Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The correlation between the solubility properties of DCCD and EDAC (carboxyl specific groups reagents) and AI, NBD-Cl and TNM (tyrosyl specific reagents) and their efficiency to penetrate through the inner mitochondrial membrane, has been done. The penetration of the reagents was evaluated by using their ability to inactivate D-3-hydroxybutyrate dehydrogenase (EC 1.1.1.30) in its natural location, i.e. in intact mitochondria, or in its inverted location, i.e. in inside-out submitochondrial vesicles. For DCCD, AI, NBD-Cl and TNM there is a good correlation between the phase partition in octanol/water and the ability to cross or not the inner mitochondrial membrane. In contrast, there is a discrepancy for EDAC reagent which is hydrophilic, while it significantly inhibits BDH in intact mitochondria. The knowledge of the properties of these reagents can be very useful to locate strategic aminoacid residues in important biological functions.
Cell Mol Biol (Noisy-le-grand) 1994 Sep
PMID:Chemical reagents of polypeptides side chain: relationships between solubility properties and ability to cross the inner mitochondrial membrane. 781 85

The full-length human glucocorticoid receptor (hGR), overexpressed in Spodoptera frugiperda (Sf9) cells, associates with heat shock protein 90 (hsp90) and hsp70 and binds dexamethasone with high affinity. Baculovirus infection of Sf9 cells grown in TNM-FH medium results in the rapid depletion of glucose from the medium within 24 h. Noting a discrepancy between hGR protein levels and ligand binding capacity in such cultures, we hypothesized that the depletion of glucose from the medium could result in intracellular ATP depletion and consequently affect the ligand binding capacity of the recombinant hGR. Supplementation of the Sf9 culture medium with additional glucose resulted in a three-fold increase in intracellular ATP levels, and a three-fold increase in 3H-dexamethasone binding capacity, without altering the protein levels of hGR, hsp90 or hsp70. However, more hsp90 co-immunoprecipitated with hGR from cells grown in glucose supplemented medium. Our data support the hypothesis that high-affinity ligand binding by hGR requires the ATP-dependent formation of the hGR:hsp90 heterocomplex. Besides having practical consequences for the production of recombinant GR and other related proteins, our findings could ultimately have relevance in diseases such as diabetes mellitus.
J Steroid Biochem Mol Biol 1997 Jan
PMID:Optimal ligand binding by the recombinant human glucocorticoid receptor and assembly of the receptor complex with heat shock protein 90 correlate with high intracellular ATP levels in Spodoptera frugiperda cells. 918 52

This analysis of 32 pairs of human squamous cell lung carcinomas and normal matched control DNA demonstrates that loss of heterozygosity (LOH) is infrequent at the nm23-H1 locus, affecting only 2 of the 18 informative cases. Both LOH cases were in the tumor stage IIIA. One tumor was of poor and the other of moderate histological grade. These and an additional 34 tumor samples were also analyzed immunohistochemically for the presence of nm23-H1 protein. Of the 66 cases tested for the presence of nm23-H1 protein 54 were negative. Eight samples exhibited up to 35% positive cells (with weak immunostaining intensity) and four between 35% and 70% (moderate immunostaining intensity); no sample showed more than 70% positive cells. Noncancerous lung parts contained no nm23-H1 protein. nm23-H1 expression was independent of TNM stage, grade, tumor size, and patient's survival. Two samples with LOH were negative for nm23-H1 protein. We therefore conclude that neither loss of heterozygosity of the nm23-H1 gene nor the intensity of specific protein expression are related to squamous cell lung carcinoma development and progression.
J Mol Med (Berl) 1997 Aug
PMID:Squamous cell lung carcinomas: the role of nm23-H1 gene. 929 29

AKT2, an oncogene encoding a protein serine-threonine kinase implicated in phosphatidylinositol-3-OH kinase signaling, is amplified in some human ovarian and pancreatic carcinomas. We previously demonstrated that the tumorigenicity and invasiveness of pancreatic ductal adenocarcinoma (PDAC) cell lines with amplified AKT2 could be markedly reduced by transfection with antisense AKT2 constructs. To evaluate further the extent of AKT2 alterations in PDAC, DNA and immunohistochemical analyses were performed to assess amplification or overexpression of AKT2, respectively, in 72 PDACs. Thirty-five PDACs were subjected to Southern analyses, and AKT2 amplification was detected in seven tumors (20%). Forty-one formalin-fixed PDAC specimens were examined immunohistochemically with an anti-AKT2 monoclonal antibody, and moderate to intense staining was observed in eight tumors (20%). AKT2 immunostaining paralleled AKT2 genomic status in each of four cases in which both Southern and immunohistochemical analyses were performed. No obvious relationship was observed between AKT2 status and tumor TNM stage or grade. These observations suggest the utility of immunohistochemical analysis in assessing alterations of AKT2 in human cancers. Furthermore, the role played by the AKT2 kinase in the signaling pathways of various mitogenic growth factors implicated in the development of pancreatic cancer suggests that alteration of AKT2 may be an important component in the pathogenesis of a substantial subset of PDACs.
Mol Carcinog 1998 Feb
PMID:Amplification and overexpression of the AKT2 oncogene in a subset of human pancreatic ductal adenocarcinomas. 949 7

Ample evidence has been provided concerning the presence of tenascin in various histological subtypes of gastric cancer. However, conflict and discussion still persist regarding the correlation with different classification systems and prognostic impact. Therefore, we studied 203 adenocarcinomas of the stomach with special emphasis to the WHO-classification, Lauren's and Goseki's subtypes as well. The immunohistochemical ABC-method was applied using a monoclonal anti-human-tenascin antibody. 30% of all tumours showed a distinct staining reaction. Tubulo-papillary carcinomas (WHO) revealed a significantly stronger reactivity than signet-ring subtypes. Adenocarcinomas of intestinal type (Lauren) were significantly more positive than the diffuse types. Mucin-poor tumours (Goseki I+III) stained positive in a much higher degree compared to mucin-rich subtypes (Goseki II+IV). However, no correlation could been demonstrated regarding TNM-stage or prognosis.
Int J Mol Med 1999 Jul
PMID:Tenascin expression in gastric cancer with special emphasis on the WHO-, Lauren-, and Goseki-classifications. 1037 35

This study evaluated the potential contribution of the APC gene to malignant transformation in patients with renal cell carcinoma. We tested 36 human renal cell carcinoma samples and 18 adjacent normal kidney tissues for the expression of APC protein, both wild and truncated types, by western blot using antibodies that recognize either the carboxy or the amino epitope of the APC protein. The same tumor samples together with autologous peripheral blood were also analyzed at the DNA level. Using specific oligonucleotide primers for exons 11 and 15, gene instability was followed by polymerase chain reaction/loss of heterozygosity (LOH) (on the basis of restriction fragment length polymorphism). Molecular data were also compared to pathohistological diagnosis, TNM stage, and patient's age using multivariate statistical methods. All normal renal tissues revealed expression of the wild-type APC protein. Neither wild nor mutant type proteins were found in 36% (13/36) of tumor samples; the rest of tumor tissues expressed the wild-type protein (312 kDa). Mutated APC protein, with a molecular weight of 117 kDa, was found in only one tumor sample. From 36 tumor samples 16 (44.4%) were informative for RsaI exon 11 polymorphic site, while only half of these (8/16) demonstrated LOH. From 13 tumor samples that had no detectable protein product by western blot analysis eight were homozygous for the exon 11 polymorphism and were tested for another polymorphic site, MspI/exon 15. The overall proportion of LOH cases for both polymorphisms tested was 52.9% (9/17). Pathohistological diagnosis and molecular data showed no correlation. However, multivariate analysis determined a stage strong positive correlation of age and TNM with the presence of LOH and the absence of the wild-type APC protein. Out results suggest that the APC tumor suppressor gene plays a role in renal carcinogenesis. Alterations in this gene are responsible for tumor evolution and progression, but cannot be considered as a first event in tumor initiation.
J Mol Med (Berl) 1999 May
PMID:Loss of heterozygosity and protein expression of APC gene in renal cell carcinomas. 1042 94

Leptin is a hormone which controls fat metabolism. Leptin plasma levels and adipose tissue mRNA expression were measured in cancer patients. Plasma levels were correlated with TNM staging, cachexia parameters, tumour markers and hormones. Breast and colorectal cancer patients showed blood plasma levels of insulin, TNF-alpha and tumour markers higher than controls. Breast cancer patients, but not colorectal cancer patients, had plasma levels and adipose tissue expression of leptin significantly higher than controls associated with elevated values of estrogen- and progesterone-receptors. These data suggest the possible use of leptin as a clinical marker.
Int J Mol Med 2000 Apr
PMID:Leptin expression in colorectal and breast cancer patients. 1071 61

Cancer invasion is induced by several proteolytic enzyme systems associated with the destruction of basement membrane and extracellular matrix. Urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) have been reported as prognostic factors in breast cancer patients and plasminogen activation is regulated by various factors such as uPAR and growth factors. Thus, we examined the tissue levels of urokinase-type plasminogen activator receptor (uPAR) in breast cancer patients. Tissue uPAR levels were measured by ELISA assay in 268 breast cancer patients. The median and mean values of tissue uPAR level in breast cancer were 3.5 ng/mg cytosol protein and 4.8+/-3.6 ng/mg cytosol protein, respectively. Tissue uPAR level was the highest in T1 stage, but there was no statistical significance between the T stages (p>0.05), nor in nodal stage, in the value of uPAR according to progression. And the value of uPAR expression was not associated with estrogen and progesterone receptor status, number of involved node and percent of node involvement. In TNM stage, tissue uPAR levels were higher in patients with stage I-II than in patients with stage III-IV (p=0.027). In univariate analysis, nodal factor (p=0.002) and TNM stage (p=0.0004) were significant. But, multivariate analysis showed that TNM stage was the only significant prognostic factor (p=0.0002). These results suggest that uPAR is mainly associated with initial tumor invasion and other factors might be involved in later stages of cancer progression.
Int J Mol Med 2000 Sep
PMID:Tissue urokinase-type plasminogen activator receptor levels in breast cancer. 1093 93

We examined the prognosis of 64 EBV-associated gastric carcinoma (EBV-GC) cases and 128 EBV-negative gastric carcinoma cases. EBV-GCs were identified by detecting EBV-encoded small RNA (EBER) using in situ hybridization assay of paraffin-embedded tissue. For each EBV-GC case, 2 EBER-negative cases (EBV-negative cases) were selected, matching the EBV-GC case with respect to age, sex, tumor location, and depth of invasion. The average follow-up period was 70.9 months (SD=61.1) in EBV-GCs and 63.8 months (SD=59.7) in EBV-negative cases. Tumor-advanced stage determined by TNM classification of UICC, tumor location, and p53 over-expression were statistically significant prognostic factors. On the other hand, EBER expression was not related to the survival of patients. However, further analysis specific for intestinal and diffuse types of Lauren classification revealed that the association of EBER expression with prognosis was different in the two histological types. EBER expression was related to poor prognosis in intestinal-type carcinoma [hazard ratio (HR) =2.5, 95% confidence intervals (CI) =1.3-4.8] after adjusting for stage, p53 over-expression, and tumor location, whereas the diffuse-type EBV-GC had better prognosis (HR=0.4, 95% CI=0.2-0.9) even when lymphoepithelioma-like carcinomas were excluded. To examine the interactive prognostic effects between EBER expression and p53 over-expression, the study subjects were divided into 4 groups on the basis of EBER expression and p53 over-expression. In intestinal-type tumors, the cases having both EBER expression and p53 over-expression showed the poorest prognosis (HR=10.0, 95% CI=3.3-30.4), and the cases with either EBER expression or p53 over-expression had an intermediate prognosis. In diffuse-type tumor, only EBER was an important prognostic factor. These results give additional evidence implicating EBV in the natural history of EBV-GCs.
Int J Mol Med 2002 Nov
PMID:Prognostic significance of Epstein-Barr virus involvement in gastric carcinoma in Japan. 1237 7

Pancreatic cancer is a malignant tumor with an extremely poor prognosis. The mechanisms of the aggressive growth and metastasis are not yet extensively understood. Over-expression of epidermal growth factor receptor (EGFR) was suggested to be associated with malignant transformation of pancreatic cancer. We examined EGFR expression in 77 cases of invasive ductal adenocarcinoma of the pancreas, and analyzed the relation between the EGFR expression pattern and clinicopathological factors. EGFR immunoreactivity was detected in 41.6% (32/77) of human pancreatic cancers; i.e. diffuse expression in 32.5% (25/77) and focal expression in 9.1% (7/77). The EGFR expression was associated with gender (p<0.05), histological differentiation (p<0.05) and metastatic status of TNM classification (p<0.01). The observations suggested that EGFR expression plays important roles in metastasis, especially liver metastasis and recurrence of human pancreatic cancer.
Int J Mol Med 2003 Mar
PMID:Epidermal growth factor receptor expression in human pancreatic cancer: Significance for liver metastasis. 1257 31


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