Vasoactive intestinal peptide signaling axis in human leukemia

The vasoactive intestinal peptide (VIP) signaling axis constitutes a master "communication coordinator" between cells of the nervous and immune systems.To date,VIP and its two main receptors expressed in T lymphocytes,vasoactive intestinal peptide receptor (VPAC)1 and VPAC2,mediate critical cellular functions regulating adaptive immunity,including arresting CD4 T cells in G 1 of the cell cycle,protection from apoptosis and a potent chemotactic recruiter of T cells to the mucosa associated lymphoid compartment of the gastrointestinal tissues.Since the discovery of VIP in 1970,followed by the cloning of VPAC1 and VPAC2 in the early 1990s,this signaling axis has been associated with common human cancers,including leukemia.This review highlights the present day knowledge of the VIP ligand and its receptor expression profile in T cell leukemia and cell lines.Also,there will be a discussion describing how the anti-leukemic DNA binding transcription factor,Ikaros,regulates VIP receptor expression in primary human CD4 T lymphocytes and T cell lymphoblastic cell lines (e.g.Hut-78).Lastly,future goals will be mentioned that are expected to uncover the role of how the VIP signaling axis contributes to human leukemogenesis,and to establish whether the VIP receptor signature expressed by leukemic blasts can provide therapeutic and/or diagnostic information.

Gallbladder cancer with tumor thrombus in the superior vena cava

BACKGROUND:Gastrointestinal cancers,especially pancreatobiliary cancers,are frequently associated with or are complicated by thromboembolic phenomena due to hypercoagulability and/or altered venous drainage,especially of the abdomen and lower limbs.This report describes an unusual and interesting case of gallbladder carcinoma developing a viable tumor thrombus in the superior vena cava(SVC)with resultant SVC obstruction,while on gefitinibbased anti-epidermal growth factor receptor(EGFR)therapy.METHODS:A 60-year-old woman was incidentally diagnosed to have gallbladder cancer on cholecystectomy.She had disease recurrence and received systemic chemotherapy followed by gefitinib-based anti-EGFR therapy.Subsequently,while on gefitinib-based therapy,she presented with clinical signs and symptoms suggestive of SVC thrombosis.RESULTS:A whole body PET scan revealed a metabolically active tumor thrombus in the SVC,besides other sites of metabolically active disease inclusive of the lung parenchyma, lymph nodes and abdomen.She was treated with antithrombotics and external beam radiotherapy directed to the SVC thrombus leading to symptomatic relief.She continues to survive on the day of writing this report.CONCLUSIONS:This rare complication,though theoretically possible,is unreported because of the short overall survival of advanced gallbladder cancer patients.This highlights that with the availability of better chemotherapeutic/biotherapeutic agents for increasing in the lifespan of cancer patients,we may come across such cases more frequently in the future.