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dc.contributor.authorFernandes, Djanira Patricia
dc.date.accessioned2017-08-30T18:22:28Z
dc.date.issued2017
dc.identifier.urihttps://hdl.handle.net/2144/23697
dc.description.abstractWhile CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone), the current standard of care for non-Hodgkin lymphoma (NHL), kills tumor cells, the accumulation of tumor cell “debris” can stimulate inflammation and tumor growth. Thus, cytotoxic cancer therapies are a double-edged sword. Previous studies have shown that apoptotic debris stimulates tumor growth. We hypothesize that (1) CHOP-generated tumor cell debris can promote lymphoma progression via release of pro-inflammatory cytokines; (2) blocking phosphatidylserine (PS), which is presented on the surface of apoptotic cells, may inhibit debris-stimulated cancer progression. METHODS: Lymphoma EL4 debris was generated by treating tumor cells with CHOP chemotherapy. EL4 debris was isolated via Ficoll gradient and co-injected with living EL4 tumor cells into immunocompetent C57BL/6 mice. Macrophage-secreted cytokines were measured via array analysis. RESULTS: Flow cytometry confirmed CHOP chemotherapy generated apoptotic/necrotic debris. Vincristine-, mafosfamide-, and prednisolone-generated lymphoma EL4 debris stimulated tumor growth by over 100-fold in a dose-dependent manner. Debris alone did not induce tumors, even at 250 days post-injection. Doxorubicin-generated EL4 debris stimulated tumor growth at low dose (1x105), but inhibited growth at high dose (9x105). Systemic administration of doxorubicin-generated EL4 debris or blocking PS in the cell debris generated by doxorubicin using annexin V or an anti-PS neutralizing antibody inhibited doxorubicin-generated debris-stimulated tumor growth. Therapy-generated debris stimulated macrophage pro-inflammatory cytokine production. CONCLUSIONS: CHOP chemotherapy-generated debris regulates tumor growth via cytokine production. Thus, harnessing the anti-tumor activity of inhibitory debris or neutralizing PS on stimulatory debris may be a novel anti-cancer approach.en_US
dc.language.isoen_USen_US
dc.subjectOncologyen_US
dc.subjectChemotherapyen_US
dc.subjectDebrisen_US
dc.subjectTumoren_US
dc.subjectNon-Hodgkin lymphomaen_US
dc.titleRegulation of tumor growth by CHOP chemotherapy-generated debrisen_US
dc.typeThesis/Dissertationen_US
dc.date.updated2017-07-11T22:13:32Z
dc.description.embargo2018-07-11T00:00:00Z
etd.degree.nameMaster of Scienceen_US
etd.degree.levelmastersen_US
etd.degree.disciplineMedical Sciencesen_US
etd.degree.grantorBoston Universityen_US


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