Stimulation of protein synthesis in human tumours by parenteral nutrition: Evidence for modulation of tumour growth

Heys, Steven Darryll; Park, K G M; McNurlan, Margaret A.; Milne, Eric; Eremin, O.; Wernerman, Jan; Keenan, R. A.; Garlick, Peter J.

doi:10.1002/bjs.1800780430

Cited by 51 publications

(14 citation statements)

References 24 publications

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“…© 2007 American Association for Cancer clincancerres.aacrjournals.org Downloaded from that seen in serum. Unfortunately, the simple replenishment of arginine to overcome this mechanism does not seem to be a simple solution to these problems because it could stimulate tumor growth (5,7,26).…”

Section: Discussionmentioning

confidence: 99%

Arginase, Prostaglandins, and Myeloid-Derived Suppressor Cells in Renal Cell Carcinoma

Ochoa

Zea

Hernandez

et al. 2007

Clinical Cancer Research

433

325

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Tumor-induced tolerance is a well-established phenomenon in cancer patients that can severely impair the therapeutic efficacy of immunotherapy. One mechanism leading to T-cell tolerance is the generation of myeloid-derived suppressor cells (MDSC) by soluble factors produced by the tumor. MDSC express CD11b + as a common marker but may vary in their stage of maturation, depending on the tumor factors being produced. Arginase production by MDSC depletes arginine from the tumor microenvironment and impairs T-cell signal transduction and function. We studied whether an increase in MDSC could explain the molecular alterations and dysfunction found in T cells of patients with renal cell carcinoma (RCC). Arginase activity in the peripheral blood mononuclear cells of 117 RCC patients was increased between 6-to 8-fold compared with normal controls. The increased arginase activity was limited to the CD11b + CD14 À myeloid cells and resulted in significantly decreased serum levels of arginine and increased ornithine in patients. Depletion of MDSC restored IFN-g production and T-cell proliferation. Preliminary data suggest that prostaglandin E 2 produced by the tumor induces arginase I expression in MDSC. Therefore, blocking MDSC activity may enhance the therapeutic efficacy of immunotherapy in RCC. Immunotherapy with cytokines, such as interleukin-2 (IL-2),has become a standard of care for patients with renal cell carcinoma (RCC). However, only 20% to 30% of patients have a partial or complete response (1), which is significantly lower than the therapeutic efficacy suggested by animal models. One possible explanation is that tumor-induced tolerance diminishes the potential therapeutic effect of T cells, the principal effector cells in most forms of immunotherapy. Over the last decade, several mechanisms by which tumors escape the immune response have been described. These can be divided into three major groups: alterations in antigen expression in tumor cells to make them less detectable, the active suppression of dendritic and T-cell function by inhibitory molecules or factors produced by tumors, and the induction of cells that can suppress the immune response, including myeloid-derived suppressor cells (MDSC) and regulatory T cells. We have focused our work on characterizing MDSC and the mechanisms by which they cause T-cell dysfunction in cancer.

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Section: Discussionmentioning

confidence: 99%

Arginase, Prostaglandins, and Myeloid-Derived Suppressor Cells in Renal Cell Carcinoma

Ochoa

Zea

Hernandez

et al. 2007

Clinical Cancer Research

433

325

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“…12 There are few relevant clinical studies. [13][14][15][16][17] Most recently, a study of PN in malnourished gastric cancer patients indicated no significant difference in tumor cell proliferation with administration of PN preoperatively. 18 Absent any overt effects, it is reasonable to ignore this theoretical consideration when contemplating the use of NST in patients.…”

mentioning

confidence: 99%

A.S.P.E.N. Clinical Guidelines: Nutrition Support Therapy During Adult Anticancer Treatment and in Hematopoietic Cell Transplantation

August

Huhmann

2009

J Parenter Enteral Nutr

442

279

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“…It is also noteworthy that the BCAA-enriched solution could be less efficient than standard solution at increasing tumor protein synthesis [24].…”

Section: Host Response To the Modulation Of Nutrientsmentioning

confidence: 99%

Artificial Nutrition in Cancer Patients: Which Route, What Composition?

et al. 1999

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The state of art of artificial nutrition in depleted cancer patients is reviewed in brief. Because cancer cachexia cannot be equated to simple nutrient deficiency but is due instead to complex metabolic abnormalities, the nutritional effects of total parenteral (TPN) and enteral (EN) nutrition are more limited than in starving subjects. TPN and EN usually prevent further deterioration of the nutritional status, although they are not able to fully reverse a state of depletion. There is evidence that quantitative and qualitative modulation of certain nutrients may obtain better results because of a favorable impact on host metabolism. Research in this field is fully warranted. Moreover, the effects of some substrates on tumor metabolism and tumor growth require further investigation to define a nutritional regimen able to maintain the host metabolism with minimum stimulation of tumor growth.

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Stimulation of protein synthesis in human tumours by parenteral nutrition: Evidence for modulation of tumour growth

Cited by 51 publications

References 24 publications

Arginase, Prostaglandins, and Myeloid-Derived Suppressor Cells in Renal Cell Carcinoma

Arginase, Prostaglandins, and Myeloid-Derived Suppressor Cells in Renal Cell Carcinoma

A.S.P.E.N. Clinical Guidelines: Nutrition Support Therapy During Adult Anticancer Treatment and in Hematopoietic Cell Transplantation

Artificial Nutrition in Cancer Patients: Which Route, What Composition?

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