Understanding telomerase in cancer stem cell biology

Comment on: Vicente-Dueñas C, et al. Oncotarget 2012; Epub ahead of print; PMID:22408137.     

一个以前列腺特异抗原密度和穿刺评分为基础的中国人群中前列腺癌根治术后病理升级预测模型的建立

目的：分析前列腺癌根治术后病理得分较穿刺得分增加的原因，并建立一个可以预测中国人群中前列腺癌根治术后病理升 级的模型。方法：以2008 年8 月至2013 年12 月在我院泌尿科行前列腺癌根治性切除术的264例患者的临床资料为基础，根据 术前和术后患者病理得分的变化将其分为升级组和未升级组。运用单因素和多因素logistic 回归分析病理升级的原因，并通过多 因素回归系数建立预测病理升级的诺模图。结果：264 例患者中，共238 例最终纳入统计分析，多因素logistic 回归分析显示前列 腺特异抗原密度(0R=3.854，P=0.001 )和穿刺Gleason(≤ 6)评分是中国人群中前列腺癌根治术后病理升级的独立危险因素。前列腺 特异抗原密度和穿刺得分的ROC 最佳截断取值为0.37 ng/ml 2和8 分。运用上述两个变量建立了一个可用于预测病理升级的诺 模图。结论：前列腺特异抗原密度和穿刺Gleason 评分是预测中国人群中前列腺癌根治术后病理升级的独立危险因素，本研究所 得的诺模图可以很好地预测前列腺癌根治术后的病理升级。     

siRNA沉默整合素beta1 基因对子宫内膜癌细胞侵袭、转移的影响

目的：探讨siRNA 沉默整合素茁1 基因对子宫内膜癌细胞侵袭、转移的影响。方法：选取子宫内膜癌ECC-1细胞系(ER阳性) 和KLE细胞系(ER阴性)，分别转染Integrin beta1 siRNA 质粒(Integrin beta1 siRNA 组)、无义序列siRNA质粒(无义序列对照组)和空载 质粒(空载对照组)，利用实时荧光定量PCR 检测各组细胞中Integrin 茁1 mRNA的表达，Western blot 检测各组细胞中Integrin beta1、 beta-catenin 和C-Myc 蛋白的表达，Transwell 小室检测各组细胞迁移和侵袭能力，MTT 法检测各组细胞的增殖情况。结果：Integrin beta1 siRNA 组ECC-1 细胞和KLE 细胞中Integrin beta1 mRNA 和蛋白相对表达量均低于无义序列对照组和空载对照组(P<0.05)； Integrin beta 1 siRNA组ECC-1 细胞和KLE细胞中beta-catenin 蛋白和C-Myc 蛋白相对表达量均低于无义序列对照组和空载对照组， 差异均有统计学意义(P<0.05)；Integrin beta1 siRNA组ECC-1 细胞和KLE 细胞中迁移细胞数和侵袭细胞数均低于无义序列对照组 和空载对照组(P<0.05)；Integrin beta1 siRNA 组ECC-1细胞和KLE 细胞的A 值均低于无义序列对照组和空载对照组(P<0.05)。结 论：特异性抑制Integrin beta1 基因可抑制子宫内膜癌细胞迁移、侵袭和增殖，可能与抑制Wnt信号传导有关。     

Prohibitin is a cholesterol‐sensitive regulator of cell cycle transit

Cholesterol is essential in establishing most functional animal cell membranes; cells cannot grow or proliferate in the absence of sufficient cholesterol. Consequently, almost every cell, tissue, and animal tightly regulates cholesterol homeostasis, including complex mechanisms of synthesis, transport, uptake, and disposition of cholesterol molecules. We hypothesize that cellular recognition of cholesterol insufficiency causes cell cycle arrest in order to avoid a catastrophic failure in membrane synthesis. Here, we demonstrate using unbiased proteomics and standard biochemistry that cholesterol insufficiency causes upregulation of prohibitin, an inhibitor of cell cycle progression, through activation of a cholesterol‐responsive promoter element. We also demonstrate that prohibitin protects cells from apoptosis caused by cholesterol insufficiency. This is the first study tying cholesterol homeostasis to a specific cell cycle regulator that inhibits apoptosis. J. Cell. Biochem. 111: 1367–1374, 2010. © 2010 Wiley‐Liss, Inc.     

From obesity to cancer: a review on proposed mechanisms

Nowadays, obesity is considered as a serious and growing global health problem. It is documented that the overweight and obesity are major risk factors for a series of noncommunicable diseases, and in recent years, the obesity‐cancer link has received much attention. Numerous epidemiological studies have shown that obesity is associated with increased risk of several cancer types, including colon, breast, endometrium, liver, kidney, esophagus, gastric, pancreatic, gallbladder, and leukemia, and can also lead to poorer treatment. We review here the epidemiological and experimental evidences for the association between obesity and cancer. Specifically, we discuss potential mechanisms focusing how dysfunctional angiogenesis, chronic inflammation, interaction of proinflammatory cytokines, endocrine hormones, and adipokines including leptin, adiponectin insulin, growth factors, estrogen, and progesterone and strikingly, cell metabolism alteration in obesity participate in tumor development and progression, resistance to chemotherapy, and targeted therapies such as antiangiogenic and immune therapies.     

What Are the Health Risks of Eating Red Meat,and How Should We Assess Them?

This paper discusses possible mechanisms that might lead to misinterpretations of collected data and makes new evidence-based medicine (EBM) recommendations to oppose the previously accepted preventive measures, or treatment options. It is focused on the danger of the “red meat” consumption, and the question whether eating pungent food is good or bad for our health and finally whether the “bad luck” concept of getting several cancer types is valid or not. These three topics got and still have significant media attention. Several mechanisms are proposed as possible causes of these apparent conflicts. Some of them have already been recognized but sadly remained less known to medical readers and also to the general population. Also see the video abstract here https://youtu.be/owjoRXrNShA .     

In vitro and in vivo studies of cancer cell behavior under nutrient deprivation

Cancer cells are confronted with nutrient deprivation because of high proliferation rate, especially at the early stage of their development. There is a frequent assumption that nutrient deprivation decreases the basal activity of cancer cells. Contrarily, there are recent evidence suggesting that cancer cells are able to modulate signaling pathways to adapt with new condition and continue their survival. This property of cancer cells is believed to be one of the prerequisites for cancer progression and chemoresistance. Moreover, recent experiments show that serum starvation in vitro as a mimic situation of nutrient deprivation in vivo triggers different signaling pathways leading to changes in cancer cell behavior, which may interfere with experimental results. Considering these facts, a better understanding of the effect of nutrient deprivation on cancer cell behavior will help us to give more accurate conclusions regarding results of in vitro studies and also to develop new strategies to treat different cancers in vivo.