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leukemia MicroEnvironment

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https://www.readbyqxmd.com/read/28454398/immunological-effects-of-vaccines-combined-with-granulocyte-colony-stimulating-factor-on-a-murine-wehi-3-leukemia-model
#1
Jinqiu Chen, Miling Zhang, Fuling Zhou, Jin Wang, Ben Niu, Wanggang Zhang
Granulocyte colony-stimulating factor (G-CSF) mobilizes regulatory T cells (Tregs) from bone marrow into the peripheral blood, by reducing the expression of stromal cell-derived factor-1α (SDF-1α). However, G-CSF has rarely been studied in acute myeloid leukemia (AML) immunotherapy. The present study performed a Transwell migration assay in vitro to determine the contribution of SDF-1α to the migration of leukemia cells, and the effects of G-CSF were evaluated. The effects of G-CSF on SDF-1α and Tregs in the AML microenvironment were examined, by employing a WEHI-3-grafted BALB/c mouse AML model (AML-M4)...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28445830/overexpression-of-heme-oxygenase-1-in-bone-marrow-stromal-cells-promotes-microenvironment-mediated-imatinib-resistance-in-chronic-myeloid-leukemia
#2
Ping Liu, Dan Ma, Zhengyu Yu, Nana Zhe, Mei Ren, Ping Wang, Meisheng Yu, Jun Huang, Qin Fang, Jishi Wang
Neoplasm cells from patients with chronic myeloid leukemia (CML) interact with stromal cells of the surrounding microenvironment. Bone marrow stromal cells (BMSCs) represent the main population in CML marrow stroma, which may play a key role in disease support and progression. Heme oxygenase-1 (HO-1) is a key enzyme of antioxidative metabolism that is associated with cell proliferation and resistance to apoptosis. We herein up-regulated HO-1 expression of BMSCs and evaluated whether BMSCs influenced K562 cells survival...
April 23, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28441794/reciprocal-interactions-of-leukemic-cells-with-bone-marrow-stromal-cells-promote-enrichment-of-leukemic-stell-cell-compartments-in-response-to-curcumin-and-daunorubicin
#3
Saeed Mohammadi, Mohsen Nikbakht, Seyed Mehdi Sajjadi, Fariba Rad, Bahram Chahardouli, Javid Sabour Takanlu, Shahrbano Rostami, Kamran Alimoghaddam, Ardeshir Ghavamzadeh, Seyed H Ghaffari
A predominant challenge in developing curative leukemia therapy is interactions of leukemic cells with the bone marrow stromal microenvironment. We aimed to investigate the role of stromal cells, such as bone marrow mesenchymal stromal cells (BMSCs) and osteoblasts (OBs), in curcumin (CUR) and daunorubicin (DNR) induced apoptosis of acute myeloid leukemia (AML) cells. We used KG1 and U937 as leukemia cell line models and treated them with CUR and DNR. The cells were then co-cultured with BMSCs or a combination of BMSCs and OBs as feeders...
March 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28435287/serum-galectin-1-in-patients-with-multiple-myeloma-associations-with-survival-angiogenesis-and-biomarkers-of-macrophage-activation
#4
Morten Nørgaard Andersen, Maja Ludvigsen, Niels Abildgaard, Irma Petruskevicius, Rikke Hjortebjerg, Mette Bjerre, Bent Honoré, Holger J Møller, Niels F Andersen
Galectin-1 (Gal-1) is known to regulate cell signaling within the immune system and may be a target for new anticancer immune therapy. In patients with chronic lymphocytic leukemia (CLL) and classical Hodgkin lymphoma (cHL), high levels of Gal-1 within the tumor microenvironment were associated with worse disease state or poor outcome. Gal-1 can be secreted from cells by an unknown mechanism, and levels in blood samples were associated with high tumor burden and worse disease state in cHL and CLL patients. However, serum levels of Gal-1 have never been investigated in patients with multiple myeloma (MM)...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28426555/creating-artificial-lymphoid-tissues-to-study-immunity-and-hematological-malignancies
#5
Shivem B Shah, Ankur Singh
PURPOSE OF REVIEW: The specialized microenvironments of lymphoid tissue affect immune cell function and progression of disease. However, current animal models are low throughput and a large number of human diseases are difficult to model in animals. Animal models are less amenable to manipulation of tissue niche components, signalling pathways, epigenetics, and genome editing than ex vivo models. On the other hand, conventional 2D cultures lack the physiological relevance to study precise microenvironmental interactions...
April 19, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28424162/pembrolizumab-in-patients-with-chronic-lymphocytic-leukemia-with-richter-s-transformation-and-relapsed-cll
#6
Wei Ding, Betsy R LaPlant, Timothy G Call, Sameer A Parikh, Jose F Leis, Rong He, Tait D Shanafelt, Sutapa Sinha, Jennifer Le-Rademacher, Andrew L Feldman, Thomas M Habermann, Thomas E Witzig, Gregory A Wiseman, Yi Lin, Erik Asmus, Grzegorz S Nowakowski, Michael J Conte, Deborah A Bowen, Casey N Aitken, Daniel L Van Dyke, Patricia T Greipp, Xin Liu, Xiaosheng Wu, Henan Zhang, Charla R Secreto, Shulan Tian, Esteban Braggio, Linda E Wellik, Ivana Micallef, David S Viswanatha, Huihuang Yan, Asher A Chanan-Khan, Neil E Kay, Haidong Dong, Stephen M Ansell
CLL patients progressed early on ibrutinib often develop Richter's transformation (RT) with short survival about 4 months. Preclinical studies suggest that programmed death 1 (PD-1) pathway is critical to inhibit immune surveillance in CLL. This phase 2 study MC1485 (NCT02332980) was designed to test the efficacy and safety of pembrolizumab, a humanized PD-1-blocking antibody, at a dose of 200 mg every 3 weeks in relapsed and transformed CLL. Twenty-five patients including 16 relapsed CLL and 9 RT (all proven diffuse large cell lymphoma) patients were enrolled and 60% received prior ibrutinib...
April 19, 2017: Blood
https://www.readbyqxmd.com/read/28409853/a-phase-1-study-of-the-cxcr4-antagonist-plerixafor-in-combination-with-high-dose-cytarabine-and-etoposide-in-children-with-relapsed-or-refractory-acute-leukemias-or-myelodysplastic-syndrome-a-pediatric-oncology-experimental-therapeutics-investigators-consortium
#7
Todd M Cooper, Edward Allan Racela Sison, Sharyn D Baker, Lie Li, Amina Ahmed, Tanya Trippett, Lia Gore, Margaret E Macy, Aru Narendran, Keith August, Michael J Absalon, Jessica Boklan, Jessica Pollard, Daniel Magoon, Patrick A Brown
BACKGROUND: Plerixafor, a reversible CXCR4 antagonist, inhibits interactions between leukemic blasts and the bone marrow stromal microenvironment and may enhance chemosensitivity. A phase 1 trial of plerixafor in combination with intensive chemotherapy in children and young adults with relapsed or refractory acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and myelodysplastic syndrome (MDS) was performed to determine a tolerable and biologically active dose. PROCEDURE: Plerixafor was administered daily for 5 days at four dose levels (6, 9, 12, and 15 mg/m(2) /dose) followed 4 hr later by high-dose cytarabine (every 12 hr) and etoposide (daily)...
April 14, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28400620/tunneling-nanotubes-facilitate-autophagosome-transfer-in-the-leukemic-niche
#8
B de Rooij, R Polak, F Stalpers, R Pieters, M L den Boer
Acute lymphoblastic leukemia (ALL) cells create a leukemic niche with mesenchymal stromal cells (MSCs). Cytoskeletal structures called tunneling nanotubes (TNTs) facilitate communication between ALL cells and MSCs by transporting molecules and inducing the secretion of pro-survival cytokines. The identity of the molecules driving these malignant processes are currently unknown. Here we investigate which structures are transported from ALL cells toward MSCs by quantifying the transfer of ectopically expressed fluorescent marker proteins using flow cytometry...
April 12, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28394200/alteration-analysis-of-bone-marrow-mesenchymal-stromal-cells-from-de-novo-acute-myeloid-leukemia-patients-at-diagnosis
#9
Laura Desbourdes, Joaquim Javary, Thomas Charbonnier, Nicole Ishac, Jerome Bourgeais, Aurore Iltis, Jean-Claude Chomel, Ali Turhan, Fabien Guilloton, Karin Tarte, Marie-Veronique Demattei, Elfi Ducrocq, Florence Rouleux-Bonnin, Emmanuel Gyan, Olivier Hérault, Jorge Domenech
Bone marrow (BM)-derived mesenchymal stromal cells (MSCs) frequently display alterations in several hematologic disorders, such as acute lymphoid leukemia, acute myeloid leukemia (AML), and myelodysplastic syndromes. In acute leukemias, it is not clear whether MSC alterations contribute to the development of the malignant clone or whether they are simply the effect of tumor expansion on the microenvironment. We extensively investigated the characteristics of MSCs isolated from the BM of patients with de novo AML at diagnosis (L-MSCs) in terms of phenotype (gene and protein expression, apoptosis and senescence levels, DNA double-strand break formation) and functions (proliferation and clonogenic potentials, normal and leukemic hematopoiesis-supporting activity)...
April 10, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28388280/duvelisib-a-phosphoinositide-3-kinase-%C3%AE-%C3%AE-inhibitor-for-chronic-lymphocytic-leukemia
#10
Hima V Vangapandu, Nitin Jain, Varsha Gandhi
Frontline chemotherapy is successful against chronic lymphocytic leukemia (CLL), but results in untoward toxicity. Further, prognostic factors, cytogenetic anomalies, and compensatory cellular signaling lead to therapy resistance or disease relapse. Therefore, for the past few years, development of targeted therapies is on the rise. PI3K is a major player in the B-cell receptor (BCR) signaling axis, which is critical for the survival and maintenance of B cells. Duvelisib, a PI3K δ/γ dual isoform specific inhibitor that induces apoptosis and reduces cytokine and chemokine levels in vitro, holds promise for CLL...
May 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28355571/identification-of-interleukin-1-by-functional-screening-as-a-key-mediator-of-cellular-expansion-and-disease-progression-in-acute-myeloid-leukemia
#11
Alyssa Carey, David K Edwards, Christopher A Eide, Laura Newell, Elie Traer, Bruno C Medeiros, Daniel A Pollyea, Michael W Deininger, Robert H Collins, Jeffrey W Tyner, Brian J Druker, Grover C Bagby, Shannon K McWeeney, Anupriya Agarwal
Secreted proteins in the bone marrow microenvironment play critical roles in acute myeloid leukemia (AML). Through an ex vivo functional screen of 94 cytokines, we identified that the pro-inflammatory cytokine interleukin-1 (IL-1) elicited profound expansion of myeloid progenitors in ∼67% of AML patients while suppressing the growth of normal progenitors. Levels of IL-1β and IL-1 receptors were increased in AML patients, and silencing of the IL-1 receptor led to significant suppression of clonogenicity and in vivo disease progression...
March 28, 2017: Cell Reports
https://www.readbyqxmd.com/read/28350342/the-role-of-pi3k-isoforms-in-regulating-bone-marrow-microenvironment-signaling-focusing-on-acute-myeloid-leukemia-and-multiple-myeloma
#12
REVIEW
Rachel E Piddock, Kristian M Bowles, Stuart A Rushworth
Despite the development of novel treatments in the past 15 years, many blood cancers still remain ultimately fatal and difficult to treat, particularly acute myeloid leukaemia (AML) and multiple myeloma (MM). While significant progress has been made characterising small-scale genetic mutations and larger-scale chromosomal translocations that contribute to the development of various blood cancers, less is understood about the complex microenvironment of the bone marrow (BM), which is known to be a key player in the pathogenesis of chronic lymphocytic leukaemia (CLL), AML and MM...
March 28, 2017: Cancers
https://www.readbyqxmd.com/read/28348148/inhibition-of-wnt-signaling-in-the-bone-marrow-niche-prevents-the-development-of-mds-in-the-apc-del-mds-mouse-model
#13
Angela Stoddart, Jianghong Wang, Chunmei Hu, Anthony A Fernald, Elizabeth M Davis, Jason X Cheng, Michelle M Le Beau
There is accumulating evidence that functional alteration(s) of the bone marrow (BM) microenvironment contributes to the development of some myeloid disorders, such as myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). In addition to a cell intrinsic role of WNT activation in leukemia stem cells, WNT activation in the BM niche is also thought to contribute to the pathogenesis of MDS and AML. We previously showed that Apc haploinsufficient mice (Apc(del/+) ) model MDS induced by an aberrant BM microenvironment...
March 27, 2017: Blood
https://www.readbyqxmd.com/read/28344315/proteomic-characterization-of-human-multiple-myeloma-bone-marrow-extracellular-matrix
#14
S V Glavey, A Naba, S Manier, K Clauser, S Tahri, J Park, M R Reagan, M Moschetta, Y Mishima, M Gambella, A Rocci, A Sacco, M E O'Dwyer, J M Asara, A Palumbo, A M Roccaro, R O Hynes, I M Ghobrial
The extracellular matrix (ECM) is a major component of the tumor microenvironment, contributing to the regulation of cell survival, proliferation, differentiation and metastasis. In multiple myeloma (MM), interactions between MM cells and the bone marrow (BM) microenvironment, including the BM ECM, are critical to the pathogenesis of the disease and the development of drug resistance. Nevertheless, composition of the ECM in MM and its role in supporting MM pathogenesis has not been reported. We have applied a novel proteomic-based strategy and defined the BM ECM composition in patients with monoclonal gammopathy of undetermined significance (MGUS), newly diagnosed and relapsed MM compared to healthy donor-derived BM ECM...
March 27, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28341737/abnormal-bone-marrow-microenvironment-contributes-to-hematopoietic-dysfunction-in-fanconi-anemia
#15
Yuan Zhou, Yongzheng He, Wen Xing, Peng Zhang, Hui Shi, Shi Chen, Jun Shi, Jie Bai, Steven D Rhodes, Fengkui Zhang, Jin Yuan, Xianlin Yang, Xiaofan Zhu, Yan Li, Helmut Hanenberg, Mingjiang Xu, Kent A Robertson, Weiping Yuan, Grzegorz Nalepa, Tao Cheng, D Wade Clapp, Feng-Chun Yang
Fanconi anemia is a complex heterogeneous genetic disorder with a high incidence of bone marrow failure, clonal evolution to acute myeloid leukemia and mesenchymal-derived congenital anomalies. Increasing evidence in Fanconi anemia and other genetic disorders points towards an interdependence of skeletal and hematopoietic development, yet the impact of the marrow microenvironment in the pathogenesis of the bone marrow failure in Fanconi anemia remains unclear. Here we demonstrated that mice with double knockout of both Fancc and Fancg gene had decreased bone formation at least partially due to impaired osteoblast differentiation from mesenchymal stem/progenitor cells...
March 24, 2017: Haematologica
https://www.readbyqxmd.com/read/28334174/dna-damage-response-in-hematopoietic-stem-cells-an-evolutionary-trade-off-between-blood-regeneration-and-leukemia-suppression
#16
REVIEW
Shahar Biechonski, Muhammad Yassin, Michael Milyavsky
Self-renewing and multipotent hematopoietic stem cells (HSCs) maintain lifelong hematopoiesis. Their enormous regenerative potential coupled with lifetime persistence in the body, in contrast with the Progenitors, demand tight control of HSCs genome stability. Indeed, failure to accurately repair DNA damage in HSCs is associated with bone marrow failure and accelerated leukemogenesis. Recent observations exposed remarkable differences in several DNA-damage response (DDR) aspects between HSCs and Progenitors, especially in their DNA-repair capacities and susceptibility to apoptosis...
April 1, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28331288/development-of-venetoclax-for-therapy-of-lymphoid-malignancies
#17
REVIEW
Huayuan Zhu, Alexandru Almasan
B-cell lymphoma-2 (BCL-2) family dysfunction and impairment of apoptosis are common in most B-cell lymphoid malignancies. Venetoclax (Venclexta™, formerly ABT-199, GDC-0199) is a highly selective BCL-2 inhibitor, which mimics its BCL-2 homology 3-domain to induce apoptosis. It was approved for treatment of previously treated chronic lymphocytic leukemia (CLL) patients with 17p deletion early in 2016. It has also been in clinical trials for other B-cell lymphoid malignancies. Unlike the other recently approved targeted agents idelalisib and ibrutinib, so far there has been no relapse reported in some patients...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28303935/multiscale-microenvironmental-perturbation-of-pluripotent-stem-cell-fate-and-self-organization
#18
Yoji Tabata, Matthias P Lutolf
The combination of microfluidics with engineered three-dimensional (3D) matrices can bring new insights into the fate regulation of stem cells and their self-organization into organoids. Although there has been progress in 3D stem cell culturing, most existing in vitro methodologies do not allow for mimicking of the spatiotemporal heterogeneity of stimuli that drive morphogenetic processes in vivo. To address this, we present a perfusion-free microchip concept for the in vitro 3D perturbation of stem cell fate...
March 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28297566/instructive-role-of-the-microenvironment-in-preventing-renal-fibrosis
#19
Kei Matsumoto, Sandhya Xavier, Jun Chen, Yujiro Kida, Mark Lipphardt, Reina Ikeda, Annie Gevertz, Mario Caviris, Antonis K Hatzopoulos, Ivo Kalajzic, James Dutton, Brian B Ratliff, Hong Zhao, Zbygniew Darzynkiewicz, Stefan Rose-John, Michael S Goligorsky
Accumulation of myofibroblasts is a hallmark of renal fibrosis. A significant proportion of myofibroblasts has been reported to originate via endothelial-mesenchymal transition. We initially hypothesized that exposing myofibroblasts to the extract of endothelial progenitor cells (EPCs) could reverse this transition. Indeed, in vitro treatment of transforming growth factor-β1 (TGF-β1)-activated fibroblasts with EPC extract prevented expression of α-smooth muscle actin (α-SMA); however, it did not enhance expression of endothelial markers...
March 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28275912/mechanisms-of-resistance-to-targeted-therapies-in-chronic-lymphocytic-leukemia
#20
Francesca Arruga, Silvia Deaglio
Even if treatment options for Chronic Lymphocytic Leukemia (CLL) patients have changed dramatically in the past few years, with the approval of targeted therapeutic agents, the disease remains incurable. Beside intrinsic genetic features characterizing the leukemic cell, signals coming from the microenvironment have a key role in promoting cell survival and in protecting CLL cells from the action of drugs. Consequently, the identification of previously unrecognized genetic lesions is important in risk-stratification of CLL patients and is progressively becoming a critical tool for choosing the best therapeutic strategy...
March 9, 2017: Handbook of Experimental Pharmacology
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