Search

Objective: To evaluate the relationship of sarcopenia with the pancreatic dose-volume histogram (DVH) in gastric cancer patients treated with adjuvant chemoradiotherapy (CRT) after radical gastrectomy., Methods: A retrospective study was performed on the data in Zhongnan Hospital of Wuhan University from January 2008 to December 2016. Skeletal muscle index (SMI) was analyzed by cross-sectional areas of body composition at the level of third lumbar (L3) vertebrae, which was measured using single-slice computer tomograph (CT) prior to CRT, at 6 months and 12 months after CRT respectively. Logistic regression analysis was conducted to explore the potential clinical risk factors of sarcopenia in this patients cohort. Regarding the dosimetrics of pancreas, the sarcopenia rate was compared between the two groups divided according to the cut-off value determined by the receiver operating characteristic (ROC) curves., Results: One hundred and fifty-three gastric cancer patients were eligible in this study. The median postoperative follow-up was 36 (7-115) months. The mean dose of pancreas was 4399.7 ± 396.0 cGy. The incidence of sarcopenia prior to CRT, at 6 months and 12 months later were 29.4% (45/153), 27.3% (35/128) and 37.0% (37/100). Both sarcopenia at 6 months (HR = 2.038, 95%CI = 1.084-3.833, P = 0.027) and sarcopenia at 12 months (HR = 2.216, 95%CI = 1.007-4.873, P = 0.048) were the independent prognostic factor of gastric cancer patients. V46 remained to be the only independent risk factor of sarcopenia at 6 months (OR = 3.889, 95%CI = 1.099-13.764, P = 0.035) and 12 months (OR = 6.067, 95%CI = 1.687-21.821, P = 0.006) in multivariate logistic regression analysis. Among the dosimetric parameters used for ROC analysis, the V46 showed the highest area under the curve (AUC = 0.707). Here is the relationship between sarcopenia rate and the cut-off value for V46. Higher sarcopenia rate at 6 months was noted in 42.6% patients with V46 ≥ 57% compared with 9% of patients with V46 < 57% (P < 0.001). The sarcopneia rate at 12 months was 52% with V46 ≥ 57% and 25% with V46 < 57% (P = 0.010)., Conclusion: Gastric cancer with sarcopenia after adjuvant CRT had poorer survival. Higher dose and larger irradiated volume of pancreas correlated with higher risk of sarcopenia. Appropriated administration of pancreas dose-volume may be conducive to reduce the risk of sarcopenia and improve survival in gastric cancer patients treated with adjuvant CRT., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

PI3K pathway is an important anti-tumor target, but its effect and mechanism is not clear in esophageal squamous cell carcinoma (ESCC). By analysis of the Cancer Genome Atlas (TCGA) datasets, we found that PI3Ks level were significantly upregulated in human esophageal cancer tissues compared with that in non-cancer tissues. The alteration of PI3K can significantly affect the overall patient survival in ESCC but not in esophageal adenocarcinoma (EAC). We found that the classic PI3K inhibitor LY294002 obviously inhibited the canonical mammalian target of rapamycin (mTOR) pathway and restrained the growth of ESCC with less toxicity to normal cells. Besides, LY294002 inhibited noncanonical PKR-like ER kinase (PERK)/elF2α/ATF4 pathway as well. Both siRNA and the small molecule inhibitor GSK2656157 against PERK/elF2α/ATF4 pathway can significantly inhibit the growth of ESCC. More importantly, GSK2656157 aggravated the inhibitory effect of LY294002 on cell growth, colony formation, and apoptosis induction of ESCC. In addition of dual high expression of PI3K and PERK pathways in the ESCC patients, the difference of overall survival (OS) was more significant than using PI3K alone. These results indicated that dual targeting of PI3K and PERK pathways might improve clinical prognosis and enhance the treatment of ESCC patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To improve clinical outcomes, parenteral nutrition, standard enteral nutrition and immuno-enhanced nutrition are widely used in the gastrointestinal tumor patients undergoing surgery, but the optimal management of postoperative nutrition support remains uncertain., Methods: We systematically searched the PUBMED, EMBASE and CNKI to identify latent studies which the effects of standard EN compared with PN or IEN on gastrointestinal tumor patients until the end of November, 2015. The quality of included trials was assessed according to the handbook for Cochrane reviewer. Statistical analysis was carried out by RevMan5.1 software., Results: 30 randomized controlled trials containing 3854 patients were contained in our meta-analysis, the results indicated that postoperative SEN could absolutely reduce the incidence of postoperative infectious (P < 0.00001) and non-infectious complications (P = 0.0003), together with its positive effect on the length of hospital stay (P < 0.00001). Additionally, enteral nutrition enhanced with immune stimulation was confirmed to be better, with a significant difference between groups in terms of total infectious (P < 0.00001) and non-infectious complications (P = 0.04), and IEN could also significantly shorten the length of hospital stay (P < 0.00001)., Conclusion: Early use of Enteral nutrition in digestive tumor patients after surgery could significantly reduce the postoperative complications and shorten the length of hospital stay, IEN should be the optimal management, while the use of parenteral nutrition should be restrict to few patients with severe intolerance to enteral nutrition., (Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Lung cancer is the leading cause of cancer related deaths worldwide. It is necessary to better understand the molecular mechanisms involved in lung cancer in order to develop more effective therapeutics for the treatment of this disease. Recent reports have shown that Wnt signaling pathway is important in a number of cancer types including lung cancer. However, the role of Frizzled-8 (Fzd-8), one of the Frizzled family of receptors for the Wnt ligands, in lung cancer still remains to be elucidated. Here in this study we showed that Fzd-8 was over-expressed in human lung cancer tissue samples and cell lines. To investigate the functional importance of the Fzd-8 over-expression in lung cancer, we used shRNA to knock down Fzd-8 mRNA in lung cancer cells expressing the gene. We observed that Fzd-8 shRNA inhibited cell proliferation along with decreased activity of Wnt pathway in vitro, and also significantly suppressed A549 xenograft model in vivo (p<0.05). Furthermore, we found that knocking down Fzd-8 by shRNA sensitized the lung cancer cells to chemotherapy Taxotere. These data suggest that Fzd-8 is a putative therapeutic target for human lung cancer and over-expression of Fzd-8 may be important for aberrant Wnt activation in lung cancer., (Copyright © 2011 Elsevier Inc. All rights reserved.)

A relationship between telomeres and radiosensitivity has been established by several studies based on non-mammalian model systems, mouse models, and few human genetic diseases. However, the relationship has not been proven in human carcinoma cells, which have more clinical significance than these other models. The present study aims to determine whether telomere length is related to radiosensitivity in human carcinoma cells, and to examine the influence of tissue or genetic background. Two HEp-2 larynx squamous carcinoma cell lines, eight hepatocellular carcinoma cell lines, and five breast cancer cell lines were used. Telomere length was determined by terminal restriction fragment (TRF) Southern blot analysis and cell survival was measured by a colony-forming assay. Our results indicated that there was a significant negative correlation of telomere length and radiosensitivity in the same tissue-derived cell lines, with or without the same genetic background. Thus, telomere length may be used as a promising tool to predict the radiosensitivity of human carcinomas.

Telomeres are shortened with each cell division and play an important role in maintaining chromosomal integrity and function. Telomerase, responsible for telomere synthesis, is activated in 90% of human tumor cells but seldom in normal somatic cells. Zidovudine (AZT) is a reverse transcriptase inhibitor. In this study, we have investigated the effects of gamma-radiation in combination with AZT on telomerase activity (TA), telomere length, DNA single-strand breaks (SSBs), DNA double-strand breaks (DSBs), and the changes in radiosensitivity of human malignant glioma cell line U251. The results showed that the TA was suppressed by AZT but enhanced by irradiation, resulting in a deceleration of restored rate of shortened telomere, decreased repair rate of DNA strand breaks, and increased radiosensitivity of U251 cells. Our results suggested that telomerase activity and telomere length may serve as markers for estimating the efficacy of cancer radiotherapy and reverse transcriptase inhibitors, such as AZT, may be used clinically as a new radiosensitizer in cancer radiotherapy.