Document Detail

Benzophenothiazine and benzoporphyrin derivative combination phototherapy effectively eradicates large murine sarcomas.
MedLine Citation:
PMID:  8657737     Owner:  NLM     Status:  MEDLINE    
The tumoricidal effects of photochemotherapy with two photosensitizers, 5-ethylamino-9-diethylaminobenzo[a] phenothiazinium chloride (EtNBS) and benzoporphyrin derivative monoacid ring A (BPD-MA), were evaluated separately and in combination against the EMT-6 fibrosarcoma implanted subcutaneously in BALB/c mice. Animals carrying tumors 8-10 mm in diameter were divided into eight different groups (approximately 20/group) and subjected to various photoirradiation and drug conditions. The tumor response to photodynamic therapy (PDT) was measured as the mean tumor wet weight 2 weeks post-PDT. The combination treatment with 5.25 mg/kg EtNBS and 2.5 mg/kg BPD-MA followed by photoirradiation with 100 J/cm2 at 652 nm and then by 100 J/cm2 at 690 nm resulted in a 95% reduction in the average tumor weights compared to controls (no light, no drugs) with 76% of the mice being tumor free 2 weeks post-PDT. Because treatment with EtNBS or BPD-MA at twice the light dose and drug concentration resulted in either no significant reduction in tumor weights or increased the lethality of treatment, respectively, the data suggest that the enhanced PDT effect observed with the combination of drugs is synergistic rather than additive. Histology of tumors 24 h post-PDT with the combination of drugs showed nearly complete destruction of the tumor mass with little or no damage to the vasculature and no extravasation of red blood cells. There was no damage to the normal skin adjacent to the tumor. Fluorescence microscopy of EMT-6 cells incubated in vitro with the two photosensitizers revealed that they were localized to different intracellular compartments. The fluorescence pattern from frozen tumor tissue slices following the in vivo administration of the photosensitizers indicated a greater intracellular localization for EtNBS vs BPD-MA.
L Cincotta; D Szeto; E Lampros; T Hasan; A H Cincotta
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Photochemistry and photobiology     Volume:  63     ISSN:  0031-8655     ISO Abbreviation:  Photochem. Photobiol.     Publication Date:  1996 Feb 
Date Detail:
Created Date:  1996-07-30     Completed Date:  1996-07-30     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0376425     Medline TA:  Photochem Photobiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  229-37     Citation Subset:  IM    
Rowland Institute for Science, Cambridge, MA 02142, USA.
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MeSH Terms
Antineoplastic Agents / pharmacology*
Mammary Neoplasms, Experimental / drug therapy*
Mice, Inbred BALB C
Neoplasm Transplantation
Photosensitizing Agents / pharmacology*
Porphyrins / pharmacology*
Sarcoma, Experimental / drug therapy*
Thiazines / pharmacology*
Reg. No./Substance:
0/Antineoplastic Agents; 0/Photosensitizing Agents; 0/Porphyrins; 0/Thiazines; 113719-89-4/benzoporphyrin D; 136825-96-2/5-ethylamino-9-diethylaminobenzo(a)phenothiazinium

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