Newer options for treating drug-resistant (MDR+) cancer cells using photoradiation therapy Journal Article


Authors: Gulati, S. C.; Lemoli, R. M.; Igarashi, T.; Atzpodien, J.
Article Title: Newer options for treating drug-resistant (MDR+) cancer cells using photoradiation therapy
Abstract: Emergence of drug resistance with conventional cytotoxic therapy is a major challenge towards the curability of many cancers, especially in patients undergoing autologous BMT with ex-vivo purged hematopoietic support. We have explored the potential role of photoradiation therapy in purging hematopoietic stem cells of various hematological malignancies. Benzoporphyrin derivative, monoacid ring A (BPD-MA), dihematoporphyrin ether (DHE), and MC-540 were evaluated for the "ex-vivo" purging of residual tumor cells from autologous bone marrow (BM) grafts. BPD-MA and DHE photosensitizing activity was tested against two human large cell lymphoma cell lines and colony forming-unit leukemia (CFU-L) derived from patients with acute myelogenous leukemia (AML). In mixing experiments four log elimination of tumor cell lines was observed after 1 hr of incubation with BPD-MA or DHE followed by white light exposure. By comparison, using the same concentration of BPD-MA or DHE, the mean recovery of normal BM progenitors was 4-5.2% for granulocyte-macrophage colony forming unit (CFU-GM) and 5-9.8% for burst forming unit erythroid (BFUE). The T lymphoblastic leukemia cell line CEM and its vinblastine (VBL)-resistant subline CEM/VBL100. along with the acute promyelocyte leukemia cell line HL-60 and its vincristine (VCR)-resistant subline HL-60/VCR, were also tested. Our results demonstrated the preferential cytotoxicity of BPD-MA and DHE toward neoplastic cell lines and CFU-L from AML patients. In addition, DHE was slightly more effective in purging tumor cells expressing the p-170 glycoprotein. These results suggest that photoradiation would be useful for "ex-vivo" purging of malignant cells. Other methods to deal with decreasing drug resistance are also detailed. © 1994 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.
Keywords: controlled study; leukemia; acute granulocytic leukemia; human cell; vincristine; cancer cell culture; cytotoxicity; drug resistance; tumor cells, cultured; cancer cell; lymphoma; hematopoietic stem cells; bone marrow cell; hematopoietic stem cell; large cell lymphoma; bone marrow transplantation; t cell leukemia; cyclosporine; multidrug resistance; colony forming unit gm; drug-resistance; glycoprotein p; photosensitizing agent; bone marrow purging; mdr; phototherapy; burst forming unit e; photosensitization; human; priority journal; article; support, non-u.s. gov't; porphyrin derivative; antobodies; bepridil; merocyanine; photofrin ii
Journal Title: Leukemia and Lymphoma
Volume: 12
Issue: 5-6
ISSN: 1042-8194
Publisher: Taylor & Francis Group  
Date Published: 1994-02-01
Start Page: 427
End Page: 433
Language: English
DOI: 10.3109/10428199409073784
PROVIDER: scopus
PUBMED: 8180606
DOI/URL:
Notes: Source: Scopus
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  1. Subhash C. Gulati
    129 Gulati
  2. Roberto M. Lemoli
    18 Lemoli