Reduction of tumor growth following treatment with a glutamine antimetabolite

Chance, William T.; Cao, Lequn; Kim, M.W.; Nelson, Jeffrey L.; Fischer, Josef E.

doi:10.1016/0024-3205(88)90627-3

Cited by 39 publications

(13 citation statements)

References 12 publications

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“…Citrulline and ornithine are intermediary amino acids of the urea cycle. In a previous study decreased arterial concentrations of these amino acids were found indicative of decreased urea cycle activity in tumor-bearing rats (16). In the current study increased concentrations of these amino acids were observed in arterial plasma and, moreover, in the liver of tumor-bearing rats.…”

Section: Discussionsupporting

confidence: 70%

“…Increased gluconeogenesis has also been held responsible for decreased plasma concentrations of other gluconeogenic amino acids, e.g. serine and threonine (16). If the carbon skeleton of amino acids is used to produce glucose, the amino group is processed to urea by the liver to be removed from the body by the kidney.…”

mentioning

confidence: 99%

“…In tumor-bearing mice decreased urea excretion (17,lS) and increased nitrogen retention (19) are observed. In addition, decreased plasma concentrations of amino acids of the urea cycle were observed and suggested to reflect a diminished urea cycle activity (16,20).…”

mentioning

confidence: 99%

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Hepatic amino acid and protein metabolism in non-anorectic, moderately cachectic tumor-bearing rats

Blaauw

Deutz

Boers

et al. 1997

Journal of Hepatology

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Section: Discussionsupporting

confidence: 70%

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confidence: 99%

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Hepatic amino acid and protein metabolism in non-anorectic, moderately cachectic tumor-bearing rats

Blaauw

Deutz

Boers

et al. 1997

Journal of Hepatology

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“…A blockade of glutamine utilization can inhibit the growth of transplantable sarcomas [30]. Notably, glycinea precursor of sarcosine-decreased during rat HCC metastasis to the lung, which is consistent with metabolic changes in human prostate cancer [31].…”

Section: Discussionmentioning

confidence: 87%

1H-NMR-based metabolomics of tumor tissue for the metabolic characterization of rat hepatocellular carcinoma formation and metastasis

Wang

Zhang

et al. 2010

Tumor Biol.

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The high mortality figures for hepatocellular carcinoma (HCC) are mostly due to high recurrence and metastasis rates. However, the metabolic characteristics of HCC metastasis have not been studied extensively. In this study, we attempted to elucidate the metabolite profile of HCC formation and metastasis through proton nuclear magnetic resonance ((1)H-NMR)-based metabolomics. We first established a hepatocellular carcinoma with lung metastasis (HLM) rat model by exposure to diethylnitrosamine. Fifteen rats were then divided into three groups based on pathologic changes: HCC, HLM, and controls. The metabolite profiles of extracts from tumor tissue were obtained using high-resolution (1)H-NMR. One-way ANOVA was used to compare the metabolite levels among the three groups. Multivariate statistical analysis (specifically, unsupervised principal components analysis and supervised partial least squares discriminant analysis (PLS-DA)) were used for HCC and HLM metabolite profiling and data interpretation. PLS-DA models could discern HCC or HLM rats from normal (control) rats. Tumor tissue from HLM showed changes in glucose, lactate, choline, lipids, and some amino acids such as glycine. The results of this pilot study suggest that alterations in glycolysis and the metabolism of glycine and choline occur during HCC invasion and metastasis.

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“…However, in the current study, no between-group difference was found in the response to chemotherapy (52.4% versus 47.8%; p ϭ .90) or survival (p ϭ .79; log-rank test). Although in vitro evidence of the dependence of tumor growth on glutamine has deterred its application in cancer patients [36], several studies have failed to show that supplemental glutamine stimulates tumor growth [37,38]. In fact, accumulating in vivo evidence suggests that glutamine may actually decrease tumor growth, possibly by upregulating the immune system [37,39].…”

Section: Discussionmentioning

confidence: 99%

Oral Glutamine Is Effective for Preventing Oxaliplatin-Induced Neuropathy in Colorectal Cancer Patients

et al. 2007

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LEARNING OBJECTIVESAfter completing this course, the reader will be able to:1. Identify the clinical features of oxaliplatin-induced neuropathy.2. Discuss the current approaches for managing chemotherapy-induced neuropathy.3. Explain the rationale for using glutamine in preventing oxaliplatin-induced neuropathy.Access and take the CME test online and receive 1 AMA PRA Category 1 Credit ™ at CME.TheOncologist.com CME CME ABSTRACTOxaliplatin is effective in the treatment of metastatic colorectal cancer (MCRC) patients; however, severe neurotoxicity develops frequently. To assess the efficacy of oral glutamine for preventing neuropathy induced by oxaliplatin, a pilot study was performed. A total of 86 patients with MCRC treated at Taipei Veterans General Hospital were enrolled. Oxaliplatin (85 mg/m 2 , days 1 and 15) plus weekly bolus 5-fluorouracil (5-FU; 500 mg/m 2 ) and folinic acid (FA; 20 mg/m 2 ) on days 1, 8, and 15 were given every 28 days as firstline treatment. Patients were randomized to receive (glutamine group; n ‫؍‬ 42) or not receive (control group; n ‫؍‬ 44) glutamine (15 g twice a day for seven consecutive days every 2 weeks starting on the day of oxaliplatin infusion). Efficacy of chemotherapy, neurological toxicity, and electrophysiological alterations were assessed. A lower percentage of grade 1-2 peripheral neuropathy was observed in the glutamine group (16.7% versus 38.6%) after two cycles of treatment, and a significantly lower incidence of grade 3-4 neuropathy was noted in the glutamine group after four cycles (4.8% versus 18.2%) and six cycles (11.9% versus 31.8%). By adding glutamine, interference with activities of daily living was lower (16.7% versus 40.9%), and need for oxaliplatin dose reduction was lower (7.1% versus 27.3%). There were no significant between-group differences in response to chemotherapy (52.4% versus 47.8%), electrophysiological abnormalities, grade 3-4 non-neurological toxicities (26.2% versus 22.8%), or survival. These data indi- Disclosure of potential conflicts of interest is found at the end of this article.

show abstract

Reduction of tumor growth following treatment with a glutamine antimetabolite

Cited by 39 publications

References 12 publications

Hepatic amino acid and protein metabolism in non-anorectic, moderately cachectic tumor-bearing rats

Hepatic amino acid and protein metabolism in non-anorectic, moderately cachectic tumor-bearing rats

1H-NMR-based metabolomics of tumor tissue for the metabolic characterization of rat hepatocellular carcinoma formation and metastasis

Oral Glutamine Is Effective for Preventing Oxaliplatin-Induced Neuropathy in Colorectal Cancer Patients

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