This article summarizes data from experimental and clinical oncology which are indicative of a pivotal role of tumor carbohydrate metabolism in malignant behavior and outcome of treatment.
In primary tumors, such as cervix carcinomas, head and neck squamous cell carcinomas or rectum adenocarcinomas, elevated lactate levels as a mirror of a high glycolytic activity, are correlated eve…
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Lactate and redox status in malignant tumors
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An association of carcinogenesis and decrease of cellular NAD concentration.
It is postulated that a decrease in nicotinamide adenine dinucleotide (NAD) concentration has a primary association with carcinogenesis. The following observations are presented as evidence:
(1) NAD and adenosine triphosphate (ATP) concentrations are lower in cancer cells; (2) chemical carcinogens and radiation can cause a lowering of NAD concentration in precancerous cells: (… |
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Mapping the role of NAD metabolism in prevention and treatment of carcinogenesis…
Studies presented here show that cellular NAD, which we hypothesize to be the relevant biomarker of niacin status, is significantly lower in humans than in the commonly studied animal models of carcinogenesis.
We show that nicotinamide and the resulting cellular NAD concentration modulate expression of the tumor suppressor protein, p53, in human breast, skin, and lung cells. Studies … |
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Correlation of high lactate levels in head and neck tumors with incidence of met…
Using quantitative bioluminescence imaging, tissue concentrations of ATP, glucose, and lactate were registered in biopsies that were taken from primary tumors of human head and neck at the time of first cancer diagnosis.
From 15 patients investigated at present, 6 had locoregional lymph node metastasis, 6 had no detectable metastatic spread, 2 biopsies contained dysplasias, and 1 bio… |
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Enhanced poly ADP-ribosylation in human leukemia lymphocytes and ovarian cancers…
Freshly isolated human peripheral blood lymphocytes from leukemia (AML, ALL, CML) subjects, showed a 2.5-3.5-fold increase in the poly ADPR transferase (poly ADPRT) activity whereas ovarian cancers showed a 2-fold increase.
This was accompanied by a drop in NAD levels of 45%-63% in leukemia cells and 40% in ovarian cancers. Tumour promoters phorbol-12-myristate-13-acetate (PMA) and m… |
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Evaluating the role of niacin in human carcinogenesis.
Our understanding of the role of ADP-ribose polymer metabolism in limiting carcinogenic events and the dependence of this metabolism on cellular NAD levels predicts that niacin deficiency leading to reduced NAD levels may enhance carcinogenesis.
This prediction has led us to initiate studies to evaluate the potential of niacin as a preventive factor in human cancer. The first approac… |
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Severe lactic acidosis in a 14-year-old female with metastatic undifferentiated …
A 14-year-old girl was found to have a large, non-tender breast mass with anemia and thrombocytopenia. The diagnosis of an undifferentiated carcinoma of unknown primary was made after open breast biopsy of the mass with negative immunohistochemical studies for breast malignancies.
Further evaluation showed extensive metastatic disease affecting the bone marrow, ribs, liver, and brain… |
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Metabolism of vitamins B1 and PP and their use in oncological practice.
Blood of patients with gastric tumor was studied after their admission to the hospital and after the chemotherapeutic course. Formation of the tumor was accompanied by development of hypovitaminoses B1 and PP.
The vitamin deficiency was more distinct after treatment of the patients with cyclophosphan: content of thiamine diphosphate (TDP) was decreased by 40%; NAD+NADP, by 30% and NA… |
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Niacin deficiency and cancer in women.
A new interest in the relationship between niacin and cancer has evolved from the discovery that the principal form of this vitamin, NAD, is consumed as a substrate in ADP-ribose transfer reactions. Poly(ADP-ribose) polymerase, an enzyme activated by DNA strand breaks, is the ADP-ribosyltransferase of greatest interest with regard to effects on the niacin status of cells since its Km for NAD is hi…
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Niacin and carcinogenesis.
The dietary status of niacin (vitamin B3) has the potential to influence DNA repair, genomic stability, and the immune system, eventually having an impact on cancer risk, as well as the side effects of chemotherapy in the cancer patient.
In addition to its well-known redox functions in energy metabolism, niacin, in the form of NAD, participates in a wide variety of ADP-ribosylation r… |
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Biochemical assessment of niacin deficiency among carcinoid cancer patients.
OBJECTIVE: Carcinoid cancer patients often have elevated levels of serotonin or its precursor 5-hydroxytryptophan. Normally, serotonin synthesis accounts for a small fraction of tryptophan catabolism, which should be directed along a pathway that allows partial conversion to niacin; hence, increased diversion of tryptophan toward serotonin could cause variable degrees of niacin deficiency in carci…
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Hexokinase and lactate dehydrogenase activity, lactic and pyruvic acid content o…
Certain glycolytic enzymes, the level of end metabolites of glycolysis and acid-base equilibrium indices were studied in 106 patients with stomach tumors (stage II-III).
It was found that prior to surgery metabolic disturbances in erythrocytes are to be observed, while acid-base indices tend toward metabolic acidosis. After radical surgery, the activity levels of hexoki… |
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NAD and adenosine triphosphate (ATP) concentrations are lower in cancer cells
It is postulated that a decrease in nicotinamide adenine dinucleotide (NAD) concentration has a primary association with carcinogenesis.
The following observations are presented as evidence: (1) NAD and adenosine triphosphate (ATP) concentrations are lower in cancer cells; (2) chemical carcinogens and radiation can cause a lowering of NAD concentration in precanc… |
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