In addition, Endo II silencing also impaired HER2 internalization in response to Trastuzumab, and led to reduced cytotoxicity response in HER2+ cancer cells treated with T-DM1. Endo II silencing also led to decreased migration and invasion of HER2+ cancer cells in vitro, and impaired lung seeding following tail vein injection in mice. Stable silencing of Endo II in HER2+ cell lines led to elevated levels of HER2 on the cell surface, impaired epidermal growth factor-induced HER2 internalization, and reduced signaling to downstream effector kinases Akt and Erk. High Endo II protein expression was detected in HER2-positive tumors, and was linked to worse overall survival in node-positive HER2+ breast cancers at the mRNA level.
The effects of Endo II silencing on the responses of HER2+ cancer cells to trastuzumab or T-DM1 treatments were tested using real-time cell motility and cytotoxicity assays. Stable silencing of Endo II was achieved in HER2+ cancer cell lines (SK-BR-3 and HCC1954) to test Endo II effects on HER2 levels, localization and signaling, cell motility and tumor metastasis. MethodsĮndo II expression in human breast tumors and lymph node metastases were analyzed by immunohistochemistry. Here, we test the involvement of the endocytic adaptor protein endophilin A2 (Endo II) in HER2+ breast cancer models, and their responses to treatments with trastuzumab and T-DM1. However, resistance to these targeted therapies can develop and limit their efficacy. Targeted therapies involving the antibody trastuzumab and trastuzumab-emtansine (T-DM1) have greatly improved outcomes for HER2-positive (HER2+) breast cancer patients. Thus, there is a need to introduce appropriate control measures of livestock diseases to minimise the rate of infection and reduce economic losses.Human epidermal growth factor receptor-2 (HER2) is amplified and a clinical target in a subset of human breast cancers with high rates of metastasis. Because of their zoonotic nature, occurrences of hydatidosis, cysticercosis, fasciolosis and tuberculosis may pose a public health risk. Pneumonia was the leading cause of lung condemnations at the rates of 3.99%, 2.43% and 2.83% in cattle, sheep and goats, respectively. Ascariasis (4.03%) was the only cause of liver condemnation in pigs. The main cause of condemnations of cattle livers was fasciolosis (8.6%), while stilesiosis in sheep and goats accounted for 8.1% and 7.3%, respectively. Livers and lungs were the most condemned organs in all four animal species. Cysticercosis was the leading cause of total carcass condemnations in cattle (0.051%) and in pig (1.397%), while emaciation accounted for 0.045% and 0.074% of carcass condemnations in sheep and goats, respectively. Out of the slaughtered cattle, 8.6% were pregnant. The current study reviews a 3-year record of slaughtered animals in Arusha abattoir to determine the causes of carcasses and organ/offal condemnations.
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