Inhibition of glypican-1 expression induces an activated fibroblast phenotype in a human bone marrow-derived stromal cell-line.

Cancer-associated fibroblasts (CAFs) are the most abundant stromal cell type in the tumor microenvironment. CAFs orchestrate tumor-stromal interactions, and contribute to cancer cell growth, metastasis, extracellular matrix (ECM) remodeling, angiogenesis, immunomodulation, and chemoresistance. However, CAFs have not been successfully targeted for the treatment of cancer. The current study elucidates the significance of glypican-1 (GPC-1), a heparan sulfate proteoglycan, in regulating the activation of human bone marrow-derived stromal cells (BSCs) of fibroblast lineage (HS-5). GPC-1 inhibition changed HS-5 cellular and nuclear morphology, and increased cell migration and contractility. GPC-1 inhibition also increased pro-inflammatory signaling and CAF marker expression. GPC-1 induced an activated fibroblast phenotype when HS-5 cells were exposed to prostate cancer cell conditioned media (CCM). Further, treatment of human bone-derived prostate cancer cells (PC-3) with CCM from HS-5 cells exhibiting GPC-1 loss increased prostate cancer cell aggressiveness. Finally, GPC-1 was expressed in mouse tibia bone cells and present during bone loss induced by mouse prostate cancer cells in a murine prostate cancer bone model. These data demonstrate that GPC-1 partially regulates the intrinsic and extrinsic phenotype of human BSCs and transformation into activated fibroblasts, identify novel functions of GPC-1, and suggest that GPC-1 expression in BSCs exerts inhibitory paracrine effects on the prostate cancer cells. This supports the hypothesis that GPC-1 may be a novel pharmacological target for developing anti-CAF therapeutics to control cancer.

Adapting Education at the Medical College of Georgia at Augusta University in Response to the COVID-19 Pandemic: the Pandemic Medicine Elective.

The Medical College of Georgia (MCG) responded to the COVID-19 pandemic's challenges to medical education with a novel, comprehensive curriculum. The Pandemic Medicine Elective was an effective solution with a safe, virtual alternative to traditional clinical experiences. As the elective evolved to include pre-clinical students and service initiatives across Georgia, students and faculty navigated online platforms to execute critical community-based projects. This curricular development utilized an interdisciplinary approach by faculty across each of MCG's regional campuses. We describe the curriculum of the electives, the student initiatives, and lessons learned while quickly adapting curriculum during the COVID-19 pandemic.

N,N'-Bis[(E)-4-nitro-benzyl-idene]-4,4'-oxydianiline.

The title compound, C(26)H(18)N(4)O(5), can be regarded as an extended ether with two terminal nitro groups. The two aryl rings bonded to the central O atom form a dihedral angle of 75.72 (6)°, and the terminal nitro groups are slightly twisted [by 6.4 (2) and 3.3 (3)°] from the benzene rings to which they are attached. The crystal packing exhibits weak inter-molecular C-H⋯O hydrogen bonds and π-π inter-actions [centroid-centroid distances = 3.794 (3) Å].