Specific Plasma MicroRNA Signatures Underlying the Clinical Outcomes of Hepatitis E Virus Infection.

The pathogenic mechanisms determining the diverse clinical outcomes of HEV infection (e.g., self-limiting versus chronic or symptomatic versus asymptomatic) are not yet understood.

A Clinically Significant Prostate Cancer Predictive Model Using Digital Rectal Examination Prostate Volume Category to Stratify Initial Prostate Cancer Suspicion and Reduce Magnetic Resonance Imaging Demand.

A predictive model including age, PCa family history, biopsy status (initial vs repeat), DRE (normal vs abnormal), serum prostate-specific antigen (PSA), and DRE prostate volume ca-tegory was developed to stratify initial PCa suspicion in 1486 men with PSA > 3 ng/mL and/or abnormal DRE, in whom mpMRI followed; 2- to 4-core TRUS-guided biopsies where Prostate Imaging Report and Data System (PI-RADS) > 3 lesions and/or 12-core TRUS systematic biopsies were performed in one academic institution between 1 January 2016−31 December 2019. The csPCa detection rate, defined as International Society of Uro-Pathology grade group 2 or higher, was 36.9%.

Effect of LHRH analogs on lower urinary tract symptoms associated with advanced prostate cancer in real clinical practice: ANALUTS study.

Aims: To estimate the prevalence of lower urinary tract symptoms (LUTS) in patients with prostate cancer scheduled to receive LHRH analogs, and to assess the effectiveness of LHRH analogs on LUTS in patients presenting moderate/severe symptoms.

Methods: Prospective, noninterventional, multicenter study conducted at 28 centers in Spain and Portugal. LUTS were evaluated using the International Prostate Symptom Score (IPSS) at baseline, 24 and 48 weeks after initiation of treatment.

Reduced humoral response 3 months following BNT162b2 vaccination in SARS-CoV-2 uninfected residents of long-term care facilities.

Background: SARS-CoV-2 vaccination is the most effective strategy to protect older residents of long-term care facilities (LTCF) against severe COVID-19, but primary vaccine responses are less effective in older adults. Here, we characterised the humoral responses of institutionalised seniors 3 months after they had received the mRNA/BNT162b2 vaccine.

Methods: plasma levels of SARS-CoV-2-specific total IgG, IgM and IgA antibodies were measured before and 3 months after vaccination in older residents of LTCF.

Spontaneous changes in brain striatal dopamine synthesis and storage dynamics ex vivo reveal end-product feedback-inhibition of tyrosine hydroxylase.

Synaptic events are important to define treatment strategies for brain disorders. In the present paper, freshly obtained rat brain striatal minces were incubated under different times and conditions to determine dopamine biosynthesis, storage, and tyrosine hydroxylase phosphorylation. Remarkably, we found that endogenous dopamine spontaneously accumulated during tissue incubation at 37 °C ex vivo while dopamine synthesis simultaneously decreased.

Phase 1 study of single-agent WNT974, a first-in-class Porcupine inhibitor, in patients with advanced solid tumours.

Background: This Phase 1 study assessed the safety and efficacy of the Porcupine inhibitor, WNT974, in patients with advanced solid tumours.

Methods: Patients (n = 94) received oral WNT974 at doses of 5-30 mg once-daily, plus additional dosing schedules.

Results: The maximum tolerated dose was not established; the recommended dose for expansion was 10 mg once-daily.

How liquid biopsies can change clinical practice in oncology.

Cell-free DNA fragments are shed into the bloodstream by tumor cells. The analysis of circulating tumor DNA (ctDNA), commonly known as liquid biopsy, can be exploited for a variety of clinical applications. ctDNA is being used to genotype solid cancers non-invasively, to track tumor dynamics and to detect the emergence of drug resistance.

A novel DNA-binding motif in prostate tumor overexpressed-1 (PTOV1) required for the expression of ALDH1A1 and CCNG2 in cancer cells.

PTOV1 is a transcription and translation regulator and a promoter of cancer progression. Its overexpression in prostate cancer induces transcription of drug resistance and self-renewal genes, and docetaxel resistance. Here we studied PTOV1 ability to directly activate the transcription of ALDH1A1 and CCNG2 by binding to specific promoter sequences.

Efficacy and safety of ozanimod in multiple sclerosis: Dose-blinded extension of a randomized phase II study.

Background: Ozanimod, an oral immunomodulator, selectively targets sphingosine 1-phosphate receptors 1 and 5.

Objective: Evaluate efficacy, safety, and tolerability of ozanimod in relapsing multiple sclerosis.

Methods: In the RADIANCE Part A phase II study (NCT01628393), participants with relapsing multiple sclerosis were randomized (1:1:1) to once-daily ozanimod hydrochloride (0.

Phase I Trial of a Tablet Formulation of Pilaralisib, a Pan-Class I PI3K Inhibitor, in Patients with Advanced Solid Tumors.

Lessons Learned: A phase I study of the pan-class I phosphoinositide 3-kinase inhibitor pilaralisib (in capsule formulation) in advanced solid tumors established the maximum tolerated dose as 600 mg once daily.The current study investigated pilaralisib in tablet formulation.Pilaralisib tablets were associated with a favorable safety profile and preliminary antitumor activity.

Relative bioavailability of three formulations of galunisertib administered as monotherapy in patients with advanced or metastatic cancer.

Objective: Galunisertib (LY2157299 monohydrate), an inhibitor of the transforming growth factor β (TGFβ) pathway, is currently under investigation in several clinical trials involving multiple tumor types. The primary objective of this study was to assess relative bioavailability of two new galunisertib formulations developed using the roller compaction (RC) dry-milled (RCD) and RC slurry-milled (RCS) processes, compared with the existing formulation developed using the high-sheer wet granulation (HSWG) process. The secondary objective was to report the safety profile after a single dose of the three formulations.

Phase I Study of the Investigational Anti-Guanylyl Cyclase Antibody-Drug Conjugate TAK-264 (MLN0264) in Adult Patients with Advanced Gastrointestinal Malignancies.

Purpose: To assess the safety, tolerability, and preliminary antitumor activity of the investigational anti-guanylyl cyclase C (GCC) antibody-drug conjugate TAK-264 (formerly MLN0264) in adult patients with advanced gastrointestinal malignancies.

Experimental Design: Adult patients with GCC-expressing gastrointestinal malignancies (H-score ≥ 10) were eligible for inclusion. TAK-264 was administered as a 30-minute intravenous infusion once every 3 weeks for up to 17 cycles.

A Phase II randomized study of galunisertib monotherapy or galunisertib plus lomustine compared with lomustine monotherapy in patients with recurrent glioblastoma.

Background: The combination of galunisertib, a transforming growth factor (TGF)-β receptor (R)1 kinase inhibitor, and lomustine was found to have antitumor activity in murine models of glioblastoma.

Methods: Galunisertib (300 mg/day) was given orally 14 days on/14 days off (intermittent dosing). Lomustine was given as approved.

The Personalization of Therapy: Molecular Profiling Technologies and Their Application.

Advances in tumor biology and human genetics that have identified driver events and critical dependencies, together with the development of drugs for specific targets, hold promise for an era of personalized oncology treatment. The efficacy of targeted therapies in patient populations selected for treatment on the basis of the molecular features of their tumors is shifting the current practice, and molecular profiling of patients to support clinical decision-making is becoming part of the everyday clinical practice in oncology. Actionable biomarkers are those that allow matching patients to specific therapies.

Urinary biomarkers for the detection of prostate cancer in patients with high-grade prostatic intraepithelial neoplasia.

Introduction: High-grade prostatic intraepithelial neoplasia (HGPIN) is a recognized precursor stage of PCa. Men who present HGPIN in a first prostate biopsy face years of active surveillance including repeat biopsies. This study aimed to identify non-invasive prognostic biomarkers that differentiate early on between indolent HGPIN cases and those that will transform into actual PCa.

Phase I Trial of the Pan-PI3K Inhibitor Pilaralisib (SAR245408/XL147) in Patients with Chronic Lymphocytic Leukemia (CLL) or Relapsed/Refractory Lymphoma.

Purpose: This phase I expansion-cohort study evaluated the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of the pan-PI3K inhibitor pilaralisib (SAR245408/XL147) in patients with chronic lymphocytic leukemia (CLL) or relapsed or refractory lymphoma.

Patients And Methods: Patients were treated with the maximum tolerated dose of pilaralisib previously determined in patients with solid tumors (600 mg capsules once daily). Adverse events (AE) and response were evaluated.

A first-in-human phase I, dose-escalation, multicentre study of HSP990 administered orally in adult patients with advanced solid malignancies.

Background: Heat-shock protein 990 (HSP990) is a potent and selective synthetic small-molecule HSP90 inhibitor. The primary objectives of this phase I first-in-human study were to determine dose-limiting toxicities (DLTs), maximum-tolerated dose (MTD) and recommended phase II dose (RP2D). Secondary objectives included characterisation of the safety profile, pharmacokinetics (PKs) and pharmacodynamics (PDs).

Pharmacokinetic, pharmacodynamic and biomarker evaluation of transforming growth factor-β receptor I kinase inhibitor, galunisertib, in phase 1 study in patients with advanced cancer.

Purpose Transforming growth factor-beta (TGF-β) signaling plays a key role in epithelial-mesenchymal transition (EMT) of tumors, including malignant glioma. Small molecule inhibitors (SMI) blocking TGF-β signaling reverse EMT and arrest tumor progression. Several SMIs were developed, but currently only LY2157299 monohydrate (galunisertib) was advanced to clinical investigation.

ETV5 transcription program links BDNF and promotion of EMT at invasive front of endometrial carcinomas.

Myometrial infiltration represents a main clinical determinant of endometrial carcinomas (EC) presenting as aggressive high-grade deeply invasive neoplasms, substantially associated with risk of recurrence and death. The up-regulation of ETV5 transcription factor linked to the promotion of epithelial to mesenchymal transition is considered as a basic mechanism underlying the initial steps of EC invasion. In this work, we aimed to investigate the transcription program of tumor invasion regulated by ETV5.

Implant survival after deep infection of an instrumented spinal fusion.

This study evaluates the long-term survival of spinal implants after surgical site infection (SSI) and the risk factors associated with treatment failure. A Kaplan-Meier survival analysis was carried out on 43 patients who had undergone a posterior spinal fusion with instrumentation between January 2006 and December 2008, and who consecutively developed an acute deep surgical site infection. All were appropriately treated by surgical debridement with a tailored antibiotic program based on culture results for a minimum of eight weeks.

Age-related survival and clinical features in systemic sclerosis patients older or younger than 65 at diagnosis.

Objective: To analyse the differences in SSc clinical features and survival in patients aged > or = 65 years compared with young SSc patients.

Methods: Of a total of 319 SSc patients, we identified 67 (21%) patients aged >65 years. Demographical data such as SSc subsets, the cutaneous complaint, internal organ involvement and the causes of morbidity and mortality were collected.