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)

While stimulating the growth of fibroblasts, transforming growth factor beta 1 (TGF-beta 1) inhibits the growth of various normal and malignant cell lines in vitro. We studied the effects of TGF-beta 1 in vivo. The level of TGF-beta 1 in serum was maximally elevated 2 h after injecting 1 muCi of 125I-TGF-beta 1 into the peritoneal cavity of nude mice. Five h after the i.p. administration of 10 micrograms of unlabeled TGF-beta 1, 20 ng/ml of TGF-beta-like material in serum were detected by a radioreceptor assay on A549 lung carcinoma cells. Trichloracetic acid-precipitable 125I-TGF-beta 1 was taken up by liver, spleen, lungs, kidneys, and tumor tissue but not by the brain. At doses exceeding 2 micrograms/day, TGF-beta 1 induced a generalized interstitial fibrosis and a cachexia, which was not mediated by elevated serum levels of tumor necrosis factor alpha as determined by Western blot analysis and enzyme-linked immunosorbent assay. A total of 200,000 cells of the estrogen receptor-negative human breast cancer line MDA-MB-231, which had been shown to be maximally growth inhibited in vitro by 40 pM TGF-beta 1 and to have high-affinity receptors (9, 11, 12), were injected into the mammary fat pad of each nude mouse. The duration of treatment was 16 days with ten animals in the control group and five animals in the treated groups. The dose ranged from 1 to 4 micrograms per animal daily. The treatment was started 24 h after the injection of the tumor cells. Tumor growth was not significantly affected at either nontoxic or toxic doses of TGF-beta 1. Thus, we have demonstrated that TGF-beta 1, apart from being a local growth factor, has systemic effects, such as cachexia and multiple fibrosis. Its role as an antitumor agent may be limited.
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PMID:Transforming growth factor beta 1 induces cachexia and systemic fibrosis without an antitumor effect in nude mice. 205 95

Metastatic thymic lymphosarcoma was diagnosed in a 16-month-old mixed-breed heifer with a history of progressive weight loss. Physical examination revealed cachexia, pale mucous membranes, large peripheral lymph nodes, and a 15 X 40-cm mass in the ventral portion of the neck, extending cranially from the thoracic inlet. Neoplastic lymphocytes were identified in aspirates of pleural effusion and bone marrow. Histologic examination of necropsy specimens substantiated metastatic dispersal of the tumor into lymphoid tissue, liver, intestine, heart, and kidney. This case differs from other reported cases of thymic lymphosarcoma because of the involvement of organs other than the thymus and lymph nodes. Analytical flow cytometry was performed on mononuclear leukocytes obtained from blood by use of density gradient centrifugation. The majority of cells (65%) appeared to be of an immature, poorly differentiated phenotype, on the basis of the small numbers of cells stained with monoclonal antibodies specific for the following cell surface markers: 8% BoCD2 (IL-A26; sheep erythrocyte receptor on T-lymphocytes); less than 10% B-lymphocytes as determined by expression of MHC class II proteins and surface immunoglobulin; 12% monocytes (IL-A24); and 5% null cells (IL-A29). Although the leukemic cell population did not express traditional surface markers for T-lymphocytes, we hypothesize that the leukemic cell population represents an early stage of T-cell maturation that has failed to differentiate and express characteristic cell surface antigens.
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PMID:Metastatic thymic lymphosarcoma in a calf. 207 79

Cancer cachexia has been listed as a major cause of death in cancer patients. In order to investigate the metabolic effects of the tumor on the host, we have evaluated an experimental model of cancer cachexia in the mouse (MAC16 colon adenocarcinoma), in which weight loss can reach 30-40% of initial weight with a tumor burden of only 2.5%, without a reduction in the intake of either food or water. The weight loss appears not to arise from tumor necrosis factor production, which is associated with a marked reduction in both food and water intake, but may be a result of catabolic factors produced by the tumor and present in the circulation. Both insulin and 3-hydroxybutyrate are effective inhibitors of the tumor catabolic factors in vitro and protect, to some extent, weight loss in vivo. However, whereas 3-hydroxybutyrate was associated with a reduction in tumor weight, insulin caused an enhancement, suggesting that the former may be more appropriate than the latter in the clinical treatment of cancer cachexia.
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PMID:Cancer cachexia. 208 20

The resting energy expenditure (REE) and postprandial energy expenditure (PPEE) were measured using closed-circuit indirect calorimetry in Walker 256 carcinosarcoma-bearing rats. The results were compared to the appropriate controls. The PPEE measurements were performed after oral test feeding. At the beginning of the tumor growth, the REE and PPEE were similar in all groups. In the second week, the tumor-bearing rats showed increased REE and decreased PPEE. The tumor-bearing rats lost weight and became anorectic. After day 14, the REE rapidly dropped to very low values and the body weight continued to decrease. This study makes it possible to differentiate three phases of cancer cachexia: silent or preclinical, hypermetabolic and hypometabolic.
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PMID:Metabolic response to enteral food in different phases of cancer cachexia in rats. 210 75

The aim of the present study was to investigate hypothalamic-pituitary function, pituitary-thyroid function as well as pituitary-adrenal function in cancer patients. 1. Hypothalamic-pituitary function: We already reported a tumor-related paradoxical increase of serum growth hormone (GH) in oral glucose tolerance test (OGTT) and TRH test, which seemed to be due to changes in pituitary GH cell, not hypothalamus. The high incidence of the paradoxical increase of GH in OGTT was found in patients with hepatocellular cancer and pancreatic cancer, whereas in TRH test it was observed in patients with pancreatic, colonic and gastric cancer. The highly sensitive GH enzyme immunoassay demonstrated in 12 non-responder patients in OGTT a significant reduction of serum GH at 30 minutes compared to basal values. 2. Pituitary-thyroid function: We already demonstrated that a high incidence of low T3 syndrome in elderly cancer patients compared to younger patients and metabolic changes in glucose must be involved in the pathogenesis. In addition, this syndrome is significantly related to prognosis. There were no significant changes in thyroid function before and after curative operation for tumors except in patients with poor prognosis. 3. Pituitary-adrenal function: It was shown that cancer cachexia is characterized by hypercortisolemia, which must be due to a defect of negative feedback control.
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PMID:[Fundamental and clinical studies of changes in endocrine conditions in cancer patients]. 210 9

The influence of eicosanoids on the proliferation of hepatoma (HTC) cells was studied in culture and in tumor-bearing rats. The cells in culture demonstrated a capacity to metabolize arachidonic acid to eicosanoids including thomboxane B2 and the prostaglandins E2 and F2 alpha a. An effect of these eicosanoids on cell proliferation was suggested by the decreased cell division seen with an inhibitor of cyclooxygenase, flurbiprofen. A biphasic effect on the proliferation of HTC cells was observed with increasing concentrations of prostaglandin F2 alpha. These studies were extended to tumor-bearing rats where inhibitory effects on the early stages of tumor growth were seen with flurbiprofen. Bleeding times were decreased in tumor-bearing rats but were restored to control values by treatment with flurbiprofen and an inhibitor of thromboxane synthetase, OKY 046. These drugs and a thromboxane/endoperoxide receptor antagonist, SQ 29, 548, were not observed to have statistically significant effects on isotope-labeled water distribution but they had substantial effects on the maintenance of body weight by tumor-bearing rats. The data suggested that the cachexia of tumor-bearing animals may be mediated at least in part by the action of eicosanoids.
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PMID:Influence of inhibitors of eicosanoid metabolism on proliferation of rat hepatoma cells and on tumor-host interaction. 211 60

We have developed an improved model for studying in vivo nonsurgical treatment of head and neck cancer. In situ oral cavity implantation has been documented, but its natural history is not defined. In light of this, an improved model is described. Forty-two nude mice had tumor cells from one of two established laryngeal squamous cell carcinoma cell lines implanted into the floor of the mouth. The tumor mass was measured and followed. When the tumor burden was great enough to cause cachexia, the animals were killed and submitted for microscopic examination. Pulmonary metastases were noted in 44%, bone invasion in 80%, angioinvasion in 76%, and soft tissue invasion in 96% of the animals. Growth characteristics in the head and neck have not been documented in previous models. Our model not only exhibits the locally invasive activity typically associated with malignant neoplasms, but also closely parallels the results of clinical studies examining the percent of end stage patients and autopsies with pulmonary metastases. Therefore, this model should open the way for more meaningful in vivo studies of nonsurgical treatment modalities for both local and metastatic tumor foci in head and neck cancer.
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PMID:Development of a new in vivo model for head and neck cancer. 212 99

The direct effects of human GH and IGF-I on PRL secretion and cell proliferation were studied on PRL secreting rat pituitary tumor 7315b cells in vitro, as well as the effects in vivo of human GH administration on body weight, IGF-I levels and tumor size in rats bearing this transplantable tumor. In the in vitro studies IGF-I levels above 5 nM stimulated PRL release in a dose-dependent manner while GH, in concentrations of 0.23-45 nM, did not affect PRL release. Cell proliferation was stimulated by IGF-I in a dose-dependent manner from 0.5 nM onwards, while GH did not have an effect. The in vivo studies showed that 1 mg GH/rat/day prevented tumor-induced cachexia and normalized the suppressed IGF-I levels without stimulating tumor growth. It is concluded that tumor-induced cachexia can be prevented by exogenous GH administration without an increase in tumor mass, even if a tumor model is used whose cultured tumor cells respond to exposure to IGF-I with a mitotic response.
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PMID:The in vitro and in vivo effects of human growth hormone administration on tumor growth of rats bearing a transplantable rat pituitary tumor (7315b). 214 83

Serum from two groups of rabbits, all offspring from the same parents, was subjected to NMR spectroscopy in order to monitor the progress of malignant disease. One group had VX-2 carcinoma implanted in the kidney while the control group were sham-operated with injection of physiological saline. Later, the control group was subjected to dietary restrictions to produce a weight loss equivalent to that of the rabbits with tumor. Progressive cancerous growth with cachexia produced characteristic changes in the lipoprotein spectra distinctly different from those induced by weight loss induced by food intake restrictions. A shoulder on the high-field side of the methylene resonance observed in the control spectra disappeared during the progress of cancerous growth. These spectral changes, however, are not adequately described by line width measurements at half-height as suggested for the original Fossel test.
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PMID:Proton nuclear magnetic resonance spectroscopy of serum lipoproteins in rabbits with implanted VX-2 carcinoma. 214 51

Severe cachexia of extremely rapid onset typifies the young Black African patient with hepatocellular carcinoma (HCC). In order to assess whether this is a consequence of tumor-associated increases in protein metabolism or simply due to inadequate dietary intake, the following study was undertaken. The technique of constant i.v. infusion of 14C-labeled leucine was used to measure whole body protein flux, breakdown, synthesis, and oxidation rates in 8 adults with HCC, 4 patients with massive hepatomegaly due to metastatic adenocarcinoma from bowel, 6 patients with chronic liver disease, and 10 controls. Endogenous protein breakdown and oxidation were similar between patients with chronic liver disease (breakdown, 4.4 +/- 1.2 g/kg/day; oxidation, 0.8 +/- 0.4 g/kg/day) and controls but were significantly (P less than 0.002) higher in patients with liver tumors, the highest rates being observed in those with HCC (breakdown, 8.5 +/- 4.3 g/kg/day; oxidation, 1.4 +/- 0.5 g/kg/day). Protein turnover was generally higher in the HCC group, with increased rates of reincorporation of amino acids into protein synthesis (P less than 0.05). In one HCC patient a synchronized diagnostic liver biopsy demonstrated high fractional synthesis of rates of HCC proteins of 86%/day. In addition, the incorporation rates of labeled amino acid into fibrinogen, immunoglobulin G, and transferrin were also highest (P less than 0.03) in HCC patients. In order to assess the relative importance of diet in weight loss, dietary intake levels were assessed from hospital records of HCC patients and by dietary recall during the week prior to study. Intakes ranged from 30 to 70% of calculated requirement levels. In conclusion, our results suggest that the rapid wasting seen in patients with HCC is due to an imbalance between the metabolic demands, which can be elevated in some patients, and inadequate dietary replenishment.
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PMID:Contribution of elevated protein turnover and anorexia to cachexia in patients with hepatocellular carcinoma. 215 53


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