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Leukemia chemoresistance

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https://www.readbyqxmd.com/read/27903981/nurse-like-cells-promote-cll-survival-through-lfa-3-cd2-interactions
#1
Frédéric Boissard, Marie Tosolini, Laetitia Ligat, Anne Quillet-Mary, Frederic Lopez, Jean-Jacques Fournié, Loic Ysebaert, Mary Poupot
In the tumoral micro-environment (TME) of chronic lymphocytic leukemia (CLL), nurse-like cells (NLC) are tumor-associated macrophages which play a critical role in the survival and chemoresistance of tumoral cells. This pro-survival activity is known to involve soluble factors, but few data are available on the relative role of cells cross-talk. Here, we used a transcriptome-based approach to systematically investigate the expression of various receptor/ligand pairs at the surface of NLC/CLL cells. Their relative contribution to CLL survival was assessed both by fluorescent microscopy to identify cellular interactions and by the use of functional tests to measure the impact of uncoupling these pairs with blocking monoclonal antibodies...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27903673/combining-anti-mir-155-with-chemotherapy-for-the-treatment-of-lung-cancers
#2
Katrien Van Roosbroeck, Francesca Fanini, Tetsuro Setoyama, Cristina Ivan, Cristian Rodriguez-Aguayo, Enrique Fuentes-Mattei, Lianchun Xiao, Ivan Vannini, Roxana Redis, Lucilla D'Abundo, Xinna Zhang, Milena S Nicoloso, Simona Rossi, Vianey Gonzalez-Villasana, Rajesha Rupaimoole, Manuela Ferracin, Fortunato Morabito, Antonino Neri, Peter Ruvolo, Vivian R Ruvolo, Chad V Pecot, Dino Amadori, Lynne Aruzzo, Steliana Calin, Xuemei Wang, M James You, Alessandra Ferrajoli, Robert Z Orlowski, William Plunkett, Tara Lichtenberg, Ramana V Davuluri, Ioana Berindan-Neagoe, Massimo Negrini, Ignacio I Wistuba, Kantarjian Hagop, Anil K Sood, Gabriel Lopez-Berestein, Michael J Keating, Muller Fabbri, George A Calin
Purpose The oncogenic miR-155 is upregulated in many human cancers and its expression is increased in more aggressive and therapy resistant tumors, but the molecular mechanisms underlying miR-155-induced therapy resistance are not fully understood. The main objectives of this study were to determine the role of miR-155 in resistance to chemotherapy and to evaluate anti-miR-155 treatment to chemosensitize tumors. Experimental Design We performed in vitro studies on cell lines to investigate the role of miR-155 in therapy resistance...
November 30, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27902471/autophagy-autophagy-associated-adaptive-immune-responses-and-its-role-in-hematologic-malignancies
#3
REVIEW
Liangshun You, Shenhe Jin, Li Zhu, Wenbin Qian
Autophagy is a tightly regulated catabolic process that leads to the degradation of cytoplasmatic components such as aggregated/misfolded proteins and organelles through the lysosomal machinery. Recent studies suggest that autophagy plays such a role in the context of the anti-tumor immune response, make it an attractive target for cancer immunotherapy. Defective autophagy in hematopoietic stem cells may contribute to the development of hematologic malignancies, including leukemia, myelodysplastic syndrome, and lymphoproliferative disorder...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27902457/tfdp3-confers-chemoresistance-in-minimal-residual-disease-within-childhood-t-cell-acute-lymphoblastic-leukemia
#4
Ming Chu, Kailin Yin, Yujun Dong, Pingzhang Wang, Yun Xue, Peng Zhou, Yuqi Wang, Yuedan Wang
Acquired drug resistance in childhood T-cell acute lymphoblastic leukemia (T-ALL) remains a significant clinical problem. In this study, a novel gene therapy target for childhood T-ALL to overcome chemoresistance was discovered: TFDP3 increased in the minimal residual disease (MRD) positive childhood T-ALL patients. Then, we established a preclinical model of resistance to induction therapy to examine the functional relevance of TFDP3 to chemoresistance in MRD derived from Jurkat/E6-1. Jurkat xenografts in NOD/SCID mice were exposed to a four drug combination (VXLD) of vincristine (VCR), dexamethasone (DEX), L-asparaginase (L-asp) and daunorubicin (DNR)...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27895780/curcumin-potentiates-the-effect-of-chemotherapy-against-acute-lymphoblastic-leukemia-cells-via-downregulation-of-nf-%C3%AE%C2%BAb
#5
Helia Judith Pimentel-Gutiérrez, Lucina Bobadilla-Morales, César Cenobio Barba-Barba, Citlalli Ortega-De-La-Torre, Fernando Antonio Sánchez-Zubieta, Jorge Román Corona-Rivera, Betsy Annel González-Quezada, Juan S Armendáriz-Borunda, Rocío Silva-Cruz, Alfredo Corona-Rivera
Acute lymphoblastic leukemia (ALL) accounts for 30% of all pediatric cancers. Currently available treatments exhibit toxicity and certain patients may develop resistance. Thus, less toxic and chemoresistance-reversal agents are required. In the present study, the potential effect of curcumin, a component of Curcuma longa, as a pharmacological co-adjuvant of several chemotherapeutic agents against ALL, including prednisone, 6-mercaptopurine, dexamethasone, cyclophosphamide, l-asparaginase, vincristine, daunorubicin, doxorubicin, methotrexate and cytarabine, was investigated in the REH ALL cell line cultures treated in combination with chemotherapeutic agents and curcumin...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27888802/low-dose-triptolide-reverses-chemoresistance-in-adult-acute-lymphoblastic-leukemia-cells-via-reactive-oxygen-species-generation-and-dna-damage-response-disruption
#6
Haijun Zhao, Pengcheng Shi, Manman Deng, Zhiwu Jiang, Yin Li, Vinodh Kannappan, Weiguang Wang, Peng Li, Bing Xu
Chemoresistance represents a major challenge for treatment of acute lymphoblastic leukemia (ALL). Thus, new drugs to overcome chemoresistance in ALL are urgently needed. To this end, we established a cytarabine (araC)-resistant ALL cell line (NALM-6/R), which interestingly displayed cross-resistance towards doxorubicin (ADM). Here we report that low dose of triptolide (TPL), a natural product used for treating inflammatory diseases such as arthritis, could reverse araC and ADM resistance and in NALM-6/R cells as well as primary cells from patients with relapsed or refractory (R/R) ALL, reflected by inhibition of cell proliferation and induction of apoptosis in vitro, and repression of tumor growth in vivo in a mouse xenograft model...
November 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/27888629/inhibition-of-bcr-signaling-using-the-syk-inhibitor-tak-659-prevents-stroma-mediated-signaling-in-chronic-lymphocytic-leukemia-cells
#7
Noelia Purroy, Júlia Carabia, Pau Abrisqueta, Leire Egia, Meritxell Aguiló, Cecilia Carpio, Carles Palacio, Marta Crespo, Francesc Bosch
Proliferation and survival of chronic lymphocytic leukemia (CLL) cells depend on microenvironmental signals coming from lymphoid organs. One of the key players involved in the crosstalk between CLL cells and the microenvironment is the B-cell receptor (BCR). Syk protein, a tyrosine kinase essential for BCR signaling, is therefore a rational candidate for targeted therapy in CLL. Against this background, we tested the efficacy of the highly specific Syk inhibitor TAK-659 in suppressing the favorable signaling derived from the microenvironment...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27831567/erk-drp1-dependent-mitochondrial-fission-is-involved-in-the-msc-induced-drug-resistance-of-t-cell-acute-lymphoblastic-leukemia-cells
#8
Jianye Cai, Jiancheng Wang, Yinong Huang, Haoxiang Wu, Ting Xia, Jiaqi Xiao, Xiaoyong Chen, Hongyu Li, Yuan Qiu, Yingnan Wang, Tao Wang, Huimin Xia, Qi Zhang, Andy Peng Xiang
The bone marrow microenvironment facilitates the proliferation and survival of leukemia cells, contributing to disease relapse. Bone marrow-derived mesenchymal stem cells (MSCs) are well known to promote cancer chemoresistance via soluble factors and cell adhesion. However, little is known about the effects of MSCs on the mitochondrial dynamics of T-cell acute lymphoblastic leukemia (T-ALL) cells, or how this may influence the chemoresistance of these cells. Here, we tested both indirect (Transwell) and direct coculture strategies, and found that MSCs protected T-ALL cells from chemotherapeutic cell death and cytotoxicity under both culture conditions...
November 10, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27823652/current-evidence-for-cancer-stem-cells-in-gastrointestinal-tumors-and-future-research-perspectives
#9
REVIEW
Miriam López-Gómez, Enrique Casado, Marta Muñoz, Sonia Alcalá, Juan Moreno-Rubio, Gabriele D'Errico, Ana María Jiménez-Gordo, Silvia Salinas, Bruno Sainz
Cancer stem cells (CSCs) are a very heterogeneous subpopulation of "stem-like" cancer cells that have been identified in many cancers, including leukemias and solid tumors. It is believed that CSCs drive tumor growth, malignant behavior and are responsible for the initiation of metastatic spread. In addition, CSCs have been implicated in chemotherapy and radiotherapy resistance. Current evidence supports the theory that CSCs share at least two main features of normal stem cells: self-renewal and differentiation, properties that contribute to tumor survival even in the presence of aggressive chemotherapy; however, the mechanism(s) governing the unique biology of CSCs remain unclear...
November 2016: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/27818289/hpip-expression-predicts-chemoresistance-and-poor-clinical-outcomes-in-patients-with-epithelial-ovarian-cancer
#10
Yao Wang, Mingxun Li, Fanling Meng, Ge Lou
This study aims to investigate the expression of HPIP, the Hematopoietic pre-B cell leukemia transcription factor (PBX)-interacting protein, and its association with platinum resistance in epithelial ovarian cancer (EOC). The protein expression of HPIP was analyzed by immunohistochemistry in 248 patients with EOC. Furthermore, we analyzed the association between HPIP expression and clinicopathological features including prognosis in EOC samples. High HPIP expression was correlated with platinum resistance in EOCs...
November 3, 2016: Human Pathology
https://www.readbyqxmd.com/read/27778231/identification-of-potential-predictive-markers-of-dexamethasone-resistance-in-childhood-acute-lymphoblastic-leukemia
#11
Nasrin Dehghan-Nayeri, Mostafa Rezaei-Tavirani, Mir Davood Omrani, Ahmad Gharehbaghian, Kourosh Goudarzi Pour, Peyman Eshghi
Response to dexamethasone (DEXA), as a hallmark drug in the treatment of childhood acute lymphoblastic leukemia (ALL), is one of the pivotal prognostic factors in the prediction of outcome in ALL. Identification of predictive markers of chemoresistance is beneficial to selecting of the best therapeutic protocol with the lowest effect adverse. Hence, we aimed to find drug targets using the 2DE/MS proteomics study of a DEXA-resistant cell line (REH) as a model for poor DEXA responding patients before and after drug treatment...
October 24, 2016: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/27756303/oligomeric-interface-modulation-causes-misregulation-of-purine-5%C3%A2-nucleotidase-in-relapsed-leukemia
#12
Aleš Hnízda, Jana Škerlová, Milan Fábry, Petr Pachl, Martina Šinalová, Lukáš Vrzal, Petr Man, Petr Novák, Pavlína Řezáčová, Václav Veverka
BACKGROUND: Relapsed acute lymphoblastic leukemia (ALL) is one of the main causes of mortality in childhood malignancies. Previous genetic studies demonstrated that chemoresistant ALL is driven by activating mutations in NT5C2, the gene encoding cytosolic 5´-nucleotidase (cN-II). However, molecular mechanisms underlying this hyperactivation are still unknown. Here, we present kinetic and structural properties of cN-II variants that represent 75 % of mutated alleles in patients who experience relapsed ALL (R367Q, R238W and L375F)...
October 19, 2016: BMC Biology
https://www.readbyqxmd.com/read/27721018/musashi-2-contributes-to-the-stemness-and-chemoresistance-of-liver-cancer-stem-cells-via-lin28a-activation
#13
Tian Fang, Hongwei Lv, Fuquan Wu, Changzheng Wang, Ting Li, Guishuai Lv, Liang Tang, Linna Guo, Shanhua Tang, Dan Cao, Mengchao Wu, Wen Yang, Hongyang Wang
Accumulating evidence suggests that cancer stem cells (CSCs), a small subset of cancer cells, are responsible for tumor initiation, progression, relapse and metastasis. Musashi 2 (MSI2), a RNA-binding protein, was proposed to be a potent oncogene playing key roles in myeloid leukemia and gastrointestinal malignancies. However, it remains elusive how MSI2 regulates stem cell features in HCC. Herein, we demonstrated that MSI2 was highly expressed in liver CSCs. Overexpression or knockdown of MSI2 altered CSC-related gene expression, self-renewal as well as resistance to chemotherapy in HCC cell lines...
January 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/27707884/ikaros-6-protects-acute-lymphoblastic-leukemia-cells-against-daunorubicin-induced-apoptosis-by-activating-the-akt-foxo1-pathway
#14
Juan Han, Runming Jin, Meiling Zhang, Qing Guo, Fen Zhou
Ikaros isoform 6 (Ik6) is associated with a poor prognosis for children with acute lymphoblastic leukemia (ALL). Our previous study demonstrated that overexpression of Ik6 enhances proliferation and chemoresistance of leukemia cells, with a possible underlying mechanism that involves antiapoptosis. In the present study, we investigated whether Ik6 protects against apoptosis by regulating the Akt-FoxO1 pathway. Bone marrow samples from children with ALL were collected and evaluated. In Ik6(+) patients, the Akt-FoxO1 pathway was activated such that expression of phosphorylated Akt and FoxO1 was significantly increased, but that of Bim and p27 decreased...
October 5, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27697766/epcam-inhibition-sensitizes-chemoresistant-leukemia-to-immune-surveillance
#15
Xiaohu Zheng, Xiaolei Fan, Binqing Fu, Meijuan Zheng, Aimei Zhang, Kai Zhong, Jialai Yan, Rui Sun, Zhigang Tian, Haiming Wei
The lack of effective tumor-associated antigens restricts the development of targeted therapies against myeloid leukemia. In this study, we compared gene expression patterns of acute myeloid leukemia (AML) and normal bone marrow samples and found that epithelial cell adhesion molecule (EpCAM) is frequently overexpressed in patients with AML, with EpCAM+ leukemic cells exhibiting enhanced chemoresistance and oncogenesis. The chemotherapeutic resistance of EpCAM-positive leukemic cells is a consequence of increased WNT5B signaling...
October 3, 2016: Cancer Research
https://www.readbyqxmd.com/read/27694928/nuclear-foxm1-drives-chemoresistance-in-aml
#16
I Khan, M Halasi, M F Zia, P Gann, S Gaitonde, N Mahmud, A L Gartel
No abstract text is available yet for this article.
October 21, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27666896/microrna-101-regulates-t-cell-acute-lymphoblastic-leukemia-progression-and-chemotherapeutic-sensitivity-by-targeting-notch1
#17
Lu Qian, Wanggang Zhang, Bo Lei, Aili He, Lianhong Ye, Xingzhou Li, Xin Dong
The present study aimed to investigate the role of microRNA (miR)-101 in acute lymphoblastic leukemia progression and chemoresistance. Furthermore, a novel target gene of miR-101 was identified. Here, we confirmed that miR-101 was significantly downregulated in the blood samples of patients with T-cell acute lymphoblastic leukemia (T-ALL) compared with the healthy controls, as determined by reverse transcription quantitative polymerase chain reaction (RTqPCR) analysis. The in vitro experiments demonstrated that miR-101 significantly repressed the proliferation and invasion, and induced potent apoptosis in Jurkat cells, as determined by CCK-8, flow cytometer and cell invasion assays...
September 21, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27662839/potential-role-of-shh-gli1-bmi1-signaling-pathway-nexus-in-glioma-chemoresistance
#18
M H Shahi, S Farheen, M P M Mariyath, J S Castresana
Chemoresistance is a common hurdle for the proper treatment of gliomas. The role of Shh-Gli1 signaling in glioma progression has been reported. However, its role in glioma chemoresistance has not been well studied yet. In this work, we found that Shh-Gli1 signaling regulates the expression of one stem cell marker, BMI1 (B cell-specific Moloney murine leukemia virus), in glioma. Interestingly, we also demonstrated high expression of MRP1 (multi-drug resistance protein 1) in glioma. MRP1 expression was decreased by BMI1 siRNA and Shh-Gli1 cell signaling specific inhibitor GANT61 in our experiments...
September 23, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/27658583/hypoxia-promotes-chemoresistance-in-acute-lymphoblastic-leukemia-cell-lines-by-modulating-death-signaling-pathways
#19
C Petit, F Gouel, I Dubus, C Heuclin, K Roget, J P Vannier
BACKGROUND: Several studies show that bone marrow (BM) microenvironment and hypoxia condition can promote the survival of leukemic cells and induce resistance to anti-leukemic drugs. However, the molecular mechanism for chemoresistance by hypoxia is not fully understood. METHODS: In the present study, we investigated the effect of hypoxia on resistance to two therapies, methotrexate (MTX) and prednisolone (PRD), in two cell models for acute lymphoblastic leukemia (ALL)...
2016: BMC Cancer
https://www.readbyqxmd.com/read/27644318/increased-pkc%C3%AE-activity-by-rack1-overexpression-is-responsible-for-chemotherapy-resistance-in-t-cell-acute-lymphoblastic-leukemia-derived-cell-line
#20
Jie Lei, Qi Li, Ying Gao, Lei Zhao, Yanbo Liu
Chemoresistant mechanisms in T-cell acute lymphoblastic leukemia (T-ALL) patients are not clarified. The apoptotic signaling mediated by receptor of activated C kinase 1 (Rack1), protein kinase C (PKC) and FEM1 homolog b (FEM1b) was investigated in two T-ALL-derived cell lines (Jurkat and CCRF-CEM) following treatment with chemotherapy drugs vincristine and prednisone. Serum starvation or chemotherapeutic drugs significantly reduced Rack1 level and PKC activation, while promoted cellular apoptosis in both cell lines...
2016: Scientific Reports
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