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uncoupling between phenotypic senescence and cell cycle arrest in aging p21-deficient fibroblasts.irreversible g(1) arrest in senescent human fibroblasts is mediated by two inhibitors of cyclin-dependent kinases (cdks), p21(cip1/sdi1/waf1) and p16(ink4a). to determine the physiological and molecular events that specifically require p21, we studied senescence in human diploid fibroblasts expressing the human papillomavirus type 16 e6 oncogene, which confers low p21 levels via enhanced p53 degradation. we show that in late-passage e6 cells, high cdk activity drives the cell cycle, but populati ...200010958672
prediction of cervical intraepithelial neoplasia grade 2-3 using risk assessment and human papillomavirus testing in women with atypia on papanicolaou smears.to determine whether human papillomavirus (hpv) dna testing and risk assessment can predict cervical intraepithelial neoplasia (cin) 2-3 on biopsies in women with atypia on papanicolaou smears.200010960635
european course on hpv associated pathology: guidelines for primary care physicians for the diagnosis and management of anogenital warts.the european course on hpv associated pathology (echpv) was founded in 1990 by a group of clinicians, pathologists, and virologists to teach important principles for the practice and management of human papillomavirus (hpv) disease to gynaecologists, dermatologists, and other medical disciplines. these guidelines are intended to assist the practice of primary care physicians for diagnosis and treatment of anogenital warts.200010961190
human papillomavirus type 16 e6/e7-specific cytotoxic t lymphocytes in women with cervical neoplasia.infection with oncogenic human papillomavirus (hpv) types is associated with the development of cervical neoplasia (cin). the e6 and e7 oncoproteins are constitutively expressed in these lesions and are therefore putative targets for the immune response against hpv. the relation between hpv 16-specific memory cytotoxic t-cell precursor (mctlp) activity to both oncoproteins and the natural course of cervical dysplasia was analyzed in 38 patients participating in a nonintervention cohort study of ...200010962445
brca1 activation of the gadd45 promoter.breast cancer susceptibility gene brca1 has been implicated in the control of gene regulation and such regulated genes are thought to mediate the biological role of brca1. overexpression of brca1 induces gadd45, a p53-regulated and stress-inducible gene. however, the molecular mechanism by which brca1 induces the expression gadd45 remains unclear. in this report, we have shown that the gadd45 promoter is strongly activated following expression of wild-type brca1. in contrast, both the tumor-deri ...200010962562
casein kinase ii phosphorylation of the human papillomavirus-18 e7 protein is critical for promoting s-phase entry.the human papillomavirus type 18 e7 protein subverts the prb/e2f pathway to promote s-phase reentry by postmitotic, differentiated primary human keratinocytes in support of viral dna amplification. we prepared a panel of hpv-18 e7 mutations in prb binding or in casein kinase ii (ckii) phosphorylation. our results showed that the ability of e7 binding to prb correlated with the activation of dna polymerase alpha or cyclin e to various extents in differentiated keratinocytes of organotypic culture ...200010965847
immunotherapy of gynaecological high-risk human papilloma virus infection with human leukocyte ultrafiltrate.in this preliminary presentation the outcome of women following systemic treatment of cervical human papilloma virus (hpv) with a leukocyte ultrafiltrate is reported.200010968593
detection of human papillomavirus type 16 dna in consecutive genital samples does not always represent persistent infection as determined by molecular variant analysis.persistent human papillomavirus (hpv) infection of the uterine cervix is a risk factor for progression to high-grade squamous intraepithelial lesions. detection in consecutive genital samples of hpv-16 dna, a frequently encountered hpv type, may represent persistent infection or reinfection. we undertook a study using pcr-single-strand conformation polymorphism (sscp) analysis and sequencing of pcr products (pcr-sequencing) to determine if consecutive hpv-16-positive samples contained the same h ...200010970388
regulation of the 26s proteasome by adenovirus e1a.we have identified the n-terminus of adenovirus early region 1a (ade1a) as a region that can regulate the 26s proteasome. specifically, in vitro and in vivo co-precipitation studies have revealed that the 19s regulatory components of the proteasome, sug1 (s8) and s4, bind through amino acids (aa) 4-25 of ad5 e1a. in vivo expression of wild-type (wt) ade1a, in contrast to the n-terminal ade1a mutant that does not bind the proteasome, reduces atpase activity associated with anti-s4 immunoprecipita ...200010970867
preventive and therapeutic vaccines for human papillomavirus-associated cervical cancers.'high risk' genotypes of the human papillomavirus (hpv), particularly hpv type 16, are the primary etiologic agent of cervical cancer. thus, hpv-associated cervical malignancies might be prevented or treated by induction of the appropriate virus-specific immune responses in patients. sexual transmission of hpv may be prevented by the generation of neutralizing antibodies that are specific for the virus capsid. in ongoing clinical trials, hpv virus-like particles (vlps) show great promise as prop ...200010971133
requirement of wild-type p53 protein for maintenance of chromosomal integrity.chromosomal double-strand breaks (dsbs) occurring in mammalian cells can initiate genomic instability, and their misrepairs result in chromosomal deletion, amplification, and translocation, common findings in human tumors. the tumor-suppressor protein p53 is involved in maintaining genomic stability. in this study, we demonstrate that the deficiency of wild-type p53 protein may allow unrepaired dsbs to initiate chromosomal instability. the human lymphoblastoid cell line tk6-e6 was established by ...200010972990
new technologies in cervical cancer precursor detection.the current literature reflects three routes toward improving cervical cancer screening. the first is to improve the test qualities of cytology-based screening. the use of liquid-based cytology and computerized analysis of papanicolaou tests are examples of attempts at this approach. secondly, through various combinations of parallel or sequential tests, either the sensitivity or the specificity of a given test could be improved depending on the tests chosen and the order in which they were perf ...200010975554
molecular identification of 7 human papillomavirus types in recurrent respiratory papillomatosis.recurrent respiratory papillomatosis (rrp) is the most frequent benign neoplasm in childhood; it originates as a mild dysphonia and results in asphyxia. the rrp has been associated with an infection caused by human papillomavirus (hpv), mainly types 6 and 11, the latter being associated with more severe rrp.200010979126
association of vitamin a deficiency with cervical squamous intraepithelial lesions in human immunodeficiency virus-infected women.to explore the relationship between vitamin a (retinol) deficiency and cervical squamous intraepithelial lesions (sils) in human immunodeficiency virus (hiv)-infected women, we measured serum retinol concentrations in 1314 women enrolled in the women's interagency hiv study and correlated the results with concurrent cervical cytology. at the baseline visit, 204 (15.5%) of the 1314 patients had retinol concentrations consistent with deficiency (<1.05 micromol/l). analysis of papanicolaou smears s ...200010979903
[human papillomavirus and the development of cervical cancer: concept of carcinogenesis].infection with high risk human papillomavirus (hrhpv) plays a central aetiological role in cervical cancer. still, cervical carcinogenesis is a multistep process which requires other events in addition to hrhpv infection. recent data have resulted in the following concept of cervical carcinogenesis: hrhpv infects normal squamous epithelium. in most cases this will not lead to a lesion or at worst give rise to a regressing low grade cervical intraepithelial neoplasia (cin). both phenomena involve ...200010981234
telomerase activity in hpv-associated vulvar vestibulitis.to find a possible correlation between telomerase activity, mean telomere length and human papillomavirus (hpv) presence and type in vulvar vestibulitis.200010986682
pregnancy-associated invasive squamous cell carcinoma of the vulva in a 28-year-old, hiv-negative woman. a case report.the incidence of invasive squamous cell carcinoma of the vulva in women under 40 years of age has been increasing, particularly in association with human papillomavirus. invasive vulvar carcinoma is rare in women under 30, as is an association with pregnancy. we report on a 28-year-old woman who was diagnosed with invasive squamous cell carcinoma of the vulva during pregnancy.200010986685
human papillomavirus infection in danish female sex workers. decreasing prevalence with age despite continuously high sexual activity.the prevalence of the human papillomavirus (hpv) has been found to decrease with age, but whether this applies to all populations is not clear. knowledge about the generalizability of this age dependency is important to understand the natural history of the infection, but may also have implications in relation to the use of hpv testing in cervical cancer screening.200010987448
a population-based five-year follow-up study of cervical human papillomavirus infection.the purpose of this study was to determine the long-term tendency for cervical human papillomavirus infections to persist in the general population.200010992174
up-regulation of epidermal growth factor-receptors (egf-r) by nicotine in cervical cancer cell lines: this effect may be mediated by egf.over-expression of epidermal growth factor-receptors (egf-r) has been described in a variety of cancers, including cervical cancer. nicotine may increase cellular proliferation rates through a mechanism involving egf or egf-r. in this study, we ascertain the effect of egf antibodies on nicotine-enhanced proliferation rates in two cervical cancer cell lines.200010994639
human papillomavirus-associated cancers in patients with human immunodeficiency virus infection and acquired immunodeficiency syndrome.human papillomavirus (hpv)-associated anogenital malignancies occur frequently in patients with human immunodeficiency virus (hiv) infection and the acquired immunodeficiency syndrome (aids). the purpose of our study was to determine if the high frequency of these cancers is due to lifestyle factors associated with both hpv and hiv infections or to immunosuppression following hiv infection.200010995805
amplification with molecular beacon primers and reverse line blotting for the detection and typing of human papillomaviruses.a novel method for the detection and typing of human papillomavirus (hpv) was developed using molecular beacon primers. the method is based on the use of hpv-specific primers containing a hairpin loop structure in which fluorescent donor and quencher groups are held in close proximity such that fluorescence is quenched. amplification of the target sequence results in the opening of the loop and the resulting fluorescence can be detected on a sequence detector system (sds) 7700 (applied biosystem ...200010996637
a recombinant vaccinia virus containing the papilloma e2 protein promotes tumor regression by stimulating macrophage antibody-dependent cytotoxicity.human papillomavirus infection is associated with cervical cancer. the e6 and e7 papillomavirus proteins are normally required for the maintenance of the malignant phenotype. expression of these proteins in infected cells is negatively regulated by the binding of the papilloma e2 protein to the long terminal control region of the papilloma virus genome. the e2 protein can also promote cell arrest and apoptosis in hela cells. therefore, it is clear that this protein has the potential of inhibitin ...200010999461
usefulness of human papilloma virus testing in the screening of cervical cancer precursor lesions: a retrospective study in 314 cases.to assess the usefulness of human papilloma virus (hpv) typing for predicting pre-malignant and malignant cervical lesions.200011000508
validity of adolescent and young adult self-report of papanicolaou smear results.to assess the validity of adolescent and young adult report of papanicolaou smear results and to determine sociodemographic, cognitive, and behavioral factors associated with incorrect reporting.200011004371
primary cervical carcinomas show 2 common regions of deletion at 3p, 1 within the fhit gene: evaluation of allelic imbalance at fhit, rb1 and tp53 in relation to survival.chromosome arm 3p is re-arranged in many tumor types, including cervical carcinomas. putative tumor-suppressor genes on 3p have been proposed, including the fhit gene, which maps to chromosome band 3p14.2. we have analyzed 79 primary cervical carcinomas for allelic imbalance (ai) at 17 chromosome 3 loci, including 3 within the fhit gene. expression of the fhit gene was evaluated after immunohistochemistry with an antibody against the pfhit protein. previously determined human papillomavirus stat ...200011004671
differential distribution of sequence variations in hpv-16 e6.the e6 regions of the oncogenic human papillomaviruses (hpvs) are important in carcinogenesis and immune recognition. we examined the e6 dna sequence from hpv-16-associated cervical cancers to determine the frequency and degree of variation from the consensus sequence in selected populations.200011006023
significance of atypical squamous cells of undetermined significance on thinprep papanicolaou smears.the aim of this study was to assess the prevalence and risk factors predictive of dysplasia among women seen in a gynecologic oncology service with the cytologic diagnosis of atypical squamous cells of undetermined significance (ascus) on papanicolaou smears obtained by the thinprep method.200011006029
correlates of the spread of human papillomavirus infection.knowledge of the correlates of human papillomavirus (hpv) seropositivity is of interest for planning of preventive measures and for evaluation of possible confounding in epidemiological studies. the epidemiological determinants for seropositivity for oncogenic and benign hpv types were assessed using a serosurvey of 275 healthy swedish women, stratified by age and lifetime number of sexual partners. seroprevalences were compared with 17 behavioral variables obtained by interview and 3 laboratory ...200011008914
the prevalence of genital human papillomavirus infections in abused and nonabused preadolescent girls.to compare the prevalence of genital human papillomavirus (hpv) infections in sexually abused and nonabused preadolescent girls and assess the feasibility of conducting a longitudinal study of the natural history of hpv infection in this population.200011015503
use of hormone replacement therapy (hrt) and detection of human papillomavirus (hpv) dna in postmenopausal women.purpose: this study investigated the association between detection of hpv dna among current and past hrt users compared to never hrt users, duration of hrt use, and type of hrt (estrogen, estrogen/progestin).methods: postmenopausal women (n = 390) were recruited from a university hospital and completed a questionnaire regarding 1) hrt use, duration, and type, 2) reproductive and sexual history, 3) smoking and alcohol use, and 4) hpv-related diseases. cervical specimens were obtained for pap smea ...200011018386
detection of human papillomavirus in epithelial lesions of the conjunctiva.many factors like exposure to uv radiation, climatic conditions, genetic predisposition, immunological state and, more recently, the presence of hpv have been implicated in the genesis of some lesions of the conjunctiva, especially the carcinoma.200011018845
treatment of external genital warts in men with imiquimod 2% in cream. a placebo-controlled, double-blind study.the purpose of this double-blind, placebo-controlled study was to evaluate the safety, clinical efficacy and tolerability of imiquimod (2%) in cream to cure external genital warts in males.200011023759
the e1e4 protein of human papillomavirus type 16 associates with a putative rna helicase through sequences in its c terminus.human papillomavirus type 16 (hpv16) infects cervical epithelium and is associated with the majority of cervical cancers. the e1e4 protein of hpv16 but not those of hpv1 or hpv6 was found to associate with a novel member of the dead box protein family of rna helicases through sequences in its c terminus. this protein, termed e4-dbp (e4-dead box protein), has a molecular weight of 66,000 (66k) and can shuttle between the nucleus and the cytoplasm. it binds to rna in vitro, including the major hpv ...200011024137
a longitudinal study of hpv detection and cervical pathology in hiv infected women.to monitor the presence and persistence of high risk (hr) human papillomavirus (hpv) in cervical brushings from hiv infected women.200011026879
histological diagnosis of cutaneous "warty" carcinoma on a pre-existing hpv lesion.a middle-aged man with an 8-year history of a fungating tumour mass on his thigh was histologically diagnosed as having an invasive "warty" carcinoma at the location of a pre-existing human papillomavirus (hpv) lesion. the tumour surface had a verruciform appearance with papillae containing fibrovascular cores. many of the malignant cells displayed changes consistent with koilocytotic atypia. we noticed a greater degree of nuclear atypia in comparison with a verrucous carcinoma. focally, some ne ...200011028866
bovine dental papilla-derived cells immortalized with hpv 18 e6/e7.in vitro investigations of cell-specific metabolism and cell interactions as well as biocompatibility studies are often hampered by the limited lifespan of primary cells originating from target tissues like the oral mucosa, gingiva or pulp. pulp cells, as do other primary cells, undergo senescence after several passages in vitro. however, senescence can be overcome by transfection of primary cells with oncogenes like the hpv 18 (human papillomavirus 18) e6/e7 oncogene, resulting in immortalized ...200011037760
primary squamous cell carcinoma of the endometrium.a rare case of primary squamous cell carcinoma of the endometrium, probably originating from adenomyosis, is presented. a 58-year-old japanese woman was referred to kitasato institution medical center hospital to explore the cause of her postmenopausal bleeding. the endometrial cytology specimen obtained with the endocyte (an device for endometrial check up) showed cells suggesting well differentiated squamous cell carcinoma. the patient underwent modified radical hysterectomy, bilateral salping ...200020563701
subcytotoxic h2o2 stress triggers a release of transforming growth factor-beta 1, which induces biomarkers of cellular senescence of human diploid fibroblasts.stress-induced premature senescence (sips) is induced 3 days after exposure of human diploid fibroblasts to subcytotoxic oxidative stress with h(2)o(2), with appearance of several biomarkers of replicative senescence. in this work, we show that transforming growth factor-beta1 (tgf-beta1) regulates the induction of several of these biomarkers in sips: cellular morphology, senescence-associated beta-galactosidase activity, increase in the steady-state level of fibronectin, apolipoprotein j, osteo ...200111060295
methemoglobin is a supplement for in vitro culture of human nasopharyngeal epithelial cells transformed by human papillomavirus type 16 dna.npc-n cells were normal human nasopharvngeal epithelial cells transformed by transfection with human papillomavirus type 16 deoxyribonucleic acid. bovine pituitary extract (bpe) was one of the indispensable ingredients for in vitro culture of npc-n cells in a serum-free medium. chromatographic fractionation of bpe and subsequent immunoblotting analyses identified the hemoglobin growth-stimulating factor. methemoglobin (methb) was then synthesized, and also found to be growth stimulating. the gro ...200111776972
rapid induction of cytotoxic t-cell response against cervical cancer cells by human papillomavirus type 16 e6 antigen gene delivery into human dendritic cells by an adeno-associated virus vector.we have shown that the pulsing of dendritic cells (dcs) with human papillomavirus type 16 (hpv-16) antigen proteins by lipofection stimulates class i-restricted cytotoxic t lymphocyte (ctl) response against primary cervical cancer cells. also, we have shown that adeno-associated virus (aav) was able to effectively deliver a cytokine gene into dcs. it has been our hypothesis that the delivery of antigen genes into dcs, resulting in endogenous and continuous antigen protein expression, may result ...200111781657
biological activities and molecular targets of the human papillomavirus e7 oncoprotein.the human papillomavirus (hpv) e7 protein is one of only two viral proteins that remain expressed in hpv-associated human cancers. hpv e7 proteins share structural and functional similarities with oncoproteins encoded by other small dna tumor viruses such as adenovirus e1a and sv40 large tumor antigen. the hpv e7 protein plays an important role in the viral life cycle by subverting the tight link between cellular differentiation and proliferation in normal epithelium, thus allowing the virus to ...200111753671
[studies on the relationship between clinicopathological features and human papillomavirus types in female lower genital tract carcinoma].to investigate the relationship between clinicopathological features and human papillomavirus types in female lower genital tract carcinoma.200111758209
[human papillomavirus (hpv) in the laryngeal carcinoma].epidemiological data and results of molecular studies suggest that human papillomavirus has been considered a risk factor in upper respiratory tract cancers. 10 out of 23 studied cases of laryngeal carcinoma revealed presence of hpv dna (43.5%). the pcr and hybrid capture ii test were used for the detection of viral dna.200111765440
human papillomaviruses and their role in cervical cancer.human papillomaviruses (hpvs) have been linked to a variety of human diseases, most notably cancer of the cervix, a disease responsible for at least 200,000 deaths per year worldwide. over 100 different types of hpv have been identified and these can be divided into two groups. low-risk hpv types are the causative agent of benign warts. high-risk hpv types are associated with cancer. this review focuses on the role of high-risk hpv types in cervical tumorigenesis. recent work has uncovered new c ...200111766888
sexual and non-sexual transmission of human papillomavirus.benign tumors and lesions of the anogenital tract are caused by human papillomaviruses (hpvs). they are also major risk factors for cervical cancer. introduction of the polymerase chain reaction (pcr) revealed that hpv infections are much more common among young asymptomatic women than it had been previously suspected. the side-specificity of genital hpvs led to the assumption that hpvs were primarily transmitted by sexual contact. however, since hpvs have been detected in virgins, infants/child ...200111791348
spontaneous malignant transformation of human ovarian surface epithelial cells in vitro.epithelial ovarian cancer has no reliable marker for early detection and no known specific premalignant changes. human ovarian surface epithelial (hose) cells expressing human papillomavirus type 16 (hpv-16) e6/e7 genes undergo crisis, and surviving cells exhibit an immortalized phenotype. cells show an increasingly invasive phenotype on collagen rafts over time. to ascertain the nature of this aberrant growth, we characterized this spontaneous progression of hose cells from a benign to an invas ...200111751530
repeatability of sexual history in longitudinal studies on hpv infection and cervical neoplasia: determinants of reporting error at follow-up interviews.misclassification of sexual history due to faulty recall or reporting bias may be the reason for variability in the association between sexual history and human papillomavirus (hpv) infection seen in studies conducted in different geographical areas. this study aimed to assess the repeatability of questionnaire information on sexual-history variables and their correlates, using information from repeat interviews by six international prospective cohort studies.200111822729
human papillomavirus, smoking, and cancer.the effect of smoking on human papillomavirus (hpv) activity and subsequent dysplasia and neoplasia remains controversial.200111907844
resolution of recurrent perianal condylomata acuminata by topical cidofovir in patients with hiv infection.anogenital condylomata acuminata are the most frequent clinical manifestation of genital human papillomavirus (hpv) infection. association between human immunodeficiency virus (hiv) and hpv infections is frequent (range: 26-60% in males). topical cidofovir (a nucleotide analogue antiviral drug active against a broad range of dna viruses) is a potential treatment for anogenital warts in immunocompromised patients. we treated three hiv-infected patients with hpv perianal condylomas with topical 1% ...200111843219
primary care of hpv management in hiv-infected women.the natural history of human papillomavirus (hpv) differs in women infected with (human immunodeficiency virus) hiv when compared with the general population. this report provides insight into the complexities of treating hpv infection and the differences found in hiv-infected women. by understanding the challenges associated with this opportunistic infection in hiv-infected women, nurse practitioners will be better prepared to provide primary care to this specific population.200111889689
parp determines the mode of cell death in skin fibroblasts, but not keratinocytes, exposed to sulfur mustard.sulfur mustard is cytotoxic to dermal fibroblasts as well as epidermal keratinocytes. we demonstrated that poly(adp-ribose) polymerase (parp) modulates fas-mediated apoptosis, and other groups and we have shown that parp plays a role in the modulation of other types of apoptotic and necrotic cell death. we have now utilized primary dermal fibroblasts, immortalized fibroblasts, and keratinocytes derived from parp(-/-) mice and their wildtype littermates (parp(+/+)) to determine the contribution o ...200111886524
human papillomavirus antigens and t-cell recognition.this review will summarize what is known about natural t-cell responses to human papillomavirus infections, including potential mechanisms for their dysregulation which may lead to the development of disease. we will also describe new strategies to enhance human papillomavirus specific t-cell responses following vaccination that are currently in development and recent reports on human vaccine trials with particular regard to the generation of appropriate t-cell responses.200111979123
[detection of hpv16 e6 gene in cervical tissues by quantitative polymerase chain reaction].to study the relationship between the quantities of hpv16 e6 gene in cervical tissues and the course of cervical disease.200111986698
immortalized testis cell lines from estrogen receptor (er) alpha knock-out and wild-type mice expressing functional eralpha or erbeta.the surprising findings that male mice lacking the estrogen receptor (er) alpha (alphaerko) have atrophic testis and are infertile proved that eralpha is involved in normal testicular function. to obtain compatible in vitro model systems for alphaerko male mice, we immortalized different cell lines from the testis of alphaerko and wild-type (c57bl/6) mice with the human papilloma virus e6/e7 genes. the established cell lines were characterized for sertoli, leydig, and peritubular cell markers by ...200111451363
the importance of biological factors (bcl-2, bax, p53, pcna, mi, hpv and angiogenesis) in invasive cervical cancer.the present study was designed to analyse the relationship between apoptosis related proteins (bcl-2 and bax), tumour suppressor protein p53, proliferation markers (pcna and mitotic index), human papillomavirus (hpv) and angiogenesis in cervical cancer and their impact on clinical outcome.200111451553
human papillomavirus infection in cyclosporin-induced gingival overgrowth in renal allograft recipients.host immunity plays an important role in the development of human papillomavirus (hpv)-associated disease. the hpv infection in oral cyclosporin-induced gingival overgrowth in renal transplant recipients has not been investigated previously. the aim of this study was to establish the hpv infection of cyclosporin-induced gingival hyperplasia in renal transplant recipients through morphological changes and use of the in situ hybridization technique.200111453235
signal-amplified colorimetric in situ hybridization for assessment of human papillomavirus infection in cervical lesions.detection and typing of human papillomavirus (hpv) infection may have a major impact in cervical-screening and follow-up. in this study various commercially available techniques for the detection of hpv were evaluated. hpv-status was determined in 86 samples of cervical cancer by pcr and direct sequencing, catalyzed signal amplified colorimetric dna in situ hybridization (csac- ish) (genpoint system, dako), immunohistochemistry (ihc) and in 12 selected cases also by conventional, non-amplified i ...200111455003
human papillomavirus type 18 in colorectal cancer.human papillomaviruses (hpvs) have been recognized as the etiological agent of warts, and they may also be associated with many cancers. hpv-18 is very common both in genital papillomas and in large bowel cancer. the relation between hpv-18 infection and natural course of colorectal cancer has not been fully defined. in this study, normal mucosa and colorectal cancer tissue were evaluated for the presence of hpv gene to determine whether or not hpv was involved in the development of colon neopla ...200111456365
a dna vaccine based on a shuffled e7 oncogene of the human papillomavirus type 16 (hpv 16) induces e7-specific cytotoxic t cells but lacks transforming activity.vaccination with oncogene-derived dna for anti-cancer treatment carries a risk of de-novo tumor induction triggered by the persisting recombinant dna. we hypothesized that an oncoprotein whose primary sequence has been rearranged ('shuffled') to maintain all possible t cell epitopes still induces cytotoxic t cells against the authentic protein but is devoid of transforming properties. as a model antigen, we used the e7 oncoprotein of the human papillomavirus (hpv) type 16, the major cause of cer ...200111457555
high risk human papillomavirus in oral squamous carcinoma: evidence of risk factors in a venezuelan rural population. preliminary report.in a search for the presence of human papillomavirus (hpv) and some etiologic cofactors in oral squamous cell carcinoma (oscc), 50 women diagnosed as oscc were analyzed by a multiplex polymerase chain reaction (pcr) assay specific for hpv types 6, 11, 16, and 18. this study revealed that 60% (30/50) of the oscc patients were positive for hpv-dna sequences. this group was analyzed according to smoking, alcohol consumption, number of pregnancies, poor oral health and low social economic status. th ...200111459321
stability of the human papillomavirus type 18 e2 protein is regulated by a proteasome degradation pathway through its amino-terminal transactivation domain.the e2 proteins of papillomaviruses regulate both viral transcription and dna replication. the human papillomavirus type 18 (hpv18) e2 protein has been shown to repress transcription of the oncogenic e6 and e7 genes, inducing growth arrest in hela cells. using hpv18 e2 fused to the green fluorescent protein (gfp), we showed that this protein was short-lived in transfected hela cells. real-time microscopy experiments indicated that the e2-dependent signal increased for roughly 24 h after transfec ...200111461997
degradation of the retinoblastoma tumor suppressor by the human papillomavirus type 16 e7 oncoprotein is important for functional inactivation and is separable from proteasomal degradation of e7.the steady-state level and metabolic half-life of retinoblastoma tumor suppressor protein prb are decreased in cells that express high-risk human papillomavirus (hpv) e7 proteins. here we show that prb degradation is a direct activity of e7 and does not reflect a property of cell lines acquired during the selection process for e7 expression. an amino-terminal domain of e7 that does not directly contribute to prb binding but is required for transformation is also necessary for e7-mediated prb deg ...200111462030
activation of the p21(cip1/waf1) promoter by bone morphogenetic protein-2 in mouse b lineage cells.bmps exert a negative growth effect on various types of cells. we have previously reported that bmp-2 inhibited the growth of hs-72 mouse hybridoma cells by inducing p21(cip1/waf1) expression. in the present study, we demonstrated that bmp-2 activated the mouse p21(cip1/waf1) promoter in hs-72 cells, and that a 29-base pair (b) region of the promoter (-1928/-1900 relative to the tata box), conserved between mice and humans, was responsive to bmp-2 as well as expression of smad1, smad4, and const ...200111466619
down modulation of il-18 expression by human papillomavirus type 16 e6 oncogene via binding to il-18.to understand modulation of a novel immune-related cytokine, interleukin-18, by human papillomavirus type (hpv) 16 oncogenes, hacat, normal keratinocyte cell line, and c-33a, hpv-negative cervical cancer cell line, were prepared to establish stable cell lines expressing e6, e6 mutant (e6m), e6e7, or e7 constitutively. expressions of various hpv oncogene transcripts were identified by rt-pcr. expression of hpv oncogene e6 was reversely correlated to the expression of interleukin-18, a novel pro-i ...200111470273
what we could do now: molecular pathology of gynaecological cancer.gynaecological tumours exemplify many of the molecular paradigms of carcinogenesis. the clinical value of many of the molecular abnormalities present is now being tested and it is likely that the identification of at least some of these will become routine in the near future. this may help to refine diagnosis and guide treatment-for example, therapeutic vaccination for human papillomavirus related disease.200111477134
human papillomavirus testing. effectiveness of testing for high risk hpv for triage of low grade abnormal smears is being assessed in tombola trial. 200111480414
microsatellite alterations in exfoliated cervical epithelia deoxyribonucleic acid as a marker for high-grade dysplasia.the purpose of this study was to evaluate the feasibility of the use of deoxyribonucleic acid microsatellite alterations in cervical epithelia in the prediction of high-grade dysplasia and to compare it with a strategy based on human papillomavirus testing.200111483913
human papillomavirus infection as a risk factor for squamous-cell carcinoma of the head and neck. 200111484705
p73 cooperates with dna damage agents to induce apoptosis in mcf7 cells in a p53-dependent manner.p73, a member of the p53 family, can induce apoptosis in cancer cells. since p53-mediated apoptosis can be augmented by various cancer chemotherapeutic agents, it has been hypothesized that the status of the endogenous p53 gene in cancer cells is a key determinant in the outcome of cancer therapy. to determine whether p73 can sensitize cancer cells to apoptosis by dna damage agents, several mcf7 adenocarcinoma cell lines that inducibly express p73 or p53 under a tetracycline-regulated promoter w ...200111494133
cost effectiveness of human papillomavirus testing to augment cervical cancer screening in women infected with the human immunodeficiency virus.to determine the cost effectiveness of incorporating molecular testing for high-risk types of human papillomavirus into a cervical cancer screening program for women infected with the human immunodeficiency virus (hiv).200111498068
both rb and e7 are regulated by the ubiquitin proteasome pathway in hpv-containing cervical tumor cells.high-risk human papillomaviruses (hpvs) are etiologically linked to human cervical and oral cancers. the e6 and e7 oncoproteins encoded by hpv target host cell tumor suppressor proteins. e6 induces proteolysis of p53 through the ubiquitin-proteasome pathway. recent studies showed that overexpression of e7 caused proteolytic degradation of the tumor suppressor rb. however, unlike p53, rb is not regulated by proteolysis in normal cells. in addition, it was unclear whether in its natural context e7 ...200111498796
expression of cyclin-dependent kinase inhibitors p16mts1, p21waf1, and p27kip1 in hpv-positive and hpv-negative cervical adenocarcinomas.inactivation or down-regulation of the cell-cycle inhibitors p16mts1, p21waf1, and p27kip1 is involved in the carcinogenesis of various human tumors. in cervical squamous cell carcinomas that are associated with human papillomavirus (hpv) infection, the expression or function of these proteins is impaired by the action of viral oncoproteins e6 and e7. comparably less is known about the role of these cyclin-dependent kinase inhibitors in cervical adenocarcinomas, 15-40% of which are hpv negative. ...200111499840
regulation of human papillomavirus type 1 replication by the viral e2 protein.the e1 and e2 proteins encoded by papillomaviruses are required for viral replication. earlier studies have shown that the viral e2 protein plays an important role in replication by targeting the e1 helicase to the origin of replication (ori). we have previously shown that the e1 protein of human papillomavirus (hpv) type 1 is sufficient for the in vivo replication of ori plasmids, although the e2 protein stimulates replication. in this study, we have further analyzed the role of the e2 protein ...200111504556
characterization of a novel genital human papillomavirus by overlapping pcr: candhpv86 identified in cervicovaginal cells of a woman with cervical neoplasia.a novel human papillomavirus (hpv), candhpv86, was cloned and characterized from cervicovaginal cells obtained from a 37-year-old hispanic woman with cervical intraepithelial neoplasia grade 1 (cin1) using an overlapping pcr technique. primers were designed by phylogenetic alignment of closely related hpv genomes using the l1 fragment sequence amplified by gp5+/6+. the 7983 bp complete nucleotide sequence of the hpv genome was determined by sequence walking. a basic local alignment sequence tool ...200111514712
prevalence, incidence, and type-specific persistence of human papillomavirus in human immunodeficiency virus (hiv)-positive and hiv-negative women.human immunodeficiency virus (hiv) infection and related immunosuppression are associated with excess risk for cervical neoplasia and human papillomavirus (hpv) persistence. type-specific hpv infection was assessed at 6-month intervals for hiv-positive and hiv-negative women (median follow-up, 2.5 and 2.9 years, respectively). the type-specific incidence of hpv infection was determined, and risk factors for hpv persistence were investigated by statistical methods that accounted for repeated meas ...200111517428
genital hpv: links to cervical cancer, treatment, and prevention.human papillomavirus is one of the most prevalent sexually transmitted viruses. it consists of over 230 different subtypes and infects the squamous epithelial cells in humans producing cutaneous, mucosal, and epidermodysplasia verruciformis type infections. there are several risk factors for human papillomavirus infections. these include a sexually active life-style beginning at a young age, having multiple lifetime sex partners, having sex with a partner with genital warts, and long term oral c ...200111517629
the retinoblastoma protein acts as a transcriptional coactivator required for osteogenic differentiation.the incidence of osteosarcoma is increased 500-fold in patients who inherit mutations in the rb gene. to understand why the retinoblastoma protein (prb) is specifically targeted in osteosarcoma, we studied its function in osteogenesis. loss of prb but not p107 or p130 blocks late osteoblast differentiation. prb physically interacts with the osteoblast transcription factor, cbfa1, and associates with osteoblast-specific promoters in vivo in a cbfa1-dependent fashion. association of prb with cbfa1 ...200111545733
detection of human papillomavirus dna and p53 gene mutations in esophageal cancer samples and adjacent normal mucosa.there is evidence of a possible etiological role of human papillomaviruses (hpvs) in the development of esophageal tumors. loss of function of the wild-type p53 tumor suppressor gene product by binding to e6 oncoproteins of high-risk hpvs is considered an important event in tumor development. the aim of this study was to verify the prevalence of hpv infection and p53 mutation in esophageal tumor tissue samples and in the adjacent normal mucosa in patients from a high-risk area in italy.200111549832
apoptotic changes in cervical intraepithelial neoplasia.we examined apoptosis in paraffin-embedded archival cervical tissues from cervical intraepithelial neoplasia (cin) cases to determine whether the apoptotic process is involved in the cellular changes of cin. apoptotic bodies, determined by the tunel method, were largely found at the surface epithelium in a few tissue specimens with no significant abnormality and in most tissues with cin. apoptotic bodies were also found within the stratified epithelium of cin lesions and were altogether absent i ...200111549862
differentiation-dependent chromatin rearrangement coincides with activation of human papillomavirus type 31 late gene expression.the life cycle of human papillomaviruses (hpvs) is tightly linked to the differentiation status of the host cell. while early genes are expressed during the initial stages of viral infection, late gene expression occurs in the suprabasal layers of the cervical epithelium. late genes encode e1-e4, a cytosolic protein, and capsid proteins l1 and l2. we have mapped over 30 initiation sites for late transcripts and show that the transcripts initiate in a 200-nucleotide region within the e7 open read ...200111559836
e5 transforming proteins of papillomaviruses do not disturb the activity of the vacuolar h(+)-atpase.papillomaviruses contain a gene, e5, that encodes a short hydrophobic polypeptide that has transforming activity. e5 proteins bind to the 16 kda subunit c (proteolipid) of the eukaryotic vacuolar h(+)-atpase (v-atpase) and this binding is thought to disturb the v-atpase and to be part of transformation. this link has been examined in the yeast saccharomyces cerevisiae. the e5 proteins from human papillomavirus (hpv) type 16, bovine papillomavirus (bpv) type 1, bpv-4 e5 and various mutants of e5 ...200111562529
immunology of human papillomavirus infection in lower genital tract neoplasia.despite its being a relatively common virus, the study of human papillomavirus infection has lagged behind that of other viruses. human papillomaviruses do not provoke strong systemic antibody or t-cell responses. furthermore, the majority of those infected do not display clinical symptoms and are able to clear the virus by unknown mechanisms. in the last decade, however, research into human papillomavirus immunology has blossomed, for two main reasons. first, there is strong circumstantial evid ...200111563868
management of atypical squamous cells of undetermined significance and low-grade squamous intra-epithelial lesion by human papillomavirus testing.cervical cytological terminology varies from country to country. in the usa, the pap smear is reported using the bethesda system. the abnormal morphological changes described by this system include two very problematic categories: atypical squamous cells of undetermined significance (ascus) and atypical glandular cells of undetermined significance (agus). the management of ascus, which is similar to the british system 'borderline' smear, has been most problematic because the majority of women wi ...200111563869
human papillomavirus as a form of risk assessment.there is a huge amount of interest in the use of human papillomavirus testing to improve both the sensitivity and specificity of cervical screening. although oncogenic human papillomavirus subtypes are recognized to be the most important factor in the development of cervical disease, only a minority of such infections results in invasive cancer. given our current, albeit limited, knowledge of the natural history of human papillomavirus infection and the development of cervical intra-epithelial n ...200111563871
human papillomavirus and vulval intra-epithelial neoplasia.the association between human papillomavirus vulval skin infection and vulval intra-epithelial neoplasia is strong. vulval skin carcinogenesis is, however, multifactorial. both human papillomavirus oncogenic subtype infection and p53 mutations are likely to contribute to the risk of malignant transformation of normal epithelium. the long-term cumulative risk of developing vulval squamous carcinoma following the diagnosis of high-grade vulval intra-epithelial neoplasia is thought to be approximat ...200111563872
significance of human papillomavirus in sinonasal papillomas.recent investigations have suggested human papillomavirus (hpv) to be involved in the development of sinonasal papillomas (snp). forty-three patients operated for snp were studied to determine the prevalence of hpv-dna sequences in these tumours and to evaluate their value as a prognostic parameter. the original sections of all cases were reviewed and reclassified according to the who. paraffin blocks available from 37 patients were subjected to in situ hybridization (ish) and polymerase chain r ...200111564296
p53 codon 72 polymorphism is linked to the development and not the progression of benign and malignant laryngeal tumours.the p53 codon 72 polymorphism, resulting in either an arginine or a proline residue has been proposed to affect the susceptibility of p53 protein to human papilloma virus (hpv) e6-mediated degradation in vitro. however, there are controversial results from several clinical studies in various human tumours. the purpose of our study was to investigate the significance of this p53 genotype with respect to the risk of neoplasia development in greek patients with benign and malignant laryngeal tumour ...200111564578
use of up-converting phosphor reporters in lateral-flow assays to detect specific nucleic acid sequences: a rapid, sensitive dna test to identify human papillomavirus type 16 infection.a lateral-flow (lf) device using the new reporter up-converting phosphor technology (upt) was applied to dna (hybridization) assays for the detection of specific nucleic acid sequences, thereby aiming to perform the test outside well-equipped laboratories. the methodology reported here is sensitive and provides a rapid alternative for more elaborate gel electrophoresis and southern blotting. in a preliminary study, it was applied to screen for the presence of human papillomavirus type 16 (hpv16) ...200111568115
co(2) laser treatment in 244 patients with respiratory papillomas.respiratory papillomas (rp) tend to recur and the difficulty in eradicating the disease makes their treatment frustrating. meticulous co(2) laser excisions every 2 months has been the most effective treatment to date. this article analyzes the results of this plan in 244 patients with rp in the nose, nasopharynx, pharynx, hypopharynx, larynx, trachea, lung parenchyma, and skin.200111568620
"low-risk" and "high-risk" hpv-infection and k-ras gene point mutations in human cervical cancer: a study of 31 cases.to analyze the coexistence of human papilloma virus (hpv) infection and k-ras gene activation in cervical neoplasia, we investigated 31 (seven pre-invasive and 24 invasive) cervical carcinomas for "low-risk" (types 6 and 11) and "high-risk" (types 16 and 18) hpvs and k-ras point mutations using pcr-based technology. "low-risk" hpvs were not detected in the group investigated; however, 20 of 31 (64%) cases were hpv 16 positive, while hpv 18 was found in only three (9.7%) samples (hpv 6/11 v. hpv ...200111569923
formation of soluble inclusion bodies by hpv e6 oncoprotein fused to maltose-binding protein.many polypeptides overexpressed in bacteria are produced misfolded and accumulate as solid structures called inclusion bodies. inclusion-body-prone proteins have often been reported to escape precipitation when fused to maltose-binding protein (mbp). here, we have examined the case of hpv 16 oncoprotein e6. the unfused sequence of e6 is overexpressed as inclusion bodies in bacteria. by contrast, fusions of e6 to the c-terminus of mbp are produced soluble. we have analyzed preparations of soluble ...200111570842
higher incidence of p53 mutation in cervical carcinomas with intermediate-risk hpv infection.inactivation of p53, either through mutation or interaction with human papillomavirus (hpv) e6 oncoprotein, is a characteristic feature of cervical carcinoma cell lines that have been previously studied. to elucidate the role of p53 in the carcinogenesis of korean cervical carcinomas, 27 hpv-positive and 13 hpv-negative cervical carcinomas were studied in order to evaluate the status of the p53 gene.200111574134
exogenous peptide and protein expression levels using retroviral vectors in human cells.pseudotyped retroviral vectors combine the advantages of broad host range, high expression, stable chromosomal integration, and ease of preparation. these vectors greatly facilitate delivery into mammalian cells of sequences encoding individual peptide inhibitors-including those with therapeutic utility-and inhibitor libraries. however, retroviral vectors vary in behavior, particularly with respect to expression levels in different cell lines. expression level is especially important in transdom ...200111708876
papillomavirus microbicidal activities of high-molecular-weight cellulose sulfate, dextran sulfate, and polystyrene sulfonate.the high-molecular-weight sulfated or sulfonated polysaccharides or polymers cellulose sulfate, dextran sulfate, and polystyrene sulfonate were tested for microbicidal activity against bovine papillomavirus type 1 (bpv-1) and human papillomavirus type 11 (hpv-11) and type 40 (hpv-40). in vitro assays included the bpv-1-induced focus-forming assay and transient infection of human a431 cells with hpvs. the compounds were tested for microbicidal activity directly by preincubation with virus prior t ...200111709319
the significance of p53 codon 72 polymorphism for the development of cervical adenocarcinomas.infection with the human papillomavirus is an important co-factor in the development of cervical carcinomas. accordingly, hpv dna is recognised in most of these tumours. polymorphism of the p53 gene, codon 72, is also considered a risk factor in the development of cervical carcinoma. however, this finding is contradicted by several observers. in the present investigation, 111 cases of adenocarcinoma of the cervix collected through the swedish cancer registry and 188 controls (females with normal ...200111710828
a comparative study of telomerase activity and malignant phenotype in multistage carcinogenesis of esophageal epithelial cells induced by human papillomavirus.to examine certain characteristics of multistep carcinogenesis, we studied telomerase activity and malignant phenotypes in the immortal, premalignant and malignant stages of esophageal epithelial cells induced by hpv. an immortalized human fetal esophageal epithelial cell line (shee) was induced by e6e7 genes of human papillomavirus (hpv) type 18. cells in the 10th passage, (shee10), 31st passage (shee31), 61st passage (shee61) and shee61a which were selected and expanded from anchorage-independ ...200111712078
detection of hpv in genital condylomata: correlation between viral load and clinical outcome.high dna viral load in human papillomavirus type 16 cervical dysplastic lesions has been proposed as a marker of progression towards malignancy. to evaluate the prognostic value of dna viral load in infection by hpv type other than hpv-16, a longitudinal study of patients with anogenital condylomata (ac) was designed. the study included 40 patients, 25 men and 15 women. clinical data were collected through standard interview and routine serum analyses. viral type in lesions was assayed by pcr wi ...200111718218
prb-expressing adenovirus ad5-rb attenuates the p53-induced apoptosis in cervical cancer cell lines.the retinoblastoma protein (prb), the gene product of the first reported tumour suppressor gene, is functionally inactivated by the e7 protein of high-risk human papillomavirus (hpv) found in most human cervical cancers. we have, in this study, constructed an adenoviral vector expressing wild-type prb (ad5-rb) and used the constructed ad5-rb to transfect the osteosarcoma cell line saos-2, and three cervical cancer cell lines hela, siha and c-33a. our results showed that prb caused g1 arrest in s ...200111720846
relationship between estradiol 16 alpha-hydroxylation and human papillomavirus infection in cervical cell transformation.the ovarian steroid hormone estradiol and its metabolite estrone were examined in 45 normal women and 127 premenopausal women with precancerous cervical lesions. interviews, colposcopy and cervical scrapings were performed. the mean +/- sd values for estradiol and estrone were 0.07 +/- 0.08 ng/ml and 0.06 +/- 0.02 ng/ml, respectively in normal subjects. corresponding data in patients with cervical intraepithelial neoplasia alone or in association with human papillomavirus (hpv) infection were 0. ...200111727355
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