Role of DNA repair machinery and p53 in the testicular germ cell cancer: a review

Notwithstanding the peculiar sensitivity to cisplatin-based treatment, resulting in a very high percentage of cures even in advanced stages of the disease, still we do not know the biological mechanisms that make Testicular Germ Cell Tumor (TGCT) "unique" in the oncology scene. p53 and MDM2 seem to play a pivotal role, according to several in vitro observations, but no correlation has been found between their mutational or expression status in tissue samples and patients clinical outcome. Furthermore, other players seem to be on stage: DNA Damage Repair Machinery (DDR) , especially Homologous Recombination (HR) proteins, above all Ataxia Telangiectasia Mutated (ATM), cooperates with p53 in response to DNA damage, activating apoptotic cascade and contributing to cell "fate". Homologous Recombination deficiency has been assumed to be a Germ Cell Tumor characteristic underlying platinum-sensitivity, whereby Poly(ADP-ribose) polymerase (PARP), an enzyme involved in HR DNA repair, is an intriguing target: PARP inhibitors have already entered in clinical practice of other malignancies and trials are recruiting TGCT patients in order to validate their role in this disease. This paper aims to summarize evidence, trying to outline an overview of DDR implications not only in TGCT curability, but also in resistance to chemotherapy

Role of Sex Hormones in the Development and Progression of Hepatitis B Virus-Associated Hepatocellular Carcinoma

Infection with hepatitis B virus (HBV) is a major risk factor for hepatocellular carcinoma (HCC) in developed countries. Epidemiological reports indicate that the incidence of HBV-related HCC is higher in males and postmenopausal females than other females. Increasing evidence suggests that sex hormones such as androgens and estrogens play an important role in the progression of an HBV infection and in the development of HBV-related HCC. While androgen is supposed to stimulate the androgen signaling pathway and cooperate to the increased transcription and replication of HBV genes, estrogen may play a protecting role against the progression of HBV infections and in the development of HBV-related HCC through decreasing HBV RNA transcription and inflammatory cytokines levels. Additionally, sex hormones can also affect HBV-related hepatocarcinogenesis by inducing epigenetic changes such as the regulation of mRNA levels by microRNAs (miRNAs), DNA methylation, and histone modification in liver tissue. This review describes the molecular mechanisms underlying the gender disparity in HBV-related HCC with the aim of improving the understanding of key factors underneath the sex disparity often observed in HBV infections. Furthermore, the review will propose more effective prevention strategies and treatments of HBV-derived diseases

Structuring the basis for performance measurement in a cancer network. An explorative analysis

This paper aims to address the topic of performance measurement in the healthcare industry by exploring the comprehension of the effects of dramatic and seamless digital evolution on the context itself. Our study aims to open new avenues of research hinged on three main topics: the digital transformation of the healthcare industry, the use of a digital platform in cancer networks, and the basis for structuring key performance indicators to monitor healthcare performance in the cancer networks effectively. The results shed light on the key role of digital platforms in KPIs constructions to assess healthcare performance. By exploring and merging the mentioned topics, we build a conceptual framework about the possible drivers for measuring healthcare performance, leading to the provision of instant care with a high degree of preventive capacity and decreasing costs. Our conceptual study could be useful for policymakers, practitioners, and academics interested in this area. From a theoretical point of view, the study offers valuable insights into two main fields: digital transformation in healthcare and performance measurement. It is a valuable tool for healthcare managers to redefine strategies based on patients. Additionally, it emphasizes the importance of institutions’ contributions to promoting digitization. It is not without limits. The results can be context-sensitive. Future research can extend the analysis to compare results in different countries making results generalizable

Role of Viral miRNAs and Epigenetic Modifications in Epstein-Barr Virus-Associated Gastric Carcinogenesis

MicroRNAs are short (21-23 nucleotides), noncoding RNAs that typically silence posttranscriptional gene expression through interaction with target messenger RNAs. Currently, miRNAs have been identified in almost all studied multicellular eukaryotes in the plant and animal kingdoms. Additionally, recent studies reported that miRNAs can also be encoded by certain single-cell eukaryotes and by viruses. The vast majority of viral miRNAs are encoded by the herpesviruses family. These DNA viruses including Epstein-Barr virus encode their own miRNAs and/or manipulate the expression of cellular miRNAs to facilitate respective infection cycles. Modulation of the control pathways of miRNAs expression is often involved in the promotion of tumorigenesis through a specific cascade of transduction signals. Notably, latent infection with Epstein-Barr virus is considered liable of causing several types of malignancies, including the majority of gastric carcinoma cases detected worldwide. In this review, we describe the role of the Epstein-Barr virus in gastric carcinogenesis, summarizing the functions of the Epstein-Barr virus-encoded viral proteins and related epigenetic alterations as well as the roles of Epstein-Barr virus-encoded and virally modulated cellular miRNAs

A SARS-CoV-2 Infection High-Uptake Program on Healthcare Workers and Cancer Patients of the National Cancer Institute of Naples, Italy

Background: From the beginning of 2020, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) quickly spread worldwide, becoming the main problem for the healthcare systems. Healthcare workers (HCWs) are at higher risk of infection and can be a dangerous vehicle for the spread of the virus. Furthermore, cancer patients (CPs) are a vulnerable population, with an increased risk of developing severe and lethal forms of Coronavirus Disease 19 (COVID-19). Therefore, at the National Cancer Institute of Naples, where only cancer patients are treated, a surveillance program aimed to prevent the hospital access of SARS-CoV-2 positive subjects (HCWs and CPs) was implemented. The study aims to describe the results of the monitoring activity for the SARS-CoV-2 spread among HCWs and CPs, from March 2020 to March 2021. Methods: This surveillance program included a periodic sampling through nasopharyngeal molecular swabs for SARS-CoV-2 (Real-Time Polymerase Chain Reaction, RT-PCR). CPs were submitted to the molecular test at least 48 h before hospital admission. Survival analysis and multiple logistic regression models were performed among HCWs and CPs to assess the main SARS-CoV-2 risk factors. Results: The percentages of HCWs tested with RT-PCR for the detection of SARS-CoV-2, according to the first and the second wave, were 79.7% and 91.7%, respectively, while the percentages for the CPs were 24.6% and 39.6%. SARS-CoV-2 was detected in 20 (1.7%) HCWs of the 1204 subjects tested during the first wave, and in 127 (9.2%) of 1385 subjects tested in the second wave (p p = 0.8). The multivariate logistic analysis provided a significant OR for nurses (OR = 2.24, 95% CI 1.23–4.08, p < 0.001) compared to research, administrative staff, and other job titles. Conclusions: Our findings show that the positivity rate between the two waves in the HCWs increased over time but not in the CPs; therefore, the importance of adopting stringent measures to contain the shock wave of SARS-CoV-2 infection in the hospital setting was essential. Among HCWs, nurses are more exposed to contagion and patients who needed continuity in oncological care for diseases other than COVID-19, such as suspected cancer

Correction: Metabolic syndrome, endocrine disruptors and prostate cancer associations: biochemical and pathophysiological evidences

[This corrects the article DOI: 10.18632/oncotarget.16725.]

Metabolic syndrome, endocrine disruptors and prostate cancer associations: biochemical and pathophysiological evidences

This review summarizes the main pathophysiological basis of the relationship between metabolic syndrome, endocrine disruptor exposure and prostate cancer that is the most common cancer among men in industrialized countries. Metabolic syndrome is a cluster of metabolic and hormonal factors having a central role in the initiation and recurrence of many western chronic diseases including hormonal-related cancers and it is considered as the world's leading health problem in the coming years. Many biological factors correlate metabolic syndrome to prostate cancer and this review is aimed to focus, principally, on growth factors, cytokines, adipokines, central obesity, endocrine abnormalities and exposure to specific endocrine disruptors, a cluster of chemicals, to which we are daily exposed, with a hormone-like structure influencing oncogenes, tumor suppressors and proteins with a key role in metabolism, cell survival and chemo-resistance of prostate cancer cells. Finally, this review will analyze, from a molecular point of view, how specific foods could reduce the relative risk of incidence and recurrence of prostate cancer or inhibit the biological effects of endocrine disruptors on prostate cancer cells. On the basis of these considerations, prostate cancer remains a great health problem in terms of incidence and prevalence and interventional studies based on the treatment of metabolic syndrome in cancer patients, minimizing exposure to endocrine disruptors, could be a key point in the overall management of this disease

Micrornas in prostate cancer: an overview

Prostate cancer is the second highest cause of cancer mortality after lung tumours. In USA it affects about 2.8 million men and the incidence increases with age in many countries. Therefore, early diagnosis is a very important step for patient clinical evaluation and for a selective and efficient therapy. The study of miRNAs' functions and molecular mechanisms has brought new knowledge in biological processes of cancer. In prostate cancer there is a deregulation of several miRNAs that may function as tumour suppressors or oncogenes. The aim of this review is to analyze the progress made to our understanding of the role of miRNA dysregulation in prostate cancer tumourigenesis

Quality of Life in Women Diagnosed with Breast Cancer after a 12-Month Treatment of Lifestyle Modifications

Healthy lifestyles are associated with better health-related quality of life (HRQoL), favorable prognosis and lower mortality in breast cancer (BC) survivors. We investigated changes in HRQoL after a 12-month lifestyle modification program in 227 BC survivors participating in DEDiCa trial (Mediterranean diet, exercise, vitamin D). HRQoL was evaluated through validated questionnaires: EQ-5D-3L, EORTC-QLQ-C30 and EORTC QLQ-BR23. Baseline changes were tested using analysis of variance. Multiple regression analyses were performed to assess treatment effects on HRQoL. Increases were observed in global health status (p &lt; 0.001), physical (p = 0.003), role (p = 0.002) and social functioning (p &lt; 0.001), body image (p &lt; 0.001), future perspective (p &lt; 0.001), well-being (p = 0.001), and reductions in fatigue (p &lt; 0.001), nausea and vomiting (p = 0.015), dyspnea (p = 0.001), constipation (p = 0.049), financial problems (p = 0.012), sexual functioning (p = 0.025), systematic therapy side effects (p &lt; 0.001) and breast symptoms (p = 0.004). Multiple regression analyses found inverse associations between changes in BMI and global health status (p = 0.048) and between serum 25(OH)D levels and breast symptoms (p = 0.002). A healthy lifestyle treatment of traditional Mediterranean diet and exercise may impact positively on HRQoL in BC survivors possibly through reductions in body weight while vitamin D sufficiency may improve BC-related symptoms. These findings are relevant to BC survivors whose lower HRQoL negatively affects treatment compliance and disease outcomes