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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human papillomavirus (HPV) type 18 is strongly associated with the development of cervical cancer. Studies of a model system with animal papillomaviruses have demonstrated the importance of neutralizing antibodies in preventing papillomavirus-associated disease. The immune response to HPV is poorly understood, and there are non- standardized serological assays to identify HPV infections. In our study, the assessment of antibody responses against HPVs (previously hampered by the lack of viral source) was enabled by the expression of the L1 major capsid viral protein type 18 (HPV18) into L929 murine cells using the pTARGET mammalian expression vector system (MEVS). The cloning was validated by PCR with specific primers for the L1 gene, as well as by enzyme restriction and in situ hybridization. The evidence for the viral cloned gene expression was acquired by RT-PCR. Presence and antigenic properties of the recombinant L1 protein were shown using it as antigen in an indirect enzyme linked immunosorbent assay (ELISA) system. Significantly higher reactivity was noted when the sera samples were from persons infected with HPV18 as compared with the non-infected individuals but a moderately different reactivity was observed when the sera from patients infected with other HPV genotypes were tested. The results showed that the murine transfected cells could be used as antigen in order to detect the presence of the specific antibodies in HPV infected persons.
Int J Mol Med 2003 Dec
PMID:Cloning and expression of the L1 major capsid protein of the human papillomavirus 18 in murine cells. 1461 84

Although the human papillomavirus (HPV) E7 oncogene is known to contribute to the development of human cervical cancer, the mechanisms of its carcinogenesis are poorly understood. The first identified and most recognized function of E7 is its binding to and inactivation of the retinoblastoma tumor suppressor (pRb), but at least 18 other biological activities have also been reported for E7. Thus, it remains unclear which of these many activities contribute to the oncogenic potential of E7. We used a Cre-lox system to abolish pRb expression in the epidermis of transgenic mice and compared the outcome with the effects of E7 expression in the same tissue at early ages. Mice lacking pRb in epidermis showed epithelial hyperplasia, aberrant DNA synthesis, and improper differentiation. In addition, Rb-deleted epidermis (i.e., epidermis composed of cells with Rb deleted) exhibited centrosomal abnormalities and failed to arrest the cell cycle in response to ionizing radiation. Transgenic mice expressing E7 in skin display the same range of phenotypes. In sum, few differences were detected between Rb-deleted epidermis and E7-expressing epidermis in young mice. However, when both E7 was expressed and Rb was deleted in the same tissue, increased hyperplasia and dysplasia were observed. These findings indicate that inactivation of the Rb pathway can largely account for E7's phenotypes at an early age, but that pRb-independent activities of E7 are detectable in vivo.
Mol Cell Biol 2003 Dec
PMID:Recapitulation of the effects of the human papillomavirus type 16 E7 oncogene on mouse epithelium by somatic Rb deletion and detection of pRb-independent effects of E7 in vivo. 1464 21

The Papanicolaou smear has contributed to a decrease in cervical cancer rates in populations that receive regular screening. However, treatment of women with mildly abnormal cells is problematic because the majority of these women do not develop neoplasia. Thus, new techniques for identification of truly precancerous cells are needed. Characterization of cellular gene expression patterns is now possible through microarray techniques that survey the expression of large numbers of genes simultaneously. Here we have assessed the feasibility of combining new microscopic and molecular technologies to determine gene expression patterns in cervical intraepithelial neoplasia grade 3 cells recovered from liquid cytology-based Papanicolaou smear slides. Laser capture microdissection was used to retrieve cervical cells from ThinPrep prepared slides. The quality of RNA recovered from these cells proved suitable for reverse transcription polymerase chain reaction and for T7 RNA polymerase-based linear amplification of messenger RNA. We developed an optimized RNA amplification protocol that permitted microarray gene expression profiling in samples of as few as 20 cervical cells. This approach combining laser capture microdissection, linear RNA amplification, and microarray gene expression analysis will enable comparison of gene expression patterns between cytologically abnormal and normal cells taken from a single slide and may assist in the differential diagnosis of histologically difficult cases.
Appl Immunohistochem Mol Morphol 2003 Dec
PMID:Liquid-based pap smears as a source of RNA for gene expression analysis. 1466 62

Cervical carcinoma is the second most common cancer worldwide. The extent of free radical induced oxidative stress can be exacerbated by the decreased efficiency of antioxidant defense mechanisms. Low levels of essential antioxidants in the circulation have been found to be associated with an increased risk of cancer. The aim of our study was to assess the extent of oxidative stress, the levels of antioxidants like superoxide dismutase (SOD), catalase (CAT), ceruloplasmin and to evaluate tumor markers such as aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and total sialic acid (TSA) levels in circulation of women with cervical carcinoma and to compare our findings with age matched controls. Low levels of SOD and CAT observed in the circulation of cervical cancer patients may be due to their increased utilization to scavenge lipid peroxides as well as sequestration by tumor cells. Higher levels of TSA, AST, ALT and ALP, in the circulation of cervical cancer patients may be used in the diagnosis and treatment monitoring of patients with cervical carcinoma.
J Biochem Mol Biol Biophys 2002 Dec
PMID:Oxidative stress and tumor markers in cervical cancer patients. 1497 92

Human papillomavirus 16 (HPV16) E6E7 pre-mRNA is bicistronic and has an intron in the E6 coding region with one 5' splice site and two alternative 3' splice sites, which produce E6(*)I and E6(*)II, respectively. If this intron remains unspliced, the resulting E6E7 mRNA expresses oncogenic E6. We found for the first time that the E6E7 pre-mRNA was efficiently spliced in vitro only when capped and that cellular cap-binding factors were involved in the splicing. The cap-dependent splicing of the E6E7 pre-mRNA was extremely efficient in cervical cancer-derived cells, producing mostly E6(*)I, but inefficient in cells transfected with a common retrovirus expression vector, pLXSN16E6E7, due to the large size of this vector's exon 1. Further studies showed that efficient splicing of the E6E7 pre-mRNA depends on the distance of the cap-proximal intron from the RNA 5' cap, with an optimal distance of less than 307nt in order to facilitate better association of U1 small nuclear RNA with the intron 5' splice site. The same was true for splicing of human beta-globin RNA. Splicing of the E6E7 RNA provided more E7 RNA templates and promoted E7 translation, whereas a lack of RNA splicing produced a low level of E7 translation. Together, our data indicate that the distance between the RNA 5' cap and cap-proximal intron is rate limiting for RNA splicing. HPV16 E6E7 pre-mRNA takes advantage of its small cap-proximal exon to confer efficient splicing for better E7 expression.
J Mol Biol 2004 Apr 09
PMID:Splicing of a cap-proximal human Papillomavirus 16 E6E7 intron promotes E7 expression, but can be restrained by distance of the intron from its RNA 5' cap. 1504 80

Human papillomavirus (HPV) infection is the cause of squamous cell carcinoma of the uterine cervix. This causative relationship has provided the rationale and incentive for development of a prophylactic vaccine. Such a vaccine, if found to be effective, could reduce the need for cervical cancer screening and have a profound effect on the incidence of cervical and other anogenital cancers. This review begins by examining the basic biological and epidemiological principles relevant to the development of HPV preventative vaccines. It then summarises studies examining the use of vaccines to prevent HPV infection in animals and humans, and, finally, discusses some of the unanswered issues surrounding vaccine development against HPV infection and cervical cancer.
Expert Rev Mol Med 2004 Apr 20
PMID:Can genital-tract human papillomavirus infection and cervical cancer be prevented with a vaccine? 1509 82

The results obtained in the Laboratory of Molecular Biology of Viruses, CRC carried out in the framework of the Human Genome program and devoted to the study of the activity of cell and viral genes in cervical cancer are summarized. DNA of human papillomaviruses persists in tumors both in episomal and integrative forms. Integration may occur in different regions of chromosomes. Viral transforming genes E6 and E7 are always present in tumor cells, while antibodies to these proteins are detected only in approximately 30% of patients. Loss of heterozygosity is detected on long and short arms of chromosome 6; some such cases are manifest already at the early stages of tumor progression, while others are typical of the late stages. Several genes that are potentially involved in tumorigenesis and are subject to hypermethylation in CpG islands were identified. Methylation of several genes is observed in approximately 30% of tumors. Tumor progression is associated with increased expression of p16ink4a, an inhibitor of cyclin-dependent kinases.
Mol Biol (Mosk)
PMID:[Interaction of viral and cellular genes in cervical tumors]. 1512 26

Current morphology-based cervical cancer screening is associated with significant false-positive and false-negative results. Tumor suppressor gene hypermethylation is frequently present in cervical cancer. It is unknown whether a cervical scraping reflects the methylation status of the underlying epithelium, and it is therefore unclear whether quantitative hypermethylation specific PCR (QMSP) on cervical scrapings could be used as a future screening method augmenting the current approach. Cervical scrapings and paired fresh frozen cervical tissue samples were obtained from 53 cervical cancer patients and 45 controls. All scrapings were morphologically scored and analyzed with QMSP for the genes APC, DAPK, MGMT, and GSTP1. To adjust for DNA input, hypermethylation ratios were calculated against DNA levels of a reference gene. Hypermethylation ratios of paired fresh frozen tissue samples and scrapings of cervical cancer patients and controls were strongly related (Spearman correlation coefficient, 0.80 for APC, 0.98 for DAPK, and 0.83 for MGMT; P < 0.001). More cervical cancer patients than controls were DAPK positive (P < 0.001). When cutoff levels for ratios were defined to be above the highest ratio observed in controls, QMSP in cervical scrapings identified 32 (67%) of 48 cervical cancer patients. This feasibility study demonstrates that QMSP on cervical scrapings holds promise as a new diagnostic tool for cervical cancer. The addition of more genes specifically methylated in cervical cancer will further improve the assay.
Mol Cancer Res 2004 May
PMID:Detecting cervical cancer by quantitative promoter hypermethylation assay on cervical scrapings: a feasibility study. 1519 22

CSL, licensee of UniQuest's HPV technology, and Aventis Pasteur MSD (a joint venture between Merck & Co and Aventis) are jointly developing a vaccine for the potential prophylaxis of genital warts and cervical cancer caused by human papilloma virus infection. Enrollment for a phase III trial has been completed.
Curr Opin Mol Ther 2004 Apr
PMID:Technology evaluation: HPV vaccine (quadrivalent), Aventis Pasteur MSD/CSL. 1519 33

Whether the human papillomavirus (HPV) status of the tumor affects the sensitivity to neoadjuvant chemotherapy, and the prognosis in advanced uterine cervical cancer (FIGO stage III or higher) remains unknown. We examined the HPV status of 43 patients who had received CDDP therapy by balloon-occluded arterial infusion (BOAI), as neoadjuvant chemotherapy for advanced uterine cervical cancer (squamous cell carcinoma) stage III or higher. DNA was extracted from formalin-fixed, paraffin-embedded tumor samples obtained by punch biopsy before the neoadjuvant chemotherapy. The detection of HPV and its typing were analyzed by a polymerase chain reaction (PCR)-based assay using consensus primers for the L1 consensus regions. HPV DNA was detected in all 43 patients (100%): 29 cases with HPV 16 (67.4%), 5 cases with HPV 33 (11.6%), 4 cases with HPV 31 (9.3%), 3 cases with HPV 35 (7.0%), 1 case with HPV 18 (2.3%) and 1 case with HPV 58 (2.3%). The HPV types were divided into 3 groups, HPV 16, HPV 33 and other HPV types (HPV 18, 31, 35, 58), and comparisons and examinations were performed among the 3 groups. Although the rates of tumor reduction and operation accomplishment after 3 courses of BOAI showed no significant differences among the 3 groups, there were significant differences in the survival rates. The survival rate of advanced uterine cervical cancer patients with HPV 33 infection was the highest, followed by that of patients with HPV 16 infection. The survival rates of patients with the other types of HPV infection were the worst among the 3 groups and significantly lower than those of patients with HPV 16 or HPV 33 infection. The differences in the curative effect after BOAI may depend on the different characters of the HPV types.
Int J Mol Med 2004 Jul
PMID:Association of HPV infection with prognosis after neoadjuvant chemotherapy in advanced uterine cervical cancer. 1520 23


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