PURPOSE To investigate whether signaling pathways that incorporate protein tyrosine kinases and phosphatases regulate PKC-sensitive, volume-sensitive Cl(-) currents (I(Cl,vol)) in cultured rabbit nonpigmented ciliary epithelial cells. METHODS Activation of I(Cl,vol) in response to hyposmotic stimulation was recorded with whole-cell patch-clamp techniques in the presence of pharmacologic agent...

The early stage of chronic myelogenous leukemia (CML) is caused by the tyrosine kinase Bcr-Abl. Imatinib mesylate (also known as STI-571 and Gleevec), a tyrosine kinase inhibitor, has shown encouraging results in CML clinical trials and has become a paradigm for targeted cancer therapeutics. Recent reports of resistance to imatinib argue for further development of therapies for CML. During stud...

objective(s):higher cellular reactive oxygen species (ros) levels is important in reducing cellular energy charge (ec) by increasing the levels of key metabolic protein, and nitrosative modifications, and have been shown to damage the cardiac tissue of diabetic mice. however, the relation between energy production and heart function is unclear. materials and methods:streptozotocin (stz, 150 mg/...

The epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) erlotinib improves survival of lung cancer as second- or third-line therapy. However, after an initial response, most patients will recur, particularly within the central nervous system. The present study reports the case of a 27-yr-old nonsmoking male presenting with a metastatic lung adenocarcinoma with EGFR exon 19 del...

Chronic myelogenous leukemia (CML) can be controlled for years with the tyrosine kinase inhibitor imatinib but because imatinib poorly penetrates the blood-brain barrier (BBB), on occasion, the CML clone will thrive and evolve to an accelerated phase in the resulting imatinib sanctuary within the central nervous system. In this, CML resembles glioblastoma in that imatinib, which otherwise may b...

Leflunomide is an immunosuppressive drug capable of inhibiting T and B cell responses in vivo. A number of studies demonstrate that leflunomide functions both as a pyrimidine synthesis inhibitor and as a tyrosine kinase inhibitor. We previously reported that leflunomide inhibits LPS-stimulated B cell proliferation, cell cycle progression, and IgM secretion. This inhibition can be reversed by th...

Mantle cell lymphoma is an aggressive B-cell malignancy. Current frontline chemoimmunotherapies produce high response rates but relapse inevitable. Furthermore, the elderly and those with comorbidities are precluded from standard regimens stem transplant, leaving them limited options. Targeted therapies, including Bruton tyrosine kinase inhibitors, effective treatment strategy in mantle lymphom...

Abscisic acid (ABA) induces a rapid and transient mitogen-activated protein (MAP) kinase activation in barley aleurone protoplasts. MAP kinase activity, measured as myelin basic protein phosphorylation by MAP kinase immunoprecipitates, increased after 1 min, peaked after 3 min, and decreased to basal levels after ~5 min of ABA treatment in vivo. Antibodies recognizing phosphorylated tyrosine re...

conclusions despite the fact that abnormalities in p53 and p27kip1 may be involved in the development of oscc, their clinical significance in the studied population seems limited. further investigation on the combined p53/p27kip1 expression may be helpful in predicting the biologic behavior of this tumor. results p53 and p27kip1 expression were found in 28.57% (8 positive versus 20 negative) an...

HER2-targeted therapy has moved beyond trastuzumab to include other monoclonals targeting the cell surface, receptor tyrosine kinase inhibitors of HER2, and antibody-drug conjugates. Afatinib, a small molecule receptor tyrosine kinase inhibitor, now joins the ranks of HER2-targeting agents in combination with trastuzumab. The combination brings new opportunities and challenges.