Abstract | PURPOSE: MATERIALS AND METHODS:
Paraffin-embedded material from 37 patients with early esophageal cancer treated with PDT ( argon dye laser after intravenous injection of hematoporphyrine derivative) was studied immunohistochemically for p53 protein nuclear accumulation and bcl-2 cytoplasmic expression. Patients with residual disease after two rounds of PDT received definitive radiotherapy. In a subsequent in vitro study, W138 human lung fibroblasts and W138-SV-40 virus transformed were assessed for their sensitivity to PDT. The constitutive bcl-2 overexpression of the transformed cells vs. normal cells (assessed with RT-PCR) was 16-fold. RESULTS: Positive bcl-2 and p53 expression was noted in 10 out of 36 (27%) and 14 out of 36 (39%) patients, respectively. Seven out of 11 tumors (63%) with bcl-2 expression responded completely to PDT vs. 6 out of 26 (23%) of cases with no bcl-2 expression (p = 0.02). No association of p53, T-stage and of histology grade with response to PDT or PDT/RT was noted. The sensitivity to PDT of transformed human fibroblasts compared to normal ones was 4 times more at a fluence of 4.3 J/cm2 (4% vs. 1% cell kill) as well as at a fluence of 5.4 J/cm2 (8% vs. 2% cell kill). CONCLUSION: Bcl-2 protein expression is associated with favorable response to PDT and can be used as a predictor of cancer response to PDT. This finding can be explained by experimental studies showing that PDT induces selective degradation of the bcl-2 protein, leading to apoptosis by decreasing the bcl-2/bax ratio. Studies on PDT combination with agents targeting bcl-2 (i.e. taxanes) are on going to eventually assess a super-additive effect.
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Authors | M I Koukourakis, L Corti, J Skarlatos, A Giatromanolaki, B Krammer, S Blandamura, M Piazza, T Verwanger, G Schnitzhofer, J Kostandelos, K Beroukas |
Journal | Anticancer research
(Anticancer Res)
2001 Jan-Feb
Vol. 21
Issue 1B
Pg. 663-8
ISSN: 0250-7005 [Print] Greece |
PMID | 11299823
(Publication Type: Journal Article)
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Chemical References |
- Neoplasm Proteins
- Proto-Oncogene Proteins c-bcl-2
- Tumor Suppressor Protein p53
- Argon
- Hematoporphyrin Derivative
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Topics |
- Adult
- Aged
- Apoptosis
(drug effects)
- Argon
- Carcinoma, Squamous Cell
(drug therapy, genetics, metabolism, mortality, radiotherapy)
- Cell Line, Transformed
(drug effects)
- Cells, Cultured
(drug effects)
- Combined Modality Therapy
- Disease-Free Survival
- Drug Resistance
- Esophageal Neoplasms
(drug therapy, genetics, metabolism, mortality, radiotherapy)
- Female
- Fibroblasts
(drug effects)
- Hematoporphyrin Derivative
(therapeutic use)
- Humans
- Lasers
- Male
- Middle Aged
- Neoplasm Proteins
(physiology)
- Photochemotherapy
- Proto-Oncogene Proteins c-bcl-2
(physiology)
- Survival Analysis
- Treatment Outcome
- Tumor Suppressor Protein p53
(physiology)
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