PSCA-targeted BPX-601 CAR T cells with pharmacological activation by rimiducid in metastatic pancreatic and prostate cancer: a phase 1 dose escalation trial.

Here we report results of a phase 1 multi-institutional, open-label, dose-escalation trial (NCT02744287) of BPX-601, an investigational autologous PSCA-directed GoCAR-T® cell product containing an inducible MyD88/CD40 ON-switch responsive to the activating dimerizer rimiducid, in patients with metastatic pancreatic (mPDAC) or castration-resistant prostate cancer (mCRPC). Primary objectives were to evaluate safety and tolerability and determine the recommended phase 2 dose/schedule (RP2D). Secondary objectives included the assessment of efficacy and characterization of the pharmacokinetics of rimiducid.

Inexpensive Carbon Based Co-Catalyst Modified Zr-MOF Towards Photocatalytic HO and H Production.

The photocatalytic HO and H production are the utmost encouraging paths to overcome the imminent energy crisis. For accomplishing these goals the photocatalysts needs to be stable, trap photons and superior exciton separation, yet these properties are scanty for aqueous stable UiO-66-NH. Hence, UiO-66-NH is armed with inexpensive Carbon nanoparticles that were incorporated through facile solvothermal procedure are employed towards photocatalytic H and HO production.

Magnetic Nanoparticle Aggregation and Complete De-encapsulation of Such Aggregates from a Liquid Drop Interior.

Magnetic nanoparticles (MNPs) have been extensively used for drug delivery, on-demand material deposition, etc. In this study, we demonstrate the capability to extract such MNPs on-demand from a magnetic nanoparticle-laden drop (MNLD) (i.e.

Site of breast cancer metastasis is independent of single nutrient levels.

Cancer metastasis is a major contributor to patient morbidity and mortality, yet the factors that determine the organs where cancers can metastasize are incompletely understood. In this study, we quantify the absolute levels of over 100 nutrients available across multiple tissues in mice and investigate how this relates to the ability of breast cancer cells to grow in different organs. We engineered breast cancer cells with broad metastatic potential to be auxotrophic for specific nutrients and assessed their ability to colonize different organs.

Circular Bioeconomy in Action: Transforming Food Wastes into Renewable Food Resources.

The growing challenge of food waste management presents a critical opportunity for advancing the circular bioeconomy, aiming to transform waste into valuable resources. This paper explores innovative strategies for converting food wastes into renewable food resources, emphasizing the integration of sustainable technologies and zero-waste principles. The main objective is to demonstrate how these approaches can contribute to a more sustainable food system by reducing environmental impacts and enhancing resource efficiency.

Body composition in recurrent prostate cancer and the role of steroidogenic genotype.

Hormone therapy (HT) to treat prostate cancer is reported to cause adverse changes in body composition. Clinically, interpatient body composition changes are heterogeneous, but the biological and clinical determinants of body composition toxicity are unknown. Herein, we test the hypothesis that inherited polymorphisms in steroidogenic genes are associated with differential changes in body composition after HT.

Body composition as a determinant of the therapeutic index with androgen signaling inhibition.

Background: Androgen signaling is central to prostate cancer and men's health. Prior data indicates that increasing body fat is unfavorable in the localized setting yet associated with favorable outcomes in men with metastatic disease. Understanding the biological links between adiposity and prostate cancer may optimize the therapeutic index with ASI.

Pan-cancer subclonal mutation analysis of 7,827 tumors predicts clinical outcome.

Intra-tumor heterogeneity is an important driver of tumor evolution and therapy response. Advances in precision cancer treatment will require understanding of mutation clonality and subclonal architecture. Currently the slow computational speed of subclonal reconstruction hinders large cohort studies.

Metabolite profiling of human renal cell carcinoma reveals tissue-origin dominance in nutrient availability.

The tumor microenvironment is a determinant of cancer progression and therapeutic efficacy, with nutrient availability playing an important role. Although it is established that the local abundance of specific nutrients defines the metabolic parameters for tumor growth, the factors guiding nutrient availability in tumor compared to normal tissue and blood remain poorly understood. To define these factors in renal cell carcinoma (RCC), we performed quantitative metabolomic and comprehensive lipidomic analyses of tumor interstitial fluid (TIF), adjacent normal kidney interstitial fluid (KIF), and plasma samples collected from patients.

Molecular Pathways and Cellular Subsets Associated with Adverse Clinical Outcomes in Overlapping Immune-Related Myocarditis and Myositis.

Immune checkpoint therapies (ICT) can induce life-threatening immune-related adverse events, including myocarditis and myositis, which are rare but often concurrent. The molecular pathways and immune subsets underlying these toxicities remain poorly understood. To address this need, we performed single-cell RNA sequencing of heart and skeletal muscle biopsies obtained from living patients with cancers treated with ICTs and admitted to the hospital with myocarditis and/or myositis (overlapping myocarditis plus myositis, n = 10; myocarditis-only, n = 1) or ICT-exposed patients ruled out for toxicity utilized as controls (n = 9).

A Modular Trial of Androgen Signaling Inhibitor Combinations Testing a Risk-Adapted Strategy in Patients with Metastatic Castration-Resistant Prostate Cancer.

Purpose: To determine the efficacy and safety of risk-adapted combinations of androgen signaling inhibitors and inform disease classifiers for metastatic castration-resistant prostate cancers.

Patients And Methods: In a modular, randomized phase II trial, 192 men were treated with 8 weeks of abiraterone acetate, prednisone, and apalutamide (AAPA; module 1) and then allocated to modules 2 or 3 based on satisfactory (≥50% PSA decline from baseline and <5 circulating tumor cell/7.5 mL) versus unsatisfactory status.

Normalizing granuloma vasculature and matrix improves drug delivery and reduces bacterial burden in tuberculosis-infected rabbits.

Host-directed therapies (HDTs) represent an emerging approach for bacterial clearance during tuberculosis (TB) infection. While most HDTs are designed and implemented for immuno-modulation, other host targets-such as nonimmune stromal components found in pulmonary granulomas-may prove equally viable. Building on our previous work characterizing and normalizing the aberrant granuloma-associated vasculature, here we demonstrate that FDA-approved therapies (bevacizumab and losartan, respectively) can be repurposed as HDTs to normalize blood vessels and extracellular matrix (ECM), improve drug delivery, and reduce bacterial loads in TB granulomas.

Integrative Molecular Analyses of the MD Anderson Prostate Cancer Patient-derived Xenograft (MDA PCa PDX) Series.

Purpose: Develop and deploy a robust discovery platform that encompasses heterogeneity, clinical annotation, and molecular characterization and overcomes the limited availability of prostate cancer models. This initiative builds on the rich MD Anderson (MDA) prostate cancer (PCa) patient-derived xenograft (PDX) resource to complement existing publicly available databases by addressing gaps in clinically annotated models reflecting the heterogeneity of potentially lethal and lethal prostate cancer.

Experimental Design: We performed whole-genome, targeted, and RNA sequencing in representative samples of the same tumor from 44 PDXs derived from 38 patients linked to donor tumor metadata and corresponding organoids.

Use of inferior vena cava guided fluid therapy in the treatment of septic shock: A randomised controlled trial.

Introduction: By administering inferior vena cava (IVC) directed fluid, it is possible to avoid the use of additional fluid and fluid overload in patients with septic shock (SS) and sepsis-induced hypoperfusion (SIH).

Methodology: In patients with SIH and SS, we conducted prospective observational research on fluid therapy. A time-motion trace of the IVC diameter was created using M-mode imaging.

A Visible Light-Driven α-MnO/UiO-66-NH S-Scheme Photocatalyst toward Ameliorated Oxy-TCH Degradation and H Evolution.

Photocatalytic hydrogen production and pollutant degradation using a heterogeneous photocatalyst remains an alternative route for mitigating the impending pollution and energy crisis. Hence, the development of cost-effective and environmentally friendly semiconducting materials with high solar light captivation nature is imperative. To overcome this challenge, α-MnO nanorod (NR)-modified MOF UiO-66-NH (UNH) was prepared via a facile solvothermal method, which is efficient toward H evolution and oxy-tetracycline hydrochloride (O-TCH) degradation.

Wnt inhibition alleviates resistance to immune checkpoint blockade in glioblastoma.

Wnt signaling plays a critical role in the progression and treatment outcome of glioblastoma (GBM). Here, we identified WNT7b as a heretofore unknown mechanism of resistance to immune checkpoint inhibition (αPD1) in GBM patients and murine models. Acquired resistance to αPD1 was found to be associated with the upregulation of Wnt7b and β-catenin protein levels in GBM in patients and in a clinically relevant, stem-rich GBM model.

Development of a Strategic Initiative at MD Anderson Cancer Center to Improve Outcomes in Immune-Related Adverse Events.

Immune checkpoint inhibitors (ICIs) have transformed the treatment paradigm for many cancer types. The clinical use of ICIs is increasing rapidly, including in combinations associated with increased risk of toxicities, termed "immune-related adverse events" (irAEs). Therefore, MD Anderson Cancer Center (MDACC) in Houston, Texas has proactively responded by developing a priority endeavor known as the Immuno-Oncology Toxicity (IOTOX) initiative.

Metabolite profiling of human renal cell carcinoma reveals tissue-origin dominance in nutrient availability.

The tumor microenvironment is a determinant of cancer progression and therapeutic efficacy, with nutrient availability playing an important role. Although it is established that the local abundance of specific nutrients defines the metabolic parameters for tumor growth, the factors guiding nutrient availability in tumor compared to normal tissue and blood remain poorly understood. To define these factors in renal cell carcinoma (RCC), we performed quantitative metabolomic and comprehensive lipidomic analyses of tumor interstitial fluid (TIF), adjacent normal kidney interstitial fluid (KIF), and plasma samples collected from patients.

Evaluation of the Aggressive-Variant Prostate Cancer Molecular Signature in Clinical Laboratory Improvement Amendments (CLIA) Environments.

(AVPCs) are a subset of metastatic castrate-resistant prostate cancers (mCRPCs) characterized by defects in ≥ two of three of , , and (AVPCm), a profile linked to lineage plasticity, androgen indifference, and platinum sensitivity. Men with mCRPC undergoing biopsies for progression were assessed for AVPCm using immunohistochemistry (IHC), next-generation sequencing (NGS) of solid tumor DNA (stDNA), and NGS of circulating tumor DNA (ctDNA) assays in CLIA-certified labs. Biopsy characteristics, turnaround times, inter-reader concordance, and inter-assay concordance were assessed.

Cardiometabolic healthcare for men with prostate cancer: an MD Anderson Cancer Center experience.

Background: Men diagnosed with prostate cancer are at risk for competing morbidity and mortality due to cardiometabolic disease given their advanced age at diagnosis, high prevalence of pre-existing risk factors, and receipt of systemic therapy that targets the androgen receptor (AR). Expert panels have stressed the importance of cardiometabolic risk assessment in the clinic and proposed evaluating key risks using consensus paradigms. Yet, there is a gap in real-world evidence for implementation of comprehensive cardiometabolic care for men with prostate cancer.

Biomethanol production from renewable resources: a sustainable approach.

The abundant availability of various kinds of biomass and their use as feedstock for the production of gaseous and liquid biofuels has been considered a viable, eco-friendly, and sustainable mode of energy generation. Gaseous fuels like biogas and liquid fuels, e.g.

Three-Dimensional Deposits from Drying Particle-Laden Drops.

Formation of inhomogeneous (in the form of a "coffee ring") or homogeneous deposits accompanies the drying of a particle-laden drop. Invariably, this deposition occurs in a two-dimensional (2D) space (, plane) (and might have a finite thickness in ), where the evaporating drop is positioned. Here, we show an interesting extension of this problem: we demonstrate the occurrence of evaporation-mediated particle deposits that span three dimensions (, , and ).

Plastic waste management for sustainable environment: techniques and approaches.

Excessive exploitation, negligence, non-degradable nature, and physical and chemical properties of plastic waste have resulted in a massive pollution load into the environment. Consequently, plastic entres the food chain and can cause serious health issues in aquatic animals and humans. The present review summarizes currently reported techniques and approaches for the removal of plastic waste.