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Upregulation of TGF-β1 and basic FGF develops elastofibroma
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JSID Abstracts / Journal of Dermatological Science 69 (2013) e1–e46
P02-19 Upregulation of TGF-1 and basic FGF develops elastofibroma Hisayoshi Imanishi 1,∗ , Daisuke Tsuruta 1 , Yasuhiko Yoshida 2 , Aya Okabayashi 2 , Chiharu Tateishi 1 , Hirofumi Ikushima 3 , Ren Nagasako 4 , Masamitsu Ishii 1 , Koichi Nakagawa 2 1
Department of Dermatology, Osaka City University Graduate School of Medicine, Osaka, Japan 2 Department of Dermatology, Saiseikai Tondabayashi Hospital, Osaka, Japan 3 Department of Surgery, Saiseikai Tondabayashi Hospital, Osaka, Japan 4 Department of Pathology, Saiseikai Tondabayashi Hospital, Osaka, Japan
Elastofibroma is a rare tumor that occurs most typically in the lower end of the subscapular space of middle-aged to elderly persons. One of the speculated etiologies is repeated trauma due to mechanical friction of the scapula against the ribs, and the other to be suggested is a nontraumatic, genetic origin. However, exact etiology of elastofibroma is still unknown. Recently, it has been reported immunohistologically that fibroblasts in elastofibroma may produce both abnormal elastic fibers and collagen fibers through the action of TGF- which promotes fibroblast proliferation. We investigated the expression of TGF-1and basic FGF (bFGF), a strong promoter of fibroblast proliferation, in elastofibroma specimens immunohistochemically. The results revealed that the 16-59% fibroblasts in elastofibroma samples were positive for TGF-1 in cytoplasm, whereas 26-67% fibroblasts in elastofibroma samples were positive for bFGF in the cytoplasm. Intriguingly, in immunohistochemical analysis of both TGF-1and bFGF, the percentage of positive cells of the smallest elastofibroma sample was lowest among three elastofibroma samples. This result may show that the more the TGF-1 and bFGF expressions in fibroblasts increase, the more elastofibroma mass increases. These results may imply that elastofibroma develops via high expression of TGF-1 and bFGF. http://dx.doi.org/10.1016/j.jdermsci.2012.11.371 P02-20 Retinoids regulates the production of matrix metalloproteinases in the human epidermal keratinocyte cell line HaCaT Satomi Hosoda ∗ , Jitlada Meephansan, Masaru Karakawa, Tomoyuki Oshio, Hidetoshi Tsuda, Mayumi Komine, Mamitaro Ohtsuki
cis retinoic acid suppressed the induction of MMP-1,9 by TNF␣, in a dose-dependent manner, but not that of MMP-13. http://dx.doi.org/10.1016/j.jdermsci.2012.11.372 P02-21 Severe scarring alopecia associated with combinational use of ficlatuzumab and gefitinib: a clinical and immunohistochemistry study Yi-Hsien Shih ∗ , Chia-Yu Chu Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib, are among the standard treatments for patients of non-small cell lung cancer (NSCLC). However, EGFR TKI resistance is commonly encountered after prolonged treatment. Hepatocyte growth factor (HGF) is the soluble ligand for the c-Met tyrosine kinase receptor, which is normally expressed by epithelial cells, frequently overexpressed in NSCLC, and contributed to EGFR TKI resistance. Thus, an anti-hepatocyte growth factor monoclonal antibody, ficlatuzumab (AV-299), is introduced to be used in combination with gefitinib in a phase 2 study conducted among Asian patients with NSCLC. We observed severe refractory scarring alopecia in patients using the above-mentioned combination. Although severe scalp inflammation with hair loss presenting as scarring or non-scarring alopecia associated with single use of gefitinib or erlotinib has been reported, our cases represented the most severe scarring variant, including a case of folliculitis decalvans, and the most rapid-onset variant of this scalp side effect. HGF and EGF both played parts in Stat3-dependent hair cycle induction. We hypothesized that simultaneous inhibition of HGF and EGF by combinational use of ficlatuzumab and gefitinib may lead to a synergistic toxicity presenting as more severe scarring hair loss. Besides the clinical significance, the expression and localization of EGFR and c-Met tyrosine kinase receptor in hair follicles have not been well studied. In this study, we present the clinical and immunohistochemistry features in both normal human hair follicles and in hair follicles from patients receiving combinational use of ficlatuzumab and gefitinib. http://dx.doi.org/10.1016/j.jdermsci.2012.11.373 P02-22 Human papillomavirus infection in Bowen disease
Department of Dermatology, Jichi Medical University
Kazutoshi Murao ∗ , Yoshiaki Kubo
Retinoids are known to induce the proliferation of fibroblasts, to promote collagen synthesis and to decrease the matrix metalloproteinases (MMPs) expression. Adapalene is a naphthoic acid derivative showing some pharmacological activities similar to the regular retinoids. It is used singly or in combination for treating acne and a few other skin disorders. MMPs are abundantly found in acne lesions and believed to worsen inflammation and scar formation. In this study, we tried to investigate the suppressive effect of adapalene, all-trans retinoic acid and 9-cis retinoic acid on the production of MMP-1, 9, and 13. Cultured HaCaT keratinocytes were stimulated with TNF␣, with or without adapalene, all-trans retinoic acid or 9-cis retinoic acid, and the supernatants were collected and subjected to ELISA. RNA was also extracted, and real-time PCR was performed. HaCaT keratinocytes produced MMP-1,9 and 13, which were induced by TNF␣. Aadapalene, all-trans retinoic acid and 9-
Department of Dermatology, Institute of Health Biosciences, The University of Tokushima Graduate School Human papillomavirus (HPV) is one of the well-known risk factors of many epithelial malignancies of the oral cavity, larynx, and skin, as well as the cervix. Among the non-melanoma skin cancers, Bowen disease (BD) of the genitalia and fingers has been shown to be strongly linked to the high-risk types of HPV infection, especially HPV 16. Recently, there have been several case reports of HPVassociated BD on other locations as well; however, there are only several reports demonstrating the frequencies of HPV infection in BD lesions. The skin specimens of 142 BD lesions from 136 patients were investigated clinicopathologically. DNA extracted from fixed and embedded tissues was analyzed for the presence of mucous, high-risk types of HPV using polymerase chain reaction (PCR) in combination with restriction fragment length polymorphisms
JSID Abstracts / Journal of Dermatological Science 69 (2013) e1–e46
P02-19 Upregulation of TGF-1 and basic FGF develops elastofibroma Hisayoshi Imanishi 1,∗ , Daisuke Tsuruta 1 , Yasuhiko Yoshida 2 , Aya Okabayashi 2 , Chiharu Tateishi 1 , Hirofumi Ikushima 3 , Ren Nagasako 4 , Masamitsu Ishii 1 , Koichi Nakagawa 2 1
Department of Dermatology, Osaka City University Graduate School of Medicine, Osaka, Japan 2 Department of Dermatology, Saiseikai Tondabayashi Hospital, Osaka, Japan 3 Department of Surgery, Saiseikai Tondabayashi Hospital, Osaka, Japan 4 Department of Pathology, Saiseikai Tondabayashi Hospital, Osaka, Japan
Elastofibroma is a rare tumor that occurs most typically in the lower end of the subscapular space of middle-aged to elderly persons. One of the speculated etiologies is repeated trauma due to mechanical friction of the scapula against the ribs, and the other to be suggested is a nontraumatic, genetic origin. However, exact etiology of elastofibroma is still unknown. Recently, it has been reported immunohistologically that fibroblasts in elastofibroma may produce both abnormal elastic fibers and collagen fibers through the action of TGF- which promotes fibroblast proliferation. We investigated the expression of TGF-1and basic FGF (bFGF), a strong promoter of fibroblast proliferation, in elastofibroma specimens immunohistochemically. The results revealed that the 16-59% fibroblasts in elastofibroma samples were positive for TGF-1 in cytoplasm, whereas 26-67% fibroblasts in elastofibroma samples were positive for bFGF in the cytoplasm. Intriguingly, in immunohistochemical analysis of both TGF-1and bFGF, the percentage of positive cells of the smallest elastofibroma sample was lowest among three elastofibroma samples. This result may show that the more the TGF-1 and bFGF expressions in fibroblasts increase, the more elastofibroma mass increases. These results may imply that elastofibroma develops via high expression of TGF-1 and bFGF. http://dx.doi.org/10.1016/j.jdermsci.2012.11.371 P02-20 Retinoids regulates the production of matrix metalloproteinases in the human epidermal keratinocyte cell line HaCaT Satomi Hosoda ∗ , Jitlada Meephansan, Masaru Karakawa, Tomoyuki Oshio, Hidetoshi Tsuda, Mayumi Komine, Mamitaro Ohtsuki
cis retinoic acid suppressed the induction of MMP-1,9 by TNF␣, in a dose-dependent manner, but not that of MMP-13. http://dx.doi.org/10.1016/j.jdermsci.2012.11.372 P02-21 Severe scarring alopecia associated with combinational use of ficlatuzumab and gefitinib: a clinical and immunohistochemistry study Yi-Hsien Shih ∗ , Chia-Yu Chu Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib, are among the standard treatments for patients of non-small cell lung cancer (NSCLC). However, EGFR TKI resistance is commonly encountered after prolonged treatment. Hepatocyte growth factor (HGF) is the soluble ligand for the c-Met tyrosine kinase receptor, which is normally expressed by epithelial cells, frequently overexpressed in NSCLC, and contributed to EGFR TKI resistance. Thus, an anti-hepatocyte growth factor monoclonal antibody, ficlatuzumab (AV-299), is introduced to be used in combination with gefitinib in a phase 2 study conducted among Asian patients with NSCLC. We observed severe refractory scarring alopecia in patients using the above-mentioned combination. Although severe scalp inflammation with hair loss presenting as scarring or non-scarring alopecia associated with single use of gefitinib or erlotinib has been reported, our cases represented the most severe scarring variant, including a case of folliculitis decalvans, and the most rapid-onset variant of this scalp side effect. HGF and EGF both played parts in Stat3-dependent hair cycle induction. We hypothesized that simultaneous inhibition of HGF and EGF by combinational use of ficlatuzumab and gefitinib may lead to a synergistic toxicity presenting as more severe scarring hair loss. Besides the clinical significance, the expression and localization of EGFR and c-Met tyrosine kinase receptor in hair follicles have not been well studied. In this study, we present the clinical and immunohistochemistry features in both normal human hair follicles and in hair follicles from patients receiving combinational use of ficlatuzumab and gefitinib. http://dx.doi.org/10.1016/j.jdermsci.2012.11.373 P02-22 Human papillomavirus infection in Bowen disease
Department of Dermatology, Jichi Medical University
Kazutoshi Murao ∗ , Yoshiaki Kubo
Retinoids are known to induce the proliferation of fibroblasts, to promote collagen synthesis and to decrease the matrix metalloproteinases (MMPs) expression. Adapalene is a naphthoic acid derivative showing some pharmacological activities similar to the regular retinoids. It is used singly or in combination for treating acne and a few other skin disorders. MMPs are abundantly found in acne lesions and believed to worsen inflammation and scar formation. In this study, we tried to investigate the suppressive effect of adapalene, all-trans retinoic acid and 9-cis retinoic acid on the production of MMP-1, 9, and 13. Cultured HaCaT keratinocytes were stimulated with TNF␣, with or without adapalene, all-trans retinoic acid or 9-cis retinoic acid, and the supernatants were collected and subjected to ELISA. RNA was also extracted, and real-time PCR was performed. HaCaT keratinocytes produced MMP-1,9 and 13, which were induced by TNF␣. Aadapalene, all-trans retinoic acid and 9-
Department of Dermatology, Institute of Health Biosciences, The University of Tokushima Graduate School Human papillomavirus (HPV) is one of the well-known risk factors of many epithelial malignancies of the oral cavity, larynx, and skin, as well as the cervix. Among the non-melanoma skin cancers, Bowen disease (BD) of the genitalia and fingers has been shown to be strongly linked to the high-risk types of HPV infection, especially HPV 16. Recently, there have been several case reports of HPVassociated BD on other locations as well; however, there are only several reports demonstrating the frequencies of HPV infection in BD lesions. The skin specimens of 142 BD lesions from 136 patients were investigated clinicopathologically. DNA extracted from fixed and embedded tissues was analyzed for the presence of mucous, high-risk types of HPV using polymerase chain reaction (PCR) in combination with restriction fragment length polymorphisms