There are growing concerns that body mass index (BMI) is related to cancer risk at various anatomical sites, including the upper gastrointestinal tract, and the existence of a causal relationship remains unclear. The Mendelian randomization (MR) method uses instrumental genetic variables of risk factors to explore whether a causal relationship exists while preventing confounding. In our study, genome-wide association study (GWAS) data from the BioBank Japan (BBJ) project were used. Genetic variants were chosen as instrumental variables using inverse-variance weighting (IVW), MR-Egger regression and weighted-median methods to estimate the causal relationship between BMI and the risk of gastro-esophageal cancer. We found no evidence to support a causal association between BMI and risk of gastric cancer [odds ratio (OR) =0.99 per standard deviation (SD) increase in BMI; 95% confidence interval (CI): (0.76-1.30); P = 0.96] or esophageal cancer [0.78(0.50-1.22); P = 0.28] using the IVW method. Sensitivity analysis did not reveal any sign of horizontal pleiotropy. Additionally, in the gender-stratified analysis, no causal association was found. Findings from this study do not support a causal effect of BMI on gastro-esophageal cancer risk. However, we cannot rule out a modest or nonlinear effect of BMI.

Anticancer bioactive peptide (ACBP), a novel bioactive peptide isolated from spleens of goats immunized with tumor extracts in our lab, can inhibit the proliferation of CRC in vitro and vivo. However, it remains unclear how the proliferation of CRC is inhibited by ACBP at the molecular level. Here, we provide evidences showing that ACBP significantly inhibits the expression of Wnt/β-catenin related genes (cyclin D1, met and c-myc) through pharmacotranscriptomic and qRT-PCR analysis in CRCs. Active β-catenin, a key protein within Wnt pathway, was compromised remarkably by ACBP in three CRCs, including HCT116, RKO and HT29. Thus nuclear accumulation of active β-catenin was retarded and finally lead to the decreased expression of oncogenes cyclin D1, met, and c-myc. In addition, we proved that active β-catenin reduction was mainly due to the inhibition of phospho-LRP6 and stimulation of phospho-β-catenin by ACBP. Based on the detection of Met and C-Myc in CRC tumor tissue without prior radiotherapy or chemotherapy, our results demonstrated that ACBP can act as a promising anticancer agent for CRC by targeting Wnt/β-catenin pathway, especially active β-catenin.

Trichomicin, a small-molecule compound isolated from fungi, has been identified with bioactivity of antitumor. In this study, a colon cancer subcutaneous mice model was used to evaluate the antitumor effects of Trichomicin in vivo. Treatment with Trichomicin significantly inhibited tumor growth in a xenograft mouse colon cancer model. The underlying molecular mechanism has also been investigated through the quantification of relevant proteins. The expression levels of IL-6 and TNFα were reduced in tumor tissues of mice treated with Trichomicin, which was consistent with results of in vitro experiments in which Trichomicin suppressed the expression of IL-6 and TNFα in tumor and stromal cells. In addition, Trichomicin inhibited TNFα-induced activation of NF-κB and basal Stat3 signaling in vitro, which resulted in reduced expression of the immune checkpoint protein PD-L1 in tumor and stromal cells. Conclusively, Trichomicin, a promising new drug candidate with antitumor activity, exerted antitumor effects against colon cancer through inhibition of the IL-6 and TNFα signaling pathways.

OBJECTIVE:To evaluate the surgical morbidity and oncologic results after concurrent chemoradiotherapy (CCRT) followed by completion surgery for advanced cervical carcinoma. METHODS:The present retrospective analysis included 192 patients with advanced cervical cancer (stage IIB-IVA) treated with CCRT followed by surgery and 186 control patients without completion surgery. Disease-free and overall survival rates were compared. RESULTS:Of the patients who underwent surgery, 27 (14.1%) had pathologic evidence of residual disease; the local control rate with CCRT was 85.9%. After a median follow-up period of 190 months, 32 (16.7%) patients who underwent completion surgery had a recurrence compared with 59 (31.7%) of those who did not. The overall survival rate among patients who underwent extrafascial hysterectomy, extended hysterectomy, or no surgery was 72.2%, 60.1%, and 45.9% at 3 years, and 53.5%, 40.7%, and 32.2% at 5 years, respectively. CONCLUSION:Surgery after CCRT for advanced cervical cancer enabled evaluation of the pathologic response to therapy, improved local disease control in patients with a partial pathologic response, and enhanced survival. The most appropriate surgical approach was extrafascial hysterectomy with pelvic lymph node dissection.

OBJECTIVE: To investigate the regulatory effects of strogen,progesterone and mifepristone on the expression of two human progesterone receptor isoforms in endometrial carcinoma cells in vitro.METHODS: Three endometrial carcinoma cell lines were cultured in vitro: HECCA-A(PRA+),HECCA-B(PRB+) and HECCA-AB(PRA+,PRB+).The cells were incubated with estrogen,progesterone and mifepristone for 24 hours and 48 hours individually.The expressions of two progesterone receptor isoforms were detected by Western Blot.RESULTS: When stimulated by estrogen for 48 hours,the expression of PRA and the ratio of PRA/PRB in HECCA-A and HECCA-AB cells raised significantly(P0.05),while after being stimulated by progesterone or mifepristone,the expression of PRB in HECCA-B and HECCA-AB cells decreased,and the ratio of PRA/PRB raised significiantly(P0.05).CONCLUSION: Estrogen can up-regulate the expression of PRA at protein level,progesterone or mifepristone can decrease the protein expression of PRB.

OBJECTIVE:To study the effects of estrogen,progesterone and mifepristone on the growth of endometrial carcinoma cell lines expressing different progesterone receptor isoforms in vitro.METHODS: Four endometrial carcinoma cell lines were cultured in vitro: HECCA(PR-),HECCA-A(PRA+),HECCA-B(PRB+) and HECCA-AB(PRA+,PRB+).The cells were divided into four groups: control group,estrogen group,estrogen and progesterone group,estrogen and progesterone group and mifepristone group.The growth of the cells were evaluated by means of microcutrue tetrazolium assay after 24,48,72 and 96 hours,the changes of cell cycle were detected by flow cytometry after 96 hours and the cell percentages of S phase(SPF) were compared.RESULTS: After stimulated by estrogen for 72 hours,the growth and SPF of four cell lines were significantly higher than the control group(P0.05).And 72 hours after being stimulated by estrogen and progesterone,growth of HECCA-B and HECCA-AB and SPF were lower than that of the estrogen group(P0.05).On the base of estrogen and progesterone,mifepristone was added,the growth and SPF of HECCA-B and HECCA-AB were higher than the groups of estrogen and progesterone(P0.05).CONCLUSIONS: Estrogen can stimulate the growth of four endometrial carcinoma cell lines.Progesterone inhibits the hyperplasia induced by estrogen mainly depending on PRB.Mifepristone antagonizes the effect of progesterone on the cells expressing PRB.