Colorectal papillomavirus infection in patients with colorectal cancer.
Bodaghi S, Yamanegi K, Xiao SY, Da Costa M, Palefsky JM, Zheng ZM. HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
PURPOSE: Infection with human papillomaviruses (HPV) is associated with the development of cervical cancer, but whether HPVs have a role in colorectal cancer remains controversial.Experimental Designs: To determine the relationship between HPV and colorectal cancer, we did a retrospective, controlled study using tumor and tumor-adjacent colorectal tissues dissected from patients with colorectal cancer, as well as colorectal tissues from control individuals with no cancer. The samples were processed in a blinded fashion for nested PCR and in situ PCR detection of HPV DNAs. The PCR products were gel-purified and sequenced for HPV genotyping.RESULTS: We found that colorectal tissues from 28 of 55 (51%) patients with colorectal cancer were positive for HPV DNA. Colorectal tissues from all 10 control individuals were negative for HPV DNA (P = 0.0034). Of the 107 usable (GAPDH(+)) samples collected as paired colorectal tissues (tumor and tumor-adjacent tissues) from the patients, 38 (36%) had HPV16 (n = 31), HPV18 (n = 5), or HPV45 (n = 2), with HPV DNA in both tumor and tumor-adjacent tissues of 10 paired samples, 13 in only the tumor, and 5 in only tumor-adjacent tissues. In situ PCR detection of the tumor tissues confirmed the presence of HPV DNA in tumor cells.CONCLUSION: Our results suggest that colorectal HPV infection is common in patients with colorectal cancer, albeit at a low DNA copy number, with HPV16 being the most prevalent type. HPV infection may play a role in colorectal carcinogenesis.
Proteomics. 2005 Apr;5(6):1481-93.
Proteomic analysis of progressive factors in uterine cervical cancer.
Choi YP, Kang S, Hong S, Xie X, Cho NH. Brain Korea 21 Project for Medical Science, Yonsei University, Seoul, South Korea.
Human papillomavirus (HPV) infections play a crucial role in the progress of cervical cancer. The high-risk HPV types are frequently associated with the development of malignant lesions. Some of the latest studies have demonstrated that the high-risk HPV 16 and 18 are predominantly detected in the more aggressive cancers. In the present study, we aimed to establish the proteomic profiles and characterization of the tumor related proteins by using two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). For proteomic analysis, patients infected by HPV 16 or 18 were included in this study. We compared nuclear protein and cytoplasmic protein, separately by using the subcellular fraction. Differential protein spots between cervical cancer with high-risk HPV, HPV 16 or HPV 18, and HaCaT cell lines were characterized by 2-DE. Those proteins analyzed by peptide mass fingerprinting based on MALDI-TOF MS and database searching were the products of oncogenes or proto-oncogenes, and the others were involved in the regulation of cell cycle, for general genomic stability, telomerase activation, and cell immortalization. However, there was no difference in protein characterization for cervical cancer between HPV 16 and HPV 18 infection. Nonetheless, these data are valuable for the mass identification of differentially expressed proteins involved in human uterine cervical cancer. Moreover, the data has enormous value for establishing the human uterine cervical cancer proteome database that can be used in screening a molecular marker for the further study of human uterine cervical cancer, and also for studying any correlation among the cancers induced by HPV.
Georgian Med News. 2005 Mar;(3):30-3.
The state of cervical and vaginal epithelial tissue in patients with hpv infection.
HPV Virus Medical Facts - Article in Russian
Maisuradze N, Sanikidze T, Topuria M, Museridze N. Zhordania Research Institute of Human reproduction, Tbilisi, Georgia.
Genital human papilloma virus (HPV) infection is the sexually transmitted disease. HPV induces the proliferation of epithelial cells. In the areas of viral inclusions vulvovaginal warts, papillomas and condylomas are developing. Some serotypes of HPV are known as a significant risk factor of cervical cancer. The aim of our study was to detect the conditions of oxidation processes in vaginal and cervical tissues in patients with HPV infection. According to our results, in patients with HPV, intensification of production of reactive forms of nitrogen and oxygen in vaginal and cervical tissues takes place which is the result of activation of leukocytes, other phagocyte cells and chaotic flow of blood in damaged tissue, as well as interchanging periods of hypoxia and reperfusion.
Gynecol Oncol. 2005 May 12; [Epub ahead of print]
Immunosuppressive activity of proteases in cervical carcinoma.
Daneri-Navarro A, Del Toro-Arreola S, Sanchez-Hernandez PE, Ramirez-Duenas MG, Armendariz-Borunda J, Perez-Montfort R. Programa de Doctorado en Ciencias Biomedicas, Departamento de Fisiologia, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, 44340 Guadalajara, Jalisco, Mexico. de la Salud, Universidad de Guadalajara, Jalisco, Mexico.
OBJECTIVE.: The host immune response is essential for restraining both HPV infections and HPV-related cervical cancer. We previously reported a direct correlation between proteolytic activity and malignant progression from precursor lesions to invasive cervical carcinoma. The present study was undertaken to investigate whether proteinases from cervical carcinoma extracts and representative purified proteinases involved in tumor progression could regulate lymphocyte proliferation to phytohemagglutinin (PHA) mitogen. METHODS.: Extracts were prepared from tissue samples obtained from patients with invasive cervical squamous carcinoma, squamous intra-epithelial lesions or women with normal cervix. Lymphocytes obtained from a single healthy donor were pre-incubated with one of these extracts in the presence or absence of proteinase inhibitors, and stimulated with PHA during 72 h. The proliferative response was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) method (re-validated with thymidine uptake). RESULTS.: Lymphocyte proliferation was significantly decreased by cervical carcinoma extracts, while only slightly decreased by squamous intra-epithelial lesions or normal extracts. Inhibitor assays indicated that proteinases from cervical carcinoma were responsible for 53.30% of total suppressive activity. We found that purified enzymes such as trypsin, cathepsin B, uPA and type IV collagenase suppressed the proliferative response in a dose-dependent fashion. CONCLUSIONS.: Our data suggest that in addition to the classic role in tumor invasion, proteases could represent an immune evasion mechanism in cervical carcinoma.
Cancer Genet Cytogenet. 2005 May;159(1):44-47.
Association between the stages of cervical cancer and chromosome 1 aneusomy.
Cortes-Gutierrez EI, Davila-Rodriguez MI, Muraira-Rodriguez M, Said-Fernandez S, Cerda-Flores RM. Genetics Division, Centro de Investigacion Biomedica del Noreste (CIBIN), Instituto Mexicano del Seguro Social (IMSS), Administracion de Correos No. 4, Apartado postal 20, C.P. 64720 Monterrey, Nuevo Leon, Mexico; Facultad de Ciencias Biologicas (FCB), Universidad Autonoma de Nuevo Leon (UANL), Monterrey, Nuevo Leon, Mexico.
The high-risk human papillomavirus is known to play a pivotal role in cervical carcinogenesis. Numerical and structural aberrations are known to be related to different behaviors of malignant cervical lesions. The aims of this study were (1) to assess the number of cervical cells with chromosome 1 aneusomy (monosomy, trisomy, and tetrasomy) in 20 women with cervical intraepithelial neoplasia (CIN 1, CIN 2, CIN 3, and invasive cancer) and three women without CIN by fluorescence in situ hybridization (FISH), (2) to determine the heterogeneity of aneusomy among women within each of the five groups studied, (3) to determine the association between the four progressive stages of cervical cancer and the number of cells with and without aneusomy, (4) to determine the association between number of cells with and without aneusomy and human papilloma virus (HPV) infection, and (5) to determine its usefulness as a biomarker of cancer risk. A hospital-based unmatched case-control study in a sample of 23 women grouped by disease stage and selected by histology from the Obstetrics and Gynecology Hospital of the Instituto Mexicano del Seguro Social (IMSS) in Mexico was conducted in 2002. Numerical aberrations of chromosome 1 in cervical smears were detected with FISH. HPV was detected with polymerase chain reaction (PCR) and typing was performed with restriction fragment length polymorphism (RFLPs). Analysis of chromosome 1 aneusomy revealed (1) homogeneity among women within each one of the five groups, (2) a positive linear trend between the aneusomy frequency and grade of lesion, and (3) an association between aneusomy and high-risk HPV infection. These findings suggest the usefulness of the number of cervical cells with chromosome 1 aneusomy as a biomarker. In order to validate this biomarker we suggest a larger prospective study of cytological samples of patients with a longer follow-up.