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Establishing 3D Organoid Models from Patient-Derived Conditionally Reprogrammed Cells to Bridge Preclinical and Clinical Insights in Pancreatic Cancer

ABSTRACT: Establishing 3D Organoid Models from Patient-Derived Conditionally Reprogrammed Cells to Bridge Preclinical and Clinical Insights in Pancreatic Cancer

PROVIDER: PRJNA1266152 | ENA |

REPOSITORIES: ENA

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Establishing 3D Organoid Models from Patient-Derived Conditionally Reprogrammed Cells to Bridge Preclinical and Clinical Insights in Pancreatic Cancer

Project description:Pancreatic cancer is a highly aggressive malignancy with limited therapeutic options. To address the limitations of traditional 2D cell culture models, we developed 3D organoid cultures from patient-derived conditionally reprogrammed cell (CRC) lines. These organoids retain the molecular and mutational profiles of the original tumor cells, providing a more accurate model for drug response prediction. Drug sensitivity assays using gemcitabine plus nab-paclitaxel (Abraxane) and FOLFIRINOX revealed that 3D organoids more closely reflect clinical outcomes than 2D cultures, with higher IC50 values consistent with in vivo drug resistance. This platform offers a promising approach for precision medicine in pancreatic cancer.

2025-06-16 | GSE297770 | GEO

Conditionally reprogrammed (CRC) and feeder free SMAD inhibited (SMADi) expanded human nasal epithelial cells label-free LC-MS/MS

Project description:Discovery of therapies that are able to correct defective CFTR requires patient derived in vitro pre-clinical cell models to be developed. Two main approaches exist to expand bronchial and nasal cultures, such as conditionally reprogrammed cells (CRC) and feeder free dual SMAD inhibition (SMADi) to overcome senescence, low cell count, and increase passages. To mimic airway epithelium the expanded cells are differentiated at air liquid Interface (ALI). This project focused to compare the global proteome of ALI differentiated CRC and SMADi expanded HNECs both treated and untreated with CFTR corrector VX-809.

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Conditionally reprogrammed cells from patient-derived xenograft to model neuroendocrine prostate cancer development

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Preclinical Models for Neuroblastoma: Establishing a Baseline for Treatment

Project description:Here we characterize and optimize both systems to increase their utility for preclinical studies. We show that TH-MYCN mice develop tumors in the paraspinal ganglia, but not in the adrenal, with cellular and gene expression patterns similar to human NB. In addition, we present a new ultrasound guided, non-invasive orthotopic xenograft method. This injection technique is rapid, provides accurate targeting of the injected cells and leads to efficient engraftment. We also demonstrate that tumors can be detected, monitored and quantified prior to visualization using ultrasound, MRI and bioluminescence. Finally we develop and test a “standard of care” chemotherapy regimen. This protocol, which is based on current treatments for neuroblastoma, provides a baseline for comparison of new therapeutic agents. A total of 17 samples are provided reprsenting TH-MYCN tumors derived from mice

2011-03-17 | E-GEOD-27516 | biostudies-arrayexpress

Strigolactone analogs induce apoptosis through activation of p38 and the stress response pathway in cancer cell lines and in conditionally reprogrammed primary prostate cancer cells

Project description:Strigolactones are a novel class of plant hormones produced in roots and regulate shoot and root development. We have previously shown that synthetic strigolactone analogues potently inhibit growth of breast cancer cells and breast cancer stem cells. Here we show that strigolactone analogues inhibit the growth and survival of an array of cancer-derived cell lines representing solid and non-solid cancer cells including: prostate, colon, lung, melanoma, osteosarcoma and leukemic cell lines, while normal cells were minimally affected. Furthermore, we tested the response of patient-matched conditionally reprogrammed normal and prostate cancer cells. The tumor cells exhibited significantly higher sensitivity to the two most potent SL analogues with increased apoptosis compared to their normal counterpart cells. Treatment of cancer cells with strigolactone analogues was hallmarked by increased expression and activity of genes involved in stress signaling, cell cycle arrest and apoptosis. All five strigolactone analogues induced G2/M cell cycle arrest, accompanied with a decrease in the expression level of cyclin B1. Apoptosis was marked by increased percentages of cells in the sub-G1 fraction and was confirmed by Annexin V staining. In conditionally reprogramed matched tumor and normal prostate cells, the cleavage of PARP1 confirmed the specific increase in apoptosis of tumor cells. In summary, Strigolactone analogues are promising candidates for anticancer therapy by their ability to specifically induce cell cycle arrest, cellular stress and apoptosis in tumor cells with minimal effects on growth and survival of normal cells.

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ena-DATASET-FIMM-19-02-2016-09:48:34:645-121 - samples

Project description:RNA sequence data for conditionally reprogrammed cells from patient HUB_5

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Patient-derived conditionally reprogrammed cells maintain intra-tumor genetic heterogeneity.

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Mucus secretions from a conditionally reprogrammed primary endocervical cell culture.

Project description:ObjectiveTo determine if the secretions collected from a conditionally reprogrammed primary endocervical cell culture are suitable surrogates for mucus studies.DesignExperimental.SettingUniversity research center.Animal(s)Female rhesus macaque (n = 2).Intervention(s)None.Main outcome measure(s)Quantitative proteomic analysis using tandem mass tag mass spectrometry liquid chromatography/tandem mass spectrometry.Result(s)We identified 3,047 proteins, common proteins present in both primary endocervical cell cultures and the mucus of rhesus macaques. We found a 71% overlap in the top 500 most prevalent proteins in the samples. Cell culture secretions contained many essential mucus proteins, including MUC5B, the primary mucin of the endocervix.Conclusion(s)Similarities in secreted proteins suggest that conditionally reprogrammed primary endocervical cells could be used to study mucus secretion in vitro.

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Project description:We developed methods for conditionally reprogramming (CR) primary human bronchial epithelial cells (HBECs) to extend their functional lifespan and permit their differentiation into both upper and lower airway lung epithelium. We also developed a bioreactor to support vascular perfusion and rhythmic breathing of decellularized mouse lungs reconstituted with CR HBECs isolated from patients with and without cystic fibrosis (CF). While conditionally reprogrammed cells only differentiate into an upper airway epithelium after 35 days at the air-liquid interface, in reconstituted lungs these cells differentiate into upper airway bronchial epithelium and lower airway alveolar structures after 12 days. Rapid scale-up and the ability to obtain clonal derivatives of primary patient-derived HBECs without the need for genetic manipulation may permit rapid reconstitution of the lung epithelium; facilitating the study of lung disease in tissue-engineered models.

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Strigolactone analogs induce apoptosis through activation of p38 and the stress response pathway in cancer cell lines and in conditionally reprogrammed primary prostate cancer cells

2014-02-10 | E-GEOD-54820 | biostudies-arrayexpress