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Cancer: Acute Leukemia

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Total 260 results found since Jan 2013.

5 ′-triphosphate siRNA targeting MDR1 reverses multi-drug resistance and activates RIG-I-induced immune-stimulatory and apoptotic effects against human myeloid leukaemia cells
Most persons with acute myeloid leukaemia fail therapy. Development of multi-drug resistance (MDR) is thought to be an important cause. MDR is characterized by cross-resistance to several anti-cancer drugs with diverse chemical structures and mechanisms-of-action [1]. MDR involves the expression and activity of an ATP-binding-cassette (ABC; CD243) transporter also known as P-glycoprotein (P-gp), an efflux pump protein which extrudes anti-cancer drugs from cells [2]. Additionally, P-gp is associated with decreased caspase activation resulting from altered activity of several chloride channels [3,4] altered intra-cellular pH...
Source: Leukemia Research - March 19, 2017 Category: Hematology Authors: Dengzhe Li, Robert Peter Gale, Yanfeng Liu, Baoxia Lei, Yuan Wang, Dongmei Diao, Mei Zhang Tags: Research paper Source Type: research

Antibody-Targeted Cyclodextrin-Based Nanoparticles for siRNA Delivery in the Treatment of Acute Myeloid Leukemia: Physicochemical Characteristics, in Vitro Mechanistic Studies, and ex Vivo Patient Derived Therapeutic Efficacy
Molecular PharmaceuticsDOI: 10.1021/acs.molpharmaceut.6b01150
Source: Molecular Pharmaceutics - February 14, 2017 Category: Drugs & Pharmacology Authors: Jianfeng Guo, Eileen G. Russell, Raphael Darcy, Thomas G. Cotter, Sharon L. McKenna, Mary R. Cahill and Caitriona M. O ’Driscoll Source Type: research

Autophagy contributes to 4-Amino-2-Trifluoromethyl-Phenyl Retinate-induced differentiation in human acute promyelocytic leukemia NB4 cells.
Abstract As a classic differentiation agent, all-trans retinoic acid (ATRA) has been widely used in treatment of acute promyelocytic leukemia (APL). However, clinical application of ATRA has limitations. Our previous studies suggested that 4-Amino-2-Trifluoromethyl-Phenyl Retinate (ATPR), a novel all-trans retinoic acid (ATRA) derivative designed and synthesized by our team, could induce differentiation of APL cells in vivo and in vitro. To explore the underlying mechanism of ATPR, the effect of ATPR on autophagy of APL cells was observed in the present study. The results showed that the differentiation effect of ...
Source: Toxicology and Applied Pharmacology - January 23, 2017 Category: Toxicology Authors: Li Y, Li G, Wang K, Xie YY, Zhou RP, Meng Y, Ding R, Ge JF, Chen FH Tags: Toxicol Appl Pharmacol Source Type: research

Targeting AMPK-ULK1-mediated autophagy for combating BET inhibitor resistance in acute myeloid leukemia stem cells.
In this study, we evaluated the mechanisms underlying LSC resistance to the BET inhibitor JQ1. We evaluated the levels of apoptosis and macroautophagy/autophagy induced by JQ1 in LSC-like leukemia cell lines and primary CD34(+) CD38(-) leukemic blasts obtained from AML cases with normal karyotype without recurrent mutations. JQ1 effectively induced apoptosis in a concentration-dependent manner in JQ1-sensitive AML cells. However, in JQ1-resistant AML LSCs, JQ1 induced little apoptosis and led to upregulation of BECN1/beclin-1, increased LC3 lipidation, formation of autophagosomes, and downregulation of SQSTM1/p62. Inhibiti...
Source: Autophagy - January 23, 2017 Category: Cytology Authors: Jang JE, Eom JI, Jeung HK, Cheong JW, Lee JY, Kim JS, Min YH Tags: Autophagy Source Type: research

miR ‐9 plays a role in IL‐10‐mediated expression of E‐cadherin in acute myelogenous leukemia cells
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Source: Cancer Science - January 19, 2017 Category: Cancer & Oncology Authors: Chie Nishioka, Takayuki Ikezoe, Bin Pan, Kailin Xu, Akihito Yokoyama Tags: Original Article Source Type: research

Inhibition of MicroRNA-149-5p Induces Apoptosis of Acute Myeloid Leukemia Cell Line THP-1 by Targeting Fas Ligand (FASLG).
CONCLUSIONS Inhibition of miR-149-5p can induce apoptosis in THP-1 cells. These inductive effects might be via targeting FASLG and activating FADD and caspases. PMID: 28013316 [PubMed - in process]
Source: Medical Science Monitor - December 27, 2016 Category: Research Tags: Med Sci Monit Source Type: research

Rocaglamide breaks TRAIL-resistance in human multiple myeloma and acute T-cell leukemia in vivo in a mouse xenogtraft model
Multiple myeloma (MM) is an incurable malignancy by the presently known therapies. TRAIL is a promising anticancer agent that virtually not shows any toxicity to normal cells. We have recently carried out clinical trials with a human circularly permuted TRAIL, CPT, against MM saw a partial response in approximate 20 – 30% of patients. In the current study, we investigated the cause of CPT resistance and revealed that the majority of the MM patients express elevated levels of c-FLIP. Knockdown of c-FLIP expression by siRNA alone was sufficient to increase CPT-mediated apoptosis in a CPT-resistant human MM cell line U266.
Source: Cancer Letters - December 17, 2016 Category: Cancer & Oncology Authors: Yin Wu, Marco Giaisi, Rebecca K öhler, Dr. Wen-Ming Chen, Peter H. Krammer, Dr. Min Li-Weber Tags: Original Articles Source Type: research

Rocaglamide breaks TRAIL-resistance in human multiple myeloma and acute T-cell leukemia in  vivo in a mouse xenogtraft model
Multiple myeloma (MM) is an incurable malignancy by the presently known therapies. TRAIL is a promising anticancer agent that virtually not shows any toxicity to normal cells. We have recently carried out clinical trials with a human circularly permuted TRAIL, CPT, against MM saw a partial response in approximate 20 –30% of patients. In the current study, we investigated the cause of CPT resistance and revealed that the majority of the MM patients express elevated levels of c-FLIP. Knockdown of c-FLIP expression by siRNA alone was sufficient to increase CPT-mediated apoptosis in a CPT-resistant human MM cell line U266.
Source: Cancer Letters - December 17, 2016 Category: Cancer & Oncology Authors: Yin Wu, Marco Giaisi, Rebecca K öhler, Wen-Ming Chen, Peter H. Krammer, Min Li-Weber Tags: Original Article Source Type: research

Suppression of protein tyrosine phosphatase PTPN22 gene induces apoptosis in T-cell leukemia cell line (Jurkat) through the AKT and ERK pathways
In this study, Jurkat cells were transfected with specific PTPN22 siRNA. Relative PTPN22 mRNA expression was measured by Quantitative Real-time PCR. Western blotting was performed to determine the protein levels of PTPN22, AKT, P-AKT, ERK, and P-ERK. The cytotoxic effects of PTPN22 siRNA were determined using the MTT assay. Apoptosis was quantified using TUNEL assay and flow cytometry. Results showed that in Jurkat cells after transfection with PTPN22 siRNA, the expression of PTPN22 in both mRNA and protein levels was effectively reduced. Moreover, siRNA transfection induced apoptosis on the viability of T-cell acute leuke...
Source: Biomedicine and Pharmacotherapy - December 6, 2016 Category: Drugs & Pharmacology Source Type: research

Suppression of protein tyrosine phosphatase PTPN22 gene induces apoptosis in T-cell leukemia cell line (Jurkat) through the AKT and ERK pathways.
In this study, Jurkat cells were transfected with specific PTPN22 siRNA. Relative PTPN22 mRNA expression was measured by Quantitative Real-time PCR. Western blotting was performed to determine the protein levels of PTPN22, AKT, P-AKT, ERK, and P-ERK. The cytotoxic effects of PTPN22 siRNA were determined using the MTT assay. Apoptosis was quantified using TUNEL assay and flow cytometry. Results showed that in Jurkat cells after transfection with PTPN22 siRNA, the expression of PTPN22 in both mRNA and protein levels was effectively reduced. Moreover, siRNA transfection induced apoptosis on the viability of T-cell acute leuke...
Source: Biomedicine and pharmacotherapy = Biomedecine and pharmacotherapie - December 5, 2016 Category: Drugs & Pharmacology Authors: Baghbani E, Baradaran B, Pak F, Mohammadnejad L, Shanehbandi D, Mansoori B, Khaze V, Montazami N, Mohammadi A, Kokhaei P Tags: Biomed Pharmacother Source Type: research

AMPK-ULK1-mediated autophagy confers resistance to BET inhibitor JQ1 in acute myeloid leukemia stem cells.
CONCLUSIONS: These findings revealed that prosurvival autophagy was one of the mechanisms involved in the resistance AML LSCs to JQ1. Targeting the AMPK/ULK1 pathway or inhibition of autophagy could be an effective therapeutic strategy for combating resistance to BET inhibitors in AML and other types of cancer. PMID: 27864418 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - November 17, 2016 Category: Cancer & Oncology Authors: Jang JE, Eom JI, Jeung HK, Cheong JW, Lee JY, Kim JS, Min YH Tags: Clin Cancer Res Source Type: research

Aberrant Expression of microRNA-9 Contributes to Development of Intracranial Aneurysm by Suppressing Proliferation and Reducing Contractility of Smooth Muscle Cells.
CONCLUSIONS Our findings show that dysregulation of miR-9 is responsible for the development of IA via targeting MYOCD. miR-9 and its direct target, MYOCD, might novel therapeutic targets in the treatment of IA. PMID: 27824808 [PubMed - in process]
Source: Medical Science Monitor - November 10, 2016 Category: Research Tags: Med Sci Monit Source Type: research

The influence of HOXA5-specific siRNA on the expression of Livin and Smac proteins.
CONCLUSIONS: HOXA5-specific siRNA effectively silenced the HOXA5 gene expression and down-regulation of HOXA5 induced the down-regulation of Livin protein expression and up-regulation of Smac protein. We suggest the HOXA5 gene to be considered as the new target for acute leukemia gene therapy. PMID: 27460741 [PubMed - in process]
Source: European Review for Medical and Pharmacological Sciences - July 29, 2016 Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research

Profiling gene mutations, translocations, and multidrug resistance in pediatric acute lymphoblastic leukemia: a step forward to personalizing medicine
Abstract Precise risk stratification and tailored therapy in acute lymphoblastic leukemia (ALL) can lead to enhanced survival rates among children. Translocations and mutations along with multidrug resistance markers are important factors that determine therapeutic efficacy. Gene mutation profiling of patients at the time of diagnosis can offer accurate clinical decision-making. Multiplex PCR was used to screen for various translocations, mutations, and P-glycoprotein (P-gp) status in pediatric ALL samples. The roles of P-gp were analyzed at the transcriptional and translational levels by using real-time PCR and immunoblo...
Source: Medical Oncology - July 22, 2016 Category: Cancer & Oncology Source Type: research

siRNA-mediated inhibition of survivin gene enhances the anti-cancer effect of etoposide in U-937 acute myeloid leukemia cells.
Authors: Jafarlou M, Baradaran B, Shanehbandi D, Saedi TA, Jafarlou V, Ismail P, Othman F Abstract Acute myeloid leukemia (AML) is one of the most frequent types of leukemia which mostly affects adult people. Resistance to therapeutic drugs is considered as a major clinical concern resulting in a weaker response to chemotherapy, disease relapse and decreased survival rate. Survivin, a member of Inhibitor of Apoptosis Proteins (IAPs), is associated with drug resistance and inhibition of apoptotic mechanisms in numerous hematological malignancies. In the present study, we examined the combined effect of etoposide and...
Source: Cellular and Molecular Biology - June 7, 2016 Category: Molecular Biology Tags: Cell Mol Biol (Noisy-le-grand) Source Type: research