1
Norwegian Radium Hospital, Comprehensive Cancer Center The influence of photodynamic therapy on folate and vitamin D levels Biophysics and PDT group, Department of Radiation Biology, Institute for Cancer Research, Rikshospitalet-Radiumhospitalet HF Group leader: Johan Moan, Prof., PhD Tel:22934268 E-mail: [email protected] A high vitamin D status (serum 25(OH)vitamin D 3 ) correlates with a decreased risk of breast-, prostate-, colon-, lung cancer and lymphomas. CAN PDT HAVE SYSTEMIC EFFECTS LIKE FOLATE DEGRADATION AND INCREASED VITAMIN D PRODUCTION? Multivariable relative risks and 95% confidence intervals for an increment of 25 nmol/L in predicted plasma 25-hydroxy-vitamin D level for individual cancers in the Health Professionals Follow- up Study (1986–2000). Giovannucci, E. et al. J Natl Cancer Inst 2006;98:451-459 Folate is an essential vitamin for cell division and cell growth. Since cancer cells divide more often than normal cells they need more folate. Therefore, several of the chemotherapeutic agents used against cancer are antifolates. The most common one is Methotrexate, which binds to the folate enzyme dihydrofolate reductase. Experiments carried out by us indicate that folate is degraded during PDT, both in vivo, in patient treated with PDT, and in vitro, in folate solutions exposed to visible light in the presence of photosensitizers. The most common folate derivative in the human body, 5- methyltetrahydrofolate, is oxidized to the biological inactive folate 5- methyldihydrofolate, because of it’s antioxidant activity. Me CO 2 H CO 2 H N N H N H O N N H H 2 N N H O S Jablonski and Chaplin, Sci. Am. 2002 Folate A cream containing ALA will be applied topically for 6 h on shaved rat skin. Subsequently the cream will be removed and rats will be exposed to blue light. Blood will be sampled before light exposure and after at different time points. Serum will be separated and vitamin D derivatives and folate will be quantified by standard methods. Furthermore, cream may be enriched with vitamin D precursors that will be absorbed in the skin and activated during light exposure in PDT. By this means, vitamin D production might be locally increased leading to a better treatment outcome. If the experimental results are encouraging, a clinical study will be designed. Blood from patients undergoing PDT treatment on extended skin areas will be drawn and vitamin D and folate levels will be assessed. TOPICAL PHOTODYNAMIC THERAPY IN DERMATOLOGY In dermatology, PDT with topical ALA or MAL is very effective in the treatment of actinic keratosis, basal cell carcinomas and Bowen's disease. In addition, very promising results have been obtained in inflammatory pathologies like morphea, sarcoidosis and infections like warts. Basal cell carcinoma Bowen’s disease Actinic keratosis Morphea Warts PHOTODYNAMIC THERAPY Photodynamic therapy (PDT) involves administration of a tumour-localizing photosensitizer or photosensitizer prodrug (5-aminolevulinic acid (ALA) or its methyl ester (MAL)) and the subsequent activation of the photosensitizer by light in combination with oxygen to produce cytotoxic reactive oxygen species that kill malignant cells by apoptosis and/or necrosis, shut down the tumour microvasculature and stimulate the host immune system. The aim of this study is to investigate the level of folate and vitamin D in serum of rats before and after PDT. ALA or MAL Light Cell destruction

Norwegian Radium Hospital, Comprehensive Cancer Center

  • Upload
    malana

  • View
    43

  • Download
    0

Embed Size (px)

DESCRIPTION

ALA or MAL. Light. Cell destruction. Basal cell carcinoma. Warts. Bowen’s disease. Actinic keratosis. Morphea. Norwegian Radium Hospital, Comprehensive Cancer Center. - PowerPoint PPT Presentation

Citation preview

Page 1: Norwegian Radium Hospital, Comprehensive Cancer Center

Norwegian Radium Hospital, Comprehensive Cancer Center

The influence of photodynamic therapy on folate and vitamin D levels

Biophysics and PDT group, Department of Radiation Biology, Institute for Cancer Research, Rikshospitalet-Radiumhospitalet HF

Group leader: Johan Moan, Prof., PhDTel:22934268 E-mail: [email protected]

A high vitamin D status (serum 25(OH)vitamin D3) correlates with a decreased risk of breast-, prostate-, colon-, lung cancer and lymphomas.

CAN PDT HAVE SYSTEMIC EFFECTS LIKE FOLATE DEGRADATION AND INCREASED VITAMIN D PRODUCTION?

Multivariable relative risks and 95% confidence intervals for an increment of 25 nmol/L in predicted plasma 25-hydroxy-vitamin D level for individual cancers in the Health Professionals Follow-up Study (1986–2000). Giovannucci, E. et al. J Natl Cancer Inst 2006;98:451-459

Folate is an essential vitamin for cell division and cell growth. Since cancer cells divide more often than normal cells they need more folate.

Therefore, several of the chemotherapeutic agents used against cancer are antifolates. The most common one is Methotrexate, which binds to the folate enzyme dihydrofolate reductase.

Experiments carried out by us indicate that folate is degraded during PDT, both in vivo, in patient treated with PDT, and in vitro, in folate solutions exposed to visible light in the presence of photosensitizers. The most common folate derivative in the human body, 5-methyltetrahydrofolate, is oxidized to the biological inactive folate 5-methyldihydrofolate, because of it’s antioxidant activity.

Me

CO 2H

CO 2 HN

NH

NH

O

N NH

H2 N

NH

O

S

Jablonski and Chaplin, Sci. Am. 2002

Folate

A cream containing ALA will be applied topically for 6 h on shaved rat skin. Subsequently the cream will be removed and rats will be exposed to blue light. Blood will be sampled before light exposure and after at different time points. Serum will be separated and vitamin D derivatives and folate will be quantified by standard methods. Furthermore, cream may be enriched with vitamin D precursors that will be absorbed in the skin and activated during light exposure in PDT. By this means, vitamin D production might be locally increased leading to a better treatment outcome. If the experimental results are encouraging, a clinical study will be designed. Blood from patients undergoing PDT treatment on extended skin areas will be drawn and vitamin D and folate levels will be assessed.

TOPICAL PHOTODYNAMIC THERAPY IN DERMATOLOGY

In dermatology, PDT with topical ALA or MAL is very effective in the treatment of actinic keratosis, basal cell carcinomas and Bowen's disease. In addition, very promising results have been obtained in inflammatory pathologies like morphea, sarcoidosis and infections like warts.

Basal cell carcinoma Bowen’s disease Actinic keratosis Morphea Warts

PHOTODYNAMIC THERAPY

Photodynamic therapy (PDT) involves administration of a tumour-localizing photosensitizer or photosensitizer prodrug (5-aminolevulinic acid (ALA) or its methyl ester (MAL)) and the subsequent activation of the photosensitizer by light in combination with oxygen to produce cytotoxic reactive oxygen species that kill malignant cells by apoptosis and/or necrosis, shut down the tumour microvasculature and stimulate the host immune system.

The aim of this study is to investigate the level of folate and vitamin D in serum of rats before and after PDT.

ALA or MAL Light Cell destruction