Thioredoxin (Trx) is a multifunctional redox protein that has growth‐promoting and anti‐apoptotic effects on cells and protects cells from endogenous and exogenous free radicals. Recently, altered expression of Trx has been reported in various cancers. In the present study, we investigated altered expression of Trx at the precancerous and carcinogenic phases during cholangiocarcinogenesis in a hamster cholangiocarcinoma (ChC) model, using semiquantitative immunohistochemical and Western blot analyses. Moreover, to determine if the results correlated well with those in human ChCs, we carried out a comparative immunohistochemical study for Trx in tissue‐arrayed human ChCs with different grades of tumor cell differentiation. Trx was found highly expressed in the cytoplasm of dysplastic bile ducts with highly abnormal growth patterns and ChCs irrespective of tumor type or tumor cell differentiation. Overexpression of Trx at the precancerous and carcinogenic phases was further supported by significant elevation of Trx protein in Western blotting. The results from the hamster ChCs were in good agreement with those from human ChCs. Our results strongly suggested that the redox regulatory function of Trx plays an important role in bile duct cell transformation and tumor progression during cholangiocarcinogenesis. (Cancer Sci 2009)

ABSTRACT. We report the first case of a primary subcutaneous leiomyosarcoma that originated in the hind leg of a hamster and metastasized to the bone marrow, lung and diaphragm. A 10-month-old female Syrian golden hamster was presented with a large, firm, white subcutaneous mass in the right hind leg. The tumor invaded into the bone marrow and small nodules were also present in the lung and diaphragm; however, no tumor masses were found in the visceral organs. Histologically, the tumors were spindle cell sarcomas, composed of densely packed pleomorphic spindle cells with oval to elongate nuclei and moderate amounts of eosinophilic cytoplasm. Immunohistochemically, the neoplastic cells were positive for vimentin, desmin, and smooth muscle actin, but negative for α-sarcomeric actin and S-100. Thus, the diagnosis was primary leiomyosarcoma of the hind leg with metastasis to the bone marrow, lung and diaphragm. To the best of our knowledge, this is the first report of spontaneous primary subcutaneous leiomyosarcoma of the hind leg with distant metastasis in laboratory animals. KEY WORDS: hamster, hind leg, subcutaneous leiomyosarcoma.J. Vet. Med. Sci. 70(5): 517-520, 2008 Leiomyosarcoma is a malignant tumor of smooth muscle origin, characterized by broad interlacing fascicles of spindle-shaped neoplastic cells with elongate nuclei and eosinophilic cytoplasm. Leiomyosarcoma also shows malignant phenotypes such as pleomorphism, invasion, a relatively high mitotic index, necrosis, and metastasis [6]. This smooth muscle cell tumor may occur at any site in the body, because smooth muscle cells are widely distributed in every tissue and organ. Visceral organs, especially the gastrointestinal tract, spleen, and genital tract, have been shown to be relatively common sites for spontaneous leiomyosarcoma in domestic and experimental animals [5,10,12,13,15,18,21]. Leiomyosarcoma rarely occurs in other organs; only a few cases of leiomyosarcoma in the oral cavity, esophagus, and urinary bladder have been reported in domestic animals and mice [4,6,11,15,17].Cutaneous or subcutaneous leiomyosarcoma is extremely rare in animals. Although it has been reported infrequently in dogs, cats, ferrets, and monkeys [2,3,6,14,16], there have been no reports in laboratory animals. The cutaneous or subcutaneous development of this tumor usually occurs on the head or neck as a solitary dermal mass in animals, and metastasis is uncommon [6,14].In the present study, we describe a case of primary leiomyosarcoma in the hind leg of a hamster, which metastasized to the bone marrow, lung and diaphragm.The 10-month-old female Syrian golden hamster presented in this study was housed at the animal facility of Kangwon National University and had been used for breeding. The hamster exhibited ataxia and behavioral coordination failure as a result of a large mass in the right hind leg.The hamster was sacrificed under ether anesthesia, and necropsy revealed a firm, whitish, large mass, measuring 50 × 50 mm, in the subcutaneous region of the hind leg, surr...