{"title":"狗皮肤乳头状瘤中有机阳离子转运体 OCT3 的表达特征。","authors":"Berenice Liyare Sanz Ressel, Gimena Gomez Castro, Eduardo Carlos Mórtola, Adriana Raquel Massone, Claudio Gustavo Barbeito","doi":"10.1111/vde.13302","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The identification of the activation of the mammalian target of rapamycin (mTOR) signalling pathway as a frequent molecular event in canine cutaneous papillomas (CPs) has provided the rational foundation to explore novel molecular-targeted therapies. Recent evidence indicates that metformin reduces the size of CPs in mice by inhibiting the mTOR signalling pathway. These effects require the expression of the organic cation transporter 3 (OCT3/SLC22A3), a well-known metformin uptake transporter.</p><p><strong>Hypothesis/objectives: </strong>The aim of the present study was to characterise the expression pattern of the metformin uptake transporter OCT3 in canine samples of CP that have shown activation of the mTOR signalling pathway in order to predict if this hyperplastic epidermal lesion is potentially sensitive to metformin.</p><p><strong>Methods: </strong>The expression of OCT3 was evaluated by immunohistochemical investigation in sections of a previously constructed tissue microarray containing 28 samples of canine CP and compared with that previously evaluated for the mTOR activation marker pS6.</p><p><strong>Results: </strong>OCT3 was highly expressed in the membrane and cytoplasm of the basal and suprabasal epidermal cells in all samples of canine CP. This OCT3 expression was localised at similar epidermal compartments to those observed for pS6.</p><p><strong>Conclusions and clinical relevance: </strong>These results show that canine CPs exhibit the expression of surrogate markers that suggest sensitivity to metformin, such as upregulated OCT3 and pS6 expression. Taken together, these findings provide the rationale for the early assessment of the use of metformin as a mechanism-based therapeutic approach for treating canine patients with persistent or multiple CPs.</p>","PeriodicalId":23599,"journal":{"name":"Veterinary dermatology","volume":null,"pages":null},"PeriodicalIF":1.9000,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Characterising the expression of the organic cation transporter OCT3 in cutaneous papillomas of dogs.\",\"authors\":\"Berenice Liyare Sanz Ressel, Gimena Gomez Castro, Eduardo Carlos Mórtola, Adriana Raquel Massone, Claudio Gustavo Barbeito\",\"doi\":\"10.1111/vde.13302\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The identification of the activation of the mammalian target of rapamycin (mTOR) signalling pathway as a frequent molecular event in canine cutaneous papillomas (CPs) has provided the rational foundation to explore novel molecular-targeted therapies. Recent evidence indicates that metformin reduces the size of CPs in mice by inhibiting the mTOR signalling pathway. These effects require the expression of the organic cation transporter 3 (OCT3/SLC22A3), a well-known metformin uptake transporter.</p><p><strong>Hypothesis/objectives: </strong>The aim of the present study was to characterise the expression pattern of the metformin uptake transporter OCT3 in canine samples of CP that have shown activation of the mTOR signalling pathway in order to predict if this hyperplastic epidermal lesion is potentially sensitive to metformin.</p><p><strong>Methods: </strong>The expression of OCT3 was evaluated by immunohistochemical investigation in sections of a previously constructed tissue microarray containing 28 samples of canine CP and compared with that previously evaluated for the mTOR activation marker pS6.</p><p><strong>Results: </strong>OCT3 was highly expressed in the membrane and cytoplasm of the basal and suprabasal epidermal cells in all samples of canine CP. This OCT3 expression was localised at similar epidermal compartments to those observed for pS6.</p><p><strong>Conclusions and clinical relevance: </strong>These results show that canine CPs exhibit the expression of surrogate markers that suggest sensitivity to metformin, such as upregulated OCT3 and pS6 expression. Taken together, these findings provide the rationale for the early assessment of the use of metformin as a mechanism-based therapeutic approach for treating canine patients with persistent or multiple CPs.</p>\",\"PeriodicalId\":23599,\"journal\":{\"name\":\"Veterinary dermatology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2024-10-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Veterinary dermatology\",\"FirstCategoryId\":\"97\",\"ListUrlMain\":\"https://doi.org/10.1111/vde.13302\",\"RegionNum\":3,\"RegionCategory\":\"农林科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"DERMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Veterinary dermatology","FirstCategoryId":"97","ListUrlMain":"https://doi.org/10.1111/vde.13302","RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"DERMATOLOGY","Score":null,"Total":0}
Characterising the expression of the organic cation transporter OCT3 in cutaneous papillomas of dogs.
Background: The identification of the activation of the mammalian target of rapamycin (mTOR) signalling pathway as a frequent molecular event in canine cutaneous papillomas (CPs) has provided the rational foundation to explore novel molecular-targeted therapies. Recent evidence indicates that metformin reduces the size of CPs in mice by inhibiting the mTOR signalling pathway. These effects require the expression of the organic cation transporter 3 (OCT3/SLC22A3), a well-known metformin uptake transporter.
Hypothesis/objectives: The aim of the present study was to characterise the expression pattern of the metformin uptake transporter OCT3 in canine samples of CP that have shown activation of the mTOR signalling pathway in order to predict if this hyperplastic epidermal lesion is potentially sensitive to metformin.
Methods: The expression of OCT3 was evaluated by immunohistochemical investigation in sections of a previously constructed tissue microarray containing 28 samples of canine CP and compared with that previously evaluated for the mTOR activation marker pS6.
Results: OCT3 was highly expressed in the membrane and cytoplasm of the basal and suprabasal epidermal cells in all samples of canine CP. This OCT3 expression was localised at similar epidermal compartments to those observed for pS6.
Conclusions and clinical relevance: These results show that canine CPs exhibit the expression of surrogate markers that suggest sensitivity to metformin, such as upregulated OCT3 and pS6 expression. Taken together, these findings provide the rationale for the early assessment of the use of metformin as a mechanism-based therapeutic approach for treating canine patients with persistent or multiple CPs.
期刊介绍:
Veterinary Dermatology is a bi-monthly, peer-reviewed, international journal which publishes papers on all aspects of the skin of mammals, birds, reptiles, amphibians and fish. Scientific research papers, clinical case reports and reviews covering the following aspects of dermatology will be considered for publication:
-Skin structure (anatomy, histology, ultrastructure)
-Skin function (physiology, biochemistry, pharmacology, immunology, genetics)
-Skin microbiology and parasitology
-Dermatopathology
-Pathogenesis, diagnosis and treatment of skin diseases
-New disease entities