Triple knockdown of , , and in T cells reduces CAR-T cell toxicity but preserves activity against solid tumors in mice.

Chimeric antigen receptor (CAR)-T cell therapies have revolutionized the landscape of cancer treatment, in particular in the context of hematologic malignancies. However, for solid tumors that lack tumor-specific antigens, CAR-T cells can infiltrate and attack nonmalignant tissues expressing the CAR target antigen, leading to on-target, off-tumor toxicity. Severe on-target, off-tumor toxicities have been observed in clinical trials of CAR-T therapy for solid tumors, highlighting the need to address this issue.

An on-Demand Oxygen Nano-vehicle Sensitizing Protein and Nucleic Acid Drug Augment Immunotherapy.

Hypoxia severely limits the antitumor immunotherapy for breast cancer. Although efforts to alleviate tumor hypoxia and drug delivery using diverse nanostructures achieve promising results, the creation of a versatile controllable oxygen-releasing nano-platform for co-delivery with immunostimulatory molecules remains a persistent challenge. To address this problem, a versatile oxygen controllable releasing vehicle PFOB@F127@PDA (PFPNPs) is developed, which effectively co-delivered either protein drug lactate oxidase (LOX) or nucleic acids drug unmethylated cytosine-phosphate-guanine oligonucleotide (CpG ODNs).

Patient-derived xenograft model in cancer: establishment and applications.

The patient-derived xenograft (PDX) model is a crucial in vivo model extensively employed in cancer research that has been shown to maintain the genomic characteristics and pathological structure of patients across various subtypes, metastatic, and diverse treatment histories. Various treatment strategies utilized in PDX models can offer valuable insights into the mechanisms of tumor progression, drug resistance, and the development of novel therapies. This review provides a comprehensive overview of the establishment and applications of PDX models.

Blocking p85β nuclear translocation by importazole enhances Alpelisib efficacy against PIK3CA-helical-domain-mutant tumors.

PIK3CA, which encodes protein p110α, is one of the most frequently mutated oncogenes and a promising drug-target for human cancer. Previously, we demonstrate that p85β is released from PI3K complex which contain PIK3CA helical domain mutations and translocates into nucleus to regulate tri-methylation of H3K27, thereby promoting tumorigenicity. Here, we identify DIRAS2 and SOWAHB as target genes of nuclear p85β in PIK3CA-helical-domain-mutant tumors.

Application of thrombopoietic agents in cancer therapy-induced thrombocytopenia: A comprehensive review.

Cancer therapy-induced thrombocytopenia (CT-IT) is one of the most common hematological toxicities of anti-cancer therapy, often leading to treatment dose reduced, postponed, or treatment plans altered or even discontinued. Thrombopoietin (TPO) is the only key regulatory factor in platelet production, and TPO receptor is considered an ideal target for the treatment of thrombocytopenia. Thrombopoietic agents, including recombinant human thrombopoietin (rhTPO) and thrombopoietin receptor agonists (TPO-RAs), bind to different regions of the TPO receptor, activating downstream signaling pathways to increase platelet levels.

Standard: Human gastric organoids.

Organoid technology provides a transformative approach to understand human physiology and pathology, offering valuable insights for scientific research and therapeutic development. Human gastric organoids, in particular, have gained significant interest for applications in disease modeling, drug discovery, and studies of tissue regeneration and homeostasis. However, the lack of standardized quality control has limited their extensive clinical applications.

ConvXGB: A novel deep learning model to predict recurrence risk of early-stage cervical cancer following surgery using multiparametric MRI images.

Background: Accurate estimation of recurrence risk for cervical cancer plays a pivot role in making individualized treatment plans. We aimed to develop and externally validate an end-to-end deep learning model for predicting recurrence risk in cervical cancer patients following surgery by using multiparametric MRI images.

Methods: The clinicopathologic data and multiparametric MRI images of 406 cervical cancer patients from three institutions were collected.

DYRK1A-TGF-β signaling axis determines sensitivity to OXPHOS inhibition in hepatocellular carcinoma.

Intervening in mitochondrial oxidative phosphorylation (OXPHOS) has emerged as a potential therapeutic strategy for certain types of cancers. Employing kinome-based CRISPR screen, we find that knockout of dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) synergizes with OXPHOS inhibitor IACS-010759 in liver cancer cells. Targeting DYRK1A combined with OXPHOS inhibitors activates TGF-β signaling, which is crucial for OXPHOS-inhibition-triggered cell death.

Liquid-liquid phase separation in hepatocellular carcinoma.

Liquid-liquid phase separation (LLPS) drives the formation of membraneless intracellular compartments within both cytoplasm and nucleus. These compartments can form distinct physicochemical environments, and in particular display different concentrations of proteins, RNA, and macromolecules compared to the surrounding cytosol. Recent studies have highlighted the significant role of aberrant LLPS in cancer development and progression, impacting many core processes such as oncogenic signalling pathways, transcriptional dysregulation, and genome instability.

CREB3L1 facilitates pancreatic tumor progression and reprograms intratumoral tumor-associated macrophages to shape an immunotherapy-resistance microenvironment.

Background: To date, a growing body of evidence suggests that unfolded protein response (UPR) sensors play a vital role in carcinogenesis. However, it remains unclear whether they are involved in pancreatic ductal adenocarcinoma (PDAC) and how they relate to clinical outcomes. This study aims to investigate the biological function and mechanism of how a novel UPR sensor, CREB3L1 works in PDAC and further evaluate its clinical application prospect.

Refining breast cancer genetic risk and biology through multi-ancestry fine-mapping analyses of 192 risk regions.

Genome-wide association studies have identified approximately 200 genetic risk loci for breast cancer, but the causal variants and target genes are mostly unknown. We sought to fine-map all known breast cancer risk loci using genome-wide association study data from 172,737 female breast cancer cases and 242,009 controls of African, Asian and European ancestry. We identified 332 independent association signals for breast cancer risk, including 131 signals not reported previously, and for 50 of them, we narrowed the credible causal variants down to a single variant.

ENO1 promotes PDAC progression by inhibiting CD8 T cell infiltration through upregulating PD-L1 expression via HIF-1α signaling.

Metabolic reprogramming is a hallmark of cancer. The"Warburg effect", also known as aerobic glycolysis, is an essential part of metabolic reprogramming and a central contributor to cancer progression. Moreover, hypoxia is one of the significant features of pancreatic ductal adenocarcinoma (PDAC).

Asparagine endopeptidase regulates lysosome homeostasis via modulating endomembrane phosphoinositide composition.

Asparagine endopeptidase (AEP) is ubiquitously expressed in both physiological and pathological contexts, yet its precise role and functional mechanism in breast cancer remain elusive. Here, we identified increased AEP expression in breast cancer tissues, which correlated with poorer survival rates and a propensity for lung metastasis among breast cancer patients. Loss of AEP impaired colony formation by breast cancer cells in vitro and suppressed lung metastasis in mice.

A comprehensive immune repertoire signature distinguishes pulmonary infiltration in SARS-CoV-2 Omicron variant infection.

Introduction: The coronavirus disease 2019 (COVID-19) global pandemic has been the most severe public health emergency since 2019. Currently, the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been the most dominant. The most prominent symptom of SARS-CoV-2 infection is respiratory.

Deciphering the role of the MALT1-RC3H1 axis in regulating GPX4 protein stability.

Ferroptosis, a unique form of iron-dependent cell death triggered by lipid peroxidation accumulation, holds great promise for cancer therapy. Despite the crucial role of GPX4 in regulating ferroptosis, our understanding of GPX4 protein regulation remains limited. Through FACS-based genome-wide CRISPR screening, we identified MALT1 as a regulator of GPX4 protein.

IMPDH2 dephosphorylation under FGFR signaling promotes S-phase progression and tumor growth.

Inosine monophosphate dehydrogenase 2 (IMPDH2) is highly expressed in human cancers; however, its physiological relevance under growth signaling remains to be investigated. Here, we show that IMPDH2 serine 122 is phosphorylated by CDK1, and this modification attenuates the catalytic activity of IMPDH2 for IMP oxidation and simultaneously represses its allosteric modulation by purine nucleotides. Fibroblast growth factor receptor (FGFR) signaling activation triggers IMPDH2-Ser122 dephosphorylation mediated by protein phosphatase 2A (PP2A), which is dependent on FGFR3-mediated PPP2R1A-Tyr261 phosphorylation leading to PPP2CA-PPP2R1A-IMPDH2 interactions.

DDX18 coordinates nucleolus phase separation and nuclear organization to control the pluripotency of human embryonic stem cells.

Pluripotent stem cells possess a unique nuclear architecture characterized by a larger nucleus and more open chromatin, which underpins their ability to self-renew and differentiate. Here, we show that the nucleolus-specific RNA helicase DDX18 is essential for maintaining the pluripotency of human embryonic stem cells. Using techniques such as Hi-C, DNA/RNA-FISH, and biomolecular condensate analysis, we demonstrate that DDX18 regulates nucleolus phase separation and nuclear organization by interacting with NPM1 in the granular nucleolar component, driven by specific nucleolar RNAs.

Tea Polyphenol-Derived Carbon Dots Alleviate Abdominal Aortic Aneurysm Progression by Mitigating Oxidative Stress and Ferroptosis.

Abdominal aortic aneurysm (AAA) is a cardiovascular disease with potentially fatal consequences, yet effective therapies to prevent its progression remain unavailable. Oxidative stress is associated with AAA development. Carbon dots have reactive oxygen species-scavenging activity, while green tea extract exhibits robust antioxidant properties.

An emerging aspect of cancer neuroscience: A literature review on chemotherapy-induced peripheral neuropathy.

The nervous system governs both ontogeny and oncology. Foundational discoveries have clarified the direct communication of neurotransmitters with tumors and indirect interactions through neural effects on the immune system and the tumor microenvironment. Meantime, the nervous system is susceptible to cancer and its treatment.

Peripheral, central, and chemotherapy-induced neuropathic changes in pancreatic cancer.

In pancreatic cancer, significant alterations occur in the local nervous system, including axonogenesis, neural remodeling, perineural invasion, and perineural neuritis. Pancreatic cancer can impact the central nervous system (CNS) through cancer cell-intrinsic factors or systemic factors, particularly in the context of cancer cachexia. These peripheral and central neuropathic changes exert substantial influence on cancer initiation and progression.

Standard: Human gastric cancer organoids.

Gastric cancer is one of the most common malignancies with poor prognosis. The use of organoids to simulate gastric cancer has rapidly developed over the past several years. Patient-derived gastric cancer organoids serve as in vitro models that closely mimics donor characteristics, offering new opportunities for both basic and applied research.

Mutational signatures define immune and Wnt-associated subtypes of ampullary carcinoma.

Background And Objective: Ampullary carcinoma (AMPAC) taxonomy is based on morphology and immunohistochemistry. This classification lacks prognostic reliability and unique genetic associations. We applied an approach of integrative genomics characterising patients with AMPAC exploring molecular subtypes that may guide personalised treatments.

Association between major depressive disorder or depressive symptoms and the risk of vascular complications among patients with type 2 diabetes, and the mediating role of metabolic biomarkers: an analysis of the UK Biobank cohort.

Background: Depression is a severe mental disorder commonly co-morbid with diabetes, but it remains to elucidate whether depression is associated with the risks of a wide range of vascular complications in people with type 2 diabetes mellitus (T2DM) and whether metabolic biomarkers may mediate this pathway.

Methods: We conducted this prospective analysis among the participants of the UK Biobank who were diagnosed with T2DM and free of vascular complications at baseline between March 13, 2006 and September 30, 2010. Major depressive disorder (MDD) was ascertained according to the hospital admission records and self-report of doctor-diagnosed conditions, while the presence of depressive symptoms was assessed using the Patient Health Questionnaire-2.

Activated kynurenine pathway metabolism by YKL-40 establishes an inhibitory immune microenvironment and drives glioblastoma development.

Background: Glioblastoma (GB) is the stage IV of glioma and mesenchymal GB represents the most common and malignant subtype characterized with elevated expression of a mesenchymal marker YKL-40 and resistance to immune drug therapy. Here, we determined if YKL-40 regulates kynurenine (Kyn) pathway (KP) metabolism that contributes to establishing an immune suppressive microenvironment in GB.

Methods: Tumor cells expressing YKL-40 from GB patients were isolated and activated cellular metabolisms were identified via gene microarray analysis.