Prostate Cancer: Quo Vadis?

Utility measures are urgently needed for clinical application of new, more sensitive diagnostics to reduce the risk of excessive intervention. © 2019 European Association of Urolog

Myeloid-derived suppressor cells in prostate cancer: Present knowledge and future perspectives

Several lines of research are being investigated to better understand mechanisms implicated in response or resistance to immune checkpoint blockade in prostate cancer (PCa). Myeloid-derived suppressor cells (MDSCs) have emerged as a major mediator of immunosuppression in the tumor microenvironment that promotes progression of various tumor types. The main mechanisms under-lying MDSC-induced immunosuppression are currently being explored and strategies to enhance anti-tumor immune response via MDSC targeting are being tested. However, the role of MDSCs in PCa remains elusive. In this review, we aim to summarize and present the state-of-the-art knowledge on current methodologies to phenotypically and metabolically characterize MDSCs in PCa. We describe how these characteristics may be linked with MDSC function and may influence the clinical outcomes of patients with PCa. Finally, we briefly discuss emerging strategies being employed to therapeutically target MDSCs and potentiate the long-overdue improvement in the efficacy of immunotherapy in patients with PCa. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Emerging Role of YAP and the Hippo Pathway in Prostate Cancer

The Hippo pathway regulates and contributes to several hallmarks of prostate cancer (PCa). Although the elucidation of YAP function in PCa is in its infancy, emerging studies have shed light on the role of aberrant Hippo pathway signaling in PCa development and progression. YAP overexpression and nuclear localization has been linked to poor prognosis and resistance to treatment, highlighting a therapeutic potential that may suggest innovative strategies to treat cancer. This review aimed to summarize available data on the biological function of the dysregulated Hippo pathway in PCa and identify knowledge gaps that need to be addressed for optimizing the development of YAP-targeted treatment strategies in patients likely to benefit. © 2022 by the authors

Factors Associated With Use of Mental Health and Substance Use Treatment Services by Justice-Involved Youths

ObjectiveNonincarcerated (community-supervised) youths who are first-time offenders have high rates of mental and substance use disorders. However, little is known about their use of psychiatric services (mental health and substance use) or factors associated with service use. This study examined the prevalence, determinants, and barriers to service use among community-supervised youths.MethodsData were from a longitudinal study of mental health and substance use outcomes among adolescents ages 12-18 from a northeastern family court in which caregivers and youths completed assessments (N=423 dyads). The Behavior Assessment System for Children, Second Edition, assessed youths' psychiatric symptoms. The Child and Adolescent Services Assessment assessed service use and barriers. Family functioning and caregiver-adolescent communication were assessed with the McMaster Family Assessment Device and the Parent-Adolescent General Communication Scale, respectively. Multivariable regression analyses examined the cross-sectional relationship between youths' service use and determinants of use at baseline.ResultsOf the 423 youths, 49% experienced psychiatric symptoms and 36% used psychiatric services in the past 4 months. The highest adjusted odds of service use were associated with youths' psychiatric symptoms and caregivers' history of a psychiatric diagnosis. The lowest odds were associated with caregivers' identifying as being from racial and ethnic minority groups. Caregiver-reported barriers to service use differed according to prior service use and by caregiver race-ethnicity.ConclusionsResults suggest a need for interventions to increase access to and engagement in psychiatric services for community-supervised youths and the importance of caregiver factors in designing such interventions

CD8+ PD-1+ T-cells and PD-L1+ circulating tumor cells in chemotherapy-naïve non-small cell lung cancer: towards their clinical relevance?

Background: Since tumor cells may escape from immune surveillance through the programmed cell death 1 (PD-1)/programmed death ligand (PD-L)1 axis, this study was designed in order to evaluate whether there is a correlation between the levels of PD-1+ and PD-L1+-expressing immune cells (ICs) and circulating tumor cells (CTCs) in patients with non-small cell lung cancer (NSCLC). Patients and methods: Peripheral blood was obtained from 37 chemotherapy-naïve patients with metastatic NSCLC before treatment. PD-1 and PD-L1 expression was evaluated (1) on ICs with anti-tumor function (CD4+ and CD8+ T-cells, B-cells, monocytes/dendritic cells) using flow cytometry, (2) on CTCs by immunofluorescence and (3) on cells from tumor tissues by immunohistochemistry. The levels of PD-1+ and PD-L1+-expressing ICs were correlated with progression-free survival (PFS). Results: The presence of PD-1+ CD8+ cells, with reduced interferon (IFN)-γ expression, but not other ICs, were positively correlated with PD-L1+ CTCs (p < 0.04). Increased percentages of PD-1+ CD8+ T-cells, were associated with a worse response to treatment (p = 0.032) and shorter PFS (p = 0.023) which, in multivariate analysis, was revealed as an independent predictor for decreased PFS [hazard ratio (HR): 4.1, p = 0.0007]. Conclusion: The results of the current study, for first time, provide evidence for a possible interaction between ICs and CTCs in NSCLC patients via the PD-1/PD-L1 axis and strongly support that the levels of PD-1+ CD8+ in these patients may be of clinical relevance. © The Author(s), 2019

Predictors of cannabis use among first-time justice-involved youth: A cohort study.

BackgroundJustice-involved youth use cannabis at higher rates than their same-aged peers increasing likelihood of adverse behavioral health consequences and continued legal involvement. This study examined individual level predictors of early onset use cannabis use (<13 years of age) and cannabis use initiation in the 12 months following first court contact.MethodsParticipants were 391 first-time justice-involved youth (56.9 % male; Mage = 14.6 years; 32.1 % White, 11.1 % Black, 14.7 % Other/Multi-racial, 42.2 % Latinx) and an involved caregiver (87.2 % female; Mage = 41.0 years). Baseline assessments captured individual level factors; cannabis use was assessed every four months post-baseline for 12 months. Primary analyses involved multivariable modified Poisson regressions and survival analysis.ResultsIn multivariable models, youth who reported lifetime cannabis use (n = 188, 48.1 %) were older, reported alcohol use and positive cannabis use expectancies. Greater self-control and self-concept were associated with lower likelihood of lifetime cannabis use. Youth who initiated cannabis during the 12-month follow-up (n = 30, 14.8 %) tended to be older, White/non-Latinx, and to report more psychiatric symptoms (posttraumatic stress, externalizing, internalizing, and affect dysregulation), delinquent behavior, lower levels of self-control, poorer self-concept, greater drug use intentions and positive cannabis expectancies. In the multivariable survival analysis, affect dysregulation, internalizing symptoms, and more positive cannabis expectancies remained independently and positively associated with cannabis initiation.ConclusionsThere is a critical and unique window of opportunity to prevent cannabis use initiation among first-time justice-involved youth. Research is needed to determine whether brief interventions that aim to modify expectancies about cannabis use reduce rates of cannabis initiation in this underserved population

Ribavirin Inhibits Parrot Bornavirus 4 Replication in Cell Culture

<div><p>Parrot bornavirus 4 is an etiological agent of proventricular dilatation disease, a fatal neurologic and gastrointestinal disease of psittacines and other birds. We tested the ability of ribavirin, an antiviral nucleoside analog with antiviral activity against a range of RNA and DNA viruses, to inhibit parrot bornavirus 4 replication in duck embryonic fibroblast cells. Two analytical methods that evaluate different products of viral replication, indirect immunocytochemistry for viral specific nucleoprotein and qRT-PCR for viral specific phosphoprotein gene mRNA, were used. Ribavirin at concentrations between 2.5 and 25 μg/mL inhibited parrot bornavirus 4 replication, decreasing viral mRNA and viral protein load, in infected duck embryonic fibroblast cells. The addition of guanosine diminished the antiviral activity of ribavirin suggesting that one possible mechanism of action against parrot bornavirus 4 may likely be through inosine monophosphate dehydrogenase inhibition. This study demonstrates parrot bornavirus 4 susceptibility to ribavirin in cell culture.</p></div