Sohrab Najafipour

Interleukin 6 expression by Hodgkin/Reed-Sternberg cells is associated with the presence of 'B' symptoms and failure to achieve complete remission in patients with advanced Hodgkin's disease.

Summary. Interleukin 6 (IL‐6) is a potent immunomodulatory cytokine that has pathogenic and prognostic significance in a number of disorders. Previous studies in Hodgkins disease (HD) have demonstrated the association between elevated serum levels of IL‐6 and unfavourable prognosis, including advanced stage and the presence of ‘B’ symptoms and with reduced survival. Although IL‐6 expression has been demonstrated in both the malignant Hodgkin/Reed–Sternberg (HRS) cells and in the various non‐malignant cells present in HD biopsies, a relationship between expression of IL‐6 by the tumour and outcome measures has not been established. The study group comprised of 97 patients with advanced HD who were recruited to two related clinical trials. IL‐6 expression was determined on paraffin‐wax sections of biopsy material by means of an immunohistochemical assay. Of the 97 patients, 27 (28%) showed staining for IL‐6 in HRS cells. IL‐6 expression by HRS cells was significantly correlated with a decreased likelihood of achieving a complete response to chemotherapy (P = 0·02) and with an increased prevalence of ‘B’ symptoms (P = 0·04). IL‐6 expression by HRS cells was not associated with Epstein–Barr virus status (P = 0·57). In summary, the results suggest that IL‐6 expression by HRS cells may contribute to the presence of ‘B’ symptoms and to a decreased likelihood to achieve a complete remission in HD patients.

The Oncogenic Protein Kinase Tpl-2/Cot Contributes to Epstein-Barr Virus-Encoded Latent Infection Membrane Protein 1-Induced NF-κB Signaling Downstream of TRAF2

ABSTRACT The Epstein-Barr virus-encoded latent infection membrane protein 1 (LMP1) is a pleiotropic protein, the activities of which include effects on cell transformation and phenotype, growth, and survival. The ability of LMP1 to mediate at least some of these phenomena could be attributed to the activation of the transcription factor NF-κB. LMP1 promotes NF-κB activation through the recruitment of the adapter protein TRAF2 and the formation of a dynamic multiprotein complex that includes the NF-κB kinase, the IκB kinases, and their downstream targets, IκBs and p105. In this study, we have identified the oncogenic kinase Tpl-2/Cot as a novel component of LMP1-induced NF-κB signaling. We show that Tpl-2 is expressed in primary biopsies from patients with nasopharyngeal carcinoma and Hodgkins disease, where LMP1 is also found. Inducible expression of LMP1 promotes the activation of Tpl-2, and a catalytically inactive Tpl-2 mutant suppresses LMP1-induced NF-κB signaling. In colocalization and coimmunoprecipitation experiments, Tpl-2 and TRAF2 were found to interact with Tpl-2 functioning downstream of TRAF2. Consistent with this observation, catalytically inactive Tpl-2 also blocked CD40-mediated NF-κB activation, which largely depends on TRAF2. The ability of Tpl-2 to influence LMP1-induced NF-κB occurs through modulation of both IκBα and p105 functions. Furthermore, Tpl-2 was found to influence the expression of angiogenic mediators, such as COX-2 in LMP1-transfected cells. These data identify Tpl-2 as a component of LMP1 signaling downstream of TRAF2 and as a modulator of LMP1-mediated effects.

Facile fabrication of uniform hollow silica microspheres using a novel biological template.

Biological templates, due to their ease of preparation and surface modifications can be a promising approach to fabricate hollow structures. In this study, for the first time, a biological template was used for the production of hollow silica microspheres. Silica was successfully deposited on Staphylococcus aureus cells surface using the Stöber method. The hollow silica spheres with a mesoporous shell of approximately 700nm in diameter were produced by applying this novel method.