論文 - 肥田　時征

Pigmented mammary Paget's disease mimicking melanoma: report of three cases

Tokimasa Hida, Akihiro Yoneta, Takahiro Nishizaka, Tousei Ohmura, Yasuyo Suzuki, Hidekazu Kameshima, Toshiharu Yamashita

EUROPEAN JOURNAL OF DERMATOLOGY ( JOHN LIBBEY EUROTEXT LTD )  22 ( 1 ) 121 - 124  2012年01月  [査読有り]

　概要を見る

Pigmented mammary Paget's disease (PMPD) is a rare subtype of mammary Paget's disease. The differential diagnosis of PMPD and melanoma is difficult clinically and sometimes histopathologically. Here we present three cases of PMPD with a variable-sized lesion. All cases showed an irregular-shaped black-brown macule, one of which was accompanied by nipple retraction. Dermoscopically, all cases showed reticular pigmentation with or without irregular black dots, regression structures and streaks, which were indistinguishable from those of melanoma. In all but one of the cases, preoperative examinations confirmed the presence of a subcutaneous mammary lesion. All patients underwent a total mastectomy with the histopathological results indicating invasive ductal carcinoma. These cases emphasize how difficult it is to distinguish PMPD from melanoma. Dermoscopic features also mimic those of melanoma, but the reticular pigmentation seen in all cases could be a feature specific to PMPD. For suspicious cases, histopathological assessment using immunohistochemistry is highly recommended.

DOI PubMed

Rab7 is a critical mediator in vesicular transport of tyrosinase-related protein 1 in melanocytes.

Tokimasa Hida, Hitoshi Sohma, Yasuo Kokai, Akinori Kawakami, Kuninori Hirosaki, Masae Okura, Noriko Tosa, Toshiharu Yamashita, Kowichi Jimbow

The Journal of dermatology   38 ( 5 ) 432 - 41  2011年05月  [査読有り]  [国際誌]

　概要を見る

How melanosomal proteins such as enzymic proteins (tyrosinase and tyrosinase-related proteins, Tyrps) and structural protein (gp100) are transported from Golgi to melanosomal compartments is not yet fully understood. A number of small GTPases have been found to be associated with melanosomes and we have identified one of them, Rab7, a regulator of vesicular transport, organelle motility, phospholipid signaling and cytosolic degradative machinery, as being involved in the transport of Tyrp1 from Golgi to stage I melanosomes. This study further characterizes the role of Rab7 as a regulator of differential sorting of melanosomal proteins in this process. Murine melanocytes were transiently transfected with a plasmid encoding either wild-type (Rab7WT), constitutively active (Rab7Q67L) or dominant-negative (Rab7N125I and Rab7T22N) Rab7. Through immunocytostaining and confocal laser scanning microscopy, we quantitatively compared the bio-distribution of melanosomal proteins between Rab7WT-expressing cells and mutant Rab7-expressing cells. We also characterized their differential elimination from melanosomal compartments by Rab7 by utilizing a proteasome inhibitor, MG132. Our findings indicate that Rab7 plays an important role in differential sorting of tyrosinase, Tyrp1 and gp100 in early melanogenesis cascade, and that it is more specifically involved with Tyrp1 than tyrosinase and gp100 in the trafficking from Golgi to melanosomes and the specific exit from the degradative process.

DOI PubMed

Cytokeratin expression patterns in multiple infundibulocystic basal cell carcinoma.

Tokimasa Hida, Kenji Saga, Tetsunori Kimura

Journal of cutaneous pathology   38 ( 3 ) 309 - 13  2011年03月  [査読有り]  [国際誌]

　概要を見る

Infundibulocystic basal cell carcinoma (IBCC) is a variant of basal cell carcinoma. Sporadic cases usually represent a solitary tumor and multiple IBCC is rare. There have been no reports in which the tumor differentiation is characterized immunohistochemically. We report a case of multiple IBCC which developed on a patient's scalp by performing histopathological and immunohistochemical examinations, using monoclonal antibodies against cytokeratins (CKs). A 76-year-old female had noticed multiple small papules on her scalp. She noticed that the tumors were growing when she underwent systemic chemotherapy for metastatic lung cancer. Routine histopathological specimens from skin biopsies revealed findings typical of IBCC. The tumor cells expressed CK14 and CK17. However, CK1 and CK10 were expressed only in a few cells in the inner area of the tumors. The present case is unique in two points. First, multiple tumors developed on the patient's scalp during the systemic chemotherapy for the lung cancer. Second, the tumor showed CK expression patterns characteristic to infundibular and trichilemmal epithelia.

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Agouti protein, mahogunin, and attractin in pheomelanogenesis and melanoblast-like alteration of melanocytes: a cAMP-independent pathway.

Tokimasa Hida, Kazumasa Wakamatsu, Elena V Sviderskaya, Andrew J Donkin, Lluis Montoliu, M Lynn Lamoreux, Bin Yu, Glenn L Millhauser, Shosuke Ito, Gregory S Barsh, Kowichi Jimbow, Dorothy C Bennett

Pigment cell & melanoma research   22 ( 5 ) 623 - 34  2009年10月  [査読有り]  [国際誌]

　概要を見る

Melanocortin-1 receptor (MC1R) and its ligands, alpha-melanocyte stimulating hormone (alphaMSH) and agouti signaling protein (ASIP), regulate switching between eumelanin and pheomelanin synthesis in melanocytes. Here we investigated biological effects and signaling pathways of ASIP. Melan-a non agouti (a/a) mouse melanocytes produce mainly eumelanin, but ASIP combined with phenylthiourea and extra cysteine could induce over 200-fold increases in the pheomelanin to eumelanin ratio, and a tan-yellow color in pelletted cells. Moreover, ASIP-treated cells showed reduced proliferation and a melanoblast-like appearance, seen also in melanocyte lines from yellow (A(y)/a and Mc1r(e)/ Mc1r(e)) mice. However ASIP-YY, a C-terminal fragment of ASIP, induced neither biological nor pigmentary changes. As, like ASIP, ASIP-YY inhibited the cAMP rise induced by alphaMSH analog NDP-MSH, and reduced cAMP level without added MSH, the morphological changes and depigmentation seemed independent of cAMP signaling. Melanocytes genetically null for ASIP mediators attractin or mahogunin (Atrn(mg-3J/mg-3J) or Mgrn1(md-nc/md-nc)) also responded to both ASIP and ASIP-YY in cAMP level, while only ASIP altered their proliferation and (in part) shape. Thus, ASIP-MC1R signaling includes a cAMP-independent pathway through attractin and mahogunin, while the known cAMP-dependent component requires neither attractin nor mahogunin.

DOI PubMed

Macrophage inhibitory cytokine-1: a new player in melanoma development.

Toshiharu Yamashita, Akihiro Yoneta, Tokimasa Hida

The Journal of investigative dermatology   129 ( 2 ) 262 - 4  2009年02月  [査読有り]  [国際誌]

　概要を見る

Macrophage inhibitory cytokine-1 (MIC-1) is a divergent member of the TGF-beta superfamily. Although it has been reported to exhibit both tumorigenic and antitumorigenic activities, Boyle et al. report in this issue that MIC-1 expression was correlated with the tumorigenicity of melanoma cells. The elucidation of signaling pathways around MIC-1 might contribute to prospective targeting therapy for melanoma.

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Spontaneous regression of bowenoid papulosis in a patient with acquired immunodeficiency syndrome after an increase in peripheral CD4+ T lymphocytes.

Akinori Kawakami, Kenji Saga, Ichiro Ono, Tokimasa Hida, Kowichi Jimbow, Toshiharu Yamashita

International journal of dermatology   48 ( 2 ) 210 - 2  2009年02月  [査読有り]  [国際誌]

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Fulminant bowel-associated dermatosis-arthritis syndrome that clinically showed necrotizing fasciitis-like severe skin and systemic manifestations

A Kawakami, K Saga, T Hida, K Jimbow, H Takahashi

JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY ( BLACKWELL PUBLISHING )  20 ( 6 ) 751 - 753  2006年07月  [査読有り]

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Testicular swelling as the presenting sign of cutaneous malignant melanoma

T Hida, K Saga, J Ogino, M Kagaya, A Kamada, R Kaneko, K Jimbow, R Inoue, A Takahashi

JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY ( BLACKWELL PUBLISHING )  20 ( 3 ) 351 - 353  2006年03月  [査読有り]

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Exploitation of melanin and melanosome biogenesis for better management of malignant melanoma

Kowichi Jimbow, Toshiharu Yamashita, Hidenobu Matsusaka, Kuninori Hirosaki, Akihiro Yoneta, Asako Kamada, Hiroyoshi Inoue, Tokimasa Hida, Akinori Kawakami, Takafumi Kamiya, Jiro Ogino, Tomoaki Takada, Makito Sato, Akiko Sakemoto, Ichiro Ono

Sapporo Medical Journal ( 札幌医科大学 )  74 ( 3 ) 23 - 31  2005年08月

　概要を見る

Management of malignant melanoma is a difficult challenge for physicians and basic scientists because cutaneous melanoma grows in the highly vascular tissue of epidermo-dermal interface and occurs at any age of generation. It can easily spread to distant organs and practically no treatment modality is available except for early diagnosis and surgical excision. In this report we review our current research efforts in establishing novel diagnostic and therapeutic approaches for malignant melanoma by exploiting our knowledge of basic biology in melanin and melanosome biogenesis. This is based upon the fact that melanin and melanosome biogenesis is biological property uniquely expressed in melanocytes, and highly accelerated and altered in their neoplastic counterpart, malignant melanoma. It is immediately apparent if one looks at the past literatures that rapid and significant progress of cancer management has been made if the biological property unique to cancer cells is exploited.

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Local administration of hepatocyte growth factor gene enhances the regeneration of dermis in acute incisional wounds.

Ichiro Ono, Toshiharu Yamashita, Tokimasa Hida, Hai-Ying Jin, Yoshinori Ito, Hirobumi Hamada, Yoshikiyo Akasaka, Toshiharu Ishii, Kowichi Jimbow

The Journal of surgical research   120 ( 1 ) 47 - 55  2004年07月  [査読有り]  [国際誌]

　概要を見る

Hepatocyte growth factor (HGF) has a number of biological activities, e.g., mitogenic, motogenic, antiapoptotic, antifibrous, and morphogenic. It also has angiogenic and angioprotective activities for endothelial cells. The aim of this study was to characterize the role of HGF in wound healing by administering the HGF gene locally to acute incisional skin wounds created on the backs of rats. To create wounds, the backs of Wistar rats were clipped and three 2-cm-long incisional wounds were made deep to the fascia. The wounds contained pannicrus carnosum and were created at intervals of 2 cm. After suturing, the HGF gene was then administered intradermally. Apoptotic cells in wound lesions were identified by TUNEL method as well as by immunological detection of active caspase-3. In the HGF-treated animals, we found almost complete suppression of apoptosis and well-organized wound healing. Histopathological examination revealed that the proliferation of fibroblasts was suppressed and that scar formation was less apparent in the HGF-treated animals compared to the controls. It is thought that administration of the HGF gene immediately after surgery may enhance the healing process through suppressing apoptosis, which occurred in the controls 1 week after suturing the incisional wound. In addition, locally increased HGF expression due to the introduction of the HGF gene to cells around wounds enhances dermal regeneration, possibly by promoting regeneration of dermal tissue, which results in less scarring due to its antifibrotic effect. Thus, HGF supplementation through gene therapy may be an effective strategy for treating wounds, as it increases the regeneration of the dermis to allow for "scarless wound healing."

DOI PubMed

Combined administration of basic fibroblast growth factor protein and the hepatocyte growth factor gene enhances the regeneration of dermis in acute incisional wounds

Ono, I, T Yamashita, T Hida, HY Jin, Y Ito, H Hamada, Y Akasaka, T Ishii, K Jimbow

WOUND REPAIR AND REGENERATION ( BLACKWELL PUBLISHING INC )  12 ( 1 ) 67 - 79  2004年01月  [査読有り]

　概要を見る

Hepatocyte growth factor (HGF) is a ligand for the c-Met receptor tyrosine kinase. This study was aimed to characterize the role of the HGF gene combined with basic fibroblast growth factor (bFGF) protein in wound healing by administering both of them locally to acute incisional skin wounds created on the backs of rats. The bFGF protein and the HGF gene were administered intradermally after incisional surgery. Apoptotic cells in wound lesions were identified by the terminal deoxynucleotide transferase-mediated nick-end labeling method, as well as by immunological detection of active caspase-3. While there was almost complete suppression of apoptosis with well-organized wound healing in animals treated with the HGF gene, the combination of bFGF protein and the HGF gene paradoxically resulted in less scarring along with the promotion of apoptosis. Histopathological examination revealed that scar formation was least apparent in rats treated with both bFGF and the HGF gene compared with controls or those treated with the bFGF or the HGF gene alone. It is thought that the combined administration of bFGF and the HGF gene immediately after skin incision may make the healing process occur closer to tissue regeneration through the induction of apoptosis, which occurred 1 week after surgery. HGF supplementation through gene therapy combined with bFGF protein may be an effective strategy for treating wounds, as it increases the apparent regeneration of the dermis to allow for "scarless wound healing."

DOI PubMed

Carney complex: report of a Japanese case associated with cutaneous superficial angiomyxomas, labial lentigines, and a pituitary adenoma.

Hiroyuki Takahashi, Tokimasa Hida

The Journal of dermatology   29 ( 12 ) 790 - 6  2002年12月  [査読有り]  [国際誌]

　概要を見る

We report the case of a 12-year-old female patient who manifested multiple cutaneous angiomyxomas and labial pigmented lesions. Although the familial history was not confirmed in the present case, autosomal dominant inheritance has been reported to be involved in the pathogenesis of this condition. In addition to the cutaneous complications, magnetic resonance (MR) images revealed the presence of a pituitary adenoma, which provoked an elevation of serum growth hormone (GH) level. On the other hand, no significant symptoms such as cardiac myxoma, myxoid fibroadenoma of the breast, or adrenocortical complaints suggesting Cushing syndrome, were detected. In the Japanese literature, only a few cases of this disorder have been described in the form of brief reports. There have been only a few similar cases described in the dermatological field, except for one report diagnosed as Carney complex in 1990. Therefore, the present case seems to be the first Japanese case of typical Carney complex manifesting major clinical complications, including angiomyxomas, lentigines, and a pituitary adenoma, which induced endocrine overactivity.

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