Interplay of Epigenetics with Gynecological Cancer

Recent data on the cell deregulation that occurs during the progression to cancer underlines the cooperation between genetic and epigenetic alterations leading to a malignant phenotype. Unlike genetic alterations, the epigenetic changes do not affect the DNA sequence of the genes, but determine the regulation of gene expression acting upon the genome. Moreover, unlike genetic changes, epigenetic ones are reversible, making them therapeutic targets in various conditions in general and in cancer disease in particular. The term epigenetics includes a series of covalent modifications that regulate the methylation pattern of DNA and posttranslational modifications of histones. Gene expression can also be regulated at the posttranscriptional level by microRNAs (miRNAs), a family of small noncoding RNAs that inhibit the translation of mRNA to protein. miRNAs can act as ‘oncomiRs’, as tumor suppressors, or both. In this chapter, we will (1) summarize the current literature on the key processes responsible for epigenetic regulation: DNA methylation, histone modifications and posttranscriptional gene regulation by miRNAs; (2) evaluate aberrant epigenetic modifications as essential players in cancer progression; (3) establish the roles of microenvironment-mediated epigenetic perturbations in the development of gynecological neoplasia; (4) evaluate epigenetic factors involved in drug resistance

ČIMBENICI UDRUŽENI S USTRAJNOM GENITALNOM INFEKCIJOM HUMANIM PAPILOMAVIRUSOM U MANJOJ SKUPINI RUMUNJSKIH ŽENA

The aim of the study was to assess the role of behavioral factors in persistence of human papillomavirus (HPV) genital infection. Out of a cohort of 605 women included in a study of HPV infection prevalence, 142 HPV positive women (aged 18-57) were retested after a 12-month interval. None of the patients underwent surgical treatment during that period. Selected patients were asked for a second smear for cytologic analysis and HPV genotyping. A questionnaire that included information regarding reproductive health, sexual activity and smoking status was filled-in. After 12 months, 46 of 142 (32.39%) women had persistent HPV infection, with genotypes 16 and 18 found in 27 cases. On the other hand, 17 of 142 (11.97%) women had acquired new infections replacing the baseline genotypes. In our study, smoking (OR=2.320, p=0.0330) and sexual behavior (OR=5.333, p=0.0180 for more than three sexual partners; OR=2.427, p=0.0238 for cases where the partner was involved in another sexual relationship) were associated with viral persistence, while long-term contraception did not yield statistically significant results.Cilj ovoga istraživanja bio je procijeniti ulogu čimbenika ponašanja na ustrajnost genitalne infekcije humanim papilomavirusom (HPV). Od 605 žena uključenih u ispitivanje učestalosti infekcije HPV-om 142 žene pozitivne na HPV (u dobi od 18 do 57 godina) ponovno su testirane nakon 12 mjeseci. Tijekom tog razdoblja nijedna od tih bolesnica nije bila podvrgnuta kirurškom liječenju. Od odabranih bolesnica zatražen je drugi obrisak za citološku analizu i genotipiziranje HPV-a. Ispunjen je upitnik s podacima o reprodukcijskom zdravlju, seksualnim aktivnostima i pušenju. Nakon 12 mjeseci 46/142 (32,39%) žena imalo je ustrajnu infekciju HPV-om; u 27 slučajeva utvrđeni su genotipovi 16 i 18. S druge strane, 17/142 (11,97%) žena imalo je novo stečene infekcije koje su zamijenile prvobitne genotipove. U našem istraživanju je pušenje (OR=2,320, p=0,0330) i spolno ponašanje (OR=5,333, p=0,0180 za više od tri seksualna partnera; OR=2,427, p=0,0238 u slučajevima kad je partner imao i drugi seksualni odnos) bilo udruženo s ustrajnošću virusa, dok dugotrajna kontracepcija nije pokazala statistički značajne rezultate

SARS-CoV-2 Variant Surveillance in Genomic Medicine Era

In the genomic medicine era, the emergence of SARS-CoV-2 was immediately followed by viral genome sequencing and world-wide sequences sharing. Almost in real-time, based on these sequences, resources were developed and applied around the world, such as molecular diagnostic tests, informed public health decisions, and vaccines. Molecular SARS-CoV-2 variant surveillance was a normal approach in this context yet, considering that the viral genome modification occurs commonly in viral replication process, the challenge is to identify the modifications that significantly affect virulence, transmissibility, reduced effectiveness of vaccines and therapeutics or failure of diagnostic tests. However, assessing the importance of the emergence of new mutations and linking them to epidemiological trend, is still a laborious process and faster phenotypic evaluation approaches, in conjunction with genomic data, are required in order to release timely and efficient control measures

Kinetics and persistence of cellular and humoral immune responses to SARS-CoV-2 vaccine in healthcare workers with or without prior COVID-19

SARS-CoV-2 vaccines are highly efficient against severe forms of the disease, hospitalization and death. Nevertheless, insufficient protection against several circulating viral variants might suggest waning immunity and the need for an additional vaccine dose. We conducted a longitudinal study on the kinetics and persistence of immune responses in healthcare workers vaccinated with two doses of BNT162b2 mRNA vaccine with or without prior SARS-CoV-2 infection. No new infections were diagnosed during follow-up. At 6 months, post-vaccination or post-infection, despite a downward trend in the level of anti-S IgG antibodies, the neutralizing activity does not decrease significantly, remaining higher than 75% (85.14% for subjects with natural infection, 88.82% for vaccinated after prior infection and 78.37% for vaccinated only). In a live-virus neutralization assay, the highest neutralization titres were present at baseline and at 6 months follow-up in persons vaccinated after prior infection. Anti-S IgA levels showed a significant descending trend in vaccinated subjects (p < 0.05) after 14 weeks. Cellular immune responses are present even in vaccinated participants with declining antibody levels (index ratio 1.1-3) or low neutralizing activity (30%-40%) at 6 months, although with lower T-cell stimulation index (p = 0.046) and IFN-γ secretion (p = 0.0007) compared to those with preserved humoral responses.1293130513EU Horizon 202