Cancer Cachexia and Protein Metabolism

Jeevanandam, Malayappa; Lowry, StephenF.; Horowitz, GlennD.; Brennan, M. F.

doi:10.1016/s0140-6736(84)91929-9

Cited by 151 publications

(39 citation statements)

References 22 publications

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“…Patients with a nutritional deficit or in a state of cachexia have a generalized reduction in most amino acids, especially the precursors of neoglycogenesis, due to the increased use of these to obtain energy 8 . However, the cancer patients in our series, with no weight loss or nutritional deficit, had an increased amino acid profile compared with the controls, except for aspartic acid, 3-methyl histidine, lysine, histidine and ornithine, the concentrations of which were reduced in lung cancer patients, and aspartic acid and 3-methyl histidine in head and neck cancer patients.…”

Section: Discussionmentioning

confidence: 99%

“…Patients with cancer and cachexia have a reduced protein synthesis and altered glucose metabolism at the level of the skeletal muscle, which has been associated with a reduction in the uptake of leucine by the muscle 7 . Alterations in the metabolism of amino acids and proteins in persons with neoplasms are usually the consequence of certain dysfunctions in the host metabolism, such as accelerated glyconeogenesis and increased protein synthesis by the liver 8 . As a result, changes in the serum profile of free amino acids are reflected in alterations in protein metabolism, as occurs in other diseases, such as diabetic ketoacidosis and protein or calorie malnutrition 9 .…”

Section: Introductionmentioning

confidence: 99%

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Specific alterations in the serum amino acid profile of patients with lung cancer and head and neck cancer

Dols¹,

Lopez

Plaza

et al. 2006

Oncología (Barc.)

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1 SummaryPurpose: Metabolism of the immediate principles is altered in cancer patients, resulting in an altered serum concentration of amino acids. The aim of this study was to find specific serum amino acid profiles in patients with cancer of the lung or head and neck. Material and methods:We analyzed the baseline serum levels of 27 amino acids in 51 patients with cancer of the lung or head and neck with no metabolic alterations or other concomitant disorders and compared the results with a control group.Results: Compared with the control group, patients with head cancer had significant differences in cysteine, aspartic acid, 3-methyl histidine, alanine, glycine, lysine, methionine, proline, serine, taurine, tyrosine, and threonine; and patients with lung cancer in cysteine, aspartic acid, 3-methyl histidine, histidine, citrulline, ornithine, alanine, glycine, lysine, methionine, proline, serine, taurine, tyrosine, and threonine. Conclusions:Variation in serum levels of certain amino acids in head and neck cancer and lung cancer is probably caused by interaction of the neoplasm with the protein metabolism. Each type of tumor has a certain specificity in the serum amino acid profile that may be useful in the diagnosis of these tumors.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Specific alterations in the serum amino acid profile of patients with lung cancer and head and neck cancer

Dols¹,

Lopez

Plaza

et al. 2006

Oncología (Barc.)

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“…Consequently, amino acid homeostasis may be altered in response to malnutrition (4,40,59) and also by various forms of pathology leading to a negative nitrogen balance (chronic pathology, AIDS, and cancer, etc.) (41,86,89). Very often, in one of these situations, the availability of one or several essential amino acids is dramatically affected.…”

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confidence: 99%

Identification of a Novel Amino Acid Response Pathway Triggering ATF2 Phosphorylation in Mammals

Chaveroux

Jousse

Chérasse

et al. 2009

Molecular and Cellular Biology

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It has been well established that amino acid availability can control gene expression. Previous studies have shown that amino acid depletion induces transcription of the ATF3 (activation transcription factor 3) gene through an amino acid response element (AARE) located in its promoter. This event requires phosphorylation of activating transcription factor 2 (ATF2), a constitutive AARE-bound factor. To identify the signaling cascade leading to phosphorylation of ATF2 in response to amino acid starvation, we used an individual gene knockdown approach by small interfering RNA transfection. We identified the mitogen-activated protein kinase (MAPK) module MEKK1/MKK7/JNK2 as the pathway responsible for ATF2 phosphorylation on the threonine 69 (Thr69) and Thr71 residues. Then, we progressed backwards up the signal transduction pathway and showed that the GTPase Rac1/Cdc42 and the protein G␣12 control the MAPK module, ATF2 phosphorylation, and AARE-dependent transcription. Taken together, our data reveal a new signaling pathway activated by amino acid starvation leading to ATF2 phosphorylation and subsequently positively affecting the transcription of amino acid-regulated genes.

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“…The conclusive evidence of many studies demonstrates that cancer can present an altered metabolism characterized by: high rate of glycolysis (Fujibayashi et al, 1997;Mathupala et al, 1997;Rodriguez-Enriquez and Moreno-Sanchez, 1998) associated with an increased rate of glucose transport (Dang et al, 1997;Reske et al, 1997); increased gluconeogenesis (Lundholm et al, 1982); reduced pyruvate oxidation with increased production of lactic acid (Mazurek et al, 1997a); increased glutaminolytic enzyme activities (Wasa et al, 1996;Fischer et al, 1998); reduced fatty acid oxidation (Prip Buus et al, 1992;Ockner et al, 1993); increased glycerol and fatty acid turnover (Shaw and Wolfe, 1987); decreased glycerol 3-phosphate shuttle and malate-aspartate shuttle activities (Mazurek et al, 1997b(Mazurek et al, , 1998; modified protein and amino acid metabolism (Heber et al, 1982;Jeevanandam et al, 1984;Souba, 1993); and increased pentose phosphate pathway enzyme activities (Boros et al, 1998).…”

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confidence: 99%

Cancer and anticancer therapy-induced modifications on metabolism mediated by carnitine system

et al. 2000

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An efficient regulation of fuel metabolism in response to internal and environmental stimuli is a vital task that requires an intact carnitine system. The carnitine system, comprehensive of carnitine, its derivatives, and proteins involved in its transformation and transport, is indispensable for glucose and lipid metabolism in cells. Two major functions have been identified for the carnitine system: (1) to facilitate entry of long-chain fatty acids into mitochondria for their utilization in energy-generating processes; (2) to facilitate removal from mitochondria of short-chain and medium-chain fatty acids that accumulate as a result of normal and abnormal metabolism. In cancer patients, abnormalities of tumor tissue as well as nontumor tissue metabolism have been observed. Such abnormalities are supposed to contribute to deterioration of clinical status of patients, or might induce cancerogenesis by themselves. The carnitine system appears abnormally expressed both in tumor tissue, in such a way as to greatly reduce fatty acid beta-oxidation, and in nontumor tissue. In this view, the study of the carnitine system represents a tool to understand the molecular basis underlying the metabolism in normal and cancer cells. Some important anticancer drugs contribute to dysfunction of the carnitine system in nontumor tissues, which is reversed by carnitine treatment, without affecting anticancer therapeutic efficacy. In conclusion, a more complex approach to mechanisms that underlie tumor growth, which takes into account the altered metabolic pathways in cancer disease, could represent a challenge for the future of cancer research.

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Cancer Cachexia and Protein Metabolism

Cited by 151 publications

References 22 publications

Specific alterations in the serum amino acid profile of patients with lung cancer and head and neck cancer

Specific alterations in the serum amino acid profile of patients with lung cancer and head and neck cancer

Identification of a Novel Amino Acid Response Pathway Triggering ATF2 Phosphorylation in Mammals

Cancer and anticancer therapy-induced modifications on metabolism mediated by carnitine system

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