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

Human papillomavirus (HPV) DNA is integrated into the host genome in cervical cancer. The cervical carcinoma cell line SW756 has integrated HPV-18 DNA in chromosome region 12q15, in the papillomavirus-associated locus-2 (PAL2). By polymerase chain reaction and hybridization of an arrayed cosmid library with oligonucleotides from the rearranged allele, we determined the pre-integration germline structure of the region. PAL2 was located approximately 10 kb from sequence-tagged site marker U27131, which was the marker most proximal to the 3' flank of the integrated viral DNA. HPV-18 DNA integration induced a complex genomic rearrangement resulting in inversion and deletion of cellular sequences. PAL2 is within the multiple aberration region, which has been shown to be affected in several types of benign tumors of mesenchymal origin. The integrated viral DNA was located 50 kb from a CpG island and 150 kb upstream of the high-mobility group I-C (HMGI-C) gene. The HMGI-C gene and the integrated HPV-18 DNA had opposite transcriptional orientations. No overexpression or altered message of the HMGI-C gene was detected in three cervical carcinoma cell lines. The integrated viral DNA did not affect any other known gene in the region and may be a marker for an unknown gene associated with malignant tumor phenotypes.
Mol Carcinog 1997 Jun
PMID:Complex genomic rearrangement within the 12q15 multiple aberration region induced by integrated human papillomavirus 18 in a cervical carcinoma cell line. 921 Sep 58

The screening technique developed by Dr. Papanicolau for cervical cancer has significantly increased opportunities for early detection and treatment of this disease. Recently there has been a great deal of concern related to the accuracy of the Pap smear screening technique for cervical cancer and the need for highly skilled technologists to reliably examine the prepared samples. The use of infrared spectroscopy as a technique to discriminate between normal and malignant cervical cell samples has been reported by several research groups. Samples of cervical cells can be prepared for spectroscopic diagnosis by centrifuging cells obtained by the normal Pap smear technique and applying them to an infrared transparent window. A major concern with diagnosis by infrared spectroscopy is the homogeneity of the sample and whether the spectral features used in the analysis are caused by localized groups of cells or can be attributed to the majority of the cells in the sample. In this paper we report on the use of automated infrared microscopic mapping techniques to measure the infrared spectra at fixed intervals across the sample covering a 5 mm spot. Various post processing techniques have been applied to the spectral results to create images revealing specific features of the sample. The techniques applied to the data include: 1) Baseline corrected peak height; 2) Band ratioing to compensate for thickness; 3) Correlation metrics; 4) Similarity matching, and 5) Mahalanobis distance classification algorithm.
Cell Mol Biol (Noisy-le-grand) 1998 Feb
PMID:The analysis of exfoliated cervical cells by infrared microscopy. 955 48

Infrared spectra of 88 normal and 32 abnormal (mild to severe dysplasia) cervical smear samples were used as a databank to investigate the usefulness of artificial neural networks (ANN) in the diagnosis of cervical smears. The spectra were first reduced, using principal component analysis (PCA), to seven wavenumber components that are the major contributors to the variance. A number of different ANN architectures were investigated that could differentiate between normal and abnormal cervical smears. Although the ANNs were trained to differentiate only normal from abnormal smears, the results using an independent test data set indicated that within the abnormal category mild dysplasia could be distinguished from severe dysplasia. The results using this restricted data set indicate that neural networks coupled to infrared microspectroscopy could provide an alternative automated means of screening for cervical cancer.
Cell Mol Biol (Noisy-le-grand) 1998 Feb
PMID:Infrared microspectroscopy and artificial neural networks in the diagnosis of cervical cancer. 955 49

A human estrogen regulated transcript, HEM45, was characterized that encodes a novel protein of 181 amino-acid residues (Mr 20300). It was identified using differential-display-PCR and mRNA from a human cervical cancer cell line (UP1) stably transfected with an estrogen receptor (ER) expression construct. The HEM45 protein has similarity to the bracket fungus protein FRT1 that can cause fruiting-body production and to a Xenopus product, XPMC2, that affects cell-cycle control. These similarities suggest that HEM45 will have a role in mediating estrogen control of cellular proliferation and differentiation. HEM45 mRNA was widely expressed at low levels in cell lines and was up regulated by E2 in ER-positive breast cancer lines. The in vivo regulation of HEM45 was confirmed by demonstrating estrogen stimulation of the rat HEM45 homolog in the rat uterus. The levels of the rat uterine HEM45 sequence were elevated by estrogen 3 to 15 h after treatment. The maximal response, at six hours, was greater than eight-fold. The uterine HEM45 response was distinct from that reported for 'early-response' genes as the increase in HEM45 mRNA levels occurred later but could be induced by lower levels of hormone. HEM45 mRNA expression in cultured cells was increased by estrogen in the presence of cycloheximide, indicating direct ER-regulation of HEM45.
J Steroid Biochem Mol Biol 1998 Jan
PMID:Expression and estrogen regulation of the HEM45 MRNA in human tumor lines and in the rat uterus. 956 7

The crystal structure of the E2 DNA-binding domain from the high-risk cervical cancer-associated strain human papillomavirus type 16 (HPV-16) is described here. The papillomavirus E2 proteins regulate transcription from all viral promoters and are required for the initiation of replication in vivo. They belong to a family of viral proteins that form dimeric beta-barrels and use surface alpha-helices for DNA interaction. Although all E2 proteins recognize the same consensus, palindromic DNA sequence, proteins from different viral strains differ in their abilities to discriminate among their specific DNA-binding sites. The structure reported here reveals that while the overall fold of the HPV-16 E2 DNA-binding domain resembles that of its counterpart from the related viral strain bovine papillomavirus type 1, the precise placement of the recognition helices is significantly different. Additionally, the charge distribution on the DNA-binding surfaces of the two proteins varies; HPV-16 E2 has a much less electropositive surface. HPV-16 E2 is thus less able to utilize charge neutralization of the phosphate groups on DNA to induce bending. These results correlate well with previous solution studies that showed decreased affinity between HPV-16 E2 and flexible DNA target sequences, and enhanced affinity towards A-tract-containing, pre-bent sequences. In summary, the crystal structure of the HPV-16 E2 DNA-binding domain shows that the protein presents a stereo-chemically and electrostatically unique surface to DNA, characteristics that can contribute to its mechanism of DNA target discrimination.
J Mol Biol 1998 Dec 18
PMID:Crystal structure of the E2 DNA-binding domain from human papillomavirus type 16: implications for its DNA binding-site selection mechanism. 987 65

Clinical trials have started to implement tumor-associated antigens in the form of antigenic peptides in order to augment CD8(+) T-cell responses directed against autologous cancer cells. One of the surrogate markers for successful immunization is the characterization of T-lymphocytes reacting to the immunizing peptide as determined by CDR3-length and DNA-sequence analysis. Most of the recent studies examining ex vivo T-cell responses in patients with cancer have focussed on expression and prevalence of the TCR Beta variable region, predominantly in non-sorted T-cell populations. Here, we show that clonal T-cell receptors (TCRs), as defined by DNA-fragment analysis and DNA-sequencing, appear to be predominantly present in the CD8(+) T-cell population and that these clonal TCRs are preferentially TCR-VA chains. This has been found to be true for PBL obtained from normal healthy subjects or from patients suffering from cancer, as well is in tumor specimens obtained from patients with cervical cancer. We suggest that a detailed analysis of the TCR-repertoire in patients undergoing immunotherapy, should include: i) examination of both TCR VA and VB families. ii) The absence of TCR VA or VB families should be noted and iii) these studies should be performed on CD4(+) or CD8(+) sorted T-cells or, if tissue specimens are analyzed, should be accompanied by a CD4 and CD8 staining.
Int J Mol Med 1999 Feb
PMID:Monoclonal TCR mRNA transcripts are preferentially detected in the TCR variable alpha chain in CD8(+) T-lymphocytes: implications for immunomonitoring. 991 20

Alterations in microsatellite sequences have been reported in a variety of human cancers. Microsatellite instability is thought to reflect the inactivation of genes involved in DNA mismatch repair (MMR), which could predispose to the accumulation of further genetic errors in affected cells. Genomic instability in human cancers might also result from the inactivation of cell cycle controls such as the p53-dependent G1 checkpoint that prevents cell replication in response to DNA damage. High-risk human papillomavirus (HPV) is thought to contribute to the development of HPV-associated cancers, including cervical carcinoma, through the interaction of the E6 and E7 viral oncoproteins with two major cell cycle regulatory proteins, namely p53 and the retinoblastoma gene product (pRb). Although the high-risk HPV is prevalent in cervical carcinomas, viral DNA is not detected in a minor proportion of the cases. The HPV infection is insufficient for the development of cervical cancer, which indicates that additional genetic events are involved in the process. This study reports the potential role of MMR gene defects (in addition to or independent of HPV infection) in patients with cervical carcinogenesis. Microsatellite instability and HPV status were analyzed in a series of 54 patients with cervical carcinomas and in two associated cell lines. Microsatellite alterations were examined at 10 loci located in different chromosomes by using semiautomated fluorescent DNA technology and polymerase chain reaction. The HPV types were detected by a general primer polymerase chain reaction method. The results indicate that microsatellite instability is very infrequent in cervical carcinoma and occurs independently of HPV status.
Diagn Mol Pathol 1998 Oct
PMID:Low incidence of microsatellite instability in patients with cervical carcinomas. 999 Apr 86

The potential association of distinct polymorphisms of the tumor suppressor gene p53 with an increased susceptibility to malignant transformation has been reported for various cancer entities. Most recently, p53 protein containing an arginine residue in codon 72 was shown to be more effectively degraded by the E6 oncoprotein of human papillomavirus (HPV) than the corresponding proline isoform in cervical carcinoma cells. Additionally, a seven times higher risk of cervical cancer for Arg homozygotes was suggested. We set out to confirm this allele-specific predisposition on a larger population, comprising 87 cervical cancer and 151 normal control samples. However, there was no significant difference in the observed frequencies of homozygous Arg genotypes in cervical cancer patients (52.8%) and normal controls (55.7%). Furthermore, the prevalence of the Arg/Arg allelotype did not vary between HPV+ (n = 75) and HPV- (n = 12) carcinoma samples. Thus, our investigation of a larger set of clinical samples does not support the proposed association of any polymorphic status of p53 at codon 72 with an elevated risk for cervical cancer.
J Mol Med (Berl) 1999 Feb
PMID:No evidence of p53 allele-specific predisposition in human papillomavirus-associated cervical cancer. 1002 83

Cervical cancer is one of the most frequently found cancers in women and appears to have a viral aetiology. Substantial evidence points to the human papillomaviruses (HPV) as the infectious agents and there is considerable interest in identifying and accurately typing the viruses. Since HPVs now comprise more than 100 different HPV types, the polymerase chain reaction (PCR) has been the preferred methodology for virus identification and typing on isolated DNA. In that context, five commonly employed PCR consensus primers have been evaluated for the detection and typing of HPV. The five consensus primer pairs were derived from the consensus sequences of either the L1 and E1 open reading frames. All primers exhibited approximately equal sensitivity, as defined by the ability to detect HPV DNA, on a series of standard HPV DNA-containing preparations. However, the five primer pairs performed differently on 24 HPV-positive and 34 HPV-negative samples obtained from cervical scrapes which had been typed by type-specific PCR for HPV 6/11, 16, 18 and 33. The values for agreement between identification of samples by a HPV type-specific PCR and the consensus primer PCR were 78, 84, 91, 93 and 98%. Three samples, which were positive with only one of the five consensus primer pairs and were negative with the PCR for HPV types 6/11, 16, 18 and 33, contained other HPV sequences or HPV-related sequences as determined by DNA sequence analysis. To our knowledge, this report represents the first extensive comparison of five different consensus primers in a polymerase chain reaction for the detection of HPV. Our results suggest that PCR typing for human papillomaviruses requires more than one consensus primer pair to identify all HPV-infected samples.
Mol Cell Probes 1999 Feb
PMID:Evaluation of human papillomavirus-consensus primers for HPV detection by the polymerase chain reaction. 1002 28

Background: ThinPrep is a fluid-based technique for collection and processing of cytologic specimens. The present study was designed to determine whether the collection solution preserved RNA for molecular analysis. Methods and Results: Cervical cancer cell lines and cord blood lymphocytes were used to test the efficacy of various protocols for fixation, storage, and extraction of RNA. Total RNA was extracted and analyzed by denaturing gel electrophoresis. Preserved cells stored for 24 hours at room temperature or 4 degreesC had intact 28S and 18S ribosomal RNA. Both cellular and viral messenger RNAs were amplified from preserved samples by reverse transcription polymerase chain reaction (RT-PCR). Viral messenger RNA (mRNA) could be detected in a mixture of preserved cells containing 10% human papillomavirus (HPV) positive cells. RNA preservation in clinical samples was adequate for RT-PCR of cellular mRNA. Conclusions: Both experimental samples and clinical samples collected in the preservation media had intact total RNA. Amplification of both cellular and HPV ad mRNA was sucessful.
Mol Diagn 1998 Jun
PMID:Characterization of RNA in Cytologic Samples Preserved in a Methanol-Based Collection Solution. 1002 57


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