The chemokine receptor CCR5 provides a portal of entry for human immunodeficiency virus type 1 (HIV-1) into susceptible CD4(+) cells. Both monoclonal antibody (MAb) and small-molecule CCR5 inhibitors have entered human clinical testing, but little is known regarding their potential interactions. We evaluated the interactions between CCR5 MAbs, small-molecule CCR5 antagonists, and inhibitors of ...

UNLABELLED Next-generation antiandrogen therapies, such as enzalutamide and abiraterone, have had a profound impact on the management of metastatic castration-resistant prostate cancer (mCRPC). However, mCRPC patients invariably develop resistance to these agents. Here, a series of clonal cell lines were developed from enzalutamide-resistant prostate tumor xenografts to study the molecular mech...

Over the past decade, the Hedgehog signaling pathway has attracted considerable interest because the pathway plays important roles in the tumorigenesis of several types of cancer as well as developmental processes. It has also been observed that Hedgehog signaling regulates the proliferation and self-renewal of cancer stem cells. A great number of Hedgehog pathway inhibitors have been discovere...

While MDM2 inhibitors hold great promise as cancer therapeutics, drug resistance will likely limit their efficacy as single agents. To identify drug combinations that might circumvent resistance, we screened for agents that could synergize with MDM2 inhibition in the suppression of cell viability. We observed broad and robust synergy when combining MDM2 antagonists with either MEK or PI3K inhib...

Introduction Case Physiology of Hemostasis Vasoconstriction Primary Hemostasis Platelet Adhesion Platelet Granule Release Reaction Platelet Aggregation and Consolidation Secondary Hemostasis: The Coagulation Cascade Regulation of Hemostasis Pathogenesis of Thrombosis Endothelial Injury Abnormal Blood Flow Hypercoagulability Pharmacologic Classes and Agents Antiplatelet Agents Cyclooxygenase Inh...

In the 1990s, serotonin receptor agonist 5-HT1B/1D (the triptans) became available on the market for migraine treatment. Although the triptans are highly effective in aborting migraine attacks, the vasoconstrictor effect in cerebral and coronary territory limits their use. In the “post-triptans” era, new molecules, without vasoactive components are about to expand migraine treatment armamentari...

Endothelins are potent peptide vasoconstrictors which were discovered two decades back. Their role in cardiovascular diseases, cancer, glaucoma, diabetes mellitus and many other diseases have been studied. Inspite of a lot of research many questions regarding their pathophysiological roles still remain unanswered. Though many endothelin receptor antagonists showed promising results in animal st...

Airway mucus hypersecretion is a significant clinical and pathological feature of chronic inflammatory airway diseases. Its clinical presentations include recurrent coughing and phlegm. Airway mucus is closely associated with the occurrence, development and prognosis of chronic inflammatory airway diseases and critically affects the lung function, quality of life, hospitalization rate and morta...

At present, a constant progress in pathophysiology understanding and treatment of the chronic heart failure (CHF) is arising. The current CHF pharmacotherapy is complex, involving factors affecting the renin-angiotensin-aldosterone system (RAAS), beta-blockers, diuretics and vasodilatators. There are also significant efforts to introduce in CHF pharmacology novel therapeutic strategies, based o...