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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2003-3-17
pubmed:abstractText
Small cell carcinoma of the prostate (SCCP), although relatively rare, is the most aggressive variant of prostate cancer, currently with no successful treatment. It was therefore tempting to evaluate the response of this violent malignancy and its bone lesions to Pd-Bacteriopheophorbide (TOOKAD)-based photodynamic therapy (PDT), already proven by us to efficiently eradicate other aggressive non-epithelial solid tumors. TOOKAD is a novel bacteriochlorophyll-derived, second-generation photosensitizer recently, developed by us for the treatment of bulky tumors. This photosensitizer is endowed with strong light absorbance (epsilon(0) approximately 10(5) mol(-1) cm(-1)) in the near infrared region (lambda=763nm), allowing deep tissue penetration. The TOOKAD-PDT protocol targets the tumor vasculature leading to inflammation, hypoxia, necrosis and tumor eradication. The sensitizer clears rapidly from the circulation within a few hours and does not accumulate in tissues, which is compatible with the treatment of localized tumor and isolated metastases. Briefly, male CD1-nude mice were grafted with the human SCCP (WISH-PC2) in 3 relevant anatomic locations: subcutaneous (representing tumor mass), intraosseous (representing bone metastases) and orthotopically within the murine prostate microenvironment. The PDT protocol consisted of i.v. administration of TOOKAD (4 mg/kg), followed by immediate illumination (650-800 nm) from a xenon light source or a diode laser emitting at 770 nm. Controls included untreated animals or animals treated with light or TOOKAD alone. Tumor volume, human plasma chromogranin A levels, animal well being and survival were used as end points. In addition, histopathology and immunohistochemistry were used to define the tumor response. Subcutaneous tumors exhibited complete healing within 28-40 days, reaching an overall long-term cure rate of 69%, followed for 90 days after PDT. Intratibial WISH-PC2 lesions responded with complete tumor elimination in 50% of the treated mice at 70-90 days after PDT as documented histologically. The response of the orthotopic model was also analyzed histologically with similar results. The study with this model suggests that TOOKAD-based PDT can reach large tumors and is a feasible, efficient and well-tolerated approach for minimally invasive treatment of local and disseminated SCCP.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0020-7136
pubmed:author
pubmed:copyrightInfo
Copyright 2003 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
104
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
782-9
pubmed:dateRevised
2007-7-24
pubmed:meshHeading
pubmed-meshheading:12640688-Animals, pubmed-meshheading:12640688-Bacteriochlorophylls, pubmed-meshheading:12640688-Bone Diseases, pubmed-meshheading:12640688-Carcinoma, Small Cell, pubmed-meshheading:12640688-Chromogranin A, pubmed-meshheading:12640688-Chromogranins, pubmed-meshheading:12640688-Humans, pubmed-meshheading:12640688-Immunoenzyme Techniques, pubmed-meshheading:12640688-Magnetic Resonance Imaging, pubmed-meshheading:12640688-Male, pubmed-meshheading:12640688-Mice, pubmed-meshheading:12640688-Mice, Nude, pubmed-meshheading:12640688-Models, Animal, pubmed-meshheading:12640688-Neoplasm Transplantation, pubmed-meshheading:12640688-Photochemotherapy, pubmed-meshheading:12640688-Photosensitizing Agents, pubmed-meshheading:12640688-Prostatic Neoplasms, pubmed-meshheading:12640688-Transplantation, Heterologous, pubmed-meshheading:12640688-Treatment Outcome, pubmed-meshheading:12640688-Tumor Cells, Cultured
pubmed:year
2003
pubmed:articleTitle
Photodynamic therapy with Pd-Bacteriopheophorbide (TOOKAD): successful in vivo treatment of human prostatic small cell carcinoma xenografts.
pubmed:affiliation
Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't