Therapy of Core Binding Factor Acute Myeloid Leukemia: Incremental Improvements Toward Better Long-Term Results

BackgroundDespite being considered as good prognostic acute myelogenous leukemia (AML), the long-term survival rate in core binding factor (CBF) AML leaves room for substantial improvement.Materials and MethodsWe reviewed relevant English language literature related to treatment of CBF AML available in PubMed. Review also included meeting abstracts.ResultsMulticycle high dose cytarabine in consolidation improves remission duration but larger groups report overall survival in the range of 40% to 50% at 5 years or longer.ConclusionsConcerted effort is needed toward improving outcomes in CBF AML through clinical trials and risk-adapted approach.     

DuCLOX-2/5 inhibition: a promising target for cancer chemoprevention

Cancer is a leading cause of death and major health concern worldwide. The animal and human studies support the presumption that inflammation directs the cancer initiation and progression. Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) are the key players in the inflammatory cascade contributing towards the angiogenesis, tumor cell invasiveness, and disruption in the pathways of cellular proliferation/apoptosis. Contemporary studies have particularized a promising role of COX-2 and 5-LOX inhibitors in cancer chemoprevention. The present review is a pursuit to define implications of dual COX-2 and 5-LOX (DuCLOX-2/5) inhibition on various aspects of cancer augmentation and chemoprevention.     

Resistant Hypertension

Hypertension affects 25 % of all adults worldwide and is a leading risk factor contributing to 62 % of all strokes and 49 % of all cases of heart disease, leading to an estimated 7.1 million deaths a year; equivalent to 13 % of total worldwide deaths. In spite of therapeutic advances, up to 30 % of hypertensive individuals fail to achieve goal blood pressure even with the use of three antihypertensive medications. Resistant hypertension (RH) is a common clinical problem faced by physicians and the incidence is increasing as the population becomes heavier and older. The diagnosis and treatment of RH, is often accompanied by other risk factors such as obesity, sleep apnea, diabetes and chronic kidney disease is important because of the associated increased end organ damage and the subsequent clinical and social impact. Pseudo resistance, lack of blood pressure control due to poor medication adherence or white coat hypertension must be excluded. A successful treatment of RH requires identification of contributing lifestyle factors and eliminating them including the use of multidrug therapy. A potential genetic causes of RH have not been well studied. African American (black) race and certain other ethnic groups are associated with higher prevalence of RH and also poor response to therapy. Studies on RH are limited, in part because of difficulties in enrolling large groups of patients and patient comorbidity, higher cardiovascular risk and other diseases, e.g. sleep apnea, diabetes and chronic kidney disease that can confound the interpretation of study results. This review provides an overview of RH, and its association with risk factors, various ethnic groups, diagnosis and treatment modalities of RH with special emphasis on the relations of the latter with race/ethnicity.     

Cardiac MRI in the management of congenital heart disease in children, adolescents, and young adults

Recent advances in MRI have made this modality an important tool for evaluating heart disease. Faster scanning techniques, high spatial resolution, lack of ionizing radiation, lack of dependence on contrast material, and capability for functional imaging have made it an emerging noninvasive diagnostic tool with great potential in younger patients with heart disease. This article discusses the role of cardiac MRI, methods of evaluation, and newer application of MRI in evaluating congenital heart disease in pediatric and young adult patients.     

Dipole tensor-based atomic-resolution structure determination of a nanocrystalline protein by solid-state NMR

Magic-angle spinning (MAS) solid-state NMR (SSNMR) techniques have emerged in recent years for solving complete structures of uniformly labeled proteins lacking macroscopic order. Strategies used thus far have relied primarily on semiquantitative distance restraints, analogous to the nuclear Overhauser effect (NOE) routinely used in solution NMR. Here, we present a complementary approach for using relative orientations of molecular fragments, determined from dipolar line shapes. Whereas SSNMR distance restraints typically have an uncertainty of approximately 1 A, the tensor-based experiments report on relative vector (pseudobond) angles with precision of a few degrees. By using 3D techniques of this type, vector angle (VEAN) restraints were determined for the majority of the 56-residue B1 immunoglobulin binding domain of protein G [protein GB1 (a total of 47 HN-HN, 49 HN-HC, and 12 HA-HB restraints)]. By using distance restraints alone in the structure calculations, the overall backbone root-mean-square deviation (bbRMSD) was 1.01 +/- 0.13 A (1.52 +/- 0.12 A for all heavy atoms), which improved to 0.49 +/- 0.05 A (1.19 +/- 0.07 A) on the addition of empirical chemical shift [torsion angle likelihood obtained from shift and sequence similarity (TALOS)] restraints. VEAN restraints further improved the ensemble to 0.31 +/- 0.06 A bbRMSD (1.06 +/- 0.07 A); relative to the structure with distances alone, most of the improvement remained (bbRMSD 0.64 +/- 0.09 A; 1.29 +/- 0.07 A) when TALOS restraints were removed before refinement. These results represent significant progress toward atomic-resolution protein structure determination by SSNMR, capabilities that can be applied to a large range of membrane proteins and fibrils, which are often not amenable to solution NMR or x-ray crystallography.