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Madalina Uzunov

Bio: Madalina Uzunov is an academic researcher from University of Paris. The author has contributed to research in topics: Transplantation & Hematopoietic stem cell transplantation. The author has an hindex of 14, co-authored 47 publications receiving 884 citations.


Papers
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Journal ArticleDOI
14 Nov 2013-Blood
TL;DR: It is shown that glutamine removal inhibits mTORC1 and induces apoptosis in AML cells, and that l-ases upregulate glutamine synthase expression in leukemic cells and that a GS knockdown enhances l-ase-induced apoptotic response in someAML cells.

238 citations

Journal ArticleDOI
20 Aug 2009-Blood
TL;DR: It is shown here that the translation inhibitor 4EGI-1 decreased the clonogenic growth of leukemic progenitors and induced apoptosis of blast cells, with limited toxicity against normal hematopoiesis, which emphasize the importance of translation deregulation in acute myeloid leukemia (AML) biology.

197 citations

Journal ArticleDOI
08 Jan 2009-Leukemia
TL;DR: This first extensive analysis of the phenotypic and functional properties of NK cells after umbilical cord blood transplantation found that following UCBT, NK cells display not only some phenotypesic features associated with maturity but also unique characteristics that make them fully functional against leukemic blasts.
Abstract: Promising results of umbilical cord blood transplantation (UCBT) from unrelated donors have been reported in patients with hematologic disorders. These transplants, having potential to trigger beneficial donor-versus-recipient natural killer (NK) cell-mediated alloreaction, we have conducted the first extensive analysis of the phenotypic and functional properties of NK cells after UCBT. NK cells from 25 patients with high-risk hematologic malignancies were compared with cells derived from both healthy adult and CB cells. We found that following UCBT, NK cells display not only some phenotypic features associated with maturity but also unique characteristics that make them fully functional against leukemic blasts. We propose that this full functionality of alloreactive donor-derived NK may drive graft-versus-leukemia reactions after UCBT.

58 citations

Journal ArticleDOI
TL;DR: Results indicate that the initial fungus load as determined by PCR was highly predictive of 90-day mortality, with the rate of the latter being 15.8% for patients with <150 copies/mL vs. patients at or above that cutoff (p <0.0001).

56 citations


Cited by
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Journal ArticleDOI
TL;DR: An updated overview of glutamine metabolism and its involvement in tumorigenesis in vitro and in vivo is provided, and the recent potential applications of basic science discoveries in the clinical setting are explored.
Abstract: The resurgence of research into cancer metabolism has recently broadened interests beyond glucose and the Warburg effect to other nutrients, including glutamine. Because oncogenic alterations of metabolism render cancer cells addicted to nutrients, pathways involved in glycolysis or glutaminolysis could be exploited for therapeutic purposes. In this Review, we provide an updated overview of glutamine metabolism and its involvement in tumorigenesis in vitro and in vivo, and explore the recent potential applications of basic science discoveries in the clinical setting.

1,285 citations

Journal ArticleDOI
TL;DR: In older patients with AML, decitabine improved response rates compared with standard therapies without major differences in safety, and an unplanned survival analysis showed a benefit for decit abine, which was not observed at the time of the primary analysis.
Abstract: Purpose This multicenter, randomized, open-label, phase III trial compared the efficacy and safety of decitabine with treatment choice (TC) in older patients with newly diagnosed acute myeloid leukemia (AML) and poor- or intermediate-risk cytogenetics. Patients and Methods Patients (N = 485) age ≥ 65 years were randomly assigned 1:1 to receive decitabine 20 mg/m2 per day as a 1-hour intravenous infusion for five consecutive days every 4 weeks or TC (supportive care or cytarabine 20 mg/m2 per day as a subcutaneous injection for 10 consecutive days every 4 weeks). The primary end point was overall survival (OS); the secondary end point was the complete remission (CR) rate plus the CR rate without platelet recovery (CRp). Adverse events (AEs) were recorded. Results The primary analysis with 396 deaths (81.6%) showed a nonsignificant increase in median OS with decitabine (7.7 months; 95% CI, 6.2 to 9.2) versus TC (5.0 months; 95% CI, 4.3 to 6.3; P = .108; hazard ratio [HR], 0.85; 95% CI, 0.69 to 1.04). An unp...

942 citations

Journal ArticleDOI
TL;DR: Clinical efforts are underway to target specific components of the translation apparatus or unique mRNA translation elements for cancer therapeutics to define a new understanding of the role of mRNA translation and protein synthesis in human cancer.
Abstract: Remarkable progress has been made in defining a new understanding of the role of mRNA translation and protein synthesis in human cancer. Translational control is a crucial component of cancer development and progression, directing both global control of protein synthesis and selective translation of specific mRNAs that promote tumour cell survival, angiogenesis, transformation, invasion and metastasis. Translational control of cancer is multifaceted, involving alterations in translation factor levels and activities unique to different types of cancers, disease stages and the tumour microenvironment. Several clinical efforts are underway to target specific components of the translation apparatus or unique mRNA translation elements for cancer therapeutics.

753 citations

Journal ArticleDOI
TL;DR: The rational use of these cells in cancer immunotherapies awaits a better understanding of their effector functions, migratory patterns and survival properties in humans.
Abstract: Natural killer (NK) cells and natural killer T (NKT) cells are subsets of lymphocytes that share some phenotypical and functional similarities. Both cell types can rapidly respond to the presence of tumour cells and participate in antitumour immune responses. This has prompted interest in the development of innovative cancer therapies that are based on the manipulation of NK and NKT cells. Recent studies have highlighted how the immune reactivity of NK and NKT cells is shaped by the environment in which they develop. The rational use of these cells in cancer immunotherapies awaits a better understanding of their effector functions, migratory patterns and survival properties in humans.

729 citations

Journal ArticleDOI
19 Sep 2014-Science
TL;DR: The existence of several “metabolic checkpoints” is proposed, refined molecular mechanisms that sense a panel of metabolic variables and emit one or more signals controlling cell fate, which might allow for the development of novel pharmacological approaches that block or stimulate cell death by inducing specific metabolic alterations.
Abstract: Beyond their contribution to basic metabolism, the major cellular organelles, in particular mitochondria, can determine whether cells respond to stress in an adaptive or suicidal manner. Thus, mitochondria can continuously adapt their shape to changing bioenergetic demands as they are subjected to quality control by autophagy, or they can undergo a lethal permeabilization process that initiates apoptosis. Along similar lines, multiple proteins involved in metabolic circuitries, including oxidative phosphorylation and transport of metabolites across membranes, may participate in the regulated or catastrophic dismantling of organelles. Many factors that were initially characterized as cell death regulators are now known to physically or functionally interact with metabolic enzymes. Thus, several metabolic cues regulate the propensity of cells to activate self-destructive programs, in part by acting on nutrient sensors. This suggests the existence of "metabolic checkpoints" that dictate cell fate in response to metabolic fluctuations. Here, we discuss recent insights into the intersection between metabolism and cell death regulation that have major implications for the comprehension and manipulation of unwarranted cell loss.

519 citations