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International journal of dermatology 03/2013; · 1.18 Impact Factor
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ABSTRACT: BACKGROUND: Angiosarcoma is one of the most life-threatening neoplasms with strong resistance to conventional chemotherapy/radiotherapy; consequently, alternative therapeutic agents are urgently required. One factor in delaying the therapy development is the limitation of experimental models. OBJECTIVE: We established a novel experimental angiosarcoma model. METHODS: From surgically resected tissue, human AS cell line was established. Using xenograft of AS cell line, we performed therapeutic experiments with the anti-human VEGF Ab or the receptor tyrosine kinase inhibitor. RESULTS: First we generated an angiosarcoma cell line, HAMON (human angiosarcoma, monoclonal), which expresses CD31 and produces tumors in immunodeficient mice. HAMON expresses VEGFR2 and that exogenous VEGF leads to HAMON proliferation in vitro. Anti-human VEGF Ab bevacizumab treatment failed to suppress HAMON proliferation in vitro and in vivo. Furthermore, the receptor tyrosine kinase inhibitor sunitinib did not suppress HAMON proliferation in vitro. Similarly, in in vivo therapeutic experiments, even high doses of sunitinib failed to inhibit tumor growth. Finally, we checked whether compensatory activation of VEGF signaling occurred after sunitinib addition. VEGF protein secretion, VEGF mRNA synthesis and VEGFR2 phosphorylation all were unaffected in HAMON after sunitinib treatment. CONCLUSION: A novel in vitro and in vivo experimental model of human angiosarcoma has been successfully established. With this model, we were able to perform therapeutic experiments. In addition, our angiosarcoma cell line, HAMON, is quite useful for identifying key molecules in angiosarcoma.
Journal of dermatological science 03/2013; · 3.71 Impact Factor
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International journal of dermatology 12/2012; 51(12):1520-2. · 1.18 Impact Factor
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ABSTRACT: To determine the beneficial effect of maintenance therapy in stage II and III melanoma by sequential local injection of low-dose interferon-β.
We reviewed 46 patients with stage II and III primary melanoma at our institution from 2004 through 2009. Twenty-one patients were treated with interferon-β maintenance therapy consisting of subcutaneous injection of natural interferon-β at a dose of 3 × 10(6) IU/day for 10 consecutive days, and 25 patients underwent observation alone.
Compared with all patients, overall survival and relapse-free survival were significantly worse in the observation group than in the interferon-β group (p = 0.024 and 0.029, respectively). In stage II, a significant difference in overall survival, but not in relapse-free survival, was seen between the two groups (p = 0.041). When the interferon-β group was stratified by subgroup, there was a statistical difference only between dosage and duration (p = 0.027 and p < 0.001, respectively).
This study demonstrates that maintenance therapy by interferon-β is beneficial in the outcome of the disease without substantial toxic effects, especially in patients with stage II melanoma. Extension of the duration of treatment beyond 2 years could further improve the therapeutic efficacy of interferon-β.
Oncology 03/2012; 82(3):139-46. · 2.27 Impact Factor
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Kazuhiro Kikuchi,
Riichiro Abe,
Satoru Shinkuma,
Erika Hamasaka,
Ken Natsuga, Hiroo Hata,
Yasuki Tateishi,
Masahiko Shibata,
Yuki Tomita,
Yukiko Abe,
Satoru Aoyagi,
Makio Mukai,
Hiroshi Shimizu
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ABSTRACT: Infantile myofibromatosis is a rare fibrous tumor of infancy. The cutaneous solitary type has typically an excellent prognosis. However, histologically, it is important to rule out leiomyosarcoma, which has a poor prognosis. The low frequency of mitosis was definitive for a diagnosis of infantile myofibromatosis. We present a cutaneous solitary-type case of infantile myofibromatosis. Following incisional biopsy, the tumor remitted spontaneously.
Case Reports in Dermatology 01/2011; 3(2):181-5.
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Acta Dermato-Venereologica 09/2010; 90(5):539-40.
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Acta Dermato-Venereologica 07/2010; 90(4):440-1.
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ABSTRACT: In some countries, intraoperative histological evaluation to control the surgical margin for non-melanoma skin cancer is widely used instead of Mohs micrographic surgery. Nevertheless, this evaluation by frozen section analysis is usually limited to suspicious areas.
To evaluate the efficacy of double-bladed scalpel for intraoperative histological margin control for non-melanoma skin cancers.
Between 2005 and 2009, 10 basal cell carcinomas and 5 squamous cell carcinomas were underwent complete histological margin control in which a double-bladed scalpel was used during the surgery at the Hokkaido University Hospital in Japan.
The mean number of re-excisions required for complete tumor resection was 1.4 times. Nine (60%) of the 15 patients obtained histological clearance of all surgical margins at the first re-excision. The mean size of total surgical margin was 6.1 mm (range: 2-12 mm). The median time from the first tumor excision to reconstruction was 124 min. No local recurrences have been reported.
This method may be used as an alternative for complete histological margin control at many hospitals where it is difficult to perform Mohs micrographic surgery.
Journal of Surgical Oncology 02/2010; 101(2):175-9. · 2.10 Impact Factor
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Journal of Cutaneous Pathology 09/2009; 36(8):919-21. · 1.56 Impact Factor
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Toshifumi Nomura,
Masashi Akiyama,
Aileen Sandilands,
Ikue Nemoto-Hasebe,
Kaori Sakai,
Akari Nagasaki,
Mitsuhito Ota, Hiroo Hata,
Alan T Evans,
Colin N A Palmer,
Hiroshi Shimizu,
W H Irwin McLean
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ABSTRACT: Mutations in the gene encoding filaggrin (FLG) have been identified as the cause of ichthyosis vulgaris (IV) and shown to be major predisposing factors for atopic dermatitis (AD). However, these studies have been mainly carried out in European populations. In early 2007, we identified two Oriental-specific FLG mutations in four Japanese families with IV and reported that filaggrin mutations were also significant predisposing factors for AD in Japan. However, the frequency of FLG mutations observed in our Japanese AD cohort (5.6%), was much lower than that seen in Europeans (up to 48%). Here, we studied a further seven Japanese families with IV and identified two additional nonsense mutations in FLG, S2889X, and S3296X. We found that more than 20% of patients in our Japanese AD case series carry FLG mutations, and there is significant statistical association between the four mutations and AD (chi(2) P=8.4 x 10(-6); heterozygote odds ratio 7.57, 95% CI 2.84-23.03). These data emphasize that skin-barrier impairment due to reduced filaggrin expression plays an important role in the pathogenesis of AD and sheds further light on the genetic architecture of atopy in Japan.
Journal of Investigative Dermatology 07/2008; 128(6):1436-41. · 6.31 Impact Factor
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International journal of dermatology 04/2008; 47(3):302-4. · 1.18 Impact Factor
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Ken Natsuga,
Masashi Akiyama,
Naoko Kato,
Kaori Sakai,
Yoriko Sugiyama-Nakagiri,
Machiko Nishimura, Hiroo Hata,
Masataka Abe,
Ken Arita,
Yukiko Tsuji-Abe,
Takashi Onozuka,
Satoru Aoyagi,
Kazuo Kodama,
Hideyuki Ujiie,
Yuki Tomita,
Hiroshi Shimizu
Journal of Investigative Dermatology 12/2007; 127(11):2669-73. · 6.31 Impact Factor
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ABSTRACT: The relative incidence of malignant lymphoma subtypes differs according to geographic location. This study investigated the epidemiology of cutaneous lymphoma subtypes in Japan and compared it with other countries.
Sixty-two patients with cutaneous lymphoma attending the Department of Dermatology, National Hospital Organization Hokkaido Cancer Center were reviewed. The World Health Organization classification of hematopoietic and lymphoid malignancies was adopted.
Of the 62 patients, 31 had primary cutaneous lymphoma (PCL) and 31 had secondary cutaneous lymphoma (SCL). T- and natural killer (NK)-cell lymphoma accounted for 80% of PCL, of which, mycosis fungoides accounted for almost 35%. Of the 31 patients with secondary cutaneous lymphoma, 17 patients (54%) had T- and NK-cell lymphoma, including nine adult T-cell leukemia/lymphoma patients, and 14 patients (46%) had B-cell lymphoma, including 11 diffuse large B-cell lymphoma patients. The majority of patients with SCL and NK-cell lymphoma with primary or secondary skin lesions had a poor outcome.
PCL in this study showed a similar incidence to that of other institutions in Japan, while also demonstrating different frequencies from that of other countries, suggesting that the relative frequency of different PCL subtypes differ according to geographical location, similar to previous reports of systemic malignant lymphoma.
Journal of Cutaneous Pathology 08/2006; 33(7):487-91. · 1.56 Impact Factor
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Journal of the American Academy of Dermatology 05/2005; 52(4):729-31. · 3.99 Impact Factor
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Acta Dermato Venereologica 02/2004; 84(3):239-40. · 3.18 Impact Factor
