Canine inflammatory mammary carcinoma (CIMC) similar to human inflammatory breast cancer is a very aggressive, metastatic type of cancer. Previous studies have introduced a new type of tumor angiogenesis called vasculogenic mimicry that may play an important role in the progression of inflammatory mammary cancer. The purpose of this study is to investigate the development process of vessels by neoplastic cells in CIMC. Patient dog, 14-year old Shit-Tzu female, had a hard and somewhat movable dark-reddish mammary tumor, sized 6.2 cm in diameter. Bloody dark turbid exudate was released from the tumor. In addition to histological examination, immunohistochemistry for pancytokeratin, VCAM-1, MECA- 32, TWIST-1, and Ki-67 was respectively performed using the ABC method. Histologically, the inflammatory mammary carcinoma was characterized by tubular solid tumor emboli within the lymphatic vessels surrounded by desmoplastic fibrous connective tissue. Some of the neoplastic cells were transforming into elongate or spindle shapes and forming small vessel-like structures in the solid tumor mass. The neoplastic cells were immunoreactive for VCAM-1 and MECA-32, but showed low immunoreactivity for Ki-67. Immunoreactive neoplastic cells for VCAM-1 and MECA-32 suggested the possibility that the neoplastic cells transform into endothelial cells of vessels by epithelial-mesenchymal transition, further supported by serial morphological changes identified by histological investigation and immunohistochemistry for TWIST-1. The high capacity of the neoplastic cells forming the vasculatures in CIMC explains the high ratio of metastasis to other regions, even though Ki-67 index was not so high.

Curcumin (diferuloylmethane), a constituent of turmeric powder derived from the rhizome of Curcuma longa, has been shown to inhibit the growth of various types of cancer cells by regulating cell proliferation and apoptosis. However, a need exists to design more effective analogs because of curcumin's poor intestinal absorption. EF-24 (diphenyl difluoroketone), the monoketone analog of curcumin, has shown good efficacy in anticancer screens. However, the effects of curcumin and EF-24 on salivary gland epidermoid carcinoma cells are not clearly established. The main goal of this study was to investigate the effects of curcumin and EF-24 on cell growth and induction of apoptosis in human salivary gland epidermoid carcinoma cells. Our studies showed that curcumin and EF-24 inhibited the growth of HTB-41 cells in a dose- and time-dependent manner, and the potency of EF-24 was > 34-fold that of curcumin. Treatment with curcumin or EF-24 resulted in nuclear condensation and fragmentation in HTB-41 cells, whereas the control HTB-41 cell nuclei retained their normal regular and oval shape. Curcumin and EF-24 promoted proteolytic cleavages of procaspase-3/-7/-9, resulting in an increase in the amount of cleaved caspase-3/-7/-9 in the HTB-41 cells. Caspase-3 and -7 activities were detected in viable HTB-41 cells treated with curcumin or EF-24. These results suggest that the curcumin and EF-24 inhibit cell proliferation and induce apoptosis in HTB-41 human salivary gland epidermoid carcinoma cells, and that they may have potential properties as an anti-cancer drug therapy.