 3 kinase (PI3K)/AKT axis, Wnt/β-catenin signaling pathway, and transforming growth factor β have been found to be associated with the pathogenesis of gastric signet ring cell cancer. Diagnosis relies mainly on histological findings. While surgical treatment includes resection and lymphadenectomy with retrieval of at least 15 lymph nodes, few patients respond well to chemotherapeutic regimens. Conclusion: Despite recent advances, more patients are being diagnosed with advanced gastric SRC. Understanding the pathogenenis of gastric signet ring cell cancer is critical in the treatment and improving the prognosis of patients.