Dietary Fat Consumption and Non-Hodgkin's Lymphoma Risk: A Meta-analysis.

OBJECTIVE: Many studies suggest that high-fat diets are linked to the etiology of non-Hodgkin's lymphoma (NHL). However, the findings are inconsistent and therefore the association between fat and non-Hodgkin's lymphoma remains unclear. In this study, we aim to quantitatively assess the association between fat consumption and the risk for NHL. METHODS: We reviewed 221 published cohort and case-control studies that reported relative risk (RRs) and corresponding 95% confidence intervals (CIs) of NHL and fat intake using PubMed, Cochrane, EMBASE, and Google Scholar databases. A random-effects model computed summary risk estimates. RESULTS: Based on our literature search, 10 of 221 studies (two cohort and eight case-control studies) were relevant to this meta-analysis. There was a significant association between total fat consumption and increased risk of NHL (RR = 1.26; 95% CI: 1.12-1.42); in addition, subgroup analysis showed a significant correlation with diffuse large B-cell lymphoma (RR = 1.41; 95% CI: 1.08-1.84) but not with follicular lymphoma (RR = 1.21; 95% CI: 0.97-1.52), small lymphocytic lymphoma/chronic lymphocytic leukemia (RR = 0.91; 95% CI: 0.68-1.23), nor with T cell lymphoma (RR = 1.12; 95% CI: 0.60-2.09). The funnel plot revealed no evidence for publication bias. CONCLUSION: Total fat consumption, particularly animal fat, increases the risk for NHL.

An effective AKT inhibitor-PARP inhibitor combination therapy for recurrent ovarian cancer.

BACKGROUND: Although the use of PARP inhibitor has received considerable amount of attention in ovarian cancer, PARP inhibitor resistance still emerges with disease progression. PI3K/AKT pathway inhibitors have been proposed to synergize with PARP inhibition to slow tumor growth, but the exact molecular mechanisms are still elusive. METHODS: Utilizing tumor samples from recurrent EOC patients with platinum resistance and prior PARP inhibitor use, Mini PDX and PDX models were established to study the anti-tumor effect of AKT inhibitor (LAE003) and LAE003/PARP inhibitor (Olaparib) in combination. Five ovarian cancer cell lines were treated with Olaparib or LAE003 or in combination in vitro. Cell viability and apoptosis rate were measured after the treatments. Combination index by the Chou-Talalay was used to evaluate in vitro combination effect of Olaparib and LAE003. The protein expression level of PARP1 and PAR was measured by Western blot in cell lines and by immunohistochemistry in PDX tumor tissues. RESULTS: Tumor cells from two out of five platinum-resistant ovarian cancer patients previously treated with PARP inhibitor were sensitive to AKT inhibition in Mini-PDX study. Inhibition of AKT further increased the response of tumor cells to Olaparib in a PDX model derived from a recurrent platinum-resistant ovarian cancer patient. Additive anti-proliferation effect of LAE003 and Olaparib was also observed in three ovarian cancer cell lines with high PARP1 protein level. Interestingly, mechanism study revealed that AKT inhibition decreased PARP enzyme activity as measured by PAR level and/or reduced PARP1 protein level in the tumor cell lines and PDX tumor tissues, which may explain the observed combined anti-tumor effect of LAE003 and Olaparib. CONCLUSION: Collectively, our results suggest that the combination of AKT inhibitor and PARP inhibitor could be a viable approach for clinical testing in recurrent ovarian cancer patients.

LncRNA XLOC_006390 facilitates cervical cancer tumorigenesis and metastasis as a ceRNA against miR-331-3p and miR-338-3p.

OBJECTIVE: Cervical cancer is one of the most common malignant tumors. Our previous results showed that long non-coding RNA (lncRNA) XLOC_006390 plays an important role in cervical cancer. In this study, we have explored the mechanism of action of lncRNA XLOC_006390. METHODS: LncRNA XLOC_006390 was proposed to exercise its function as a competing endogenous RNA (ceRNA), and its potential targeted miRNAs was predicted through the database LncBase Predicted v.2. Two miRNAs, miR-331-3p, and miR-338-3p, were chosen for the study. Expression of miRNAs and lncRNA in cervical cancer cells and tissues was detected by reverse transcription polymerase chain reaction. To determine the correlation, silencing of XLOC_006390, over-expression of miR-331-3p, and miR-338-3p was performed in SiHa and Caski cell lines, respectively. RESULTS: Based on the interactive effect between miRNA and lncRNA, miR-331-3p and miR-338-3p were significantly downregulated in cervical cancer cells and tissues, and their expression levels were negatively related to that of lncRNA. Our results also showed that the expression of miR-331-3p target gene NRP2, miR-338-3p target genes PKM2, EYA2 was significantly downregulated when the XLOC_006390 was knocked down. Further, XLOC_006390 was found to facilitate cervical cancer tumorigenesis and metastasis by downregulating miR-331-3p and miR-338-3p expression. CONCLUSION: Taken together, our study demonstrated that XLOC_006390 may serve as a ceRNA and reversely regulates the expression of miR-331-3p and miR-338-3p, thus facilitating cervical cancer tumorigenesis and metastasis.

Long non-coding RNA XLOC_006390 promotes cervical cancer proliferation and metastasis through the regulation of SET domain containing 8.

The long non-coding RNA (lncRNA) XLOC_006390 is increased in various human cancer tissues and it plays important roles in cell growth and migration. However, the role of lncRNA XLOC_006390 in the progression and metastasis of cervical cancer has not been evaluated and remains unclear. In the present study, we hypothesized that lncRNA XLOC_006390 is also increased in cervical cancer, and upregulation of lncRNA XLOC_006390 contributes to cervical cancer metastasis. The expression of lncRNA XLOC_006390 in cervical cancer tissues and cell lines was analyzed using quantitative reverse-transcription-polymerase chain reaction (qRT-PCR). RNA interference approach and an overexpression system were used to investigate the cellular functions of XLOC_006390 and SET domain containing 8 (SET8). Cell Counting Kit-8 (CCK-8) assay was performed to detect cell proliferation. Cell migration and invasion abilities were evaluated by Transwell assays. Western blotting and immunofluorescence were performed to detect SET8 protein expression. The results revealed that XLOC_006390 was increased in cervical cancer tissues. Patients with high XLOC_006390 expression were associated with FIGO stages III and IV (P=0.0170), lymphatic metastasis (P=0.0078) and distant metastasis (P=0.0025). Furthermore, SET8 was also increased in cervical cancer tissues and its expression was positively associated with XLOC_006390, and XLOC_006390 regulated SET8 expression. In addition, knockdown or overexpression of XLOC_006390 and SET8 expression suppressed or promoted cervical cancer cell proliferation, migration and invasion in vitro, respectively. In conclusion, our data suggest that lncRNA XLOC_006390 promotes cervical cancer cell growth and metastasis through the regulation of SET8, at least partly, which indicate the critical roles of XLOC_006390 and SET8 in cervical cancer progression and metastasis.

Diabetes mellitus and the risk of cholangiocarcinoma: an updated meta-analysis.

INTRODUCTION: A number of studies have shown that diabetes mellitus is implicated in susceptibility to several cancers. However, the relationship between diabetes and cholangiocarcinoma remain unclear. AIM: To quantitatively assess the relationship between diabetes and incidence of cholangiocarcinoma in cohort and case-control studies. MATERIAL AND METHODS: A literature search was performed for entries from 1996 to 2014 using the PubMed and EMBASE databases. Studies were included if they reported odds ratios (OR) and corresponding 95% CI of cholangiocarcinoma with respect to diabetes mellitus. RESULTS: Twenty studies met the inclusion criteria, which included fifteen case-control studies and five cohort studies from Asia (n = 11), the United States (n = 5), and Europe (n = 4). Compared with individuals without diabetes, the pooled OR of cholangiocarcinoma was 1.74 (95% CI: 1.62-1.87, p = 0.568 for heterogeneity) for patients with diabetes, ICC (summary RR, 1.93; 95% CI: 1.65-2.25; p = 0.037 for heterogeneity), and ECC (summary RR, 1.66; 95% CI: 1.39-1.98; p = 0.001 for heterogeneity). The funnel plot revealed no evidence for publication bias concerning diabetes and the risk of CC (including ICC and ECC). CONCLUSIONS: The findings from this meta-analysis suggest that diabetes may increase the risk of cholangiocarcinoma. This relationship needs to be confirmed by further follow-up studies.