Publications by authors named "J E Bowser"
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 compared with conventional 2D monolayers. Using a genetic screening platform, we identify MAPK14 (which encodes the protein kinase p38α) as a specific requirement for HGEC in spheroid culture.
View Article and Find Full Text PDFMissense mutations in exon 3 of , the gene encoding β-catenin, are associated with poor outcomes in endometrial carcinomas (EC). Clinically, mutation status has been difficult to use as a predictive biomarker as β-catenin oncogenic activity is modified by other factors, and these determinants are unknown. Here we reveal that CD73 restrains the oncogenic activity of exon 3 β-catenin mutants, and its loss associates with recurrence.
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- - Regulatory CD8 T cells (CD8 Treg) usually help control harmful CD4 T cells, but in autoimmune diseases, they often fail, partly due to inhibitory receptors that limit their activation.
- - A new bispecific antibody called MTX-101 targets these inhibitory receptors and CD8 T cells to enhance the ability of CD8 Treg to eliminate pathogenic CD4 T cells in various experimental models.
- - In studies, MTX-101 improved CD8 Treg activity, reduced harmful CD4 T cell expansion, and protected tissues from damage without triggering excessive inflammation, showing promise for treating autoimmune disorders.
Article Synopsis
- The standard treatment for metastatic prostate cancer involves drugs that target androgen receptor (AR) signaling, but resistance to these treatments is common.
- Research shows that the AR inhibitor enzalutamide causes DNA replication stress in AR-positive prostate cancer cells, leading to increased DNA damage.
- Combining enzalutamide with a translesion DNA synthesis (TLS) inhibitor, JH-RE-06, enhances the sensitivity of these cancer cells to treatment and significantly reduces tumor growth in a mouse model.
Article Synopsis
- Understanding the molecular mechanisms behind High Grade Endometrial Carcinoma (HGEC) is crucial, as its metastatic behavior is not well understood.
- This research shows that HGEC cell lines grown in 3D spheroid cultures better mimic the characteristics of malignant peritoneal effusions compared to traditional 2D cultures, highlighting significant differences in their molecular profiles.
- The study identifies the protein kinase p38α as critical for sustaining tumor growth in spheroid cultures, linking it to cancer stem cell enrichment and revealing unique biological programs that are not observed in 2D cultures.