1,721,380 research outputs found
Efficacy of dasatinib in conjunction with alpha-interferon for the treatment of imatinib-resistant and dasatinib-resistant Ph+ acute lymphoblastic leukemia
No full textDespite notable progresses in the past few years, and, in
particular, the advent of first- and second-generation tyrosine
kinase inhibitors (TKI), the treatment of adult BCR-ABL1 acute
lymphoblastic leukemia (ALL) patients still remains an unsolved
problem. In fact, though chemotherapy (CHT) and TKI are
effective for inducing complete remission (CR), durable responses
and possibly cure seem be achievable, at present, with stem cell
transplantation only. We describe a unique case of BCR-ABL1þ
ALL, relapsed after CHT, autologous stem cell transplantation
(ASCT), imatinib and dasatinib courses, successfully treated with a
combination of dasatinib and a-interferon (a-IFN)
BCR-ABL independent mechanisms of resistance in chronic myeloid leukemia
Full text linkNot all chronic myeloid leukemia (CML) patients are cured with tyrosine kinase inhibitors (TKIs), and a proportion of them develop resistance. Recently, continuous BCR-ABL gene expression has been found in resistant cells with undetectable BCR-ABL protein expression, indicating that resistance may occur through kinase independent mechanisms, mainly due to the persistence of leukemia stem cells (LSCs). LSCs reside in the bone marrow niche in a quiescent state, and are characterized by a high heterogeneity in genetic, epigenetic, and transcriptional mechanisms. New approaches based on single cell genomics have offered the opportunity to identify distinct subpopulations of LSCs at diagnosis and during treatment. In the one hand, TKIs are not able to efficiently kill CML-LSCs, but they may be responsible for the modification of some LSCs characteristics, thus contributing to heterogeneity within the tumor. In the other hand, the bone marrow niche is responsible for the interactions between surrounding stromal cells and LSCs, resulting in the generation of specific signals which could favor LSCs cell cycle arrest and allow them to persist during treatment with TKIs. Additionally, LSCs may themselves alter the niche by expressing various costimulatory molecules and secreting suppressive cytokines, able to target metabolic pathways, create an anti-apoptotic environment, and alter immune system functions. Accordingly, the production of an immunosuppressant milieu may facilitate tumor escape from immune surveillance and induce chemo-resistance. In this review we will focus on BCR-ABL-independent mechanisms, analyzing especially those with a potential clinical impact in the management of CML patients
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
All-trans retinoic acid shows multiple effects on the survival, proliferation anddifferentiation of human fetal CD34+ haemopoietic progenitor cells
No full textTo evaluate the effect of all-trans retinoic acid (RA) on fetal haemopoiesis, we
performed serum-free liquid and semisolid cultures using CD34+ cells purified
from midtrimester human fetal blood samples. RA, at both physiological (10(-11)
and 10(-12)M) and pharmacological (10(-6) and 10(-7)M) concentrations,
significantly (P < 0.01) promoted the survival of fetal CD34+ cells in liquid
cultures from day 3 onwards, by suppressing apoptosis induced by serum and growth
factor deprivation. On the other hand, RA alone had no significant effect on the
proliferation and differentiation of fetal haemopoietic progenitors. In the
presence of optimal concentrations of recombinant interleukin-3 (IL-3), stem cell
factor (SCF), granulocyte/macrophage-colony stimulating factor (GM-CSF), and
erythropoietin (Epo), low and high doses of RA induced striking differential
effects on CD34+ cell proliferation in liquid cultures and colony formation in
semisolid assays. In fact, 10(-11)M and 10(-12)M RA were able to: (i)
significantly (P < 0.05) increase 3H-thymidine uptake by fetal CD34+ cells in
liquid cultures, and (ii) variably promote the growth of pluripotent (CFU-GEMM, P
< 0.05), early (BFU-meg) and late (CFU-meg, P < 0.01) megakaryocyte,
granulocyte/macrophage (CFU-GM, P < 0.01) and erythroid (BFU-E) progenitors in
semisolid cultures. On the contrary, 10(-6) and 10(-7)M RA induced: (i) an
overall inhibition (P < 0.01) of CD34+ cell growth in liquid cultures; (ii) a
marked suppression of BFU-E colony formation (P < 0.01) at all Epo concentrations
examined (0.002-4 IU/ml); and (iii) a significant (P < 0.01) stimulation of
CFU-GM with a shift from mixed granulocyte/macrophage to pure granulocyte
colonies, whereas it had little effect on the growth of CFU-GEMM, BFU-meg and
CFU-meg. Our data, as a whole, demonstrate that RA has direct complex effects on
the survival, growth and clonal expansion of fetal haemopoietic progenitor cells,
mainly depending on the presence of recombinant cytokines, the type of progenitor
and the concentrations of RA
In vitro growth of human fetal CD34+ cells in the presence of variouscombinations of recombinant cytokines under serum-free culture conditions
No full textCD34+ cells were purified from midtrimester human fetal blood and adult bone
marrow samples and seeded in serum-free fibrin-clot cultures in order to evaluate
the number and the responsiveness to recombinant cytokines of pluripotent
(CFU-GEMM), erythroid (BFU-E), megakaryocyte (BFU-meg and CFU-meg) and
granulocyte/macrophage (CFU-GM) haemopoietic progenitor cells. The number of the
different haemopoietic progenitors/1 x 10(3) CD34+ cells, except CFU-meg, was
significantly higher in fetal blood than in adult bone marrow in cultures
stimulated by any combination of cytokines including interleukin-3 (IL-3),
granulocyte/macrophage colony stimulating factor (GM-CSF) or stem cell factor
(SCF) plus erythropoietin (Epo). Nevertheless, whereas adult BFU-E showed a
maximal growth in the presence of Epo plus IL-3 or Epo plus SCF, fetal BFU-E
showed an optimal growth in the presence of Epo alone, the sensitivity of fetal
BFU-E to suboptimal concentrations of Epo being approximately 10-15-fold higher
than that of adult BFU-E. Addition of optimal concentrations of IL-3, GM-CSF or
SCF, alone or in various combinations, to Epo-containing cultures induced a
significant increase in both the number and size of fetal CFU-GEMM, and CFU-GM,
and a parallel decrease of fetal BFU-E. Finally, SCF potently synergized with
IL-3 in increasing the growth of both classes of fetal megakaryocyte progenitors,
BFU-meg and CFU-meg
Liposome encapsulated daunorubicin (daunoxome) for acute leukemia
No full textDaunoxome (DNX, Nexstar) was given, as a single agent, to 11 patients with very poor-risk acute leukemia. Pharmacokinetic data were also obtained from 9 of the 11 cases. This small pilot study show that the toxic profile of this liposomal-encapsulated anthracycline is low
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