BETA prime: a first-in-man phase 1 study of AdAPT-001, an armed oncolytic adenovirus for solid tumors.

AdAPT-001 is an oncolytic adenovirus (OAV) with a transforming growth factor beta (TGF-ß) trap, which neutralizes the immunosuppressive and profibrotic cytokine, TGF-ß. The aim or purpose of this phase 1 study was to assess the safety and tolerability and, secondarily, the efficacy of AdAPT-001 after single intratumoral injection (IT) (Part 1) and multidose IT injection (Part 2) in patients with superficially accessible, advanced refractory solid tumors. Part 1 enrolled 9 patients with a 3 + 3 single dose-escalation safety run-in involving 2.

Combination of Itacitinib or Parsaclisib with Pembrolizumab in Patients with Advanced Solid Tumors: A Phase I Study.

Purpose: This phase Ib open-label, multicenter, platform study (NCT02646748) explored safety, tolerability, and preliminary activity of itacitinib (Janus kinase 1 inhibitor) or parsaclisib (phosphatidylinositol 3-kinase δ inhibitor) in combination with pembrolizumab [programmed death-1 (PD-1) inhibitor].

Experimental Design: Patients with advanced or metastatic solid tumors with disease progression following all available therapies were enrolled and received itacitinib (Part 1 initially 300 mg once daily) or parsaclisib (Part 1 initially 10 mg once daily; Part 2 all patients 0.3 mg once daily) plus pembrolizumab (200 mg every 3 weeks).

Exercise-Related Physical Activity Relates to Brain Volumes in 10,125 Individuals.

Background: The potential neuroprotective effects of regular physical activity on brain structure are unclear, despite links between activity and reduced dementia risk.

Objective: To investigate the relationships between regular moderate to vigorous physical activity and quantified brain volumes on magnetic resonance neuroimaging.

Methods: A total of 10,125 healthy participants underwent whole-body MRI scans, with brain sequences including isotropic MP-RAGE.

Response to OKN-007 and NAC in a Patient with Unilateral Hearing Loss and Chronic Tinnitus from Vestibular Schwannoma.

Background: Tinnitus is the perception of sound in the absence of external acoustic stimulation. Being one of the most common diseases of the ear, it has a global prevalence ranging from 4.1 to 37.

Pilot Study of High-Dose Pemetrexed in Patients with Progressive Chordoma.

Purpose: Chordomas are ultrarare tumors of the axial spine and skull-base without approved systemic therapy. Most chordomas have negative expression of thymidylate synthase (TS), suggesting a potential for responding to the antifolate agent pemetrexed, which inhibits TS and other enzymes involved in nucleotide biosynthesis. We evaluated the therapeutic activity and safety of high-dose pemetrexed in progressive chordoma.

Chromatin insulation orchestrates matrix metalloproteinase gene cluster expression reprogramming in aggressive breast cancer tumors.

Background: Triple-negative breast cancer (TNBC) is an aggressive subtype that exhibits a high incidence of distant metastases and lacks targeted therapeutic options. Here we explored how the epigenome contributes to matrix metalloprotease (MMP) dysregulation impacting tumor invasion, which is the first step of the metastatic process.

Methods: We combined RNA expression and chromatin interaction data to identify insulator elements potentially associated with MMP gene expression and invasion.

A phase 2 open-label extension study of prekallikrein inhibition with donidalorsen for hereditary angioedema.

Background: Hereditary angioedema (HAE) is a potentially fatal disease characterized by unpredictable, recurrent, often disabling swelling attacks. In a randomized phase 2 study, donidalorsen reduced HAE attack frequency and improved patient quality-of-life (ISIS721744-CS2, NCT04030598). We report the 2-year interim analysis of the phase 2 open-label extension (OLE) study (ISIS 721744-CS3, NCT04307381).

Multi-omic profiling reveals discrepant immunogenic properties and a unique tumor microenvironment among melanoma brain metastases.

Melanoma brain metastases (MBM) are clinically challenging to treat and exhibit variable responses to immune checkpoint therapies. Prior research suggests that MBM exhibit poor tumor immune responses and are enriched in oxidative phosphorylation. Here, we report results from a multi-omic analysis of a large, real-world melanoma cohort.

MiR-181a targets STING to drive PARP inhibitor resistance in BRCA- mutated triple-negative breast cancer and ovarian cancer.

Background: Poly (ADP-ribose) polymerase inhibitors (PARPi) are approved for the treatment of BRCA-mutated breast cancer (BC), including triple-negative BC (TNBC) and ovarian cancer (OvCa). A key challenge is to identify the factors associated with PARPi resistance; although, previous studies suggest that platinum-based agents and PARPi share similar resistance mechanisms.

Methods: Olaparib-resistant (OlaR) cell lines were analyzed using HTG EdgeSeq miRNA Whole Transcriptomic Analysis (WTA).

Is therapeutic lymph node dissection of value for lymph node recurrence in melanoma?

Background: Therapeutic lymphadenectomy (TLND) is still performed in most melanoma patients to treat nodal recurrences after initial negative lymph node biopsy (-SLNB), despite the lack of evidence for survival benefit. We sought to compare melanoma-specific survival (MSS) and distant metastasis-free survival (DMFS) of patients who underwent TLND versus no TLND using our institutional and MSTL-1 databases.

Methods: We identified 146 patients with nodal recurrence following -SLNB: 132 underwent TLND and 14 did not.