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• In this study, blood-brain barrier (BBB)-forming brain endothelial-like cells were generated from apolipoprotein E gene allele E4 (APOE4, high AD risk) and allele E3 (APOE3, lower AD risk) carrying patient-derived induced pluripotent stem cells (iPSCs). Cells were subsequently exposed to focused ultrasound and microbubbles (FUS+MB) to induce BBB opening and their transcriptome analysed. RNA sequencing (RNA-seq) results demonstrated minimal changes in the gene expression following FUS+MB suggesting safety of FUS+MB application in the clinical setting.

  The blood-brain barrier (BBB) is a major impediment to therapeutic intracranial drug delivery for the treatment of neurodegenerative diseases, including Alzheimer’s disease (AD). Focused ultrasound applied together with microbubbles (FUS+MB) is a novel technique to transiently open the BBB and increase drug delivery. Evidence suggests that FUS+MB is safe, however the effects of FUS+MB on human BBB cells, especially in relation to AD, remain sparsely investigated. Here we developed a human sporadic AD BBB cell platform to investigate the effects of FUS+MB on BBB cells and screen for the delivery of two potentially therapeutic AD antibodies. We generated BBB cells from apolipoprotein E gene allele E4 (APOE4, high AD risk) and allele E3 (APOE3, lower AD risk) carrying patient-derived induced pluripotent stem cells (iPSCs). We utilized this robust and reproducible platform to demonstrate increased delivery of potentially therapeutic antibodies across the BBB, including an analogue of Aducanumab (AduhelmTM) following FUS+MB treatment. Our results also demonstrate the safety of FUS+MB indicated by minimal changes in the cell transcriptome as well as little or no changes in cell viability and inflammatory responses within first 24 h post FUS+MB, with potentially important implications in a clinical setting. Finally, we report a more physiologically relevant hydrogel-based 2.5D BBB model as a key development for FUS+MB-mediated drug delivery screening, with potentially higher translational utility. Our results provide an important advancement for identifying FUS+MB-deliverable drugs and screening for cell- and patient-specific effects of FUS+MB, accelerating its use as a therapy in AD.

  Study EGAS00001005944

• NEOPREDICT-Lung: Neoadjuvant Immunotherapy for Resectable NSCLC

  Links via: DOI: https://doi.org/10.1038/s41591-024-02965-0 PubMed: https://pubmed.ncbi.nlm.nih.gov/38689060/ Journal: https://www.nature.com/articles/s41591-024-02965-0 Abstract Antibodies targeting the immune checkpoint molecules PD-1, PD-L1 and CTLA-4 administered alone or in combination with chemotherapy are standard of care in most patients with metastatic non-small cell lung cancers. When given prior to curative surgery, tumor responses and improved event-free survival are achieved. New antibody combinations may be more efficacious and tolerable. In an ongoing, open-label phase II study, 60 biomarker-unselected, treatment-naïve patients with resectable non-small cell lung cancer were randomized to receive two preoperative doses of nivolumab (anti-PD-1) with or without relatlimab (anti-LAG-3) antibody therapy. The primary study endpoint was feasibility of surgery within 43 days, which was met by all patients. Curative resection was achieved in 95% of patients. Secondary endpoints included pathological and radiographic response rates, pathologically complete resection rates, disease-free and overall survival rates, and safety. Major pathological (≤10% viable tumor cells) and objective radiographic responses were achieved in 27% and 10% (nivolumab), and 30% and 27% (nivolumab and relatlimab) of patients, respectively. In 100% (nivolumab) and 90% (nivolumab and relatlimab) of patients tumors and lymph nodes were pathologically completely resected. With 12 months median duration of follow-up, disease-free survival and overall survival rates at 12 months were 89% and 93% (nivolumab), and 93% and 100% (nivolumab and relatlimab). Both treatments were safe with grade ≥ 3 treatment-emergent adverse events reported in 10% and 13% of patients per study arm. Exploratory analyses provided insights into biological processes triggered by preoperative immunotherapy. This study establishes the feasibility and safety of dual targeting of PD-1 and LAG-3 prior to lung cancer surgery.

  Study EGAS00001007753

• Genome-Wide Scan for Genetic Variants Associated with Early-Onset Prostate Cancer

  This is a genome-wide association scan of 931 early-onset prostate cancer cases of European ancestry. The samples were selected from prostate cancer studies at the University of Michigan. Controls were previously genotyped individuals selected from the Cancer Genetics Markers of Susceptibility (CGEMS) and Illumina's iControlDB database.

  Study phs001185

• RNA-seq analysis of BMP-stimulated glioma initiating cells

  Bone morphogenetic protein (BMP) signaling has been shown to suppress progression of glioblastoma by promoting astrocytic differentiation; however, roles of BMP signaling in cell proliferation and apoptosis of glioblastoma cells remains to be elucidated. We here performed RNA-seq analysis of glioma initiating cells to identify transcriptional target(s) of BMP.

  Study JGAS000077

• RNA of peripheral blood for pancreatic cancer and chronic pancreatitis

  Samples of nucleated cells found in peripheral blood from over 300 patients suffering from resectable pancreatic ductal adenocarcinoma, non-resectable pancreatic cancer, chronic pancreatitis, or none of these. Please cite this article when using data: Al-Fatlawi, A.; Malekian, N.; García, S.; Henschel, A.; Kim, I.; Dahl, A.; Jahnke, B.; Bailey, P.; Bolz, S.N.; Poetsch, A.R.; Mahler, S.; Grützmann, R.; Pilarsky, C.; Schroeder, M. Deep Learning Improves Pancreatic Cancer Diagnosis Using RNA-Based Variants. Cancers 2021, 13, 2654. https://doi.org/10.3390/cancers13112654

  Dataset EGAD00001006915

• Childhood Cancer Data Initiative (CCDI): OncoKids - NGS Panel for Pediatric Malignancies

  This study aimed to systematically collect clinical, registry and genomic data on pediatric cancer patients, and to contribute to the CCDI Pediatric Data Ecosystem. Clinical, treatment and outcome data on 1,039 pediatric cancer patients whose molecular profile was characterized on OncoKids gene panel at Children's Hospital Los Angeles was abstracted and harmonized for submission to the NCI’s Cancer Data Service. The OncoKids panel was designed to detect DNA mutations and amplification in almost 200 oncogenes and tumor suppressor genes, a limited number of pharmacogenomic targets and 1,700 disease-associated gene fusions at the RNA level. The panel encompasses the vast majority of FDA’s relevant pediatric molecular target list, as well as additional genes associated with ultra-rare pediatric tumors. The final data elements included DNA/RNA sequence data, OncoKids test results, clinical data on demographics, diagnosis, comorbidity and adverse events and treatment data.

  Study phs002518

• African American Breast Cancer GWAS

  The GWAS includes African American participants from 9 epidemiological studies of breast cancer, comprising a total of 3,153 cases and 2,831 controls (cases/controls: The Multiethnic Cohort Study (MEC), 734/1,003; The Los Angeles component of The Women's Contraceptive and Reproductive Experiences (CARE) Study, 380/224; The Women's Circle of Health Study (WCHS), 272/240; The San Francisco Bay Area Breast Cancer Study (SFBCS), 172/231; The Northern California Breast Cancer Family Registry (NC-BCFR), 440/53;The Carolina Breast Cancer Study (CBCS), 656/608; The Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) Cohort, 64/133; The Nashville Breast Health Study (NBHS), 310/186; and, The Wake Forest University Breast Cancer Study (WFBC), 125/153). Quality control of the GWAS data and additional details can be found in Chen et al. Hum Genet. 2013 (PMID: 22923054)

  Study phs000851

• The CHOP Pediatric Genetic Sequencing (PediSeq) Project : Applying Genomic Sequencing in Pediatrics

  The purpose of this research study is to learn more about newer types of genetic testing called whole exome sequencing and whole genome sequencing. Current genetic testing usually examines one gene or a few genes at a time. Exome and genome sequencing allow us to test most of a person's genes at one time with a single test. This testing might identify the reason for a person's unexplained condition or diagnosis. We hope this study will help us identify the best methods for: Educating patients and families about exome and genome sequencing Analyzing exome and genome sequencing data to identify results relevant to patients Giving results to families in a clear, appropriate, and informative manner The current data only includes WES for 159 samples. The WGS samples for 20 samples will be uploaded in the near future.

  Study phs000935

• Neuroblastoma Genome-Wide Association Study (NBL-GWAS)

  Neuroblastoma is a malignancy of the developing sympathetic nervous system that most commonly affects young children and is often lethal. The etiology of this embryonal cancer is not known. We have performed a whole genome scan for association of neuroblastoma with SNP genotypes and copy number variation to discover predisposition loci. We therefore initiated a genome-wide association study (GWAS) in 2007 focused on neuroblastoma patients identified through the Children's Oncology Group (COG; 238 member institutions). Control patients for this study are children cared for at the Children's Hospital of Philadelphia (CHOP) without a diagnosis of cancer. The study was designed to collect up to 5000 neuroblastoma cases and 10,000 controls and is powered to detect common susceptibility variants in Caucasian and African American patients. Whole genome genotyping is being performed on the Illumina HH550 SNP array.

  Study phs000124

• eMERGE III: Columbia GENIE (Genomic Integration with EHR)

  The Columbia GENIE study contributes and shares phenotype and genotype data for individuals who were treated with our healthcare facilities and consented to share their data with dbGaP for scientific discovery. Some of these individuals have kidney or neurological problems and some are healthy volunteers from the Washington Height patient community. The purpose of this NOMAS study is to obtain information about physical features of the brain, carotid arteries, and heart. Some of our patients are pediatric patients with cardiac conditions. The study sample consists of four patient cohorts: Northern Manhattan Study (NOMAS), N=1072 Pediatric Cardiac Genomic Consortium (PCGC), n=374 Caribbean Hispanics with Familial and Sporadic Late Onset Alzheimer's disease (Caribbean Hispanics/AD), n=330 Alzheimer's Disease Sequencing Project (ADSP, n=44) Genetics of Chronic Kidney Disease Study, n=1256

  Study phs000961