Search results for "SELECTION"
showing 10 items of 1940 documents
Advances in haploidentical stem cell transplantation for hematologic malignancies
2016
One of the most important advances in allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the use of alternative donors and cell sources, such as haploidentical transplants (haplo-HSCT) from family donors. Several approaches have been developed to overcome the challenging bidirectional alloreactivity. We discuss these approaches, including ex vivo T-cell-depleted grafts with megadose of CD34(+) cells, not requiring immunosuppression after allogeneic transplantation for graft-versus-host disease (GVHD) prophylaxis, and other strategies using unmanipulated T-cell-replete grafts with intensive immunosuppression or post-transplantation cyclophosphamide to minimize the GVHD. We als…
The role of hypoxia-induced factors in tumor progression.
2004
Abstract Learning Objectives After completing this course, the reader will be able to: Describe hypoxia-induced mechanisms for cell survival. Discuss hypoxia-induced gene expression. Relate hypoxia and glucose metabolism. Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit atCME.TheOncologist.com Hypoxia is a common characteristic of locally advanced solid tumors that has been associated with diminished therapeutic response and, more recently, with malignant progression, that is, an increasing probability of recurrence, locoregional spread, and distant metastasis. Emerging evidence indicates that the effect of hypoxia on malignant progression is mediated by a…
RNA-sequencing and bioinformatic analysis to pre-assess sensitivity to targeted therapeutics in recurrent glioblastoma.
2019
e13533 Background: This study developed molecular guided tools for individualized selection of chemotherapeutics for recurrent glioblastoma (rGB). A consortium involving clinical neurooncologists, molecular biologists and bioinformaticians identified gene expression patterns in rGB and quantitatively analyzed pathways involved in response to FDA approved oncodrugs. Methods: From2016 to 2018 biopsies from GB were collected using a multisampling approach. Biopsy material was used to isolate glioma stem-like cells and examined by RNA-sequencing. RNA-seq results were subjected to differential expression (DE) analysis and Oncobox analysis – a bioinformatic tool for quantitative pathway activati…
The Fitness Effects of Random Mutations in Single-Stranded DNA and RNA Bacteriophages
2009
Mutational fitness effects can be measured with relatively high accuracy in viruses due to their small genome size, which facilitates full-length sequencing and genetic manipulation. Previous work has shown that animal and plant RNA viruses are very sensitive to mutation. Here, we characterize mutational fitness effects in single-stranded (ss) DNA and ssRNA bacterial viruses. First, we performed a mutation-accumulation experiment in which we subjected three ssDNA (ΦX174, G4, F1) and three ssRNA phages (Qβ, MS2, and SP) to plaque-to-plaque transfers and chemical mutagenesis. Genome sequencing and growth assays indicated that the average fitness effect of the accumulated mutations was similar…
Experimental evolution of an oncolytic vesicular stomatitis virus with increased selectivity for p53-deficient cells
2014
Experimental evolution has been used for various biotechnological applications including protein and microbial cell engineering, but less commonly in the field of oncolytic virotherapy. Here, we sought to adapt a rapidly evolving RNA virus to cells deficient for the tumor suppressor gene p53, a hallmark of cancer cells. To achieve this goal, we established four independent evolution lines of the vesicular stomatitis virus (VSV) in p53-knockout mouse embryonic fibroblasts (p53-/- MEFs) under conditions favoring the action of natural selection. We found that some evolved viruses showed increased fitness and cytotoxicity in p53-/- cells but not in isogenic p53+/+ cells, indicating gene-specifi…
Pharmacogenomics: a tool to prevent and cure coronary heart disease.
2007
Inflammation and genetics play an important role in the pathogenesis of coronary heart disease (CHD). This is supported by epidemiological studies which have thoroughly investigated the association between CHD and gene polymorphisms of the inflammatory molecules. Moreover, efforts to find elective therapy have not been rewarding and, despite the increasing appreciation of the role of genetics in CHD and myocardial infarction (MI) pathogenesis, pharmacogenomic approaches to uncover drug target have not been extensively explored. A critical search of published literature has suggested few inflammatory genes directly involved in the risk to develop CHD and MI. The selected genes are, the pro- …
Selection and Gratitude: Anonymity and gratitude
2018
What kind of candidate is selected into a job when the principal has to appoint a committee to measure the candidate's ability and select a winner through a call specifying a wage for the job? In a model where the principal fixes the wage anticipating the committee's choice, under a rather natural assumption about the committee's objective we find that if the committee takes into account the candidate's gratitude a candidate with less than first best ability will be selected in equilibrium. First best selection is achieved if the committee is anonymous to the candidates. If the committee could also set the wage the first best candidate would be selected, but the principal would be worse off…
OFN Capital Budgeting Under Uncertainty and Risk
2017
The aim of this chapter is to propose a new approach to incorporating uncertainty into capital budgeting. The chapter presents methods that can be used by an investor when the decision maker wants to be able to make an investment decision where there are alternative investment projects. This kind of problem is undertaken under the conditions of uncertainty and risk using Ordered Fuzzy Numbers (OFN). The starting point is the concept of Ordered Fuzzy Numbers. The chapter illustrates the implementation of the proposed approach with an example where two alternative investment projects are analyzed. The authors present the capital budgeting problem using a numerical example. The described metho…
Selection and micropropagation of valuable caper genotypes
2020
The high quality of the various biotypes present in the natural or cultivated state is one of the main features for caper production. Up to now, however, no selection activity has been carried out in order to identify the most suitable accessions for providing better quality products. In this paper, we report the first results of a selection of caper genotypes characterised by significant qualitative traits. A micropropagation protocol was evaluated in order to improve and allow the multiplication of the most promising Capparis spinosa L. subsp. spinosa genotypes, selected in Salina (Aeolian Islands), Sicily (Italy), in collaboration with the most important local growers.
Regulatory T-Cells in Antitumor Therapy: Isolation and Functional Testing of CD4<SUP>+</SUP>CD25<SUP>+</SUP> Regulatory T-Cel…
2004
Naturally occurring CD4+CD25+ T regulatory cells originate from the thymus and play a central role regarding the maintenance of peripheral tolerance by suppression of autoreactive T-cell populations. However, T regulatory cells can have beneficial as well as harmful effects. On the one hand, they prevent a variety of autoimmune and inflammatory diseases; but on the other hand, they concomitantly inhibit antitumor immune reactions by suppressing tumor-specific T-cell responses. Therefore, these ambivalent properties of T regulatory cells require detailed investigation especially with respect to a potential therapeutic exploitation of these cells. A prerequisite for such analyses is the isola…