Matched three-dimensional organoids and two-dimensional cell lines of melanoma brain metastases mirror response to targeted molecular therapy DOI Creative Commons
William H. Hicks, Lauren C. Gattie, Mohamad El Shami

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Oct. 22, 2024

Despite advances in the treatment paradigm for patients with metastatic melanoma, melanoma brain metastasis (MBM) continues to represent a significant challenge. The study of MBM is limited, part, by shortcomings existing preclinical models. Surgically eXplanted Organoids (SXOs) are ex vivo, three-dimensional cultures prepared from primary tissue samples minimal processing that recapitulate genotypic and phenotypic features parent tumors without an artificial extracellular scaffold. SXOs were created novel protocol incorporating techniques establishing glioma cutaneous organoids. A BRAFV600K-mutant BRAF-wildtype sample collected directly operating room. cultured optimized culture medium Concurrently, matched patient-derived cell lines created. Organoid growth was observed within 3–4 weeks, retained histological tissue, including pleomorphic epithelioid cells abundant cytoplasm, large nuclei, focal melanin accumulation, strong SOX10 positivity. After sufficient growth, organoids could be manually parcellated increase number replicates. Matched demonstrated sensitivity BRAF MEK inhibitors. Further using may improve translational relevance studies enable tumor microenvironment.

Language: Английский

Impact of physiological media on acute myeloid leukemia bioenergetics and cell proliferation DOI Creative Commons
Brett R Chrest, McLane M. Montgomery, Raphael Taiwo Aruleba

et al.

Cancer & Metabolism, Journal Year: 2025, Volume and Issue: 13(1)

Published: May 26, 2025

Increasing emphasis has been placed on improving the physiological relevance of cell culture media with formulations such as Human Plasma-Like Medium (HPLM). Given that shifts in mitochondrial metabolism and nutrient use are emerging anti-cancer targets, present study sought to investigate impact formulation bioenergetics cancer growth. To do this, we used acute myeloid leukemia (AML) cells compared chronic effects HPLM versus different supraphysiological medias. The AML phenotype was largely unaffected by exposure either or medias, establishing key features mitochondria remain phenotypically stable under diverse conditions proliferation rates. Both culturing slowed proliferation. However, merely identifying supplementing single nutrients were deficient did not improve sufficient pinpoint actionable fuel preferences. Transferring back native Iscove's Modified Dulbecco's (IMDM) immediately restored proliferative phenotype, suggesting responsiveness entirety environment. Supraphysiological medias other than IMDM all characterized slower proliferation; however, none associated changes viability, demonstrating medium is optimal if experimental aim maximal Despite Eagle (DMEM) being similar composition categorized supraphysiological, both DMEM resulted growth, akin what observed HPLM. Altogether, independent unperturbed media, rather specific relevance, influenced complete profile.

Language: Английский

Citations

0
Organoid Intelligence: Bridging Artificial Intelligence for Biological Computing and Neurological Insights DOI Creative Commons
Sangeeta Ballav, Amit Ranjan,

Shubhayan Sur

et al.

Biochemistry, Journal Year: 2024, Volume and Issue: unknown

Published: March 8, 2024

Brain organoid implications have opened vast avenues in the realm of interdisciplinary research, particularly growing field intelligence (OI). A brain is a three-dimensional (3D), lab-grown structure that mimics certain aspects human organization and function. The integration technology with computational methods to enhance understanding behavior predict their responses various stimuli known as OI. ability organoids adapt memorize, key area exploration. OI encapsulates confluence breakthroughs stem cell technology, bioengineering, artificial (AI). This chapter delves deep into myriad potentials OI, encompassing an enhanced cognitive functions, achieving significant biological proficiencies. Such advancements stand offer unique complementarity conventional computing methods. sphere signify transformative stride towards more intricate grasp its multifaceted intricacies. intersection biology machine learning rapidly evolving reshaping our life health. convergence driving numerous areas, including genomics, drug discovery, personalized medicine, synthetic biology.

Language: Английский

Citations

2
Matched three-dimensional organoids and two-dimensional cell lines of melanoma brain metastases mirror response to targeted molecular therapy DOI Creative Commons
William H. Hicks, Lauren C. Gattie, Jeffrey I. Traylor

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 23, 2024

Abstract Purpose Despite significant advances in the treatment paradigm for patients with metastatic melanoma, melanoma brain metastasis (MBM) continues to represent a challenge. The study of MBM is limited, part, by shortcomings existing preclinical models. Surgically eXplanted Organoids (SXOs) are ex vivo, three-dimensional cultures prepared from primary tissue samples minimal processing that recapitulate genotypic and phenotypic features parent tumors grown without artificial extracellular scaffolding. We aimed develop first matched patient-derived SXO cell line models investigate responses targeted therapy. Methods SXOs were created novel protocol incorporating techniques establishing glioma cutaneous organoids. A BRAF V600K -mutant BRAF-wildtype sample collected directly operating room downstream experiments. cultured an optimized culture medium scaffold. Concurrently, lines created. Drug screens conducted assess response lines. Results Organoid growth was observed within 3-4 weeks, retained histological tissue, including pleomorphic epithelioid cells abundant cytoplasm, large nuclei, focal melanin accumulation, strong SOX10 positivity. After sufficient growth, organoids could be manually parcellated increase number replicates. Matched demonstrated sensitivity MEK inhibitors. Conclusion Here, we describe creation scaffold-free organoid model MBM. Further using may improve translational relevance studies enable tumor microenvironment.

Language: Английский

Citations

0
Hypoxanthine in the microenvironment can enable thiopurine resistance in acute lymphoblastic leukemia DOI Creative Commons
Xiaohong Wang,

Jason Ostergaard,

Jongseok Kang

et al.

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: July 19, 2024

Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy, with relapse being a major obstacle to successful treatment. Our understanding of mechanisms driving chemotherapy resistance and ultimately in remains incomplete. Herein, we investigate impact tumor microenvironment on cell drug responses using human plasma-like media (HPLM), designed mimic physiological conditions more accurately ex vivo . We demonstrate that while chemotherapeutics maintain an efficacy HPLM comparable standard tissue culture media, thiopurines 6-mercaptopurine (6-MP) 6-thioguanine (6-TG) exhibit significantly reduced potency against both B- T- cells HPLM. By merging our thiopurines’ mechanism action metabolites supplemented compared proposed subsequently validated hypothesis hypoxanthine, purine derivative, responsible for conferring thiopurines. Importantly, concentration hypoxanthine required levels found , supporting clinical relevance. findings utility physiologic identifying characterizing by which can enable resistance. Understanding such interactions may inform strategies overcome improve therapeutic outcomes leukemia.

Language: Английский

Citations

0
A reference for selecting an appropriate method for generating glioblastoma organoids from the application perspective DOI Creative Commons

Jing Liang,

Peng He

Discover Oncology, Journal Year: 2024, Volume and Issue: 15(1)

Published: Sept. 18, 2024

Glioblastoma organoids (GBOs) serve as a powerful and reliable tool to study glioblastoma stem cells (GSCs) (GBM). GBOs can be derived from different materials using methods. To identify the predominant generation methods most applications of GBOs, we searched four databases (PubMed, Embase, Web Science, Wiley Online Laboratory) August 2021 2023. After screening, 42 out 295 articles were included analyzed. in these generated only one material, such tumor tissues, cells, gene-edited multifunctional or simultaneously two materials, normal organoids. Methodologically, direct cultivation GBM tissues was commonly used method generate GBOs. Embryonic (ESCs) induced pluripotent (iPSCs) frequently by silencing P53, NF1, PTEN CRISPR/Cas9. In terms applications, tissue had including molecular mechanisms, therapy, culture technique. This review provides theoretical reference for selecting an appropriate when studying GSCs GBM.

Language: Английский

Citations

0
Matched three-dimensional organoids and two-dimensional cell lines of melanoma brain metastases mirror response to targeted molecular therapy DOI Creative Commons
William H. Hicks, Lauren C. Gattie, Mohamad El Shami

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Oct. 22, 2024

Despite advances in the treatment paradigm for patients with metastatic melanoma, melanoma brain metastasis (MBM) continues to represent a significant challenge. The study of MBM is limited, part, by shortcomings existing preclinical models. Surgically eXplanted Organoids (SXOs) are ex vivo, three-dimensional cultures prepared from primary tissue samples minimal processing that recapitulate genotypic and phenotypic features parent tumors without an artificial extracellular scaffold. SXOs were created novel protocol incorporating techniques establishing glioma cutaneous organoids. A BRAFV600K-mutant BRAF-wildtype sample collected directly operating room. cultured optimized culture medium Concurrently, matched patient-derived cell lines created. Organoid growth was observed within 3–4 weeks, retained histological tissue, including pleomorphic epithelioid cells abundant cytoplasm, large nuclei, focal melanin accumulation, strong SOX10 positivity. After sufficient growth, organoids could be manually parcellated increase number replicates. Matched demonstrated sensitivity BRAF MEK inhibitors. Further using may improve translational relevance studies enable tumor microenvironment.

Language: Английский

Citations

0