• TNM分期不能准确预测辅助化疗的结肠癌(CC)患者的预后;
  • 汇总参与N0147 和PETACC3 III期辅助化疗临床试验的3016例患者的数据,建构5年生存率的多变量Cox模型,并进行内部和外部验证;
  • 多变量分析提示TNM分期、MSI和BRAFV600E是独立的预后因素;
  • 在TNM分期总体生存期模型中引入MSI、BRAFV600E和KRAS突变状态,可精确预测II期和III期CC患者的预后,但在包括临床病理特征的多变量模型中预测的准确度仅有轻度提高,尤其是化疗患者。
Annals of Oncology [IF:18.274]

Prediction of overall survival in stage II and III colon cancer beyond TNM system: a retrospective, pooled biomarker study



2017-02-09, Article

Abstract & Authors:展开

Non-melanoma skin cancers (NMSCs) are the leading cause of skin cancer-related morbidity and mortality. Effective strategies are needed to control NMSC occurrence and progression. Non-toxic, plant-derived extracts have been shown to exert multiple anti-cancer effects. Graviola (), a tropical fruit-bearing plant, has been used in traditional medicine against multiple human diseases including cancer. The current study investigated the effects of graviola leaf and stem extract (GLSE) and its solvent-extracted fractions on two human NMSC cell lines, UW-BCC1 and A431. GLSE was found to: (i) dose-dependently suppress UW-BCC1 and A431 cell growth, motility, wound closure, and clonogenicity; (ii) induce G₀/G₁ cell cycle arrest by downregulating cyclin/cdk factors while upregulating cdk inhibitors, and (iii) induce apoptosis as evidenced by cleavage of caspases-3, -8 and PARP. Further, GLSE suppressed levels of activated hedgehog (Hh) pathway components Smo, Gli 1/2, and Shh while inducing SuFu. GLSE also decreased the expression of pro-apoptotic protein Bax while decreasing the expression of the anti-apoptotic protein Bcl-2. We determined that these activities were concentrated in an acetogenin/alkaloid-rich dichloromethane subfraction of GLSE. Our data identify graviola extracts and their constituents as promising sources for new chemopreventive and therapeutic agent(s) to be further developed for the control of NMSCs.

First Authors:
R Dienstmann

Correspondence Authors:
R Dienstmann

All Authors:
R Dienstmann, M J Mason , F A Sinicrope , A I Phipps , S Tejpar , A Nesbakken , S A Danielsen , A Sveen , D D Buchanan, M Clendenning , C Rosty, B Bot , S R Alberts , J Milburn Jessup, R A Lothe , M Delorenzi, P A Newcomb , D Sargent, J Guinney