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https://www.readbyqxmd.com/read/29160745/the-unveiling-of-the-warburg-effect-and-the-inscribed-innovative-approach-to-a-radical-non-toxic-anticancer-therapy
#1
Olivia Crociani, Ilaria Marzi, Maria Grazia Cipolleschi, Antonella Mannini, Massimo Contini, Massimo Olivotto
The purpose of this research has been deciphering the Warburg paradox, the biochemical enigma unsolved since 1923. This paradox consists of the aerobic pyruvate conversion to lactate brought about by anaplastic cancer, through the metabolic pathway known as aerobic glycolysis. This pathway implies a heavy energetic waste. We solved the enigma by demonstrating that its specific character, i.e. the forced aerobic lactate exportation, represents a crucial metabolic device to counteract the cytotoxic effect produced by an excess of pyruvate at the connection of glycolysis with the Krebs cycle...
November 21, 2017: Cell Cycle
https://www.readbyqxmd.com/read/29160119/a-review-of-the-infection-pathogenesis-and-prophylaxis-recommendations-in-patients-with-chronic-lymphocytic-leukemia
#2
Tamar Tadmor, Manfred Welslau, Iwoma Hus
The majority of patients with chronic lymphocytic leukemia (CLL) will obtain an infectious complication at some point during their disease, accounting for up to an estimated 60% of deaths in CLL. Patients are predisposed to infection due to inherent immune defects related to the primary disease, and as a result of therapy. The range of infectious complications has evolved alongside therapeutic advances in the treatment of CLL. More recently several novel targeted therapeutic compounds have been introduced in CLL, whose unique safety profiles will probably have an impact on the prophylaxis and management of infectious complications in these patients Areas covered: This review describes the pathogenesis of infections due to intrinsic CLL or therapy-related immunosuppression, and deals with the importance of proactive and reactive infection management as a key focus of patient care...
November 21, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/29159986/l-asparaginase-isolated-from-streptomyces-ansochromogenes-promotes-th1-profile-and-activates-cd8-t-cells-in-human-pbmc-an-in-vitro-investigation
#3
Glêzia Renata da Silva Lacerda, Cristiane Moutinho Lagos de Melo, Ana Karine de Araújo Soares, Leyllane Rafael Moreira, Marília Cavalcanti Coriolano, Gláucia Manoella de Souza Lima, Thiago Henrique Napoleão, Virgínia Maria Barros de Lorena, Leonor Alves de Oliveira da Silva, Silene Carneiro do Nascimento
AIMS: A new L-asparaginase produced by Streptomyces ansochromogenes UFPEDA 3420 actinobacteria was used in this study against human lymphocyte cultures to evaluate the immunological profile induced by this enzyme. METHODS AND RESULTS: Cultures of lymphocytes were stimulated with S. ansochromogenes L-asparaginase and cytotoxicity, cell viability, cell stimulation and cytokine production were analyzed. This new S. ansochromogenes L-asparaginase induced activation and proliferation of the TCD8(+) lymphocyte subset and produced higher TNF-α, IFN-γ, IL-2 and IL-10 levels in a 24 hour assay...
November 21, 2017: Journal of Applied Microbiology
https://www.readbyqxmd.com/read/29159711/treatment-of-richter-s-syndrome
#4
REVIEW
Adalgisa Condoluci, Davide Rossi
Based on the available literature, mostly derived from retrospective or non-randomized phase I or II studies, it is difficult to define an optimized treatment approach for patients developing Richter's syndrome (RS). Early recognition of chronic lymphocytic leukemia (CLL) patients presenting clinical features suspected for a transformation is useful to avoid exposing them to multiple lines of therapy that, being targeted to CLL progression, have poor efficacy against RS. Because of the low specificity (~ 50-60%) of clinical signs of RS (such as rapid and discordant bulky localized lymphadenopathies, elevated LDH levels, emergent physical deterioration, and/or fever in the absence of infection), a (18)FDG PET/CT and a biopsy are recommended to confirm RS...
November 21, 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/29159556/effects-of-arsenic-trioxide-on-inf-gamma-gene-expression-in-mrl-lpr-mice-and-human-lupus
#5
Hongye Hu, Enjiu Chen, Yongji Li, Xiaochun Zhu, Ting Zhang, Xiaofang Zhu
Arsenic trioxide (As2O3; ATO), a traditional Chinese medicine, is used to treat patients with acute promye-locytic leukemia, while its application for treatment of systemic lupus erythematosus (SLE) is still under evaluation. The high expression of INF-gamma (INF-γ) is a primary pathogenic factor in SLE. It is found that ATO can reduce INF-γ expression levels in lupus-prone mice, whereas it is not clear whether ATO has the same effect on SLE patients. Therefore, this study was to investigate the underlying mechanism of the effects of ATO on the expression of INF-γ in splenocytes of MRL/lpr mice and PBMCs of human lupus...
November 20, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/29159499/redistribution-of-cell-cycle-by-arsenic-trioxide-is-associated-with-demethylation-and-expression-changes-of-cell-cycle-related-genes-in-acute-promyelocytic-leukemia-cell-line-nb4
#6
Saeed Hassani, Ali Khaleghian, Shahin Ahmadian, Shaban Alizadeh, Kamran Alimoghaddam, Ardeshir Ghavamzadeh, Seyed H Ghaffari
PML-RARα perturbs the normal epigenetic setting, which is essential to oncogenic transformation in acute promyelocytic leukemia (APL). Transcription induction and recruitment of DNA methyltransferases (DNMTs) by PML-RARα and subsequent hypermethylation are components of this perturbation. Arsenic trioxide (ATO), an important drug in APL therapy, concurrent with degradation of PML-RARα induces cell cycle change and apoptosis. How ATO causes cell cycle alteration has remained largely unexplained. Here, we investigated DNA methylation patterns of cell cycle regulatory genes promoters, the effects of ATO on the methylated genes and cell cycle distribution in an APL cell line, NB4...
November 20, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/29159200/analyzing-the-genotoxicity-of-retroviral-vectors-in-hematopoietic-cell-gene-therapy
#7
REVIEW
Luca Biasco, Michael Rothe, Hildegard Büning, Axel Schambach
Retroviral vectors, including those derived from gammaretroviruses and lentiviruses, have found their way into the clinical arena and demonstrated remarkable efficacy for the treatment of immunodeficiencies, leukodystrophies, and globinopathies. Despite these successes, gene therapy unfortunately also has had to face severe adverse events in the form of leukemias and myelodysplastic syndromes, related to the semi-random vector integration into the host cell genome that caused deregulation of neighboring proto-oncogenes...
March 16, 2018: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/29158176/decreased-mcl-1-protein-level-in-the-striatum-of-1-methyl-4-phenyl-1-2-3-6-tetrahydropyridine-mptp-treated-mice
#8
Edward Lu, Sumit Sarkar, James Raymick, Merle G Paule, Qiang Gu
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a well-known neurotoxicant that can selectively destroy dopaminergic neurons and MPTP-treated animals are often used as models for studying aspects of Parkinson's disease (PD). While apoptosis has been suggested as a possible mechanism underlying MPTP-induced cell death and several apoptosis-associated proteins have been implicated in MPTP-animal models, relevant information regarding the possible involvement of Mcl-1 (myeloid cell leukemia 1) protein is missing...
November 17, 2017: Brain Research
https://www.readbyqxmd.com/read/29157973/when-the-good-go-bad-mutant-npm1-in-acute-myeloid-leukemia
#9
REVIEW
Preethi Kunchala, Sudhakiranmayi Kuravi, Roy Jensen, Joseph McGuirk, Ramesh Balusu
Nucleophosmin 1 (NPM1) is a nucleolar phosphoprotein that performs diverse biological functions including molecular chaperoning, ribosome biogenesis, DNA repair, and genome stability. Acute myeloid leukemia (AML) is a heterogeneous disease, more than half of the AML cases exhibit normal karyotype (NK). Approximately 50-60 percent of patients with NK-AML carry NPM1 mutations which are characterized by cytoplasmic dislocation of the NPM1 protein. In AML, mutant NPM1 (NPM1c+) acts in a dominant negative fashion and also blocks the differentiation of myeloid cells through gain-of-function for the AML phenotype...
November 4, 2017: Blood Reviews
https://www.readbyqxmd.com/read/29156850/harness-the-synergy-between-targeted-therapy-and-immunotherapy-what-have-we-learned-and-where-are-we-headed
#10
REVIEW
Xiaoyan Liu, Qing Zhou, Yan Xu, Minjiang Chen, Jing Zhao, Mengzhao Wang
Since the introduction of imatinib for the treatment of chronic myelogenous leukemia, several oncogenic mutations have been identified in various malignancies that can serve as targets for therapy. More recently, a deeper insight into the mechanism of antitumor immunity and tumor immunoevasion have facilitated the development of novel immunotherapy agents. Certain targeted agents have the ability of inhibiting tumor growth without causing severe lymphocytopenia and amplifying antitumor immune response by increasing tumor antigenicity, enhancing intratumoral T cell infiltration, and altering the tumor immune microenvironment, which provides a rationale for combining targeted therapy with immunotherapy...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156771/novel-post-transcriptional-and-post-translational-regulation-of-pro-apoptotic-protein-bok-and-anti-apoptotic-protein-mcl-1-determine-the-fate-of-breast-cancer-cells-to-survive-or-die
#11
Benjamin Onyeagucha, Panneerdoss Subbarayalu, Nourhan Abdelfattah, Subapriya Rajamanickam, Santosh Timilsina, Rosa Guzman, Carla Zeballos, Vijay Eedunuri, Sanjay Bansal, Tabrez Mohammad, Yidong Chen, Ratna K Vadlamudi, Manjeet K Rao
Deregulation of apoptosis is central to cancer progression and a major obstacle to effective treatment. The Bcl-2 gene family members play important roles in the regulation of apoptosis and are frequently altered in cancers. One such member is pro-apoptotic protein Bcl-2-related Ovarian Killer (BOK). Despite its critical role in apoptosis, the regulation of BOK expression is poorly understood in cancers. Here, we discovered that miR-296-5p regulates BOK expression by binding to its 3'-UTR in breast cancers...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156756/mir-221-regulated-kit-level-by-wild-type-or-leukemia-mutant-runx1-a-determinant-of-single-myeloblast-fate-decisions-that-collectively-drives-or-hinders-granulopoiesis
#12
Stefano Rossetti, Michael J Anauo, Nicoletta Sacchi
RUNX1, a master transcription factor of hematopoiesis, was shown to orchestrate both cell proliferation and differentiation during granulopoiesis by regulating microRNAs (miRs). In this study, taking advantage of the miR-ON reporter system, we monitored first, how the granulocyte colony stimulation factor (GCSF) temporally modulates the concomitant level variation of miR-221 and one of its prototypic targets, the stem cell factor receptor KIT, in single 32D(miR-ON-221) myeloblasts expressing wild type RUNX1...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156691/neutrophils-in-chronic-lymphocytic-leukemia-are-permanently-activated-and-have-functional-defects
#13
Gayane Manukyan, Tomas Papajik, Petr Gajdos, Zuzana Mikulkova, Renata Urbanova, Gabriela Gabcova, Milos Kudelka, Peter Turcsányi, Pavlina Ryznerova, Vit Prochazka, Eva Kriegova
A growing body of studies highlights involvement of neutrophils in cancer development and progression. Our aim was to assess the phenotypic and functional properties of circulating neutrophils from patients with chronic lymphocytic leukemia (CLL). The percentage of CD54+ and CD64+ neutrophils as well as CD54 expression on these cells were higher in CLL patients than in age-matched healthy controls. Neutrophils from CLL produced more reactive oxygen species (ROS) compared to controls in both resting and activated conditions...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156682/pharmacologic-inhibition-of-pi3k-p110%C3%AE-in-mutant-shp2e76k-expressing-mice
#14
Lisa Deng, Elizabeth L Virts, Reuben Kapur, Rebecca J Chan
Juvenile myelomonocytic leukemia is a childhood malignancy that lacks effective chemotherapies and thus has poor patient outcomes. PI3K p110δ has been found to promote hyperproliferation of cells expressing mutant Shp2. In this study, we tested the efficacy of a PI3Kδ inhibitor in mice expressing the Shp2 gain-of-function mutation, E76K. We found that in vivo treatment of mice led to significantly decreased splenomegaly, reduced frequency of bone marrow progenitor cells, and increased terminally differentiated peripheral blood myeloid cells...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156206/cytokine-release-syndrome-who-is-at-risk-and-how-to-treat
#15
REVIEW
Noelle Frey
T-cell engaging therapies such as blinatumomab and anti-CD19 chimeric antigen receptor (CAR) T cells have revolutionized our approach to patients with relapsed and refractory acute lymphoblastic leukemia (ALL). However, the immune activation responsible for high remission rates is also responsible for the unique treatment-related toxicity of cytokine release syndrome (CRS). The clinical signs of CRS include fever, hemodynamic instability, and capillary leak, which correlate with T-cell activation and elevated cytokine levels...
December 2017: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29156204/autologous-hematopoietic-cell-transplantation-for-adult-acute-myeloid-leukemia-an-obsolete-or-resurfacing-concept
#16
REVIEW
Hillard M Lazarus, Najla El Jurdi
Improving long-term outcomes of adult acute myeloid leukemia (AML) patients remains a challenge. Major scientific and clinical advances have led to a better understanding of the disease biology, and the majority of patients achieve a complete remission (CR) after induction therapy. Relapse risk, however, remains considerable and is the leading cause of death in this patient population. Significant efforts to improve outcomes emphasize use of post-remission therapies such as hematopoietic cell transplantation (HCT), an increasingly utilized modality...
December 2017: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29156203/impact-of-allogeneic-hematopoietic-cell-transplantation-on-the-outcome-of-older-patients-with-acute-myeloid-leukemia
#17
REVIEW
Frederick R Appelbaum
For younger patients with intermediate- or high-risk acute myeloid leukemia (AML) in first remission, allogeneic hematopoietic cell transplantation (HCT) offers the best chance of cure and therefore is the treatment of choice. The role of allogeneic HCT in the treatment of older patients is less well defined. In this review, four issues concerning the role of HCT in the treatment of older AML patients will be addressed: the frequency of allogeneic HCT in the older AML population in the US; the impact of age on the outcome of HCT; the comparative outcome of allogeneic HCT versus chemotherapy in older AML patients; and some of the barriers to the effective use of HCT in older AML patients...
December 2017: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29156202/relapsed-acute-lymphoblastic-leukemia-is-it-crucial-to-achieve-molecular-remission-prior-to-transplant
#18
REVIEW
Mary Eapen
In patients with acute lymphoblastic leukemia (ALL) the risk of recurrent leukemia influences the choice of treatment between chemotherapy and allogeneic hematopoietic cell transplantation. The evaluation of minimal residual disease (MRD) is now considered to be the greatest progress in risk stratification in regard to leukemia recurrence. Achieving molecular remission at the end of induction therapy after diagnosis or after relapse has influenced treatment choice. Failure to achieve molecular remission is considered "high risk" and allogeneic hematopoietic cell transplantation with a suitable donor, the accepted standard...
December 2017: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29156201/which-new-agents-will-be-incorporated-into-frontline-therapy-in-acute-myeloid-leukemia
#19
REVIEW
Richard M Stone
For 4 decades, new agents had not been permanently approved for use in treating acute myeloid leukemia (AML). The long dry spell was broken in 2017, however, with the approval of several agents: midostaurin for addition to chemotherapy in mutant FLT3 patients undergoing intensive chemotherapy, enasidenib in advanced mutant IDH2 patients, CPX-351 in secondary AML patients, and gemtuzumab ozogamicin in conjunction with standard chemotherapy in AML. This review surveys the use of tyrosine kinase inhibitors to treat patients with mutant FLT3 AML, mutant KIT AML, as well as IDH inhibitors and explores some questions regarding their integration into the treatment armamentarium for AML...
December 2017: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29156200/do-cytogenetics-affect-the-post-remission-strategy-for-older-patients-with-aml-in-cr1
#20
REVIEW
James M Foran
Data have shown that intensified cytarabine in consolidation for treatment of acute myeloid leukemia (AML) does not equally benefit patients older than 60 years, and older patients experience significantly more neurotoxicity than younger patients. In addition, older patients are more likely to have abnormal or unfavorable cytogenetics, which also tend to confer limited efficacy with intensified cytarabine. This poses a treatment dilemma as to the best post remission therapy to treat older patients. This review explores some of the consolidation treatment strategies and options available for the older AML patient...
December 2017: Best Practice & Research. Clinical Haematology
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