巨噬细胞抑制因子-1与癌症相关恶病质

0 引言 癌症相关恶病质(cancer-associated cachexia,CAC)是各种晚期癌症患者的主要并发症,约80％的晚期癌症患者存在厌食和体重下降等症状,约22％的癌症患者直接死于由恶病质引起的心肺功能衰竭,而非癌症本身[1].由于CAC在晚期癌症患者中普遍存在,它已成为影响晚期癌症患者生活质量和生存预后的主要因素,探讨CAC的发病机制及有效的防治措施,对提高癌症患者的生活质量及降低其病死率具有十分重要的意义.研究发现,巨噬细胞抑制因子-1(macrophage inhibitory cytokine-1,MIC-1)是与食欲直接相关的细胞因子,下调MIC-1的表达可逆转癌症相关性厌食及体重下降[2].随着越来越多的证据表明MIC-1在大多数癌症中普遍存在,并且在癌症的发生发展中起着重要作用,其干预食欲及体重的机制也在进一步被证实和深入研究中.目前国内有关MIC-1在CAC防治中的研究报道极少,该文主要综述国外的相关研究现状,为国内进一步研究MIC-1在防治CAC中的作用机制提供依据.     

膳食因素与癌症

进入21世纪,癌症仍然是人类面临的重大健康问题,在发达国家,癌症占总死亡原因的20%,仅次于心血管疾病。预计未来20年,癌症的新发病例将会急剧增加,而我国的癌症死亡率亦呈明显的上升趋势。环境因素在癌症的形成过程中具有重要作用,膳食作为人类接触环境的最直接、最常见的环境因素在癌症的发生过程中扮演着双重角色。食物中不仅含有人体必需的营养成分,同时还有许多致癌/致突变及抗癌/抗突变物质。此外,除已证实的致癌物以外,最近的研究又证实食物中所含的新的致癌、致突变物。植物化学物是近年来提出的一种食物中所含有的新的生物活性物质,其抗癌、抗突变作用更是研究的热点。近年来,饮食习惯与癌症之间的关系也引起人们的广泛关注。     

人参对癌化学预防的研究进展

癌症治疗方法近年来虽有很大的改进 ,但大多数恶性肿瘤患者的生存率仍很低 ,生存质量差 ,昂贵的治疗费用往往使病家及社会背上沉重的经济负担 ,因此“防患于未然”被认为是最有效的癌症防治策略[1] 。从天然食物或传统中草药中筛选并分离有效、广谱的癌化学预防剂是目前癌症防治研究热点[2 ] 。人参是我国传统的保健品 ,最近的实验及人群流行病学研究表明其具有潜在广谱癌症预防作用 ,使其又成为癌症化学预防研究的热点。1　人参的分类及主要成份人参主要分为 4种 :( 1)高丽参 (ＰａｎａｘｇｉｎｓｅｎｇＣ .Ａ .Ｍｅｙｅｒ) :主要分布于朝…     

维生素C作用的防癌与致癌双重性

本文对维生素C (VitC)在癌症预防及治疗中的作用的最新进展作了简要综述 ,认为VitC可能具有双重作用 ,应用VitC预防癌症应持慎重态度     

外源化学物的雌性生殖毒性研究进展

生殖和发育功能障碍是当前严重影响人体健康的主要公共卫生问题之一。一些外源化学物作用于雌性生殖系统可能导致卵巢周期紊乱或不孕,使自发性流产率增加、子代发育异常、生育力下降等,因此鉴定具有雌性生殖毒性的外源化学物,探求其毒性作用机制,对防治外源化学物引起的生殖系统危害具有重要意义。本文总结了外源化学物对雌性生殖系统、孕期胎仔的毒性研究进展,根据其来源用途进行分类,并探索可能的机制及未来展望。     

C型性格与恶性肿瘤的相关性研究

恶性肿瘤是导致人类死亡的主要疾病之一，虽然其致病因素目前尚不明确，但随着对其病因的相关研究及临床观察，发现C型性格（社会心理因素）在恶性肿瘤的发生、发展中起着很重要的作用。因此，对癌症患者的治疗，除了外科手术、放疗、化疗和分子靶向等治疗手段外，还应重视心理治疗（尤其是C型性格的患者）；提倡健康的情绪表达方式、乐观的生活态度，改善癌症患者的心理状态，对恶性肿瘤的预防和治疗具有重要价值。     

膳食烷基间苯二酚在癌症预防中的研究进展

烷基间苯二酚（alkylresorcinols,ARs）是一种酚类脂类化合物,主要来源于小麦、黑麦等全谷物的麸皮。目前研究认为ARs可作为全谷物摄入量的膳食生物标志物,同时广泛应用于全谷物与癌症等慢性疾病的流行病学研究中。ARs具有抗氧化、抗肿瘤、抗菌、调节人体代谢以及调节肠道菌群等生物活性,可能在癌症的化学预防中发挥重要作用。本文基于膳食ARs的化学结构和生物来源,阐述膳食ARs在癌症预防中的作用及相关机制,以期为癌症预防研究提供新线索。     

辣椒素预防及抗肿瘤作用机制研究进展

应用天然果蔬中的活性化合物进行预防和治疗肿瘤是目前研究的热点。辣椒素是在辣椒皮质部分中存在的一种生物碱,具有预防和抗肿瘤作用,其抗肿瘤作用机制复杂,主要通过靶向激活辣椒素受体或其他信号通路,引起肿瘤细胞周期停滞、代谢抑制、肿瘤坏死、 凋亡和自噬,抗血管生成和降低癌细胞的转移能力,对多种肿瘤细胞,产生抗肿瘤作用,可作为癌症预防和治疗的潜在药物,特别是与其他抗癌药物联合应用,具有广泛的应用前景。本文就辣椒素预防及抗肿瘤作用机制相关研究进展进行综述。     

维生素C作用的防癌与致癌双重性

本文对维生素C（VitC)在癌症预防及治疗中的作用的最新进展作了简要综述，认为VitC可能具有双重作用，应用VitC预防癌症应持慎重态度。     

大豆异黄酮抗瘤效应及其机制的研究进展

大豆异黄酮(SIF)是具有能与雌激素受体结合、诱导产生弱雌激素样作用的植物化学物质。最近的研究表明,SIF是一种很有潜力的癌症化学预防剂,对乳腺癌、结肠癌和前列腺癌、肺癌等发生具有一定的预防作用。其可能的抗瘤机制包括雌激素和抗雌激素作用、抑制酪氨酸蛋白激酶(TPK)活性、诱导癌细胞凋亡分化及与抗癌药协同作用等。     

New opportunities in chemoprevention research

The importance of prevention in reducing the morbidity and mortality from cancer has been widely recognized. With the demonstration of tamoxifen's ability to prevent breast cancer in women, the feasibility of cancer chemoprevention in humans is now established. Future clinical chemoprevention studies should focus on phytochemicals, cancer preventive compounds in fruits, vegetables and other plants. Many phytochemicals are excellent potential chemopreventive agents, because, in addition to their cancer preventive effects, they are relatively non-toxic and inexpensive, they can be taken orally and some of them have other health benefits as well. New opportunities in clinical chemoprevention research include investigating chemopreventive effects of phytochemicals and conducting studies in patients with cancer. There is also a great need to investigate potential benefits and risks of administering phytochemicals before, during or after conventional therapies, such as surgery, chemotherapy, radiation or hormonal therapy. In addition, administration of chemopreventive agents prior to surgery provides an opportunity to investigate the modulation of genetic and epigenetic pathways by putative cancer preventive compounds and nutrients.     

Cancer Chemoprevention by Phytochemicals and their Related Compounds

Cancer chemoprevention by phytochemicals may be one of the most feasible approaches for cancer control. For ‍example, phytochemicals obtained from vegetables, fruits, spices, teas, herbs and medicinal plants, such as carotenoids, ‍phenolic compounds and terpenoids, have been proven to suppress experimental carcinogenesis in various organs. ‍These candidates should be evaluated by intervention studies, before acceptance as cancer preventive agents for human ‍application. Phytochemicals may also be useful to develop “designer foods” or “functional foods” for cancer prevention. ‍We are now planning animal foods, such as meats, eggs and milk, which contain anti-carcinogenic phytochemicals. In ‍prototype experiments, expression of genes for synthesis of phytochemicals, such as phytoene and limonene, has been ‍successful in cultured animal cells.     

Epigenetic regulation by selected dietary phytochemicals in cancer chemoprevention

The growing interest in cancer epigenetics is largely due to the reversible nature of epigenetic changes which tend to alter during the course of carcinogenesis. Major epigenetic changes including DNA methylation, chromatin modifications and miRNA regulation play important roles in tumorigenic process. There are several epigenetically active synthetic molecules such as DNA methyltransferase (DNMTs) and histone deacetylases (HDACs) inhibitors, which are either approved or, are under clinical trials for the treatment of various cancers. However, most of the synthetic inhibitors have shown adverse side effects, narrow in their specificity and also expensive. Hence, bioactive phytochemicals, which are widely available with lesser toxic effects, have been tested for their role in epigenetic modulatory activities in gene regulation for cancer prevention and therapy. Encouragingly, many bioactive phytochemicals potentially altered the expression of key tumor suppressor genes, tumor promoter genes and oncogenes through modulation of DNA methylation and chromatin modification in cancer. These bioactive phytochemicals either alone or in combination with other phytochemicals showed promising results against various cancers. Here, we summarize and discuss the role of some commonly investigated phytochemicals and their epigenetic targets that are of particular interest in cancer prevention and cancer therapy.     

Chemopreventive characteristics of avocado fruit

Phytochemicals are recognized as playing an important role in cancer prevention by fruits and vegetables. The avocado is a widely grown and consumed fruit that is high in nutrients and low in calories, sodium, and fats. Studies have shown that phytochemicals extracted from the avocado fruit selectively induce cell cycle arrest, inhibit growth, and induce apoptosis in precancerous and cancer cell lines. Our recent studies indicate that phytochemicals extracted with chloroform from avocado fruits target multiple signaling pathways and increase intracellular reactive oxygen leading to apoptosis. This review summarizes the reported phytochemicals in avocado fruit and discusses their molecular mechanisms and targets. These studies suggest that individual and combinations of phytochemicals from the avocado fruit may offer an advantageous dietary strategy in cancer prevention.     

Phytochemicals in the Fight Against Cancer

Phytochemicals are chemical compounds from fruits, vegetables, or grains and they have been used to treat various diseases for thousands of years. More than one million people in the United States get cancer each year. Although recent advances in medicine have improved the outcomes for cancer patients, there is still a need for novel approaches in the fight against cancer. One such approach that has shown promise in recent years is the use of phytochemicals alone or as synergistic agents. In this review, we will discuss the use of phytochemicals as therapeutic agents against cancer with an emphasis on apple extract.     

Chemoprevention of prostate cancer

Chemoprevention is prevention of cancer by administering natural or synthetic chemicals. Anti-androgens are among the promising chemopreventive agents for prostate cancer because prostate epithelium is androgen dependent. A National Cancer Institute supported large, randomized, clinical prostate cancer chemoprevention trial has been conducted to test the efficacy of finasteride, an inhibitor of 5--reductase, which converts testosterone to 5-hydroxy-testosterone. Now the focus is on micronutrients and phytochemicals, which have potential preventive effects against prostate cancer. Lycopene, soy isoflavones, vitamin E and selenium are among the most promising nutritional chemopreventive agents. Another NCI supported large clinical chemoprevention trial was recently started to investigate the efficacy of selenium and vitamin E, alone or in combination in the prevention of prostate cancer. Inclusion of appropriate biomarkers in clinical trials will help elucidate the mechanisms by which genetic and epigenetic pathways of carcinogenesis are modulated by nutrients and phytochemicals.     

Dietary polyphenolic phytochemicals—promising cancer chemopreventive agents in humans? A review of their clinical properties

Epidemiological and preclinical evidence suggests that polyphenolic phytochemicals exemplified by epigallocatechin gallate from tea, curcumin from curry and soya isoflavones possess cancer chemopreventive properties. Whilst such naturally occurring polyphenols have been the subject of numerous mechanistic studies in cells, information on their clinical properties, which might help assess their promise as human cancer chemopreventive agents, is scarce. Therefore, we present a review of pilot studies and trials with a cancer chemoprevention-related rationale, in which either healthy individuals or patients with premalignant conditions or cancer received polyphenolic phytochemicals. The review identifies trial design elements specifically applicable to polyphenolic phytochemicals. The available evidence for tea polyphenols tentatively supports their advancement into phase III clinical intervention trials aimed at the prevention of progression of prostate intraepithelial neoplasia, leukoplakia or premalignant cervical disease. In the case of curcumin and soya isoflavones more studies in premalignacies seem appropriate to optimise the nature and design of suitable phase III trials. The abundance of flavonoids and related polyphenols in the plant kingdom makes it possible that several hitherto uncharacterised agents with chemopreventive efficacy are still to be identified, which may constitute attractive alternatives to currently used chemopreventive drugs.     

常见植物药对结肠癌的防治作用及其作用机制

植物药对结肠癌具有良好的防治作用。姜黄素、多糖(苹果多糖、香菇多糖)、皂苷(重楼皂苷、人参皂苷)、白藜芦醇、槲皮素等植物药可通过不同信号通路抑制结肠癌细胞的增殖,促进细胞凋亡。此外,植物药还具有抗炎、抗氧化、抗血管生成、减轻化疗药物不良反应、逆转肿瘤细胞耐药等作用。了解植物药对结肠癌的防治作用及其可能的作用机制,能为结肠癌的临床防治提供更多的理论依据及治疗思路。     

Suppression of cell proliferation and gene expression by combinatorial synergy of EGCG, resveratrol and gamma-tocotrienol in estrogen receptor-positive MCF-7 breast cancer cells

Numerous dietary phytochemicals have shown anti-breast carcinogenic activities when tested in vitro; however, in most cases, the demonstrated efficacy of individual phytochemicals requires doses not readily achievable in vivo. Therefore, whether diets might exert translational promises and benefits in clinical settings and prevention of breast cancer remain unclear. Since cancer cells are endowed with complex, redundant, converging and diverging pathways spanning both the genetic and metabolic networks that are not merely replicates of those in normal cells, it is of interest to test whether a multicomponent approach involving lower, physiologically relevant doses of natural dietary agents may be developed as a chemopreventive strategy for breast cancer. Herein, we investigated, using the estrogen receptor-positive MCF-7 breast cancer cells as a model, whether the combination of epigallocatechin gallate (EGCG), resveratrol and gamma-tocotrienol at suboptimal doses elicits synergism in suppressing cell proliferation, modulating gene expression, and increasing antioxidant activity, as compared to each of the three phytochemicals added alone. The results showed that there was a approximately 33, 50 and 58% inhibition of cell proliferation by >/=50 microM EGCG, >/=25 microM resveratrol and >/=10 microM gamma-tocotrienol, respectively, added as a single agent. When a suboptimal dose (10 microM) of each phytochemical was used, a significant additive effect in suppression of cell proliferation was observed with the combination of resveratrol and gamma-tocotrienol whereas the three phytochemicals added together did not produce more pronounced inhibition of cell proliferation. A significant additive effect in reducing cyclin D1 and bcl-2 expression was found when gamma-tocotrienol was added with either EGCG or resveratrol. Functional synergism among the three phytochemicals was only observed in the induction of quinone reductase NQO1. These results suggest that diet-based protection against breast cancer may partly derive from synergy amongst dietary phytochemicals directed against specific molecular targets in responsive breast cancer cells, and provide support for the feasibility of the development of a diet-based combinatorial approach in the prevention and treatment of breast cancer.     

Molecular targets of phytochemicals for cancer prevention

Although successful for a limited number of tumour types, the efficacy of cancer therapies, especially for late-stage disease, remains poor overall. Many have argued that this could be avoided by focusing on cancer prevention, which has now entered the arena of targeted therapies. During the process of identifying preventive agents, dietary phytochemicals, which are thought to be safe for human use, have emerged as modulators of key cellular signalling pathways. The task now is to understand how these chemicals perturb these pathways by modelling their interactions with their target proteins.