Precision Oncology Through Dialogue: AI-HOPE-RTK-RAS Integrates Clinical and Genomic Insights into RTK-RAS Alterations in Colorectal Cancer.

The RTK-RAS signaling cascade is a central axis in colorectal cancer (CRC) pathogenesis, governing cellular proliferation, survival, and therapeutic resistance. Somatic alterations in key pathway genes-including KRAS, NRAS, BRAF, and EGFR-are pivotal to clinical decision-making in precision oncology. However, the integration of these genomic events with clinical and demographic data remains hindered by fragmented resources and a lack of accessible analytical frameworks.

N4-acetylcytidine modification of LINC02802 promotes non-small cell lung cancer progression by modulating mitochondrial NAD+/NADH ratio.

Long non-coding RNAs (lncRNAs) have emerged as key regulators of cancer progression through their interaction with microRNAs and modulation of gene expression. However, their role in mitochondrial metabolism, particularly in non-small cell lung cancer (NSCLC), remains poorly defined. In this study, we found that LINC02802 was significantly upregulated in NSCLC tissues and associated with poor prognosis.

Differential tropisms of old and new world hantaviruses influence virulence and developing host-directed antiviral candidates.

Hantaviruses are zoonotically transmitted from rodents to humans through the respiratory route, with no currently approved antivirals or widely available vaccines. The recent discovery of interhuman-transmitted Andes virus (ANDV) necessitates the systematic identification of cell tropism, infective potential, and potent therapeutic agents. We utilized human primary lung endothelial cells, various pluripotent stem cell-derived heart and brain cell types, and established human lung organoid models to evaluate the tropisms of Old World Hantaan (HTNV) and New World ANDV and Sin Nombre (SNV) viruses.

Conversational AI agent for precision oncology: AI-HOPE-WNT integrates clinical and genomic data to investigate WNT pathway dysregulation in colorectal cancer.

Introduction: The WNT signaling pathway is a key driver of colorectal cancer (CRC) initiation and progression, particularly in early-onset CRC (EOCRC) among underserved populations. However, interrogating WNT pathway dysregulation across clinical and genomic dimensions remains technically challenging, limiting both translational insight and personalized intervention strategies. To address this gap, we developed AI-HOPE-WNT, the first conversational artificial intelligence (AI) agent purpose-built to investigate WNT signaling in CRC using natural language-driven, integrative bioinformatics.

Understanding monocyte-driven neuroinflammation in Alzheimer's disease using human cortical organoid microphysiological systems.

Increasing evidence strongly links neuroinflammation to Alzheimer's disease (AD) pathogenesis. Peripheral monocytes are crucial components of the human immune system, but their contribution to AD pathogenesis is still largely understudied partially due to limited human models. Here, we introduce human cortical organoid microphysiological systems (hCO-MPSs) to study AD monocyte-mediated neuroinflammation.

Whole exome sequencing identifies FANCM as a susceptibility gene for estrogen-receptor-negative breast cancer in Hispanic/Latina women.

Breast cancer (BC) is one of the most common cancers globally. Genetic testing facilitates screening and informs targeted risk-reduction and treatments. However, genes included in testing panels are from European-ancestry studies.

Advancing Prostate Cancer Treatment: Innovations and Challenges in Immunotherapy.

Prostate cancer (PCa), a leading cause of cancer mortality in men, has experienced a paradigm shift with the rise of immunotherapy. This chapter examines the immunological landscape of PCa and highlights key immunotherapeutic approaches, including cancer vaccines, immune checkpoint inhibitors (ICIs), adoptive cell therapies, and cytokine-based treatments. Emerging innovations, such as oncolytic viruses, neoantigen-based therapies, and bispecific antibodies, are also examined.

Reproductive factors and risk of contralateral breast cancer by age and hormone receptor status: The California Breast Cancer Survivorship Consortium.

Associations between reproductive factors and the risk of developing a contralateral second primary invasive breast cancer (CBC) are inconclusive. A pooled cohort of women with a first primary invasive breast cancer (FBC) from five California-based studies (8045 stage I-III FBC diagnosed from 1994 to 2009) was linked with the California Cancer Registry; 532 CBC were identified. We analyzed harmonized data and evaluated associations with reproductive factors using Fine and Gray regression to estimate hazard ratios (HR) and 95% confidence intervals (CI), adjusted for study, age at FBC diagnosis, race and ethnicity, and other risk factors previously identified in this pooled dataset (hormone receptor status, first-degree family history of breast cancer).

FTO degrader impairs ribosome biogenesis and protein translation in acute myeloid leukemia.

Targeting ribosome biogenesis and protein translation has emerged as a promising avenue for cancer therapy. The fat mass and obesity-associated protein (FTO), an RNA -methyladenosine (mA) eraser, has been identified as an oncogenic factor in acute myeloid leukemia (AML). Here, we present the development of an FTO degrader that selectively degrades FTO in AML cells, demonstrating superior efficacy both in vitro and in vivo.

MicroRNA210 Suppresses Mitochondrial Metabolism and Promotes Microglial Activation in Neonatal Hypoxic-Ischemic Brain Injury.

Neuroinflammation is the major contributor to the pathology of neonatal hypoxic-ischemic (HI) brain injury. Our previous studies have demonstrated that microRNA210 (miR210) inhibition with antisense locked nucleic acid (LNA) inhibitor mitigates neuroinflammation and provides neuroprotection after neonatal HI insult. However, the underlying mechanisms remain elusive.

Overall and central adiposity and risk of contralateral breast cancer: The California Breast Cancer Survivorship Consortium.

Data on associations between overall adiposity measured by body mass index (BMI) and risk of contralateral second primary breast cancer (CBC) are inconsistent, and associations with central adiposity have not been investigated. We analyzed harmonized data from six studies for 9479 women with a first primary invasive stage I-III breast cancer (FBC) diagnosed from 1993 through 2009. Linkage of this cohort with the California Cancer Registry identified 610 CBC, diagnosed more than 180 days after FBC.

Molecular PET imaging: Unlocking the secrets of cancer metabolism.

Cancer metabolism is a dynamic and complex field, offering insights into tumor growth, progression, and therapy resistance. Molecular positron emission tomography (PET) imaging has emerged as a pivotal tool for visualizing and quantifying metabolic alterations in cancer, shedding light on processes like glycolysis, amino acid metabolism, lipid synthesis, and hypoxia. This review explores the foundational principles of PET imaging, highlighting key radiotracers such as [F]-FDG, glutamine-based tracers, and hypoxia-sensitive agents.

ALKBH1 drives tumorigenesis and drug resistance via tRNA decoding reprogramming and codon-biased translation.

Cancer cells utilize codon-biased translation to fuel tumorigenesis and drug resistance, but underlying mechanisms remain poorly understood. Here, we show ALKBH1 is overexpressed in acute myeloid leukemia (AML) and essential for leukemia stem/initiating cell (LSC/LIC) self-renewal and AML development/maintenance, whereas dispensable for normal hematopoiesis. ALKBH1 enhances mitochondrial assembly/function and oxidative phosphorylation (OXPHOS), crucial for AML survival/proliferation and resistance to venetoclax, a potent BCL2 inhibitor and widely-used first-line targeted therapy for AML in clinic.

Exosomal Liquid Biopsy for the Early Detection of Gastric Cancer: The DESTINEX Multicenter Study.

Importance: Gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide, primarily attributed to delayed detection. The invasive and cost-prohibitive nature of endoscopy for GC screening highlights the urgent need for noninvasive biomarkers.

Objective: To develop an exosome-based diagnostic signature to facilitate blood-based, early detection of patients with GC.

Mutations in GFAP Alter Early Lineage Commitment of Organoids.

Glial fibrillary acidic protein (GFAP) is a type-3 intermediate filament protein mainly expressed in astrocytes in the central nervous system. Mutations in GFAP cause Alexander disease (AxD), a rare and fatal neurological disorder. How exactly mutant GFAP eventually leads to white and gray matter deterioration in AxD remains unknown.

RNA mA modification: a key regulator in normal and malignant processes.

The dedicated control of gene abundance is essential for both biological and pathological processes in mammals. Multiple layers of gene expression regulation, including transcriptional, post-transcriptional, translational, and post-translational regulation, collectively determine the highly dynamic equilibrium of functional protein abundance. Epigenetic modifications play indispensable roles in fine-tuning gene expression at either DNA, RNA, or protein level.

Therapeutic Plasma Exchange: Current and Emerging Applications to Mitigate Cellular Signaling in Disease.

Therapeutic plasma exchange (TPE) is a blood purification technique which functions to remove pathological plasma constituents such as autoantibodies, inflammatory cytokines, immune complexes, and extracellular vesicles (EVs) that contribute to a range of disease states. In this review, we examine current and emerging indications for TPE across cardiovascular, metabolic, neurological, inflammatory, and oncological diseases. We cover emerging preclinical animal models and new applications, emphasizing the roles of cellular signaling and EV biology in mediating plasma functions, and discuss unique therapeutic "windows of opportunity" offered by TPE.

Decoding the JAK-STAT Axis in Colorectal Cancer with AI-HOPE-JAK-STAT: A Conversational Artificial Intelligence Approach to Clinical-Genomic Integration.

: The Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway is a critical mediator of immune regulation, inflammation, and cancer progression. Although implicated in colorectal cancer (CRC) pathogenesis, its molecular heterogeneity and clinical significance remain insufficiently characterized-particularly within early-onset CRC (EOCRC) and across diverse treatment and demographic contexts. We present AI-HOPE-JAK-STAT, a novel conversational artificial intelligence platform built to enable the real-time, natural language-driven exploration of JAK/STAT pathway alterations in CRC.

Metabolic reprogramming in breast cancer: Pathways driving progression, drug resistance, and emerging therapeutics.

Breast cancer (BC), one of the most frequent causes of cancer-related death in women, is known to be a highly heterogeneous disease in regard to molecular subtypes, which seem to possess different metabolic profiles. Aberrant metabolism is well understood as one of the hallmarks of cancer and it contributes to BC progression, therapeutic resistance, and metastasis. Here, we analyze BC metabolism and how certain cancer types, such as hormone receptor-positive, HER2-positive, and triple-negative BC, use glycolysis, lipid metabolism, amino acid compulsion, and mitochondrial biogenesis to feed and proliferate.

Knowledge to action: a pilot quality improvement intervention on breast cancer specimen handling in operating rooms in Southern Ethiopia.

Background: Appropriate handling of surgical specimens is critical to the accurate diagnosis and treatment of Breast cancer (BC) and is urgently needed in sub-Saharan Africa. This study piloted a quality improvement training program in southern Ethiopia.

Methods: A train-the-trainer implementation strategy was used.

Lymphocytes and monocytes undergo swift suppression of IL-10R, IL-6R, and IL-2Rβγ signaling under high concentrations of different cytokines.

The JAK-STAT signaling pathway is fundamental for immune system regulation. It involves phosphorylation of several types of STAT proteins in response to binding of cytokines to immune cell receptors. Traditionally, the immune signaling studies focus on measuring the levels of phosphorylated STATs (pSTATs) following individual cytokine application.

Targeting the oncoprotein RLIP as novel therapy for ovarian cancer.

Ral-interacting/binding protein (RLIP/) is a multifunctional protein found in the plasma membrane, cytosol, and nucleus, with broad expression across various tissues, including the ovary. In tumorigenesis, RLIP is closely linked to the progression of solid tumors. As a non-ABC anti-apoptotic transporter, it facilitates glutathione (GSH) conjugate transport, which plays a role in receptor-ligand endocytosis and contributes to drug transport and resistance.