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Leukemia expression

Gaoliang Cheng, Zhi Wang, Jinyu Yang, Yu Bao, Qihao Xu, Linxiang Zhao, Dan Liu
HDAC inhibitors and BRD4 inhibitors were considered to be potent anti-cancer agents. Recent studies have demonstrated that HDAC and BRD4 participate in the regulation of some signal paths like PI3K-AKT. In this work, a series of indole derivatives that combine the inhibitory activities of BRD4 and HDAC into one molecule were designed and synthesized through the structure-based design method. Most compounds showed potent HDAC inhibitory activity and moderate BRD4 inhibitory activity. In vitro anti-proliferation activities of the synthesized compounds were also evaluated...
December 10, 2018: Bioorganic Chemistry
Tianjiao Wang, Brandi Glover, Gayla Hadwiger, Christopher A Miller, Orsola di Martino, John S Welch
SMC3 encodes a subunit of the cohesin complex that has canonical roles in regulating sister chromatids segregation during mitosis and meiosis. Recurrent heterozygous mutations in SMC3 have been reported in acute myeloid leukemia (AML) and other myeloid malignancies. In this study, we investigated whether the missense mutations in SMC3 might have dominant-negative effects or phenocopy loss-of-function effects by comparing the consequences of Smc3 deficient and haploinsufficient mouse models. We found that homozygous deletion of Smc3 during embryogenesis or in adult mice led to hematopoietic failure, suggesting that SMC3 missense mutations are unlikely to be associated with simple dominant negative phenotypes...
December 13, 2018: Experimental Hematology
Yuhua Ding, Huihui Xu, Luyang Li, Yibiao Yuan, Yong Xu
Diabetic retinopathy (DR) is one of the most devastating complications of diabetes mellitus. When exposed to high glucose (HG), retinal epithelial cells undergo profound alterations both morphologically and functionally in a well-conserved process known as epithelial-to-mesenchymal transition (EMT). The mechanism governing HG-induced EMT in retinal epithelial cells is not completely understood. Here we report that treatment with 25 mM glucose led to EMT in retinal pigmented epithelial cells (RPE) characterized by a simultaneous down-regulation of E-Cadherin (encoded by CDH1) and up-regulation of alpha smooth muscle actin (encoded by ACTA2)...
December 13, 2018: Biochemical and Biophysical Research Communications
Rik A Brooimans, Vincent H J van der Velden, Nancy Boeckx, Jennita Slomp, Frank Preijers, Jeroen G Te Marvelde, Ngoc M Van, Antoinette Heijs, Erik Huys, Bronno van der Holt, Georgine E de Greef, Angele Kelder, Gerrit Jan Schuurhuis
Flow-cytometric detection of now termed measurable residual disease (MRD) in acute myeloid leukemia (AML) has proven to have an independent prognostic impact. In a previous multicenter study we developed protocols to accurately define leukemia-associated immunophenotypes (LAIPs) at diagnosis. It has, however, not been demonstrated whether the use of the defined LAIPs in the same multicenter setting results in a high concordance between centers in MRD assessment. In the present paper we evaluated whether interpretation of list-mode data (LMD) files, obtained from MRD assessment of previously determined LAIPs during and after treatment, could reliably be performed in a multicenter setting...
November 27, 2018: Leukemia Research
Julhash U Kazi, Lars Rönnstrand
The receptor tyrosine kinase FLT3 is expressed almost exclusively in the hematopoietic compartment. Binding of its ligand, FLT3 ligand (FL), induces dimerization and activation of its intrinsic tyrosine kinase activity. This leads to autophosphorylation of FLT3 on several tyrosine residues which constitute high affinity binding sites for signal transduction molecules. Recruitment of these signal transduction molecules to FLT3 leads to the activation of several signal transduction pathways that regulate cell survival, cell proliferation and differentiation...
December 12, 2018: International Journal of Biochemistry & Cell Biology
Qun Luo, Wanglong Deng, Haiwei Wang, Huiyong Fan, Ji Zhang
Bromodomain-containing 4 (BRD4) has been considered as an important requirement for disease maintenance and an attractive therapeutic target for cancer therapy. This protein can be targeted by JQ1, a selective small-molecule inhibitor. However, few studies have investigated whether BRD4 influenced acute promyelocytic leukemia (APL), and whether BRD4 had interaction with promyelocytic leukemia-retinoic acid receptor α (PML/RARα) fusion protein to some extent. Results from cell viability assay, cell cycle analysis, and Annexin-V/PI analysis indicated that JQ1 inhibited the growth of NB4 cells, an APL-derived cell line, and induced NB4 cell cycle arrest at G1 and apoptosis...
December 2018: Frontiers of Medicine
Jong-Heon Won, Kyung-Sook Chung, Eun-Young Park, Jeong-Hun Lee, Jung-Hye Choi, Leon Azefack Tapondjou, Hee-Juhn Park, Masaaki Nomura, Ahmed H E Hassan, Kyung-Tae Lee
The natural product 23-hydroxyursolic acid (23-HUA) is a derivative of ursolic acid, which is known to induce cancer cell apoptosis. However, apoptotic effects and mechanisms of 23-HUA have not been well characterized yet. Herein, we investigated the molecular mechanisms of 23-HUA-induced apoptosis in HL-60 human promyelocytic leukemia cells. 23-HUA-treated HL-60 cells showed apoptotic features including internucleosomal DNA condensation and fragmentation as well as externalization of phosphatidylserine residues...
December 13, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Xiaochuan Su, Junyan Teng, Guoguo Jin, Jitian Li, Zhenjiang Zhao, Xiangyang Cao, Yanxing Guo, Malong Guo, Xiaoling Li, Jun Wu, Chuanzhen Wang, Zhiping Guo, Qing Guo
Osteosarcoma (OS) is the commonest malignant bone tumor in the world. High incidence of OS has gradually become a social problem. Recent years, numerous studies have revealed that long non-coding RNAs (lncRNAs) are crucial regulators in the tumor progression. As a member of lncRNA family, MIR100HG has been reported to be an oncogene in breast cancer and acute megakaryoblastic leukemia. Nevertheless, the specific role of MIR100HG in osteosarcoma is still unclear. In this study, we investigated the biological function and molecular mechanism of MIR100HG in the progression of osteosarcoma...
January 2019: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Zahra Payandeh, Armina Alagheband Bahrami, Reyhaneh Hoseinpoor, Yousef Mortazavi, Masoumeh Rajabibazl, Azam Rahimpour, Amir Hossein Taromchi, Saeed Khalil
B-lymphocyte antigen CD20 (called CD20) is known as an activated-glycosylated phosphoprotein which is expressed on the surface of all B-cells. CD20 is involved in the regulation of trans-membrane Ca2+ conductance and also play critical roles in cell-cycle progression during human B cell proliferation and activation. The appearance of monoclonal antibody (mAb) technology provided an effective field for targeted therapy in treatment of a variety of diseases such as cancer, and autoimmune diseases. Anti-CD20 is one of important antibodies which could be employed in treatment of several diseases...
January 2019: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Jinfeng Xiang, Gang Wang, Tian Xia, Zhixin Chen
Mutation of PHF6 has been identified in Börjeson-Forssman-Lehmann syndrome and some types of subsets of childhood leukemia. However, the molecular function and the relationship of PHF6 mutation with glucocorticoid drug resistance during T-ALL treatment remains elusive. Here we report the influence of PHF6 expression on the drug response of T-ALL to prednisolone, and the underlying mechanism of this. Through sanger sequencing and western blotting assays, we identified two T-ALL cell lines with wild-type PHF6 expression, including SIL-ALL and CCRF-CEM, and two T-ALL cell lines without PHF6 expression, including TALL-1 and HPB-ALL, due to the nonsense and frameshift mutations in the coding region of PHF6...
January 2019: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Rastislav Jendželovský, Zuzana Jendželovská, Barbora Kuchárová, Peter Fedoročko
Breast cancer resistance protein (BCRP) belongs to the family of ATP-binding cassette (ABC) transporters, overexpression of which can confer a multidrug-resistant phenotype in cancer cells and tumors. BCRP mediates efflux of numerous xenobiotics, including various chemotherapeutic agents and photosensitizers. Hypericin (HY) is a naturally-occurring photosensitizer synthesized by plants of the genus Hypericum. Our recently published results indicate that accumulation of HY in cancer cells of different tissue origin can be affected mostly by BCRP...
January 2019: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Min Xin, Yong Wang, Qianyao Ren, Yanhong Guo
Many breast cancer patients suffer from obvious side effects induced by chemotherapy. Formononetin (FM), one kind ingredient of Chinese herbal medicine, has been suggested to inhibit MCF-7 breast cancer cells. And recently metformin (MET) has gained more attention as a potential anti-cancer drug. The aim of this study was to investigate the synergistic effects of FM and MET on the proliferation of MCF-7 cells and to clarify the possible molecular mechanism involved. MCF-7 cells were treated with various concentrations of FM (40 and 80 μM) or FM (40 and 80 μM) combined with MET (150 μM) for 48 h...
January 2019: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Qun Li, Wei Song, Jianmin Wang
Increasing evidence has suggested the involvement of long non-coding RNA (lncRNA) taurine upregulated gene 1 (TUG1) in chemoresistance of cancer treatment. However, its function and molecular mechanisms in acute myeloid leukemia (AML) chemoresistance are still not well elucidated. In the present study, we investigate the functional role of TUG1 in Adriamycin (ADR) resistance of AML and discover the underlying molecular mechanism. Our study revealed that TUG1 was up-regulated in ADR-resistant AML tissues and cells...
January 2019: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Qiuju Zhao, Shihao Zhao, Jinling Li, Huiwu Zhang, Cheng Qian, He Wang, Jianjun Liu, Yuqi Zhao
Acute lymphoblastic leukemia (ALL) is characterized by abnormal lymphoblasts accumulation in the bone marrow and blood. Despite great efforts have been made in exploring novel therapeutic method, the prognosis of children with ALL is still unsatisfied. Glucocorticoid (GC) resistance is a great obstacle for the clinical treatment of ALL. Therefore, it is essential to investigate the molecular mechanism underlying the GC resistance. According to previous reports, long noncoding RNAs (lncRNAs) are involved in drug resistance of various human cancers...
January 2019: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Yan-Lai Tang, Xi Sun, Li-Bin Huang, Xiao-Jian Liu, Ge Qin, Li-Na Wang, Xiao-Li Zhang, Zhi-Yong Ke, Jie-Si Luo, Cong Liang, Chun-Jin Peng, Wen-Yan Tang, Yu Li, Wenlin Huang, Xue-Qun Luo, Wuguo Deng
MLL-rearranged leukemia is an aggressive malignancy associated with poor outcome, which is refractory to conventional treatment. Melatonin has been proven to exert anti-tumor activity, but the effect of melatonin on MLL-r leukemia and the underlying mechanism remain poorly understood. In this study, melatonin inhibited cell proliferation and induced apoptosis by activating the caspase-dependent apoptotic pathway in MLL-r leukemia cells. Mechanistic investigations revealed that melatonin suppressed the expression of hTERT by abrogating the binding activity of RBFOX3 to the hTERT promoter...
December 10, 2018: Cancer Letters
Yuki Kageyama, Hiroshi Miwa, Rino Arakawa, Isao Tawara, Kohshi Ohishi, Masahiro Masuya, Kazunori Nakase, Naoyuki Katayama
CD25 is expressed on leukemic cells in 10-20% cases of acute myeloid leukemia (AML), and its expression is associated with poor prognosis. We reevaluated the relationship between CD25 expression and the leukemia-initiating cell (LIC) properties of AML using a patient-derived xenograft model. We divided lineage marker-negative (Lin-) CD34+CD38- or Lin-CD34+ cells from CD25-positive AML into CD25-positive and -negative populations, and then transplanted each population into NOD.Cg-PrkdcscidIl2rgtm1Wjl/Sz mice...
2018: PloS One
Shlomit Yehudai-Resheff, Shira Attias-Turgeman, Rawan Sabbah, Tal Gabay, Raneem Musallam, Anna Friedman-Dror, Tsila Zuckerman
Hematopoietic progenitors, residing in the bone marrow (BM) niche, are supported by mesenchymal stromal cells (MSCs). Cytogenetic and molecular aberrations in these progenitors lead to acute myeloid leukemia (AML). The BM-MSC role in leukemogenesis is not fully elucidated. In the current study, an ex-vivo system of patient's own stroma (POS), best mimicking the in-vivo BM niche, has been developed aiming to unravel interactions and crosstalk between MSCs and AML cells. POS derived from AML patients at diagnosis (Dx), relapse (Rx) and remission (Rm) was compared with healthy donor MSCs in terms of their morphology, growth pattern, support of leukemia cell viability and cytokine profile...
December 13, 2018: International Journal of Cancer. Journal International du Cancer
Haruka Shinohara, Nobuhiko Sugito, Yuki Kuranaga, Kazuki Heishima, Yosuke Minami, Tomoki Naoe, Yukihiro Akao
Therapy based on targeted inhibition of BCR-ABL tyrosine kinase has greatly improved the prognosis for patients with Philadelphia chromosome (Ph)-positive leukemia and tyrosine kinase inhibitors (TKIs) have become the standard therapy. However, some patients acquire resistance to TKIs that is frequently associated with point mutations in the BCR-ABL. We previously reported that a medium-chain fatty-acid derivative AIC-47 induced transcriptional suppression of BCR-ABL and perturbation of the Warburg effect, leading to growth inhibition in Ph-positive leukemia cells...
December 12, 2018: Cancer Science
Sedigheh Eskandari, Razieh Yazdanparast
Tyrosine kinase inhibitor (TKI)-based therapy has created promising results among much chronic myeloid leukemia (CML) patients. Imatinib as a relatively specific inhibitor of Bcr-Abl is at present one of the undisputed therapeutic agent for newlydiagnosed patients with CML. However, the occurrence of imatinib-resistance enlightens the urgent need to identify other therapeutic agents against CML. Juglone (5-hydroxy-2-methyl-1, 4-naphthoquinone) exerts cytotoxic effects against various human cancer cell lines...
December 11, 2018: Journal of Cellular Biochemistry
Sreejit Parameswaran, Frederick S Vizeacoumar, Kalpana Kalyanasundaram Bhanumathy, Fujun Qin, Md Fahmid Islam, Behzad M Toosi, Chelsea E Cunningham, Darrell D Mousseau, Maruti C Uppalapati, Peter C Stirling, Yuliang Wu, Keith Bonham, Andrew Freywald, Hui Li, Franco J Vizeacoumar
Chromosomal rearrangements involving the mixed-lineage leukemia (MLL1) gene are common in a unique group of acute leukemias, with more than 100 fusion partners in this malignancy alone. However, do these fusions occur or have a role in solid tumors? We performed extensive network analyses of MLL1-fusion partners in patient datasets, revealing that multiple MLL1-fusion partners exhibited significant interactions with the androgen-receptor signaling pathway. Further exploration of tumor sequence data from TCGA predicts the presence of MLL1 fusions with truncated SET domain in prostate tumors...
December 8, 2018: Molecular Oncology
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