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a highly sensitive quantum dots-dna nanobiosensor based on fluorescence resonance energy transfer for rapid detection of nanomolar amounts of human papillomavirus 18.a very sensitive and convenient nanobiosensor based on fluorescence resonance energy transfer (fret) was developed for the detection of a 22-mer oligonucleotides sequence in human papillomavirus 18 virus (hpv18) gene. for this purpose, water-soluble cdte quantum dots (qds) were synthesized and, subsequently, amino-modified 11-mer oligonucleotide as one of the two necessary probes was attached to qds surface to form functional qds-dna conjugates. right after addition of the qds-dna and a second c ...201728081500
circulating human papillomavirus dna detected using droplet digital pcr in the serum of patients diagnosed with early stage human papillomavirus-associated invasive carcinoma.specific human papillomavirus genotypes are associated with most ano-genital carcinomas and a large subset of oro-pharyngeal carcinomas. human papillomavirus dna is thus a tumour marker that can be detected in the blood of patients for clinical monitoring. however, data concerning circulating human papillomavirus dna in cervical cancer patients has provided little clinical value, due to insufficient sensitivity of the assays used for the detection of small sized tumours. here we took advantage o ...201627917295
brd4 activates early viral transcription upon human papillomavirus 18 infection of primary keratinocytes.human papillomaviruses (hpvs) replicate in the cutaneous and mucosal epithelia, and the infectious cycle is synchronous with the differentiation program of the host keratinocytes. the virus initially infects dividing cells in the lower layers of the epithelium, where it establishes a persistent infection. the viral genome is maintained as a low-copy-number, extrachromosomal element in these proliferating cells but switches to the late stage of the life cycle in differentiated cells. the cellular ...201627879331
serine/arginine-rich splicing factor 3 and heterogeneous nuclear ribonucleoprotein a1 regulate alternative rna splicing and gene expression of human papillomavirus 18 through two functionally distinguishable cis elements.human papillomavirus 18 (hpv18) is the second most common oncogenic hpv type associated with cervical, anogenital, and oropharyngeal cancers. like other oncogenic hpvs, hpv18 encodes two major (one early and one late) polycistronic pre-mrnas that are regulated by alternative rna splicing to produce a repertoire of viral transcripts for the expression of individual viral genes. however, rna cis-regulatory elements and trans-acting factors contributing to hpv18 alternative rna splicing remain unkn ...201627489271
an exploration of individual- and population-level impact of the 2-dose hpv vaccination schedule in pre-adolescent girls.since 2014, several countries have implemented a 2-dose schedule for human papillomavirus (hpv) vaccination. licensure of the 2-dose schedule was based on non-inferiority results from immunobridging studies, comparing the antibody levels of the 2-dose schedule in young girls to those of the 3-dose schedule in young adults. since licensure, additional data on antibody levels and other aspects of the immune response and clinical effectiveness have become available. this review will discuss the cur ...201627171128
human papillomavirus 18 genetic variation and cervical cancer risk worldwide.human papillomavirus 18 (hpv18) is the second most carcinogenic hpv type, after hpv16, and it accounts for approximately 12% of squamous cell carcinoma (scc) as well as 37% of adenocarcinoma (adc) of the cervix worldwide. we aimed to evaluate the worldwide diversity and carcinogenicity of hpv18 genetic variants by sequencing the entire long control region (lcr) and the e6 open reading frame of 711 hpv18-positive cervical samples from 39 countries, taking advantage of the international agency for ...201526269181
in silico docking to explicate interface between plant-originated inhibitors and e6 oncogenic protein of highly threatening human papillomavirus 18.the leading cause of cancer mortality globally amongst the women is due to human papillomavirus (hpv) infection. there is need to explore anti-cancerous drugs against this life-threatening infection. traditionally, different natural compounds such as withaferin a, artemisinin, ursolic acid, ferulic acid, (-)-epigallocatechin-3-gallate, berberin, resveratrol, jaceosidin, curcumin, gingerol, indol-3-carbinol, and silymarin have been used as hopeful source of cancer treatment. these natural inhibit ...201526175664
gene silencing and activation of human papillomavirus 18 is modulated by sense promoter associated rna in bidirectionally transcribed long control region.recently various studies have demonstrated the role of promoter associated non-coding rnas (prna) in dsrna induced transcriptional gene silencing and activation. however the exact mechanistic details of these processes with respect to the orientation of prnas are poorly defined.201526047143
the nuclear dna sensor ifi16 acts as a restriction factor for human papillomavirus replication through epigenetic modifications of the viral promoters.the human interferon-inducible ifi16 protein, an innate immune sensor of intracellular dna, was recently demonstrated to act as a restriction factor for human cytomegalovirus (hcmv) and herpes simplex virus 1 (hsv-1) infection by inhibiting both viral-dna replication and transcription. through the use of two distinct cellular models, this study provides strong evidence in support of the notion that ifi16 can also restrict human papillomavirus 18 (hpv18) replication. in the first model, an immort ...201525972554
a novel dithiocarbamate derivative induces cell apoptosis through p53-dependent intrinsic pathway and suppresses the expression of the e6 oncogene of human papillomavirus 18 in hela cells.dithiocarbamates (dtcs) exhibit a broad spectrum of antitumor activities, however, their molecular mechanisms of antitumor have not yet been elucidated. previously, we have synthesized a series of novel dithiocarbamate derivatives. these dtcs were examined for cytotoxic activities against five human cancer cell lines. in this study, one of dithiocarbamate (dtc1) with higher potential for hela cells was chosen to investigate molecular mechanisms for its anti-tumor activities. dtc1 could inhibit p ...201525772545
inconclusive evidence for non-inferior immunogenicity of two- compared with three-dose hpv immunization schedules in preadolescent girls: a systematic review and meta-analysis.the european medicines agency (ema) recently approved two-dose immunization schedules for bivalent (hpv 16/18) and quadrivalent (hpv 6/11/16/18) human papillomavirus (hpv) vaccines in nine to fourteen and thirteen year-old-girls, respectively. registration was based on trials comparing immunogenicity of two-dose schedules in girls 9-14 years to three-dose schedules in young women 15-26 years. we evaluate comparability of antibody levels between and within age groups and discuss potential implica ...201525709084
ccctc-binding factor recruitment to the early region of the human papillomavirus 18 genome regulates viral oncogene expression.host cell differentiation-dependent regulation of human papillomavirus (hpv) gene expression is required for productive infection. the host cell ccctc-binding factor (ctcf) functions in genome-wide chromatin organization and gene regulation. we have identified a conserved ctcf binding site in the e2 open reading frame of high-risk hpv types. using organotypic raft cultures of primary human keratinocytes containing high-risk hpv18 genomes, we show that ctcf recruitment to this conserved site regu ...201525694598
mir-34a inhibits viability and invasion of human papillomavirus-positive cervical cancer cells by targeting e2f3 and regulating survivin.previous studies confirmed that high-risk human papillomavirus (hr-hpv) infection is a risk factor of cervical cancer, and the infection was associated with significantly reduced mir-34a expression during carcinogenesis. however, the downstream targets of mir-34a and their roles are still not well understood. this study explored the regulative role of mir-34a on e2f3 and survivin expression and the viability and invasion of hpv-positive cervical cancer cells.201525675046
zombies in tcga.next-generation sequencing results obtained to detect somatic mutations in human cancers can also be searched for viruses that contribute to cancer. recently, human papillomavirus 18 rna was detected in tumor types not typically associated with hpv infection. analyses reported in this issue of journal of virology demonstrate that the apparent presence of hpv18 rna in these atypical tumors is due in at least some cases to contamination of samples with hela cells, which harbor hpv18.201525631081
hela nucleic acid contamination in the cancer genome atlas leads to the misidentification of human papillomavirus 18.we searched the cancer genome atlas (tcga) database for viruses by comparing non-human reads present in transcriptome sequencing (rna-seq) and whole-exome sequencing (wxs) data to viral sequence databases. human papillomavirus 18 (hpv18) is an etiologic agent of cervical cancer, and as expected, we found robust expression of hpv18 genes in cervical cancer samples. in agreement with previous studies, we also found hpv18 transcripts in non-cervical cancer samples, including those from the colon, r ...201525631090
human papillomavirus 18 as a poor prognostic factor in stage i-iia cervical cancer following primary surgical treatment.this study evaluates the effect of the specific human papillomavirus (hpv) genotype as a prognostic factor in stage i-iia cervical cancer patients following primary surgical treatment.201425469338
human papillomavirus genotype distribution in cervical intraepithelial neoplasia grade 2/3 and invasive cervical cancer in japanese women.human papillomavirus vaccines are being introduced worldwide and are expected to reduce the incidence of cervical cancer. here we report a cross-sectional study using a validated human papillomavirus genotyping method to reveal the human papillomavirus prevalence and genotype distribution in japanese women with cervical intraepithelial neoplasia grade 2/3 and invasive cervical cancer.201425156680
comprehensive high-throughput rna sequencing analysis reveals contamination of multiple nasopharyngeal carcinoma cell lines with hela cell genomes.in an attempt to explore infectious agents associated with nasopharyngeal carcinomas (npcs), we employed our high-throughput rna sequencing (rna-seq) analysis pipeline, rna compass, to investigate the presence of ectopic organisms within a number of npc cell lines commonly used by npc and epstein-barr virus (ebv) researchers. sequencing data sets from both cne1 and hone1 were found to contain reads for human papillomavirus 18 (hpv-18). subsequent real-time reverse transcription-pcr (rt-pcr) anal ...201424991015
a dna methylation classifier of cervical precancer based on human papillomavirus and human genes.testing for high-risk (hr) types of human papillomavirus (hpv) is highly sensitive as a screening test of high-grade cervical intraepithelial neoplastic (cin2/3) disease, the precursor of cervical cancer. however, it has a relatively low specificity. our objective was to develop a prediction rule with a higher specificity, using combinations of human and hpv dna methylation. exfoliated cervical specimens from colposcopy-referral cohorts in london were analyzed for dna methylation levels by pyros ...201424535756
optimization of virus detection in cells using massively parallel sequencing.massively parallel sequencing (mps)-based virus detection has potential regulatory applications. we studied the ability of one of these approaches, based on degenerate oligonucleotide primer (dop)-polymerase chain reaction (pcr), to detect viral sequences in cell lines known to express viral genes or particles. dop-pcr was highly sensitive for the detection of small quantities of isolated viral sequences. detected viral sequences included nodavirus, bracovirus, and endogenous retroviruses in hig ...201424309095
mycoplasma genitalium infection is associated with microscopic signs of cervical inflammation in liquid cytology specimens.cervicitis is a common clinical finding often attributed to sexually transmitted infections (stis), but no etiologic agent is identified in the majority of cases. in this study, we comparatively assessed inflammation among the common infectious etiologies of cervicitis and assessed the potential value of liquid cytology specimens for predicting stis. among 473 louisiana women at low risk for acquiring stis, the prevalences of mycoplasma genitalium, chlamydia trachomatis, neisseria gonorrhoeae, a ...201424759719
papillary squamous cell carcinoma of the trachea associated with human papillomavirus-18 infection.a 75-year-old man presented with the chief complaints of coughing and dyspnea. chest computed tomography revealed narrowing of the trachea. a tumor measuring 40×33×15 mm in size that caused -90% reduction in the cross-sectional area of the trachea 4 cm above the carina was cauterized with high-frequency electrocautery via a rigid bronchoscope. a pathological examination revealed papillary squamous cell carcinoma with immunohistochemical p16 overexpression. multiplex polymerase chain reaction con ...201324334586
a low density microarray method for the identification of human papillomavirus type 18 variants.we describe a novel microarray based-method for the screening of oncogenic human papillomavirus 18 (hpv-18) molecular variants. due to the fact that sequencing methodology may underestimate samples containing more than one variant we designed a specific and sensitive stacking dna hybridization assay. this technology can be used to discriminate between three possible phylogenetic branches of hpv-18. probes were attached covalently on glass slides and hybridized with single-stranded dna targets. p ...201324077317
evolution and taxonomic classification of alphapapillomavirus 7 complete genomes: hpv18, hpv39, hpv45, hpv59, hpv68 and hpv70.the species alphapapillomavirus 7 (alpha-7) contains human papillomavirus genotypes that account for 15% of invasive cervical cancers and are disproportionately associated with adenocarcinoma of the cervix. complete genome analyses enable identification and nomenclature of variant lineages and sublineages.201323977318
prognostic value of human papillomavirus types 16 and 18 dna physical status in cervical intraepithelial neoplasia.the aim of this work was to assess the value of the physical status of human papillomavirus (hpv) dna as a disease marker for cervical cancer development in a set of 248 dna samples previously genotyped as hpv 16 or 18, by calculating the e2/e6 ratio through real-time pcr. there was a significant difference in integration status according to disease grade for both genotypes (p <0.001). furthermore, especially for hpv 18, determining the dna physical status could be a useful biomarker in predicti ...201323659555
engagement of the atr-dependent dna damage response at the human papillomavirus 18 replication centers during the initial amplification.we have previously demonstrated that the human papillomavirus (hpv) genome replicates effectively in u2os cells after transfection using electroporation. the transient extrachromosomal replication, stable maintenance, and late amplification of the viral genome could be studied for high- and low-risk mucosal and cutaneous papillomaviruses. recent findings indicate that the cellular dna damage response (ddr) is activated during the hpv life cycle and that the viral replication protein e1 might pla ...201323135710
human papillomavirus 18 e1^e4 protein interacts with cyclin a/cdk 2 through an rxl motif.the human papilloma virus e4 protein is highly expressed in late times of infection. evidence to date suggests that e4 is essential for amplification of the viral genome and that it can influence cell cycle. examination of the sequences encoding the e4 proteins from several genotypes of human papillomavirus revealed the presence of rxl-containing motifs reminiscent of the cyclin-binding motifs that have been identified in several cyclin-binding proteins. when baculovirus-produced human cyclin e ...201323065011
mediator probe pcr: a novel approach for detection of real-time pcr based on label-free primary probes and standardized secondary universal fluorogenic reporters.the majority of established techniques for monitoring real-time pcr amplification involve individual target-specific fluorogenic probes. for analysis of numerous different targets the synthesis of these probes contributes to the overall cost during assay development. sequence-dependent universal detection techniques overcome this drawback but are prone to detection of unspecific amplification products. we developed the mediator probe pcr as a solution to these problems.201222923452
anal canal neuroendocrine carcinoma associated with squamous intraepithelial neoplasia: a human papillomavirus 18-related lesion.neuroendocrine carcinoma (nec) of the anal canal is exceedingly rare and its histogenesis is poorly understood. we present a case of small-cell nec of the anal canal in a 70-year-old woman. the nec appeared as a submucosal tumor at the dentate line and was associated with squamous intraepithelial neoplasia (sin). the nec was positive for neuroendocrine markers including synaptophysin, chromogranin a and cd56, whereas the sin component did not express any of these markers. both components exhibit ...201222524667
clear cell adenosquamous carcinoma of the cervix: a case report with discussion of the differential diagnosis.clear cell adenosquamous carcinoma is an extremely rare and recently described variant of adenosquamous carcinoma of the cervix. it has a unique histologic appearance and has been shown to be associated with human papillomavirus-18. its significance lies in the fact that it is associated with an aggressive clinical course and has to be differentiated microscopically from clear cell carcinoma and glassy cell carcinoma.201222498949
effect of sinecatechins on hpv-activated cell growth and induction of apoptosis.green tea catechins possess a wide range of pharmacological properties, including antiviral, anti-infective, and immunostimulatory properties. they also have demonstrated inhibitory effects on a variety of enzymatic and metabolic pathways involved in cancer development. catechins have been shown to have antiproliferative properties in various cell lines and may have direct virucidal effect. the united states food and drug administration has approved a topical ointment formulation of sinecatechin ...201222468171
site-directed mutagenesis of human papillomavirus 18 promoter elements and tissue-specific expression in cervical carcinoma cells.in this study, the effect of mutations in transcription factor-binding elements was investigated in the human papillomavirus (hpv) 18 p(105) promoter. site-directed mutagenesis activities, in the ap1/yy1-, krf-1-, gre/yy1-, sp1- and the double mutation (ap1/yy1- and gre/yy1)-binding sites were assessed in five human cell lines: hela (hpv18-positive cervical carcinoma), siha (hpv16-positive cervical carcinoma), c33a (hpv-negative cervical carcinoma), h1299 (non-small cell lung carcinoma) and mrc- ...201222350992
human papillomavirus 18 e6 inhibits phosphorylation of p53 expressed in hela cells.abstract: background: in hpv infected cells p53 function is abrogated by e6 and even ectopically expressed p53 is unable to perform tumor suppressor functions. in addition to facilitating its degradation, e6 may also inhibit p53 transactivity, though the mechanisms are still poorly understood. it has been reported that inhibition of p300, an acetyltransferase responsible for p53 acetylation is inactivated by e6. activation of overexpressed p53 to cause cell growth inhibition is facilitated by i ...201222244155
Human papillomavirus genotype distribution and human papillomavirus 16 and human papillomavirus 18 genomic integration in invasive and in situ cervical carcinoma in human immunodeficiency virus-infected women.Women infected with human immunodeficiency virus (HIV) are at increased risk of developing precancerous and cancerous lesions in cervix because of persistence of oncogenic human papillomavirus (HPV) infection. Scarce information about the HPV genotypes attributed to cervical cancer in the HIV-infected population is available, especially in countries with a low prevalence of this pathology.201121892092
detection of human papillomavirus 18 in cervical cancer samples using pcr-elisa (diapops).human papillomavirus (hpv) infection is a major risk factor for adenocarcinoma of the cervix. the high-risk types of the virus such as hpv16 and hpv18, which possess the e6 and e7 oncogenes, are responsible for approximately 50% of all cervical cancers. a rapid, sensitive and specific test has been proposed for detection of hpv to improve cervical cancer screening programs.201122530085
implication of human papillomavirus-66 in vulvar carcinoma: a case report.abstract:201121702970
Integration of human papillomavirus 18 DNA in esophageal carcinoma 109 cells.To detect human papillomavirus (HPV) DNA in esophageal carcinoma (EC) 109 cells and investigate the relationship between HPV and EC.201122072858
is human papillomavirus genotype an influencing factor on radiotherapy outcome? ambiguity caused by an association of hpv 18 genotype and adenocarcinoma histology.to evaluate whether human papillomavirus (hpv) genotype is associated with poor prognosis of uterine cervical cancer treated primarily with radiotherapy.201121607093
accumulation of p21 proteins at dna damage sites independent of p53 and core nhej factors following irradiation.the cyclin-dependent kinase (cdk) inhibitor p21 plays key roles in p53-dependent dna-damage responses, i.e., cell cycle checkpoints, senescence, or apoptosis. p21 might also play a role in dna repair. p21 foci arise at heavy-ion-irradiated dna-double-strand break (dsb) sites, which are mainly repaired by nonhomologous dna-end-joining (nhej). however, no mechanisms of p21 accumulation at double-strand break (dsb) sites have been clarified in detail. recent works indicate that ku70 and ku80 are es ...201121787748
the use of a human papillomavirus 18 promoter for tissue-specific expression in cervical carcinoma cells.the use of tissue-specific promoter elements in the treatment of cervical cancer has been explored in this paper. the p(105) promoter of human papillomavirus 18 (hpv18) was utilised to direct tissue-specific expression in a number of cell types. expression was examined in three cervical carcinoma cell lines: hela (hpv18 positive), siha (hpv16 positive), and c33a cells (hpv negative); the epithelial cell line, h1299; and the foetal fibroblast cell line, mrc5, utilising a luciferase expression vec ...201121786035
associations of human leukocyte antigen class ii genotypes with human papillomavirus 18 infection and cervical intraepithelial neoplasia risk.background: only a small proportion of women infected with human papillomavirus type 18 (hpv18) may progress to persistent infection and cervical neoplasia. this community-based cohort study aimed to assess associations with human leukocyte antigen (hla) class ii genotypes for natural infection of hpv18 and subsequent risk of cervical neoplasia. methods: among 10,190 cytologically normal participants, 125 with hpv18 infection were identified by hpv blot kit. hpv18 viral load at study entry was e ...201121692064
regulation of na(+)-coupled glucose carrier sglt1 by human papillomavirus 18 e6 protein.tumor cells utilize preferably glucose for energy production. they accomplish cellular glucose uptake in part through na(+)-coupled glucose transport mediated by sglt1 (slc5a1). this study explored the possibility that the human papillomavirus 18 e6 protein hpv18 e6 (e6) participates in the stimulation of sglt1 activity. e6 is one of the two major oncoproteins of high-risk human papillomaviruses, which are the causative agent for cervical carcinoma. according to western blotting, sglt1 is expres ...201021156162
characterization of physical binding between human papillomavirus 18 protein e7 and centromere protein c.human papillomaviruses (hpvs) have been linked to a variety of human diseases, most notably cancer of the cervix. in the majority of cases, hpv proteins e6 and e7 are continuously expressed and bind a variety of cellular proteins. the precise mechanism of hpv-induced carcinogenesis has not been fully elucidated; therefore, we attempted to identify the cellular proteins that interact with hpv18 e7 to better understand the function of this important protein. using yeast 2-hybrid screening, we iden ...201021358210
cd4+ t cells against human papillomavirus-18 e7 in patients with high-grade cervical lesions associate with the absence of the virus in the cervix.cervical neoplastic lesions are associated with infection by high-risk human papilloma-viruses (hpv). the two genotypes most frequently found in the lesions are hpv-16 and hpv-18 with a prevalence of 50-60% and 15-18%, respectively. the e6 and e7 viral oncoproteins are involved in the transformation process and represent foreign antigens for the host. we previously reported that anti-hpv-18 e6 cd4(+) t cells are present in patients with high-grade hpv-18-expressing cervical lesions but also in 5 ...201020545782
[clinical features and prognosis of cervical cancer in young women].to investigate the prevalence, etiology, clinical presentation and pathological features, treatment and prognosis of cervical cancer in young women.201020818083
a c-terminal hydrophobic, solvent-protected core and a flexible n-terminus are potentially required for human papillomavirus 18 e7 protein functionality.the oncogenic potential of the high-risk human papillomavirus (hpv) relies on the expression of genes specifying the e7 and e6 proteins. to investigate further the variation in oligomeric structure that has been reported for different e7 proteins, an hpv-18 e7 cloned from a hispanic woman with cervical intraepithelial neoplasia was purified to homogeneity most probably as a stable monomeric protein in aqueous solution. we determined that one zinc ion is present per hpv-18 e7 monomer by amino aci ...201020211680
assessing protein stability of the dimeric dna-binding domain of e2 human papillomavirus 18 with molecular dynamics.the objective of this study is to understand the structural flexibility and curvature of the e2 protein of human papillomavirus type 18 using molecular dynamics (6 ns). e2 is required for viral dna replication and its disruption could be an anti-viral strategy. e2 is a dimer, with each monomer folding into a stable open-faced beta-sandwich. we calculated the mobility of the e2 dimer and found that it was asymmetric. these different mobilities of e2 monomers suggest that drugs or vaccines could b ...201020428668
human papillomavirus-16/18 as04-adjuvanted cervical cancer vaccine: immunogenicity and safety in healthy chinese women from hong kong.to assess the immunogenicity and safety of human papillomavirus-16/18 as04-adjuvanted cervical cancer vaccine in chinese women aged 18 to 35 years enrolled from hong kong.201020519752
e6 variants of human papillomavirus 18 differentially modulate the protein kinase b/phosphatidylinositol 3-kinase (akt/pi3k) signaling pathway.intra-type genome variations of high risk human papillomavirus (hpv) have been associated with a differential threat for cervical cancer development. in this work, the effect of hpv18 e6 isolates in akt/pkb and mitogen-associated protein kinase (mapks) signaling pathways and its implication in cell proliferation were analyzed. e6 from hpv types 16 and 18 are able to bind and promote degradation of human disc large (hdlg). our results show that e6 variants differentially modulate hdlg degradation ...200919007961
distribution of human papillomavirus genotypes in archival cervical lesions in eastern inner mongolian autonomous region, china.human papillomavirus (hpv) is the main etiologic factor for cervical cancer (cc). to investigate the prevalence of hpv types in archival cc and its precursors collected form tongliao area, which is located in the east of inner mongolian autonomous region, china, and compare the genotype distribution of hpv in cervical lesions between han chinese and mongolian.200919574785
human papilloma virus as a possible factor in the pathogenesis of oral lichen planus.oral lichen planus (olp) is a common chronic inflammatory mucocutaneous disease. clinical diagnosis of olp requires clinical work-up and histologic examination to rule out possible dysplasia and carcinoma. it is possible that oral mucosal viral infections including hpv infection may have a causative role in olp pathogenesis. the aim of this study was to examine the coincidence of human papilloma virus type 18 and oral lichen planus.200921528036
expression and purification of human papillomavirus 18 l1 virus-like particle from saccharomyces cerevisiae.cervical cancer caused by human papillomavirus (hpv) might be successfully prevented by hpv vaccination and screening. hpv vaccination and hpv serology assays have been investigated using hpv virus-like particles (vlps). in this study we produced hpv18 l1 vlps in saccharomyces cerevisiae and purified them. the hpv18 l1 gene was cloned into the yeast expression vector yegalpha-hir525, and transformed into saccharomyces cerevisiae. expression of hpv18 l1 protein was demonstrated by western blottin ...200818365691
[antisense targeting to human papillomavirus 18 e6/e7 affects the proliferation and apoptosis of human cervical carcinoma: an in vitro experiment with hela cells].to investigate the effect of eukaryotic fluorescent expression vector carrying antisense human papillomavirus (hpv) 18 e6/e7 on the growth and proliferation of human cervical carcinoma.200717803852
[cervical-uterine-cancer associated factors in nayarit state, mexico].to establish the association between high-grade intraepithelial lesions and cervical-uterine-cancer, and the infection by human papillomavirus, genetic antecedents, socioeconomics, sexual behavior and gynecology and obstetrics factors in women of the state of nayarit, mexico.200718297855
high-throughput detection of human papillomavirus-18 l1 gene methylation, a candidate biomarker for the progression of cervical neoplasia.the l1 gene of human papillomavirus-18 (hpv-18) is consistently hypermethylated in cervical carcinomas, but frequently hypo- or unmethylated in exfoliated cells from asymptomatic patients. in precancerous lesions, l1 is sporadically hypermethylated, correlating with the severity of the neoplasia. in order to explore the potential of using l1 methylation as a workable biomarker for carcinogenic progression of hpv-18 infections in routinely taken samples, our aim was to develop methylation-detecti ...200717175003
retinoic acid receptor beta silences human papillomavirus-18 oncogene expression by induction of de novo methylation and heterochromatinization of the viral control region.retinoic acid receptor beta2 (rar beta2) is often down-regulated during the multistep process to cervical cancer. in that way, its inhibitory function on the transcription factor ap-1, indispensable to maintain human papillomavirus (hpv) gene expression is relieved. using hpv-18 positive hela cells as a model system, we show that ectopic expression of rar beta2 is able to down-regulate hpv-18 transcription by selectively abrogating the binding of ap-1 to the viral regulatory region in a ligand-i ...200717686773
intratumor injection of small interfering rna-targeting human papillomavirus 18 e6 and e7 successfully inhibits the growth of cervical cancer.human papillomavirus (hpv) 18 is related not only to squamous cell carcinoma of the cervix, but also to adenocarcinoma and small cell carcinoma of the cervix, in which prognosis is known to be poor. small interfering rna (sirna) that targets hpv18 e6 and e7 was tested in hpv18-positive cell lines to investigate its effect and investigate its mechanism of action. nude mice were also tested in a combination of sirna and atelocollagen to determine whether it might be useful as a new molecule-target ...200616865269
induction of cell death in human papillomavirus 18-positive cervical cancer cells by e6 sirna.human cervical cancer is caused by high-risk types of human papillomavirus (hpv) such as hpv16 and hpv18, which possess the e6 and e7 oncogenes, whose concurrent expression is a prerequisite for cancer development and maintaining malignant phenotypes. silencing these oncogenes is considered to be applicable in molecular therapies of human cervical cancer. however, it remains to be determined whether e6, e7, or both should be silenced to obtain most efficient antitumor activity by an hpv small-in ...200616138119
methylation of the human papillomavirus-18 l1 gene: a biomarker of neoplastic progression?epigenetic transcriptional regulation plays an important role in the life cycle of human papillomaviruses (hpvs) and the carcinogenic progression of anogenital hpv associated lesions. we performed a study designed to assess the methylation status of the hpv-18 genome, specifically of the late l1 gene, the adjacent long control region (lcr), and part of the e6 oncogene in cervical specimens with a range of pathological diagnoses. in asymptomatic infections and infections with precancerous (precur ...200616472835
cd4+ t cell immunity against the human papillomavirus-18 e6 transforming protein in healthy donors: identification of promiscuous naturally processed epitopes.infection by 'high-risk' human papillomaviruses (hpv) is associated with the development of neoplastic lesions. hpv-18 is responsible for a very aggressive form of cancer and poor survival. as for other hpv types, immune surveillance has probably a role in the control of the infection. however, very little is known on hpv-18 immunogenicity. cd4(+) t cells from 16 healthy donors were tested ex vivo for reactivity to synthetic peptides corresponding to 3 sequences on the hpv-18 e6 transforming pro ...200515719368
update on pathophysiologic mechanisms of human papillomavirus.the role of the human papillomavirus in the pathogenesis has been the subject of many publications in the recent literature. the physical state of the human papillomavirus and the role of chromosomal aneuploidy has been reported. this review discusses the recent pathological mechanisms described in the genesis of human papillomavirus-related disease.200515711413
chemotherapy compounds in cervical cancer cells primed by reconstitution of p53 function after short interfering rna-mediated degradation of human papillomavirus 18 e6 mrna: opposite effect of sirna in combination with different drugs.constant expression of e6 and e7 mrna by high-risk human papillomaviruses (hpv) abrogates p53 and retinoblastoma protein function, respectively, and is essential for the development of cervical cancer. despite e6, some chemotherapy drugs can stabilize p53 in cervical cancer cells. it is not known how chemotherapy-induced p53 activation and cytotoxicity are affected when the amount of e6 mrna is decreased before the drug treatment. in this study, hpv18-positive hela cervical cancer cells were tra ...200515908516
the human papillomavirus-18 genome is efficiently targeted by cellular dna methylation.human papillomaviruses (hpvs) infect epithelia, including the simple and the squamous epithelia of the cervix, where they can cause cancer and precursor lesions. the molecular events leading from asymptomatic hpv infections to neoplasia are poorly understood. there is evidence that progression is modulated by transcriptional mechanisms that control hpv gene expression. here, we report the frequent methylation of hpv-18 genomes in cell culture and in situ. dna methylation is generally known to le ...200415207633
presence of human papillomavirus-18 and epstein-barr virus in a squamous cell carcinoma of the tongue in a 20-year-old patient. case report and review of the current literature.we report on a squamous cell carcinoma of the tongue in a 20-year-old woman with co-infection of the tumor with human papilloma virus type 18 and epstein-barr virus. to our knowledge, this is the first case of co-infection in carcinoma of the tongue to be reported. we review the present data and theories concerning viral oncogenesis of oral carcinomas.200415450520
transcription-independent triggering of the extrinsic pathway of apoptosis by human papillomavirus 18 e2 protein.cervical carcinomas are most frequently associated with human papillomaviruses (hpv), whose e6 and e7 oncogenes products induce cellular immortalization. the papillomavirus e2 protein is a transcription factor, which represses the expression of the viral oncogenes, and activates viral dna replication during the vegetative viral cycle. this protein is specifically inactivated in hpv18-associated carcinoma cells, suggesting that e2 functions prevent carcinogenic progression. indeed, ectopic expres ...200312527886
comparison of human papillomavirus genotypes, sexual, and reproductive risk factors of cervical adenocarcinoma and squamous cell carcinoma: northeastern united states.although human papillomavirus causes essentially all cervical carcinoma, cofactors may differ by cancer histologic type. we examined human papillomavirus genotypes and sexual and reproductive risk factors for cervical adenocarcinoma and squamous cell carcinoma.200312634637
cloning and expression of the l1 major capsid protein of the human papillomavirus 18 in murine cells.human papillomavirus (hpv) type 18 is strongly associated with the development of cervical cancer. studies of a model system with animal papillomaviruses have demonstrated the importance of neutralizing antibodies in preventing papillomavirus-associated disease. the immune response to hpv is poorly understood, and there are non- standardized serological assays to identify hpv infections. in our study, the assessment of antibody responses against hpvs (previously hampered by the lack of viral sou ...200314612984
prevalence and determinants of human papillomavirus genital infection in men.four-hundred-forty-five husbands of women with invasive cervical carcinoma, 165 of women with in situ cervical cancer, and 717 of control women (age range 19-82 years) were interviewed and a sample of exfoliated cells from the penis obtained in seven case-control studies conducted by the international agency for research on cancer. the characteristics of human papillomavirus-positive and human papillomavirus-negative husbands were compared using odds ratios and 95% confidence intervals. thirteen ...200211875730
three regions of the prb pocket domain affect its inactivation by human papillomavirus e7 proteins.a critical event in papillomavirus transformation of human cells is the inactivation of prb by the e7 protein. e7, like many other viral oncoproteins, possesses a well-characterized lxcxe peptide motif that interacts with the pocket domain of prb. disruption of the lxcxe-binding cleft on prb renders it resistant to e7 binding and inactivation. such binding cleft mutants of prb are capable of inducing a g(1) arrest in the human papillomavirus 18-transformed hela cell line. we show here that the e ...200212021356
isolated human papillomavirus 18-positive extragenital bowenoid papulosis and idiopathic cd4+ lymphocytopenia.we report a case of isolated extragenital bowenoid papulosis (bp) in a young man with an idiopathic low cd4 count. the lesions occurred on the dorsal aspect of his left middle finger and were not associated with genital involvement. polymerase chain reaction studies of a biopsy demonstrated human papillomavirus 18. as far as we are aware, this is the first documented case of bp (genital or extragenital) associated with idiopathic cd4 lymphocytopenia.200111260028
localization of tumor suppressor gene candidates by cytogenetic and short tandem repeat analyses in tumorigenic human bronchial epithelial cells.radon exposure is associated with increased risk for bronchogenic carcinoma. mutagenesis analyses have revealed that radon induces mostly multi-locus chromosome deletions. based on these findings, it was hypothesized that deletion analysis of multiple radon-induced malignant transformants would reveal common mutations in chromosomal regions containing tumor suppressor genes responsible for malignant transformation. this hypothesis was supported by a previous study in which tumorigenic derivative ...200010657959
poor clinical outcome in early stage cervical cancer with human papillomavirus-18 positive lymph nodes.epidemiologic and molecular studies have proven that human papillomavirus (hpv) plays an important role in the development of cervical cancer. however, the role of the virus in the progression of the disease, i.e. in the development of lymph node metastasis and in the adverse clinical outcome is poorly understood. we have been using the polymerase chain reaction (pcr) to study the presence and typing of human papillomavirus dna since 1980 in cervical cancers and pelvic lymph nodes from the same ...200010767518
the structural basis of dna target discrimination by papillomavirus e2 proteins.the papillomavirus e2 proteins regulate the transcription of all papillomavirus genes and are necessary for viral dna replication. disruption of the e2 gene is commonly associated with malignancy in cervical carcinoma, indicating that e2 has a role in regulating tumor progression. although the e2 proteins from all characterized papillomaviruses bind specifically to the same 12-base pair dna sequence, the cancer-associated human papillomavirus e2 proteins display a unique ability to detect dna fl ...200010906136
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
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
development, characterization and distribution of adoptively transferred peripheral blood lymphocytes primed by human papillomavirus 18 e7--pulsed autologous dendritic cells in a patient with metastatic adenocarcinoma of the uterine cervix.we describe a 27-year-old woman with systemic chemoresistant and radioresistant metastatic disease secondary to a recurrence of human papillomavirus (hpv) 18 infected cervical adenocarcinoma of the uterine cervix who received adoptive transfer of peripheral blood t cells stimulated with hpv 18 e7-pulsed autologous dendritic cells (dc). extensive in vitro characterization of the dc-activated t cells derived from peripheral blood mononuclear cells (pbmc) included phenotypic analysis, cytotoxicity ...200010726612
human papillomavirus 18 oncoproteins e6 and e7 enhance irradiation- and chemotherapeutic agent-induced apoptosis in p53 and rb mutated cervical cancer cell lines.tumor suppressor genes p53 and rb are important in cell cycle control. necessity of wild type p53 is implicated in irradiation-induced apoptosis. numerous tumor cells carry p53 mutations and yet are sensitive to irradiation or chemotherapeutic agents. therefore p53-and rb-independent pathways must exist to account for irradiation-induced apoptosis. we evaluated the apoptotic response of a p53- and rb-mutated, human papilloma virus (hpv) negative cervical cancer cell line (c33a), and c33a cell li ...199910410876
cervical cancer in older women: a molecular analysis of human papillomavirus types, hla types, and p53 mutations.the purpose of this study was to evaluate cervical cancers in older women to determine whether they differed from tumors in younger women with respect to human papillomavirus types, frequencies of p53 mutations, and presence of a proposed high-risk hla-dr2 haplotype.19989704765
acinar differentiation by non-malignant immortalized human prostatic epithelial cells and its loss by malignant cells.invasive prostatic carcinomas and prostatic intraepithelial neoplasia (pin) are characterized by a loss of normal cell organization, cell polarity, and cell:cell and cell:basement membrane adhesion. the objective of this study was to establish in vitro three-dimensional (3-d) cell models which can be used to investigate mechanisms involved in acinar morphogenesis and differentiation in normal prostatic epithelium and their abnormalities in cancer cells. the process of acinar morphogenesis, inclu ...19979214606
detection of hela cell contamination--presence of human papillomavirus 18 dna as hela marker in jtc-3, og and oe cell lines.there are warnings of the contamination of cell cultures with hela cells in many laboratories in the world. the cell lines jtc-3, og and oe that were established in okayama in 1959, 1969 and 1971, respectively, were examined for human papillomavirus (hpv) 18 dna by southern blot hybridization. the hpv 18 dna detected in these three cell lines showed hybridization patterns characteristic of the hpv 18 dna in the hela cell line established in 1951. southern hybridization patterns of hpv 18 dna in ...19979556756
androgen responsive adult human prostatic epithelial cell lines immortalized by human papillomavirus 18.prostate cancer and benign tumors of the prostate are the two most common neoplastic diseases in men in the united states, however, research on their causes and treatment has been slow because of the difficulty in obtaining fresh samples of human tissue and a lack of well characterized cell lines which exhibit growth and differentiation characteristics of normal prostatic epithelium. non-neoplastic adult human prostatic epithelial cells from a white male donor were immortalized with human papill ...19979214605
effect of herpes simplex virus on the dna of human papillomavirus 18.some types of human papillomaviruses (hpv) appear to be associated with carcinoma of the cervix or other tissues, but patients infected with hpv do not necessarily develop carcinoma. some epidemiological studies of risk factors for cervical carcinoma have indicated the involvement of herpes simplex virus (hsv). to study the effect of hsv on the genome of hpv, total dnas were extracted and analyzed after hela cells, or a431 cells, transiently transfected with hpv18 dna, were infected with hsv-1 o ...19979298725
cytogenetic and molecular genetic analysis of tumorigenic human bronchial epithelial cells induced by radon alpha particles.to establish a cell culture model for lung carcinogenesis, independent populations of the human papillomavirus 18-immortalized human bronchial epithelial cell line bep2d were treated with high linear energy transfer radon-simulated alpha-particles, expanded and xenotransplanted into nu/nu mice. six independent cell lines were established from tumors that developed from three separate radiation treatments as follows: treatment (tx) 1 (30 cgy--two doses), h2bt, tx 2 (30 cgy--single dose), r30t1l, ...19979214610
[primary carcinoma of bartholin's glands with hpv 18 detection].a primary carcinoma of the bartholin's gland is a rarely type of vulva-carcinoma. the patients median age are 55 years and the etiology of the carcinoma are still unknown. viral influences are discussed. most frequent types of carcinomas of bartholin's gland are those of squamous cells and adenocarcinomas. this article reports on a 55 year old patient with a primary carcinoma of bartholin's gland. the human papillomavirus 18 was detected by a polymerase chain reaction. the correct diagnosis was ...19979173772
binding of human virus oncoproteins to hdlg/sap97, a mammalian homolog of the drosophila discs large tumor suppressor protein.the 9orf1 gene encodes an adenovirus e4 region oncoprotein that requires a c-terminal region for transforming activity. screening a lambdagt11 cdna expression library with a 9orf1 protein probe yielded a novel cellular pdz domain-containing protein, 9bp-1, which binds to wild-type, but not a transformation-defective, c-terminal, mutant 9orf1 protein. the fact that pdz domains complex with specific sequences at the free c-terminal end of some proteins led to the recognition that the 9orf1 c-termi ...19979192623
complex genomic rearrangement within the 12q15 multiple aberration region induced by integrated human papillomavirus 18 in a cervical carcinoma cell line.human papillomavirus (hpv) dna is integrated into the host genome in cervical cancer. the cervical carcinoma cell line sw756 has integrated hpv-18 dna in chromosome region 12q15, in the papillomavirus-associated locus-2 (pal2). by polymerase chain reaction and hybridization of an arrayed cosmid library with oligonucleotides from the rearranged allele, we determined the pre-integration germline structure of the region. pal2 was located approximately 10 kb from sequence-tagged site marker u27131, ...19979210958
re-expression of interleukin 1 in human papillomavirus 18 immortalized keratinocytes inhibits their tumorigenicity in nude mice.the ability to form tumors in nude mice developed spontaneously in the human papillomavirus (hpv)-18 immortalized keratinocyte cell line, 18-11, and is shown here to be accompanied by a loss of interleukin 1 (il-1) alpha and beta expression at both the rna and protein level. in addition, a separate tumorigenic 18-11 derivative and two cervical carcinoma-derived cell lines, hela and caski, were found to have significantly decreased or lost il-1 alpha and il-1 beta expression. using retroviral exp ...19968959334
cytokine regulation of the matrix metalloproteinases and their inhibitors in human papillomavirus-18 transformed human prostatic tumor cell lines.cytokines may play a critical role in influencing the invasive and metastatic behavior of advanced cancers. to investigate the influence of cytokines on tissue inhibitor of metalloproteinase (timp) and matrix metalloproteinase (mmp) expression we have established cultures from prostate tissues of low gleason sum 5 and high gleason sum 10 cancers. we have examined the influence of different cytokines (interleukin [il]-10, il-4, il-6, il-2, and interferon-gamma) on timp-2, mmp-2, and mmp-9 protein ...19968938794
activation of tumor suppressor genes in nontumorigenic revertants of the hela cervical carcinoma cell line.two nontransformed revertants of hela cells, designated ha and hf, were isolated using a selection procedure based on prolonged retention of the fluorescent dye rhodamine 123 within the mitochondria of hela (atcc ccl2) cells versus normal epithelial cells. unlike the parental hela cells, the revertants expressed markedly reduced levels of the bone-liver-kidney, placental, and intestinal isoforms of alkaline phosphatase, exhibited a flat nonrefractile morphology, and failed to grow in suspension ...19968780886
clear cell adenosquamous carcinoma of the cervix. an aggressive tumor associated with human papillomavirus-18.it is well recognized that adenocarcinomas and adenosquamous carcinomas of the cervix are frequently associated with human papillomavirus (hpv)-16 or -18. however, few studies have investigated associations between histologic variants of these tumors and specific types of hpv.19958635063
interferon-alpha elicits downregulation of human papillomavirus 18 mrna in hela cells by selective repression of endogenous viral transcription.we have reported that interferon-alpha inhibits hpv-18 mrna in hela cells. here we examine mechanisms by which ifn could modulate hpv expression. in northern blot experiments, we observed that interferon-alpha 2b treatment reduced hpv-18 mrna levels in a time- and dose-dependent manner, with a maximal effect achieved at 48 h. simultaneously, induction of 2-5a synthetase mrna was verified as indicative of ifn action. the ifn regulatory effect on hpv-18 mrna at 48 h required de novo protein synthe ...19957553218
deletion in human chromosome region 12q13-15 by integration of human papillomavirus dna in a cervical carcinoma cell line.in human cervical carcinomas papillomavirus dna is frequently integrated in the cell genome. we have cloned the integration site of human papillomavirus-18 dna in human chromosome region 12q13-15 present in the sw756 cervical carcinoma cell line. viral dna is broken from nucleotides 2643 to 3418 in the e1 and e2 open reading frames, resulting in a deletion of 775 bases of viral dna. cloning and sequence analysis of the rearranged and germline alleles shows that there is no homology between the t ...19957592643
human papillomavirus types important in progression of inverted papilloma.recent evidence suggests that human papillomavirus may play a role in the pathogenesis of inverted papilloma, a benign but locally aggressive neoplasm with a high recurrence rate and an association with squamous cell carcinoma. histologic features of inverted papilloma have not been useful in discriminating lesions at high risk for malignant transformation. we studied archival pathology specimens from 39 patients with inverted papilloma treated at the university of michigan between 1980 and 1994 ...19957478645
integration site of human papillomavirus type-18 dna in chromosome band 8q22.1 of c4-i cervical carcinoma: dnase i hypersensitivity and methylation of cellular flanking sequences.the c4-i cell line derived from a non-keratinizing squamous cell carcinoma of the uterine cervix contains integrated human papillomavirus-18 dna. fluorescence in situ hybridization of c4-i cells demonstrated a single viral integration site at 8q22.1 on a derivative chromosome originating from an 8q;12q translocation. 8q22 is a site of chromosome fragility and is also recombinogenic in several human malignancies. dnase i hypersensitivity of the integration site was studied with a cellular flankin ...19947507697
human papillomavirus 18-immortalized endocervical cells with in vitro cytokeratin expression characteristics of adenocarcinoma.to determine whether human papillomavirus (hpv) 18 has a role in the development of adenocarcinoma from human endo- or ectocervical cells.19947507226
combined effects of human papillomavirus-18 and n-methyl-n'-nitro-n-nitrosoguanidine on the transformation of normal human oral keratinocytes.we immortalized oral keratinocytes by transfecting them with recombinant human papillomavirus (hpv) type 18 dna and established three cell lines. these lines were morphologically different from their normal counterpart, contained integrated entire hpv-18 dna, and expressed the viral e6/e7 genes. the cells contained less p53 protein and more c-myc mrna than normal cells. however, they proliferated only in keratinocyte growth medium (kgm) containing low calcium and were not tumorigenic in nude mic ...19948142012
laryngeal carcinoma in a 12-year-old child. association with human papillomavirus 18 and 33.a laryngeal squamous cell carcinoma was observed in a 12-year-old child. there was no history of preceding papillomatosis or radiotherapy. we searched for an association with human papillomavirus (hpv).19948123236
keratinocytes immortalized by human papillomavirus-18 exhibit alterations dependent upon host genetic background and complexity of viral genes transfected.keratinocytes immortalized by the human papillomaviruses (hpvs) vary in cell morphology, growth properties, resistance to inducers of terminal differentiation, and karyotype. to determine the contribution of the host cell genetic background and the hpv genes to these cellular alterations, we have generated and characterized 6 human keratinocyte lines from two different newborn foreskins (a and b) using either the full-length hpv18 genome or the isolated hpv18 e6/e7 genes. the growth properties o ...19948031475
detection of hpv dna in oral carcinoma using polymerase chain reaction together with in situ hybridization.this study determined the prevalence of human papillomavirus 16/18 dna in deparaffinized oral carcinoma specimens on slides with the use of the different sensitivities of in situ hybridization and a technique that combines polymerase chain reaction and in situ hybridization. human papillomavirus dna was not detected in the 30 biopsy specimens analyzed by in situ hybridization alone using biotinylated dna probes specific for human papillomavirus 16/18. twenty of 30 specimens (66.7%) were found to ...19948028871
increased e6/e7 transcription in hpv 18-immortalized human keratinocytes results from inactivation of e2 and additional cellular events.we characterized the state of the viral genome and transcription of human papillomavirus 18 oncogenes, e6 and e7, in immortalized human keratinocytes. at passage 9 after transfection with hpv 18 a homogeneous population of immortal clones was present. these cells have the viral dna integrated within the e2 orf, accompanied by its partial deletion, similarly to what has been found in cervical carcinoma specimens. transcription of the e6 and e7 oncogenes is mediated by the major viral early promot ...19921641976
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