Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin-like growth factor I (IGF-I) has been implicated in the regulation and maintenance of skeletal muscle protein balance and thus may be of potential benefit in attenuating the cancer-cachectic process. To examine this hypothesis, 47 sham or tumor-implanted Fischer 344 rats were randomized to receive either continuous subcutaneous IGF-I (220 or 400 micrograms/day) or saline as control. In the tumor-bearing (TB) population, IGF-I-treated groups showed a dose-dependent increase in host weight gain (P less than 0.05), final carcass weight (P less than 0.05), and gastrocnemius muscle weights (P less than 0.05) and protein contents (0.50 +/- 0.02, 0.40 +/- 0.01, and 0.52 +/- 0.03 g/100 g host wt, for non-TB saline, TB saline, and TB 400 mg IGF-I groups, respectively; P less than 0.01, IGF-I vs. saline). Similar increases in muscle RNA and DNA contents (P less than 0.01) were induced by IGF-I treatment (P less than 0.05). IGF-I treatment in this rat sarcoma model significantly reduced the proportion of aneuploid cells in the tumor (aneuploid-to-diploid ratio: TB saline 1.1 +/- 0.2 vs. TB IGF-I 0.5 +/- 0.1; P less than 0.05). IGF-I treatment attenuated host muscle protein and lean tissue depletion without stimulation of tumor growth. The tumor aneuploid population was reduced in response to IGF-I treatment. Thus IGF-I may be a potential therapeutic agent in cancer-induced cachexia.
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PMID:Insulin-like growth factor I preserves host lean tissue mass in cancer cachexia. 137 40

The cancer-related cachexia/anorexia syndrome is not well understood. It is related to several factors like metabolic changes, tumor types, and disease extent and is frequently accompanied by decreased performance status. An important aspect of anorexia is the psychosocial problem: the patient is unable to join the family for meals precisely when he or she most needs familial support. Several randomized studies have shown that megestrol acetate, possibly in a dose-dependent fashion, can improve appetite and lead to weight gain. This effect seems to be most prevalent in patients with breast cancer and also occurs in the absence of a tumor response. We have retrospectively analyzed 176 patients with cancer types other than breast cancer who received only palliative treatment. The patients were treated with megestrol acetate (160 mg tid) because they complained of anorexia. After 10 days of treatment, megestrol acetate was continued only in those patients whose appetite and/or general well-being improved. Fifty-seven patients (32%) experienced such an improvement and asked for continuation of therapy. Many basic questions are still unanswered; nonetheless, from a practical clinical view it seems worthwhile to offer anorectic patients a chance to improve, especially since side effects of megestrol acetate are absent or mild, and the distinction between responders and nonresponders can be made by 10 days of treatment.
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PMID:Cachexia and cancer: a clinician's view. 138 53

The mechanisms by which tumor cells metastasize to bone are not well understood. We have investigated the role of the basement membrane glycoprotein, laminin, in bone metastasis, since antagonists to laminin have been shown to inhibit the formation of lung metastases. We studied the formation of osteolytic metastases caused by a human tumor which is known to cause osteolysis and hypercalcemia in nude mice. We found that tumor-bearing nude mice developed hypercalcemia, cachexia, and characteristic osteolytic lesions throughout the skeleton after injection of this human melanoma cell line (A375) into the left ventricle. When we gave injections to nude mice with A375 cells which had been exposed to C(YIGSR)3-NH2, a laminin-derived synthetic peptide containing three linear sequences of YIGSR with an amino-terminal cysteine which competes with laminin for its receptor, we found a decrease in the formation of detectable osteolytic bone metastases. The tumor cells were incubated with the antagonist and then inoculated into nude mice which were administered the antagonist i.p. Hypercalcemia and cachexia were also decreased in tumor-bearing mice treated with the laminin antagonist. In contrast, laminin itself increased the number of osteolytic bone metastases, as has been shown for other tumor cells. These data suggest that laminin plays a role in the formation of osteolytic bone metastases in this model and that laminin antagonists may be useful in the prevention of bone metastases in some human tumors.
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PMID:A synthetic antagonist to laminin inhibits the formation of osteolytic metastases by human melanoma cells in nude mice. 139 44

Cachexia occurs in the majority of cancer patients before death. It is the result of major metabolic changes produced by tumor-released substances as well as by cytokines and some endogenous peptides. The most significant clinical manifestation is profound anorexia. Aggressive parenteral nutrition has not been able to increase patient survival or produce any significant symptomatic improvement. Recent research, therefore, has focused on drugs that might result in symptomatic improvement, even if no significant nutritional changes are detected. Corticosteroids have been shown to increase appetite for a brief period of time, but they do not appear to improve caloric intake or nutritional status. In addition to appetite stimulation, corticosteroids also improve a number of other symptoms transiently. Progestational drugs have been found in a number of studies to increase appetite, caloric intake, and nutritional status. The most effective type and dose of progestational drugs have not been clearly established. Cyproheptadine, hydrazine sulfate, and cannabinoids have all been suggested to have beneficial effects on appetite; their effectiveness, however, needs to be confirmed in prospective, controlled trials. Some of these trials are currently under way. Current data suggest that megestrol acetate or other progestational agents could be useful--because of effects on not only appetite but also overall nutritional status--in patients who have profound anorexia as the main manifestation of cachexia, provided expected survival can be measured in weeks or months. In patients with shorter expected survival or those who have problems tolerating progestational drugs, a brief course of corticosteroids may provide short-term symptomatic effects. Future studies should focus on (1) improving understanding of both the pathophysiology of cancer cachexia and the interaction of some of the major syndromes of terminal cancer--e.g., pain, cachexia, and cognitive failure--and (2) characterizing the symptomatic effects of different drugs more completely.
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PMID:Clinical management of anorexia and cachexia in patients with advanced cancer. 146 26

Activities of superoxide dismutase (SOD) and catalase as well as content of malonyl dialdehyde (MDA) were estimated in the blood of patients with tumor of gastrointestinal tract. In the early stage of development of tumor SOD activity and concentration of MDA in whole blood was decreased while catalase activity was increased significantly. In the cases of metastases spreading and cachexia both SOD and catalase activities were greatly decreased; the content of MDA was increased.
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PMID:[Free radical reactions and cancer]. 149 95

In a recent report we showed that IL-6 is an important mediator of experimental cancer cachexia in the colon-26 (C-26) tumor system. In culture, on a per cell basis, C-26.IVX cell line (which develops tumors and induces severe cachexia of syngeneic hosts) produces up to 60-fold less IL-6 than single cell suspensions prepared from freshly excised tumors. In this study, the mechanism behind this observation was investigated. Analysis of the cellular composition of progressing C-26 tumors indicated they contained up to 6% of macrophages. T cells, B cells, and granulocytes were not detected in the tumors. Because C-26.IVX line grown in vitro contained no macrophages, the possibility that macrophage products may augment IL-6 synthesis by the tumor cells was tested. Indeed, IL-1 beta in a dose-dependent manner and at picogram amounts could potentiate IL-6 production by the C-26 cell line. The presence of high affinity receptors for IL-1 on the C-26.IVX cell line was established. These cells expressed approximately 1500 IL-1 sites per cell with a dissociation constant of approximately 20 pM. Next, we attempted to mimic the situation in vivo by coculture of C-26.IVX cells with syngeneic peritoneal macrophages and found that this condition gives rise to an augmented IL-6 production similar to that observed with in vivo derived tumor cells or rIL-1 beta-treated C-26.IVX cells. Furthermore, anti-IL-1 type I receptor antibody completely blocked C-26.IVX IL-6 production induced by either rIL-1 beta or by peritoneal macrophages. Taken together, these data suggest a pathway of IL-6 production by C-26 tumors that involves a cellular interaction between IL-1R-expressing tumor cells and host-derived macrophages. The results also suggest that this interaction significantly contributes to cachectic events endured by the tumor-bearing host.
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PMID:Mechanisms of experimental cancer cachexia. Interaction between mononuclear phagocytes and colon-26 carcinoma and its relevance to IL-6-mediated cancer cachexia. 153 1

Cancer cachexia is characterized by progressive, involuntary weight loss in patients with cancer. Cachexia is a common cause of death in patients with cancer in the advanced stage. It is well known that cancer patients with significant weight loss are subject to a high risk of postoperative complications. Intravenous hyperalimentation (IVH) has been applied to anticancer treatment when patients are unable to take sufficient nutrients orally. It is mandatory to take efficacy of antineoplastic therapies into account in attempting to assess response to nutritional repletion in cancer patients. Nutritional support is effective in maintaining body weight of malnourished cancer patients, although it is difficult to maintain body cell mass expressed as intracellular water. In other words, there is a discrepancy between changes in body composition and weight loss in undernourished patients with cancer. It seems that intravenous hyperalimentation has no documented benefit to cancer patients undergoing antineoplastic treatment from the standpoint of improved patient survival in the prospective, randomized trials of nutritional support. Therefore, further studies are needed in order to improve tumor-bearing host survival by means of nutritional management, i.e., glutamine enriched solution, amino acid imbalance solution, and anticachectic drugs on the basis of the deranged metabolism in cancer.
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PMID:[Response to nutritional management in cancer patients]. 154 58

The derangements in energy/substrate metabolism seen in oncology patients are similar regardless of the tumor's site of origin, and in advanced disease these metabolic derangements can be manifested as cancer cachexia. The relationship between tumor size and the degree of metabolic abnormality, however, remains unclear. Using primed constant infusions of stable and radiolabeled isotopes and indirect calorimetry, the authors have determined the rates of net protein catabolism (NPC), glucose oxidation, Cori cycling of glucose, and oxygen consumption in 85 patients with cancer. They have assessed the association between bulk of tumor and metabolic abnormality using regression analysis. A positive correlation was found between tumor bulk and the rates of NPC (r2 = 0.8), plasma glucose appearance (r2 = 0.72), plasma glucose clearance (r2 = 0.70), the percentage of tissue glucose uptake recycled to lactate (r2 = 0.62), and oxygen consumption (r2 = 0.79). The percentage of tissue glucose uptake oxidized was negatively correlated with tumor bulk (r2 = 0.75). The data indicate that the degree of metabolic abnormality seen in cancer patients is closely related to the quantity of malignant tissue present. Progressive increase in tumor size is associated with an increase in peripheral substrate mobilization, an increase in the rate of hepatic glucose production, an increase in tissue glucose uptake, an increase in energy-expensive glucose cycling to lactate, and an increase in protein loss.
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PMID:The effect of tumor bulk on the metabolic response to cancer. 154 2

We report the case of a 76-year-old patient with cachexia, abdominal pain and anemia who was referred for computed tomography to exclude the possibility of a malignoma. We diagnosed retractile mesenteritis, which was verified by laparoscopy with exploratory excision and histological examination. Exploratory laparatomy, recommended even today, could be prevented. In this procedure, extensive parts of the mesenterium and intestine are often resected because of the possibility of a tumor. After therapy with prednisone, there was clinical recovery and the symptoms regressed, as shown by computed tomography.
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PMID:[Retractile mesenteritis]. 154 60

A transplantable ascites-forming osteosarcoma (J. H. 1-AOS) derived from the 35th generation of spontaneous osteosarcoma, J. H. 1-OS, grown in Fischer 344 syngeneic rats was established. Tumorigenicity, histochemical and ultrastructural characteristics were investigated. Rats carrying the ascites form osteosarcoma died of cachexia about 15 days after transplantation, 1.5-2.5 x 10(6) cells/ml of tumor cells generally being involved in the ascites and tumor nodules formed in the mesentery. After inoculation into the back subcutaneous space, tumor growth was very rapid. Small round cells were detected in the Giemsa stain smear, and although osteoid formation was histologically lacking, cell surface alkaline phosphatase activity was noted both light and electron microscopically. Polyacrylamide gel electrophoresis demonstrated that alkaline phosphatase (Al-p) extracted from this tumor was consistent with Al-p from rat fetal calvaria. Thus maintenance of osteogenic potential is suggested for these ascites osteosarcoma cells, indicating their usefulness for further studies of biological behaviors of this tumor type.
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PMID:[Establishment and characterization of an ascites-forming rat osteosarcoma cell line]. 154 42


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