The use of patient-derived organoids (PDOs) to characterize therapeutic sensitivity and resistance (pharmacotyping) is a promising precision medicine approach. The potential of this approach to inform clinical decisions is now being tested in several large multi-institutional clinical trials. PDOs are cultivated in extracellular matrix from basement membrane extracts (BMEs) that are most commonly acquired commercially. Each clinical site utilizes distinct BME lots and may be restricted due to the availability of commercial BME sources. However, the impact of different sources and lots of BMEs on organoid drug response is unknown. Here, we tested the impact of BME source and lot on proliferation, chemotherapy and targeted therapy drug response, and gene expression in mouse and human pancreatic ductal adenocarcinoma (PDA) organoids. Both human and mouse organoids displayed increased proliferation in Matrigel (Corning) compared to Cultrex (RnD) and UltiMatrix (RnD). However, we observed no substantial impact on drug response when oragnoids were cultured in Matrigel, Cultrex, or UltiMatrix. We also did not observe major shifts in gene expression across the different BME sources, and PDOs maintained their Classical or Basal-like designation. Overall, we find that BME source (Matrigel, Cultrex, UltiMatrix) does not shift PDO dose-response curves and drug testing results, indicating that PDO pharmacotyping is a robust approach for precision medicine.
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http://dx.doi.org/10.1101/2023.01.26.525757 | DOI Listing |
Genet Med
December 2024
Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN; Center for Digital Genomic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN; Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN; Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN. Electronic address:
Purpose: The value of genetic information for improving the performance of clinical risk prediction models has yielded variable conclusions. Many methodological decisions have the potential to contribute to differential results. We performed multiple modeling experiments integrating clinical and demographic data from electronic health records (EHR) with genetic data to understand which decisions may affect performance.
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December 2024
School of Chemistry, Faculty of Engineering and Physical Sciences, University of Southampton, Life Sciences Building 85, University Road, Highfield, Southampton, SO17 1BJ, UK.
Osteoarthritis (OA) is a complex disease of cartilage characterised by joint pain, functional limitation, and reduced quality of life with affected joint movement leading to pain and limited mobility. Current methods to diagnose OA are predominantly limited to X-ray, MRI and invasive joint fluid analysis, all of which lack chemical or molecular specificity and are limited to detection of the disease at later stages. A rapid minimally invasive and non-destructive approach to disease diagnosis is a critical unmet need.
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December 2024
College of Advanced Manufacturing Innovation, King Mongkut's Institute of Technology Ladkrabang, Bangkok, Thailand.
Vector-borne diseases pose a major worldwide health concern, impacting more than 1 billion people globally. Among various blood-feeding arthropods, mosquitoes stand out as the primary carriers of diseases significant in both medical and veterinary fields. Hence, comprehending their distinct role fulfilled by different mosquito types is crucial for efficiently addressing and enhancing control measures against mosquito-transmitted diseases.
View Article and Find Full Text PDFJ Neurol
December 2024
Department of Neurosciences Rita Levi Montalcini, University of Turin, Turin, Italy.
Introduction: Non-motor symptoms (NMS) in Parkinson's disease (PD) can fluctuate daily, impacting patient quality of life. The Non-Motor Fluctuation Assessment (NoMoFA) Questionnaire, a recently validated tool, quantifies NMS fluctuations during ON- and OFF-medication states. Our study aimed to validate the Italian version of NoMoFA, comparing its results to the original validation and further exploring its clinimetric properties.
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December 2024
Department of Forensic Medicine, Guizhou Medical University, Guiyang, 550025, China.
Multi-insertion/deletion polymorphisms (Multi-InDels), as the novel genetic markers, show great potential in forensic research. Whereas, forensic researchers mainly focus on the multi-InDels on the autosomes, which can provide relatively limited information in some complex paternity cases. In this study, a novel X chromosomal multi-InDel multiplex amplification system was designed, containing 22 multi-InDels and one STR locus on the X chromosome.
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