Effect of Supplemental Dietary Glutamine on Methotrexate Concentrations in Tumors

Klimberg, V. Suzanne; Pappas, Alex A.; Nwokedi, Emmanuel; Jensen, Joseph; Broadwater, J. R.; Lang, Nicholas P.; Westbrook, Kent C.

doi:10.1001/archsurg.1992.01420110063013

Cited by 32 publications

(21 citation statements)

References 13 publications

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“…Oral glutamine supplementation enhanced the effectiveness of chemotherapy against rhabdomyosarcoma and reduced chemotherapy-associated toxicity in a rat methotrexate model. 26,27 The significance of glutamine in tumor growth in malignant cell lines and animal models has been reviewed extensively by Souba. 28 Thus, it would appear that the augmentation of tumor growth by glutamine is counterbalanced by support of host glutamine stores, glutathione production, and increased immune function, particularly natural killer cell (NK) activity.…”

Section: Discussionmentioning

confidence: 99%

Oral glutamine reduces the duration and severity of stomatitis after cytotoxic cancer chemotherapy

Anderson

Schroeder

Skubitz

1998

Cancer

221

124

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Supported by grants from the Viking's Children's Fund, Hedberg Foundation, Children's Cancer Research Fund, and Mayo Clinic Cancer Center.Drs. Anderson and Skubitz currently are developing a glutamine suspension product for commercial use in the treatment of mucositis.The authors thank Gary Carlson of the University of Minnesota Investigational Pharmacy for his assistance in the formulation of a palatable, sweet suspension that was acceptable to patients, especially children who had prior mouth sores. The assistance of Darlette Luke and Deb Landrith of the University of Minnesota Investigational Pharmacy and Kevin Graner and Brad Christianson of the Mayo Clinic Pharmacy are recognized and appreciated. The authors also are grateful for the encouragement to pursue these studies by numerous pediatric oncologists in the Children's Oncology Group of the Upper Midwest including Dr. Bruce Bostrom. The authors also thank Les Robison, Ph.D., for study design suggestions and Dr. Charles Loprinzi for review of the article.

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Section: Discussionmentioning

confidence: 99%

Oral glutamine reduces the duration and severity of stomatitis after cytotoxic cancer chemotherapy

Anderson

Schroeder

Skubitz

1998

Cancer

221

124

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“…Previous studies in our laboratory indicated that GLN supplementation stimulated the host GSH production, accompanied by decreased intratumoral GSH levels in an implantable sarcoma model [6,20,21]. Further studies with DMBAinduced breast cancer have shown that GLN supplementation reduced tumor growth and reversed the depressed GSH levels in normal tissue [22,23].…”

Section: Introductionmentioning

confidence: 96%

Effect of dietary glutamine on tumor glutathione levels and apoptosis-related proteins in DMBA-induced breast cancer of rats

Тодорова

Harms

Kaufmann

et al. 2004

Breast Cancer Res Treat

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Glutamine (GLN) is a non-essential amino acid that is present in nearly every biochemical pathway and is the major intraorgan nitrogen carrier. GLN via glutamate, is one of the precursors for the synthesis of glutathione (GSH), the major endogenous antioxidant in mammalian cells, which protects them from oxidative injury and cell death. Cancer cells have higher GSH levels than the surrounding normal cells, which attributes to a higher rate of cell proliferation and resistance to chemotherapy. Therefore, selective tumor depletion of GSH presents a promising strategy in cancer treatment. Experimental studies have associated decreased GSH levels with inhibition of proliferation and stimulation of apoptosis. Previous results of our laboratory have provided evidence that dietary GLN diminished tumor development in implantable as well as 7,12-dimethylbenz[a]anthracene (DMBA)-induced breast cancer and elevated GSH in the host tissues. In this study we examined the effects of GLN on GSH levels in DMBA-induced mammary tumors and correlated the results with protein and mRNA expression of apoptosis-related proteins Bcl-2, Bax and caspase-3 in tumor cells. The results have shown that GLN supplementation caused a significant decrease in the tumor GSH levels and the ratio GSH/oxidized GSH (GSSG), accompanied by up-regulation of Bax and caspase-3, and down-regulation of Bcl-2. These findings suggest that dietary GLN supplementation suppresses mammary carcinogenesis by activation of apoptosis in tumor cells and this probably is a result of GSH down-regulation.

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“…Biochemical analysis, in vitro and in vivo, animal and human studies along with phase I-phase II human clinical trials with pilot phase III clinical trials have shown that oral GLN is a safe and effective strategy to prevent and treat mucositis, stomatitis and cachexia [2][3][4][5][6]8,11,12,[15][16][17][18][20][21][22]25,26,[29][30][31][32][33][34]38,39 (M. M. Schubert, unpublished data, 2004). Concerns about GLN being preferentially used by the cancer cells, giving a tumorprotective effect, have been addressed in the research.…”

Section: Resultsmentioning

confidence: 99%

“…4,9,[20][21][22] This ability to evade chemoresistance is a very important finding to add to the strategies of integrative oncology.…”

Section: Resultsmentioning

confidence: 99%

“…This suggests that GLN may enhance the selectivity of antitumor drugs and radiotherapies by sensitizing the tumor cells to the oncological therapeutic agents while protecting normal cells in healthy tissues. 4,9,[20][21][22] Diarrhea is a direct effect of enterocolitis or damage to intestinal epithelium by chemotherapeutics and radiation therapies. Diarrhea adds proportionately to cancer cachexia malnutrition in patients during chemotherapy and radiation treatment.…”

Section: Cancer Cachexia Prevention and Treatment With Glutaminementioning

confidence: 99%

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L-Glutamine Use in the Treatment and Prevention of Mucositis and Cachexia: A Naturopathic Perspective

Noé

2009

Integr Cancer Ther

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Abstractl-Glutamine (l-GLN) is considered a nonessential amino acid that has a variety of applications in naturopathic medicine. It has been postulated that in the critically ill patient, GLN becomes an essential amino acid for recovery, restoration, and repair at a cellular level. Mucositis is an intestinal mucosal damage of the gastrointestinal tract-mouth, throat, stomach, intestines, rectum, and anus-that is caused directly by chemotherapies and radiotherapies. Cancer cachexia is a significant biochemical event, which is characterized by weight loss, fatigue, and indicative of depletion of skeletal muscle GLN-a hypercatabolic state. There has been some question as to the use of GLN in this patient population because of its role as a preferred energy source not only for enterocytes and lymphocytes but for malignant cells as well. This article will address the questions of safety, efficacy, dosing, and toxicity of GLN used as an integrative therapeutic in ongoing integrative cancer treatment.

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Effect of Supplemental Dietary Glutamine on Methotrexate Concentrations in Tumors

Abstract: \ s=b\ This study evaluated the effects of supplemental dietary glutamine (GLN)

Cited by 32 publications

References 13 publications

Oral glutamine reduces the duration and severity of stomatitis after cytotoxic cancer chemotherapy

Oral glutamine reduces the duration and severity of stomatitis after cytotoxic cancer chemotherapy

Effect of dietary glutamine on tumor glutathione levels and apoptosis-related proteins in DMBA-induced breast cancer of rats

L-Glutamine Use in the Treatment and Prevention of Mucositis and Cachexia: A Naturopathic Perspective

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