DEAD/H Box 5 (DDX5) Augments E2F1-Induced Cell Death Independent of the Tumor Suppressor p53.

In almost all cancers, the p53 pathway is disabled and cancer cells survive. Hence, it is crucially important to induce cell death independent of p53 in the treatment of cancers. The transcription factor E2F1 is controlled by binding of the tumor suppressor pRB, and induces apoptosis by activating the gene, an upstream activator of p53, when deregulated from pRB by loss of pRB function.

Enhancing Clinical Applications by Evaluation of Sensitivity and Specificity in Whole Exome Sequencing.

The cost-effectiveness of whole exome sequencing (WES) remains controversial due to variant call variability, necessitating sensitivity and specificity evaluation. WES was performed by three companies (AA, BB, and CC) using reference standards composed of DNA from hydatidiform mole and individual blood at various ratios. Sensitivity was assessed by the detection rate of null-homozygote (N-H) alleles at expected variant allelic fractions, while false positive (FP) errors were counted for unexpected alleles.

A Machine Learning-Based Model for Preoperative Assessment and Malignancy Prediction in Patients with Atypia of Undetermined Significance Thyroid Nodules.

The aim of this study was to investigate the preoperative clinical and hematologic variables, including the neutrophil-to-lymphocyte ratio (NLR), that can be used to predict malignancy in patients with atypia of undetermined significance (AUS) thyroid nodules; we further aimed to develop a machine learning-based prediction model. We enrolled 280 patients who underwent surgery for AUS nodules at the Wonju Severance Christian Hospital between 2018 and 2022. A logistic regression-based model was trained and tested using cross-validation, with the performance evaluated using metrics such as the area under the receiver operating characteristic curve (AUROC).

Targeting Refractory Triple-Negative Breast Cancer with Sacituzumab Govitecan: A New Era in Precision Medicine.

Advanced triple-negative breast cancer (TNBC) has poorer outcomes due to its aggressive behavior and restricted therapeutic options. While therapies like checkpoint inhibitors and PARP inhibitors offer some benefits, chemotherapy remains ineffective beyond the first line of treatment. Antibody-drug conjugates (ADCs) like sacituzumab govitecan-hziy (SG) represent a significant advancement.

GPR68 Mediates Lung Endothelial Dysfunction Caused by Bacterial Inflammation and Tissue Acidification.

Tissue acidification resulting from dysregulated cellular bioenergetics accompanies various inflammatory states. GPR68, along with other members of proton-sensing G protein-coupled receptors, responds to extracellular acidification and has been implicated in chronic inflammation-related diseases such as ischemia, cancer, and colitis. The present study examined the role of extracellular acidification on human pulmonary endothelial cell (EC) permeability and inflammatory status per se and investigated potential synergistic effects of acidosis on endothelial dysfunction caused by bacterial lipopolysaccharide (LPS, ).

Discovery of Carbonic Anhydrase 9 as a Novel CLEC2 Ligand in a Cellular Interactome Screen.

Membrane proteins, especially extracellular domains, are key therapeutic targets due to their role in cell communication and associations. Yet, their functions and interactions often remain unclear. This study presents a general method to discover interactions of membrane proteins with immune cells and subsequently to deorphanize their respective receptors.

Critical Role of Extracellular Vesicles in Diffuse Large B-Cell Lymphoma; Pathogenesis, Potential Biomarkers, and Targeted Therapy-A Narrative Review.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin's lymphoma, characterized by its aggressive nature and heterogeneity. Despite significant advances in understanding DLBCL pathogenesis, there is still a need to elucidate the intricate mechanisms involved in disease progression and identify novel therapeutic targets. Extracellular vesicles (EVs), including exosomes and microvesicles, have emerged as crucial mediators of intercellular communication in various physiological and pathological processes, including cancer.

Efficacy and Safety of Pazopanib in the Treatment of Thyroid Cancer: A Systematic Review.

Pazopanib, a multi-targeted tyrosine kinase inhibitor, has been explored for its efficacy in treating various subtypes of thyroid cancer, including differentiated thyroid carcinoma (DTC), medullary thyroid carcinoma (MTC), and anaplastic thyroid carcinoma (ATC). This systematic review assesses the efficacy and safety of pazopanib, focusing on the progression-free survival (PFS), overall survival (OS), and response rates and adverse events. A comprehensive search was conducted in databases including PubMed, Scopus, and Web of Science up to October 2024 to identify randomized controlled trials and phase II clinical trials that investigated the use of pazopanib in thyroid cancer.

Diagnostics and Therapy for Malignant Tumors.

Malignant tumors remain one of the most significant global health challenges and contribute to high mortality rates across various cancer types. The complex nature of these tumors requires multifaceted diagnostic and therapeutic approaches. This review explores current advancements in diagnostic methods, including molecular imaging, biomarkers, and liquid biopsies.

A Machine Learning Classification Model for Gastrointestinal Health in Cancer Survivors: Roles of Telomere Length and Social Determinants of Health.

Background: Gastrointestinal (GI) distress is prevalent and often persistent among cancer survivors, impacting their quality of life, nutrition, daily function, and mortality. GI health screening is crucial for preventing and managing this distress. However, accurate classification methods for GI health remain unexplored.

Non-Invasive miRNA Profiling for Differential Diagnosis and Prognostic Stratification of Testicular Germ Cell Tumors.

Background/objectives: Testicular germ cell tumors (TGCT) are common in young adult men and have high cure rates. Conventional serum tumor markers and imaging are not able to differentiate between histologic subtypes of the disease, which portend different prognoses and require distinct therapeutic strategies. Micro-RNAs (miRNAs) are small non-coding transcripts involved in the post-transcriptional regulation of gene expression, which have emerged as promising biomarkers in a variety of tumors.

Decoding the Nexus: Cellular and Molecular Mechanisms Linking Stroke and Neurotoxic Microenvironments in Brain Cancer Patients.

Stroke is an often underrecognized albeit significant complication in patients with brain cancer, arising from the intricate interplay between cancer biology and cerebrovascular health. This review delves into the multifactorial pathophysiological framework linking brain cancer to elevated stroke risk, with particular emphasis on the crucial role of the neurotoxic microenvironment (NTME). The NTME, characterized by oxidative stress, neuroinflammation, and blood-brain barrier (BBB) disruption, creates a milieu that promotes and sustains vascular and neuronal injury.

The Proteomics of T-Cell and Early T-Cell Precursor (ETP) Acute Lymphocytic Leukemia: Prognostic Patterns in Adult and Pediatric-ETP ALL.

Background: The 5-year overall survival (OS) rates of T-cell lymphocytic leukemia (T-ALL) are better for children (>90%) compared to adults (~57%). The early T-cell precursor (ETP) T-ALL subtype is prognostically unfavorable in adults, but less significant in pediatric T-ALL, and the diagnosis and prognosis of "near"-ETP is controversial. We compared protein and RNA expression patterns in pediatric and adult T-ALL to identify prognostic subgroups, and to further characterize ETP and near-ETP T-ALL in both age groups.

Phosphoproteomic Profiling Reveals mTOR Signaling in Sustaining Macrophage Phagocytosis of Cancer Cells.

: Macrophage-mediated cancer cell phagocytosis has demonstrated considerable therapeutic potential. While the initiation of phagocytosis, facilitated by interactions between cancer cell surface signals and macrophage receptors, has been characterized, the mechanisms underlying its sustentation and attenuation post-initiation remain poorly understood. : Through comprehensive phosphoproteomic profiling, we interrogated the temporal evolution of the phosphorylation profiles within macrophages during cancer cell phagocytosis.

Impact of Vitamin D Levels on Progression-Free Survival and Response to Neoadjuvant Chemotherapy in Breast Cancer Patients: A Systematic Review and Meta-Analysis.

Breast cancer remains the leading cause of cancer-related deaths among women despite advances in early detection. Neoadjuvant chemotherapy (NACT) is now standard for early-stage BC, with vitamin D (VD) emerging as a potential prognostic biomarker considering its positive pleiotropic effects. This review and meta-analysis assess the impact of baseline VD levels on outcomes in BC patients undergoing NACT.

Obesity, Physical Activity, and Cancer Incidence in Two Geographically Distinct Populations; The Gulf Cooperation Council Countries and the United Kingdom-A Systematic Review and Meta-Analysis.

Background: The relationship between obesity, physical activity, and cancer has not been well studied across different countries. The age-standardized rate of cancer in the UK is double-triple that in the Gulf Cooperation Council Countries (GCCCs). Here, we study the association between obesity, physical activity, and cancer incidence with the aim to elucidate cancer epidemiology and risk factors in two geographically, ethnically, and climatically different parts of the world.

Succinate Regulates Endothelial Mitochondrial Function and Barrier Integrity.

Endothelial dysfunction is a hallmark of several pathological conditions, including cancer, cardiovascular disease and inflammatory disorders. In these conditions, perturbed TCA cycle and subsequent succinate accumulation have been reported. The role of succinate as a regulator of immunological responses and inflammation is increasingly being recognized.

Overview of Clinical Relevance of Antibodies Against Oxidized Low-Density Lipoprotein (oLAb) Within Three Decades by ELISA Technology.

One of the most prominent actions of oxidative stress is the attack of free radicals on poylyunsaturated fatty acids (PUFAs), initiating a chain reaction to modify these PUFAs and generate oxidized modifications on all biomolecules. In the last quarter of the 20th century, intensive research was carried out to identify antibodies against such modifications. In the mid-1990s, the first enzyme-linked immunosorbent assay (ELISA) was introduced to the market, significantly accelerating research activities and knowledge gain.

JP4-039 Mitigates Cisplatin-Induced Acute Kidney Injury by Inhibiting Oxidative Stress and Blocking Apoptosis and Ferroptosis in Mice.

Cisplatin is a commonly used chemotherapeutic agent in the treatment of a wide array of cancers. Due to its active transport into the kidney proximal tubule cells, cisplatin treatment can cause a buildup of this nephrotoxic compound in the kidney, resulting in acute kidney injury (AKI). About 30% of patients receiving cisplatin chemotherapy develop cisplatin-induced AKI.

Refinement of a Published Gene-Physical Activity Interaction Impacting HDL-Cholesterol: Role of Sex and Lipoprotein Subfractions.

Large-scale gene-environment interaction (GxE) discovery efforts often involve analytical compromises for the sake of data harmonization and statistical power. Refinement of exposures, covariates, outcomes, and population subsets may be helpful to establish often-elusive replication and evaluate potential clinical utility. Here, we used additional datasets, an expanded set of statistical models, and interrogation of lipoprotein metabolism via nuclear magnetic resonance (NMR)-based lipoprotein subfractions to refine a previously discovered GxE modifying the relationship between physical activity (PA) and HDL-cholesterol (HDL-C).

Anti-oxidants as therapeutic agents for oxidative stress associated pathologies: future challenges and opportunities.

Free radicals have been implicated in the pathogenesis of cancer along with cardiovascular, neurodegenerative, pulmonary and inflammatory disorders. Further, the relationship between oxidative stress and disease is distinctively established. Clinical trials using anti-oxidants for the prevention of disease progression have indicated some beneficial effects.

A noninvasive urinary microRNA-based assay for the detection of pancreatic cancer from early to late stages: a case control study.

Background: Pancreatic cancer is highly aggressive and has a low survival rate primarily due to late-stage diagnosis and the lack of effective early detection methods. We introduce here a novel, noninvasive urinary extracellular vesicle miRNA-based assay for the detection of pancreatic cancer from early to late stages.

Methods: From September 2019 to July 2023, Urine samples were collected from patients with pancreatic cancer (n = 153) from five distinct sites (Hokuto Hospital, Kawasaki Medical School Hospital, National Cancer Center Hospital, Kagoshima University Hospital, and Kumagaya General Hospital) and non-cancer participants (n = 309) from two separate sites (Hokuto Hospital and Omiya City Clinic).

Medication non-adherence: reflecting on two decades since WHO adherence report and setting goals for the next twenty years.

Background: Non-adherence to medication remains a persistent and significant challenge, with profound implications for patient outcomes and the long-term sustainability of healthcare systems. Two decades ago, the World Health Organization (WHO) dedicated its seminal report to adherence to long-term therapies, catalysing notable changes that advanced both research and practice in medication adherence. The aim of this paper was to identify the most important progress made over the last 2 decades in medication adherence management and to initiate a discussion on future objectives, suggesting priority targets for the next 20 years.

Asynchronous Transitions from Hepatoblastoma to Carcinoma in High-Risk Pediatric Tumors.

Most malignant hepatocellular tumors in children are classified as either hepatoblastoma (HB) or hepatocellular carcinoma (HCC), but some tumors demonstrate features of both HB and HCC. These tumors have been recognized under a provisional diagnostic category by the World Health Organization and are distinguished from HB and HCC by a combination of histological, immunohistochemical, and molecular features. Their outcomes and cellular composition remain an open question.

Efficacy of natural NF-κB inhibitors in the treatment of fibrosarcoma: an in vitro model study.

Introduction: NF-κB plays a pivotal role in the progression of cancers, including myosarcomas such as fibrosarcoma. Plants possess considerable potential for the provision of chemotherapeutic effects against cancer. The present study assessed, among others, the cytotoxicity, migration capacity and DNA damage induced by several natural compounds (berberine, curcumin, biochanin A, cucurbitacin E (CurE) and phenethyl caffeic acid (CAPE)) in cancer cells (WEHI-164) and normal muscle cells (L6).