Papilomavirus humano e inestabilidad cromosomica en pacientes con cáncer cervicouterino en el noreste de México

Tesis (Doctorado en Ciencias Biológicas con Especialidad en Genética) UANLUANLhttp://www.uanl.mx

Human papillomavirus as a single infection in pregnant women from Northeastern Mexico: Cross-sectional study

Background: The role of human papillomavirus (HPV) as single or multiple infections in pregnant women would be relevant to determining the time to progression and/or the time to regression of cervical lesions. Objective: In this preliminary study, we determined the prevalence of HPV as single or multiple infections in pregnant women from Northeastern Mexico. Materials and Methods: Samples from 31 pregnant and 62 nonpregnant women were examined between January 2015 and November 2015 at UMAE-23 of the Instituto Mexicano del Seguro Social (IMSS). The samples of cervicovaginal exudate were obtained for HPV DNA detection using the INNO-LiPA test, and HPV infections were analyzed as single or multiple infections. Participants completed a questionnaire on sociodemographic, gynecological, obstetric, and sexual behavior characteristics. Results: The mean age of the pregnant women was 25.7 ± 4.8 yr, with an average time of pregnancy of 6 ± 1 months at the time of the study. With respect to age, parity, smoking history, or oral contraceptive use no statistically significant differences between the two studied groups was observed. The HPV infection was 2.7 times higher in pregnant women (35%) than in the control group (13%). In total, 78% of the pregnant women who were HPV-positive presented with single infections compared with 28% of the nonpregnant women. Conclusion: A higher prevalence of HPV as a single infection was found in this sample of pregnant Mexican women. Follow-up is necessary to evaluate the persistence or regression of the infection. Key words: Papillomavirus infection, Pregnant women, Uterine cervical dysplasia

Leptin receptor expression during the progression of endometrial carcinoma is correlated with estrogen and progesterone receptors

Abstract Introduction: The hormone leptin, which is produced in the adipose tissue, may influence tumorigenesis directly via its receptor (Ob-R). Thus, a role for Ob-R in endometrial carcinogenesis has been proposed. However, most studies neither included samples of the entire histological progression of endometrial carcinoma nor examined Ob-R jointly with the estrogen and progesterone receptors (ER and PR, respectively). Material and methods: To determine the fluctuations of Ob-R, ER, and PR during the histological progression of endometrial carcinoma, we assessed their expression via immunohistochemistry (IHC) in six histological types of endometrium (proliferative, secretory, nonatypical and atypical hyperplasia, and endometrioid and nonendometrioid endometrial carcinoma), in which we performed histopathological and digital scoring for the quantification of receptors. Results: We found that Ob-R expression was positively correlated with that of ER and PR (r = 1, p < 0.001; r = 0.943, p < 0.005, respectively), and there was a significant difference in Ob-R expression among proliferative normal endometrium, hyperplasias, and carcinomas, according to their relative digitally scored Ob-R expression (p < 0.001). In addition, we observed that Ob-R expression in the secretory endometrium was more similar to that of carcinomas than to its proliferative counterpart. Conclusions: These results indicate that Ob-R expression fluctuates during endometrial carcinogenesis in correlation with ER and PR, suggesting that Ob-R expression in vivo is highly dependent on estrogen and progesterone activities in the endometrium and on its ER and PR status, as suggested previously by in vitro studies. Key words: Ob-R, endometrial carcinoma, immunohistochemistr

Expression of the HPV18/E6 oncoprotein induces DNA damage

Abstract This study investigated possible variations in DNA damage in HeLa cells with silenced expression of the HPV/E6oncogene compared with HeLa cells with normal expression of the E6oncogene using the DNA breakage detection-fluorescence in situ hybridization (DBD-FISH) technique and a whole human genome DNA probe. The variable levels of DNA breaks present were measured quantitatively using image analysis after whole-genome DNA hybridization. HeLa cells with silenced expression of the HPV18/E6 oncogene showed a significant decrease in DNA damage compared with parental cells with normal expression of the E6oncogene. These results were confirmed by alkaline comet assay. In conclusion, we demonstrated a decrease in DNA damage in HeLa clones associated with low expression of the HPV/E6 oncogene

Mycobacterium tuberculosis promotes genomic instability in macrophages

BACKGROUND Mycobacterium tuberculosis is an intracellular pathogen, which may either block cellular defensive mechanisms and survive inside the host cell or induce cell death. Several studies are still exploring the mechanisms involved in these processes. OBJECTIVES To evaluate the genomic instability of M. tuberculosis-infected macrophages and compare it with that of uninfected macrophages. METHODS We analysed the possible variations in the genomic instability of Mycobacterium-infected macrophages using the DNA breakage detection fluorescence in situ hybridisation (DBD-FISH) technique with a whole human genome DNA probe. FINDINGS Quantitative image analyses showed a significant increase in DNA damage in infected macrophages as compared with uninfected cells. DNA breaks were localised in nuclear membrane blebs, as confirmed with DNA fragmentation assay. Furthermore, a significant increase in micronuclei and nuclear abnormalities were observed in infected macrophages versus uninfected cells. MAIN CONCLUSIONS Genomic instability occurs during mycobacterial infection and these data may be seminal for future research on host cell DNA damage in M. tuberculosis infection. Key words: Mycobacterium tuberculosis - alkaline-labile sites - DNA breakage detection fluorescence in situ hybridisation (DBD-FISH

Chromosome segregation and chromatin integrity in spermatozoa from a t(2;8)(p24;p21)mat carrier: A case-report

Abstract Background: Chromosome rearrangements can produce genomic imbalance in gametes which causes a drastic decrease in fertility. Several studies have described the relationship between high levels of DNA damage and chromosomal alterations in the spermatozoa of infertile or subfertile males. However, the nature of this relation is poorly understood. In this study, the meiotic segregation pattern and chromatin integrity were analyzed in the ejaculated spermatozoa of a 46, XY, t(2;8)(p24;p21)mat carrier with normozoospermia and a lack of conception. Case: A 39-year-old infertile man with a 46, XY, t(2;8)(p24;p21)mat inherited from his mother, was studied. The wife of the proband (30 yrs old) had a normal karyotype and no reproductive problems. The meiotic segregation pattern and aneuploidy of chromosome-8 and chromosome-2 were analyzed by FISH. Sperm DNA damage was evaluated by the Sperm Dispersion Chromatin, alkaline comet assay and DNA breaking detection. Five healthy male donors were included as controls. The frequency of genetically unbalanced spermatozoa was 61.6%. Analysis of the aneuploidy of chromosome-8 and chromosome-Y revealed approximately three and 24 fold increased level respectively in comparison with that of the control group. Conclusion: We suggest that the accumulation of genetically unbalanced spermatozoa, and increased sperm aneuploidy level is related to male infertility. Interestingly, the case described here has a high level of sperm chromosomal imbalance appears to be linked to sperm DNA fragmentation status. This information could be useful in assisted reproductive techniques