JARID1D-dependent androgen receptor and JunD signaling activation of osteoclast differentiation inhibits prostate cancer bone metastasis through demethylating H3K4.

Bone metastasis and skeletal-related complications are primary causes of mortality in advanced-stage prostate cancer (PCa). Epigenetic regulation, particularly histone modification, plays a key role in this process; however, the underlying mechanisms remain elusive. In mouse models, JARID1D was an important mediator of both visceral and bone metastases.

Resveratrol amplifies the anti-tumor effect of α-PD-1 by altering the intestinal microbiome and PGD2 content.

The anti-PD-1 mAb may be further considered along with PGD2 or active molecules that can promote PGD2 synthesis to enhance the anti-tumor immune response.

Novel research model for in vitro immunotherapy: co-culturing tumor organoids with peripheral blood mononuclear cells.

Tumor organoids have emerged as powerful tools for in vitro cancer research due to their ability to retain the structural and genetic characteristics of tumors. Nevertheless, the absence of a complete tumor microenvironment (TME) limits the broader application of organoid models in immunological studies. Given the critical role of immune cells in tumor initiation and progression, the co-culture model of organoids and peripheral blood mononuclear cells (PBMCs) may provide an effective platform for simulating the interactions between immune and tumor cells in vitro.

Engineered Bacteria Manipulate Cysteine Metabolism to Boost Ferroptosis-Based Pancreatic Ductal Adenocarcinoma Therapy.

Cysteine metabolism is a key determinant of the defense against ferroptosis in pancreatic ductal adenocarcinoma (PDAC). Blocking cysteine metabolism may trigger potent ferroptosis in PDAC cells by generating lipid peroxides during tumor metabolic processes. However, current methods to limit cysteine availability fall short, failing to efficiently block cysteine metabolism due to inadequate tumor targeting and compensatory cysteine sources.

Nascent RNA kinetics with complex promoter architecture: Analytic results and parameter inference.

Transcription is a stochastic process that involves several downstream operations which make it difficult to model and infer transcription kinetics from mature RNA numbers in individual cell. However, recent advances in single-cell technologies have enabled a more precise measurement of the fluctuations of nascent RNA that closely reflect transcription kinetics. In this paper we introduce a general stochastic model to mimic nascent RNA kinetics with complex promoter architecture.

Curcumin blunts epithelial-mesenchymal transition to alleviate invasion and metastasis of prostate cancer through the JARID1D demethylation.

Prostate cancer (PCa) is one of the most common and prevalent cancers in men worldwide. The majority of PCa-related deaths result from metastasis rather than primary tumors. Several studies have focused on the relationship between male-specific genes encoded on the Y chromosome and PCa metastasis; however, the relationship between the male specific protein encoded on the Y chromosome and tumor suppression has not been fully clarified.

YAP1 Inhibition Induces Phenotype Switching of Cancer-Associated Fibroblasts to Tumor Suppressive in Prostate Cancer.

Prostate cancer rarely responds to immune-checkpoint blockade (ICB) therapies. Cancer-associated fibroblasts (CAF) are critical components of the immunologically "cold" tumor microenvironment and are considered a promising target to enhance the immunotherapy response. In this study, we aimed to reveal the mechanisms regulating CAF plasticity to identify potential strategies to switch CAFs from protumorigenic to antitumor phenotypes and to enhance ICB efficacy in prostate cancer.

Comprehensive review on the novel immunotherapy target: Leucine-rich repeat-containing 8A/volume-regulated anion channel.

Leucine-rich repeat-containing 8A (LRRC8A) is a key component of the volume-regulated anion channel (VRAC) that influences essential homeostatic processes in various immune cells. These processes include the regulation of cell volume and membrane potential and the facilitation of the transport of organic agents used as anticancer drugs and immune-stimulating factors. Therefore, understanding the structure-function relationship of LRRC8A, exploring its physiological role in immunity, assessing its efficacy in treating diseases, and advancing the development of compounds that regulate its activity are important research frontiers.

Genetically Engineered Membrane-Coated Nanoparticles for Enhanced Prostate-Specific Membrane Antigen Targeting and Ferroptosis Treatment of Castration-Resistant Prostate Cancer.

Conventional androgen deprivation therapy (ADT) targets the androgen receptor (AR) inhibiting prostate cancer (PCa) progression; however, it can eventually lead to recurrence as castration-resistant PCa (CRPC), which has high mortality rates and lacks effective treatment modalities. The study confirms the presence of high glutathione peroxidase 4 (GPX4) expression, a key regulator of ferroptosis (i.e.

Peripheral CD8PD-1 T cells as novel biomarker for neoadjuvant chemoimmunotherapy in humanized mice of non-small cell lung cancer.

Neoadjuvant immunotherapy has shown promising clinical activity in the treatment of early non-small cell lung cancer (NSCLC); however, further clarification of the specific mechanism and identification of biomarkers are imperative prior to implementing it as a daily practice. The study investigated the reprogramming of T cells in both tumor and peripheral blood following neoadjuvant chemoimmunotherapy in a preclinical NSCLC mouse model engrafted with a human immune system. Samples were also collected from 21 NSCLC patients (Stage IA-IIIB) who received neoadjuvant chemoimmunotherapy, and the dynamics of potential biomarkers within these samples were measured and further subjected to correlation analysis with prognosis.

Metastasis-associated protein 1 participates in regulating luminal acidification of the epididymis via repressing estrogen receptor alpha transcription.

Background: As a component of the nucleosome remodeling and deacetylating (NuRD) complex, metastasis-associated protein 1 (MTA1) has been reported to be abundant in male reproductive system and might participate in spermatogenesis and sperm maturation, whereas the precise functional role of MTA1 in these processes is still undetermined.

Objective: To investigate the effect and potential function of MTA1 in male fertility.

Materials And Methods: Mta1 knockout mice (Mta1) were employed to detect their reproductive phenotype.

Targeting monoamine oxidase A: a strategy for inhibiting tumor growth with both immune checkpoint inhibitors and immune modulators.

Monoamine oxidase A (MAOA) is a membrane-bound mitochondrial enzyme present in almost all vertebrate tissues that catalyzes the degradation of biogenic and dietary-derived monoamines. MAOA is known for regulating neurotransmitter metabolism and has been implicated in antitumor immune responses. In this review, we retrospect that MAOA inhibits the activities of various types of tumor-associated immune cells (such as CD8 T cells and tumor-associated macrophages) by regulating their intracellular monoamines and metabolites.

Pregnancy diagnosis and sex identification with urinary glycopatterns of two mammal species.

Glycome in urine could be promising biomarkers for detecting pregnancy diagnosis and sex noninvasively for animals, especially for rare species. We explore the applicability of grouping golden snub-nosed monkeys by sex or diagnosing pregnancy based on their urinary glycopatterns, which are determined via lectin microarray combining mass spectrometry analysis. Sprague-Dawley rats are used to verify whether this approach and whether the glycomic biomarkers can be generalized to other mammalian species.

Interaction between the EPHB2 receptor and EFNB1 ligand drives gastric cancer invasion and metastasis via the Wnt/β-catenin/FAK pathway.

The survival benefit for patients with gastric cancer (GC) is modest due to its high transfer potential. Targeted therapy for metastasis-related genes in GC may be a viable approach, however, inhibitors specifically targeting GC are limited. In this study, GC patient-derived xenografts (PDX) with metastatic burden were established via orthotopic transplantation.

Establishment of organoid models for pancreatic ductal adenocarcinoma and screening of individualized therapy strategy.

Background: Patients with pancreatic ductal adenocarcinoma (PDAC) who undergo surgical resection and receive effective chemotherapy have the best chance for long-term survival. Unfortunately, because of the heterogeneity of pancreatic cancer, it is difficult to find a personalized treatment strategy for patients. Organoids are ideal preclinical models for personalized medicine.

Stochastic modeling of the mRNA life process: A generalized master equation.

The mRNA life cycle is a complex biochemical process, involving transcription initiation, elongation, termination, splicing, and degradation. Each of these molecular events is multistep and can create a memory. The effect of this molecular memory on gene expression is not clear, although there are many related yet scattered experimental reports.

Monoamine oxidase A (MAOA): A promising target for prostate cancer therapy.

Monoamine oxidase A (MAOA) is a mitochondrial enzyme that catalyzes the oxidative deamination of monoamine neurotransmitters and dietary amines. Previous studies have shown that MAOA is clinically associated with prostate cancer (PCa) progression and plays a key role in almost each stage of PCa, including castrate-resistant prostate cancer, neuroendocrine prostate cancer, metastasis, drug resistance, stemness, and perineural invasion. Moreover, MAOA expression is upregulated not only in cancer cells but also in stromal cells, intratumoral T cells, and tumor-associated macrophages; thus, targeting MAOA can be a multi-pronged approach to disrupt tumor promoting interactions between PCa cells and tumor microenvironment.

Screening of an individualized treatment strategy for an advanced gallbladder cancer using patient-derived tumor xenograft and organoid models.

Gallbladder cancer is a highly aggressive malignancy with poor sensitivity to postoperative radiotherapy or chemotherapy; therefore, the development of individualized treatment strategies is paramount to improve patient outcomes. Both patient-derived tumor xenograft (PDX) and patient-derived tumor organoid (PDO) models derived from surgical specimens can better preserve the biological characteristics and heterogeneity of individual original tumors, display a unique advantage for individualized therapy and predicting clinical outcomes. In this study, PDX and PDO models of advanced gallbladder cancer were established, and the consistency of biological characteristics between them and primary patient samples was confirmed using pathological analysis and RNA-sequencing.

LRRC8A Is a Promising Prognostic Biomarker and Therapeutic Target for Pancreatic Adenocarcinoma.

Pancreatic adenocarcinoma (PAAD) is a highly malignant tumor of the digestive system with increasing morbidity and mortality. The lack of sensitive and reliable biomarkers is one of the main reasons for the poor prognosis. Volume-regulated anion channels (VRAC), which are ubiquitously expressed in the vertebrate cell membrane, are composed of leucine-rich repeat-containing 8A (LRRC8A) and four other homologous family members (LRRC8B-E).

Combined pembrolizumab and bevacizumab therapy effectively inhibits non-small-cell lung cancer growth and prevents postoperative recurrence and metastasis in humanized mouse model.

Antibodies targeting the programmed cell death protein 1/programmed cell death ligand-1 (PD-1/PD-L1) pathway have dramatically changed the treatment landscape of advanced non-small cell lung cancer (NSCLC). However, combination approaches are required to extend this benefit beyond a subset of patients. In addition, it is of equal interest whether these combination therapy can be applied to neoadjuvant therapy of early-stage NSCLC.