BackgroundMicroRNAs (miRNAs) are involved in cancer development and progression, acting as tumor suppressors or oncogenes. Our previous studies have revealed that miR-148a and miR-152 are significantly down-regulated in gastrointestinal cancers. Interestingly, miR-148b has the same "seed sequences" as miR-148a and miR-152. Although aberrant expression of miR-148b has been observed in several types of cancer, its pathophysiologic role and relevance to tumorigenesis are still largely unknown. The purpose of this study was to elucidate the molecular mechanisms by which miR-148b acts as a tumor suppressor in gastric cancer.ResultsWe showed significant down-regulation of miR-148b in 106 gastric cancer tissues and four gastric cancer cell lines, compared with their non-tumor counterparts by real-time RT-PCR. In situ hybridization of ten cases confirmed an overt decrease in the level of miR-148b in gastric cancer tissues. Moreover, the expression of miR-148b was demonstrated to be associated with tumor size (P = 0.027) by a Mann-Whitney U test. We also found that miR-148b could inhibit cell proliferation in vitro by MTT assay, growth curves and an anchorage-independent growth assay in MGC-803, SGC-7901, BGC-823 and AGS cells. An experiment in nude mice revealed that miR-148b could suppress tumorigenicity in vivo. Using a luciferase activity assay and western blot, CCKBR was identified as a target of miR-148b in cells. Moreover, an obvious inverse correlation was observed between the expression of CCKBR protein and miR-148b in 49 pairs of tissues (P = 0.002, Spearman's correlation).ConclusionsThese findings provide important evidence that miR-148b targets CCKBR and is significant in suppressing gastric cancer cell growth. Maybe miR-148b would become a potential biomarker and therapeutic target against gastric cancer.

Titanium dioxide nanoparticles (TiO2 NPs) have potential applications as food additives, but concerns persist about their safety. Children are identified as having the highest exposure and may face the greatest health risks. However, the toxicological sensitivity of TiO2 NPs in different ages is not clear. Here, a comparative toxicity study of TiO2 NPs in 3-week (youth) and 8-week (adult) old Sprague-Dawley rats is reported following oral exposure at doses of 0, 10, 50, 200 mg kg(-1) body weight per day for 30 days. The organ mass and histology, blood biochemistry and redox state, intestinal function, and biodistribution of NPs are characterized. The results show that TiO2 NPs induce different toxic effects on young and adult rats. The liver edema, heart injuries and non-allergic mast cell activation in stomach tissues are found in young rats. On the other hand, only slight injury in the liver and kidney and decreased intestinal permeability and molybdenum contents are found in adult rats. Furthermore, TiO2 NP exposure can provoke reductive stress (i.e., increased reduced glutathione (GSH)/oxidized glutathione (GSSG) ratios) in plasmas through enhancing the glucose and GSH levels in young rats or reducing the glutathione peroxidase (GSH-Px) acitivity and GSSG levels in adult rats. These results suggest that different ages may require different biomarkers for identifying and monitoring oral toxicity of nanoparticles.

An original gadolinium-hybridized plasmonic gold nanocomposite is fabricated to provide an insightful and attractive strategy to overcome both the physiological and pathological barriers of tumor, and increase the transportation and permeability of imaging agents and drugs in tumor interior for achieving high-sensitive multimodal imaging and simultaneously improving the therapeutic efficacy of cancer.

BackgroundPalliative gastrectomy for patients with advanced gastric cancer remains controversial. The objective of the present meta-analysis was to analyze survival outcomes and establish a consensus on whether palliative gastrectomy is suitable for patients with incurable advanced gastric cancer and which type of patients should be selected to receive palliative gastrectomy.MethodsA literature search was conducted in PubMed, EMBASE and the Cochrane Library. The results for overall survival in the meta-analysis are expressed as hazard ratios (HRs) with 95% confidence intervals (CIs).ResultsOf 1647 articles and abstracts reviewed, 14 studies with 3003 patients were eligible for the final analysis. The meta-analysis revealed that palliative gastrectomy is associated with a significantly improvement in overall survival (HR 0.56; 95%CI 0.39–0.80; p < 0.002) compared that of patients treated without palliative gastrectomy. An improvement in survival was also observed in patients with stage M1 gastric cancer who received palliative gastrectomy (HR 0.62; 95%CI 0.49–0.78; p < 0.0001), especially those with peritoneal dissemination (HR = 0.76, 95%CI 0.63–0.92), liver metastasis (HR = 0.41, 95%CI 0.30–0.55), or distant lymph-node metastasis (HR = 0.36, 95%CI 0.23–0.59). Combined hepatic resection may be beneficial for patients who under palliative gastrectomy (HR 0.30; 95%CI 0.15–0.61; p = 0.0008). The overall survival of patients who underwent palliative gastrectomy combined with chemotherapy was significantly improved (HR 0.63; 95%CI 0.47–0.84; p = 0.002).ConclusionsFrom the results of the meta-analysis, palliative gastrectomy for patients with incurable advanced gastric cancer may be associated with longer survival, especially for patients with stage M1 gastric cancer. Combined hepatic resection for patients with liver metastasis and chemotherapy may be beneficial factors compared to simple palliative gastrectomy.

No abstract

The seventh edition of TNM staging system on TDs satisfactorily predicts patients' outcome for those without LNM. Patients who categorized as T3N2bM0TD (+) and T4N2bM0TD (-/+) should be reclassified as stage IV. Number of TDs was not an independent prognostic parameter in the TNM staging system.

The preoperative prognostic nutritional index (PNI) may forecast colorectal cancer (CRC) outcomes, but the evidence is not conclusive. Here, we retrospectively analyzed a cohort of patients from the Department of Surgical Oncology at the First Hospital of China Medical University (CMU-SO). We also conducted a meta-analysis of eleven cohort studies. Bayesian Information Criterion (BIC) was used to determine the optimal PNI cut-off values for classifying prognosis in the patients from the CMU-SO. The result from CMU-SO and meta-analysis both confirmed that low PNI was significantly associated with a poor prognosis and advanced TNM stages. Among the patients from the CMU-SO, the optimal cut-off values were “41-45-58” (PNI < 41, 41 ≤ PNI < 45, 45 ≤ PNI < 58, PNI ≥ 58), which divided patients into 4 stages. The BIC value for TNM staging combined with the PNI was smaller than that of TNM staging alone (−325.76 vs. −310.80). In conclusion, low PNI was predictive of a poor prognosis and was associated with clinicopathological features in patients with CRC, and the 41-45-58 four-stage division may be suitable for determining prognosis. PNI may thus provide an additional index for use along with the current TNM staging system to determine more accurate CRC prognoses.

MicroRNAs (miRNAs) play an important role in the regulation of a variety of cellular processes, including cell growth, differentiation, apoptosis and carcinogenesis. The purpose of this study was to elucidate the molecular mechanisms by which miR-148b acts as a tumor suppressor in colorectal cancer. The expression of miR-148b was significantly downregulated in 96 pairs of human colorectal cancer tissues (p < 0.0001) and three cell lines (p < 0.01) compared with non-tumor adjacent tissues by quantitative real-time PCR. The results of in situ hybridization highlighted that miR-148b was important in the cancer transformation process. Using statistical analysis, we found that the expression level of miR-148b was associated with tumor size (p 5 0.033) in colorectal cancer patients. Moreover, overexpression of miR-148b in HCT-116 and HT-29 cells could inhibit cell proliferation in vitro and suppress tumorigenicity in vivo. Importantly, the result of luciferase activity assay and western blot showed that the cholecystokinin-2 receptor gene (CCK2R) was a target of miR-148b and was downregulated by miR-148b at the translational level. Then, we used siRNA, radioimmunoassay and ELISA to demonstrate that miR-148b might have an effect on cell proliferation by regulating the expression of CCK2R which functioned depending on the gastrin in colorectal cancer. Taken together, our data provides the first evidences that miR-148b acts as a tumor suppressor in colorectal cancer and should be further evaluated as a biomarker and therapeutic tool against colorectal cancer.Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. 1 The CRC incidence and mortality rates in China have increased rapidly in the past several decades. 2 Although the pathogenesis of CRC is well characterized, new molecules that play a role in this process are still being discovered. MicroRNAs (miRNAs) are $22 nucleotide noncoding RNA molecules that regulate a variety of cellular processes, including cell differentiation, cell cycle progression and apoptosis. [3][4][5][6] It has been demonstrated that miRNAs play a significant role in tumorigenesis by downregulating tumor suppressor genes or oncogenes. 7,8 An increasing number of studies have found miRNA related mechanisms in the development of CRC, potential miRNAs as biomarkers in the diagnosis and prognosis of CRC and promising effects with miRNAs in the treatment of cancer at the molecular level. [9][10][11][12]