Faculty Collaboration Database

Anti-tumor effect of Merocyanine 540-mediated photochemotherapy combined with Edelfosine: potential implications for the ex vivo purging of hematopoietic stem cell grafts from breast cancer patients. J Photochem Photobiol B 2002 Nov;68(2-3):101-8

Date

12/07/2002

Pubmed ID

12468204

DOI

10.1016/s1011-1344(02)00377-9

Scopus ID

2-s2.0-1842854337 (requires institutional sign-in at Scopus site)   24 Citations

Abstract

High-dose chemotherapy combined with autologous stem cell support has improved response rates in high-risk and metastatic breast cancer, but has failed to improve long-term survival. Breast cancer has a tendency to metastasize to the bone marrow, and live tumor cells are known to circulate in the peripheral blood of breast cancer patients. Sensitive immunohistochemical, culture-based, and reverse transcriptase polymerase chain reaction (RT-PCR)-based methods have shown that about 50% of histologically normal stem cell grafts from breast cancer patients are contaminated with occult tumor cells, which may cause or contribute to tumor recurrences. Merocyanine 540 (MC540)-mediated photodynamic therapy (PDT) inactivates a wide range of leukemia and lymphoma cells and is well tolerated by normal hematopoietic stem and progenitor cells. Unfortunately, most solid tumor cells (including breast cancer cells) are only moderately sensitive or refractory to MC540-PDT. We report here that if MC540-PDT is followed by a 1-h incubation with the alkyl-lysophospholipid, Edelfosine (ET-18-OCH(3)), the depletion of murine and human breast cancer cells is greatly enhanced whereas the recovery of normal hematopoietic stem and progenitor cells is only minimally degraded. When used under conditions that reduce CD34-positive human bone marrow cells only 5.1-fold, and murine and human granulocyte/macrophage progenitors 6.8- and 3-fold, respectively, combination purging with MC540-PDT and Edelfosine depletes murine (Mm5MT) and human (MDA-MB-435S) breast cancer cells >17,000- and >125,000-fold, respectively. These data suggest that combination purging with MC540-PDT and Edelfosine may offer a simple, safe and effective method for the ex vivo purging of autologous stem cell grafts from breast cancer patients.

Author List

Anderson GS, Miyagi K, Sampson RW, Sieber F

Author

Fritz Sieber PhD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Antigens, CD
Antigens, CD34
Antineoplastic Agents
Antineoplastic Combined Chemotherapy Protocols
Breast Neoplasms
Cryopreservation
Female
Hematopoietic Stem Cells
Humans
Mice
Phospholipid Ethers
Photochemotherapy
Pyrimidinones
Radiation-Sensitizing Agents
Tumor Cells, Cultured
Tumor Stem Cell Assay