Browsing by Subject "Genomic"

Now showing 1 - 5 of 5
  • Thumbnail Image
    Item
    Implementation of a Laboratory Information Management System To Manage Genomic Samples
    (2013-09-05) Witty, Derick; Merchant, Mahesh; Perumal, Narayanan B.; Turpin, Joseph
    A Laboratory Information Management Systems (LIMS) is designed to manage laboratory processes and data. It has the ability to extend the core functionality of the LIMS through configuration tools and add-on modules to support the implementation of complex laboratory workflows. The purpose of this project is to demonstrate how laboratory data and processes from a complex workflow can be implemented using a LIMS. Genomic samples have become an important part of the drug development process due to advances in molecular testing technology. This technology evaluates genomic material for disease markers and provides efficient, cost-effective, and accurate results for a growing number of clinical indications. The preparation of the genomic samples for evaluation requires a complex laboratory process called the precision aliquotting workflow. The precision aliquotting workflow processes genomic samples into precisely created aliquots for analysis. The workflow is defined by a set of aliquotting scheme attributes that are executed based on scheme specific rules logic. The aliquotting scheme defines the attributes of each aliquot based on the achieved sample recovery of the genomic sample. The scheme rules logic executes the creation of the aliquots based on the scheme definitions. LabWare LIMS is a Windows® based open architecture system that manages laboratory data and workflow processes. A LabWare LIMS model was developed to implement the precision aliquotting workflow using a combination of core functionality and configured code.
  • Thumbnail Image
    Item
    Osteoblast suppression in multiple myeloma bone disease
    (Elsevier, 2018-09-15) Adamik, Juraj; Galson, Deborah L.; Roodman, G. David; Medicine, School of Medicine
    Multiple myeloma (MM) is the most frequent cancer to involve the skeleton with patients developing osteolytic bone lesions due to hyperactivation of osteoclasts and suppression of BMSCs differentiation into functional osteoblasts. Although new therapies for MM have greatly improved survival, MM remains incurable for most patients. Despite the major advances in current anti-MM and anti-resorptive treatments that can significantly improve osteolytic bone lysis, many bone lesions can persist even after therapeutic remission of active disease. Bone marrow mesenchymal stem cells (BMSCs) from MM patients are phenotypically distinct from their healthy counterparts and the mechanisms associated with the long-term osteogenic suppression are largely unknown. In this review we will highlight recent results of transcriptomic profiling studies that provide new insights into the establishment and maintenance of the persistent pathological alterations in MM-BMSCs that occur in MM. We will we discuss the role of genomic instabilities and senescence in propagating the chronically suppressed state and pro-inflammatory phenotype associated with MM-BMSCs. Lastly we describe the role of epigenetic-based mechanisms in regulating osteogenic gene expression to establish and maintain the pro-longed suppression of MM-BMSC differentiation into functional OBs.
  • Thumbnail Image
    Item
    Phase II Clinical and Translational Study of Everolimus ± Paclitaxel as First-Line Therapy in Cisplatin-Ineligible Advanced Urothelial Carcinoma
    (Oxford University Press, 2022) Jun, Tomi; Hahn, Noah M.; Sonpavde, Guru; Albany, Constantine; MacVicar, Gary R.; Hauke, Ralph; Fleming, Mark; Gourdin, Theodore; Jana, Bagi; Oh, William K.; Taik, Patricia; Wang, Huan; Ramakrishnan Varadarajan, Ajay; Uzilov, Andrew; Galsky, Matthew D.; Medicine, School of Medicine
    Background: Treatment options have been historically limited for cisplatin-ineligible patients with advanced urothelial carcinoma (UC). Given the need for alternatives to platinum-based chemotherapy, including non-chemotherapy regimens for patients with both impaired renal function and borderline functional status, in 2010 (prior to the immune checkpoint blockade era in metastatic UC), we initiated a phase II trial to test the activity of everolimus or everolimus plus paclitaxel in the cisplatin-ineligible setting. Methods: This was an open-label phase II trial conducted within the US-based Hoosier Cancer Research Network (ClinicalTrials.gov number: NCT01215136). Patients who were cisplatin-ineligible with previously untreated advanced UC were enrolled. Patients with both impaired renal function and poor performance status were enrolled into cohort 1; patients with either were enrolled into cohort 2. Patients received everolimus 10 mg daily alone (cohort 1) or with paclitaxel 80 mg/m2 on days 1, 8, and 15 of each 28-day cycle (cohort 2). The primary outcome was clinical benefit at 4 months. Secondary outcomes were adverse events, progression-free survival (PFS), and 1-year overall survival (OS). Exploratory endpoints included genomic correlates of outcomes. The trial was not designed for comparison between cohorts. Results: A total of 36 patients were enrolled from 2010 to 2018 (cohort 1, N = 7; cohort 2, N = 29); the trial was terminated due to slow accrual. Clinical benefit at 4 months was attained by 0 (0%, 95% confidence interval [CI] 0-41.0%) patients in cohort 1 and 11 patients (37.9%, 95% CI 20.7-57.7%) in cohort 2. Median PFS was 2.33 (95% CI 1.81-Inf) months in cohort 1 and 5.85 (95% CI 2.99-8.61) months in cohort 2. Treatment was discontinued due to adverse events for 2 patients (29%) in cohort 1 and 11 patients (38%) in cohort 2. Molecular alterations in microtubule associated genes may be associated with treatment benefit but this requires further testing. Conclusion: Everolimus plus paclitaxel demonstrates clinical activity in cisplatin-ineligible patients with metastatic UC, although the specific contribution of everolimus cannot be delineated. Patients with both impaired renal function and borderline functional status may be difficult to enroll to prospective trials.
  • Thumbnail Image
    Item
    Provision and Availability of Genomic Medicine Services in Level IV Neonatal Intensive Care Units
    (Elsevier, 2023) Wojcik, Monica H.; Callahan, Katharine P.; Antoniou, Austin; del Rosario, Maya C.; Brunelli, Luca; ElHassan, Nahed O.; Gogcu, Semsa; Murthy, Karna; Rumpel, Jennifer A.; Wambach, Jennifer A.; Suhrie, Kristen; Fishler, Kristen; Chaudhari, Bimal P.; Pediatrics, School of Medicine
    Purpose: To describe variation in genomic medicine services across level IV neonatal intensive care units (NICUs) in the United States and Canada. Methods: We developed and distributed a novel survey to the 43 level IV NICUs belonging to the Children's Hospitals Neonatal Consortium, requesting a single response per site from a clinician with knowledge of the provision of genomic medicine services. Results: Overall response rate was 74% (32/43). Although chromosomal microarray and exome or genome sequencing (ES or GS) were universally available, access was restricted for 22% (7/32) and 81% (26/32) of centers, respectively. The most common restriction on ES or GS was requiring approval by a specialist (41%, 13/32). Rapid ES/GS was available in 69% of NICUs (22/32). Availability of same-day genetics consultative services was limited (41%, 13/32 sites), and pre- and post-test counseling practices varied widely. Conclusion: We observed large inter-center variation in genomic medicine services across level IV NICUs: most notably, access to rapid, comprehensive genetic testing in time frames relevant to critical care decision making was limited at many level IV Children's Hospitals Neonatal Consortium NICUs despite a significant burden of genetic disease. Further efforts are needed to improve access to neonatal genomic medicine services.
  • Thumbnail Image
    Item
    Rare Hematologic Malignancies and Pre-Leukemic Entities in Children and Adolescents Young Adults
    (MDPI, 2024-02-29) Brown, Amber; Batra, Sandeep; Pediatrics, School of Medicine
    There are a variety of rare hematologic malignancies and germline predispositions syndromes that occur in children and adolescent young adults (AYAs). These entities are important to recognize, as an accurate diagnosis is essential for risk assessment, prognostication, and treatment. This descriptive review summarizes rare hematologic malignancies, myelodysplastic neoplasms, and germline predispositions syndromes that occur in children and AYAs. We discuss the unique biology, characteristic genomic aberrations, rare presentations, diagnostic challenges, novel treatments, and outcomes associated with these rare entities.