Development of Alginate-Based Biodegradable Radioactive Microspheres Labeled with Positron Emitter through Click Chemistry Reaction: Stability and PET Imaging Study.

Biodegradable radioactive microspheres labeled with positron emitters hold significant promise for diagnostic and therapeutic applications in cancers and other diseases, including arthritis. The alginate-based polymeric microspheres offer advantages such as biocompatibility, biodegradability, and improved stability, making them suitable for clinical applications. In this study, we developed novel positron emission tomography (PET) microspheres using alginate biopolymer radiolabeled with gallium-68 (Ga) through a straightforward conjugation reaction.

Trametinib Potentiates Anti-PD-1 Efficacy in Tumors Established from Chemotherapy-Primed Pancreatic Cancer Cells.

Despite advances in immune checkpoint inhibitors, chemotherapy remains the standard therapy for patients with pancreatic ductal adenocarcinoma (PDAC). As the combinations of chemotherapy, including the FOLFIRINOX [5-fluorouracil, F; irinotecan, I; and oxaliplatin, O (FIO)] regimen, and immune checkpoint inhibitors have failed to demonstrate clinical benefit in patients with metastatic PDAC tumors, there is increasing interest in identifying therapeutic approaches to potentiate ICI efficacy in patients with PDAC. In this study, we report that neoadjuvant FOLFIRINOX-treated human PDAC tumors exhibit increased MEK/ERK activation.

Neuroblastoma, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology.

Neuroblastoma is the most common extracranial solid tumor diagnosed in children. This inaugural version of the NCCN Guidelines for Neuroblastoma provides recommendations for the diagnosis, risk classification, and treatment of neuroblastoma. The information in these guidelines was developed by the NCCN Neuroblastoma Panel, a multidisciplinary group of representatives with expertise in neuroblastoma, consisting of pediatric oncologists, radiologists, pathologists, surgeons, and radiation oncologists from NCCN Member Institutions.

Exploring the Relationship Among Financial Hardship, Anxiety, and Depression in Patients With Cancer: A Longitudinal Study.

Purpose: Financial hardship (FH) is a complex issue in cancer care, affecting material conditions, well-being, and coping behaviors. This study aimed to longitudinally examine FH, anxiety, depressive symptoms, and their associations while incorporating social determinants of health and health care cost covariates in a sample of patients diagnosed with cancer.

Methods: This prospective, longitudinal cohort study analyzed data from 2,305 participants from the Northwestern University Improving the Management of Symptoms during and following Cancer Treatment trial.

Arid1a-dependent canonical BAF complex suppresses inflammatory programs to drive efficient germinal center B cell responses.

The mammalian Brg1/Brm-associated factor (BAF) complexes are major regulators of nucleosomal remodeling that are commonly mutated in several cancers, including germinal center (GC)-derived B cell lymphomas. However, the specific roles of different BAF complexes in GC B cell biology are not well understood. Here we show that the AT-rich interaction domain 1a (Arid1a) containing canonical BAF (cBAF) complex is required for maintenance of GCs and high-affinity antibody responses.

Measuring perceived utility of genomic sequencing: Development and validation of the GENEtic Utility (GENE-U) scale for adult screening.

Purpose: As population-based screening programs to identify genetic conditions in adults using genomic sequencing (GS) are increasingly available, validated patient-centered outcome measures are needed to understand participants' experience. We aimed to develop and validate an instrument to assess the perceived utility of GS in the context of adult screening.

Methods: Informed by a 5-domain conceptual model, we used a 5-step approach to instrument development and validation: (1) item writing, (2) cognitive testing, (3) pilot testing and item reduction, (4) psychometric testing, and (5) evaluation of construct validity.

Targeting BCL2 with Venetoclax Enhances the Efficacy of the KRASG12D Inhibitor MRTX1133 in Pancreatic Cancer.

MRTX1133 is currently being evaluated in patients with pancreatic ductal adenocarcinoma (PDAC) tumors harboring a KRASG12D mutation. Combination strategies have the potential to enhance the efficacy of MRTX1133 to further promote cell death and tumor regression. In this study, we demonstrated that MRTX1133 increased the levels of the proapoptotic protein BIM in PDAC cells and conferred sensitivity to the FDA-approved BCL2 inhibitor venetoclax.

Prevalence of and gene regulatory constraints on transcriptional adaptation in single cells.

Background: Cells and tissues have a remarkable ability to adapt to genetic perturbations via a variety of molecular mechanisms. Nonsense-induced transcriptional compensation, a form of transcriptional adaptation, has recently emerged as one such mechanism, in which nonsense mutations in a gene trigger upregulation of related genes, possibly conferring robustness at cellular and organismal levels. However, beyond a handful of developmental contexts and curated sets of genes, no comprehensive genome-wide investigation of this behavior has been undertaken for mammalian cell types and conditions.

BET Inhibition Rescues Acinar-Ductal-Metaplasia and Ciliogenesis and Ameliorates Chronic Pancreatitis-Driven Changes in Mice With Loss of the Polarity Protein Par3.

Background & Aims: The apical-basal polarity of pancreatic acinar cells is essential for maintaining tissue architecture. However, the mechanisms by which polarity proteins regulate acinar pancreas injury and regeneration are poorly understood.

Methods: Cerulein-induced pancreatitis was induced in mice with conditional deletion of the polarity protein Par3 in the pancreas.

Differential impact of intratumor heterogeneity (ITH) on survival outcomes in early-stage lung squamous and adenocarcinoma based on tumor mutational burden (TMB).

Background: Molecular biomarkers are reshaping patient stratification and treatment decisions, yet their precise use and best implementation remain uncertain. Intratumor heterogeneity (ITH), an area of increasing research interest with prognostic value across various conditions, lacks defined clinical relevance in certain non-small cell lung cancer (NSCLC) subtypes. Exploring the relationship between ITH and tumor mutational burden (TMB) is crucial, as their interplay might reveal distinct patient subgroups.

Loss of STK11 Suppresses Lipid Metabolism and Attenuates KRAS-Induced Immunogenicity in Patients with Non-Small Cell Lung Cancer.

Unlabelled: As many as 30% of the patients with non-small cell lung cancer harbor oncogenic KRAS mutations, which leads to extensive remodeling of the tumor immune microenvironment. Although co-mutations in several genes have prognostic relevance in KRAS-mutated patients, their effect on tumor immunogenicity are poorly understood. In the present study, a total of 189 patients with non-small cell lung cancer underwent a standardized analysis including IHC, whole-exome DNA sequencing, and whole-transcriptome RNA sequencing.

Validity of a single-item indicator of treatment side effect bother in patients with head and neck cancer.

Purpose: Patients with head/neck squamous cell carcinomas (HNSCC) experience significant tumor- and treatment-related side effects. No efficient summary measure capturing the totality of side effect burden currently exists. We examined associations between a single patient-reported outcome (PRO) item evaluating side effect bother (FACT GP5, "I am bothered by side effects of treatment") with overall side effects in HNSCC.

Social isolation, depression, and anxiety among young adult cancer survivors: The mediating role of social connectedness.

Background: Social isolation and social connectedness are health determinants and aspects of social well-being with strong associations with psychological distress. This study evaluated relationships among social isolation, social connectedness, and psychological distress (i.e.

Shared decision-making and disease management in advanced cancer and chronic kidney disease using patient-reported outcome dashboards.

Objectives: To assess the use of a co-designed patient-reported outcome (PRO) clinical dashboard and estimate its impact on shared decision-making (SDM) and symptomatology in adults with advanced cancer or chronic kidney disease (CKD).

Materials And Methods: We developed a clinical PRO dashboard within the Northwestern Medicine Patient-Reported Outcomes system, enhanced through co-design involving 20 diverse constituents. Using a single-group, pretest-posttest design, we evaluated the dashboard's use among patients with advanced cancer or CKD between June 2020 and January 2022.

AP-1 Mediates Cellular Adaptation and Memory Formation During Therapy Resistance.

Cellular responses to environmental stimuli are typically thought to be governed by genetically encoded programs. We demonstrate that melanoma cells can form and maintain cellular memories during the acquisition of therapy resistance that exhibit characteristics of cellular learning and are dependent on the transcription factor AP-1. We show that cells exposed to a low dose of therapy adapt to become resistant to a high dose, demonstrating that resistance was not purely selective.

Devimistat (CPI-613) With Modified Fluorouarcil, Oxaliplatin, Irinotecan, and Leucovorin (FFX) Versus FFX for Patients With Metastatic Adenocarcinoma of the Pancreas: The Phase III AVENGER 500 Study.

Purpose: Metastatic pancreatic adenocarcinoma (mPC) remains a difficult-to-treat disease. Fluorouarcil, oxaliplatin, irinotecan, and leucovorin (FFX) is a standard first-line therapy for mPC for patients with a favorable performance status and good organ function. In a phase I study, devimistat (CPI-613) in combination with modified FFX (mFFX) was deemed safe and exhibited promising efficacy in mPC.

Engineered uterine primary myometrial cells with high-mobility group AT-hook 2 overexpression display a leiomyoma-like transcriptional and epigenomic phenotype.

Objective: To determine if engineered high-mobility group AT-hook 2 (HMGA2) overexpressing uterine primary myometrial cells recapitulate the transcriptional and epigenomic features of HMGA2-subtype leiomyomas.

Design: Isolated primary, "normal" myometrial cells from three patients were engineered to overexpress HMGA2 to determine how HMGA2 establishes transcriptomic and epigenomic features of HMGA2-overexpressing leiomyoma.

Setting: Academic research laboratory.