BackgroundTransposable Elements (TEs) comprise nearly 45% of the entire genome and are part of sophisticated regulatory network systems that control developmental processes in normal and pathological conditions. The retroviral/retrotransposon gene machinery consists mainly of Long Interspersed Nuclear Elements (LINEs-1) and Human Endogenous Retroviruses (HERVs) that code for their own endogenous reverse transcriptase (RT). Interestingly, RT is typically expressed at high levels in cancer cells. Recent studies report that RT inhibition by non-nucleoside reverse transcriptase inhibitors (NNRTIs) induces growth arrest and cell differentiation in vitro and antagonizes growth of human tumors in animal model. In the present study we analyze the anticancer activity of Abacavir (ABC), a nucleoside reverse transcription inhibitor (NRTI), on PC3 and LNCaP prostate cancer cell lines.Principal FindingsABC significantly reduces cell growth, migration and invasion processes, considerably slows S phase progression, induces senescence and cell death in prostate cancer cells. Consistent with these observations, microarray analysis on PC3 cells shows that ABC induces specific and dose-dependent changes in gene expression, involving multiple cellular pathways. Notably, by quantitative Real-Time PCR we found that LINE-1 ORF1 and ORF2 mRNA levels were significantly up-regulated by ABC treatment.ConclusionsOur results demonstrate the potential of ABC as anticancer agent able to induce antiproliferative activity and trigger senescence in prostate cancer cells. Noteworthy, we show that ABC elicits up-regulation of LINE-1 expression, suggesting the involvement of these elements in the observed cellular modifications.
The association between nasal cancer and various occupations was investigated in a case-control study in the provinces of Verona and Vicenza (northeastern Italy) and Siena (central Italy). Cases of malignant epithelial neoplasm of the nasal cavities and paranasal sinuses diagnosed in the years 1982-1987 in the hospitals of Verona, Legnago, Bussolengo, Vicenza, and Siena comprised the study. Controls were patients admitted to the same hospitals as the cases, with any diagnosis except chronic rhino-sinusal disease and nasal bleeding. Age, gender, residency, and date of admission were taken into account by matching. Cases and controls, or their next of kin, were interviewed or required to fill in a mailed questionnaire; the overall response rate was 70%. Altogether, 78 cases and 254 controls provided information on occupational history. Significantly increased risks were associated (in males) with work in the wood industry (odds ratio [O.R.]: 5.8; 90% confidence interval [C.I.]: (2.2-16) and in the leather industry (6.8; 1.9-25). Textile workers, furnacemen, construction workers, and workers with possible exposure to organic dusts showed increased risks even if statistical significance was not reached.
An increase in measles cases worldwide, with outbreaks, has been registered in the last few years, despite the availability of a safe and highly efficacious vaccine. In addition to an inadequate vaccination coverage, even in high-income European countries studies proved that some vaccinated people were also found seronegative years after vaccination, thus increasing the number of people susceptible to measles infection. In this study, we evaluated the immunization status and the seroprevalence of measles antibodies among 1092 healthy adults, either vaccinated or naturally infected, in order to investigate the persistence of anti-measles IgG. Among subjects who received two doses of measles vaccine, the neutralizing antibody titer tended to decline over time. In addition, data collected from a neutralization assay performed on 110 healthy vaccinated subjects suggested an inverse correlation between neutralizing antibody titers and the time elapsed between the two vaccinations, with a significant decline in the neutralizing titer when the interval between the two doses was ≥11 years. On the basis of these results, monitoring the serological status of the population 10-12 years after vaccination could be important both to limit the number of people who are potentially susceptible to measles, despite the high efficacy of MMR vaccine, and to recommend a booster vaccine for the seronegatives.
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