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cyclin-dependent kinase inhibitor indirubin-3'-oxime selectively inhibits human papillomavirus type 16 e7-induced numerical centrosome anomalies.dysregulation of the centrosome duplication cycle has been implicated in tumorigenesis. our previous work has shown that the human papillomavirus type 16 (hpv-16) e7 oncoprotein rapidly induces aberrant centrosome and centriole duplication in normal human cells. we report here that hpv e7-induced abnormal centriole duplication is specifically abrogated by a small molecule cdk inhibitor, indirubin-3'-oxime (io), but not a kinase-inactive derivative. importantly, normal centriole duplication was n ...200415378001
loss of c-abl facilitates anchorage-independent growth of p53- and rb- deficient primary mouse embryonic fibroblasts.the c-abl tyrosine kinase is the proto-oncogene of the v-abl oncogene of the abelson murine leukemia virus. although mutational variants of c-abl can exhibit gain of function and can produce a transformed phenotype, the function of c-abl in transformation remained unclear. here, we report that the loss of c-abl facilitates transformation. c-abl-knockout mouse embryonic fibroblasts (mefs) immortalized by sv40 t antigen acquired anchorage-independent growth, and by constructing mutational variants ...200415378021
risk of high-grade squamous intraepithelial lesion in hiv-infected adolescents.the risk of developing the human papillomavirus (hpv)-associated precancer high-grade squamous intraepithelial lesion (hsil) in human immunodeficiency virus (hiv)-infected adolescents is unknown. we examined the risk of developing hsil among adolescents with and without hiv infection.200415378433
expression of hypoxic-inducible factor 1alpha predicts metastasis-free survival after radiation therapy alone in stage iiib cervical squamous cell carcinoma.hypoxia-inducible factor-1alpha (hif-1alpha) is an intrinsic marker of tumor hypoxia. it has been considered that the hypoxic status reduces radiosensitivity, but the role of hif-1alpha in advanced cervical carcinoma is still unclear. the objective of this study was to clarify the impact of hif-1alpha, human papillomavirus (hpv), and other molecular factors, such as p53, bax, bcl-2, and their correlations on the outcome of patients with stage iiib cervical carcinoma in radiation therapy.200415380586
american society of pediatric otolaryngology members' experience with recurrent respiratory papillomatosis and the use of adjuvant therapy.to evaluate how evolving treatment technologies have affected our management of recurrent respiratory papilloma (rrp) since the last comprehensive survey of pediatric otolaryngologists in 1998.200415381589
p16(ink4a) expression is related to grade of cin and high-risk human papillomavirus but does not predict virus clearance after conization or disease outcome.the role of p16(ink4a) as a marker of hr-hpv and in the diagnosis of cin has been well established, but its predictive value in the clearance of the virus after cin treatment and its use as a prognostic marker of cervical cancer has not been studied. a series of 302 archival samples, including 150 squamous cell carcinomas (sccs) and 152 cin lesions, were subjected to immunohistochemical staining for p16(ink4a) and hpv testing using pcr with three primer sets (my09/11, gp5/gp6, spf). follow-up da ...200415381905
small cell neuroendocrine carcinomas of the uterine cervix: a histological, immunohistochemical, and molecular genetic study.small cell carcinomas of the uterine cervix are rare tumors with an aggressive behavior. although these tumors can exhibit neuroendocrine differentiation, the criteria for neuroendocrine differentiation are subjective and not well defined. in this study, the authors tentatively defined small cell neuroendocrine carcinoma (scnec) as a tumor composed of small cells with at least two of the following: argyrophilic cytoplasm, chromogranin a immunoreactivity, and synaptophysin immunoreactivity. we fo ...200415381906
prognostic relevance of tgf-beta1 and pai-1 in cervical cancer.cervical carcinoma is a human papilloma virus (hpv)-related immunogenic type of malignancy, in which escape of the tumor from the hosts' immune response is thought to play an important role in carcinogenesis. the multifunctional cytokine transforming growth factor-beta(1) (tgf-beta(1)) is involved in immunosuppression, stroma and extracellular matrix formation and controlling (epithelial) cell growth. the plasminogen activating (pa) system plays a key role in the cascade of tumor-associated prot ...200415386352
apoptosis-related proteins and cervical intraepithelial neoplasia in human immunodeficiency virus-seropositive women.to evaluate the expression of bcl-2, p-53, ki-67, and apoptosis as evidenced by nuclear dna fragmentation in cervical biopsies obtained from human immunodeficiency virus (hiv)-seropositive and hiv-seronegative women with a history of intravenous drug abuse.200415581953
[a case of dandy-walker malformation futus and 18-trisomy]. 200416136993
risk factors for cervical cancer development: what do women think?the current cervical cancer prevention strategy is exclusively directed towards screening, without taking into account any relationship with sexual risk factors. the introduction of human papillomavirus (hpv) detection into the screening procedure implicates that we should give attention to this relationship. the aim of this study was to investigate what knowledge women have of the relation between hpv and cervical cancer.200416335302
a tailored multi-media campaign to promote the human papillomavirus cohort study to young women.human papillomavirus (hpv), a sexually transmitted disease, is now recognized as the major cause of cervical cancer. the cancer research center of hawaii developed a low-cost and culturally sensitive multimedia campaign to recruit oahu women to their hpv cohort study, specifically targeting women 18 to 35 years of age.200415916999
characterization of dna vaccines encoding the domains of calreticulin for their ability to elicit tumor-specific immunity and antiangiogenesis.antigen-specific cancer immunotherapy and antiangiogenesis are feasible strategies for cancer therapy because they can potentially treat systemic tumors at multiple sites in the body while discriminating between neoplastic and non-neoplastic cells. we have previously developed a dna vaccine encoding calreticulin (crt) linked to human papillomavirus-16 e7 and have found that this vaccine generates strong e7-specific antitumor immunity and antiangiogenic effects in vaccinated mice. in this study, ...200415893626
[association between high-risk human papillomavirus dna load and cervical intraepithelial lesion].to determine the association between viral load of high risk type human papillomavirus (hr-hpv) and stage of cervical intraepithelial neoplasia (cin) lesion.200415769315
[papilloma virus infection in pretumor and tumor masses of the larynx].there has been recent evidence suggesting that papilloma virus infection is of no small importance in the pathogenesis of tumors of the head and neck. this study has involved a screening of the mucosa having laryngeal pretumors and tumors for papilloma virus infection by polymerase chain reaction and immunohistochemistry. specimens were studied in 130 patients. all the patients with laryngeal papillomatosis were found to have human papilloma virus (hpv) types 6 and 11. hpv-18 was detected in 6 ( ...200415678687
genomic and proteomic expression patterns in hpv-16 e6 gene transfected stable human carcinoma cell lines.cdna microarray and proteomics studies were performed to analyze the genomic and proteomic expression patterns in hpv-16 e6 gene transfected stable human carcinoma cell lines. among 1024 known genes and ests tested by cdna microarray, we found 50 upregulated and 35 downregulated genes in rc10.1 hpv-16 e6 transfected human colon adenocarcinoma cells compared to rko cells, and 27 upregulated and 43 downregulated genes in a549e6 hpv-16 e6 transfected human lung adenocarcinoma cells compared to a549 ...200415684709
optimal cutoff of the hybrid capture ii human papillomavirus test for self-collected vaginal, vulvar, and urine specimens in a colposcopy referral population.to estimate the optimal relative light unit ratio, as a measure of viral load, of the hybrid capture ii human papillomavirus (hpv) test in self-collected specimens for detecting cervical intraepithelial neoplasia (cin).200415874834
performance of direct visual inspection of the cervix with acetic acid and magnification in a previously screened population.to assess the screening performance of direct visual inspection with acetic acid and x2 magnification (viam) in a previously screened population, as performed by experienced gynecologic nurses with minimal training in viam.200415874851
beyond human papillomavirus: the cervix, exogenous secondary factors, and the development of cervical precancer and cancer.human papillomavirus (hpv) is the necessary but probably not sufficient cause of cervical precancer and cancer. secondary exogenous and endogenous factors, hpv cofactors, may contribute to the probability of a cancer-associated (oncogenic) hpv infection progressing to cervical precancer and cancer. for these cofactors to influence the natural history of hpv infection, they must act on cervical tissue to promote viral persistence, progression to precancer or cancer given viral persistence, or bot ...200415874868
false-negative hybrid capture ii results related to altered adhesion molecule distribution in women with atypical squamous cells pap smear results and tissue-based human papillomavirus-positive high-grade cervical intraepithelial neoplasia.we investigated the detection of high-risk human papillomavirus dna with the hybrid capture ii test (hcii; digene corporation, beltsville, md) and the presence and pattern of distribution of adhesion molecules in biopsy-proven high-grade neoplastic lesions containing high-risk hpv-dna from women with asc cytology results.200415874874
matrix metalloproteinase-2, squamous cell carcinoma antigen, and tissue polypeptide-specific antigen expression in egyptian patients with cervical carcinoma: relationship with prognosis.matrix metalloproteinases (mmps), a family of proteolytic enzymes produced by both stromal and tumor cells, appear to have a key role in the events leading to local invasion and metastasis by malignant neoplasms. in the present study, we evaluated the role of mmp-2, squamous cell carcinoma antigen (scca), and tissue polypeptide - specific antigen (tps) in cervical neoplasia. using western blotting and enzyme immunoassay (eia), we analyzed 50 patients with cervical carcinoma (cc) and 25 normal co ...200415665394
testing positive for human papillomavirus in routine cervical screening: examination of psychosocial impact.to examine the psychosocial impact of testing positive for high risk human papillomavirus (hpv) among women attending primary cervical screening.200415663132
cost-effectiveness of cervical cancer screening strategies.despite its low incidence in the developed world, cervical cancer is the second most common cancer among women worldwide and the third most common cause of cancer-related deaths. screening saves lives. when diagnosed and treated in the preinvasive stage, 5-year survival probabilities approach 100%. this review addresses the cost-effectiveness of the various screening strategies commonly used worldwide. the starting age of screening, interval between screens and age of women at cessation of scree ...200419807311
[malignancy arising in seborrheic keratosis: two cases report].seborrheic keratosis are one of the most common benign epidermal tumors encountered in clinical practice. malignant transformation is exceptional. it may occur by the involvement of human papilloma virus. we report two cases of seborrheic keratosis in respectively 58 and 60-years-old women, which, on biopsy, revealed the presence of bowen's disease for the former and squamous cell carcinoma for the later.200317722804
detection of human cytomegalovirus dna in 986 women studied for human papillomavirus-associated cervical neoplasia.the aim of this study was to assess the association of human cytomegalovirus (cmv) infection with cervical histologic findings and possible interaction with human papillomavirus (hpv) infection.200317051067
participants at the asccp 2000 biennial meeting adhere to published guidelines in their management of atypical squamous cells and atypical glandular cells on pap test.to determine practice patterns of the american society for colposcopy and cervical pathology (asccp) 2000 biennial meeting participants for management of women with atypical squamous cells of undetermined significance (ascus) and atypical glandular cells of undetermined significance (agus).200317051084
[low yield of hpv dna determination in the distal region of the male urethra].to assess the prevalence of human papillomavirus (hpv) deoxyribonucleic acid (dna), and of clinical and subclinical condilomatosis in men whose sex partners had been diagnosed with cervical intraepithelial neoplasia.200314974269
hypothesis: the act of taking a papanicolaou smear reduces the prevalence of human papillomavirus infection: a potential impact on the risk of cervical cancer.based on data collected in a case-control study of hormonal contraceptive use and invasive cervical cancer among south african colored and black women, we have reported a five-fold reduction in incidence among women who in their lifetimes had previously received as few as two papanicolaou (pap) smears. given the conditions prevailing in the community under study, a reduction in risk of this magnitude was surprising. we hypothesized that the act of performing a pap smear may trigger an immune res ...200314750534
[identification and typification of the human papilloma virus in women using the "timely detection of cancer" program in durango, mexico].in mexico, the cervical carcinoma is a public health problem, representing more of 36% of the neoplasms. this carcinoma has been etiologically associated with the human papillomavirus (hpv) infection and the polymerase chain reaction (pcr) has been considered as one of the most sensitive methods for its detection. the aim of this study was to determine the hpv types by pcr-rflps in 111 women attending in the doc programs in gomez palacio, durango.200314686060
the epidemiology of cervical cancer.cervical cancer is one of the most common neoplastic diseases affecting women, with a combined worldwide incidence of almost half a million new cases annually, second only to breast cancer. basic and epidemiologic research conducted during the past 15-20 years have provided overwhelming evidence for an etiologic role for infection with certain types of sexually-transmitted human papillomavirus (hpv) as the primary cause of cervical cancer. the relative risks of cervical cancer following hpv infe ...200314690309
molecular detection of infections associated with neoplasia.this article discusses the molecular targets and the methods for identification of human papillomavirus and the human gammaherpesviruses, epstein-barr virus and human herpesvirus type 8.200314711098
preventative and therapeutic vaccines for cervical cancer."high-risk" genotypes of the human papillomavirus (hpv), most commonly hpv genotype 16, are the primary etiologic agents of cervical cancer. indeed hpv dna is detected in 99% of cervical carcinomas. thus, cervical cancer and other hpv-associated malignancies might be prevented or treated by the induction of the appropriate viral-antigen-specific immune responses. transmission of papillomavirus may be prevented by the generation of antibodies to capsid proteins l1 and l2 that neutralize viral inf ...200314711335
prospects for controlling cervical cancer at the turn of the century.cervical cancer morbidity and mortality have decreased substantially during the last 50 years mostly due to successful organized or opportunistic screening with pap cytology in high and middle income countries. in many low income countries pap cytology screening is yet to be effectively implemented or has failed to reduce cervical cancer rates to an appreciable extent. the fact that infection with certain human papillomavirus (hpv) types is now recognized as a necessary cause of this disease has ...200314746030
detection of human papillomavirus in cervical lymph nodes: a highly effective strategy for localizing site of tumor origin.patients with head and neck squamous cell carcinoma (hnscc) often come to clinical attention with a neck mass due to metastatic spread to lymph nodes. treatment is dictated by the subsequent determination of primary tumor site and stage. however, the primary site remains elusive in some patients even after an exhaustive examination. human papillomavirus type 16 (hpv-16) is an important etiologic agent for hnsccs that arise within the oropharynx but less so for tumors from nonoropharyngeal sites. ...200314695150
notch1 can contribute to viral-induced transformation of primary human keratinocytes.the human papillomavirus (hpv) is the most significant causative agent in the development of cervical cancer. despite its presence in almost all cervical cancers, hpv by itself is unable to transform a normal cell to a cancerous one. instead, additional cellular mutations are required to supplement the hpv oncoproteins e6 and e7. activation of the notch1 signaling pathway has been proposed as one of the cellular changes that cooperate with the e6 and e7 proteins to cause cervical cancers. this p ...200314695182
geldanamycin and 17-allylamino-17-demethoxygeldanamycin potentiate the in vitro and in vivo radiation response of cervical tumor cells via the heat shock protein 90-mediated intracellular signaling and cytotoxicity.ansamycin antibiotics inhibit function of the heat shock protein (hsp) 90, causing selective degradation of several intracellular proteins regulating such processes as proliferation, cell cycle regulation, and prosurvival signaling cascades. hsp90 has been identified previously as a molecular target for anticancer agents, including ionizing radiation (ir). therefore, we hypothesized that the ansamycin geldanamycin and its 17-allylamino-17-demethoxy analog (17-aag), which inhibit hsp90, would enh ...200314695217
[population-based study of human papillomavirus infection in high-risk area for cervical cancer in shanxi province, china].to investigate the prevalence of oncogenic type of human papillomavirus (hpv) infection and identify the high risk population for conducting immuno/chemoprevention of cervical cancer.200312974078
human papillomaviruses in the normal oral cavity of children in japan.the purpose of this study was to determine the frequency of human papillomavirus (hpv) infections in the normal oral cavity of children in japan. oral squamous cell specimens were collected from 77 children (44 boys and 33 girls), aged 3 and 5 years. extracted dna was evaluated for hpv infections by polymerase chain reaction (pcr) methods, using consensus primers for the l1 region, specific primers, and direct dna sequencing analysis. thirty-seven of 77 specimens (48.1%) were positive for hpv dn ...200313679205
human papillomavirus and oral cancer: the international agency for research on cancer multicenter study.human papillomavirus (hpv), the causal agent of cervical cancer, appears to be involved in the etiology of cancer of the oral cavity and oropharynx. to investigate these associations, we conducted a multicenter case-control study of cancer of the oral cavity and oropharynx in nine countries.200314652239
prevalence and determinants of chlamydia trachomatis infections in women from bogota, colombia.chlamydia trachomatis infection in the cervix and uterus has been hypothesised to be a co-factor for cervical cancer. we performed a cross sectional study in bogota, colombia, where cervical cancer rates are high, to determine the prevalence and determinants of c trachomatis infection, and in particular its association with human papillomavirus (hpv).200314663124
high-risk human papillomaviruses may have an important role in non-oral habits-associated oral squamous cell carcinomas in taiwan.to evaluate the etiologic role of human papillomavirus (hpv) in oral carcinogenesis, dna samples were purified from 103 oral squamous cell carcinoma (oscc) and 30 normal oral mucosal (nom) specimens. a nested polymerase chain reaction, dna sequencing, and gene-chip hpv typing were used to identify multiple hpv types in our samples. we found that the positive rates of all hpv types and of high-risk hpv types were significantly higher in oscc samples (49.5% and 41.7%, respectively) than in nom sam ...200314671980
serum immunoglobulin a response to human papillomavirus type 16 virus-like particles in human immunodeficiency virus (hiv)-positive and high-risk hiv-negative women.serum samples from 2008 human immunodeficiency virus (hiv)-positive and 551 hiv-negative women were tested for immunoglobulin a (iga) to human papillomavirus (hpv) type 16 capsids. iga seropositivity was lower than previously reported igg seropositivity (7% vs. 51%), but, like igg antibodies, hpv 16 iga was associated with sexual behavior, cervicovaginal hpv 16 dna, and cytological abnormalities. iga seropositivity was higher in hiv-positive women than in hiv-negative women (7.7% vs. 4.9%; p=.02 ...200314673762
presence of human papillomavirus dna in plucked eyebrow hairs is associated with a history of cutaneous squamous cell carcinoma.a role for cutaneous human papillomaviruses (hpv) has been proposed in the development of skin cancer. well-designed epidemiologic studies to demonstrate an association between hpv infection and skin cancer are extremely rare. to identify hpv infection as a potential risk factor, we investigated the association between the presence of hpv dna in eyebrow hairs and a history of cutaneous squamous cell carcinoma. a case-control study was designed consisting of 155 immunocompetent individuals with a ...200314675206
the human papillomavirus type 11 and 16 e6 proteins modulate the cell-cycle regulator and transcription cofactor trip-br1.the genital human papillomaviruses (hpvs) are a taxonomic group including hpv types that preferentially cause genital and laryngeal warts ("low-risk types"), such as hpv-6 and hpv-11, or cancer of the cervix and its precursor lesions ("high-risk types"), such as hpv-16. the transforming processes induced by these viruses depend on the proteins e5, e6, and e7. among these oncoproteins, the e6 protein stands out because it supports a particularly large number of functions and interactions with cel ...200314675634
prevention of cervical cancer in africa: a daunting task?africa has a high estimated incidence of cervical cancer, thus requiring the development of an effective prevention strategy. cytology-based screening is beyond the capacity of many african countries, hence the need for alternatives. visual inspection of the cervix after application of 3-5% acetic acid (via) is a promising screening test, with similar sensitivity to that of cytology but lower specificity. the same accounts for other via methods using magnification devices, visual inspection afte ...200314677294
cervical human papillomavirus infections in commercial sex workers-risk factors and behaviours.we have investigated the prevalence of, and risk factors for, cervical human papillomavirus (hpv) infection in commercial sex workers (csws) and controls attending the same sexual health clinics in sydney. a self-administered 'risk factor' questionnaire was completed and a pap smear and a specimen for hpv detection and typing were taken. results from the 288 csws and 266 controls were assessed by univariate and multivariate analyses. no significant difference in the rates of cervical hpv infecti ...200314678594
rna interference: a potential tool against kaposi's sarcoma-associated herpesvirus.rna interference is a conserved cellular function that controls viral infection, the expression of transposable elements, repetitive sequences and genes in embryonic development. originally described as an antiviral mechanism in plants, known as posttranscriptional gene silencing, it is now appreciated that this phenomenon occurs in all living cells. double-stranded rna, when acting as part of rna interference, reduces expression of genes with sequence similarity, but has no effect on the expres ...200314624111
molecular analysis of human papillomavirus type 52 isolates detected in the genital tract of human immunodeficiency virus-seropositive and -seronegative women.human papillomavirus (hpv) type 52 dna was detected in cervicovaginal lavage samples from 91 (12.4%) of 732 human immunodeficiency virus (hiv)-seropositive women and 23 (7.1%) of 323 hiv-seronegative women (p=.0004). hiv infection was an independent predictor for hpv-52 infection when controlling for age and sexual activity (odds ratio, 2.21; 95% confidence interval, 1.30-3.75: p=.003). we describe the genomic polymorphism of 114 hpv-52 isolates. long control region (lcr) mutations defined 27 hp ...200314624377
successful immortalization of endometrial glandular cells with normal structural and functional characteristics.the human endometrium is a dynamic tissue, the proliferative activity of which dramatically changes throughout the menstrual cycle, with exquisite regulation by sex-steroid hormones. primary endometrial epithelial cells fall into senescence within 2 weeks when cultured on plastic dishes, and more complete understanding of endometrial biology has been delayed because of, in part, a lack of an in vitro culture model for endometrial epithelial cells. our goal was to establish immortalized human end ...200314633600
an alpha helix conformationally restricted peptide is recognized by cervical carcinoma patients' sera.human papillomavirus type 16 (hpv-16) represents the major cervical carcinoma associated virus among women, especially in colombia. it has thus become important to develop reliable inexpensive tests for detecting the presence of this virus. it has been shown that hpv16-e7 oncoprotein structural features have three alpha-helical structures and a loop-like structure. the hydrazone link approach was used to mimic helix secondary substructures. sera from women with invasive cervical carcinoma were t ...200314640547
optical systems for in vivo molecular imaging of cancer.progress toward a molecular characterization of cancer would have important clinical benefits; thus, there is an important need to image the molecular features of cancer in vivo. in this paper, we describe a comprehensive strategy to develop inexpensive, rugged and portable optical imaging systems for molecular imaging of cancer, which couples the development of optically active contrast agents with advances in functional genomics of cancer. we describe initial results obtained using optically a ...200314640761
association between esophageal squamous cell carcinoma and human papillomavirus detected by hybrid capture ii assay.from july 1999 to july 2000, 40 patients from the surgical oncology and gastroenterology departments of irmandade da santa casa de misericórdia de porto alegre were enrolled in a prospective study in order to find the frequency of human papillomavirus dna (hpv-dna) in esophageal squamous cell carcinoma. they were compared to 10 normal individuals (controls). digene inc. (digene corporation, gaithersburg md, usa) hybrid capture ii assay, a chemoluminescent method, was used in both groups. the sam ...200314641314
human papillomavirus dna in sera of cervical cancer patients as tumor marker.persistent infection with human papillomavirus (hpv) has been widely recognized to induce carcinoma of the uterine cervix. viral dna has been documented to occur as tumor dna in the circulation of patients with primary tumors caused by viral infection. the aim of this study was to evaluate the utility of serum hpv dna as tumor marker in cervical cancer patients. sera taken from 94 cervical cancer patients at the date of diagnosis and follow-up serum samples from 24 patients were examined for hpv ...200314643453
genetic susceptibility to infection with human papillomavirus and development of cervical cancer in women in brazil.human papillomavirus (hpv) is considered to be a necessary but not sufficient cause for cervical cancer and, therefore, other factors contribute to the carcinogenic process. a hereditary component for this neoplasia has been reported and several studies indicate that genetic background of the host is important for cervical cancer susceptibility. among genetic factors that could participate in the susceptibility to this tumor and disease outcome, polymorphic genes of the major histocompatibility ...200314644340
infection, replication, and cytopathology of human papillomavirus type 31 in trophoblasts.human papillomavirus (hpv) dna is preferentially found in spontaneous abortions, specifically residing in trophoblasts, and transfected hpv-16 dna replicates and produces progeny in 3a trophoblasts in culture. in this study 3a trophoblasts were shown to display both hpv receptors and infection by hpv-31b and hpv-6 virus resulted in de novo (increasing) hpv dna replication in these cells (inhibited by neutralizing anti-hpv31b antibodies). reverse transcription-polymerase chain reaction analysis r ...200314644610
an adenoviral vector cancer vaccine that delivers a tumor-associated antigen/cd40-ligand fusion protein to dendritic cells.to develop a method to overcome the anergy that exists in tumor hosts to cancer, we have designed an adenoviral vector for the in vivo activation and tumor antigen loading of dendritic cells. this adenoviral vector encodes a fusion protein composed of an amino-terminal tumor-associated antigen fragment fused to the cd40 ligand (cd40l). subcutaneous injection of an adenoviral vector encoding a fusion protein of the human papillomavirus e7 foreign antigen linked to the cd40l generates cd8+ t cell- ...200314645711
in vitro and in vivo growth suppression of human papillomavirus 16-positive cervical cancer cells by e6 sirna.human papillomavirus type 16 (hpv16), a causative agent of cervical cancers, encodes the e6 and e7 oncogenes, whose simultaneous expression is pivotal for malignant transformation and maintenance of malignant phenotypes. in the hope of developing a gene-specific therapy for hpv-related cancer, we examined the effects of e6 short-interfering rna (sirna) on the expression of these oncogenes and on the cell growth of hpv16-related cervical cancer cells. using siha cervical cancer cells, we demonstr ...200314599809
in vitro downregulation of growth factors by insulin-like growth factor binding protein-3 in cervical cancer.our hypothesis is that insulin-like growth factor binding protein 3 (igf-bp3) would downregulate epidermal growth factor receptor (egf-r) levels in cervical cancer cell lines, thereby reducing cellular igf-ii and angiogenesis-related vascular endothelial cell growth factor (vegf). as folate deficiency is a risk factor in cervical cancer, we sought to determine if folic acid treatment might increase igf-bp3 production, thereby inhibiting malignant cell proliferation.200314599874
innovations in understanding the biology of cervical cancer.revelation of the connection between the human papillomavirus (hpv) and cervical neoplasia and invasive cervical cancer is prompting new investigations to expand that understanding and promote vaccines, gene therapy, and other interventions. at the second international conference on cervical cancer (houston, tx, april 11-14, 2002), laboratory and clinical researchers reported advances in new studies meant to increase understanding of the natural history of hpv and cervical intraepithelial neopla ...200314603543
distribution of human papillomavirus types 16 and 18 variants in squamous cell carcinomas and adenocarcinomas of the cervix.the distributions of human papillomavirus (hpv) types detected in cervical adenocarcinomas and squamous cell tumors differ. however, whether the distributions of intratypic hpv variants seen in these two histological forms of cervical disease differ is unknown. our objective was to compare the distribution of hpv intratypic variants observed in squamous cell carcinomas (scc) and cervical tumors of glandular origin (e.g., adenocarcinomas; ac) for two hpv types commonly observed in cervical tumors ...200314612516
the prevalence of human papillomavirus genotypes in nonmelanoma skin cancers of nonimmunosuppressed individuals identifies high-risk genital types as possible risk factors.nonmelanoma skin cancer is the most commonly diagnosed malignant disease in caucasians. known risk factors include fair skin, sun exposure, male gender, advancing age, and the presence of solar keratosis. no viral risk factors have been established thus far. to examine the association between nonmelanoma skin cancer and infection with human papilloma virus (hpv) types, we performed a retrospective study in which skin biopsies were collected from 496 nonimmunosuppressed patients attending dermato ...200314612553
extended duration of the detectable stage by adding hpv test in cervical cancer screening.the human papillomavirus test (hpv) test could improve the (cost-) effectiveness of cervical screening by selecting women with a very low risk for cervical cancer during a long period. an analysis of a longitudinal study suggests that women with a negative pap smear and a negative hpv test have a strongly reduced risk of developing cervical abnormalities in the years following the test, and that hpv testing lengthens the detectable stage by 2-5 years, compared to pap smear detection alone.200314612887
cervical cytology screening in teens.new guidelines for when to initiate cervical cancer screening have recently been revised. the american cancer society now recommends that screening be initiated within 3 years of the onset of vaginal intercourse but no later than 21 years of age. natural history studies of human papillomavirus (hpv; the cause of abnormal cytology and cervical cancer) suggest that there is little risk of a significant precancerous lesion going undetected within the first 3 to 5 years after the onset of sexual act ...200314613663
vaccinia-expressed human papillomavirus 16 and 18 e6 and e7 as a therapeutic vaccination for vulval and vaginal intraepithelial neoplasia.anogenital intraepithelial neoplasia is a chronic disorder associated with infection by high-risk human papillomavirus (hpv) types. it is frequently multifocal and recurrence after conventional treatment is high. boosting hpv-specific cell-mediated immune responses may reduce progression to carcinoma and could lead to disease clearance. we have tested the safety, immunogenicity, and efficacy of a recombinant vaccinia candidate vaccine (ta-hpv) in women with anogenital intraepithelial neoplasia.200314614000
peptides inhibitory for the transcriptional regulatory function of human papillomavirus e2.human papillomavirus (hpv) infections are associated with cervical neoplasia. cellular and viral proteins are known to interact with the papillomavirus e2 protein to initiate transcription and dna replication in the hpv life cycle. our aim was to identify peptides that bind to the hpv16 e2 protein and thereby inhibit its ability to alter the transcriptional activity of other genes.200314614029
detection and genotyping of human papillomavirus dna in cervical cancer tissues with fluorescence polarization.to evaluate the type-specific prevalence of eight common types of human papillomavirus (hpv) in patients with cervical cancer living in shanxi, china, with fluorescence polarization detection, crude dna extracted from 137 samples of early-stage cervical cancer (within stage iia) and chronic cervicitis was subjected to hpv l1 consensus gp5+/gp6+ system. then, the hpv-positive products identified by gp5 + /gp6+ pcr were genotyped based on template-directed dye-terminator incorporation assay with f ...200314614542
microsatellite analysis of early stage (ia-iib) uterine cervical squamous carcinoma.cervical cancer is the most common gynecologic malignancy of the developing world. the oncogenic role of human papilloma virus (hpv) is well known. attention is now focusing on the complicit genetic changes, which allow progression of these tumors. regarding these changes, deletion of tumor suppressor genes (loss of heterozygosity [loh]) is the preferred pathway of progression with only a subset manifesting microsatellite instability (msi). implicated loci include 3p14.1-22. several studies sugg ...200314615820
viral warts in organ transplant recipients: new aspects in therapy.the long-term success of organ transplantation depends on the prevention of allograft rejection and improvement in quality of life for the patients. this has been achieved through better immunosuppressive regimens with lower dosages and a new generation of immunosuppressive drugs. however, these immunosuppressive agents not only impair the patient's reactivity to the graft, but also to infectious organisms, thereby making them more susceptible to opportunistic pathogens. because of this, organ t ...200314616341
association of human papillomavirus viral load with hpv16 and high-grade intraepithelial lesion.the aim of the present study was to evaluate the relationship between viral type and copy number of human papillomavirus (hpv) with respect to the grade of cervical disease, and also to identify the existence of an hpv type-dependent viral load effect. dna from 275 exocervical specimens, previously evaluated for histologic diagnosis, were evaluated for hpv presence, hpv type, and viral load. viral load determination was performed using the low stringency pcr method (ls-pcr). significant differen ...200312657116
is bacterial vaginosis associated with cervical intraepithelial neoplasia?previous research has produced conflicting results regarding the association of bacterial vaginosis (bv) and cervical intraepithelial neoplasia (cin). these studies have been weakened in their conclusions mainly by failure to adequately control for the presence of sexually transmitted infections (stis). one proposed mechanism suggesting that carcinogenic nitrosamines acting either independently or via human papilloma virus (hpv) has not been fully tested previously. we undertook a prospective, c ...200312657117
[definitive role of polar residue clusters in b-dna major groove recognition by protein factors].the 3d structural data for a number of protein-dna complexes were used to analyze the regions of specific contact with the major groove of b-dna double helix. the set included seven nonhomologous complexes featuring 12 dna-binding domains of transcription factors and regulatory factors. the protein domains differed in structure, contained different motifs in the binding region, and broadly varied in chain length, from 30 to 200 residues. protein-dna interaction was assessed as hydrogen bonding b ...200312723474
infection with the oncogenic human papillomavirus type 59 alters protein components of the cornified cell envelope.infection of the genital tract with human papillomaviruses (hpvs) leads to proliferative and dysplastic epithelial lesions. the mechanisms used by the virus to escape the infected keratinocyte are not well understood. infection of keratinocytes with hpv does not cause lysis, the mechanism used by many viruses to release newly formed virions. for hpv 11, a type associated with a low risk of neoplastic disease, the cornified cell envelope (cce) of infected keratinocytes is thin and fragile, and tr ...200312726726
brca1 associates with human papillomavirus type 18 e2 and stimulates e2-dependent transcription.brca1 is a breast and ovarian cancer-related tumor suppressor and has a role in transcriptional activation. we show here that brca1 enhances human papillomavirus type 18 (hpv-18) e2-dependent transcription in vivo. using biochemical approaches, we discovered that brca1 interacts with the carboxyl-terminus of hpv-18 e2 protein in vivo and in vitro. point mutations in the c-terminus make brca1 defective in transcriptional activation in e2-dependent transcription. this finding suggests that the c-t ...200312767931
anogenital human papillomavirus infection in males. 200315122164
comparison of human papillomavirus dna levels in gynecological cancers: implication for cancer development.we have previously demonstrated the presence of human papillomavirus (hpv) dna in several gynecological cancers using conventional pcr. in the present study, to further understand the role of hpv in malignant transformation of these cancers, the infection rates and viral loads of hpv 16 and 18 in gynecological cancers were analyzed using real-time quantitative pcr (qpcr). hpv 16 dna was detected in 61.0% (58/95), 15.2% (7/46) and 32.1% (18/56) of cases of cervical, endometrial and ovarian cancer ...200315004491
identification of a novel promoter in the e2 open reading frame of the human papillomavirus type 18 genome.northern blot and rt-pcr analyses indicated that the human papillomavirus e4 open reading frame is expressed in hela cells. because integration at the e1 or e2 open reading frame would place the viral upstream regulatory region downstream of the viral late genes, the expression of e4 in hela cells is most likely regulated by host cellular promoter(s) or unidentified viral promoter(s) in the e2 region. primer extension analysis and transient transfection experiments with luciferase reporter const ...200312436488
coupling of chemical extraction and expanded-bed adsorption for simplified inclusion-body processing: optimization using surface plasmon resonance.integration of the chemical extraction of recombinant inclusion-body protein from escherichia coli, and its recovery by metal-affinity expanded-bed adsorption (imac-eba) under denaturing conditions, was investigated. the viral coat protein l1 with a hexa-histidine tag was expressed in escherichia coli hms174(de3) as a model protein. interference of released host dna with adsorbent fluidization in the eba step was solved by selective precipitation using spermine and low-speed centrifugation. howe ...200312451558
the nd10 component promyelocytic leukemia protein relocates to human papillomavirus type 1 e4 intranuclear inclusion bodies in cultured keratinocytes and in warts.human papillomavirus type 1 (hpv1) e4 protein is associated with cytoplasmic and nuclear inclusions in productively infected keratinocytes. here we have used transient expression of hpv1 e4 (also known as e1e4) protein in keratinocytes to reproduce formation of e4 inclusions. immunofluorescence analysis showed that progressive formation of inclusions correlated with diminished colocalization between e4 and keratin intermediate filaments (ifs). our results support a model in which the hpv1 e4-ker ...200312477870
p16ink4a as a marker for cervical dyskaryosis: cin and cgin in cervical biopsies and thinprep smears.to examine the potential of p16(ink4a) as a biomarker for dysplastic squamous and glandular cells of the cervix in tissue sections and thinprep smears.200312499437
endogenous human papillomavirus e6 and e7 proteins differentially regulate proliferation, senescence, and apoptosis in hela cervical carcinoma cells.cervical cancer cells express high-risk human papillomavirus (hpv) e6 and e7 proteins, and repression of hpv gene expression causes the cells to cease proliferation and undergo senescence. however, it is not known whether both hpv proteins are required to maintain the proliferative state of cervical cancer cells, or whether mutations that accumulate during carcinogenesis eliminate the need for one or the other of them. to address these questions, we used the bovine papillomavirus e2 protein to r ...200312502868
baseline cytology, human papillomavirus testing, and risk for cervical neoplasia: a 10-year cohort analysis.annual pap smear screening has been favored over less frequent screening in the united states to minimize the risk of cervical cancer. we evaluated whether simultaneous screening with a pap test and human papillomavirus (hpv) testing is useful for assessing the risk for cervical intraepithelial neoplasia (cin) 3 or cervical cancer.200312509400
human papillomavirus type 16 e2 protein has no effect on transcription from episomal viral dna.the human papillomavirus (hpv) e2 protein plays an important role in viral dna replication. many studies with high-risk hpvs have demonstrated that the e2 protein can also repress transcription of the e6 and e7 oncogenes. this conclusion, based on experiments carried out with cervical cancer cells bearing integrated hpv genomes, is currently assumed to be applicable to the normal hpv life cycle, in which the viral genomes are episomal. here, we have tested experimentally whether this assumption ...200312525636
the e6 and e7 proteins of the cutaneous human papillomavirus type 38 display transforming properties.several studies have suggested the involvement of cutaneous human papillomaviruses (hpvs) in the development of nonmelanoma skin cancers. here we have characterized the in vitro properties of e7 proteins of three cutaneous hpv types, 10, 20, and 38, which are frequently detected in skin specimens. we show that hpv38 e7 is able to inactivate the tumor suppressor prb and induces loss of g(1)/s transition control, a key event in carcinogenesis. in contrast, hpv10 and hpv20 e7 proteins do not displa ...200312525654
antibody response to a viral transcriptional regulator.the e2 transcriptional activator of the human papillomavirus regulates the expression of most viral transcripts. its binding to specific target dna sequences involves large conformational changes in the interacting macromolecules. the high stability of the e2:dna complex prompted us to analyze the role of macromolecular interactions and adjuvant emulsions in the appearance of conformation-specific antibodies. we demonstrate that immunization with free or dna-complexed e2 emulsified in an oil-in- ...200312527387
abrogation of the retinoblastoma tumor suppressor checkpoint during keratinocyte immortalization is not sufficient for induction of centrosome-mediated genomic instability.deregulation of the retinoblastoma (prb) tumor suppressor pathway and telomerase activation have been identified as rate-limiting steps for immortalization of primary human epithelial cells. however, additional molecular aberrations including p53 inactivation, ras activation, and deregulation of protein phosphatase 2a activity are necessary for full transformation of immortalized epithelial cells. genomic instability is observed in most human tumors and constitutes an important mechanism to allo ...200312543805
the changing clinical spectrum of human immunodeficiency virus (hiv)-related oral lesions in 1,000 consecutive patients: a 12-year study in a referral center in mexico.in developing countries, the variations in the clinical spectrum of human immunodeficiency virus (hiv)-related oral lesions over time, and the possible effects of antiretroviral therapy, have not been described. in this study we evaluate the clinical spectrum of oral lesions in a series of hiv-infected patients when first examined at the acquired immunodeficiency syndrome (aids) clinic of a tertiary care institution in mexico city, mexico, and the changes observed over 12 years. all hiv-infected ...200312544709
evaluation of antibody response to human papillomavirus early proteins in women in whom cervical cancer developed 1 to 20 years later.infection with oncogenic human papillomaviruses (hpvs) is the most important cause of cervical cancer worldwide. after infection there is a long latency period of at least 10 to 15 years during which cervical cancer develops in a small proportion of originally infected women. up to 50% of these women have at diagnosis antibodies to the hpv oncoproteins e6 and e7, which are rarely found among healthy women. our purpose was to evaluate whether antibodies to hpv16 and hpv18 e6 and e7 proteins are u ...200312548195
polymorphisms and mutations found in the regions flanking exons 5 to 8 of the tp53 gene in a population at high risk for esophageal cancer in south africa.a previous study in esophageal cancer (ec) patients from south africa showed that 17% of tumors contained somatic mutations, including small deletions, insertions, and point mutations, resulting in frameshifts or amino acid changes in exons 5-8 of the tp53 gene. in the present study, polymerase chain reaction single-strand conformation polymorphism and dna sequence analysis were used to search for sequence variation in the regions flanking exons 5-8 in a series of 74 primary human esophageal squ ...200312550754
polymorphisms for chemical metabolizing genes and risk for cervical neoplasia.infection with high-risk human papillomavirus (hpv) plays a major role in the etiology of cervical cancer (cc). however, most infected women do not develop cancer. therefore, exposure to other carcinogenic agents may be a contributing risk factor for cc. we investigated the hypothesis that environmental exposure to cigarette smoke and inheritance of polymorphic chemical metabolizing genes (cyp2e1, gstm1, and meh) significantly increase the risk for neoplasia. we selected 76 cases with high-grade ...200312552594
human papillomavirus type 18 and rapidly progressing cervical intraepithelial neoplasia.human papillomavirus type 18 (hpv-18) is the second most frequent of the hpv types detected when squamous-cell cancer is diagnosed and the type most strongly associated with adenocarcinoma of the cervix. however, in cross-sectional studies, hpv-18 is rarely detected at the time of diagnosis of high-grade cervical intraepithelial neoplasia (cin). we used a longitudinal study design to describe the occurrence of cytological abnormality after incident hpv-18 and hpv-16 infections.200312517465
giant condyloma of buschke-loewenstein in association with erythroderma.the buschke-loewenstein tumour is regarded as a type of verrucous carcinoma occurring on anogenital mucosal surfaces. the tumour is locally invasive but displays a benign cytology and rarely metastasizes. it is associated with human papillomavirus types 6 and 11. we describe a case of buschke-loewenstein tumour occurring in a 61-year-old man which behaved in a locally aggressive manner and was associated with human papillomavirus type 16 and erythroderma which proved resistant to treatment. the ...200312558630
epidemiologic classification of human papillomavirus types associated with cervical cancer.infection with human papilloma virus (hpv) is the main cause of cervical cancer, but the risk associated with the various hpv types has not been adequately assessed.200312571259
treatment of human papillomavirus (hpv) type 16-infected cells using herpes simplex virus type 1 thymidine kinase-mediated gene therapy transcriptionally regulated by the hpv e2 protein.human papillomavirus type 16 (hpv-16) is associated with development of anogenital squamous cell cancers (sccs) and their precursor, intraepithelial neoplasia (in). few approaches to the treatment of in to prevent scc are targeted specifically to hpv. we have designed an hpv-specific therapy using the herpes simplex virus type 1 thymidine kinase (hsv-1 tk) gene driven by an hpv-specific promoter in the hpv-16 long control region (lcr) (nucleotide 7450-nucleotide 104), which is regulated by the h ...200312573058
gene transfer to subdermal tissues via a new gene gun design.although particle-mediated gene transfer technology (gene gun) has been applied for gene transfer to external tissues, the application of this technology to other tissues has met with limited success. here we report the development of a new design of a gene gun that uses helium discharge to propel dna-coated gold beads that are suspended in liquid. higher discharge pressures allow for the delivery of dna to deeper tissues. using the new gene gun to deliver a luciferase expression plasmid resulte ...200312573061
a transcriptional initiator overlaps with a conserved yy1 binding site in the long control region of human papillomavirus type 16.a single promoter has so far been found in the long control region (lcrs) of human papillomavirus-16 (hpv-16). multiple promoters exist in the lcrs of several other papillomaviruses, which are spliced to become mrnas for late and some early genes. here we have investigated whether such promoters exist in the lcr of hpv-16. in in vitro transcription experiments, we detected a strong transcript starting 280 bp downstream from the 3' end of the l1 gene between a nuclear matrix attachment region and ...200312573593
combined suicide gene and immunostimulatory gene therapy using aav-mediated gene transfer to hpv-16 transformed mouse cell: decrease of oncogenicity and induction of protection.to test the effects of combined transduction of a suicide gene and genes coding for various immunostimulatory factors on the oncogenicity and immunogenicity of tc-1 cells (hpv-16 transformed c57bl/6 mouse cells), several bicistronic recombinant adeno-associated viruses (raav) were constructed. each of these constructs carried, and in infected cells expressed, the herpes simplex type 1 thymidine-kinase gene (hsv-tk) and the gene of one of the following immunostimulatory factors: human monocyte ch ...200312579310
chemoimmunotherapy in mice carrying hpv16-associated, mhc class i+ and class i- tumours: effects of cbm-4a potentiated with il-2, il-12, gm-csf and genetically modified tumour vaccines.the effectiveness of chemoimmunotherapy with ifosfamide derivative cbm-4a and recombinant il-2, il-12, gm-csf, or genetically modified, cytokine-producing tumour vaccines was examined in mice carrying hpv16-associated, mhc class i+ (tc-1), and mhc class i- (mk16) tumours. intraperitoneal treatment of tc-1 or mk16 tumour-bearing mice with cbm-4a produced a significant tumour-inhibitory effect. when the i.p. treatment of the mhc class i+ tc-1 tumour-bearing mice with cbm-4a was followed by peritum ...200312579325
urbanization and the incidence of abnormalities of squamous and glandular epithelium of the cervix.the large data bases of the dutch cervical screening program can be exploited to establish the relation between urbanization and the incidence of abnormalities of the squamous and glandular epithelium, including mild or greater changes of the squamous and glandular epithelium of the cervix.200312589639
topical imiquimod 5% cream as an effective treatment for external genital and perianal warts in different patient populations.genital infection with human papillomavirus, the cause of genital warts, is one of the most common sexually transmitted diseases.200312567169
distribution of human papillomavirus in a family planning population in nairobi, kenya.in sub-saharan africa, cervical cancer is the leading cancer among women. the causative role of different human papillomavirus (hpv) types in cervical cancer is established, but the distribution of hpv types within this region is largely unknown.200312567172
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