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

Various isoforms of the glycolytic enzyme pyruvate kinase are expressed in different cell types. One of these isoforms, Tu M2-PK, is over-expressed in tumor cells and released into body fluids. Plasma determination of Tu M2-PK has been shown to discriminate between benign and malignant lesions. Tu M2-PK was quantitated in the plasma of 50 patients with cervical carcinoma, 10 patients with chronic cervicitis and 10 healthy controls. The concentration of Tu M2-PK was determined by commercial kits using a sandwich enzyme linked immunosorbent assay based on two monoclonal antibodies (clone I and II) specific for Tu M2-PK. The sensitivity of the test for discrimination of malignant from non-malignant condition was 82% with a specificity of 60%. Highly significant statistical difference was found in the means of three groups (P = 0.0002). The present results indicate that Tu M2-PK can be used as a tumor marker in follow-up of patients with cervical carcinoma.
 ...
PMID:Evaluation of the Pyruvate Kinase isoenzyme tumor (Tu M2-PK) as a tumor marker for cervical carcinoma. 1521 41

Proliferating cells, especially tumour cells, express a special isoenzyme of pyruvate kinase, termed M2-PK, which can occur in a tetrameric form with a high affinity to its substrate, phosphoenolpyruvate (PEP), and in a dimeric form with a low PEP affinity. In tumour cells, the dimeric form is usually predominant and is therefore termed Tumour M2-PK. The levels of Tumour M2-PK within tumours and in EDTA-plasma correlate with staging and the ability of the tumour cells to metastasise. Since most colorectal tumours grow intraluminally, it appeared interesting to determine whether Tumour M2-PK is detectable in the faeces of tumour patients. Stool samples were tested by ELISA from controls without colorectal cancer and colorectal cancer patients. Whereas Tumour M2-PK levels were low in the control group (mean value+/-s.e.m.: 3.3+/-0.4, n=144), they were high in the case of colorectal cancer (56.1+/-15.3, n=60). At a cutoff value of 4 U ml(-1), the sensitivity was 73%. TNM and Dukes' classification of the tumours revealed a strong correlation between faecal Tumour M2-PK levels and staging. The determination of Tumour M2-PK in faeces provides a new promising screening tool for colorectal tumours.
 ...
PMID:Faecal tumour M2 pyruvate kinase: a new, sensitive screening tool for colorectal cancer. 1526 15

Lung cancer, a leading cause of cancer deaths, consists of two major groups: small cell lung cancer (SCLC) and nonsmall cell lung cancer (NSCLC) with the NSCLC accounting for approximately 75% cases of lung cancers. It has been suggested that molecular changes including overexpression of oncogenes and decreased expression of tumor suppressor genes are responsible for lung carcinogenesis. In this study, we analyzed protein profiles of four different human NSCLC cell lines compared with normal human bronchial epithelial cells using two-dimensional PAGE and MALDI-TOF mass spectrometry. We identified 12 protein spots with different expressions between the normal and cancer cells. Of these proteins, vimentin, cytokeratin 8, YB-1, PCNA, Nm23, hnRNP A2/B1, and HSP90beta were known to be up-regulated in lung cancers, which is consistent with the current study. We also found that the expression of M-type pyruvate kinase is altered in NSCLC likely due to changes in translational control and/or differential phosphorylation of the protein. Interestingly, the expression of the tumor suppressor gene 14-3-3sigma is down-regulated while that of the proto-oncogene TEF1delta is up-regulated in NSCLC cells. On the basis of these observations and previous studies, we propose that the altered expression of 14-3-3sigma and TEF1delta may be involved in lung carcinogenesis.
 ...
PMID:Tumor suppressor gene 14-3-3sigma is down-regulated whereas the proto-oncogene translation elongation factor 1delta is up-regulated in non-small cell lung cancers as identified by proteomic profiling. 1535 25

An isoenzyme of pyruvate kinase (Tu M2-PK) is overexpressed by tumor cells and can be measured in blood by a specific immunoenzymatic assay. Our objective was to investigate the diagnostic value of Tu M2-PK in comparison with that of CA 19-9 in pancreatic cancer. We studied 265 subjects: 60 with histologically confirmed pancreatic cancer, 43 with benign pancreatic diseases (acute and chronic pancreatitis), 5 with benign cystic neoplasms of the pancreas, 9 with neuroendocrine tumors, 77 with other abdominal malignancies, 47 with benign digestive diseases, and 24 healthy controls. Levels of plasma Tu M2-PK and serum CA 19-9 were determined by commercially available specific immunoassays. The diagnostic sensitivity and specificity of Tu M2-PK for pancreatic cancer were 85 and 41%, respectively, while those of CA 19-9 were 75 and 81%. The combination of the two tests significantly increased sensitivity (97%) but lowered specificity (38%). In discriminating between pancreatic cancer and acute or chronic pancreatitis, Tu M2-PK turned out to be less accurate than CA 19-9. In patients without pancreatic tumor, cholestasis appeared not to affect the values of Tu M2-PK, while CA 19-9 was found to be significantly higher. Tu M2-PK was also abnormally high in the majority of patients with other digestive malignancies or neuroendocrine tumors. The results demonstrate that Tu M2-PK has a satisfactory sensitivity but a poor specificity in the diagnosis of pancreatic cancer. Used together with CA 19-9, the sensitivity increases considerably.
 ...
PMID:Tumor M2-pyruvate kinase, a new metabolic marker for pancreatic cancer. 1538 37

Malignant gliomas (astrocytomas) are lethal tumors that invade the brain. Invasive cell migration is initiated by extension of pseudopodia into interstitial spaces. In this study, U87 glioma cells formed pseudopodia in vitro as cells pushed through 3 microm pores of polycarbonate membranes. Harvesting pseudopodia in a novel two-step method provided material for proteomic analysis. Differences in the protein profiles of pseudopodia and whole cells were found using differential gel electrophoresis (DIGE) and immunoblotting. Proteins from two-dimensional (2D) gels with M(R)'s of 20-100 kDa and pI's of 3.0-10.0 were identified by peptide mass fingerprinting analysis using mass spectrometry. For DIGE, lysates of pseudopodia and whole cells were each labeled with electrophilic forms of fluorescent dyes, Cy3 or Cy5, and analyzed as mixtures. Analysis was repeated with reciprocal labeling. Differences in protein distributions were detected by manual inspection and computer analysis. Topographical digital maps of the scanned gels were used for algorithmic spot matching, normalization of background, quantifying spot differences, and elimination of artifacts. Pseudopodial proteins in Coomassie-stained 2D gels included isoforms of glycolytic enzymes as the largest group, seven of 24 proteins. Peptide mass fingerprint analysis of DIGE gels demonstrated increased isoforms of annexin (Anx) I, AnxII, enolase, pyruvate kinase, and aldolase, and decreased mitochondrial manganese superoxide dismutase and transketolase in pseudopodia. Specific antibodies showed restricted immunoreactivity of the hepatocyte growth factor (HGF) alpha chain to pseudopodia, indicating localization of its active form. Met (the HGF receptor), actin, and total AnxI were increased in pseudopodial lysates on immunoblots. Increased constituents of the pseudopodial proteome in glioma cells, identified in this study as actin, HGF, Met, and isoforms of AnxI, AnxII, and several glycolytic enzymes, represent therapeutic targets to consider for suppression of tumor invasion.
 ...
PMID:Proteomic characterization of harvested pseudopodia with differential gel electrophoresis and specific antibodies. 1565 57

Rats (FLF1) were pretreated with 2 and 20 mg/kg/day fluvastatin (Flu), and after 6 weeks, hepatocellular tumor cells were inoculated under the left renal capsule. At different times, growth and pyruvate kinase (PK) activity of the primary tumors and lymph node metastases were determined. Flu had a dose-dependent inhibitory effect on primary and metastatic tumors, and the inhibitory effect on growth and PK activity in metastases were higher than in primary tumors. Finally, Flu had an earlier inhibitory effect on the early appeared PK activity in metastases than in primary tumors.
 ...
PMID:Different anticancer effects of fluvastatin on primary hepatocellular tumors and metastases in rats. 1583 37

Proliferating cells and tumor cells in particular express the pyruvate kinase isoenzyme type M2 (M2-PK). Within the tumor metabolome M2-PK regulates the proportions of glucose carbons that are channelled to synthetic processes (inactive dimeric form) or used for glycolytic energy production (highly active tetrameric form, a component of the glycolytic enzyme complex). In tumor cells, the dimeric form of M2-PK (Tumor M2-PK) is always predominant. The dimerization is caused by direct interaction of M2-PK with certain oncoproteins. The switch between the tetrameric and dimeric form of M2-PK allows tumor cells to survive in environments with varying oxygen und nutrient supply.
 ...
PMID:Pyruvate kinase type M2 and its role in tumor growth and spreading. 1590 30

Proliferating cells express the pyruvate kinase isoenzyme type M2 (M2-PK). This enzyme exists as an active tetramer and an inactive dimer. The dimeric form is predominantly found in tumor cells and is therefore termed Tumor M2-PK (TuM2-PK). TuM2-PK molecules are released into the peripheral blood and may hereby function as a marker of tumor load in cancer patients. Our study was aimed to investigate TuM2-PK as a potential plasma marker in melanoma patients compared to the well-established serum marker S100beta. We measured the concentration of TuM2-PK in plasma and S100beta in corresponding serum samples from 300 melanoma patients and 53 healthy controls using a sandwich ELISA and an immunoluminometric assay, respectively. Plasma concentrations of TuM2-PK were significantly increased in melanoma patients compared to healthy controls (9.30 U/ml vs. 7.20 U/ml; p = 0.0036) and correlated with tumor load (p < 0.0005) and disease stage (p < 0.0005). Patients with elevated plasma TuM2-PK (cut-off = 15 U/ml) presented a reduced overall (p < 0.000005) and progression-free (p = 0.023) survival. Multivariate analysis revealed plasma TuM2-PK and serum S100beta as independent predictors of overall survival in metastasized patients. Neither plasma TuM2-PK nor serum S100beta showed prognostic relevance for tumor-free patients. Although the sensitivity and specificity to predict disease progression or death was higher for serum S100beta compared to plasma TuM2-PK, the combination of both markers improved the estimation of prognosis compared to that of serum S100beta alone.
 ...
PMID:Tumor type M2 pyruvate kinase (TuM2-PK) as a novel plasma tumor marker in melanoma. 1595 65

Four isozymes of pyruvate kinase are differentially expressed in human tissue. Human pyruvate kinase isozyme M2 (hPKM2) is expressed in early fetal tissues and is progressively replaced by the other three isozymes, M1, R, and L, immediately after birth. In most cancer cells, hPKM2 is once again expressed to promote tumor cell proliferation. Because of its almost ubiquitous presence in cancer cells, hPKM2 has been designated as tumor specific PK-M2, and its presence in human plasma is currently being used as a molecular marker for the diagnosis of various cancers. The X-ray structure of human hPKM2 complexed with Mg(2+), K(+), the inhibitor oxalate, and the allosteric activator fructose 1,6-bisphosphate (FBP) has been determined to a resolution of 2.82 A. The active site of hPKM2 is in a partially closed conformation most likely resulting from a ligand-induced domain closure promoted by the binding of FBP. In all four subunits of the enzyme tetramer, a conserved water molecule is observed on the 2-si face of the prospective enolate and supports the hypothesis that a proton-relay system is acting as the proton donor of the reaction (1). Significant structural differences among the human M2, rabbit muscle M1, and the human R isozymes are observed, especially in the orientation of the FBP-activating loop, which is in a closed conformation when FBP is bound. The structural differences observed between the PK isozymes could potentially be exploited as unique structural templates for the design of allosteric drugs against the disease states associated with the various PK isozymes, especially cancer and nonspherocytic hemolytic anemia.
 ...
PMID:Structural basis for tumor pyruvate kinase M2 allosteric regulation and catalysis. 1599 96

The aim of this study was to investigate selected proteomic markers of the metabolic phenotype of breast carcinomas as prognostic markers of cancer progression. For this purpose, a series of 101 breast carcinomas and 13 uninvolved breast samples were examined for quantitative differences in protein expression of mitochondrial and glycolytic markers. The beta-subunit of the mitochondrial H(+)-ATP synthase (beta-F1-ATPase) and heat shock protein 60 (Hsp60), and the glycolytic glyceraldehyde-3-phosphate dehydrogenase, pyruvate kinase and lactate dehydrogenase were identified by immunological techniques. Correlations of the expression level of the protein markers and of the ratios derived from them were established with the clinicopathological information of the tumors and the follow-up data of the patients. The metabolic proteome of breast cancer specimens revealed a pronounced shift towards an enhanced glycolytic phenotype concurrent with a profound alteration on the mitochondrial beta-F1-ATPase/Hsp60 ratio when compared with normal samples. Discriminant analysis using markers of the metabolic signature as predictor variables revealed a classification sensitivity of approximately 97%. Kaplan-Meier survival analysis showed that several of the proteomic variables significantly correlated with overall and disease-free survival of the patients. The expression level of beta-F1-ATPase per se allowed the identification of a subgroup of breast cancer patients with significantly worse prognosis. Multivariate Cox regression analysis indicated that tumor expression of beta-F1-ATPase is a significant marker independent from clinical variables to assess the prognosis of the patients. We conclude that the alteration of the mitochondrial and glycolytic proteomes is a hallmark feature of breast cancer further providing relevant markers to aid in the prognosis of breast cancer patients.
 ...
PMID:Breast carcinomas fulfill the Warburg hypothesis and provide metabolic markers of cancer prognosis. 1603 70


<< Previous 1 2 3 4 5 6 7 8 9 10