Radiological Patterns of Drug-induced Interstitial Lung Disease (DILD) in Early-phase Oncology Clinical Trials.

Purpose: Drug-induced interstitial lung disease (DILD) is a rare, but potentially fatal toxicity. Clinical and radiological features of DILD in the early experimental setting are poorly described.

Patients And Methods: A total of 2,499 consecutive patients with advanced cancer on phase I clinical trials were included.

Phase 1 Study of Molibresib (GSK525762), a Bromodomain and Extra-Terminal Domain Protein Inhibitor, in NUT Carcinoma and Other Solid Tumors.

Background: Bromodomain and extra-terminal domain proteins are promising epigenetic anticancer drug targets. This first-in-human study evaluated the safety, recommended phase II dose, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of the bromodomain and extra-terminal domain inhibitor molibresib (GSK525762) in patients with nuclear protein in testis (NUT) carcinoma (NC) and other solid tumors.

Methods: This was a phase I and II, open-label, dose-escalation study.

Clinical outcomes in men of diverse ethnic backgrounds with metastatic castration-resistant prostate cancer.

Background: We have shown previously in multivariable analysis that black men had 19% lower risk of death than white men with metastatic castration-resistant prostate cancer (mCRPC) treated with a docetaxel and prednisone (DP)-based regimen. The primary goal of this analysis was to compare progression-free survival (PFS), biochemical PFS, ≥50% decline in prostate-specific antigen (PSA) from baseline and objective response rate (ORR) in white, black and Asian men with mCRPC treated with a DP-based regimen.

Patients And Methods: Individual patient data from 8820 mCRPC men randomized on nine phase III trials to a DP-containing regimen were combined.

Metabolomic changes of the multi (-AGC-) kinase inhibitor AT13148 in cells, mice and patients are associated with NOS regulation.

Introduction: To generate biomarkers of target engagement or predictive response for multi-target drugs is challenging. One such compound is the multi-AGC kinase inhibitor AT13148. Metabolic signatures of selective signal transduction inhibitors identified in preclinical models have previously been confirmed in early clinical studies.

Systematic Review of Efficacy and Health Economic Implications of Real-world Treatment Sequencing in Prostate Cancer: Where Do the Newer Agents Enzalutamide and Abiraterone Fit in?

Context: Optimal treatment sequencing of abiraterone and enzalutamide in chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) is challenging. Real-world data (RWD) allow a better understanding of health economic implications in the real world.

Objective: To determine survival and cost outcomes for two real-world treatment sequences, comparing abiraterone to enzalutamide (AA → ENZ) with enzalutamide to abiraterone (ENZ → AA).

CDCP1 overexpression drives prostate cancer progression and can be targeted in vivo.

The mechanisms by which prostate cancer shifts from an indolent castration-sensitive phenotype to lethal castration-resistant prostate cancer (CRPC) are poorly understood. Identification of clinically relevant genetic alterations leading to CRPC may reveal potential vulnerabilities for cancer therapy. Here we find that CUB domain-containing protein 1 (CDCP1), a transmembrane protein that acts as a substrate for SRC family kinases (SFKs), is overexpressed in a subset of CRPC.

Genetic manipulation of LKB1 elicits lethal metastatic prostate cancer.

Gene dosage is a key defining factor to understand cancer pathogenesis and progression, which requires the development of experimental models that aid better deconstruction of the disease. Here, we model an aggressive form of prostate cancer and show the unconventional association of LKB1 dosage to prostate tumorigenesis. Whereas loss of Lkb1 alone in the murine prostate epithelium was inconsequential for tumorigenesis, its combination with an oncogenic insult, illustrated by Pten heterozygosity, elicited lethal metastatic prostate cancer.

Molecular and immunological features of a prolonged exceptional responder with malignant pleural mesothelioma treated initially and rechallenged with pembrolizumab.

Background: This case represents an exceptional response to pembrolizumab in a patient with epithelioid mesothelioma with a further response on rechallenge.

Case Presentation: A 77-year-old woman with advanced epithelioid mesothelioma extensively pretreated with chemotherapy demonstrated a prolonged response of 45 months to 52 cycles of pembrolizumab. On rechallenge with pembrolizumab, further disease stability was achieved.

Two first-in-human studies of xentuzumab, a humanised insulin-like growth factor (IGF)-neutralising antibody, in patients with advanced solid tumours.

Background: Xentuzumab, an insulin-like growth factor (IGF)-1/IGF-2-neutralising antibody, binds IGF-1 and IGF-2, inhibiting their growth-promoting signalling. Two first-in-human trials assessed the maximum-tolerated/relevant biological dose (MTD/RBD), safety, pharmacokinetics, pharmacodynamics, and activity of xentuzumab in advanced/metastatic solid cancers.

Methods: These phase 1, open-label trials comprised dose-finding (part I; 3 + 3 design) and expansion cohorts (part II; selected tumours; RBD [weekly dosing]).

Genomic-based identification of environmental and clinical Listeria monocytogenes strains associated with an abortion outbreak in beef heifers.

Background: In a beef cattle facility an outbreak of abortions occurred over a 36-day period and included samples from two aborted (non-viable) fetuses and 21 post-abortion clinical cases. There are numerous etiologies, including clinical listeriosis. At the species level, Listeria monocytogenes is ubiquitous in cattle production environments, including soil, feed, and occasionally water sources, and is a common enteric resident of cattle and other mammals.

Complete Genome Sequencing of Four Arcobacter Species Reveals a Diverse Suite of Mobile Elements.

Arcobacter species are recovered from a wide variety of sources, including animals, food, and both fresh and marine waters. Several Arcobacter species have also been recovered from human clinical samples and are thus associated tentatively with food- and water-borne human illnesses. Genome sequencing of the poultry isolate Arcobacter cibarius H743 and the Arcobacter acticola, Arcobacter pacificus, and Arcobacter porcinus type strains identified a large number and variety of insertion sequences.

Management of Patients with Advanced Prostate Cancer: Report of the Advanced Prostate Cancer Consensus Conference 2019.

Background: Innovations in treatments, imaging, and molecular characterisation in advanced prostate cancer have improved outcomes, but there are still many aspects of management that lack high-level evidence to inform clinical practice. The Advanced Prostate Cancer Consensus Conference (APCCC) 2019 addressed some of these topics to supplement guidelines that are based on level 1 evidence.

Objective: To present the results from the APCCC 2019.

Publisher Correction: A Computational Method to Quantify the Effects of Slipped Strand Mispairing on Bacterial Tetranucleotide Repeats.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Circulating cell-free DNA: Translating prostate cancer genomics into clinical care.

Only in the past decade tremendous advances have been made in understanding prostate cancer genomics and consequently in applying new treatment strategies. As options regarding treatments are increasing so are the challenges in selecting the right treatment option for each patient and not the least, understanding the optimal time-point and sequence of applying available treatments. Critically, without reliable methods that enable sequential monitoring of evolving genotypes in individual patients, we will never reach effective personalised driven treatment approaches.

Tumour-derived extracellular vesicles in blood of metastatic cancer patients associate with overall survival.

Background: Circulating tumour cells (CTCs) in blood associate with overall survival (OS) of cancer patients, but they are detected in extremely low numbers. Large tumour-derived extracellular vesicles (tdEVs) in castration-resistant prostate cancer (CRPC) patients are present at around 20 times higher frequencies than CTCs and have equivalent prognostic power. In this study, we explored the presence of tdEVs in other cancers and their association with OS.

Diverse Gene Rearrangements Mediate Resistance to Androgen Receptor Inhibitors in Metastatic Prostate Cancer.

Purpose: Prostate cancer is the second leading cause of male cancer deaths. Castration-resistant prostate cancer (CRPC) is a lethal stage of the disease that emerges when endocrine therapies are no longer effective at suppressing activity of the androgen receptor (AR) transcription factor. The purpose of this study was to identify genomic mechanisms that contribute to the development and progression of CRPC.

Efficacy of manipulation under anesthesia beyond three months following total knee arthroplasty.

Background: Stiffness after total knee arthroplasty (TKA) is often treated with manipulation under anesthesia (MUA) to improve range of motion (ROM). However, many authors recommend against MUA beyond 3 months after TKA. This study investigates the timing of MUA for stiffness after TKA, focusing on MUA performed at >12 weeks.

Midterm follow-up of total hip arthroplasty in a patient with contralateral Van Nes rotationplasty for congenital proximal femoral focal deficiency.

Total hip arthroplasty is a durable and effective operation in those with normal gait patterns. However, to our knowledge, there is no current literature on longevity in patients who have had a contralateral Van Nes rotationplasty for proximal femoral focal deficiency. We found evidence that patients who underwent rotationplasty have increased demands on the contralateral extremity and higher percentage of their gait cycle on the unaffected extremity.

Comparative analysis of microbiota along the length of the gastrointestinal tract of two tree squirrel species ( and ) living in sympatry.

Microbiota inhabiting the gastrointestinal (GI) tract of animals has important impacts on many host physiological processes. Although host diet is a major factor influencing the composition of the gut micro-organismal community, few comparative studies have considered how differences in diet influence community composition across the length of the GI tract. We used 16S sequencing to compare the microbiota along the length of the GI tract in Abert's () and fox squirrels () living in the same habitat.

Association Between New Unconfirmed Bone Lesions and Outcomes in Men With Metastatic Castration-Resistant Prostate Cancer Treated With Enzalutamide: Secondary Analysis of the PREVAIL and AFFIRM Randomized Clinical Trials.

Importance: For men with metastatic castration-resistant prostate cancer (mCRPC) whose condition is responding to enzalutamide, new unconfirmed bone lesions detected at posttreatment scinitigraphy may reflect an osteoblastic reaction that represents healing, known as pseudoprogression, which can lead to premature discontinuation of therapy.

Objective: To determine the association between new unconfirmed lesions detected on a follow-up bone scintigram (bone scan) and outcomes in enzalutamide-treated men with mCRPC.

Design, Setting, And Participants: This post hoc, retrospective secondary analysis of 1672 enzalutamide-treated men from 2 phase 3, randomized mCRPC studies (PREVAIL and AFFIRM) before or after treatment with docetaxel was conducted from April 12, 2018, to July 25, 2019.

LCO Receptors Involved in Arbuscular Mycorrhiza Are Functional for Rhizobia Perception in Legumes.

Bacterial lipo-chitooligosaccharides (LCOs) are key mediators of the nitrogen-fixing root nodule symbiosis (RNS) in legumes. The isolation of LCOs from arbuscular mycorrhizal fungi suggested that LCOs are also signaling molecules in arbuscular mycorrhiza (AM). However, the corresponding plant receptors have remained uncharacterized.