Medroxyprogesterone acetate and cancer cachexia: Interleukin-6 involvement

Cancer cachexia is a significant problem facing both patients and physicians. Many interventions have been tried in an attempt to remedy undernutrition in cancer patients. However, there is no convincing evidence that enteral/parenteral nutrition or the use of anabolic steroids is of any benefit in patients with cachexia. A recent prospective study revealed that oral medroxyprogesterone acetate (MPA) treatment reduces serum levels of interleukin (IL)-6, an important mediator of cancer cachexia, in patients with metastatic breast carcinoma regardless of response to the therapy. A decrease in serum IL-6 levels was well associated with subjective improvement in patients with metastatic breast carcinoma. Furthermore, clinically attainable concentrations of MPA can inhibit the growth of some human pancreatic carcinoma cells by inducing apoptosis in association with the phosphorylation of bcl-2. These results suggest that this agent may contribute to improved quality of life in patients with various cancers.     

益气清热养阴中药对肺癌恶病质小鼠的免疫调节作用

目的:研究益气清热养阴中药时晚期肺癌恶病质小鼠Th1/Th2相关细胞因子的调节作用.方法:建立小鼠Lewis肺癌胸腔移植恶病质模型,以甲羟孕酮(MPA)作为对照药物,观察益气清热养阴中药(TCM)治疗后,恶病质小鼠脾淋巴细胞悬液中相关细胞因子IL-2、IL-4及IL-10等水平的变化.结果:TCM能够提高恶病质小鼠IL-2的表达水平,降低L-4、IL-10的表达水平(P＜0.05).结论:TCM可能通过调节反映免疫平衡状态的Th1/Th2相关细胞因子的表达水平,改善晚期肺癌恶病质的免疫功能紊乱状况.     

瓣膜病合并心脏恶液质的外科治疗

目的总结瓣膜病合并心脏恶液质（SOCC）的外科治疗体会。方法总结上海交通大学医学院附属仁济医院1996年1月至2005年12月行917例瓣膜手术,其中SOCC患者90例。结果SOCC组90例病例,死亡6例,死亡率6.7%,死亡原因为低心排、呼吸衰竭、恶性心律失常、DIC、多脏器功能衰竭。非SOCC组827例,死亡率4.8%。结论瓣膜病合并心脏恶液质患者的术前准备,手术时机的选择,术中三尖瓣的处理,术后低心排的处理,围术期营养支持和多脏器功能的维护很重要。     

Biomarkers for cancer cachexia: is there also a genetic component to cachexia?

Introduction Cancer cachexia is a severe debilitating disorder, which causes significant morbidity and mortality. In clinical practice, cachexia is often not treated until a late stage, when therapeutic options are limited. Objective It is therefore of great interest to analyse early biomarkers of this syndrome. Conclusion In this review article, we summarise recent biomarkers found in various body compartments. We also explore the likelihood of a genetic predisposition to cachexia and focus on the potential role of single nucleotide polymorphisms in genes coding for pro- and anti-inflammatory cytokines, and ‘atrogenes’ associated with wasting in skeletal muscle. An erratum to this article can be found at     

Nutrition in cancer patients

Many factors can modify nutritional status in cancer patients, including cachexia, nausea and vomiting, decreased caloric intake or oncologic treatments capable of determining malabsorption. Cachexia is a complex disease characterized not only by a poor intake of nutrients or starvation, but also by metabolic derangement. Nausea and vomiting may limit the nutrient intake and are most often the consequences of oncologic treatments or opioid chronic therapy. Decreased caloric intake is considered to be one of the major causes of malnutrition, although the causes of anorexia remain unclear. Malabsorption is generally attributed to the consequences of oncologic treatments reducing the gastrointestinal absorption. Biochemical measurements and immunological tests may be not reliable indicators of nutritonal status in cancer patients. Therefore, medical history, physical examination, estimates of daily oral intake, weight changes and an appropriate consideration of the nutritional requirements according to the stage of disease must still be assessed. The therapeutic approaches should be individualized and realistic. Whenever possible, oral nutrition is the method of choice, with due consideration for specific dietary needs. Nausea and anorexia can be reduced by different kinds of drugs. A careful decision based on good clinical judgement is necessary before deciding to start either enteral or parenteral nutrition, to avoid a useless, costly and difficult treatment. In choosing the route for administration of nutrients, availability of and access to a functioning gastrointestinal tract, compliance and comfort of the patient, gastrointestinal toxicity due to chemotherapy or radiotherapy fields, different costs, duration and place of treatment should be considered rather than the different capacity of parenteral versus enteral nutrition. However, postoperative periods after massive intestinal resection often require prolonged parenteral nutrition. The benefits of parenteral nutrition are not often demonstrable in patients with bowel obstruction. Different ethical aspects are presented. Flexibility in attempting to meet the nutrition needs of each patient is probably the most useful guide.     

Increase in serum adiponectin concentration in patients with heart failure and cachexia: relationship with leptin, other cytokines, and B-type natriuretic peptide.

AIMS: Adiponectin is a fat-derived hormone involved in the regulation of metabolism. Adiponectin concentration is inversely related to body weight and, in animals, causes weight loss. We, therefore, measured adiponectin concentration in patients with heart failure (HF) and cachexia. METHODS AND RESULTS: Serum adiponectin concentrations were measured in three groups of patients with coronary artery disease (CAD): (i) HF, reduced left ventricular systolic function, and cachexia (n = 10); (ii) HF, reduced systolic function but no cachexia (n = 20); (iii) HF-controls-patients with CAD, no HF, and preserved systolic function (n = 10); and in a healthy control group (n = 7). Patients with HF and cachexia had higher concentrations of adiponectin [23.8 (10.2-37.2) microg/mL] than all other groups: HF-no cachexia 8.1 (0.5-16.6) microg/mL; CAD-controls 7.1 (0.4-13.5) microg/mL; and healthy controls 8.7 (2.5-16.8) microg/mL) (P < 0.05 for each comparison). Adiponectin correlated negatively with body mass index, percentage of body fat, waist circumference and insulin resistance, and positively with B-type natriuretic peptide (BNP) and tumour necrosis factor-alpha. CONCLUSION: Cachexia in HF is associated with an increase in adiponectin concentration. This may represent preservation of the physiological response to change in body fat but might also suggest that adiponectin plays a role in the pathogenesis of cachexia. The correlation between BNP and adiponectin also raises the possibility that the former might increase the secretion of the latter.     

Effects of tumour necrosis factor alpha (TNFα) on glucose transport and lipid metabolism of newly-differentiated human fat cells in cell culture

Summary Tumour necrosis factor alpha (TNFα) has been found to cause a delipidation of fat cells and a decrease of the adipose tissue mass. In the present study, we tried to elucidate some of the mechanisms responsible for this phenomenon by investigating the action of TNFα on specific pathways which are involved in lipid storage. Cultured stromal cells from human adipose tissue were induced to differentiate into adipose cells by exposure to adipogenic factors and subsequently used for studying the effects of TNFα on fat cell metabolism. Presence of 5 nmol/l TNFα for 24 h resulted in a complete loss of the stimulatory effect of insulin on 2-deoxy-glucose transport. This inhibitory action was paralleled by a decrease of GLUT4 protein and mRNA levels. The amount of cellular GLUT4 protein was reduced by 49 ± 3 % after a 24-h exposure and by 82 ± 18 % after a 72-h exposure to 5 nmol/l TNF a . GLUT4 mRNA was almost undetectable after a 24-h incubation with 5 nmol/l TNFα. In a similar time-dependent manner, TNFα dramatically reduced the lipoprotein lipase mRNA content of the cells. Furthermore, incubation of cultured human fat cells with TNFα resulted in a marked dose-dependent stimulation of lipolysis, assessed by glycerol release, by up to 400 % above controls, which became apparent after a 6-h exposure at the earliest. These data suggest that TNFα induces a catabolic state in human adipose tissue which includes a loss of the stimulatory effect of insulin on glucose transport. These multiple actions of TNFα may contribute to the loss of adipose tissue observed during cachexia in man. [Diabetologia (1995) 38: 764–771] Received: 19 August 1994 and in revised form: 12 December 1994     

血管紧张素转化酶抑制剂抗肿瘤作用的研究进展

血管紧张素转化酶抑制剂(ACEI)类药物是临床心脑血管系统常用药物,一些流行病学研究发现其具有抗肿瘤作用。研究表明ACEI类药物具有抑制肿瘤发生、生长,抗肿瘤血管生成,抑制细胞外基质降解和治疗恶病质等多种作用。作者就其最新研究进展综述如下。     

肠道菌群在癌性恶病质营养代谢及治疗中的作用

癌性恶病质严重影响肿瘤病人短期和长期临床结局。近年来,肠道菌群在恶性肿瘤发生发展及治疗中的作用备受关注,为癌性恶病质的机制研究和临床防治积累了大量新的研究证据。肠道菌群参与了骨骼肌、脂肪组织、消化道、炎症反应、营养代谢等恶病质发生相关组织器官的病理生理过程,有望成为癌性恶病质防治的新靶点。