Project description:Approximately 30 years ago, endoglin was identified as a transforming growth factor (TGF)-β coreceptor with a crucial role in developmental biology and tumor angiogenesis. Its selectively high expression on tumor vessels and its correlation with poor survival in cancer patients led to the exploration of endoglin as a therapeutic target for cancer. The endoglin neutralizing antibody TRC105 (Carotuximab®, Tracon Pharmaceuticals (San Diego, CA, USA) was subsequently tested in a wide variety of preclinical cancer models before being tested in phase I-III clinical studies in cancer patients as both a monotherapy and in combination with other chemotherapeutic and anti-angiogenic therapies. The combined data of these studies have revealed new insights into the role of endoglin in angiogenesis and its expression and functional role on other cells in the tumor microenvironment. In this review, we will summarize the preclinical work, clinical trials and biomarker studies of TRC105 and explore what these studies have enabled us to learn and what questions remain unanswered.

| S-EPMC7795616 | biostudies-literature

Denosumab for Fibrous Dysplasia: Promising, but Questions Remain.

Project description: Not available

| S-EPMC7497813 | biostudies-literature

Managing Patients with Failing Kidney Allograft: Many Questions Remain.

Project description:Patients who receive a kidney transplant commonly experience failure of their allograft. Transplant failure often comes with complex management decisions, such as when and how to wean immunosuppression and start the transition to a second transplant or to dialysis. These decisions are made in the context of important concerns about competing risks, including sensitization and infection. Unfortunately, the management of the failed allograft is, at present, guided by relatively poor-quality data and, as a result, practice patterns are variable and suboptimal given that patients with failed allografts experience excess morbidity and mortality compared with their transplant-naive counterparts. In this review, we summarize the management strategies through the often-precarious transition from transplant to dialysis, highlighting the paucity of data and the critical gaps in our knowledge that are necessary to inform the optimal care of the patient with a failing kidney transplant.

| S-EPMC8975040 | biostudies-literature

Understanding <i>Aspergillus fumigatus</i> galactosaminogalactan biosynthesis: A few questions remain.

Project description:Half a century after their discovery, polymers of N-acetylgalactosamine produced by the Aspergilli have garnered new interest as mediators of fungal virulence. Recent work has focused on the Aspergillus fumigatus secreted and cell wall-associated heteropolymer, galactosaminogalactan (GAG). This polymer, composed of galactose (Gal) and partially deacetylated N-acetylgalactosamine (GalNAc), plays a role in a variety of pathogenic processes including biofilm formation, immune modulation and evasion, and resistance to antifungals. Given its many potential contributions to fungal pathogenesis, GAG is a promising therapeutic target for novel antifungal strategies. As such, several studies have sought to elucidate the biosynthetic pathways required for GAG production and secretion. Herein we review the progress made in the understanding of the molecular mechanisms underlying GAG synthesis and identify several gaps in our understanding of this process.

| S-EPMC9860509 | biostudies-literature

Milestones 2.0: A Step Forward.

Project description: Not available

| S-EPMC6008021 | biostudies-literature

Blinding Assessment: One Step Forward.

Project description: Not available

| S-EPMC8754420 | biostudies-literature

Structural step forward for NHEJ.

Project description:In a recent paper published in Cell Research, a cryo-EM structure reveals the interface between DNA-PKcs and the Ku70/80:DNA complex, together forming the DNA-dependent protein kinase holoenzyme in non-homologous DNA end joining. Insight from this structure suggests how an allosteric rearrangement of DNA-PKcs driven by Ku70/80:DNA binding regulates kinase activity in this largest member of a family of structurally homologous phosphoinositide 3-kinase-related protein kinases that includes mTOR, ATR, and ATM.

| S-EPMC5674156 | biostudies-literature

One step forward to personalized medicine?

Project description: Not available

| S-EPMC10652033 | biostudies-literature

Intraventricular immunovirotherapy; a translational step forward.

Project description:Oncolytic virotherapy with intratumoral engineered type-1 herpes simplex virus (HSV) has been proven safe with promising efficacy in recent clinical trials for treatment of both pediatric and adult high-grade glioma. However, this approach excludes patients with tumors in surgically inaccessible and/or eloquent brain regions. Current delivery methods are also unable to access/treat those patients with metastatic disease in the spinal cord and/or leptomeningeal disease. A recent preclinical study has paved the way for clinical translation of intraventricular administration of oHSV by identifying and mitigating the toxicity associated with this route for therapeutic benefit in murine models of disseminated medulloblastoma. This work may ultimately allow for targeting of intractable disease and provides a feasible option for the repetitive dosing of clinically relevant immunovirotherapy, G207.

| S-EPMC9836381 | biostudies-literature

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