Genetic characteristics of blastic plasmacytoid dendritic cell neoplasm: A single institution experience.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy with poorly characterized molecular features. To identify disease-specific mutational profiles, we performed targeted next-generation sequencing (NGS) on a cohort of 21 BPDCN patients. Our study revealed that (57%) and (33%) were the most frequently mutated genes, followed by (29%), (14%), (14%), and (14%).

Cabozantinib plus atezolizumab in metastatic prostate cancer (CONTACT-02): final analyses from a phase 3, open-label, randomised trial.

Background: Patients with metastatic castration-resistant prostate cancer (mCRPC) with extrapelvic soft-tissue metastases that has progressed on an androgen receptor pathway inhibitor (ARPI) have a poor prognosis with few treatment options. We aimed to assess efficacy and safety of cabozantinib, a tyrosine kinase inhibitor with immunomodulatory properties, plus the PD-L1 inhibitor atezolizumab in these patients.

Methods: CONTACT-02 is an open-label, randomised, phase 3 study that enrolled patients at 184 sites across 24 countries (in Europe, North America, Asia-Pacific, and Latin America).

Nivolumab-AVD Versus Brentuximab Vedotin-AVD in Older Patients With Advanced-Stage Classic Hodgkin Lymphoma Enrolled on S1826.

Older patients with classic Hodgkin lymphoma (cHL) have inferior survival compared with younger patients. We report a subset analysis of older patients (60 years and older) enrolled in the phase three S1826 trial conducted by SWOG that randomly assigned patients with newly diagnosed advanced-stage (III-IV) cHL to six cycles of nivolumab (N)-AVD or brentuximab vedotin (BV)-AVD. Of 103 enrolled patients 60 years and older, 99 were eligible.

Trop-2 expression as a biomarker of response to sacituzumab govitecan in patients with HER2-negative metastatic breast cancer: A pilot study.

Background: Sacituzumab govitecan (SG) is an anti-Trop-2 antibody-drug conjugate (ADC) approved for use in HER2-negative metastatic breast cancer (MBC). This study explores whether Trop-2 expression serves as a biomarker of excellent response versus non-response to sacituzumab govitecan (SG) in HER2-negative MBC.

Methods: Trop-2 expression was determined from patients with HER2-negative MBC categorized as non-responders and excellent responders to SG.

Methylglyoxal-induced RNA modifications decrease RNA stability and translation and are associated with type 2 diabetes.

Objectives: Methylglyoxal (MG), a reactive aldehyde generated as a byproduct of glucose and lipid metabolism, is known to modify nucleic acids and proteins, altering their structure and function. While MG-induced DNA and protein adducts have been extensively studied and associated with type 2 diabetes (T2D) and its complications, the formation, biological relevance, and functional consequences of MG-induced RNA adducts remain poorly understood. This study aimed to define the chemical structures of MG-derived RNA adducts, assess their presence in clinical samples, and determine their impact on RNA stability and translation.

CYR61 as a Potential Biomarker and Target in Cancer Prognosis and Therapies.

Cysteine-rich protein 61 (CYR61) is a matricellular protein in the CCN family that is involved in cellular adhesion, migration, proliferation, and angiogenesis. CYR61 interacts with integrins α6β1, αvβ3, αvβ5, and αIIbβ3 to modulate tumor progression and metastasis while modifying the tumor microenvironment. CYR61 exhibits context-dependent roles in cancer, acting as both a tumor promoter and suppressor.

Pharmacokinetic Analysis of Carboplatin and Fluorescein Brain Retention following Ultrasound-Based Blood-Brain Barrier Opening.

Purpose: The blood-brain barrier (BBB) impedes the passage of most circulating drugs into the brain. Low-intensity pulsed ultrasound with microbubbles (LIPU/MB) transiently opens the BBB, improving parenchymal drug penetration. Parenchymal drug retention following short-lived BBB opening is unknown.

Clinical Outcomes in Patients With Muscle-Invasive Urothelial Carcinoma Treated With Nivolumab.

Importance: Nivolumab is a standard-of-care adjuvant therapy for patients with muscle-invasive urothelial carcinoma (MIUC) at high risk for recurrence after radical resection. However, a better understanding of its use and clinical effectiveness in general patient populations is needed.

Objective: To examine treatment patterns and clinical outcomes for patients with MIUC treated with adjuvant nivolumab in a community setting.

Quantitation of Tuvusertib (M1774) in Human Plasma by LC-MS/MS.

Ataxia-telangiectasia and Rad3-related (ATR) protein kinase is an essential regulator of the DNA damage response (DDR) at stalled and collapsed replication forks. Tuvusertib (M1774) is a selective, orally available small molecule ATR inhibitor currently in preclinical and clinical development for cancer treatment. This study presents a robust and simple 5-min assay designed for the quantification of single agent tuvusertib in human plasma utilizing liquid chromatography tandem mass spectrometry (LC-MS/MS).

Urothelial carcinoma: Perioperative considerations from top to bottom.

Urothelial carcinoma is an aggressive entity that is associated with significant morbidity, but there have been major advances in both our understanding of and treatment options for patients with this disease. In this review, the authors focus on novel therapeutic and diagnostic approaches in the perioperative setting, with an emphasis on patient-centered and individualized care. For urothelial carcinoma of the bladder (UCB), advances in nonplatinum-based therapies, specifically immunotherapy and antibody-drug conjugates, have expanded the therapeutic arsenal for patients with muscle-invasive UCB in both the neoadjuvant and adjuvant settings to improve survival outcomes.

Mitochondrial Dynamics Through the Lens of Nonlinear Chemical Oscillations: A Theoretical Exploration Inspired by the Belousov-Zhabotinsky Reaction.

In biology, oscillations are observed across a wide spectrum of processes and systems. Oscillatory systems are typically leveraged to transmit information within cells. However, they can also serve to transmit information between organisms underscoring their fundamental role in regulating transitions, maintaining stability, and responding to environmental stimuli.

GUIDE: a prospective cohort study for blood-based early detection of gastrointestinal cancers using targeted DNA methylation and fragmentomics sequencing.

Background: Gastrointestinal (GI) cancers are among the most prevalent and lethal malignancies worldwide. Early, non-invasive detection is essential for timely intervention and improved survival. To address this clinical need, we developed GutSeer, a blood-based assay combining DNA methylation and fragmentomics for multi-GI cancer detection.

Radiation therapy in clinically node positive HER2 positive breast cancer after primary systemic therapy and breast conserving surgery: pooled analysis of TRYPHAENA and NeoSphere trials.

Background: The benefit of regional nodal irradiation (RNI) following modern primary systemic therapy (PST) in HER2-positive breast cancer (HER2 + BC) remains under investigation. The current study evaluates RNI practice patterns and outcomes based on the pathological response to PST in clinically node-positive (cN+) HER2 + BC.

Methods: TRYPHAENA and NeoSphere are two randomized phase II trials that investigated PST for HER2 + BC.

Long-Term (≥5-Year) Remission and Survival After Treatment With Ciltacabtagene Autoleucel in CARTITUDE-1 Patients With Relapsed/Refractory Multiple Myeloma.

CARTITUDE-1 evaluated ciltacabtagene autoleucel (cilta-cel) in patients with heavily pretreated relapsed/refractory multiple myeloma (RRMM). We describe overall survival (OS), ≥5-year progression-free outcomes, associated biomarkers, and safety, with a median study follow-up of 61.3 months.

CEACAM1 as a mediator of B-cell receptor signaling in mantle cell lymphoma.

B-cell receptor (BCR) signaling plays an important role in the pathogenesis of mantle cell lymphoma (MCL), but the detailed mechanisms are not fully understood. In this study, through a genome-wide loss-of-function screen, we identify carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) as an essential factor in a subset of MCL tumors. Our signal transduction studies reveal that CEACAM1 plays a critical role in BCR activation through involvement in two dynamic processes.

Beyond Citations: Exploring Gender and Racial Gaps in Urology Publications Through Citation and Altmetric Analysis.

Objective: To examine the effects of author gender and race on citation metrics, including Altmetric Attention Scores (AAS), in urology publications.

Methods: We analyzed 91,100 urology publications published between 2009 and 2023, retrieved from the Altmetric database via Drexel University. Author gender was identified using GenderGuesser, and race was estimated using a published name-based algorithm.

Analysis of more than 400,000 women provides case-control evidence for BRCA1 and BRCA2 variant classification.

Clinical genetic testing identifies variants causal for hereditary cancer, information that is used for risk assessment and clinical management. Unfortunately, some variants identified are of uncertain clinical significance (VUS), complicating patient management. Case-control data is one evidence type used to classify VUS.

Loss of SMARCA4 Leads to Intron Retention and Generation of Tumor-Associated Antigens in Small Cell Carcinoma of the Ovary, Hypercalcemic Type.

Unlabelled: Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), is a rare, deadly form of ovarian cancer that uniformly harbors mutations in SMARCA4, a member of the SWI/SNF chromatin remodeling complex. SWI/SNF impacts RNA splicing, and dysregulation of splicing can generate immunogenic tumor antigens. In this study, we explored the relationship between SMARCA4 loss and RNA splicing dysregulation.

The Role of EBV in the Pathogenesis of Diffuse Large B-Cell Lymphoma.

There are multiple established risk factors for DLBCL; these risk factors share an underlying biology, which generally cause immune dysfunction, spanning immunosuppression to chronic inflammation. EBV is an established risk factor for DLBCL and approximately 10% of DLBCLs are EBV-positive. EBV is a ubiquitous infection, and it is thus among populations that are immunocompromised, by age or medically defined, where EBV-positive DLBCLs arise.