36 research outputs found
p53 and Notch signaling in chronic lymphocytic leukemia: clues to identifying novel therapeutic strategies
No full textThe p53 tumor suppressor protein has a key role in the induction of apoptosis of chronic lymphocytic leukemia (CLL) cells. Abnormalities within the p53 pathway identify a subset of patients with a poor prognosis. This review describes recent advances in understanding the mechanisms that regulate p53 levels and the role of p53 in the control of the cell cycle and of apoptosis. The classical model of p53-mediated apoptosis emphasizes the transcriptional activation of proapoptotic genes. In contrast, a novel model emphasizes p53's non-transcriptional actions as the major route of apoptosis induction, whereas its transcriptional arm predominantly upregulates antiapoptotic genes, thus providing a negative feedback mechanism that limits apoptosis. Further studies have identified the Notch pathway as a candidate p53-induced antiapoptotic mechanism. In contrast to the classical model, the novel model predicts that pharmacological inhibition of p53's transcriptional function or of the Notch signaling pathway will augment apoptosis induction by cytotoxic agents. Therapeutic strategies based on the novel model, which we review here for the first time, may significantly augment the antitumor actions of cytotoxic agents in CLL and in other malignancie
The sesquiterpene lactone parthenolide induces selective apoptosis of B-chronic lymphocytic leukemia cells in vitro.
No full textWe have studied the in vitro actions of the sesquiterpene lactone parthenolide (PTL) on cells isolated from patients with chronic lymphocytic leukemia (CLL). Dye reduction viability assays showed that the median LD(50) for PTL was 6.2 muM (n=78). Fifteen of these isolates were relatively resistant to the conventional agent chlorambucil but retained sensitivity to PTL. Brief exposures to PTL (1-3 h) were sufficient to induce caspase activation and commitment to cell death. Chronic lymphocytic leukemia cells were more sensitive towards PTL than were normal T lymphocytes or CD34(+) haematopoietic progenitor cells. The mechanism of cell killing was via PTL-induced generation of reactive oxygen species, resulting in turn in a proapoptotic Bax conformational change, release of mitochondrial cytochrome c and caspase activation. Parthenolide also decreased nuclear levels of the antiapoptotic transcription factor nuclear factor-kappa B and diminished phosphorylation of its negative regulator IkappaB. Killing of CLL cells by PTL was apparently independent of p53 induction. This is the first report showing the relative selectivity of PTL towards CLL cells. The data here warrant further investigation of this class of natural product as potential therapeutic agents for CLL
Differential N-ethylmaleimide inhibition of two enzymes of the DNA α-polymerase-fraction from calf thymus
No full textDo leukotrienes play a role in the regulation of proliferation of normal and leukemic hemopoietic cells?
No full textMalaria and Primary Education : A Cross-Country Analysis on Primary Repetition and Completion Rates
No full textThis paper explores the link between P. Falciparum malaria - most of malaria morbidity and mortality is due to the malignant Plasmodium Falciparum - and primary education in terms of school performances at the macroeconomic stage. Cross-country regression analysis shows that the relation between school results (measured by repetition and completion rates) and the P. Falciparum malaria index is strong. The results implies that the achievement of the education Millennium Development Goals will require more than just focusing on expenditure in primary education. It does not imply that resources in education are unnecessary but that increasing resources in education and improving education resources management alone are unlikely to be sufficient. This paper suggests that health conditions and especially diseases that alter cognitive capacities of children such as malaria should be taken into account much more seriously. This study also sees the need to place emphasis on research that will improve the quality of interventions to prevent malaria. Specific education expenditure to face Malaria should be examined in addition to health policies.Malaria incidence, human capital, development.
Antioxidants enhance the susceptibility of colon carcinoma cells to 5-fluorouracil by augmenting the induction of the bax protein
No full textAuthor Correction: Identification of genetic effects underlying type 2 diabetes in South Asian and European populations
No full textAuthor Correction to: Identification of genetic effects underlying type 2 diabetes in South Asian and European population
Author Correction: The power of genetic diversity in genome-wide association studies of lipids (Nature, (2021), 600, 7890, (675-679), 10.1038/s41586-021-04064-3)
No full textCorrection to: Nature Published online 9 December 2021 In the version of this article initially published, Noha A. Yousri (Department of Genetic Medicine, Weill Cornell Medicine-Qatar, Doha, Qatar and Department of Computer and Systems Engineering, Alexandria University, Egypt) and Steven C. Hunt (Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA and Department of Genetic Medicine, Weill Cornell Medicine-Qatar, Doha, Qatar) were not included in the author list. In addition, Hieab H. H. Adams (Department of Radiology and Nuclear Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands and Department of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands) was shown with an incorrect second affiliation in the HTML and PDF versions of the article. Finally, in the HTML version, Cristen J. Willer was mistakenly listed with an extra affiliation (Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia). The authors and affiliations have been corrected in the HTML and PDF versions of the article. © 2023, The Author(s), under exclusive licence to Springer Nature Limited
Involvement of Tis11b, an AU-rich binding protein, in induction of apoptosis by rituximab in B cell chronic lymphocytic leukemia cells [Letter to editor]
No full textB-cell chronic lymphocytic leukemia is the commonest form of leukemia in the Western world, characterized by an accumulation of monoclonal CD5+ B cells in the peripheral blood and lymphoid organs. It is clinically a heterogenous disease with overall variable response to many drugs used either alone or in combination, and is currently untreatable
