Repurposing of PSMA-targeted diagnostic and therapeutic agents for the detection and treatment of giant cell tumors of bone.

Giant cell tumor of bone (GCTB) is a rare bone tumor often necessitating surgical intervention, radiation therapy, or treatment with bisphosphonates or denosumab. Tc-MDP bone scintigraphy for GCTB has limited specificity, and the relatively high uptake of F-FDG in GCTB makes it challenging to differentiate it from other benign bone tumors. More specific detection and treatment modalities for GCTB are needed to enhance patient monitoring and outcomes.

Single nucleotide polymorphisms and Zn transport by ZIP11 shape functional phenotypes of HeLa cells.

Zinc (Zn) is a vital micronutrient with essential roles in biological processes like enzyme function, gene expression, and cell signaling. Disruptions in the cellular regulation of Zn2+ ions often lead to pathological states. Mammalian Zn transporters, such as ZIP11, play a key role in homeostasis of this ion.

Assessment of diversity-based approaches used by American Universities to increase recruitment and retention of biomedical sciences research faculty members: A scoping review protocol.

Diversity enriches the educational experience by improving intellectual engagement, self-motivation, citizenship, cultural engagement, and academic skills like critical thinking, problem-solving, and writing for students of all races. Faculty role models from similar backgrounds are essential for students from traditionally underrepresented groups as it sends a powerful message of support, belonging, and the confidence to pursue higher education. However, in the biomedical sciences, the percentage of historically underrepresented tenure-track faculty is far lower than that of their white colleagues.

Therapeutic potential of targeting mirnas to prostate cancer tumors: using psma as an active target.

Prostate cancer (PC) is a commonly diagnosed malignancy in men and is associated with high mortality rates. Current treatments for PC include surgery, chemotherapy, and radiation therapy. However, recent advances in targeted delivery systems have yielded promising new approaches to PC treatment.

ZIP11 Regulates Nuclear Zinc Homeostasis in HeLa Cells and Is Required for Proliferation and Establishment of the Carcinogenic Phenotype.

Zinc (Zn) is an essential trace element that plays a key role in several biological processes, including transcription, signaling, and catalysis. A subcellular network of transporters ensures adequate distribution of Zn to facilitate homeostasis. Among these are a family of importers, the Zrt/Irt-like proteins (ZIP), which consists of 14 members (ZIP1-ZIP14) that mobilize Zn from the extracellular domain and organelles into the cytosol.

Prostate-Specific Membrane Antigen-Targeted Turn-on Probe for Imaging Cargo Release in Prostate Cancer Cells.

The tunable nature of phosphoramidate linkers enables broad applicability as pH-triggered controlled-release platforms, particularly in the context of antibody- and small-molecule-drug conjugates (ADCs and SMDCs), where there remains a need for new linker technology. Herein, we explored in-depth the release of turn-on fluorogenic payloads from a homoserinyl-based phosphoramidate acid-cleavable linker. Kinetics of payload release from the scaffold was observed in buffers representing the pH conditions of systemic circulation, early and late endosomes, and lysosomes.

The innate immune response to ischemic injury: a multiscale modeling perspective.

Background: Cell death as a result of ischemic injury triggers powerful mechanisms regulated by germline-encoded Pattern Recognition Receptors (PRRs) with shared specificity that recognize invading pathogens and endogenous ligands released from dying cells, and as such are essential to human health. Alternatively, dysregulation of these mechanisms contributes to extreme inflammation, deleterious tissue damage and impaired healing in various diseases. The Toll-like receptors (TLRs) are a prototypical family of PRRs that may be powerful anti-inflammatory targets if agents can be designed that antagonize their harmful effects while preserving host defense functions.

PSMA redirects MAPK to PI3K-AKT signaling to promote prostate cancer progression.

Increased Prostate Specific Membrane Antigen expression promotes tumor progression in prostate epithelium by dysregulating the β1-integrin/type I insulin-like growth factor receptor axis, resulting in a shift in signaling from the less aggressive mitogen-activated protein kinase-extracellular signal-regulated kinases 1 and 2 pathway to the pro-survival protein kinase B(AKT)/phosphatidylinositol 3-kinase pathway.

PSMA redirects cell survival signaling from the MAPK to the PI3K-AKT pathways to promote the progression of prostate cancer.

Increased abundance of the prostate-specific membrane antigen (PSMA) on prostate epithelium is a hallmark of advanced metastatic prostate cancer (PCa) and correlates negatively with prognosis. However, direct evidence that PSMA functionally contributes to PCa progression remains elusive. We generated mice bearing PSMA-positive or PSMA-negative PCa by crossing PSMA-deficient mice with transgenic PCa (TRAMP) models, enabling direct assessment of PCa incidence and progression in the presence or absence of PSMA.

Molecular mechanisms regulating CD13-mediated adhesion.

CD13/Aminopeptidase N is a transmembrane metalloproteinase that is expressed in many tissues where it regulates various cellular functions. In inflammation, CD13 is expressed on myeloid cells, is up-regulated on endothelial cells at sites of inflammation and mediates monocyte/endothelial adhesion by homotypic interactions. In animal models the lack of CD13 alters the profiles of infiltrating inflammatory cells at sites of ischaemic injury.

Tyrosine phosphorylation of CD13 regulates inflammatory cell-cell adhesion and monocyte trafficking.

CD13 is a large cell surface peptidase expressed on the monocytes and activated endothelial cells that is important for homing to and resolving the damaged tissue at sites of injury. We showed previously that cross-linking of human monocytic CD13 with activating Abs induces strong adhesion to endothelial cells in a tyrosine kinase- and microtubule-dependent manner. In the current study, we examined the molecular mechanisms underlying these observations in vitro and in vivo.

Prostate specific membrane antigen (PSMA) regulates angiogenesis independently of VEGF during ocular neovascularization.

Background: Aberrant growth of blood vessels in the eye forms the basis of many incapacitating diseases and currently the majority of patients respond to anti-angiogenic therapies based on blocking the principal angiogenic growth factor, vascular endothelial growth factor (VEGF). While highly successful, new therapeutic targets are critical for the increasing number of individuals susceptible to retina-related pathologies in our increasingly aging population. Prostate specific membrane antigen (PSMA) is a cell surface peptidase that is absent on normal tissue vasculature but is highly expressed on the neovasculature of most solid tumors, where we have previously shown to regulate angiogenic endothelial cell invasion.

The neurosecretory vesicle protein phogrin functions as a phosphatidylinositol phosphatase to regulate insulin secretion.

Phogrin is a transmembrane protein expressed in cells with stimulus-coupled peptide hormone secretion, including pancreatic beta cells, in which it is localized to the membrane of insulin-containing dense-core vesicles. By sequence, phogrin is a member of the family of receptor-like protein-tyrosine phosphatases, but it contains substitutions in conserved catalytic sequences, and no significant enzymatic activity for phogrin has ever been reported. We report here that phogrin is able to dephosphorylate specific inositol phospholipids, including phosphatidylinositol (PI) 3-phosphate and PI 4,5-diphosphate but not PI 3,4,5-trisphosphate.