Biology subjects

Bae-Jump, V.

Publications and source records attributed to Bae-Jump, V..

3 recordsLinked to original sources

bioRxiv2024

MAPK14/p38α Shapes the Molecular Landscape of Endometrial Cancer and promotes Tumorigenic Characteristics

The molecular underpinnings of High Grade Endometrial Carcinoma (HGEC) metastatic growth and survival are poorly understood. Here we show that ascites-derived and primary tumor HGEC cell lines in 3D spheroid culture faithfully recapitulate key features of malignant peritoneal effusion and exhibit fundamentally distinct transcriptomic, proteomic and metabolomic landscapes when compared with conventional 2D monolayers. Using genetic screening platform we identify MAPK14 (which encodes the protein kinase p38) as a specific requirement for HGEC in spheroid culture. MAPK14/p38 has broad roles in programing the phosphoproteome, transcriptome and metabolome of HGEC spheroids, yet has negligible impact on monolayer cultures. MAPK14 promotes tumorigenicity in vivo and is specifically required to sustain a sub-population of spheroid cells that is enriched in cancer stemness markers. Therefore, spheroid growth of HGEC activates unique biological programs, including p38 signaling, that cannot be captured using 2D culture models and are highly relevant to malignant disease pathology.

cancer biology↗

bioRxiv2024

A Novel ex-vivo platform for personalized treatment in metastatic ovarian cancer.

The lack of functional precision models that recapitulate the pathology and structure/function relationship of advanced ovarian cancer (OC) within an appropriate anatomic setting constitutes a hurdle on the path to developing more reliable therapies and matching those therapies with the right patients. Here, we developed and characterized an Organotypic Mesentery Membrane Culture (OMMC) model as a novel ex-vivo platform where freshly resected human patient OC tumor tissue or established cell lines are seeded directly atop living intact rat mesenteric membranes, rapidly engraft, and enable functional assessment of treatment response to FDA-approved standard care of treatment as single and combination drug therapies within just five days. This study showed successful survival of dissected mesentery tissue, survival and engraftment of tumor cells and patient tumor tissue seeded on OMMCs, mesentery-tumor cell interaction, and quantification of tumor response to treatment and off-target toxicity. Summarized "drug sensitivity scores", using a multi-parametric algorithm, were also calculated for each patients treatment response, enabling us to suggest the most effective therapeutic option. Finally, we compared drug sensitivity results from patient tumor tissue on OMMCs to matched outcomes of individual patients in the clinic and identified positive correlations in drug sensitivity, beginning to validate the functionality of OMMCs as a functional predictor of treatment response. Summary sentenceWe have successfully developed and characterized a novel ex-vivo platform for personalized treatment of metastatic ovarian cancer.

cancer biology↗

bioRxiv2019

Hematological and Neurological Expressed 1 (HN1): a predictive and pharmacodynamic biomarker of metformin response in endometrial cancers.

Preoperative use of metformin in obese women with endometrioid endometrial cancer (EEC) reduces tumor proliferation and inhibits the mammalian target of rapamycin (mTOR) pathway, though is only effective in select cases. This study sought to identify a predictive and/or pharmacodynamic proteomic signature of metformin response to tailor its pharmacologic use. Matched pre- and post-metformin treated tumor tissues from a recently completed phase 0 window trial of metformin in EEC patients (ClinicalTrials.gov: NCT01911247), were analyzed by mass spectrometry (MS)-based proteomic and immunohistochemical analyses. Hematological and neurological expressed 1 (HN1) was significantly elevated in metformin responders (n=13) versus non-responders (n=7), which was also found to decrease in abundance in metformin responders following treatment; observations that were verified by immunohistochemical staining for HN1. Metformin response and loss of HN1 was assessed in RL95-2 and ACI-181 endometrial cancer cell lines. We further identified that silencing of HN1 abundance does not alter cellular response to metformin or basal cell proliferation, but that HN1 abundance does decrease in response to metformin treatment in RL95-2 and ACI-181 endometrial cancer cell lines. These data suggest that HN1 represents a predictive and pharmacodynamic biomarker of metformin response that, if validated in larger patient populations, may enable pre-operative EEC patient stratification to metformin treatment and the ability to monitor patient response.\n\nNovelty and ImpactHematological and Neurological Expressed 1 (HN1) is elevated in endometrioid endometrial cancer (EEC) patients that respond to metformin vs non-responders and decreases after treatment. HN1 decreases after metformin treatment of EEC cells in vitro, but is not necessary for metformin response or proliferation. We report HN1 as a novel predictive and pharmacodynamic biomarker of metformin response in EEC that may enable pre-operative EEC patient stratification to metformin treatment and the ability to monitor patient response.

cancer biology↗