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)

Mouse renal cell tumors (RCTs) were induced in male CBA mice by 5 subcutaneous injections of 8 mg 1,2-dimethylhydrazine (DMH)/kg body weight once a week. After a lag period of 2 yr kidneys were removed, and serial cryostat sections of the kidneys were histochemically analyzed for the following parameters: glycogen content, basophilia, and the activities of glycogen synthase (SYN), glycogen phosphorylase (PHO), glucose-6-phosphatase (G6Pase), glucose-6-phosphate dehydrogenase (G6PDH), hexokinase (HK), pyruvate kinase (PK), lactate dehydrogenase (LDH), malic enzyme (ME), succinate dehydrogenase (SDH), alkaline phosphatase (ALPase) and gamma-glutamyltranspeptidase (GGT). RCTs displayed the same histochemical profile irrespective of their size and growth pattern. In comparison with the normal kidney epithelium, the neoplastic cells exhibited elevated activities of enzymes for glycolysis (HK, PK, LDH) and the pentose phosphate pathway (G6PDH), while negative G6Pase and low SDH activity were observed in these cells. The majority of RCTs showed high PHO activity and weak staining for SYN. Activities of ALPase and GGT were negative in most of the RCTs. Markedly enlarged cells with atypical nuclei were detected in some advanced RCTs. Higher activities of glycolytic and mitochondrial enzymes and G6PDH were found in these enlarged cells than in other tumor cells. Tubular preneoplastic lesions were similar to neoplastic lesions in morphological and histochemical characteristics. The present study revealed that a markedly elevated capacity for glycolysis and the pentose phosphate pathway occurred in RCTs in mice. A similar histochemical pattern in the few preneoplastic tubular lesions observed suggests that these metabolic aberrations emerge early during carcinogenesis, but additional studies on early stages of renal carcinogenesis are needed to substantiate this assumption.
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PMID:Enzymic pattern of preneoplastic and neoplastic lesions induced in the kidney of CBA mice by 1,2-dimethylhydrazine. 781 30

Japanese white rabbits transplanted with VX2 liver tumors are considered to be a suitable experimental model for the evaluation of therapeutic modalities. However, there has been no adequate method of assessing the changes of tumor metabolism during treatment. In the present study, 15 rabbits with VX2 liver tumors were examined by PET using 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG). After an intravenous injection of 18F-FDG, serial arterial blood sampling was performed. One hour after tracer injection, small pieces of normal liver tissue and tumor tissue were excised to determine radioactivity. Dynamic PET images were obtained in 11 of the tumor-bearing rabbits, and tumor enzyme activities were determined in six rabbits. Fluorine-18-FDG uptake by the VX2 liver tumors was 3.5 +/- 0.9 times higher than that by the normal liver tissue; so good contrast between tumor and normal liver tissue was achieved on PET scans. The enzyme activity study showed that VX2 tumors had increased levels of hexokinase and pyruvate kinase activity, suggesting an increase of glycolysis. We conclude that transplanted VX2 liver tumors could be appropriately evaluated by 18F-FDG PET.
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PMID:Evaluation of experimental liver tumors using fluorine-18-2-fluoro-2-deoxy-D-glucose PET. 825 99

We have used subtractive hybridization to isolate cDNAs overexpressed in SK-PC-1 pancreas cancer cells. Forty-five independent clones corresponding to 11 genes were identified. Their expression in cultured pancreas cancer cells, normal pancreas tissue, and normal exocrine pancreas cultures was examined by Northern blotting. cDNA clones can be grouped into two broad categories: (1) those corresponding to genes expressed at high levels both in tumor cell lines and in primary cultures of normal pancreas, but not in normal tissue (i.e. thymosin beta4(3), cytokeratin 18, beta-actin, pyruvate kinase and mitochondrial genes); and (2) those corresponding to genes expressed at high levels in pancreas cancer cultures but not in normal pancreas tissue or cultured cells (i.e. tissue-type plasminogen activator and cathepsin H). The overexpression of these proteases in pancreas cancers suggests that they play a role in the aggressive biological behavior of this tumor.
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PMID:Isolation of tissue-type plasminogen activator, cathepsin H, and non-specific cross-reacting antigen from SK-PC-1 pancreas cancer cells using subtractive hybridization. 864 71

As demonstrated previously, liver acini draining the blood from intraportally transplanted pancreatic islets in streptozotocin-diabetic rats are altered in various respects. The hepatocytes in these acini store glycogen and/or fat, and they show an increase in proliferation as well as in apoptotic activity. Thus, they are phenotypically similar to carcinogen-induced preneoplastic liver foci (glycogen-storing foci and sometimes also mixed cell foci). By means of catalytic enzyme histochemistry or immunohistochemistry, we investigated the activity of key enzymes of alternative pathways of carbohydrate metabolism and some additional marker enzymes (well known from studies on preneoplastic hepatic foci) in the altered liver acini surrounding the islet isografts. In addition, the expression of glucose transporter proteins 1 and 2 (GLUT-1 and GLUT-2) were investigated immunohistochemically. The activities of hexokinase, pyruvate kinase, glyceraldehyde-3-phosphate dehydrogenase, and glucose-6-phosphate dehydrogenase were increased, whereas the activities of glycogen phosphorylase, adenylate cyclase, glucose-6-phosphatase, and membrane-bound adenosine triphosphatase were decreased in the altered liver acini. The expression of GLUT-2 was also decreased. GLUT-1 and glutathione S-transferase placental form were not expressed, and the activities of glycogen synthase and gamma-glutamyl-transferase remained unchanged. All changes of the enzyme activities were in line with the well known effects of insulin and resembled alterations characteristic of preneoplastic liver foci observed in different models of hepatocarcinogenesis. It remains to be clarified in long-term experiments whether or not these foci represent preneoplastic lesions and may proceed to neoplasia.
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PMID:Altered liver acini induced in diabetic rats by portal vein islet isografts resemble preneoplastic hepatic foci in their enzymic pattern. 864 65

Mouse renal cell tumors (RCT) were induced in male CBA male mice by 5 subcutaneous injections of 8 mg 1,2-dimethylhydrazine (DMH) per kg body weight once a week. After a lag period of two years the kidneys were removed, and serial cryostat sections of the kidneys were histochemically analyzed for the following parameters: Glycogen content, basophilia, and activities of glycogen synthase (SYN), glycogen phosphorylase (PHO), glucose-6-phosphatase (G6Pase), glucose-6-phosphate dehydrogenase (G6PDH), hexokinase (HK), pyruvate kinase (PK), lactate dehydrogenase (LDH), malic enzyme (ME), succinate dehydrogenase (SDH), alkaline phosphatase (ALPase) and glutamyl-transpeptidase (GGT). RCT displayed the same histochemical profile irrespective of their size and growth pattern. In comparison with normal kidney epithelium, the neoplastic cells exhibited elevated activities of enzymes for glycolysis (HK, PK LDH) and the pentose phosphate pathway (G6PDH) while negative G6Pase and low SDH activity were observed in these cells. The majority of RCT showed high PHO activity and weak staining for SYN. Activities of ALPase and GGT were negative in most of the RCT. Giant cells were detected in some large RCT. Higher activities of glycolytic and mitochondrial enzymes and G6PDH were found in giant cells compared with other tumor cells. Tubular preneoplastic lesions were similar to neoplastic lesions in morphological and histochemical characteristics. The present study revealed that a markedly elevated capacity for glycolysis and the pentose phosphate pathway occurred in renal cell tumors in mice. A similar histochemical pattern in the few preneoplastic tubular lesions observed suggests that these metabolic aberrations emerge early in carcinogenesis, but studies on earlier stages of renal carcinogenesis are needed to substantiate this assumption.
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PMID:[Enzymic spectrum of preneoplastic and neoplastic changes induced by 1,2-dimethylhydrazine in mouse kidneys]. 874 89

We studied the effect of cyclic polylactates ranging in size from a degree of polymerization number of 3 to 13 on pyruvate kinase, lactic dehydrogenase, anaerobic glycolysis, growth of tumor cells and survival of tumor bearing mice. Pyruvate kinase and lactic dehydrogenase activities were both inhibited by cyclic polylactates, and the inhibition mechanism of cyclic polylactates on lactic dehydrogenase was noncompetitive. About half the anaerobic glycolytic activity of FM3A ascites tumor cells was inhibited and tumor cell growth was also effectively inhibited by cyclic polylactates. Mice, which were treated with cyclic polylactates after inoculation of FM3A ascites tumor cells lived significantly longer than mice, which were treated with vehicle or non mice.
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PMID:Effect of cyclic polylactates on tumor cells and tumor bearing mice. 931 77

The monoclonal antibody pyruvate kinase type tumor M2 (TUM2-PK) has been shown to have a high binding capacity to pancreatic cancer. In present study TUM2-PK serum levels were measured in pancreatic cancer and compared with the reference tumor markers CA19-9, CA50, CA72-4 and CEA. Overall 100 patients were included in this study, 64 patients had a histologically confirmed pancreatic carcinoma, 36 patients gastrointestinal cancer (stomach, colon), 666 healthy volunteers served as controls. Measurements were done by enzymimmunoassay. For the healthy blood donors a cut-off value of 22.5 U/ml was evaluated, which corresponds to 95% specificity. In patients with pancreatic cancer the sensitivities of TUM2-PK, CA19-9, CEA, CA72-4 and CA50 were 71%; 68%, 37%, 49% and 63.4% respectively. Linear regression analysis indicated that there was a positive correlation (r = 0.79). According to the results of our study TUM2-PK has comparable sensitivity but higher specificity than the reference tumor marker CA19-9.
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PMID:Value of the serum levels of the tumor marker TUM2-PK in pancreatic cancer. 932 93

Proliferating and tumor cells express a certain isoenzyme of pyruvate kinase, called PK type M2. This isoenzyme can be isolated in an active tetrameric and an inactive dimeric form. We have termed this form tumor type M2-PK. This tumor type pyruvate kinase can be quantified by a specific ELISA in blood sera and tumor homogenates. In this study we have compared 26 normal colon mucosa and colon cancer specimens from the same patients. The total specific pyruvate kinase activity and the amount of the tumour type M2-PK measured by ELISA was increased in the tumor samples compared to the normal colon mucosa of the same patient. In normal colon mucosa the specific PK-activity ranged between 0.21 and 1.25 U/mg protein whereas in colon carcinoma we found activities between 0.99 and 7.08 U/mg. The amount of tumor M2-PK measured by ELISA ranged between 0.82 and 27.10 U/mg protein in normal colon mucosa and between 1.96 and 242.40 U/mg protein in colon carcinoma. The tumor M2-PK content in the serum of 666 healthy blood donors was measured by ELISA and compared to sera from 15 colon carcinoma patients and showed a highly significant difference (Mann-Whitney rank sum test, p < 0.001). The values for the 50%-percentiles (median) of blood donors were 10.8 U/ml and 55.0 U/ml for colon carcinoma.
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PMID:Quantification of tumor type M2 pyruvate kinase (Tu M2-PK) in human carcinomas. 932 24

A common characteristic of tumor cells is the constant overexpression of glycolytic and glutaminolytic enzymes. In tumor cells the hyperactive hexokinase and the partly inactive pyruvate kinase lead to an expansion of all phosphometabolites from glucose 6-phosphate to phosphoenolpyruvate. In addition to the glycolytic phosphometabolites, synthesis of their metabolic derivatives such as P-ribose-PP, NADH, NADPH, UTP, CTP, and UDP-N-acetyl glucosamine is also enhanced during cell proliferation. Another phosphometabolite derived from P-ribose-PP, AMP, inhibits cell proliferation. The accumulation of AMP inhibits both P-ribose-PP-synthetase and the increase in concentration of phosphometabolites derived from P-ribose-PP. In cells with low glycerol 3-phosphate and malate-aspartate shuttle capacities the inhibition of the lactate dehydrogenase by low NADH levels leads to an inhibition of glycolytic ATP production. Several tumor-therapeutic drugs reduce NAD and NADH levels, thereby inhibiting glycolytic energy production. The role of AMP, NADH, and NADPH levels in the success of chemotherapeutic treatment is discussed.
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PMID:The role of phosphometabolites in cell proliferation, energy metabolism, and tumor therapy. 938 92

The effect of pH and the presence of FBP on the interaction of skeletal muscle (PK-M1) and kidney or tumor meningioma (PK-M2) pyruvate kinase with the phospholipids liposomes were investigated by ultracentrifugation and steady-state kinetics and were compared with those results obtained using the bovine heart (PK-M1) isoenzyme which we previously studied. Pyruvate kinase specific activity increases upon the interaction with liposomes. The activation is specifically sensitive to presence of phosphatidylserine (PS) in liposomes. Liposomes made of phosphatidylcholine + phosphatidylserine mixture are good adsorptive systems for both human and bovine of M-type isozymes at low ionic strength. Interaction of PK-M1 with PS liposomes results in the change of Vmax and K(m) values for PEP without marked effect on Hill coefficients. Addition of PS liposomes to PK-M2 induces hyperbolic saturation curves for PEP.
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PMID:Interaction of M1 and M2 isozymes pyruvate kinase from human tissues with phospholipids. 954 53


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