Flavonoids: A Myth or a Reality for Cancer Therapy?

Nutraceuticals are biologically active molecules present in foods; they can have beneficial effects on health, but they are not available in large enough quantities to perform this function. Plant metabolites, such as polyphenols, are widely diffused in the plant kingdom, where they play fundamental roles in plant development and interactions with the environment. Among these, flavonoids are of particular interest as they have significant effects on human health. In vitro and/or in vivo studies described flavonoids as essential nutrients for preventing several diseases. They display broad and promising bioactivities to fight cancer, inflammation, bacterial infections, as well as to reduce the severity of neurodegenerative and cardiovascular diseases or diabetes. Therefore, it is not surprising that interest in flavonoids has sharply increased in recent years. More than 23,000 scientific publications on flavonoids have described the potential anticancer activity of these natural molecules in the last decade. Studies, in vitro and in vivo, show that flavonoids exhibit anticancer properties, and many epidemiological studies confirm that dietary intake of flavonoids leads to a reduced risk of cancer. This review provides a glimpse of the mechanisms of action of flavonoids on cancer cells.     

Tracking Cancer Metastasis In Vivo by Using an Iridium‐Based Hypoxia‐Activated Optical Oxygen Nanosensor

We have developed a nanosensor for tracking cancer metastasis by noninvasive real‐time whole‐body optical imaging. The nanosensor is prepared by the formation of co‐micelles from a poly(N‐vinylpyrrolidone)‐conjugated iridium(III) complex (Ir‐PVP) and poly(ε‐caprolactone)‐b‐poly(N‐vinylpyrrolidone) (PCL‐PVP). The near‐infrared phosphorescence emission of the nanosensor could be selectively activated in the hypoxic microenvironment induced by cancer cells. The detection ability of the nanosensor was examined in cells and different animal models. After intravenous injection, the nanosensor can be effectively delivered to the lung and lymph node, and cancer cell metastasis through bloodstream or lymphatics can be quickly detected with high signal‐to‐background ratio by whole‐body imaging and organ imaging. Moreover, the nanosensor exhibits good biocompatibility both in vitro and in vivo. The nanosensor is believed to be a powerful tool for the diagnosis of cancer metastasis.     

Nek2 Kinase Signaling in Malaria,Bone, Immune and Kidney Disorders to Metastatic Cancers and Drug Resistance: Progress on Nek2 Inhibitor Development

Cell cycle kinases represent an important component of the cell machinery that controls signal transduction involved in cell proliferation, growth, and differentiation. Nek2 is a mitotic Ser/Thr kinase that localizes predominantly to centrosomes and kinetochores and orchestrates centrosome disjunction and faithful chromosomal segregation. Its activity is tightly regulated during the cell cycle with the help of other kinases and phosphatases and via proteasomal degradation. Increased levels of Nek2 kinase can promote centrosome amplification (CA), mitotic defects, chromosome instability (CIN), tumor growth, and cancer metastasis. While it remains a highly attractive target for the development of anti-cancer therapeutics, several new roles of the Nek2 enzyme have recently emerged: these include drug resistance, bone, ciliopathies, immune and kidney diseases, and parasitic diseases such as malaria. Therefore, Nek2 is at the interface of multiple cellular processes and can influence numerous cellular signaling networks. Herein, we provide a critical overview of Nek2 kinase biology and discuss the signaling roles it plays in both normal and diseased human physiology. While the majority of research efforts over the last two decades have focused on the roles of Nek2 kinase in tumor development and cancer metastasis, the signaling mechanisms involving the key players associated with several other notable human diseases are highlighted here. We summarize the efforts made so far to develop Nek2 inhibitory small molecules, illustrate their action modalities, and provide our opinion on the future of Nek2-targeted therapeutics. It is anticipated that the functional inhibition of Nek2 kinase will be a key strategy going forward in drug development, with applications across multiple human diseases.     

Poria Acid,Triterpenoids Extracted from Poria cocos,Inhibits the Invasion and Metastasis of Gastric Cancer Cells

Background: Poria cocos (P. cocos) is an important medicinal fungus in traditional Chinese medicine. Poria acid (PA), a triterpenoid compound, is an effective component of traditional Chinese medicine P. cocos. This experiment investigated the anti-gastric cancer biological activity of PA in vitro. Methods: The effect of PA on the viability of gastric cancer cells was detected by the thiazolyl blue (MTT) assay. Cell adhesion assays were used to detect changes in the adhesion of cells treated after PA (0, 20, 40, and 80 µmol/L). The ability of cell invasion and migration were detected by Transwell assays and wound healing assays. A high-content imaging system was used to dynamically record the motility of the gastric cancer cells after PA (0, 20, 40, and 80 µmol/L) treatment. Western blotting was used to detect the expression of epithelial–mesenchymal transformation (EMT), invasion and migration related proteins. Results: The MTT assay showed that the proliferation of gastric cancer cells was significantly inhibited after PA treatment. Cell adhesion experiments showed that the adhesion of gastric cancer cells was significantly decreased after PA treatment. Compared with the control group, the wound healing area of the gastric cancer cells treated with different concentrations of PA decreased. The Transwell assay showed that the number of gastric cancer cells passing through the cell membrane were significantly reduced after PA treatment. In addition, after PA treatment, the cells’ movement distance and average movement speed were significantly lower than those of the control group. Finally, PA can significantly alter the expression of EMT-related proteins E-cadherin, N-cadherin, and Vimentin and decreased the expressions of metastasis-related proteins matrix metalloproteinase (MMP) 2, MMP-9 and tissue inhibition of matrix metalloproteinase (TIMP)1 in the gastric cancer cells. Conclusions: Triterpenoids from P. cocos have significant biological activity against gastric cancer, and the mechanism may be involved in the process of epithelial–mesenchymal transformation.     

Mechanochemistry in cancer cell metastasis

In this review, we introduced the mechanical factors in cancer cell metastasis, intracellular mechanical sensors and methods to measure the mechanical forces of tumor cells for evaluating the mechanochemistry in cancer metastasis.     

结肠癌根治术中经门静脉属支一次性化疗预防肝转移

目的：预防结肠癌根治术后的肝转移。方法：自1992－1994年，我们对59例结肠癌患者施行结肠癌根治术，在术中从肠系膜上静脉或肠系膜下静脉或其它任何一个门静脉属支一次性注入5．Fu1．0克。结果：术后随访3年，肝转移年6．78％。结论：结肠癌根治术中经门静脉属支一次性化疗可明显降低肝转移率。     

Rapid biochemical profiling of endothelial dysfunction in diabetes,hypertension and cancer metastasis by hierarchical cluster analysis of Raman spectra

Raman spectroscopy is a label free, versatile, simple and fast method that is increasingly used to detect pathological changes in the cells and tissues that could be useful in medical diagnostics. In this work, we tested the hypothesis that Raman spectroscopy may serve to detect endothelial dysfunction in murine models of lifestyle diseases associated with endothelial dysfunction. For that purpose, we analysed spectra from ex vivo vessels taken from mice with diabetes, hypertension and cancer metastasis. We extracted 50–70 random, single spectra, recorded in 0.2 s, from endothelium of mice with diseases and respective control animals and subjected them to hierarchical cluster analysis. Independently on the sample preparation protocol, very good discrimination was obtained for three‐tested murine models, i.e. diabetes, hypertension and cancer metastasis. Obtained sensitivity and specificity parameters were between 93% and 96% (with the exception of sensitivity in the diabetes model equalled to 88%). Our results show that single, random spectra of endothelium, recorded in less than a second, contains enough information on biochemical content of the endothelium to detect endothelial dysfunction. Furthermore, we demonstrated that biochemical profile of the endothelial dysfunction in diabetes, hypertension or cancer metastasis differs with a very high specificity and sensitivity. This conclusion can be a good starting point for the development of in vivo fast diagnostic methodology of endothelium in the future. Copyright © 2016 John Wiley & Sons, Ltd.     

激素受体阳性乳腺癌预后影响因素分析

目的 分析激素受体阳性乳腺癌患者预后影响因素并为乳腺癌的临床治疗提供帮助。方 法根据入组标准收集2006 年1 月1日至2008 年12 月31 日收治的激素受体阳性乳腺癌患者285 例,并回顾性分析285 例乳腺癌患者的临床病理特点、治疗方式与患者无病生存率（disease free survival,DFS）与总生存率（overall survival,OS）之间的关系,探究其预后的影响因素。结果 随访的285 例中,5年DFS 为90.3%,5 年OS 为94.6%。年龄≤35 岁患者相比35~60 岁患者DFS 与OS 均缩短（P＜0.01）。淋巴结未转移患者比转移患者预后更佳（P＜0.01）。术后辅助化疗、术后辅助放疗、内分泌治疗可显著改善患者的DFS 及OS（P＜0.01）。间断或中断内分泌治疗能影响患者DFS 与OS（P＜0.01）。中药巩固治疗能改善患者DFS（P＜0.05）,但未能影响OS。结论 淋巴结转移是全组患者的不良预后因素。辅助化疗、辅助放疗、内分泌治疗均能改善激素受体阳性乳腺癌的生存,加强术后的个体化管理对规范内分泌治疗意义重大。     

非小细胞肺癌脑转移放化疗联合治疗的临床观察

目的评价Topote Call联合顺铂方案（TPTP方案）治疗非小细胞肺癌脑转移的临床疗效。方法64例非小细胞肺癌伴脑转移的患者随机分两组,全脑放疗后给予TPTP方案或GP方案化疗2-4周期,观察患者对该方案的疗效及毒性反应。结果TPTP方案组脑部病灶客观有效率59．38％,肺部病灶的有效率为62．50％。GP方案组脑部病灶客观有效率53．13％,肺部病灶的有效率为56．25％,‘I哪方案组有效率高于GP组,两组之间差异有统计学意义（P=0．023）。毒性反应TPTP方案组腹泻、脱发发生率高,GP方案组血小板减少发生率高,组问有统计学差异（P〈0．05）,但均叮耐受。结论Topotecan联合顺铂方案是一种有效的治疗非小细胞肺癌脑转移的化疗方案。     

高转移的人卵巢癌细胞遗传学研究

本文对自建的人卵巢癌细胞系（ＨＯ－８９１０）和用该细胞建成的高转移人卵巢癌裸鼠皮下移植癌模型（ＮＳＭＯ）进行了细胞遗传学的比较研究。结果提示：两株细胞均属超二倍体核型，众数为５４条。１、３、１５和２２号染色体常见缺失，１０、１６、１９和２２号染色体常见增加，部分核型中Ｘ染色体有１条缺失，同时发现由１、３、１３、１４和１５号染色体异常而形成的４个标记染色体。ＨＯ－８９１０核型不同的特征是除了４个出现频率较高的标记染色体外，还可见一些其他异常染色体，而ＮＳＭＯ核型中只出现与ＨＯ－８９１０同样的４个标记染色体，很少见有其他异常的染色体，这４个标记染色体可能是高转移卵巢癌独特的遗传特征，这对深入探讨卵巢癌病因和癌变机理有其重要意义。