Ketone-body metabolism in tumour-bearing rats

Rofe, Allan M.; Bais, Renze; Conyers, R. A. J.

doi:10.1042/bj2330485

Cited by 32 publications

(36 citation statements)

References 34 publications

(15 reference statements)

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“…The dark agouti rat represents an ideal model for assessing the effects of different chemotherapy agents on the gut (mucositis) and for utilization of the non-invasive sucrose breath test (SBT). [10][11][12]27 The additional advantage of utilizing this particular strain of rat is that a specific mammary adenocarcinoma can be experimentallyimplanted, 28 thereby allowing further investigation of any putative treatment and its effects in the presence of a tumor. 26,29,30 Thus, this study sought to assess the effects of TH-4 on MTXinduced small intestinal mucositis and tumor progression in tumor-bearing rats.…”

Section: Resultsmentioning

confidence: 99%

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Oral ingestion ofStreptococcus thermophilusdoes not affect mucositis severity or tumor progression in the tumor-bearing rat

Tooley

Howarth²,

Lymn³

et al. 2011

Cancer Biology & Therapy

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Section: Resultsmentioning

confidence: 99%

“…The mammary adenocarcinoma used in this DAR (DAMA) model arose spontaneously in the 1970s. 28,37,38 This cancer cell line was kindly donated by Drs. A. Rofe (IMVS, Adelaide, Australia) and R. Gibson (Hanson Institute, IMVS, Adelaide, Australia).…”

Section: Discussionmentioning

confidence: 99%

Oral ingestion ofStreptococcus thermophilusdoes not affect mucositis severity or tumor progression in the tumor-bearing rat

Tooley

Howarth²,

Lymn³

et al. 2011

Cancer Biology & Therapy

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“…Ketone bodies might be expected to preserve lean body mass during periods of weight loss and to be poor metabolic substrates for the tumour (Tisdale & Brennan, 1983;Rofe et al, 1986). Additional rationalization for the use of a ketogenic diet for the reversal of the weight loss in cancer cachexia has come from recent studies showing inhibition of lipolytic and proteolytic factors produced by the MAC16 tumour by sodium D-(-)3-hydroxybutyrate (Beck & Tisdale, 1987).…”

Section: Discussionmentioning

confidence: 99%

“…In our initial studies we utilized MCT emulsion as a caloric source since the yield of ketone bodies was expected to be higher than for LTC (Cotter et al, 1987). Although ketosis is absent in cancer cachexia, tumour-bearing animals respond to starvation with an enhanced ketonaemia and marked ketonuria, when compared with non tumour-bearing controls (Rofe et al, 1986). This shows that there is no functional impairment of the ketogenic capacity of the liver in the tumour-bearing state, and this has been confirmed by the increased plasma levels of acetoacetate and 3-hydroxybutyrate previously observed in weight-losing, tumour-bearing animals fed high levels of MCT .…”

Section: Discussionmentioning

confidence: 99%

A comparison of long-chain triglycerides and medium-chain triglycerides on weight loss and tumour size in a cachexia model

Tisdale

Brennan²

1988

Br J Cancer

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Summary A comparison has been made between the ability of long-chain triglycerides (LCT) and mediumchain triglycerides (MCT) to prevent weight loss induced by the cachexia-inducing colon adenocarcinoma (MAC16) and to reduce tumour size. There was no difference in calorie consumption or nitrogen intake between the various groups. When compared with a normal control high carbohydrate, low fat diet, animals fed MCT showed a reduced weight loss and a marked reduction in tumour size. In contrast neither weight loss nor tumour size differed significantly from the controls in animals fed the LCT diet. An elevated plasma level of 3-hydroxybuturate was found only in the animals fed the MCT diets. Administration of LCT caused an increase in the plasma level of FFA, which was not observed in the MCT group. These results suggest that diets containing MCT would provide the best ketogenic regime to reverse the weight loss in cancer cachexia with a concomitant reduction in tumour size.Weight loss is a common feature of many neoplastic diseases (De Wys, 1986) and appears to be independent of the tumour burden and often precedes clinical diagnosis. The end result of the continuing decline in nutritional status is the clinical syndrome of cancer cachexia. Patients with weight loss have a poorer response to chemotherapy and a shorter survival time than those without weight loss (De Wys et al., 1980).We have utilized the MAC 16 adenocarcinoma of the mouse colon as an experimental model of human cachexia, where weight loss arises from the metabolic effects of the tumour on the host (Bibby et al., 1987). Animals bearing the MAC16 tumour show weight loss at small tumour burdens (less than 1% of the host weight) and without a reduction in either food or water intake. Weight loss is characterized by a progressive loss of both body fat and muscle dry weight, which increases in direct proportion to the tumour burden (Beck & Tisdale, 1987). Although there is extensive mobilization of body fat reserves ketosis does not occur (Bibby et al., 1987). Ketonuria has also been shown not to occur in cancer patients . Since ketone bodies are believed to play an important role in the regulation of lean body mass during starvation we and others (Tisdale, 1982;Magee et al., 1979;Williamson & Matthaei, 1981) have suggested that a high fat/low carbohydrate ketogenic diet should also preserve lean body mass during cancer cachexia, and would not be expected to be utilized by a poorly vascularized tumour, which would depend primarily on glucose as an energy source. In addition 3-hydroxybutyrate has recently been shown to inhibit the lipolytic and proteolytic factors produced by the MAC16 tumour and which may be responsible for the cachexia (Beck & Tisdale, 1987). Such an approach has been vindicated since mice bearing the MAC16 tumour fed a diet in which up to 80% of the energy was supplied as medium-chain triglycerides (MCT) show a reduction in both the extent of weight loss and tumour weight . A ketogenic diet containing 70% MCT and supplemented with D-3-...

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“…These recruits may have no previous chemotherapy, may have progressed on chemotherapy, or may be on chemotherapy break. They must possess a performance status of at least Karnofsky Score 1 and measurable solid disease detectable on Positron Emission Tomography PETComputerized Tomography CT imaging [1].…”

Section: Recruitmentmentioning

confidence: 99%

Ketogenic Diet in Advanced Cancer: A Pilot Feasibility and Safety Trial in the Veterans Affairs Cancer Patient Population

Tan-Shalaby¹,

Seyfried²

2013

J Clin Trials

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Ketone-body metabolism in tumour-bearing rats

Cited by 32 publications

References 34 publications

Oral ingestion ofStreptococcus thermophilusdoes not affect mucositis severity or tumor progression in the tumor-bearing rat

Oral ingestion ofStreptococcus thermophilusdoes not affect mucositis severity or tumor progression in the tumor-bearing rat

A comparison of long-chain triglycerides and medium-chain triglycerides on weight loss and tumour size in a cachexia model

Ketogenic Diet in Advanced Cancer: A Pilot Feasibility and Safety Trial in the Veterans Affairs Cancer Patient Population

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