Functional Cellular Anti-Tumor Mechanisms are Augmented by Genetic Proteoglycan Targeting.

While recent research points to the importance of glycans in cancer immunity, knowledge on functional mechanisms is lacking. In lung carcinoma among other tumors, anti-tumor immunity is suppressed; and while some recent therapies boost T-cell mediated immunity by targeting immune-checkpoint pathways, robust responses are uncommon. Augmenting tumor antigen-specific immune responses by endogenous dendritic cells (DCs) is appealing from a specificity standpoint, but challenging.

Glycan Sulfation Modulates Dendritic Cell Biology and Tumor Growth.

In cancer, proteoglycans have been found to play roles in facilitating the actions of growth factors, and effecting matrix invasion and remodeling. However, little is known regarding the genetic and functional importance of glycan chains displayed by proteoglycans on dendritic cells (DCs) in cancer immunity. In lung carcinoma, among other solid tumors, tumor-associated DCs play largely subversive/suppressive roles, promoting tumor growth and progression.

Functional Importance of a Proteoglycan Coreceptor in Pathologic Lymphangiogenesis.

Rationale: Lymphatic vessel growth is mediated by major prolymphangiogenic factors, such as vascular endothelial growth factor (VEGF-C) and VEGF-D, among other endothelial effectors. Heparan sulfate is a linear polysaccharide expressed on proteoglycan core proteins on cell membranes and matrix, playing roles in angiogenesis, although little is known about any function(s) in lymphatic remodeling in vivo.

Objective: To explore the genetic basis and mechanisms, whereby heparan sulfate proteoglycans mediate pathological lymphatic remodeling.

Examining Roles of Glycans in Chemokine-Mediated Dendritic-Endothelial Cell Interactions.

Interactions between glycosaminoglycans (GAGs) and chemokines play a critical role in multiple physiological and pathological processes, including tumor metastasis and immune-cell trafficking. During our studies examining the genetic importance of the GAG subtype known as heparan sulfate (HS) on lymphatic endothelial cells (LECs), we established a repertoire of methods to assess how HS affects chemokine-mediated cell-cell interactions. In this chapter, we describe methods for monitoring migration and adhesion interactions of dendritic cells (DCs), the most potent antigen-presenting cells, with LECs.

Mitomycin--C-induced thrombotic thrombocytopenic purpura/hemolytic uremic syndrome: cumulative toxicity of an old drug in a new era.

Mitomycin-C (MMC) is a first-line therapy for anal squamous cell carcinoma (ASCC), and it continues to be used for several other indications. Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) are serious complications of MMC therapy. Herein, we describe a 73-year-old woman with recurrent ASCC treated with MMC who developed chronic microangiopathic hemolytic anemia (MAHA) and thrombocytopenia after receiving a cumulative dose of 50 mg/m(2).

Better late than never: diagnosis and successful treatment in late adulthood of supravalvular aortic stenosis secondary to Williams-Beuren syndrome.

This is a case report of a patient diagnosed at age 50 with supravalvular aortic stenosis secondary to Williams-Beuren Syndrome and successfully treated with aortic valve replacement and excision of supravalvular tissue.

Thoracic endometriosis: an unusual cause of hemothorax.

In this report we describe the clinical presentation, diagnosis, treatment and outcome of a 45-year-old woman with thoracic endometriosis. Four clinical presentations have been described. The majority have presented with catamenial pneumothorax, followed by hemothorax, hemoptysis and lung nodules.