Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ascites 13762 rat mammary adenocarcinoma cells contain an abundant heterodimeric cell surface glycoprotein complex. It is composed of a transmembrane subunit and a sialomucin subunit and is the product of a single gene. The transmembrane subunit has two EGF-like domains and activates the proto-oncogene receptor kinase p185neu. Southern blot comparisons of the ascites tumor and rat liver demonstrated the presence of the gene encoding the complex in normal tissues and showed an amplification of about fivefold in the ascites tumor. Polymerase chain reaction assays showed the presence of mRNA for the complex in rat brain and lung, but not in liver, pancreas, placenta, intestine, kidney, ovary and uterus. Northern blot analyses showed that the 9 kb transcript for the complex is expressed at an approximately 500-fold higher level in the ascites cells than in rat brain. Immunocytochemical studies using antiserum directed against the transmembrane subunit showed its presence in bronchial epithelium, brain ependymal and neurons of four day old animals and in the endoderm and neuronal cells of embryos. Similar immunocytochemical studies showed the presence of the transmembrane subunit in some human breast tumors. These results suggest that the gene encoding this complex is regulated in a tissue-specific manner, is overexpressed in some tumors and may play a role in tumor progression.
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PMID:Tissue and tumor expression of a cell surface glycoprotein complex containing an integral membrane glycoprotein activator of p185neu. 793 36

Quercetin, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), and okadaic acid are found in various foods and have been shown to have mutagenic or promoter-like activity. The effects of these three compounds on the transmission of the inactive X chromosome were examined in MST-C6 murine tumor cells, which were derived from hybrid F1 mice from matings between C57BL/6 and MSM mice. Polymerase chain reaction analysis using polymorphic markers on the X chromosome detected transmission distortion of the inactive X chromosome due to nondisjunction as a copy-number imbalance in allelic bands. The cells exposed to all three chemicals (but not untreated cells) exhibited such imbalances at high frequencies under exposure conditions similar to those in previous experiments in which tumor progression and recombination were observed. The cells also showed increased frequencies of tumor formation when subcutaneously injected. These results suggest that the three chemicals are capable of inducing transmission distortion of the inactive X chromosome and that such activity may be a causative factor in promoting the tumorigenicity of MST-C6 cells.
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PMID:Induction of karyotype instability in a murine tumor cell line by quercetin, 2-amino-1-methyl-6 phenylimidazo[4,5-b]pyridine, and okadaic acid, as revealed by transmission distortion of the inactive X chromosome. 851 20

Mutation of the p53 gene plays an important role in neoplastic progression in human tumorigenesis. Polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) techniques are now available for the detection of point mutations. The original method using polyacrylamide gel electrophoresis is disadvantageous, particularly for clinical tests and for analysis of large numbers of samples. Therefore, using an automated capillary electrophoresis (CE) technique with a molecular-sieving polymer solution, we have devised a completely automatic fluorescence-based PCR-SSCP system (CE-FSSCP) for the differential detection of point mutations that dose not require SSCP with radioisotopes and polyacrylamide gels. The automatic CE-FSSCP system was developed for reproducible operations in the denaturation of double-stranded DNA and electrophoresis of single-stranded DNA. The detection system consists of a 100 W I2 lamp and photomultiplier. We performed CE-FSSCP with a 2% linear polyacrylamide polymer solution containing 5% glycerol. Four tissue specimens of lung tumors with mutations in exon 7 of the p53 gene were found to have mutant alleles; six-base-pair deletion at codons 247-248, a one-base-pair deletion at codon 260, a one-base-pair deletion at codon 244 and a GGC to CGC substitution at codon 244. We expect this technique to prove useful for the clinical DNA diagnosis of human cancers, determination of the therapeutic effect of anticancer agents and for the study of the molecular aspects of the mechanisms involved in the pathogenesis of human cancers.
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PMID:Fluorescence-based polymerase chain reaction-single-strand conformation polymorphism analysis of p53 gene by capillary electrophoresis. 884 80

Evidence from pathophysiological studies support the concept that embryonic development, tumor progression, and hormonally-regulated tissue masses such as adult prostate and corpus luteum are angiogenesis-dependent. We examined if the prostatic expression of vascular endothelial growth factor (VEGF), the major regulator of normal and pathological angiogenesis, was regulated by testosterone. Northern blot of VEGF messenger ribonucleic acid (mRNA) extracted from a human immortalized epithelial prostatic cell line (PNT1) showed that dihydrotestosterone (DHT) up-regulated VEGF mRNA at a level comparable to that observed upon exposure to growth factors. Polymerase chain reaction of reverse transcribed mRNA demonstrated that the ratio of the two splice variants encoding the 121 and 165 isoforms of VEGF were not affected by DHT. VEGF biological activity, measured in the conditioned medium by radio receptor assay, was increased by DHT. Injection of testosterone in adult rats induced a transient increase of the ventral lobe weight and the specific activity of prostatic VEGF, leading to a 7-fold increase in the prostate content of VEGF.
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PMID:Vascular endothelial growth factor is up-regulated in vitro and in vivo by androgens. 979 Sep 48

Infection with specific genotypes of human papillomavirus (HPV) has been strongly implicated in cervical carcinogenesis. However, HPV infection alone is insufficient for malignant transformation of the cervical epithelium. An alteration of microsatellite repeats is the result of slippage owing to strand misalignment during DNA replication and is referred to as microsatellite instability (MSI). These defects in DNA repair pathways have been related to human carcinogenesis; however, the role of MSI in the tumorigenesis of cervical cancer remains unclear. The clinical and pathological features of cervical cancers which are MSI-positive have also not been fully characterized. This study investigated the prevalence of MSI in cervical cancer and its relationship to clinico-pathological characteristics and HPV infection. Polymerase chain reaction-based microsatellite assay combined with tissue microdissection was used to examine for MSI in 50 cervical squamous cell carcinomas in Hong Kong women. In addition, the immunohistochemical staining was performed to determine the expression of major DNA mismatch repair genes, hMSH2 and hMLH1. Six cases (12%) displayed a low frequency of MSI (MSL-L) showing MSI at one locus only in 5 loci examined. Seven cases (14%) showed a high frequency of MSI (MSI-H) having MSI at 2 or more loci. Grouping MSI-L and MSI-H cases together as MSI-positive, statistical analysis of HPV infection, tumor grade, clinical stage and clinical status failed to disclose differences between MSI-positive and MSI-negative cases (p > 0.05). However, MSI-H correlated with advanced stage of disease (p < 0.05). Individuals with MSI-H tumors appeared to have reduced overall survival compared to individuals with MSI-L and MSI-negative tumors, but the difference was not statistically significant (p = 0.059). An absence of either MSH2 or MLH1 expression was observed in 2 MSI-L and 4 MSI-H cases, respectively. The results suggest that MSI is present in a subgroup of cervical squamous cell carcinomas, and defects resulting in MSI may be related to tumor progression and possibly poor prognosis in cervical cancer.
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PMID:Microsatellite instability, expression of hMSH2 and hMLH1 and HPV infection in cervical cancer and their clinico-pathological association. 1158 36

Frequent loss of heterozygosity (LOH) on the short arm of chromosome 1 (1p) has been reported in a series of human malignancies. To investigate the possible existence of tumor suppressor locus (or loci), we examined 41 primary oral squamous cell carcinomas (OSCCs) for LOH using a panel of 15 polymorphic microsatellite markers located on 1p. LOH was observed in 30 of 41 cases (73%) that were informative for at least one of the loci analyzed. Two distinct regions of common allelic loss were identified: a distal region at D1S243 (1p36.3), and proximal region at D1S160 (1p36.1). In addition, the possible involvement of the p73, a candidate tumor suppressor gene located on 1p36.3, was also evaluated. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis revealed no mutation of the gene in all samples analyzed (n=41). On the other hand, semi-quantitative reverse transcription-PCR (RT-PCR) demonstrated that 25% of primary tumors (n=20) had absent or reduced mRNA expression of the p73 gene. All cases showing down-regulation of the p73 gene were clinically classified as stage IV, but we could not detect any LOH at the gene locus in the same samples. Furthermore, re-expression of the p73 gene mRNA was induced in OSCC-derived cell lines showing down-regulation of the gene expression after treatment with 5-aza-2'-deoxycytidine, a DNA demethylating agent. These findings suggest that there may be at least two distinct tumor suppressor genes inactivated by allelic deletion on 1p31.1 and 1p31.3, respectively. In addition, the p73 gene could be inactivated by the methylation-dependent silencing of this gene, and associated with the tumor progression of human OSCC.
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PMID:Frequent allelic losses on the short arm of chromosome 1 and decreased expression of the p73 gene at 1p36.3 in squamous cell carcinoma of the oral cavity. 1178 1

Urokinase is thought to be involved in the formation of oral cancer, although there is a lack of genetic evidence. Our aim was to study single nucleotide polymorphisms in order to investigate the possibility. A total of 130 oral cancer patients and 105 controls were studied. Polymerase chain reaction (PCR) based restriction analysis was used to identify the C/T polymorphism of the urokinase gene, which is located on the 3'-untranslated region (3'-UTR) of chromosome 10. There was a significant difference in the distribution of the urokinase gene 3'-UTR C/T polymorphism frequency between cancer patients and the normal control group (P < 0.05). The "T" allele was prominent in the cancer group. The odds ratio for the risk of the "T" allele in cancer patients was 2.71 (95% CI = 1.325 approximately 5.562). The cancer patients were further categorized according to gender and whether or not they were habitual smokers or betel nut chewers. These clinical parameters were then compared with tumor cell differentiation and tumor progression. No significant differences were found. Therefore, the urokinase gene 3'-UTR "T" allele is associated with oral cancer and may play a role in oral cancer formation. However, we did not find the relationship between tumor progression and this polymorphism.
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PMID:Urokinase gene 3'-UTR T/C polymorphism is associated with oral cancer. 1535 78

Squamous cell carcinoma evolving from squamous papilloma in both the upper and lower respiratory tract in the same patient is uncommon. The molecular mechanisms underlying the progression have not been well investigated. We herein describe a case of squamous cell carcinoma arising from respiratory papilloma in two independent occasions. The patient initially had oropharyngeal squamous cell carcinoma arising in a squamous papilloma at the age of 25 years. He subsequently developed squamous cell carcinoma in the left lower lobe of the lung, which was also associated with squamous papilloma, 8 years after the complete excision of the oropharyngeal lesion. Polymerase chain reaction-based broad-spectrum human papillomavirus DNA amplification and typing showed the presence of human papillomavirus type 11 DNA in both oropharyngeal and pulmonary tumors. Immunohistochemical studies showed that the expression status of p53, Rb, and p16 proteins was unaltered during tumor progression. These observations indicate that human papillomavirus 11-associated neoplastic transformation and tumor progression in the respiratory tract may not involve aberrant regulation of the p53 and Rb signaling pathways.
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PMID:Metachronous squamous cell carcinomas evolving from independent oropharyngeal and pulmonary squamous papillomas: association with human papillomavirus 11 and lack of aberrant p53, Rb, and p16 protein expression. 1566 1

Pleural malignant mesothelioma is a locally aggressive tumor of mesothelial cell origin. In other tumor types high expression of matrix metalloproteinase (MMP)-2, together with membrane-type1-MMP (MT1-MMP), and low levels of the tissue inhibitor of MMP (TIMP)-2 have been correlated with aggressive tumor progression and low survival rates. Therefore, we compared the expression and activation of these three factors and their regulation by two mesothelioma associated growth factors, platelet-derived growth factor (PDGF)-BB, and transforming growth factor (TGF)-beta1 in six human mesothelioma and one mesothelial cell line. Polymerase chain reaction (PCR), immunoblotting, zymography, and small inhibitory RNAs (siRNA) were used to study gene expression, protein activation, and signal transduction. To proof the relevance of our in vitro data immunohistochemistry was performed in tissue sections. PDGF-BB induced, while TGF-beta1 inhibited cell proliferation. PDGF-BB was a chemoattractant for mesothelial cells, and its effect was increased in the presence of TGF-beta1. TGF-beta1 stimulated the de novo synthesis of pro-MMP-2 in both cell types. Pro-MMP-2 synthesis involved p38 MAP kinase. In cell culture and tissue sections only mesothelial cells expressed MT1-MMP. Migration of mesothelioma cells was dependent on the presence of MT1-MMP. Migration, but not proliferation of mesothelioma cells was inhibited by oleoyl-N-hydroxylamide, TIMP-2, and siRNA for MT1-MMP. Our data suggest that in mesothelioma cells the phosphorylation of p38 MAP kinase is deregulated and is involved in pro-MMP-2 expression. Mesothelioma progression depends on an interaction with mesothelial cells that provide MT1-MMP necessary to activate pro-MMP-2 to facilitate migration through an extracellular matrix (ECM) layer.
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PMID:ERK1/2 and p38 MAP kinase control MMP-2, MT1-MMP, and TIMP action and affect cell migration: a comparison between mesothelioma and mesothelial cells. 1644 44

Gliomas (GLs) are characterized by highly variable biologic behavior. After surgical resection and postoperative therapy, they frequently recur with the same or higher-grade histology. Although a number of genetic aberrations have been described in different histologic types of GLs, the molecular mechanisms of histologic and clinical progression are poorly understood. In this study, we have performed longitudinal mismatch repair gene polymerase chain reaction-single strand conformation polymorphism and methylation analysis in paired samples of primary and recurrent GLs to reveal whether the inactivation of the normal DNA repair mechanism is associated with tumor progression. Polymerase chain reaction-single strand conformation polymorphism analysis of the hMLH1 gene was performed in 24 cases, in each case the samples of the first and second biopsies being evaluated simultaneously, but no alterations in the hMLH1 gene were found. Methylation analysis of the CpG sites in the hMLH1 promoter revealed a total of 4 (16.6%) hypermethylations in recurrent GLs. These results suggest that hMLH1 promoter hypermethylation may occur in low-grade GLs, associated with the development and progression of moderate malignant GL, but not with structural alterations in the hMLH1 gene. It seems that hMLH1 promoter hypermethylation is an early event in the development and progression or the clonal evolution of GLs, this gene inactivation proving stable even on tumor recurrence.
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PMID:Epigenetic inactivation of the hMLH1 gene in progression of gliomas. 1752 80


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