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1.
J Dermatol ; 29(1): 33-7, 2002 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11837572

RESUMO

The patient was a 54-year-old Japanese man with a seven-month history of an eroded lesion on the scrotum. Skin biopsy confirmed the diagnosis of extramammary Paget's disease, and a CT scan revealed multiple metastases to the lymph nodes along the iliac artery and aorta. The patient underwent combination chemotherapy with mitomycin C, epirubicin, vincristine, cisplatin, and 5-fluorouracil. After two courses of the regimen, the primary lesions on the scrotum regressed, however, the lymph node metastases did not respond. A regimen of continuous administration of low-dose cisplatin and 5-fluorouracil was not effective for the metastases either. Hence, administration of docetaxel at a dose of 60 mg/m2/every four weeks was started. After two courses, the lymph node metastases decreased by 75% compared to the pre-treatment size, and the effect was judged a partial response. The major toxicities were neutropenia, alopecia, pitting edema, and facial erythema, but these were tolerable. Five courses of this regimen were followed by four courses of weekly administration of 25 mg/m2 docetaxel. The partial response persisted for more than 12 months and the patient was able to enjoy daily life. Docetaxel may be an effective drug for patients with advanced extramammary Paget's disease.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Paclitaxel/análogos & derivados , Paclitaxel/administração & dosagem , Doença de Paget Extramamária/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Taxoides , Cisplatino/administração & dosagem , Docetaxel , Esquema de Medicação , Epirubicina/administração & dosagem , Fluoruracila/administração & dosagem , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Doença de Paget Extramamária/diagnóstico por imagem , Doença de Paget Extramamária/secundário , Radiografia , Escroto , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/patologia , Vincristina/administração & dosagem
2.
Jpn J Cancer Res ; 93(8): 935-43, 2002 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12716472

RESUMO

Calponin h1 (CNh1) is a basic actin-binding protein that is abundantly expressed in smooth muscle cells and involved in smooth muscle contraction by inhibiting actomyosin MgATPase. In recent studies, CNh1 was noted to suppress cell proliferation and tumorigenicity in leiomyosarcoma and tumor growth in fibrosarcoma cell lines. To further investigate the function of CNh1 as a tumor suppressor, we transfected the human CNh1 gene into a v-src-transformed rat fibroblast cell line SR-3Y1. The volume of the tumors derived from one randomly selected CNh1-transfectant (C1) in nude mice was reduced to 34.1% of that from a randomly selected vector transfectant (V1). A similar tendency was observed in another independent pair (C2, V2). Pathological analysis showed a significant decrease in the number of mitotic cells in the CNh1-transfectants. Further, a marked reduction in the number of vessels in the CNh1-transfectant was observed. DNA synthesis under conditions without serum was significantly reduced in the CNh1-transfectant (C1) compared with the control transfectant (V1), while no significant difference was seen in the cellular growth in the presence of 10% serum. A slight but significant reduction in in vitro cellular motility in the CNh1-transfectant was also observed. While the suppression of growth potential and cell motility by CNh1 transfer was significant but partial, a marked reduction in vascular endothelial growth factor (VEGF) mRNA and the secretion of VEGF protein was observed in the CNh1-transfectant. These results suggest that CNh1 plays a role as tumor suppressor in SR-3Y1 mainly by decreasing VEGF expression and angiogenesis in vivo and partially through reducing cellular proliferative potential and cell motility.


Assuntos
Proteínas de Ligação ao Cálcio/fisiologia , Neovascularização Patológica , Animais , Western Blotting , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas de Ligação a Calmodulina/metabolismo , Divisão Celular , Linhagem Celular Transformada , Movimento Celular , Fatores de Crescimento Endotelial/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Linfocinas/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteínas dos Microfilamentos , Transplante de Neoplasias , RNA Mensageiro/metabolismo , Ratos , Transdução de Sinais , Fatores de Tempo , Transfecção , Células Tumorais Cultivadas , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio Vascular , Calponinas
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