癌症恶病质研究进展

癌症恶病质是导致晚期癌症患者死亡的主要病症之一.但至今尚无满意可解释本病发病机制的理论,更无有效手段控制癌症恶病质的发展.本文从晚期癌症患者机体营养摄取不足、恶性肿瘤能量消耗增加、代谢紊乱、细胞因子的作用等角度出发来阐释本病的发病机制,并介绍了国际、国内针对本病的治疗方法.     

癌症恶病质研究进展

癌症恶病质（cancercachedaCC）是指癌症患者有食欲不振、体重下降、贫血、乏力和衰竭等表现的综合征，同时也包括与癌的进行性生长相关的能量和代谢方面的异常。大约有切叽的晚期癌症患者主要死于恶痛质。尽管临床上对癌症恶病质认识较早，并对此进行研究，但至今尚无一种满意的理论能解释癌症恶病质的发生机理，更无有效手段控制恶痛质的发展。近年来随着姑息医学的发展，晚期癌症病人的姑息治疗日益受到重视，癌症恶痛质研究将成为下一世纪癌症防治研究的一个热点。一、癌症恶病质的机理三．机体营养摄取不足早年人们认为癌症恶病质是继…     

癌症恶病质的诊断及药物治疗进展

癌症恶病质是恶性肿瘤的常见并发症,是由多因素引起的一系列虚弱症状为临床表现的综合征。全文就癌症恶病质的定义、诊断规范化及药物治疗研究进展进行综述。     

罗红霉素治疗癌症恶病质的实验

目的 研究罗红霉素对癌症恶病质小鼠的治疗作用并探讨其可能机制。方法 于皮下接种小鼠结肠腺癌Colon26细胞于雄性BALb/c小鼠后9天建立癌症恶病质模型。实验动物分为三组：正常对照组、模型对照组、恶病质罗红霉素治疗组。观察癌症恶病质鼠治疗后的一般指标（体质量、去瘤体质量、食物摄入量、左侧腓肠肌重量）,血清营养指标（白蛋白、血糖、甘油三酯）,并用ELISA法检测血清肿瘤坏死因子-α(tumor necrosis factor-α, TNF-α)、白介素-6(interleukin-6, IL-6)水平。结果 荷瘤小鼠去瘤体质量明显下降,严重的代谢紊乱（白蛋白、血糖水平降低、甘油三酯水平升高）,血清TNF-α、IL-6水平升高。罗红霉素治疗组与模型组相比左侧腓肠肌重量增加,血糖升高,甘油三酯降低,血清TNF-α降低。结论 罗红霉素具有抗癌症恶病质的作用,其机制可能是通过降低升高的TNF-α产生。     

癌症恶病质与肿瘤坏死因子关系的临床研究

 目的　初步探讨肿瘤坏死因子(TNF -α)含量与癌症恶病质的关系。方法　用苯丙酸诺龙及营养支持疗法对19 例恶病质患者治疗三周,观察治疗前后患者血清中TNF-α,体重、右上臂中部周径、三头 肌 皮摺厚度,KPS评分、总蛋白、白蛋白的变化,并与17例健康对照组进行比较。结果 　疾病组治疗前TNF-α值明显高于对照组(P＜0.01),治疗后TNF-α值较治 疗前明显下降(P＜0.01),并接近对照组,治疗后其余各项指标较治疗前均增加,病 情好转时TNF-α值是下降的。结论　TNF-α可能是参与恶病质过程的重要 细胞因子之一,其水平高低与病情轻重相关联。     

康莱特抗癌症恶病质实验研究

研究通过Ｔ７３９小鼠接种ＬＡ７９５（小鼠肺腺癌）建立癌症恶病质动物模型，并采用康莱特对癌症恶病质鼠进行治疗，观察癌症恶病质鼠治疗后生理状况（体重、摄食量等）的改善及与癌症恶病质发生、发展相关的血清细胞因子如ＴＮＦ－α、ＩＬ－１和ＩＬ－６的水平变化。ＴＮＦ－α血清水平用ＲＩＡ检测，ＩＬ－１及ＩＬ－６用ＥＬＩＳＡ法。结果表明：与生理盐水治疗荷瘤小鼠相比，康莱特能明显阻止癌症恶病质鼠体重下降、增加其摄食量、延长生存期、延缓肿瘤生长、并使部分肿瘤液化、坏死。血清ＴＮＦ－α和ＩＬ－１水平同时也明显下降，实验所见均提示康莱特具有明显的抗癌症恶病质作用。     

细胞因子与癌症恶病质关系的实验研究

癌症恶病质是指由癌症患者的体重丧失、厌食、贫血、无力以及体内代谢异常等组成的临床综合征。我们采用ＬＡ795接种Ｔ739小鼠建立癌症恶病质模型 ,初步探讨细胞因子与恶病质的关系 ,同时观察胰岛素对恶病质的疗效。一、材料与方法1.癌症恶病质动物模型的建立 :取新鲜ＬＡ795瘤块 ,经剪碎、研磨、过滤及稀释后制成含癌细胞 10 7/ｍｌ的单细胞悬液 ,取 0 1ｍｌ接种于小鼠右侧腹皮下。接种后第 8天小鼠进入恶病质状态。2 .动物分组及治疗方案 :将 32只小鼠随机分为 4组 ,分别为非荷瘤空白对照组 (ＮＴＢ)、荷瘤非治疗组 (ＮＴ)、荷瘤生理盐水…     

细胞因子在实验性癌症恶病质中的作用

目的 探讨细胞因子TNF-α、IL－1、IL－6与癌症恶病质的关系,观察消炎痛对癌症恶病质的治疗效果。方法 且肺腺癌（LA795)接种T739小鼠建立癌症恶病质实验模型,测定荷瘤前后不同阶段小鼠血清IL－6、IL－1、TNF－α的水平及血糖、甘油三酯和总蛋白的变化及体重变化,并且观察消炎痛对癌症恶病质的治疗效果。结果 癌症恶病质小鼠的体重、血糖、血甘油三酯、血总蛋白显著低于非荷瘤组,而血清IL－6、TNF－α和IL－1水平显著高于非荷瘤组。消炎痛治疗后,恶病质小鼠的体重、摄食量、血糖、血甘油三酯和血总蛋白水平较生理盐水对照组显著提高且生存时间延长,同时IL－6、TNF－α、IL－1的血清水平显著低于生理盐水对照组。结论 IL－6、TNF-α、IL－1参与了本动物模型的癌症恶病质诱导。通过抑制IL-6、TNF-α、IL－1的升高,消炎痛具有改善癌症恶病质的作用。     

癌症恶病质的中医药研究进展

癌症恶病质是晚期肿瘤患者常见的一种病症.从临床和基础研究两个方面回顾了近年来中医在癌症恶病质方面研究的进展情况.并对目前研究中存在的问题和今后的研究方向做了简要评述.     

癌性恶病质相关因子及EPA在癌性恶病质中的作用

癌症引起的恶病质即癌性恶病质(CC)是导致癌症患者死亡的主要原因,其致死率高达80%,但至今其发生机制尚不明确,更无有效手段逆转或控制其发展。二十碳五烯酸(EPA)能够促进瘦肌群的合成,因此有望成为治疗CC的主要药物。本文就CC相关的细胞因子、蛋白诱导分解因子、脂肪诱导因子等在CC发生中的作用作一综述,并探讨EPA逆转癌性恶病质的可行性。     

恶性肿瘤恶病质骨骼肌萎缩分子机制研究进展

目的：总结国内外对恶性肿瘤恶病质状态下骨骼肌萎缩的分子机制研究进展。方法：应用PubMed和维普期刊资源整合平台,以“恶性肿瘤、恶病质、骨骼肌萎缩、泛素-蛋白酶体途径和自噬信号通路”作为关键词,检索2002—01—01—2013—12—31相关文献。纳入标准：1）恶性肿瘤;2）恶病质;3）骨骼肌萎缩;4）泛素-蛋白酶体途径;5）自噬信号通路。根据纳入标准符合分析的文献33篇。结果：机体在各种刺激下主要通过UPP和ALP降解骨骼肌细胞,ALP在恶病质状态下活性明显升高,UPP可能在恶性肿瘤恶病质中晚期激活。在饥饿和应激等情况下,UPP和ALP可能主要经Akt／PI3K-／mTOR调控;在恶性肿瘤恶病质状态下,FoxO被抑制,骨骼肌萎缩可能主要与NF-κB和p38MAPK有关。NF-gB能调控E3s转录,并且在Beclinl的基因序列上有相应结合位点;p38MAPK抑制剂SB202190能使E3s及LC3表达下调。结论：对恶性肿瘤恶病质状态下骨骼肌萎缩调控机制的研究将有助于靶向药物的研发,以期改善恶性肿瘤恶病质患者的预后。     

Pathogenesis of cancer cachexia

Cachexia is a progressive wasting syndrome characterized by extensive loss of adipose tissue and skeletal muscle. It occurs in about half of all cancer patients. While anorexia also may be present, the energy deficit alone does not explain the pathogenesis of cachexia. The presence of an acute phase response (APR) has been linked to accelerated weight loss and a shortened survival time. The APR is thought to be initiated by cytokines such as interleukin (IL)-6 and IL-8, production of which is induced by a tumor factor, proteolysis inducing factor (PIF). Cachectic cancer patients also show an increased expression of uncoupling protein-3 in muscle, which may act as an energy sink, increasing energy expenditure. Loss of adipose tissue appears to be due to an increase in degradation of triglycerides, rather than a decrease in synthesis. One candidate for this effect is a tumor lipid mobilizing factor, which stimulates lipolysis directly through a cyclic AMP-mediated process via interaction with a beta3-adrenergic receptor. Loss of skeletal muscle arises from both a depression in protein synthesis and an increase in protein degradation. The major proteolytic pathway involved in intracellular protein breakdown in cachectic muscle is the ATP-ubiquitin-dependent proteolytic pathway. Both PIF and tumor necrosis factor-alpha, but not other cytokines, can induce expression of the key regulatory components of this pathway. Eicosapentaenoic acid, found in oily fish, effectively attenuates protein degradation in cachectic muscle by inhibiting the increased proteasome expression and can stabilize body weight in cachectic cancer patients.     

Mechanisms of cancer cachexia

It is currently hypothesized that the mechanisms of cancer cachexia involve the host's production of inflammatory cytokines, which in turn orchestrate a series of complex interrelated steps that ultimately lead to a chronic state of wasting, malnourishment, and death (see Fig. 1). The metabolic changes seen in the tumor-bearing host are similar, but not identical, to those seen in sepsis and inflammation and appear to result from a generalized response of the host to the stimulus of invasion--the tumor. Although there are likely to be several humoral factors, of either host or tumor origin (see Fig. 1), involved in cancer cachexia, recombinant DNA methodology has provided sufficient amounts of only a few cytokines to enable careful investigation of their cachectic potential. TNF/cachectin has been most extensively studied and appears to play a clear role, because administration of low-dose continuous or escalating doses simulates changes associated with cancer cachexia. In addition, these cachectic changes have been blocked by a specific antisera. IL-1, IL-6, and interferon-gamma all have potential as mediators of cancer cachexia and more work is clearly indicated. It is possible that, given our current understanding of the mechanisms of cancer cachexia, it can be theorized that TNF, which causes many of the manifestations of cancer cachexia, and IL-1 are released by macrophages in response to tumor (see Fig. 1). Interferon-gamma appears to potentiate these effects and may also be necessary for the complete syndrome of cancer cachexia. IL-6 probably is released as another mediator, principally mediating the acute phase response seen in cancer cachexia. Other factors are certain to be involved. Further study into the mechanisms and possible treatment of cancer cachexia is needed, because a large proportion of cancer patients who are incurable by current therapies continue to suffer from this lethal wasting diathesis. Furthermore, specific strategies to reverse the cachectic changes associated with cancer will likely improve antitumor treatment.     

Multitargeted treatment of cancer cachexia

Cancer cachexia is defined as a multifactorial syndrome characterized by an ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment. The prominent clinical feature of cachexia is weight loss in adults. Anorexia, inflammation, insulin resistance, and increased muscle protein breakdown frequently are associated with cachexia. One single therapy may not be completely successful in the treatment of cachexia because of the complexity of the pathogenesis and symptoms of the cachexia syndrome. Among effective treatments, progestogens currently are considered the best available treatment option and are the only approved drugs in Europe for the treatment of cancer- and AIDS-related cachexia. However, they have limited efficacy in treating cancer cachexia. However, thalidomide, selective COX-2 inhibitors, ghrelin mimetics, and selective androgen receptor modulators showed promising results but should be defined further and confirmed in clinical trials. Therefore, to date, despite several years of coordinated efforts in basic and clinical research, the practice guidelines for the prevention and treatment of cancer-related anorexia cachexia syndrome (CACS) are lacking. The management of CACS is a complex challenge that should address the different causes underlying this clinical event. Recent studies showed that integrated, multitargeted approaches are more effective than single-agent approaches for the treatment of CACS. Further clinical trials to improve and refine current strategies to counteract cancer cachexia using multimodal interventions, including nutritional supplementation, anabolic agents, and antiinflammatory drugs along with an appropriate physical exercise program, are warranted.     

癌性恶病质内科治疗进展

癌症恶病质是晚期肿瘤患者常见综合征,是肿瘤组织与机体相互作用的结果,肿瘤组织产生炎性细胞因子及特定因子作用于机体,而机体应激产生全身急性反应及神经内分泌反应,如此相互作用导致恶病质.同时,患者的年龄、体力活动水平和肌肉蛋白的异常代谢也被认为与癌性恶病质发生相关.目前,临床治疗癌性恶病质的策略主要针对改善患者的厌食症状,随着对发病机制深入了解,一些具有明确靶点的药物研究成为热点.     

癌症恶病质与细胞因子的关系及消炎痛干预的实验研究

目的　探讨癌症恶病质实验模型中细胞因子IL 1、IL 6、TNF α、IFN γ水平的变化 ,观察常规剂量消炎痛对癌症恶病质的改善效果以及对小鼠生存时间的影响。方法　用Lewis肺癌细胞株接种纯种C57小鼠建立癌症恶病质的实验模型 ,检测小鼠在不同阶段血清IL 1、IL 6、TNF α、IFN γ的水平及体重变化 ,同时观察每日腹腔内注射常规剂量消炎痛对癌症恶病质的治疗疗效。结果　癌症恶病质组小鼠血清IL 1、IL 6、TNF α的水平显著高于健康对照组 (P <0 .0 5 ) ,而体重明显低于健康对照组 (P <0 .0 5 )。癌症恶病质小鼠中 ,消炎痛治疗组小鼠的体重明显高于生理盐水对照组且生存时间延长 (P <0 .0 5 ) ,而血清IL 1、IL 6、TNF α的水平显著低于生理盐水对照组 (P <0 .0 5 )。血清IFN γ在癌症恶病质小鼠与健康对照组之间 ,在消炎痛治疗组与生理盐水对照组之间比较差异均无显著性 (P >0 .0 5 )。结论　IL 1、IL 6、TNF α可能参与癌症恶病质的发生发展 ,通过采用消炎痛积极干预 ,能明显降低血清IL 1、IL 6、TNF α的水平 ,改善恶病质 ,延长生存期。IFN γ不参与癌症恶病质的发生发展。