Cutaneous melanoma: From pathogenesis to therapy (Review)

In less than 10 years, melanoma treatment has been revolutionized with the approval of tyrosine kinase inhibitors and immune checkpoint inhibitors, which have been shown to have a significant impact on the prognosis of patients with melanoma. The early steps of this transformation have taken place in research laboratories. The mitogen-activated protein kinase (MAPK) pathway, phosphoinositol-3-kinase (PI3K) pathway promote the development of melanoma through numerous genomic alterations on different components of these pathways. Moreover, melanoma cells deeply interact with the tumor microenvironment and the immune system. This knowledge has led to the identification of novel therapeutic targets and treatment strategies. In this review, the epidemiological features of cutaneous melanoma along with the biological mechanisms involved in its development and progression are summarized. The current state-of-the-art of advanced stage melanoma treatment strategies and the currently available evidence of the use of predictive and prognostic biomarkers are also discussed

The role of nutraceutical medications in men with non bacterial chronic prostatitis and chronic pelvic pain syndrome: A prospective non blinded study utilizing flower pollen extracts versus bioflavonoids

Introduction: Chronic prostatitis (CP)/chronic pelvic pain syndrome (CPPS) represents a challenge for the urologist, since the therapeutic efficacy does not always result in a satisfactory quality of life for the patients. Often the side effects of the medications used (antiinflammatories, antibiotics, alpha blockers) far outweighs the benefits gained with their admission. The choice of nutraceutical medications is preferred for their effectiveness, that has been accepted and proven by the scientific community, and for the low incidence of side effects. The objective of this study to compare the therapeutic efficacy of the flower pollen extracts (Deprox®) versus Bioflavonoids in terms of reduction of symptoms, and in the average waiting time of the variation of the National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI), and to evaluate the quality of life improvement of the patients affected by CP/CPPS. Methods: Among the 68 patients presented with prostatic symptoms to the Hospital “Umberto I” in Rome, Italy between March 2016 and June 2016, 54 patients met the clinical diagnosis of CP/CPPS (class IIIa or IIIb according to the NIH classification). The patients were assigned to either treatment with Deprox® or quercetin based on a randomization scheme previously determined.The NIH- CPSI, IPSS, QoL questionnaires were administered. Every patient underwent bacterial cultures and trans-rectal ultrasound. Results: There was a statistically significant improvement of the NIH-CPSI score and QoL in the Deprox® group (p = < 0.0001 and p = 0.003 respectively). The average waiting time of the variation of the National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI) was statistically significant (p = 0.0019). In the absence of efficacy of the “conventional” medications, which also carries significant side effects, the dietary supplements may represent a valid alternative. Conclusions: DEPROX® has demonstrated a significant improvement of the symptoms and quality of life of patients diagnosed with by CP/CPPS. Furthermore, there was a statistical difference in the average waiting time of the variation of the NIH-CPSI) score without side effects as compared to the bioflavonoids complex with quercetin

Cutaneous melanoma: From pathogenesis to therapy (Review)

In less than 10 years, melanoma treatment has beenrevolutionized with the approval of tyrosine kinase inhibitorsand immune checkpoint inhibitors, which have been shownto have a significant impact on the prognosis of patients withmelanoma. The early steps of this transformation have takenplace in research laboratories. The mitogen-activated proteinkinase (MAPK) pathway, phosphoinositol-3-kinase (PI3K)pathway promote the development of melanoma throughnumerous genomic alterations on different components of thesepathways. Moreover, melanoma cells deeply interact with thetumor microenvironment and the immune system. This knowledge has led to the identification of novel therapeutic targets andtreatment strategies. In this review, the epidemiological featuresof cutaneous melanoma along with the biological mechanismsinvolved in its development and progression are summarized.The current state-of-the-art of advanced stage melanoma treatment strategies and the currently available evidence of the use ofpredictive and prognostic biomarkers are also discussed

Malaria blood stage infection suppresses liver stage infection via host-induced interferons but not hepcidin

Abstract Malaria-causing Plasmodium parasites first replicate as liver stages (LS), which then seed symptomatic blood stage (BS) infection. Emerging evidence suggests that these stages impact each other via perturbation of host responses, and this influences the outcome of natural infection. We sought to understand whether the parasite stage interplay would affect live-attenuated whole parasite vaccination, since the efficacy of whole parasite vaccines strongly correlates with their extend of development in the liver. We thus investigated the impact of BS infection on LS development of genetically attenuated and wildtype parasites in female rodent malaria models and observed that for both, LS infection suffered severe suppression during concurrent BS infection. Strikingly and in contrast to previously published studies, we find that the BS-induced iron-regulating hormone hepcidin is not mediating suppression of LS development. Instead, we demonstrate that BS-induced host interferons are the main mediators of LS developmental suppression. The type of interferon involved depended on the BS-causing parasite species. Our study provides important mechanistic insights into the BS-mediated suppression of LS development. This has direct implications for understanding the outcomes of live-attenuated Plasmodium parasite vaccination in malaria-endemic areas and might impact the epidemiology of natural malaria infection