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Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

C57BL/6 mice bearing either a transplantable methylcholanthrene-induced sarcoma or Lewis lung adenocarcinoma were passively immunized every other day with a rabbit immunoglobulin fraction raised against murine cachectin/tumor necrosis factor-alpha. Mice bearing methylcholanthrene-induced sarcoma developed tumor-associated hypophagia that was attenuated by anticachectin immunoglobulin treatment. In the same tumor-bearing animals, anticachectin treatment also significantly reduced the extent of carcass protein and fat loss, and reduced tumor weight. Mice bearing Lewis lung adenocarcinoma did not develop significant anorexia or carcass lean tissue depletion as tumor growth progressed, but they lost carcass lipid. Treatment of Lewis lung adenocarcinoma bearing mice with anticachectin antibodies diminished the degree of carcass lipid depletion and prevented plasma hypertriglyceridemia. However, in both tumor models, anticachectin treatment did not affect either the development of anemia, hypoalbuminemia or the increase in serum amyloid P concentrations seen with increasing tumor burden. We conclude that an endogenous cachectin response, inhibitable by exogenously administered antibody, contributes to anorexia and to changes in body fat and protein metabolism in these tumor-bearing animals. Neutralizing endogenous cachectin production with antibodies offers the potential to reduce tissue wasting that is frequently associated with neoplastic disease, but it does not appear to affect all of the hematologic and acute phase responses in these murine tumor models.
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PMID:Anticachectin/tumor necrosis factor-alpha antibodies attenuate development of cachexia in tumor models. 272 56

Adult sarcoma-bearing mice were used to demonstrate whether hypoglycemia was the immediate cause of death in experimental animals with rapidly growing tumors without metastases. This kind of tumor model is representative of the majority of animal models used in experimental cancer research. Tumor-bearing animals died with severe hypoglycemia under all experimental conditions, while pair-killed controls were normoglycemic. Anorexia prevented tumor-bearing animals from attenuating the hypoglycemia by drinking glucose-containing water while completely starved control animals survived more than 14 days with glucose-containing water as the only energy source. Adrenalectomy shortened survival in tumor-bearing animals, but survival of adrenalectomized tumor-bearing animals could be normalized by daily injections of pharmacologic doses of hydrocortisone (25 mg/25 g body wt/day) but not by physiologic replacement (20 micrograms/25 g body wt/day). Injections of pharmacologic doses of hydrocortisone did not influence on survival or body composition in tumor-bearing animals with intact adrenals. Glucagon was without effect on either survival, tumor growth or body composition. Based on the results in this study and in our previous reports we conclude that hypoglycemia is the cause of death in the majority of murine tumor models. This hypoglycemic theory is important, since any treatment modality in animal experiments that influences glucose metabolism in the host may indirectly change tumor growth and may thus be misinterpreted as a direct tumor effect.
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PMID:The cause of death in non-metastasizing sarcoma-bearing mice. A study with relevance for tumor treatment experiments in mice. 280 52

The studies included in this chapter examine the learned food aversions that develop as a result of cancer and cancer treatment. Clinical studies have shown that cancer patients can develop learned aversions to a novel ice cream flavor when it is consumed before drug treatments that produce nausea and vomiting. They also provided evidence that patients can acquire aversions to food in their usual diets when these foods are eaten before similar drug treatments. Observations in the clinic, supported by complementary studies with animal models, suggest that learned aversions are more likely to arise to protein foods than to other nutrient sources and that the presentation of a novel food in association with drug treatments may act as a "scapegoat" in blocking the development of aversions to foods in the normal diet. Laboratory studies using transplantable tumors in rats have shown that tumor growth can be associated with the development of strong aversions to the available diet. These aversions are specific to the diet eaten during tumor growth and they appear to play a causal role in the development of tumor-induced anorexia. The food aversions apparent in animals with certain experimental tumors point to physiological consequences of tumor growth that act as unconditioned stimuli in taste aversion conditioning. The identification of these changes and development of methods for correcting them are the current goals of our research in this area.
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PMID:Learned food aversions in the progression of cancer and its treatment. 299 Feb 86

As the lengthy but nonetheless incomplete review suggests, paraneoplastic syndromes are protean in their manifestations and, for the most part, poorly understood. Indeed, some of the more common abnormalities in cancer patients that might be considered paraneoplastic--such as anorexia-cachexia syndrome or unexplained fever--have not been discussed because they are so poorly understood. Most of the syndromes reviewed are either clearly paraneoplastic or strongly associated with cancer. Their clinical importance does not lie in the number of patients affected; it is a small minority. Instead, the syndromes may occasionally be helpful in the diagnosis of cancer or in monitoring response to cancer therapy. They may also be confused with the effects of metastatic disease. In some patients, amelioration of the syndromes can reverse the patient's dominant symptoms and thus provide significant clinical palliation. In a more general context, studies of etiologic mechanisms in paraneoplastic syndromes may offer insights into a variety of unexplained abnormalities in cancer patients. The best-understood syndromes result from tumor production of biologically active substances or, to a lesser extent, from autoimmune phenomena. These would appear to be probable mechanisms in many recognized paraneoplastic syndromes of uncertain etiology and perhaps in some heretofore unrecognized paraneoplastic syndromes. Finally, paraneoplastic syndromes could also hold clues to the neoplastic process. Better understanding of the ways in which tumors regulate remote effects--such as release of TGFs--may ultimately enhance our knowledge of tumor growth itself.
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PMID:Paraneoplastic syndromes. 304 Jul 85

The relationship between circulating thyroid hormones and nutritional status was studied in sarcoma-bearing inbred C57BL/6J mice and control mice. Supplementation with exogenous thyroxine (T4) was also evaluated. Tumor-bearing animals had depressed levels of circulating thyroid hormones. This was also found in food-restricted (pair-fed and pair-weighed) controls. Plasma levels of thyroid hormones decreased with increased tumor burden. Thyrotropin-releasing hormone caused an increased response of thyroid-stimulating hormone in tumor-bearing animals. Low levels of thyroid hormones in sarcoma-bearing mice were due to depressed hormone production by the thyroid gland rather than to increased clearance rate of hormones. Plasma levels of triiodothyronine (T3) correlated to the amount of whole-body nitrogen among sarcoma-bearing mice and food-restricted controls. Exogenous T4 increased food intake by 20% in sarcoma-bearing mice. The benefit of this was probably counteracted by an increased metabolic rate, since reversal of plasma levels of T3 and free T4 had no net effect on body composition of freely eating sarcoma-bearing mice, although it had a negative effect on body and muscle composition in food-restricted controls. Exogenous T4 did not stimulate tumor growth. The results indicate that low circulating levels of thyroid hormones in experimental cancer cachexia are probably caused by the reduced food intake (anorexia), which is in agreement with findings in clinical cancer. Depression of thyroid hormones is probably a physiological means to reduce energy expenditure and to preserve substrates in progressive cancer disease.
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PMID:Thyroid hormones and experimental cancer cachexia. 309 Mar 41

Hydrazine sulfate is an anticachexia agent which interrupts host energy wasting as a result of the malignant process. An inhibitor of gluconeogenesis at the phosphoenolpyruvate carboxykinase (PEP CK) reaction, this agent has been shown in randomized, placebo-controlled, double-blind trials to improve glucose tolerance, reduce glucose turnover, increase caloric intake, and increase or stabilize weight; in single-arm controlled trials, this agent has been shown to increase appetite, improve performance status, decrease pain, diminish anorexia, normalize laboratory indices, stabilize tumor growth, induce tumor regression, and promote survival, while inducing little to no important clinical side effects. In view of its demonstrated capacity to effect anticancer response, this drug is suggested for trial as a sole agent in early drug-resistant cancer, in combination with cytotoxic and related therapies, and in conjunction with total parenteral nutrition. It is postulated that effective control of the mechanisms associated associated with cancer cachexia may contribute to control of malignant disease.
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PMID:Hydrazine sulfate: a current perspective. 310 88

Cachectin/tumor necrosis factor (TNF) is a macrophage product which may have a role in cancer cachexia. Recombinant human cachectin/TNF (Cetus Corporation) was administered i.p. twice daily to male F344 rats at varying, nonlethal dosages for either 5 or 10 days, and daily rat food intake and body weight were measured. There was a dose-dependent cachectin/TNF-induced decline in food intake and body weight gain over the treatment period. However, after 1 day rats became tolerant to these effects and increased food intake and gained body weight despite receiving cachectin/TNF. Rats were subsequently inoculated with a transplantable methylcholanthrene-induced sarcoma, and survival was measured. Rats previously treated with high-dose (either 100 or 200 micrograms/kg/day) cachectin/TNF survived significantly longer following tumor inoculation than did control rats given saline or rats given 10 micrograms/kg/day of cachectin/TNF. Analysis of tumor growth curves and tumor weight indicated that high-dose cachectin pretreatment did not retard tumor growth. Analysis of food intake and tumor burden following tumor inoculation indicated that high-dose cachectin pretreatment decreased the reduction in food intake associated with progressive tumor growth and allowed rats to withstand a greater tumor burden at death. Rats immunized with low-dose human cachectin/TNF developed high IgG titers against human TNF, but failed to demonstrate the same protection against a methylcholanthrene-induced tumor challenge as rats made tolerant with repetitive twice daily high-dose cachectin/TNF. The observation of reduced cancer-associated anorexia and increased survival of tumor-bearing rats associated with previous tolerance to exogenous cachectin/TNF strengthens the contention that endogenously produced cachectin may be a factor in the pathogenesis of cancer anorexia in the tumor-bearing rat. The mechanism of this tolerance is unclear but does not appear to be a humoral immune response.
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PMID:Cachectin/tumor necrosis factor: a possible mediator of cancer anorexia in the rat. 316 53

Cancer cachexia describes a syndrome of progressive weight loss, anorexia, and persistent erosion of host body cell mass in response to a malignant growth. Although often associated with preterminal patients bearing disseminated disease, cachexia may be present in the early stages of tumor growth before any signs or symptoms of malignancy. A decline in food intake relative to energy expenditure (which may be increased, normal, or decreased) is the fundamental physiologic derangement leading to cancer-associated weight loss. In addition, abnormalities of host carbohydrate, protein, and fat metabolism lead to continued mobilization and ineffective repletion of host tissue, despite adequate nutritional support. Mediators of cancer anorexia and associated abnormalities are unknown. Cachectin/TNF or other host-derived cytokines (produced as a defense against malignancy) have been implicated as signal molecules in cachexia, based upon similar metabolic derangements produced by these cytokines in other chronic wasting illnesses. Nutritional support is effective in maintaining body weight of cachectic cancer patients, but ineffective in maintaining lean body mass. Although in one study parenteral nutritional support has improved operative morbidity and mortality in cancer patients, it has not yet improved response to chemotherapy or radiation therapy. Because of metabolic derangements seen in cancer cachexia, effective nutritional treatment regimens will probably require manipulation of host intermediary metabolism in addition to feeding. Insulin therapy or exercise are two such methods which appear to preserve host composition by preferential feeding of the host at the expense of the tumor. Future studies which more clearly define the role of signal molecules in producing cancer cachexia syndrome may lead to new treatment strategies, possibly involving modulation of the effects of such molecules on host metabolism.
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PMID:Cancer cachexia. 329 98

To test whether the anorexia and host depletion following doxorubicin chemotherapy can be improved by concomitant insulin therapy, 70 F344 rats were divided equally between tumor-bearing (TB) and non-tumor-bearing (NTB) groups and studied for food intake, host weight, and tumor size changes. Sarcoma fragments were implanted s.c. in TB rats and 18 days later all rats received an i.v. dose of doxorubicin (8 mg/kg). The following day TB and NTB rats were randomized to receive neutral protaminehagedorn insulin (2 units/100 g/24 h) or normal saline until food intake returned to normal. Following doxorubicin administration food intake and host weight declined in an identical pattern in both NTB and TB rats treated with saline. However, beginning on day 6 insulin-treated TB and NTB rats ate significantly more than saline-treated controls. Insulin-treated animals returned to normal food intake levels in 50% less time than controls. This improved food intake resulted in an improved host mass beginning also on day 6 for both TB and NTB rats. In addition, it appeared that insulin treatment significantly improved the tumor shrinkage initiated by doxorubicin. Following doxorubicin, insulin-treated TB rats had a greater reduction of tumor size (10.6 +/- 1.2 cm3) compared to saline-treated rats (6.6 +/- 0.8 cm3, P less than 0.01). To further characterize the effect of insulin and/or doxorubicin on tumor growth, the experiment was repeated in the same manner except for two additional TB groups: saline- and insulin-treated tumor bearers with treatment beginning 19 days after tumor implant. Rats treated with doxorubicin had a significant reduction in tumor size compared to rats not treated with doxorubicin (P less than 0.001). Insulin alone did not affect tumor growth, but insulin plus doxorubicin significantly decreased tumor size compared to doxorubicin alone (P less than 0.01). In a second experiment using 80 rats insulin treatment had no apparent effect on reduction of peripheral blood counts including white blood cells, neutrophils, lymphocytes, platelets, and hematocrit induced by doxorubicin in either NTB or TB rats. Insulin given 24 h previously had minimal effect on plasma glucose. The marked improvement in food intake and host weight, as well as additional tumor reduction with exogenous insulin following doxorubicin, suggests that insulin may have a role in reversal of doxorubicin host nutritional toxicity and perhaps improvement of antitumor efficacy.
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PMID:Impact of insulin on doxorubicin-induced rat host toxicity and tumor regression. 330 Sep 63

Although the causes of cancer anorexia remain poorly understood, it now seems evident that the symptoms of appetite and weight loss which occur in cancer patients are multiply-determined. Thus, the actual causes of specific clinical problems will depend on the type of disease and treatment involved. This report examines research aimed at understanding the mechanisms responsible for cancer anorexia. Particular emphasis is placed on studies examining the contribution of learned food aversions to the anorexia induced by tumors and antitumor therapy. Evidence from the clinic and the laboratory indicates that learned food aversions occur as a result of the association of foods with symptoms induced by chemotherapy and/or tumor growth. The role these aversions play in the etiology of cancer anorexia is discussed and studies aimed at developing methods for preventing them are described.
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PMID:Etiology of anorexia in cancer. 346 94


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