癌性恶病质发生发展机制研究进展

癌性恶病质以短期内体重下降、脂肪及肌肉消耗为临床特征,此外还有厌食、低血糖、水肿、衰竭等。近年研究发现,引起恶病质的主要原因为代谢异常、宿主免疫系统产生致炎细胞因子、体循环中肿瘤产生的分解代谢因子等。全文就癌性恶病质发生发展机制的研究进展作一综述。     

塞来昔布治疗癌痛的临床研究

[目的]评价塞来昔布(西乐葆,celecoxib)治疗癌痛的效果及安全性。[方法]前瞻性观察西乐葆治疗不同程度和部位癌痛的效果和副反应,164例按癌痛程度分为1组(轻度组)31例、2组(中度组)99例和3组(重度组)34例;按癌痛部位分为:A组(骨和转移性骨癌组)58例,B组(内脏、软组织和淋巴结转移组)51例和C组(复发和术后组)55例。西乐葆起始剂量200mgpoq12h,疼痛不缓解,增加至400mgpoq12h,1￣3d内调到理想剂量,用药5d疼痛仍不能缓解,改用二、三阶梯止痛药物。[结果]止痛有效率为75.6%,其中1、2、3组为100%、79.8%、41.2%(P<0.01);A、B、C组为77.6%、76.5%、72.7%(P>0.05)。中位止痛有效时间21d(8￣491d)。活动障碍、KPS及生活质量改善率分别为66.7%、55.4%和37.2%。副反应中上腹不适1.8%(3/163),1例停药;上消化道出血1例(0.6%)停药;皮疹0.6%。[结论]西乐葆治疗轻、中度癌痛安全、有效;疗效与癌痛程度有关,和部位无关。并可改善2/3患者的活动障碍,1/2患者的体能状况和1/3患者的生活质量。     

癌性恶病质发病机制的研究进展

目的:总结癌性恶病质发病机制及实验研究现状,探讨厌食、机体代谢异常、细胞因子在恶病质发生中的作用机制,整理恶病质基础实验研究进展。方法:应用PubMed及CNKI期刊全文数据库检索系统,以"恶病质"、"发病机制"和"实验研究"等为主题词,检索2005-2011年的相关文献,共检索到61篇文献。纳入标准:1)恶病质的发病机制研究;2)厌食、机体代谢异常、细胞因子在恶病质发生中的作用;3)有关恶病质的基础实验研究。根据纳入标准符合分析的文献有29篇。结果:恶病质是晚期癌症患者死亡的重要原因。厌食、机体代谢异常、细胞因子变化促使了恶病质的发生,许多学者通过基础实验研究了恶病质动物模型及药物干预作用,并取得了良好效果。结论:恶病质发病机制较为复杂,有待进一步深入系统研究。药物干预尤其是中医中药的治疗,是防治恶病质的一个重要措施。     

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。     

癌性恶病质与细胞因子

癌性恶病质是晚期恶性肿瘤患者常见的一种临床综合征,恶病质的原因和发生机制十分复杂,多种细胞因子在恶病质的发生发展中起了非常重要的作用,与此相关的治疗方法是目前的研究热点。现就与癌性恶病质相关的细胞因子及其与之相关的防治对策作一综述。     

癌性恶病质与细胞因子

癌性恶病质是晚期恶性肿瘤患者常见的一种临床综合征,恶病质的原因和发生机制十分复杂,多种细胞因子在恶病质的发生发展中起了非常重要的作用,与此相关的治疗方法是目前的研究热点。现就与癌性恶病质相关的细胞因子及其与之相关的防治对策作一综述。     

癌性恶病质的诊断和治疗

 癌性恶病质传统的治疗方法一般在晚期进行干预,以增加营养摄入为主,并且多以体重做为判断疗效的标准,大量临床试验证明效果并不理想。最近的研究表明在恶病质早期即以蛋白酶体为靶点进行靶向治疗,并与传统治疗相结合,治疗后核因子-κB（NF-κB）水平降低,肌纤维蛋白破坏终止,血浆蛋白及瘦体数量升高,功能好转。     

癌性恶病质发病机制及治疗的研究进展

伴发肿瘤的恶病质称肿瘤相关癌性恶病质(cancerchexia，以下简称恶病质)，以短期内体重下降，脂肪及肌肉消耗为临床特征，此外还有厌食、低血糖、水肿、衰竭等。癌症晚期约50％、终末期约80％发生恶病质，在老年患和儿童更为常见，并随进程而加重。总体来看，实体瘤发病率较高，80％晚期消化道和60％的晚期胃癌有相当程度的体重减轻。。恶病质往往是癌症病人死亡的主要原因之一。     

癌性恶病质发病机制及治疗的研究进展

癌性恶病质（ｃａｎｃｅｒ ｃａｃｈｅｘｉａ，ＣＣ）在癌症晚期病人发生率较高，是导致癌症死亡的常见原因，其发病机制尚不完全清楚，参与发病的主要有ＴＮＦ－α、ＩＬ－６、ＩＬ－Ｉ及ＩＦＮ－γ等多种细胞因子，另外，白血病掏因子和脂肪动员因子等肿瘤细胞代谢产物及其他因子在ＣＣ的发生发展过程中可能也起着重要的作用。治疗上目前尚无特效药，但有些物质，如ＥＰＡ、ＩＬ－１２及５′－脱氧氟尿嘧啶等将有可能成为防治恶病     

癌性恶病质发生的分子机制及其逆转

癌性恶病质（cancer cachexia,CC）主要是由肿瘤毒性产物及机体释放的细胞因子引起的以全身代谢紊乱为特征的一种继发性反应,其发生的确切分子机制至今尚不完全清楚。通过对CC发病机制的深人研究,针对发病机制为基础的治疗药物将明显改善CC患者的预后。同时作者提出CC的诊断标准供参考。[第一段]     

Activation of intestinal mucosal immunity in tumor-bearing mice by lactoferrin.

We have previously demonstrated that oral administration of bovine lactoferrin (bLF) markedly increases CD4(+) and CD8(+) T cells and NK (asialoGM1(+) ) cells in the blood of tumor-bearing mice and enhances anti-metastatic activity. In this paper, we document that oral administration of bLF and bLF-hydrolysate (bLFH) is associated with strong increases in CD4(+) and CD8(+) T, as well as asialoGM1(+) cells in lymphoid tissues and lamina propria of the small intestine in mice, especially in tumor-bearing animals in which Co26Lu cells were implanted subcutaneously. Moreover, IgM(+) and IgA(+) B cells in lamina propria of the small intestine were also significantly increased by bLF and bLFH. Bovine apo-transferrin (bTF) did not exhibit such activity. In the colon, only CD8(+) cells were significantly increased by treatment with bLF, while asialoGM1(+) cells were significantly decreased. bLF and bLFH induced cytokines to activate T, B and asialoGM1(+) cells. Administration of bLF and bLFH, but not bTF, increased production of interleukin-18 (IL-18), interferon-gamma (IFN-gamma) and caspase-1 in the mucosa of the small intestine. Particularly high levels of IL-18 were found in the epithelial cells of the small intestine. Moreover, administration of bLF and bLFH, but not bTF, induced IFN-gamma presenting cells in the small intestine. Caspase-1, which processes proIL-18 to mature IL-18, was also induced in the epithelial cells of the small intestine following treatment with bLF and bLFH, but not with bTF. These results suggest that enhanced production of IL-18 and IFN-gamma and caspase-1 induction by treatment with bLF may be important for elevation of intestinal mucosal immunity.     

Experimental cancer cachexia induced by transplantable colon 26 adenocarcinoma in mice

The present study investigates a tumor model for cachectic mice. Among various murine transplantable tumors, used for assessing cytostatics, we identified colon 26 adenocarcinoma (colon 26) as capable of causing cachexia. Fifteen days after inoculation, the tumor grew to about 6% of the body weight causing substantial carcass weight loss of 3.4 g (14.5% of the carcass weight). When the tumor size was 2.7 g at 3 weeks after the inoculation, the carcass weight was 12 g less than the age-matched control. The tumor continued to grow while the mice maintained this weight, surviving for an average of 45 days. This extensive weight loss was essentially the wasting of adipose and muscle tissues. Hypoglycemia and hypercorticism occurred during the time of the weight loss. In addition, the colon 26 caused disorders of hepatic functions: the concentration of acute phase proteins in serum increased; the number of hepatic glucocorticoid-cytosol receptors decreased; and activities of hepatic catalase and drug-metabolizing enzymes decreased. On the other hand, noncachectic mice with Meth A fibrosarcoma gained weight, which was somewhat less than the control, and had neither hypoglycemia nor hypercorticism, although some mild disorders of hepatic functions were found. Mice bearing colon 26 is an appropriate model for elucidating the mechanism that causes cachexia.     

Induction of cachexia in mice by a product isolated from the urine of cachectic cancer patients.

Urine from cancer patients with weight loss showed the presence of an antigen of M(r) 24,000 detected with a monoclonal antibody formed by fusion of splenocytes from mice with cancer cachexia. The antigen was not present in the urine of normal subjects, patients with weight loss from conditions other than cancer or from cancer patients who were weight stable or with low weight loss (1 kg month(-1)). The antigen was present in the urine from subjects with carcinomas of the pancreas, breast, lung and ovary. The antigen was purified from urine using a combination of affinity chromatography with the mouse monoclonal antibody and reversed-phase high-performance liquid chromotography (HPLC). This procedure gave a 200,000-fold purification of the protein over that in the original urine extract and the material isolated was homogeneous, as determined by silver staining of gels. The N-terminal amino acid sequence showed no homology with any of the recognized cytokines. Administration of this material to mice caused a significant (P<0.005) reduction in body weight when compared with a control group receiving material purified in the same way from the urine of a normal subject. Weight loss occurred without a reduction in food and water intake and was prevented by prior administration of the mouse monoclonal antibody. Body composition analysis showed a decrease in both fat and non-fat carcass mass without a change in water content. The effects on body composition were reversed in mice treated with the monoclonal antibody. There was a decrease in protein synthesis and an increase in degradation in skeletal muscle. Protein degradation was associated with an increased prostaglandin E2 (PGE2) release. Both protein degradation and PGE2 release were significantly reduced in mice pretreated with the monoclonal antibody. These results show that the material of M(r) 24,000 present in the urine of cachectic cancer patients is capable of producing a syndrome of cachexia in mice.     

The cancer cachexia syndrome.

The provision of additional calories and protein alone has not been shown to be efficacious in patients with cancer cachexia. Although primary research continues to unravel the complex metabolic derangements and diverse mediator pathways underlying cancer cachexia, the future lies in drugs and neutracenticals that may modulate this altered metabolism and enable conventional nutritional support to effectively replenish vital lean tissue.     

肿瘤坏死因子抗体和高聚金葡素对抗癌症恶病质的初步探讨

目的利用荷瘤动物模型初步探讨癌症恶病质发生机理，评估肿瘤坏死因子抗体（ＴＮＦ－αＡＢ）及高聚金葡素（ＢＭ８２８）治疗恶病质的疗效。方法建立Ｔ７３９／ＬＡ７９５荷瘤小鼠恶病质模型，同时另组小鼠用ＴＮＦ－α作诱导。用放射免疫分析方法测定各组小鼠血清ＴＮＦ－α水平。用ＴＮＦ－αＡＢ和ＢＭ８２８治疗恶病质小鼠，观察各组小鼠摄食量及体重的变化。结果小鼠荷瘤２周后其体重及摄食量明显下降，该组小鼠血清ＴＮＦ－α水平显著高于非荷瘤组；ＴＮＦ－α能诱导小鼠出现类似恶病质的表现。结论ＴＮＦ－α可能是癌症恶病质发生的主要细胞因子之一。ＴＮＦ－αＡＢ及ＢＭ８２８在一定程度上能缓减恶病质发展。     

Simultaneous onset of acute inflammatory response,sepsis-like symptoms and intestinal mucosal injury after cancer chemotherapy

Chemotherapy is 1 method for the treatment of cancer, but serious side effects can sometimes limit the dosage given. Mild fever and diarrhea are common side effects of cancer chemotherapy. Gastrointestinal injury induced by chemotherapeutic agents may result in bacterial/endotoxin translocation from the gut into the systemic circulation. An experimental study was therefore conducted to clarify the effect of systemic chemotherapeutic agents on gastrointestinal barrier function. Male Wistar rats were divided into a 5-fluorouracil (5-FU) group (100 mg/kg/day for 4 days; n = 27) and a control group (n = 5). All rats were fasted and central venous catheterization was performed for total parenteral nutrition and blood sampling. Intestinal tissue was also sampled for pathological examination. Plasma levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFalpha) were determined by ELISA, bacterial translocation was quantified by lymph node culture and plasma endotoxin content of portal blood was measured by the Limulus-amebocyte-lysate test. In the 5-FU group on day 4, a proportion of rats exhibited severe watery diarrhea (73.9%) and occasional vomiting (86.2%). The levels of plasma TNFalpha and IL-6 were seen to increase, peaking at day 6 (IL-6, 350.0 +/- 67.8 pg/ml; TNFalpha, 26.1 +/- 3.2 pg/ml). The pathological findings also changed on day 4. On day 6, 90% of the rats in the 5-FU group showed dramatic sepsis-like manifestations, whereas the control group did not. Within the 5-FU group, only at day 6 was bacterial translocation in the rat mesenteric lymph nodes or significantly elevated levels of endotoxin evident. These results suggest that bacterial/endotoxin translocation might cause sepsis-like manifestations after systemic chemotherapy.     

Targeting apoptosis pathways by Celecoxib in cancer

Celecoxib is a paradigmatic selective inhibitor of cyclooxygenase-2 (COX-2). This anti-inflammatory drug has potent anti-tumor activity in a wide variety of human epithelial tumor types, such as colorectal, breast, non-small cell lung, and prostate cancers. Up to now, the drug found application in cancer prevention in patients with familial adenomatous polyposis. Moreover, the use of Celecoxib is currently tested in the prevention and treatment of pancreatic, breast, ovarian, non-small cell lung cancer and other advanced human epithelial cancers.