33 research outputs found
The EHA research roadmap: anemias
In 2016, the European Hematology Association (EHA) published the EHA Roadmap for European Hematology Research1 aiming to highlight achievements in the diagnostics and treatment of blood disorders, and to better inform European policy makers and other stakeholders about the urgent clinical and scientific needs and priorities in the field of hematology. Each section was coordinated by one to two section editors who were leading international experts in the field. In the five years that have followed, advances in the field of hematology have been plentiful. As such, EHA is pleased to present an updated Research Roadmap, now including eleven sections, each of which will be published separately. The updated EHA Research Roadmap identifies the most urgent priorities in hematology research and clinical science, therefore supporting a more informed, focused, and ideally a more funded future for European hematology research. The eleven EHA Research Roadmap sections include Normal Hematopoiesis; Malignant Lymphoid Diseases; Malignant Myeloid Diseases; Anemias and Related Diseases; Platelet Disorders; Blood Coagulation and Hemostatic Disorders; Transfusion Medicine; Infections in Hematology; Hematopoietic Stem Cell Transplantation; CAR-T and Other Cellbased Immune Therapies; and Gene Therap
Emerging issues of the expression profiling technologies for the study of gynecologic cancer
Evaluation of the prognostic parameters of gynecologic cancer has shown
their failure for classification according to the clinical behavior or
the prediction of its outcome. This weakness has important implications
on prognosis and treatment. The increasing understanding of the
complexity of the human genome, coupled with the development of high
throughput analysis techniques and bioinformatics tools, has changed our
concepts on cancer biology, by shifting our targets to a global analysis
of the transcriptome and the proteome, linking genes and their products
into functional pathways. These approaches permit the documentation of
expression patterns of thousands of genes within a cell. With the use of
DNA microarray technology, it is feasible to identify signature patterns
of expression in tumor samples that faithfully correlate with its
biology, providing accurate prognosis for each cancer patient and thus a
rational customized treatment. At this stage, there is a need for
systematic studies for the validation of these novel approaches. In this
review, we provide a basic back-round of the concept of the technology,
highlight several ernerging issues from their applications on
gynecologic cancer, discuss a series of important themes and problems
regarding their interpretation and relevance for the clinicians, and
comment on future areas of research. (C) 2005 Elsevier Inc. All rights
reserved
Structural analysis and expression profile of a novel gene on chromosome 5q23 encoding a Golgi-associated protein with six splice variants, and involved within the 5q deletion of a Ph(-) CML patient.
We have identified a novel gene, upstream of the cytokine gene cluster region in 5q23-31, residing within one of the most common deleted segments associated with MDS. The novel gene exhibits significant alternative splicing generating at least six splice variants encoding four putative proline-rich protein isoforms, one of which is Golgi-associated. The gene is ubiquitously expressed and conserved among species with the C. elegans homologue being the most interesting, since it resides within an operon with two other genes, phospholipase D and dishevelled, a member of the Wnt pathway, suggesting a functional association. In addition, the novel gene and other key regulatory genes of the region, such IL3, Ril, AF5q31 and TCF-1, were found to be deleted in an atypical CML case, thus underscoring the significance of this subregion in the leukemogenesis process
Spindle shaped human mesenchymal stem/stromal cells from amniotic fluid promote neovascularization
Human amniotic fluid obtained at amniocentesis, when cultured, generates at least two morphologically distinct mesenchymal stem/stromal cell (MSC) subsets. Of these, the spindle shaped amniotic fluid MSCs (SS-AF-MSCs) contain multipotent cells with enhanced adipogenic, osteogenic and chondrogenic capacity. Here, we demonstrate, for the first time, the capacity of these SS-AF-MSCs to support neovascularization by umbilical cord blood (UCB) endothelial colony forming cell (ECFC) derived cells in both in vitro and in vivo models. Interestingly, although the kinetics of vascular tubule formation in vitro were similar when the supporting SS-AF-MSCs were compared with the best vasculogenic supportive batches of bone marrow MSCs (BMSCs) or human dermal fibroblasts (hDFs), SS-AF-MSCs supported vascular tubule formation in vivo more effectively than BMSCs. In NOD/SCID mice, the human vessels inosculated with murine vessels demonstrating their functionality. Proteome profiler array analyses revealed both common and distinct secretion profiles of angiogenic factors by the SS-AF-MSCs as opposed to the hDFs and BMSCs. Thus, SS-AF-MSCs, which are considered to be less mature developmentally than adult BMSCs, and intermediate between adult and embryonic stem cells in their potentiality, have the additional and very interesting potential of supporting increased neovascularisation, further enhancing their promise as vehicles for tissue repair and regeneration
Structural analysis and expression profile of a novel gene on chromosome 5q23 encoding a Golgi-associated protein with six splice variants, and involved within the 5q deletion of a Ph(-) CML patient
We have identified a novel gene, upstream of the cytokine gene cluster
region in 5q23-31, residing within one of the most common deleted
segments associated with MDS. The novel gene exhibits significant
alternative splicing generating at least six splice variants encoding
four putative proline-rich protein isoforms, one of which is
Golgi-associated. The gene is ubiquitously expressed and conserved among
species with the C elegans homologue being the most interesting, since
it resides within an operon with two other genes, phospholipase D and
dishevelled, a member of the Wnt pathway, suggesting a functional
association. In addition, the novel gene and other key regulatory genes
of the region, such IL3, Ril, AF5q31 and TCF-1, were found to be deleted
in an atypical CML case, thus underscoring the significance of this
subregion in the leukemogenesis process. (C) 2004 Elsevier Ltd. All
rights reserved
Functional role of the four different types of (AT)(X)T-Y motifs 5 ` to the beta-globin gene and their distribution in the Greek population
The polymorphic sequence (AT)(X)T-Y motif residing 0.5 kb 5’ to the
human beta-globin gene has been shown to be a binding site for a
putative repressor protein, BP1, in K562 cells. The (AT)(X)T-Y sequence
is characterized by variable length and several configurations. The
precise role of the (AT)(X)T-Y repeats on the regulation of the
beta-globin gene remains unclear. In the present study, we identified
the (AT)(X)T-Y motifs which prevail in the Greek population, established
their frequency, and directly investigated their role on P-globin gene
expression by comparing the effects of the four identified (AT)(X)T-Y
motifs using transient expression assays. Four different configurations
were found in the Greek population: the (AT),T, motif was the most
abundant (81.8%) representing the reference sequence, the (AT)(8)T-5
motif (16.1%), and the (AT)(11)T-3 motif (2%), while the (AT)(8)T-4
motif was absent from normal beta(A) chromosomes and was exclusively
found on beta(s) chromosomes. To evaluate their different role on
transcriptional regulation, the four motifs were subcloned upstream of
the luciferase reporter gene. Two expression systems were used; MEL
cells were transfected with a pGL-2 basic plasmid containing one of the
four (AT)(X)T-Y repeats, the beta-globin gene promoter, and the
luciferase gene, while HeLa cells were transfected with a similar
construct (pGL-2 enhancer) including the SV40 enhancer. After 48 h
following transient transfection of the cell lines, the expression level
of the reporter gene was estimated using a photoilluminometer. The
transfected MEL cells exhibited a clearly reduced expression of the
luciferase gene driven by the beta-globin promoter containing the
(AT)(X)T-Y and (AT)(11)T-3 configurations. In contrast, HeLa cells did
not exhibit any differences among the four motifs. On the basis of these
results, we postulate that the (AT),T, and (AT),T, variants residing 0.5
kb 5’ to the beta-globin gene do not represent simple polymorphisms and
can affect its expression in an erythroid environment. (C) 2002 Elsevier
Science (USA)