Acute Myeloid Leukemia: Focus on Novel Therapeutic Strategies

Acute myeloid leukemia (AML) is a heterogeneous disease with variable clinical outcomes. Cytogenetic analysis reveals which patients may have favorable risk disease, but 5-year survival in this category is only approximately 60%, with intermediate and poor risk groups faring far worse. Advances in our understanding of the biology of leukemia pathogenesis and prognosis have not been matched with clinical improvements. Unsatisfactory outcomes persist for the majority of patients with AML, particularly the elderly. Novel agents and treatment approaches are needed in the induction, post-remission and relapsed settings. The additions of clofarabine for relapsed or refractory disease and the hypomethylating agents represent recent advances. Clinical trials of FLT3 inhibitors have yielded disappointing results to date, with ongoing collaborations attempting to identify the optimal role for these agents. Potential leukemia stem cell targeted therapies and treatments in the setting of minimal residual disease are also under investigation. In this review, we will discuss recent advances in AML treatment and novel therapeutic strategies

The Composition of Cosmic Rays at the Knee

The observation of a small change in spectral slope, or 'knee' in the fluxes of cosmic rays near energies 10^15 eV has caused much speculation since its discovery over 40 years ago. The origin of this feature remains unknown. A small workshop to review some modern experimental measurements of this region was held at the Adler Planetarium in Chicago, USA in June 2000. This paper summarizes the results presented at this workshop and the discussion of their interpretation in the context of hadronic models of atmospheric airshowers.Comment: 36 pages, 10 figure

Charged particle production in the Pb+Pb system at 158 GeV/c per nucleon

Charged particle multiplicities from high multiplicity central interactions of 158 GeV/nucleon Pb ions with Pb target nuclei have been measured in the central and far forward projectile spectator regions using emulsion chambers. Multiplicities are significantly lower than predicted by Monte Carlo simulations. We examine the shape of the pseudorapidity distribution and its dependence on centrality in detail.Comment: 17 pages text plus 12 figures in postscript 12/23/99 -- Add TeX version of sourc

Fundamental sputtering studies: Nonresonant ionization of sputtered neutrals

Because of the practical importance of sputtering, numerous theories and computer simulations are used for predicting many aspects of the sputtering process. Unfortunately, many of the calculated sputtering results are untested by experiment. Until recently, most sputtering experiments required either very high ion fluences or the detection of only minor constituents of the sputtered flux, i.e., ions. These techniques may miss the subtleties involved in the sputtering process. High-detection-efficiency mass spectrometry, coupled with the laser ionization of neutral atoms, allows the detection of the major sputtered species with very low incident ion fluences. The depth-of-origin of sputtered atoms is one example of an important but poorly understood aspect of the sputtering process. By following the sputtering yield of a substrate atom with various coverages of an adsorbed overlayer, the depth of origin of sputtered atoms has been determined. Our results indicate that two-thirds of the sputtered flux originates in the topmost atomic layer. The ion-dose dependence of sputtering yields has long been assumed to be quite minor for low- to-moderate primary ion fluences. We have observed a two-fold decrease in the sputtering yield of the Ru(0001) surface for very low primary ion fluences. Data analysis results in a cross section for damage of 2.7 {plus minus} 1.0 {times} 10{sup {minus}15}cm{sup 2}. 40 refs., 3 figs., 2 tabs

Role of genetic testing for inherited prostate cancer risk: Philadelphia prostate cancer consensus conference 2017

Purpose: Guidelines are limited for genetic testing for prostate cancer (PCA). The goal of this conference was to develop an expert consensus-dri

RANTES/CCL5 and risk for coronary events: Results from the MONICA/KORA Augsburg case-cohort, Athero-express and CARDIoGRAM studies

Background: The chemokine RANTES (regulated on activation, normal T-cell expressed and secreted)/CCL5 is involved in the pathogenesis of cardiovascular disease in mice, whereas less is known in humans. We hypothesised that its relevance for atherosclerosis should be reflected by associations between CCL5 gene variants, RANTES serum concentrations and protein levels in atherosclerotic plaques and risk for coronary events. Methods and Findings: We conducted a case-cohort study within the population-based MONICA/KORA Augsburg studies. Baseline RANTES serum levels were measured in 363 individuals with incident coronary events and 1,908 non-cases (mean follow-up: 10.2±

Vascular Remodeling in Health and Disease

The term vascular remodeling is commonly used to define the structural changes in blood vessel geometry that occur in response to long-term physiologic alterations in blood flow or in response to vessel wall injury brought about by trauma or underlying cardiovascular diseases.1, 2, 3, 4 The process of remodeling, which begins as an adaptive response to long-term hemodynamic alterations such as elevated shear stress or increased intravascular pressure, may eventually become maladaptive, leading to impaired vascular function. The vascular endothelium, owing to its location lining the lumen of blood vessels, plays a pivotal role in regulation of all aspects of vascular function and homeostasis.5 Thus, not surprisingly, endothelial dysfunction has been recognized as the harbinger of all major cardiovascular diseases such as hypertension, atherosclerosis, and diabetes.6, 7, 8 The endothelium elaborates a variety of substances that influence vascular tone and protect the vessel wall against inflammatory cell adhesion, thrombus formation, and vascular cell proliferation.8, 9, 10 Among the primary biologic mediators emanating from the endothelium is nitric oxide (NO) and the arachidonic acid metabolite prostacyclin [prostaglandin I2 (PGI2)], which exert powerful vasodilatory, antiadhesive, and antiproliferative effects in the vessel wall