Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The differences in properties of pyruvate kinase (EC 2.1.7.40) from normal tissues and animal or human tumors are described and their significance for various metabolic abnormalities is reviewed. The tumor variant gamma3 from M2 isoenzyme of pyruvate kinase sensitive to L-cysteine inhibition, when over-expressed, can be used as a marker of tumorigenic transformation. It seems that this variant represents a tumor-specific oncoprotein, involved in a novel metabolic strategy of energy generation during increased cell proliferation.
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PMID:Tumor-specific pyruvate kinase isoenzyme M2 involved in biochemical strategy of energy generation in neoplastic cells. 958 51

Preneoplastic liver foci and neoplasms of different morphological phenotypes were induced in rats with N-nitrosomorpholine (NNM; 120 mg/l in drinking water for 7 weeks) and the peroxisome proliferator dehydroepiandrosterone (DHEA; 0.6% in the diet for up to 84 weeks). Preneoplastic glycogen storage foci (GSF) occurred mainly upon treatment with NNM, and amphophilic cell foci (APF) were mainly observed in rats treated with DHEA alone or in combination with NNM. The 2 types of lesions belong to 2 different cellular lineages, the glycogenotic/basophilic lineage and the amphophilic lineage, which are characterized by distinct patterns of alterations in key enzymes of energy metabolism. Whereas in GSF enzymes of glucose metabolizing pathways were modified (increase in glucose-6-phosphate dehydrogenase and pyruvate kinase, decrease in glucose-6-phosphatase), APF mainly demonstrated alterations in mitochondrial enzymes (increase in cytochrome c oxidase, succinate dehydrogenase and glycerol-3-phosphate dehydrogenase) and, to a lower extent, in peroxisomal enzymes (increase in peroxisomal hydratase and acyl-CoA oxidase). The alterations in enzyme expression reflect an insulinomimetic effect in GSF and a thyromimetic effect in APF. Neoplasms resulting from APF show a more differentiated phenotype than those arising from GSF. We suggest that the different and in many aspects opposite effects of the 2 carcinogens on key enzymes of distinct pathways of energy metabolism modulate the process of neoplastic liver cell transformation and result in phenotypically different preneoplasias and neoplasias reflecting different cellular lineages.
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PMID:Differential expression of key enzymes of energy metabolism in preneoplastic and neoplastic rat liver lesions induced by N-nitrosomorpholine and dehydroepiandrosterone. 964 43

We report here that the E7 oncoprotein encoded by the oncogenic human papillomavirus (HPV) type 16 binds to the glycolytic enzyme type M2 pyruvate kinase (M2-PK). M2-PK occurs in a tetrameric form with a high affinity to its substrate phosphoenolpyruvate and a dimeric form with a low affinity to phosphoenolpyruvate, and the transition between both conformations regulates the glycolytic flux in tumor cells. The glycolytic intermediate fructose 1, 6-bisphosphate induces the reassociation of the dimeric to the tetrameric form of M2-PK. The expression of E7 in an experimental cell line shifts the equilibrium to the dimeric state despite a significant increase in the fructose 1,6-bisphosphate levels. Investigations of HPV-16 E7 mutants and the nononcogenic HPV-11 subtype suggest that the interaction of HPV-16 E7 with M2-PK may be linked to the transforming potential of the viral oncoprotein.
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PMID:Modulation of type M2 pyruvate kinase activity by the human papillomavirus type 16 E7 oncoprotein. 999 17

The diagnostic value of the tumor marker pyruvate kinase type tumor M2 was evaluated in patients with benign, malignant and metastasizing pancreatic lesions and compared to the reference markers CA19-9 and CEA. This prospective study comprised 166 individuals; 66 patients had various pancreatic pathologies (38 histologically proven pancreatic cancer, 28 benign pancreatic lesions such as pseudotumorous pancreatitis, pseudocysts or pancreatic (cyst)adenoma) and 100 healthy blood donors served as controls. With a cut-off value of 28 U/ml (corresponding to a specificity of 90%) the sensitivity of TUM2-PK for pancreatic cancer (as related to the control group) was 79% (CA19-9: 65%, CEA: 22%). There was a good correlation between the TUM2-PK levels and tumor metastasis (p < 0.001 for no versus distant metastasis, p = n.s. for CA19-9 and CEA). However, TUM2-PK was also elevated in 64.3% of the patients with benign pancreatic pathologies. In our study TUM2-PK had good diagnostic qualities for pancreatic cancer and also showed better correlation to metastasis than CA 19-9 and CEA.
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PMID:TUM2-PK (pyruvate kinase type tumor M2), CA19-9 and CEA in patients with benign, malignant and metastasizing pancreatic lesions. 1021 4

Various isoforms of the glycolytic enzyme pyruvate kinase are expressed in different cell-types. One of these isoforms, the type Tu M2-PK, is strongly overexpressed by tumor cells and released into body fluids. The concentration of Tu M2-PK in body fluids can be quantitatively determined by a commercially available enzyme-linked immunosorbent assay (ELISA)-kit. Using this kit, the Tu M2-PK concentration was measured in EDTA-plasma of 64 patients with renal carcinoma and 10 patients suffering from nephritis. The ranges of the Tu M2-PK-concentrations of the two groups did not overlap, indicating a highly significant discrimination of renal carcinoma and benign renal diseases. Furthermore, the Tu M2-PK-concentration in EDTA-plasma correlates strongly with the Robson tumor stage of the 64 patients. The present results indicate that the Tu M2-PK might be the first tumor marker which could be an excellent complementation of the diagnostic program for renal carcinoma.
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PMID:The pyruvate kinase isoenzyme tumor M2 (Tu M2-PK) as a tumor marker for renal carcinoma. 1047 Feb 1

The majority of tumors express an isoform of the glycolytic enzyme pyruvate kinase, the type tumor M2. The isoenzyme exists in an active tetrameric and a less active dimeric form. The dimeric form is strongly overexpressed in tumor cells and this new tumor marker is thus called tumor M2-PK. This isoenzyme is released from tumor cells and is quantitatively detectable in body fluids by a sensitive enzyme-linked immunosorbent assay (ELISA). To establish the ELISA for the routine diagnostic in a clinical laboratory, the sample stability was evaluated. Therefore, blood samples were collected in different ways from healthy donors. Reproducibility of tumor M2-PK detection in EDTA-plasma was not affected by the day to day 'stress' in a clinical routine (e.g. shaking, leaving the samples at room temperature for several hours without prior centrifugation). Similar results were obtained with citrate-plasma, whereas detection in serum and heparin-plasma was only reproducible when the blood samples were centrifuged within 2 hrs after collection. It appears that lymphocytes contain small amounts of the tumor M2-PK isoenzyme. They might release tumor M2-PK in heparin-plasma and serum samples, but not in EDTA-plasma samples. The results indicated that EDTA-plasma appears to be most appropriate for the routine diagnostic of tumor M2-PK as a tumor marker.
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PMID:Quantitative detection of tumor M2-PK in serum and plasma. 1047 Feb 35

Tumor cell metabolism is characterized by a high rate of aerobic glycolysis. The metabolic differences require changes in glycolytic enzyme activities and isoenzyme patterns. The inactive form of the M2 pyruvate kinase (Tu M2-PK) is specifically expressed in tumor cells and has been detected immunohistochemically in tumor tissue but also in peripheral blood of patients with different malignant tumors. In this study, Tu M2-PK in the plasma of patients with renal cell carcinoma (RCC) was compared with healthy volunteers. Tu M2-PK was quantified with a commercially available enzyme linked immunosorbent assay (ELISA) kit. Using the ELISA kit, plasma probes of 57 healthy individuals were compared to 63 patients with RCC (51 patients with non-metastatic RCC, 12 patients with metastatic RCC). Statistical analysis was performed with the non-parametric ANOVA test according to Kruskal-Wallis. In patients with renal cell carcinoma, Tu M2-PK was significantly higher than in healthy volunteers. For organ-defined, non-metastatic tumors, sensitivity was only 27.5%, if the 95% reference values of the control group were used for discrimination. The differences were more pronounced in patients with metastatic disease. Tu M2-PK was significantly enhanced compared to healthy controls, but also to the group with non-metastatic disease, the sensitivity was 66.7%. Our data show that Tu M2-PK has no impact as an unspecific marker for the diagnosis of renal cell carcinoma. This is especially relevant to organ-defined, non-metastatic RCC. In advanced metastatic disease, a potential importance as a parameter for treatment control in palliative therapeutic approaches can be assumed, and warrants further investigations.
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PMID:[Tumor M2 pyruvate kinase in renal cell carcinoma. Studies of plasma in patients]. 1113 78

Lung cancer is one of the predominant causes of cancer death. The aim of this project is the development of a screening method in persons with high risk for developing lung cancer, based on the measurement of Tumor M2-pyruvate kinase (Tumor M2-PK). Tumor M2-PK is quantitatively detectable in ethylenediaminetetraacetic acid-plasma with a sensitive enzyme-linked immunosorbent assay. So far, 60 patients with newly diagnosed lung cancer were included. These were compared to 24 patients with acute inflammatory lung diseases, 56 patients with pneumoconiosis, 22 patients with obstructive airway diseases, and 28 healthy persons. Tumor patients and some individuals suffering from severe inflammatory lung diseases had significantly higher Tumor M2-PK concentrations in ethylenediaminetetraacetic acid-plasma than all the other groups. The histologic tumor type had no influence on the plasma levels of Tumor M2-PK. Tumor M2-PK concentrations correlate strongly with the tumor stage, showing significantly increasing concentrations with progressive tumor stages. The present data indicate that Tumor M2-PK could be a valuable tumor marker for the detection of lung cancer.
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PMID:Quantitative detection of tumor M2-pyruvate kinase in plasma of patients with lung cancer in comparison to other lung diseases. 1119 66

The pyruvate kinase isoenzyme M2-PK is known to be associated with a metabolic shift that is characteristic for tumor cells. Meanwhile, the universal expression of this isoenzyme is the basis for the detection of various tumor diseases in human clinical diagnosis. Other enzymes which are known to be essential for this tumor specific metabolic shift in rat chemical carcinogenesis are the NADP-dependent enzymes malic enzyme, isocitrate dehydrogenase and glucose 6-phosphate dehydrogenase. To evaluate the role of these enzymes in human carcinogenesis, we compared their enzymatic activities in normal colon mucosa and tissues derived from primary colon tumors. Histochemical staining showed that the enzyme activities were restricted to mucosal colon cells and colon cancer cells. The enzymes were strongly but heterogeneously expressed in the tumor tissues, whereas staining of normal mucosa was weak. Tumor M2-PK showed the most prominent differences in normal colon mucosa and colon cancer cells.
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PMID:Tumor M2-PK and glutaminolytic enzymes in the metabolic shift of tumor cells. 1132 87

In in vitro cultures, the cell is virtually isolated and can no longer rely on mechanisms for physiological regulation of substrate availability found in tissues. More emphasis is laid on utilization of preponderant substrate in a proposed reciprocal relationship between glycolysis and free fatty acid (FFA) oxidation for energy. Supraphysiological concentrations of gamma-linolenic acid and some other polyunsaturated fatty acids (PUFAs) therefore suppress glycolysis but also inhibit FFA oxidation initiated through a cytochrome P450-mediated epoxidation of PUFA to inhibit fatty acid synthase (FAS) activity. FAS inhibition accumulates malonyl CoA which inhibits carnitine palmitoyl transferase I and prevents FFA oxidation. The cell is starved of energy and anabolic intermediates, leading to decreased proliferation or death for tumor cells. Tumor cells are more vulnerable to this induced toxicity due to possession of specific phenotypes of elevated expression for FAS and pyruvate kinase, type M2, both factors inducing tumor cell apoptosis on inhibition.
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PMID:Repression of cellular anaplerosis as the hypothesized mechanism of gamma-linolenic acid-induced toxicity to tumor cells. 1138 72


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