Ahmad Khalili; Zuhair Muhammad Hassan; Shahram Shahabi; Ali Akbar Pourfathollah; Seyed Nasser Ostad; Shokoofe Noori; Mehdi Mahdavi; Habib Haybar; Ladan Langroudi
Volume 10, Issue 2 , June 2013, , Pages 70-82
Abstract
Background: Noradrenaline (NA), the principal neurotransmitter released from sympathetic nerve terminals, influences T-cell maturation, not only directly in developing T cells, but also indirectly, by acting on the thymic nonlymphoid cells. In vitro and in vivo studies have demonstrated the anti-proliferative, ...
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Background: Noradrenaline (NA), the principal neurotransmitter released from sympathetic nerve terminals, influences T-cell maturation, not only directly in developing T cells, but also indirectly, by acting on the thymic nonlymphoid cells. In vitro and in vivo studies have demonstrated the anti-proliferative, anti-migratory, antiangiogenic and cytotoxic properties of propranolol, β-AR blocker, against various cancers. Objectives: To evaluate the effect of propranolol on efficacy of HSP-70 rich lysate vaccine in immunotherapy of fibrosarcoma. Methods: Mouse fibrosarcoma WEHI-164 cells were used to immunize tumor-bearing mice with or without propranolol and HSP-70. Splenocytes proliferation, cytotoxic activity of the splenocytes, naturally occurring CD4+ CD25high T-reg cells and IFN-γ and IL-4 secretion as well as tumor size, were assessed to describe the anti-tumor immune response. Results: A significant increase in the level of IFN-γ in the mice vaccinated with WEHI-164 cells enriched with HSP-70 and co-treated with propranolol was observed compared to controls. However, HSP enrichment or propranolol treatment alone did not enhance the immune response as measured by the level of IFN-γ. Likewise, a decrease in tumor growth in the test group (p<0.01) and a significant increase in CTL activity (p<0.05) was observed. Conclusion: HSP enriched vaccine shows anti-tumor activity, probably due to the modulation of immune responses.
Shokoofe Noori; Zuhair Mohammad Hassan; Omid Salehian
Volume 10, Issue 1 , March 2013, , Pages 10-21
Abstract
Background: Sclareol is a phytochemical used in people's diet in Southeast Asia. Objective: To investigate the immunotherapeutic effectiveness of Sclareol against breast cancer by direct intraperitoneal injection. Methods: Sclareol was isolated and purified from Salvia sclarea. Effect of Sclareol on ...
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Background: Sclareol is a phytochemical used in people's diet in Southeast Asia. Objective: To investigate the immunotherapeutic effectiveness of Sclareol against breast cancer by direct intraperitoneal injection. Methods: Sclareol was isolated and purified from Salvia sclarea. Effect of Sclareol on cell growth inhibition was evaluated by MTT assay. Intraperitoneally injected Sclareol effects on reducing the tumor volume and shifting the cytokine profile were investigated. We also assessed if intraperitoneally injected Sclareol could improve the outcome of cancer therapy through suppressing the regulatory T cells. Results: The results confirmed a significant decrease in the tumor size. Furthermore, a significant decrease in the level of IL-4 and an increase in the level of IFN-γ were noticed in the intraperitoneally injected Sclareol group (p<0.05). It was also observed that the splenocytes of treated animals significantly increase in cell proliferation assay. Moreover, measurements of splenic T regulatory cell indicated that intraperitoneally injected Sclareol significantly decreased the number of splenic T regulatory cell. Conclusion: Our results suggest that Sclareol, by reducing T-reg cells frequency and also tumor size can enhance the effect of cancer therapy as an immunostimulant.
Shokoofe Noori; Mohammad Taghikhani; Zuhair M. Hassan; Abdolamir Allameh; Ali Mostafaei
Volume 6, Issue 4 , December 2009, , Pages 216-224
Abstract
Background: Artemisia diffusa contains a new type of sesquiterpene lactone with an endoperoxide group (Tehranolide). Objective: Due to the existing similarity between the structures of Tehranolide and Artemisinin, it was hypothesized that Tehranolide would have similar effects as Artemisinin. In this ...
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Background: Artemisia diffusa contains a new type of sesquiterpene lactone with an endoperoxide group (Tehranolide). Objective: Due to the existing similarity between the structures of Tehranolide and Artemisinin, it was hypothesized that Tehranolide would have similar effects as Artemisinin. In this study, the immunotherapeutic effec-tiveness of Tehranolide was investigated by direct intra-tumoral injection. Methods: Tehranolide was purified from Artemisia diffusa, and its effect on the tumor volume was investigated. The splenocyte proliferation, shifting of cytokine profile, and the presence of naturally-occurring CD4+CD25+Foxp3+ Treg cells were assessed to describe the anti-tumor immune response. Results: Analysis of immune response showed that, intra-tumoral injection of Tehranolide decreased the rate of tumor growth compared to control group. Furthermore, the proliferative response of mice treated with Tehranolide was en-hanced. In comparison with the control group, production of both IL-4 and IFN-γ was in-duced (p<0.05). The results indicated a decrease in tumor CD4+CD25+Foxp3+ T lym-phocytes in the Tehranolide-treated group compared to the control group. Conclusion: Treatment of tumors with Tehranolide attenuated CD4+CD25+Foxp3+ Treg cell-mediated immune suppression and elicited a persistent anti-tumor immunity against can-cer.