the use of retinoids in the treatment of non melanoma skin cancer

1
125 097(EL) 098 NEW ADVANCES IN SKIN IMAGING IN VlVO BY GENERATION OF HUMAN AUTOLOGOUS CUTANEOUS B CELL ULTRASOUND AND MAGNETIC RESONANCE LYMPHOMA-SPECIFIC CYTOTOXIC T CELLS FROM TUMOR- J.L. LEVEQUE INFILTRATING LYMPHOCYTES Laboratoires de Recherche de I’OREAL - 1, Avenue Eug&ne Schueller - Aulnay Sous Bois - France. K. MAEDA. M. OISHI AND M. TAKAHASHI Sapporo Medical College. Minami I. Nishi 16, Sapporo, Japan. Due to its weak dimensions, the skin was the only organ which did not beneficiatc of any imaging technology in-viva. These last years. high frequency ultrasonic scanners were dcvelopped allowing a relatively easy and precise imaging of the skin in its different layers Examples will be presented concerning normal skin, pathologies, skin aging and the effect of different products. Magnetic Resonance Imaging (MRI) is based on completely different principles and needs a heavy and very complicated instrumentation. However, it has been possible to adapt this instrumentation to the problem of the skin and high resolution images have been recorded on different sites. Because tbe MR signal is due to proton density and mobility, these images can be used to discuss quantitalivciy rile binding states of water molecules in the different skin layers. 099 SERUM IGE-BF IN THE PATIENT WITH BULLOUS PEMPHIGOID N Maekawa’. H. Hosokawa’, H. Sob’. H lzuml’, J. Yodel’ and Y. Asada’, ‘Department of Dermatology,Kansai MedIcal Unwers~ty. 1 Humizono-cho, Monguchl. Osaka. Japan. and ‘lnstltute for Virus Research, Kyota Unwersity. 53 Shogoin-Kawaracho, Sakyo, Kyoto. Japan The low afflnlty Fc receptor for IgE (FceRWCD23) 1s expressed on var~o”s hematopoletlc cell types. IgE-BFs (sCD23) are proteolytlcally claved portlons of cell surface Fc~RlliCD23. Both the FaRll/CD23 expression and the IgE-BFs productlon are variably regulated by some cytokines and IgE. Enhanced production of this molecule seems to be associated not only wth IgE-medlated allergic conditions but also autolmmune disease. In previous study. we found IgE-bearing and FuRlI expressmg cells m upper dermis and along the BMZ m leslonal skm of BP patlents. Under suspicion that IgE-medlated immune responses may play a role in the pathogenex. of this disease, we tested the serum levels of IgE-BFs m BP patents and compared them wth the dtsease actwty The serum levels of IgE-BFs in BP patients were slgntfaantly higher than healthy controls (p-&01), and in 11 out of 12 patients the alteration of serum IgE-BFs levels correlated well wth the disease actlwty. These results suggest that the serum level of IgE-BFs IS useful as a new paramater for disease act,v,ty in BP Cytotoxic T lymphocytes (CTL) specific for autologous human cotaneoos B cell lymphoma (CBCL) have been successfully generated m vitro from tumor infiltrating lymphocytes (TIL). TIL were cultured in wrum free medium (AIM-V) containing 500 U/ml of recombinant interleukin-? (RIL-2) plus 5% v/v anti-CD3 culture supernatants. Specific cytotoxicity of CTL were achieved in 4 to 8 weeks of culture. The predominant populations I” cultured CTL derived from TIL were CD?+. CD3+, CD4-. CD8+. and CD56- T cells. These data suggested that CTL from TIL cultured with RIL- 2 plus anti-CD3 may have therapeutic benefits for further human adoptive immunotherapy including CBCL. lOO(EL) 1) THE USE OF RETINOIDS IN THE TREATMENT OF NON :IIELANOiJA SKIN CANCER R. XARKS, University of wales, College of Medicine Health Park, Cardiff All forms of non melanoma skin cancer and precancer are increasing in incidence. The reasons for this include 1. increased longevity, 2. increased exposure to U"R and 3. increased numbers of immuno- suppressed subjects. Solitary lesions are the exception rather than rule as in most cases the entire exposed skin has been significantly photo- damaged. Although individual lesions can be effectivelv treated suraicallv, there are often larqe numbers of both establi;hed malignant lesions and vrecancers. In this nresentation treatment of multiple non melanoma skin cancers with oral retinol druos and the use of toDica1 retinodis for the , treatment of solar keratoses will be reviwed. The experience of the Cardiff qraup in the treatment Of non melanoma skin cancer and solar keratoses with oral Ro13-6298 etretlnate and acitretin and with topical tretinoin and isotretinoin will be addressed In-particular. Evidence from histometric and cell kinetic studies stronalv sucaest that the effective- ness of these drugs is via the modulation of cell differentiation rather than by affecting the rate of cell proliferation. It 1s clear from these and other studies that retinoid drugs possess both prophylactic and therapeutic effects in skin cancers are invaluable for some groups of sublects with the propensity to the development of multiple non melanoma ?ki cancer lesions.

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097(EL) 098 NEW ADVANCES IN SKIN IMAGING IN VlVO BY GENERATION OF HUMAN AUTOLOGOUS CUTANEOUS B CELL ULTRASOUND AND MAGNETIC RESONANCE LYMPHOMA-SPECIFIC CYTOTOXIC T CELLS FROM TUMOR-

J.L. LEVEQUE INFILTRATING LYMPHOCYTES

Laboratoires de Recherche de I’OREAL - 1, Avenue Eug&ne Schueller - Aulnay Sous Bois - France.

K. MAEDA. M. OISHI AND M. TAKAHASHI Sapporo Medical College. Minami I. Nishi 16, Sapporo, Japan.

Due to its weak dimensions, the skin was the only organ which did not beneficiatc of any imaging technology in-viva. These last years. high frequency ultrasonic scanners were dcvelopped allowing a relatively easy and precise imaging of the skin in its different layers Examples will be presented concerning normal skin, pathologies, skin aging and the effect of different products. Magnetic Resonance Imaging (MRI) is based on completely different principles and needs a heavy and very complicated instrumentation. However, it has been possible to adapt this instrumentation to the problem of the skin and high resolution images have been recorded on different sites. Because tbe MR signal is due to proton density and mobility, these images can be used to discuss quantitalivciy rile binding states of water molecules in the different skin

layers.

099 SERUM IGE-BF IN THE PATIENT WITH BULLOUS PEMPHIGOID

N Maekawa’. H. Hosokawa’, H. Sob’. H lzuml’, J. Yodel’ and Y. Asada’,

‘Department of Dermatology,Kansai MedIcal Unwers~ty. 1 Humizono-cho,

Monguchl. Osaka. Japan. and ‘lnstltute for Virus Research, Kyota Unwersity.

53 Shogoin-Kawaracho, Sakyo, Kyoto. Japan

The low afflnlty Fc receptor for IgE (FceRWCD23) 1s expressed on var~o”s

hematopoletlc cell types. IgE-BFs (sCD23) are proteolytlcally claved portlons

of cell surface Fc~RlliCD23. Both the FaRll/CD23 expression and the IgE-BFs

productlon are variably regulated by some cytokines and IgE. Enhanced

production of this molecule seems to be associated not only wth IgE-medlated

allergic conditions but also autolmmune disease. In previous study. we found

IgE-bearing and FuRlI expressmg cells m upper dermis and along the BMZ

m leslonal skm of BP patlents. Under suspicion that IgE-medlated immune

responses may play a role in the pathogenex. of this disease, we tested the

serum levels of IgE-BFs m BP patents and compared them wth the dtsease

actwty The serum levels of IgE-BFs in BP patients were slgntfaantly higher

than healthy controls (p-&01), and in 11 out of 12 patients the alteration of

serum IgE-BFs levels correlated well wth the disease actlwty. These results

suggest that the serum level of IgE-BFs IS useful as a new paramater for

disease act,v,ty in BP

Cytotoxic T lymphocytes (CTL) specific for autologous human cotaneoos B

cell lymphoma (CBCL) have been successfully generated m vitro from

tumor infiltrating lymphocytes (TIL). TIL were cultured in wrum free

medium (AIM-V) containing 500 U/ml of recombinant interleukin-? (RIL-2)

plus 5% v/v anti-CD3 culture supernatants. Specific cytotoxicity of CTL

were achieved in 4 to 8 weeks of culture. The predominant populations I”

cultured CTL derived from TIL were CD?+. CD3+, CD4-. CD8+. and

CD56- T cells. These data suggested that CTL from TIL cultured with RIL-

2 plus anti-CD3 may have therapeutic benefits for further human adoptive

immunotherapy including CBCL.

lOO(EL) 1) THE USE OF RETINOIDS IN THE TREATMENT OF NON :IIELANOiJA SKIN CANCER R. XARKS, University of wales, College of Medicine Health Park, Cardiff

All forms of non melanoma skin cancer and precancer are increasing in incidence. The reasons for this include 1. increased longevity, 2. increased exposure to U"R and 3. increased numbers of immuno- suppressed subjects. Solitary lesions are the exception rather than rule as in most cases the entire exposed skin has been significantly photo- damaged. Although individual lesions can be effectivelv treated suraicallv, there are often larqe numbers of both establi;hed malignant lesions and vrecancers. In this nresentation treatment of multiple non melanoma skin cancers with oral retinol druos and the use of toDica1 retinodis for the , treatment of solar keratoses will be reviwed. The experience of the Cardiff qraup in the treatment Of non melanoma skin cancer and solar keratoses with oral Ro13-6298 etretlnate and acitretin and with topical tretinoin and isotretinoin will be addressed In-particular. Evidence from histometric and cell kinetic studies stronalv sucaest that the effective- ness of these drugs is via the modulation of cell differentiation rather than by affecting the rate of cell proliferation. It 1s clear from these and other studies that retinoid drugs possess both prophylactic and therapeutic effects in skin cancers are invaluable for some groups of sublects with the propensity to the development of multiple non melanoma ?ki cancer lesions.