Cyclin D1, B and A expression and cell turnover in psoriatic skin lesions before and after cyclosporin treatment

Background Cyclosporin induces a dramatic reversal to normality in psoriatic lesions, with a reduction of inflammatory infiltrate and epidermal proliferation. It is known that the cell cycle and cell proliferation are regulated by the sequential activation of cyclin‐dependent kinase/cyclin complexes...

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Veröffentlicht in:British journal of dermatology (1951) 2000-11, Vol.143 (5), p.950-956
Hauptverfasser: Miracco, C., Pellegrino, M., Flori, M.L., Vatti, R., Materno, M., Andreassi, L.
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container_end_page 956
container_issue 5
container_start_page 950
container_title British journal of dermatology (1951)
container_volume 143
creator Miracco, C.
Pellegrino, M.
Flori, M.L.
Vatti, R.
Materno, M.
Andreassi, L.
description Background Cyclosporin induces a dramatic reversal to normality in psoriatic lesions, with a reduction of inflammatory infiltrate and epidermal proliferation. It is known that the cell cycle and cell proliferation are regulated by the sequential activation of cyclin‐dependent kinase/cyclin complexes. Aim We evaluated epidermal cell turnover and thickness, as well as the expression of cyclins D1, B and A in psoriatic skin before and after therapy with cyclosporin. Methods Epidermal thickness, mitotic and apoptotic indices (MI, AI), as well as the percentages of epidermal cell nuclei positive for Ki‐67 and cyclins D1, B and A were calculated. Cytoplasmic positivity to cyclin B was also evaluated. Results After 6 weeks of therapy, we observed a clinical improvement of the disease and normalization of the epidermis. Epidermal thickness and Ki‐67‐, cyclins B‐ and A‐positive nuclei percentage were significantly higher before therapy than after (0·52 ± 0·05 mm vs. 0·21 ± 0·03 mm, P 
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It is known that the cell cycle and cell proliferation are regulated by the sequential activation of cyclin‐dependent kinase/cyclin complexes. Aim We evaluated epidermal cell turnover and thickness, as well as the expression of cyclins D1, B and A in psoriatic skin before and after therapy with cyclosporin. Methods Epidermal thickness, mitotic and apoptotic indices (MI, AI), as well as the percentages of epidermal cell nuclei positive for Ki‐67 and cyclins D1, B and A were calculated. Cytoplasmic positivity to cyclin B was also evaluated. Results After 6 weeks of therapy, we observed a clinical improvement of the disease and normalization of the epidermis. Epidermal thickness and Ki‐67‐, cyclins B‐ and A‐positive nuclei percentage were significantly higher before therapy than after (0·52 ± 0·05 mm vs. 0·21 ± 0·03 mm, P &lt; 0·001; 19 vs. 2·6, 19 vs. 3, and 12 vs. 1, respectively; P &lt; 0·0005); cytoplasmic positivity to cyclin B was slightly higher before therapy (score 3 vs. 2–3). Cyclin D1 was negative or expressed in a low percentage of nuclei in psoriasis before therapy (0·78), whereas it was always negative after therapy. MI was 0·15 before therapy, whereas mitoses were almost absent afterwards. Apoptoses were undetectable before therapy, whereas a few apoptoses were observed after treatment (AI = 0·4). Conclusions Overexpression of cyclins B and A, rather than D1 seems to characterize psoriasis. Their evaluation could provide further insights in understanding the development of this disorder and could be used to verify the efficacy of currently used therapies as well as future ones.</description><identifier>ISSN: 0007-0963</identifier><identifier>EISSN: 1365-2133</identifier><identifier>DOI: 10.1046/j.1365-2133.2000.03826.x</identifier><identifier>PMID: 11069501</identifier><identifier>CODEN: BJDEAZ</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Science Ltd</publisher><subject>Adult ; Biological and medical sciences ; Biomarkers - analysis ; Cell Division - drug effects ; Cyclin A - metabolism ; Cyclin B - metabolism ; Cyclin D1 - metabolism ; cyclins ; Cyclins - metabolism ; Cyclosporine - therapeutic use ; Dermatologic Agents - therapeutic use ; Dermatology ; Epidermis - metabolism ; Epidermis - pathology ; Female ; Follow-Up Studies ; Humans ; Immunosuppressive Agents - therapeutic use ; Male ; Medical sciences ; Middle Aged ; Pharmacology. 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It is known that the cell cycle and cell proliferation are regulated by the sequential activation of cyclin‐dependent kinase/cyclin complexes. Aim We evaluated epidermal cell turnover and thickness, as well as the expression of cyclins D1, B and A in psoriatic skin before and after therapy with cyclosporin. Methods Epidermal thickness, mitotic and apoptotic indices (MI, AI), as well as the percentages of epidermal cell nuclei positive for Ki‐67 and cyclins D1, B and A were calculated. Cytoplasmic positivity to cyclin B was also evaluated. Results After 6 weeks of therapy, we observed a clinical improvement of the disease and normalization of the epidermis. Epidermal thickness and Ki‐67‐, cyclins B‐ and A‐positive nuclei percentage were significantly higher before therapy than after (0·52 ± 0·05 mm vs. 0·21 ± 0·03 mm, P &lt; 0·001; 19 vs. 2·6, 19 vs. 3, and 12 vs. 1, respectively; P &lt; 0·0005); cytoplasmic positivity to cyclin B was slightly higher before therapy (score 3 vs. 2–3). Cyclin D1 was negative or expressed in a low percentage of nuclei in psoriasis before therapy (0·78), whereas it was always negative after therapy. MI was 0·15 before therapy, whereas mitoses were almost absent afterwards. Apoptoses were undetectable before therapy, whereas a few apoptoses were observed after treatment (AI = 0·4). Conclusions Overexpression of cyclins B and A, rather than D1 seems to characterize psoriasis. Their evaluation could provide further insights in understanding the development of this disorder and could be used to verify the efficacy of currently used therapies as well as future ones.</description><subject>Adult</subject><subject>Biological and medical sciences</subject><subject>Biomarkers - analysis</subject><subject>Cell Division - drug effects</subject><subject>Cyclin A - metabolism</subject><subject>Cyclin B - metabolism</subject><subject>Cyclin D1 - metabolism</subject><subject>cyclins</subject><subject>Cyclins - metabolism</subject><subject>Cyclosporine - therapeutic use</subject><subject>Dermatologic Agents - therapeutic use</subject><subject>Dermatology</subject><subject>Epidermis - metabolism</subject><subject>Epidermis - pathology</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Humans</subject><subject>Immunosuppressive Agents - therapeutic use</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Pharmacology. Drug treatments</subject><subject>psoriasis</subject><subject>Psoriasis - drug therapy</subject><subject>Psoriasis - metabolism</subject><subject>Psoriasis - pathology</subject><subject>Psoriasis. Parapsoriasis. Lichen</subject><subject>Skin, nail, hair, dermoskeleton</subject><subject>therapy</subject><issn>0007-0963</issn><issn>1365-2133</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkUtv1DAQgC0EotvCX0AWSJyaMI5jJzlwaLcPQKVIFajcLMceS9lmk9TO0t1_X2d3tUicOPkx3zf2zBBCGaQMcvlpkTIuRZIxztMMAFLgZSbT9QsyOwReklmMFAlUkh-R4xAWAIyDgNfkiDGQlQA2I8N8Y9qmoxfslJ5T3Vl6RnE9eAyh6bvthcG2pePKd_0f9DSyQ-h9o8fG0PAQjy1OaKA1ut7jVtFujKiJqfswRLijo0c9LrEb35BXTrcB3-7XE_Lr6vLn_Ety8-P66_zsJjEiy2XCnHYic5wxKwS3ugLHTI1FXoHAyoIuMatqh9JybWvpCoA8s6aw0uTIbcVPyMdd3sH3jysMo1o2YSpFd9ivgiqyHERZsgi-_wdc9LHY-Dc1tVayvCwjVO4g4_sQPDo1-Gap_UYxUNNI1EJNnVdT57ee2o5EraP6bp9_VS_R_hX3M4jAhz2gg9Gt87ozTThwJUheTNTnHfXUtLj57-fV-beLaRf9ZOc3YcT1wdf-QcmCF0Ld316r7Pf9XX73_VZJ_gwc3bYJ</recordid><startdate>200011</startdate><enddate>200011</enddate><creator>Miracco, C.</creator><creator>Pellegrino, M.</creator><creator>Flori, M.L.</creator><creator>Vatti, R.</creator><creator>Materno, M.</creator><creator>Andreassi, L.</creator><general>Blackwell Science Ltd</general><general>Blackwell</general><general>Oxford University Press</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope></search><sort><creationdate>200011</creationdate><title>Cyclin D1, B and A expression and cell turnover in psoriatic skin lesions before and after cyclosporin treatment</title><author>Miracco, C. ; Pellegrino, M. ; Flori, M.L. ; Vatti, R. ; Materno, M. ; Andreassi, L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5246-1faf52f311d553da90f1cbe74905e9d0a8e29bfe6d3adb6f70042dc7d6c4e3d93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Adult</topic><topic>Biological and medical sciences</topic><topic>Biomarkers - analysis</topic><topic>Cell Division - drug effects</topic><topic>Cyclin A - metabolism</topic><topic>Cyclin B - metabolism</topic><topic>Cyclin D1 - metabolism</topic><topic>cyclins</topic><topic>Cyclins - metabolism</topic><topic>Cyclosporine - therapeutic use</topic><topic>Dermatologic Agents - therapeutic use</topic><topic>Dermatology</topic><topic>Epidermis - metabolism</topic><topic>Epidermis - pathology</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Humans</topic><topic>Immunosuppressive Agents - therapeutic use</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Pharmacology. Drug treatments</topic><topic>psoriasis</topic><topic>Psoriasis - drug therapy</topic><topic>Psoriasis - metabolism</topic><topic>Psoriasis - pathology</topic><topic>Psoriasis. Parapsoriasis. Lichen</topic><topic>Skin, nail, hair, dermoskeleton</topic><topic>therapy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Miracco, C.</creatorcontrib><creatorcontrib>Pellegrino, M.</creatorcontrib><creatorcontrib>Flori, M.L.</creatorcontrib><creatorcontrib>Vatti, R.</creatorcontrib><creatorcontrib>Materno, M.</creatorcontrib><creatorcontrib>Andreassi, L.</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>British journal of dermatology (1951)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Miracco, C.</au><au>Pellegrino, M.</au><au>Flori, M.L.</au><au>Vatti, R.</au><au>Materno, M.</au><au>Andreassi, L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cyclin D1, B and A expression and cell turnover in psoriatic skin lesions before and after cyclosporin treatment</atitle><jtitle>British journal of dermatology (1951)</jtitle><addtitle>Br J Dermatol</addtitle><date>2000-11</date><risdate>2000</risdate><volume>143</volume><issue>5</issue><spage>950</spage><epage>956</epage><pages>950-956</pages><issn>0007-0963</issn><eissn>1365-2133</eissn><coden>BJDEAZ</coden><abstract>Background Cyclosporin induces a dramatic reversal to normality in psoriatic lesions, with a reduction of inflammatory infiltrate and epidermal proliferation. It is known that the cell cycle and cell proliferation are regulated by the sequential activation of cyclin‐dependent kinase/cyclin complexes. Aim We evaluated epidermal cell turnover and thickness, as well as the expression of cyclins D1, B and A in psoriatic skin before and after therapy with cyclosporin. Methods Epidermal thickness, mitotic and apoptotic indices (MI, AI), as well as the percentages of epidermal cell nuclei positive for Ki‐67 and cyclins D1, B and A were calculated. Cytoplasmic positivity to cyclin B was also evaluated. Results After 6 weeks of therapy, we observed a clinical improvement of the disease and normalization of the epidermis. Epidermal thickness and Ki‐67‐, cyclins B‐ and A‐positive nuclei percentage were significantly higher before therapy than after (0·52 ± 0·05 mm vs. 0·21 ± 0·03 mm, P &lt; 0·001; 19 vs. 2·6, 19 vs. 3, and 12 vs. 1, respectively; P &lt; 0·0005); cytoplasmic positivity to cyclin B was slightly higher before therapy (score 3 vs. 2–3). Cyclin D1 was negative or expressed in a low percentage of nuclei in psoriasis before therapy (0·78), whereas it was always negative after therapy. MI was 0·15 before therapy, whereas mitoses were almost absent afterwards. Apoptoses were undetectable before therapy, whereas a few apoptoses were observed after treatment (AI = 0·4). Conclusions Overexpression of cyclins B and A, rather than D1 seems to characterize psoriasis. Their evaluation could provide further insights in understanding the development of this disorder and could be used to verify the efficacy of currently used therapies as well as future ones.</abstract><cop>Oxford, UK</cop><pub>Blackwell Science Ltd</pub><pmid>11069501</pmid><doi>10.1046/j.1365-2133.2000.03826.x</doi><tpages>7</tpages></addata></record>
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source Oxford University Press Journals All Titles (1996-Current); MEDLINE; Wiley Online Library Journals Frontfile Complete
subjects Adult
Biological and medical sciences
Biomarkers - analysis
Cell Division - drug effects
Cyclin A - metabolism
Cyclin B - metabolism
Cyclin D1 - metabolism
cyclins
Cyclins - metabolism
Cyclosporine - therapeutic use
Dermatologic Agents - therapeutic use
Dermatology
Epidermis - metabolism
Epidermis - pathology
Female
Follow-Up Studies
Humans
Immunosuppressive Agents - therapeutic use
Male
Medical sciences
Middle Aged
Pharmacology. Drug treatments
psoriasis
Psoriasis - drug therapy
Psoriasis - metabolism
Psoriasis - pathology
Psoriasis. Parapsoriasis. Lichen
Skin, nail, hair, dermoskeleton
therapy
title Cyclin D1, B and A expression and cell turnover in psoriatic skin lesions before and after cyclosporin treatment
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