Severe obesity may be associated with significant perioperative respiratory complications. This article reviews potential respiratory and sleep complications, screening, and management of these problems.”
“Dasatinib is approved for the treatment of chronic myeloid leukemia (CML) in patients with resistance or intolerance to imatinib. This article reviews pharmacokinetic, pharmacodynamic, and clinical data on dasatinib, and highlights some of the most important issues that need to be addressed.
Imatinib and Autophagy inhibitor dasatinib both target the tyrosine kinase activity of the BCR/ABL oncogenic fusion protein. In terms of pharmacodynamics, the two agents differ in several ways: (i) dasatinib is >300-fold more potent than imatinib
in inhibiting BCR/ABL activity; (ii) inhibition profiles on other tyrosine kinases differ between imatinib and dasatinib; and (iii) dasatinib has other peculiar effects on the leukemogenic signaling, including activation of p38 mitogen-activated protein kinase (MAPK) and reduction of the apoptotic-inactive form of the BCL2-associated agonist of cell death (BAD) protein.
Recent pharmacodynamic data suggested combination therapy with dasatinib and PFTα mouse signaling inhibitors (e.g. flavopiridol, farnesyl transferase inhibitors, or histone deacetylase inhibitors) may be beneficial.
In contrast to other tyrosine kinase inhibitors (TKIs), dasatinib has a reduced half-life and no active metabolites.
In a randomized, open-label, phase III trial, dasatinib 100 mg once daily Selleck AZD1208 demonstrated similar efficacy and a better tolerability profile than 70 mg twice daily. This unexpected result has been confirmed in recent studies, in which a dose of dasatinib 100 mg once daily was sufficient to trigger apoptosis in leukemic cells. Furthermore, cytogenetic responses correlate with BCR/ABL inhibition.
Data suggest dasatinib 100 mg once daily achieves oncogenic shock and chronic inhibition of BCR/ABL activity, suggesting that in the future, pulse therapy with TKIs may be an option in some specific patients with CML.”
“The epithelial-to-mesenchymal transition (EMT) is a developmental
programme that regulates embryonic morphogenesis and involves significant morphological and molecular changes in cells. Experimental models have revealed that EMT also contributes to various malignant features of cancer cells, including motile, invasive, anti-apoptotic and stem-like phenotypes. Clinically, correlative studies have indicated that mesenchymal-like features of tumour cells are associated with poor tumour differentiation as well as worse patient prognosis. Nevertheless, due to its transitory nature, demonstration of an actual occurrence of EMT during human carcinogenesis is challenging, and most of the evidence to date has been limited to breast and colorectal cancers. However, recent studies suggest that EMT may occur during lung cancer development, although such evidence is still limited.