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Category: biotech/medical – Page 64

Novel radioligand therapy proven superior for metastatic prostate cancer patients

A novel prostate cancer treatment—225 Ac-PSMA-617 radioligand therapy—has been shown to increase the progression free survival (PFS) and overall survival (OS) of metastatic castration-resistant prostate cancer (mCRPC) patients, according to research published by The Journal of Nuclear Medicine. Ninety-one percent of patients experienced a greater than 50% reduction of their initial PSA (prostate specific antigen) value after treatment with 225 Ac-PSMA-617, resulting in a PFS of 22 months and an OS not yet reached at the conclusion of the study.

While the five-year survival rate of localized is nearly 100%, for mCRPC patients it is only 30%. Clinical studies have demonstrated the efficacy and safety of several therapies, including 177 Lu-PSMA in the post-androgen deprivation therapy (ADT) setting in patients with mCRPC. Additional therapies, such as 225 Ac-PSMA-617, are often considered once the disease begins to progress again.

“Previous research has shown a remarkable therapeutic efficacy of 225 Ac-PSMA-617 in heavily pre-treated mCRPC patients, as demonstrated by the initial work from Kratochwil et al. from Germany,” said Mike Sathekge, professor and head of the Nuclear Medicine Department at the University of Pretoria and Steve Biko Academic Hospital in Pretoria, South Africa. “In this study we sought to compare 225 Ac-PSMA-617 to other common post-ADT treatments, such as chemotherapy, enzalutamide, and abiraterone acetate or docetaxel, administered in a comparable setting.”

Time-restricted eating may help retain cognitive function in older adults

Results from a small clinical trial suggest it may be possible to reduce the risk of dementia by eating during fewer hours of the day. The pilot study, which involved a weight-loss program for older women with overweight or obesity, showed modest cognitive improvements among those who limited their daily eating window instead of just reducing their calorie intake.

“Losing weight alone will ward off some of the aging-related cognitive decline, and these data suggest that there may be additional benefits if you stop eating four hours before going to sleep and reduce food intake to 8–9 hours per day, compared with the usual eating window of 12 hours per day,” said Sue Shapses, Ph.D., RD, DFASN, professor at Rutgers University and Rutgers-RWJ Medical Center and the study’s principal investigator.

Shapses’ group will present the findings at NUTRITION 2026, the flagship annual meeting of the American Society for Nutrition, held July 25–28 in National Harbor, Maryland, just outside Washington, D.C.

Simple biological age score flags higher cognitive decline risk in older adults

A study of 4,818 middle-aged and older Chinese adults found that higher light BioAge was associated with greater risks of cognitive impairment, episodic memory decline, and reduced mental intactness. The simple measure, based on age, creatinine, glucose, and CRP, added modest predictive information but requires further validation before clinical use.

HypoxiaInduced Epas1Myl9/12 Axis Shapes the Pathology of Pulmonary Hypertension

BACKGROUND: Pulmonary hypertension (PH) is a progressive cardiopulmonary disorder characterized by vascular remodeling, abnormal vasoconstriction of small lung arteries, and right heart failure. Hypoxia causes vascular damage, leading to vessel stenosis or occlusion by aberrant endothelial cells, hypertrophy of the tunica media, and thrombus formation. But the precise molecular mechanisms underlying the pathology of PH have been uncertain. METHODS: To investigate the pathogenic role of Myl (myosin light chain) 9/12 in PH, we utilized the Sugen/hypoxia mouse model, generated by administration of the VEGF (vascular endothelial growth factor) receptor inhibitor SU5416 under hypoxic conditions (10% O2). Lung tissues of patients with PH and human lung microvascular endothelial cells were used to examine their endothelial changes.

Comparative Cardiovascular Outcomes of Tirzepatide and Glucagon‐Like Peptide‐1 Receptor Agonists in Patients With Type 2 Diabetes and Atherosclerotic Cardiovascular Disease

BackgroundTo evaluate the association between tirzepatide use and 1‐year risk of major adverse cardiovascular events in patients with type 2 diabetes and atherosclerotic cardiovascular disease, compared with GLP‐1 (glucagon‐like peptide‐1) receptor agonists.

SingleCell Studies Advance Understanding of the Genetic and Molecular Basis of Atherosclerosis

Foundational models pretrained on millions of single cells (Geneformer, scGPT, and scBERT) now provide transferable embeddings that can help improve and automate cellular annotation, integration, cross-species mapping, and zero-shot predictions.49–51 While there has been considerable contribution to pretraining with immune and tumor data sets, other cell type–specific data for vascular resident parenchymal cells remain sparse, and the applications in atherosclerosis are still emerging. Therefore, overreliance on early foundational models may lead to mislabeling atherosclerosis-specific subtypes and rare cell states, and this area is still being actively investigated with improved consensus in cell types, such as vascular cells (SMC), forthcoming. While promising, we anticipate that these tools will improve with further fine-tuning and robust vascular tissue validation, and interpreted with pathway and genetics-based constraints. Currently, with more modest-sized vascular disease single-cell data sets available, probabilistic variational autoencoder–based methods, such as scVI, MultiVI, and GLUE,44,45,52 offer a good tradeoff between robustness, interpretability, and analytical efficiency. Another exciting area of research is expanding through the development and application of in silico perturbations. While TF perturbation using tools such as CellOracle has provided a first step, improved regulatory network predictions have long been pursued but are still in early stages of implementation.53,54

Deep learning approaches to study TF-DNA interactions are now being utilized to advance our understanding of the DNA regulatory grammar.55 Beyond simple chromatin syntax predictions, deep learning models can provide functional insights, affinity predictions for TF cooperativity, link allelic variation, and chromatin accessibility to cellular epigenetic and transcriptional functions (see below).56 Implementation of a deep learning approach has dramatically extended the capability of scATAC-seq to identify at single basepair resolution the TF motifs that are functional in a cell-specific context to modulate chromatin accessibility, TF binding, and gene expression (Figure 2). Furthermore, allelic variants that are identified with this method are highly enriched among those associated with the complex human traits and diseases that are being investigated. ChromBPNet is a fully convolutional neural network that uncovers the genomic grammar at dynamic enhancers in loci of interest.

A new drug that can potentially overcome cancer therapy resistance

Researchers at Baylor College of Medicine have developed a drug called CS18 that disrupts cancer cells’ ability to survive therapy. The findings, published in Science Advances, support exploring the possibility of using CS18 to treat human cancer in the future.

“Therapeutic resistance is a main obstacle to achieving effective and durable cancer treatments,” said corresponding author Dr. Weei-Chin Lin, professor of medicine—hematology and oncology—and molecular and cellular biology at Baylor. “While some therapies are effective at the beginning, many patients eventually relapse because cancer cells can activate compensatory and convergent biological pathways that allow them to overcome the toxic effects of therapy, promoting survival.”

In the current study, the researchers’ goal was to develop a drug that would target a “biological switchboard”—topoisomerase IIβ-binding protein 1 (TopBP1)—that controls several cancer-driving pathways at once and to determine whether this strategy could deliver durable responses and overcome resistance.

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