• Title/Summary/Keyword: Human papillomavirus 18

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Human Papillomavirus Type 16/18 Oncoproteins: Potential Therapeutic Targets in Non-smoking Associated Lung Cancer

  • Zhang, Er-Ying;Tang, Xu-Dong
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.11
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    • pp.5363-5369
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    • 2012
  • High-risk human papillomavirus (HPV) especially HPV-16 and HPV-18 types are speculated to be important risk factors in non-smoking associated lung cancer in Asia. Increasing evidence has demonstrated that HPV oncoproteins may contribute to lung tumorigenesis and cell transformation. Importantly, HPV 16/18 E6 and E7 oncoproteins can mediate expression of multiple target genes and proteins, such as p53/pRb, VEGF, HIF-$1{\alpha}$, cIAP-2, and hTERT, and contribute to cell proliferation, angiogenesis and cell immortalization through different signaling pathways in lung cancer. This article provides an overview of experiment data on HPV-associated lung cancer, describes the main targets on which HPV E6/E7 oncoproteins act, and further discusses the potential signaling pathways in which HPV E6/E7 oncoproteins are involved. In addition, we also raise questions regarding existing problems with the study of HPV-associated lung cancer.

Cervical Pathology in High-Risk Human Papillomavirus-Positive, Cytologically Normal Women

  • Supho, Buasorn;Supoken, Amornrat;Kleebkaew, Pilaiwan;Kietpeerakool, Chumnan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.18
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    • pp.7977-7980
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    • 2014
  • This study was undertaken to evaluate the prevalence of significant cervical pathology among women who are high-risk human papillomavirus (HR-HPV)-positive/cytology negative, the most common combination of positive co-tests. The records of 244 women HR-HPV-positive/cytology-negative who had undergone colposcopy at Srinagarind Hospital, Khon Kaen University during January 2010 and April 2014 were reviewed. Mean age was 46.4 years. Of these 224 women, 75 were positive for HPV types 16/18 (33.5%) and 123 were positive for non-16/18 types (54.9%). HR-HPV was not genotyped in the remaining 26 women (11.6%). Prevalence of significant lesions for the entire cohort was 2.4%, and 2.6% and 3.3%, respectively, for those with HPV 16/18 and other oncogenic HPV types. One woman with HPV 16/18 (1.3%) had invasive cervical cancer. Multiparous women were more likely to be infected with HPV 16/18 compared to nulliparous women (36.3% versus 17.6%, respectively). In conclusion, the prevalence of significant cervical lesion among our study population was 2.4%. Multiparous women were more likely to be infected with HPV 16/18 compared to nulliparous women.

In Silico Docking to Explicate Interface between Plant-Originated Inhibitors and E6 Oncogenic Protein of Highly Threatening Human Papillomavirus 18

  • Kumar, Satish;Jena, Lingaraja;Sahoo, Maheswata;Kakde, Mrunmayi;Daf, Sangeeta;Varma, Ashok K.
    • Genomics & Informatics
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    • v.13 no.2
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    • pp.60-67
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    • 2015
  • 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 inhibitors have been shown to block HPV infection by different researchers. In the present study, we explored these natural compounds against E6 oncoprotein of high risk HPV18, which is known to inactivate tumor suppressor p53 protein. E6, a high throughput protein model of HPV18, was predicted to anticipate the interaction mechanism of E6 oncoprotein with these natural inhibitors using structure-based drug designing approach. Docking analysis showed the interaction of these natural inhibitors with p53 binding site of E6 protein residues 108-117 (CQKPLNPAEK) and help reinstatement of normal p53 functioning. Further, docking analysis besides helping in silico validations of natural compounds also helped elucidating the molecular mechanism of inhibition of HPV oncoproteins.

A Novel Mutant of Human Papillomavirus Type 18 E6E7 Fusion Gene and its Transforming Activity

  • Zhou, Zhi-Xiang;Zhao, Chen;Li, Qian-Qian;Zeng, Yi
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.17
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    • pp.7395-7399
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    • 2014
  • Background: Persistent human papillomavirus (HPV) infection, especially with high-risk types such as HPV16 and HPV18, has been identified as the primary cause of cervical cancer. E6 and E7 are the major onco-proteins of high-risk HPVs, which are consistently expressed in HPV infected tissues but absent in normal tissues and represent ideal therapeutic targets for immunotherapy of cervical cancer. Materials and Methods: In this study, the optimized fusion gene HPV18 E6E7 (HPV18 ofE6E7) was constructed according to genetic codon usage for human genes. At the same time, for safety future clinical application, a mutant of HPV18 ofE6E7 fusion gene was generated by site-directed mutagenesis at L52G for the E6 protein and C98G for the E7 protein. Results: HPV18-E6E7 mutant (HPV18 ofmE6E7) constructed in this work not only lost the transformation capability for NIH 3T3 cells and tumorigenicity in BALB/c nude mice, but also maintained very good stability and antigenicity. Conclusion: These results suggest that the mutant should undergo further study for application as a safe antigenspecific therapeutic vaccine for HPV18-associated tumors.

Construction of Artificial Epithelial Tissues Prepared from Human Normal Fibroblasts and C9 Cervical Epithelial Cancer Cells Carrying Human Papillomavirus Type 18 Genes

  • Eun Kyung Yang;Seu
    • Biotechnology and Bioprocess Engineering:BBE
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    • v.3 no.1
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    • pp.1-5
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    • 1998
  • One cervical cancer cell line, C9, carrying human papillomavirus type 18 (HPV18) genes that is one of the major etiologic concoviruses for cervical cancer was characterized. This cell line was further characterized for its capacity related to the epithelial cell proliferation, stratification and differentiation in reconstituted artificial epithelial tissue. The in vitro construction of three dimensional artificial cervical opithelial tissue has been engineered using C9 epithelial cancer cells, human foreskin fibroblasts and a matrix made of type I collagen by organotypic culture of epithelial cells. The morphology of paraffin embedded artificial tissue was examined by histochemical staining. The artificial epithelial tissues were well developed having multilayer. However, the tissue morphology was similar to the cervical tissus having displasia induced by HPV infection. The characteristics of the artificial tissues were examined by determinining the expression of specific marker proteins. In the C9 derived artificial tissues, the expression of EGF receptor, as epithelial proliferation marker proteins for stratum basale was observed up to the stratum spinosum. Another epithelial proliferation marker for stratum spinosum, cytokerations 5/6/18, were observed well over the stratum spinosum. For the differentiation markers, the expression of involucrin and filaggrin were observed while the terminal differentiation marker, cytokeratins 10/13 was not detected at all. Therefore the reconstituted artificial epithelial tissues expressed the same types of differentiation marker proteins that are expressed in normal human cervical epithelial tissues but lacked the final differentiation capacity representing characteristics of C9 cell line as a cancer tissue devived cell line. Expression of HPV18 E6 oncoprotein was also observed in this artifical cervical opithelial tissue though the intensity of the staining was weak. Thus this artificial epithelial tissue could be used as a useful model system to examine the relationship between HPV-induced cervical oncogenesis and epithelial cell differentiation.

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Prevalence of Human Papillomavirus in Women from Saudi Arabia

  • Turki, Rola;Sait, Khalid;Anfinan, Nisreen;Sohrab, Sayed Sartaj;Abuzenadah, Adel Mohammed
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.5
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    • pp.3177-3181
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    • 2013
  • Background: Human papillomavirus (HPV) infection is the main causes of cervical cancer in women worldwide. The goal of the present study was to determine the prevalence and distribution of HPV genotypes in women from Saudi Arabia. Recently, several HPV detection methods have been developed, each with different sensitivities and specificities. Methods: In this study, total forty cervical samples were subjected to polymerase chain reaction and hybridization to BioFilmChip microarray assessment. Results: Human papillomavirus (HPV) infections were found in 43% of the specimens. The most prevalent genotypes were HPV 16 (30%) HPV 18 (8.0%) followed by type HPV 45, occurring at 5.0%. Conclusion: Our finding showed the HPV infection and prevalence is increasing at alarming rate in women of Saudi Arabia. There was no low risk infection detected in the tested samples. The BioFilmChip microarray detection system is highly accurate and suitable for detection of single and multiple infections, allowing rapid detection with less time-consumption and easier performance as compared with other methods.

HPV DNA TYPING OF ADULT-ONSET LARYNGEAL PAPILLOMATOSIS (성인의 후두유두종에 대한 Human Papillomavirus의 DNA Typing)

  • 장문수;임영묵;나기상;유장렬;박찬일
    • Proceedings of the KOR-BRONCHOESO Conference
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    • 1991.06a
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    • pp.19-19
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    • 1991
  • 성인의 후두유두종은 Human Papillonavirus에 의해 발생하는 것으로 알려져 있다. 저자들은 1985년 4월부터 1989년 12월까지 충남대학교병원 이비인후과에서 후두유두종으로 수술받은 19예중 보관된 Paraffin block의 이용이 가능하였던 14예에서 Human Papillomavirus type 6, 11, 16 및 18에 대해 In situ hybridization 방법으로 DNA typing을 시행하여 다음과 같은 결과를 얻었다. 14예중 10예에서 type 6에 양성을 보였고 type 6에 양성을 보인 10예중 6예에서 type 11에 대해서도 양성을 보였다. Type 11 단독으로 양성을 보인 예는 없었다. 또한, type 16 및 18에 대해서는 모두 음성을 보였다. 이상의 결과로 성인의 후두유두종은 Human Papillomavirus type 6 및 11과 밀접한 관계가 있을 것으로 사료된다.

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Detection of Human Papillomavirus in Laryngeal Squamous Cell Carcinomas (후두편평세포암종에서 인유두종 바이러스의 검출)

  • 김완수;박성용;마현웅;도남용;김용기;이도용;나한조
    • Korean Journal of Bronchoesophagology
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    • v.4 no.2
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    • pp.197-204
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    • 1998
  • Human papillomavirus(HPV) is epitheliotrophic virus invading the anogenital tract and the upper aerodigestive tract HRV produces a diversity of benign and maljgnant tumors. In this study, the author determined the frequency of association of human papillomavirus(HPV) and laryngeal carcinomas and investigated the significance of HRV infection of different subtypes in the tumorigenesis of laryngeal carcinoma. Laryngeal squamous cell cancinomas from 34 patients who did not have preexisting papillomas by clinical history were retrieved from formalin-fixed, paraffin-embedded blocks and analyzed for HPV. Nineteen cases were tumors of the true vocal folds, 11 were supraglottic and 4 were transglottic. HPV detection was dane using polymerase chain reaction amplification with HPV L$_1$consensus primer. HPV type was determined by the same method using HPV-6, 11 and 16,-18 type-specific E6 primers. The results were as follows : 1) HPV DNA was detected in 7 cases among the 34 patients(20.6%). According to the type of HPV DNA HPV-11 was detected in 3 cases, HPV-16 was detected in 2 cases and HPV-6 and HPV-18 were detected in 1 case, respectively. 2) These 7 HPV-positive patients were advanced cancinoma cases. From these results, we concluded that HPV was thought to be the etiological factor of laryngeal squamous cell carcinomas.

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DETECTION OF HUMAN PAPILLOMAVIRUS DNA IN RESPIRATORY TRACT PAPILLOMA USING POLYMERASE CHAIN REACTION(PCR) (중합효소 반응을 이용한 후두유두종 Human papillomavirus DNA의 검색)

  • 김광현;성명훈;정원호;최영민;박경찬
    • Proceedings of the KOR-BRONCHOESO Conference
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    • 1991.06a
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    • pp.18-18
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    • 1991
  • 후두유두종은 호흡기계에 발생하는 양성종양중 가장 흔한 질환으로 연령에 따라 소아형과 성인형으로 분류하는데 다발성 병변이 흔하고 재발율이 높다고 알려져 있다. 후두유두종의 원인으로는 human papillomavirus의 감염으로 생각되며 잠복 감염으로 인하여 후두유두종이 재발된다고 알려져 있다. Gissman등에 의해 HPV 11이 발견되었음이 보고된 이래 최근까지 HPV 6와 11이 후두유두종의 원인이 된다고 알려져 있다. HPV의 검출에는 Southern blotting이나 in-situ hybridization 방법이 알려져 있는데 저자들은 현재까지의 바이러스 검색방법 중 가장 예민한 방법인 PCR을 이용하여 후두유두종의 HPV DNA를 조사하여 보고자 한다. 저자들은 1989년 10월부터 1900년 12월까지 서울대병원 이비인후과에서 수술을 시행받은 후두유두종 환자 15예를 대상으로 하였으며 이중 소아형은 9예이었고 성인형은 6예였으며 대부분 다발성 병변이었다. HPV 6는 15예중 10예에서 HPV 11은 15예중 6예에서 발견되었으며 두가지 형이 같이 발견된 경우는 1예가 있었다. 소아형의 경우에는 HPV 6와 11이 각각 5예로 비슷한 비율로 검출된 반면 성인형에서는 HPV 6가 주로 검출되었다.

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The Prevalence and Genotype of Human Papillomavirus from Patients with Genital Warts in Eastern Guangdong Province

  • Luo, Zhao-Yun;Chen, Qiang;Yang, Hui;Lin, Min;Chen, Chan-Yu;Yang, Chun;Yang, Li-Ye
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.14
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    • pp.5675-5679
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    • 2015
  • Background: Low-risk human papillomavirus (LR-HPV) infection is the main cause of genital warts. LRHPV genotypes 6 and 11 are associated with genital warts, but there have only been a few published studies about the genotype-specific prevalence of HPV in genital warts in China. The objective of our study was to assess the prevalence of HPV genotypes for clinical cases involving both men and women and to evaluate the potential benefit of a quadrivalent (genotypes 6, 11, 16, and 18) HPV vaccine in eastern Guangdong province of China. Materials and Methods: A total of 696 eligible patients with genital warts were enrolled during the period Aug 2009 through Oct 2014. Specimens were collected from genital warts, the HPV GenoArray test was used for HPV detection and genotyping, which could detect 21 HPV genotypes, including genotypes 6, 11, 16, and 18. Results: Among the 696 cases, 675 samples were successfully genotyped. The median age of patients was 32.1 years (range, 16-67 years). The most prevalent genotypes were HPV-6 (285/675, 42.2%), HPV-11 (265/675, 39.3%), HPV-52 (52/675, 7.7%), HPV-16 (51/675, 7.56%), HPV-81 (50/675, 7.40%) and HPV-58 (37/675, 5.48%). Low-risk genotypes predominated, with a prevalence of 96.59%. The cumulative prevalence of genotypes 6 and 11 was 78.7% (531/675), the cumulative prevalence of genotypes 16 and 18 was 11.6% (78/675), and the cumulative prevalence of genotypes 6, 11, 16, and 18 was 82.5% (557/675). Conclusions: Our results provide strong evidence that, in eastern Guangdong, different from Western countries, the most prevalent low risk HPV genotypes in patients with genital warts are 6, 11 and 81. The quadrivalent HPV vaccine could prevent 82.5% of genital warts in eastern Guangdong.