Blastomycosis of the vocal folds with life-threatening upper airway obstruction: a case report

Blastomycosis is a chronic fungal disease that primarily affects the lower respiratory tract. The acute inflammatory phase of the primary pulmonary infection is characterized by a lymphohematogenous spread to extrapulmonary sites, especially the skin. The presence of disseminated infection with Blastomyces dermatitidis in the larynx is unusual. In areas of the United States where this fungus is endemic, failure to consider laryngeal involvement might lead to inappropriate therapy and thus worsening inflammation and airway compromise.     

Vaccinia virus complement control protein inhibits hyperacute xenorejection in a guinea pig-to-rat heterotopic cervical cardiac xenograft model by blocking both xenoantibody binding and complement pathway activation

Vaccinia virus complement control protein (VCP) binds the activated third and fourth complement components and inhibits both alternative and classical pathways of activation. The ability of VCP to bind heparan sulfate allows the protein to attach itself to the cell surface, enabling it with many additional activities. Altogether, the many functions of VCP have been shown to suppress the inflammatory response of the host, helping the vaccinia virus to evade immune destruction. VCP has recently been shown to inhibit human anti-Gal alpha1-3 Gal antibody attachment to cultured porcine endothelial cells and reduce human neutrophil and NK killing of pig aortic endothelial cells through its ability to bind heparan sulfate. Here we demonstrate that in an in vivo guinea pig-to-rat heterotopic cervical cardiac xenograft model, recombinant VCP (rVCP) is able to block hyperacute xenograft rejection, significantly prolonging graft survival. Histopathological examination of transplanted hearts from rats receiving rVCP revealed a significant reduction in cardiac tissue damage as compared to control hearts. Finally, rVCP treated recipients demonstrated marked rVCP deposition on the endothelium and significantly less C3, IgG and IgM deposition in the tissue. rVCP is therefore able to inhibit hyperacute xenorejection by binding the endothelial surface, blocking complement fixation and activation, and preventing xenoantibody attachment.     

Recombinant toxin DAB389EGF is cytotoxic to human pancreatic cancer cells

Few malignancies have frustrated the persistent efforts of the oncologist like pancreatic cancer. Pancreatic cancer is usually unresectable at the time of diagnosis because of metastasis or local extension. Despite the aggressive nature of this deadly disease, systemic treatment options are limited. Even the recent introduction of the deoxycytidine analogue gemcitabine does not extend median survival of responders beyond a year. Clearly, alternative, more effective regimens are needed for treating pancreatic carcinoma. In pancreatic cancer, there is overexpression of growth factors and growth factor receptors, including epidermal growth factor receptor (EGFR). Targeted toxins consist of a targeting polypeptide covalently linked to a peptide toxin. DAB(389)EGF is a fusion protein composed of the catalytic and translocation domains of diphtheria toxin fused via a His-Ala linker to human epidermal growth factor (EGF). The authors have previously shown that DAB(389)EGF is selectively toxic to EGFR-overexpressing cells, including human brain tumour and lung carcinoma cell lines. Pancreatic adenocarcinoma should be responsive to this fusion protein based on its EGFR overexpression. However, the cytotoxic effect of DAB(389)EGF on human pancreatic carcinoma cell lines has yet to be explored. The authors describe preliminary data showing the potent cytotoxicity of DAB(389)EGF to human pancreatic carcinoma cell lines. Because of the nonspecific toxicity to liver and kidney (which possess EGFR) of systemic administration, they also propose a potential novel drug delivery system for direct toxin implantation into pancreatic tumours using endoscopic ultrasound guided fine-needle injection (EUS-FNI). Hopefully, the use of these targeted therapeutic approaches in combination with other modalities may further extend survival and quality of life in patients with pancreatic adenocarcinoma.     

Cystic neoplasms of the pancreas

Opinion statement  

Primary diffuse leptomeningeal glioneuronal tumors of the central nervous system: Report of three cases and review of literature

Abstract

Primary diffuse leptomeningeal glioneuronal tumors (DLGNT) are rare tumors, recently recognized as a unique entity based on their unique pathologic and clinical characteristics. We report three cases of DLGNT and compare their clinical characteristics and presentation with other reported cases, and with primary leptomeningeal gliomatosis. Because their prognosis is better than that of diffuse leptomeningeal gliomatosis, and pathologic diagnosis may be difficult, clinicians should consider this diagnosis in patients who present with new neurological symptoms, hydrocephalus and diffuse leptomeningeal enhancement on MRI. Further studies are required to better understand the unique biological characteristics of these tumors and to improve therapy.