Gene Expression Changes and Signal Transduction Pathway Alterations in Primary Human Oral Epithelial Cells Exposed to Smokeless Tobacco Extracts

Smokeless tobacco (ST), an alternative to smoking, has gained wide popularity among tobacco users. This study is conducted to determine the time course of gene expression associated with specific signaling pathways in human oral epithelial cells after exposure to smokeless tobacco extract (STE). A differentiated layer of epithelial cell is created as a way to mimic reasonably similar physiological atmosphere. A dose and time dependent response is observed for cell viability and cell proliferation assays indicating that this model system is responsive to the treatment. Expressions of 84 genes representing 18 different signal transduction pathways are quantitated. This is accomplished by using real-time polymerase chain reaction arrays at 1 h, 3 h, 6 h and 24 h time points following exposure to STE. Changes in gene expression are observed on many cellular processes including cell cycle regulation, cell adhesion, inflammation, apoptosis, and DNA breaks-down including Akt pathway activation. Short time exposure (1 h) leads more genes to down regulate whereas longer incubation time results in more genes up regulation. Most notable differences in the expression of genes during the course of treatment are BCL2A1, BIRC3, CCL20, CDK2, EGR1, FOXA2, HOXA1, IGFBP3, IL1A, IL-8, MMP10, NOS2, NRIP1, PTGS2, SELPLG and TNF-a. This study provides an insight on gene expression on oral epithelial cells as a result of STE exposure. This may also postulate greater understanding on biological effects and the mechanism of action of STE particularly at the transcriptional level.

Epstein-Barr virus-associated post-transplant lymphoproliferative disorders:beyond chemotherapy treatment

Post-transplant lymphoproliferative disorder(PTLD)is a rare but life-threatening complication of both allogeneic solid organ(SOT)and hematopoietic cell transplantation(HCT).The histology of PTLD ranges from benign polyclonal lymphoproliferation to a lesion indistinguishable from classic monoclonal lymphoma.Most commonly,PTLDs are Epstein-Barr virus(EBV)positive and result from loss of immune surveillance over EBV.Treatment for PTLD differs from the treatment for typical non-Hodgkin lymphoma because prognostic factors are different,resistance to treatment is unique,and there are specific concerns for organ toxicity.While recipients of HCT have a limited time during which they are at risk for this complication,recipients of SOT have a lifelong requirement for immunosuppression,so approaches that limit compromising or help restore immune surveillance are of high interest.Furthermore,while EBV-positive and EBV-negative PTLDs are not intrinsically resistant to chemotherapy,the poor tolerance of chemotherapy in the post-transplant setting makes it essential to minimize potential treatment-related toxicities and explore alternative treatment algorithms.Therefore,reduced-toxicity approaches such as single-agent CD20 monoclonal antibodies or bortezomib,reduced dosing of standard chemotherapeutic agents,and non-chemotherapy-based approaches such as cytotoxic T cells have all been explored.Here,we review the chemotherapy and non-chemotherapy treatment landscape for PTLD.