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leukemia cancer stem cell

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https://www.readbyqxmd.com/read/28220124/in-vivo-efficacy-of-umbilical-cord-blood-stem-cell-derived-nk-cells-in-the-treatment-of-metastatic-colorectal-cancer
#1
John P Veluchamy, Silvia Lopez-Lastra, Jan Spanholtz, Fenna Bohme, Nina Kok, Daniëlle A M Heideman, Henk M W Verheul, James P Di Santo, Tanja D de Gruijl, Hans J van der Vliet
Therapeutic monoclonal antibodies against the epidermal growth factor receptor (EGFR) act by inhibiting EGFR downstream signaling and by eliciting a natural killer (NK) cell-mediated antitumor response. The IgG1 mAb cetuximab has been used for treatment of RAS(wt) metastatic colorectal cancer (mCRC) patients, showing limited efficacy. In the present study, we address the potential of adoptive NK cell therapy to overcome these limitations investigating two allogeneic NK cell products, i.e., allogeneic activated peripheral blood NK cells (A-PBNK) and umbilical cord blood stem cell-derived NK cells (UCB-NK)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28217708/aberrant-rna-splicing-and-mutations-in-spliceosome-complex-in-acute-myeloid-leukemia
#2
COMMENT
Jianbiao Zhou, Wee-Joo Chng
The spliceosome, the cellular splicing machinery, regulates RNA splicing of messenger RNA precursors (pre-mRNAs) into maturation of protein coding RNAs. Recurrent mutations and copy number changes in genes encoding spliceosomal proteins and splicing regulatory factors have tumor promoting or suppressive functions in hematological malignancies, as well as some other cancers. Leukemia stem cell (LSC) populations, although rare, are essential contributors of treatment failure and relapse. Recent researches have provided the compelling evidence that link the erratic spicing activity to the LSC phenotype in acute myeloid leukemia (AML)...
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/28211886/a-novel-approach-for-the-identification-of-efficient-combination-therapies-in-primary-human-acute-myeloid-leukemia-specimens
#3
I Baccelli, J Krosl, G Boucher, I Boivin, V-P Lavallée, J Hébert, S Lemieux, A Marinier, G Sauvageau
Appropriate culture methods for the interrogation of primary leukemic samples were hitherto lacking and current assays for compound screening are not adapted for large-scale investigation of synergistic combinations. In this study, we report a novel approach that efficiently distills synthetic lethal interactions between small molecules active on primary human acute myeloid leukemia (AML) specimens. In single-dose experiments and under culture conditions preserving leukemia stem cell activity, our strategy considerably reduces the number of tests needed for the identification of promising compound combinations...
February 17, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28205621/cryogel-supported-stem-cell-factory-for-customized-sustained-release-of-bispecific-antibodies-for-cancer-immunotherapy
#4
Roberta Aliperta, Petra B Welzel, Ralf Bergmann, Uwe Freudenberg, Nicole Berndt, Anja Feldmann, Claudia Arndt, Stefanie Koristka, Marcello Stanzione, Marc Cartellieri, Armin Ehninger, Gerhard Ehninger, Carsten Werner, Jens Pietzsch, Jörg Steinbach, Martin Bornhäuser, Michael P Bachmann
Combining stem cells with biomaterial scaffolds provides a promising strategy for the development of drug delivery systems. Here we propose an innovative immunotherapeutic organoid by housing human mesenchymal stromal cells (MSCs), gene-modified for the secretion of an anti-CD33-anti-CD3 bispecific antibody (bsAb), in a small biocompatible star-shaped poly(ethylene glycol)-heparin cryogel scaffold as a transplantable and low invasive therapeutic machinery for the treatment of acute myeloid leukemia (AML). The macroporous biohybrid cryogel platform displays effectiveness in supporting proliferation and survival of bsAb-releasing-MSCs overtime in vitro and in vivo, avoiding cell loss and ensuring a constant release of sustained and detectable levels of bsAb capable of triggering T-cell-mediated anti-tumor responses and a rapid regression of CD33(+) AML blasts...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28202613/the-activating-human-nk-cell-receptor-kir2ds2-recognizes-a-%C3%AE-2-microglobulin-independent-ligand-on-cancer-cells
#5
Lavanya Thiruchelvam-Kyle, Sigurd E Hoelsbrekken, Per C Saether, Elisabeth Gyllensten Bjørnsen, Daniela Pende, Sigbjørn Fossum, Michael R Daws, Erik Dissen
The functions of activating members of the killer cell Ig-like receptor (KIR) family are not fully understood, as the ligands for these receptors are largely unidentified. In this study, we report that KIR2DS2 reporter cells recognize a ligand expressed by cancer cell lines. All cancer targets recognized by KIR2DS2 were also recognized by KIR2DL2 and KIR2DL3 reporters. Trogocytosis of membrane proteins from the cancer targets was observed with responding reporter cells, indicating the formation of KIR2DS2 ligand-specific immunological synapses...
February 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28202504/expression-profiling-of-circulating-microvesicles-reveals-intercellular-transmission-of-oncogenic-pathways
#6
Gloria Milani, Tobia Lana, Silvia Bresolin, Sanja Aveic, Anna Pasto, Chiara Frasson, Geertruy Te Kronnie
: Circulating microvesicles (MVs) have been described as important players in cell-to-cell communication carrying biological information under normal or pathological condition. MVs released by cancer cells may incorporate diverse biomolecules (e.g. active lipids, proteins and RNA) which can be delivered and internalized by recipient cells, potentially altering gene expression of recipient cells and eventually impacting disease progression. Leukemia in vitro model systems were used to investigate MVs as vehicles of protein-coding messages...
February 15, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28198960/quality-of-life-of-patients-with-graft-versus-host-disease-gvhd-post-hematopoietic-stem-cell-transplantation
#7
Sibéli de Fátima Ferraz Simão Proença, Celina Mattos Machado, Raquel de Castro Figueiredo Pereira Coelho, Leila Maria Mansano Sarquis, Paulo Ricardo Bittencourt Guimarães, Luciana Puchalski Kalinke
OBJECTIVE: Assessing the quality of life of adult patients with hematological cancer in the 100 days after transplantation of hematopoietic stem cells and verifying whether the variable graft-versus-host disease (GvHD) is predictive of worse results. METHOD: An observational correlational and quantitative study with 36 adult participants diagnosed with hematologic cancer who underwent hematopoietic stem cell transplantation from September 2013 to June 2015. RESULT: The mean age was 37 years, 52...
November 2016: Revista da Escola de Enfermagem da U S P
https://www.readbyqxmd.com/read/28194062/performance-of-galactomannan-antigen-beta-d-glucan-and-aspergillus-lateral-flow-device-for-the-diagnosis-of-invasive-aspergillosis
#8
Gökhan Metan, Muzaffer Keklik, Gökçen Dinç, Çiğdem Pala, Afra Yıldırım, Berkay Saraymen, Mustafa Yavuz Köker, Leylagül Kaynar, Bülent Eser, Mustafa Çetin
Aspergillus lateral-flow device (LFD) was recently introduced as a practical tool for the diagnosis of invasive aspergillosis (IA). We investigated the performance of Aspergillus-LFD as a point-of-care test for the diagnosis of IA. Serum samples were collected twice weekly from patients who received intensive chemotherapy for acute leukemia, or recepients of allogeneic stem cell transplantation. Aspergillus galactomannan (GM) antigen, 1,3-beta-d-glucan and Aspergillus-LFD tests were carried out according to manufacturers' recommendations...
March 2017: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/28188793/activation-of-wnt-signaling-pathway-by-af1q-enriches-stem-like-population-and-enhance-mammosphere-formation-of-breast-cells
#9
Charlotte Olivia Tse, Soojin Kim, Jino Park
Wnt signaling pathway is believed to be responsible for control over various types of stem cells and may act as a niche factor to maintain stem cells in a self-renewing state. Moreover, dysregulated Wnt signaling pathway is strongly associated with several diseases including cancer. Previously, we have shown that AF1q associates with a poor prognosis in leukemia, myelodysplastic syndromes, multiple myeloid, ovarian cancer, and breast cancer. Also, AF1q plays a pivotal role as an oncogene and metastasis enhancer in breast cancer via activation of Wnt signaling pathway...
February 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28183295/meta-analysis-of-gene-expression-in-relapsed-childhood-b-acute-lymphoblastic-leukemia
#10
Yock-Ping Chow, Hamidah Alias, Rahman Jamal
BACKGROUND: Relapsed pediatric B-acute lymphoblastic leukemia (B-ALL) remains as the leading cause of cancer death among children. Other than stem cell transplantation and intensified chemotherapy, no other improved treatment strategies have been approved clinically. Gene expression profiling represents a powerful approach to identify potential biomarkers and new therapeutic targets for various diseases including leukemias. However, inadequate sample size in many individual experiments has failed to provide adequate study power to yield translatable findings...
February 10, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28178623/t-cell-leukemia-lymphoma-1a-predicts-the-clinical-outcome-for-patients-with-stage-ii-iii-colorectal-cancer
#11
Hao Li, Xuebing Yan, Liguo Liu, Linsheng Huang, Mingming Yin, Cheng Pan, Peng Zhang, Huanlong Qin
T-cell leukemia/lymphoma-1A (TCL1A) as a stem cell marker is abundantly expressed in embryonic stem cells and has been identified as an oncogene in various hematological malignancies such as chronic lymphocytic leukemia and B-cell lymphoma. However, with regard to its role in solid tumors, few studies are available and less are for colorectal cancer (CRC). In this study, we aim to investigate the expression and clinical significance of TCL1A in a cohort of 278 stage II/III CRC patients. As a result, we find TCL1A expression is higher in CRC tissues than that in adjacent normal tissues, and significantly correlated with tumor differentiation, TNM stage and Ki-67 positive rate...
February 5, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28168387/effective-laparoscopic-management-lymph-node-dissection-for-gallbladder-cancer
#12
Eduardo A Vega, Suguru Yamashita, Yun Shin Chun, Michael Kim, Jason B Fleming, Matthew H Katz, Ching-Wei Tzeng, Kanwal P Raghav, Jean-Nicolas Vauthey, Jeffrey E Lee, Claudius Conrad
BACKGROUND: Part of optimal prognostication of gallbladder cancer is optimal lymph node staging. (1,2) Accurate laparoscopic lymph node staging is dependent on a systematic approach to sampling N1 and N2 lymph node stations. (3) Stations with the highest risk of involvement are 12a, b, p and c, 13 and 16, as well as 8 and 9. (4) PATIENT: A 59-year-old man underwent stem cell transplantation for acute myeloid leukemia. Thirty-nine days later he developed acute cholecystitis, which was managed with a cholecystostomy tube...
February 6, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28164252/snap-tag-technology-a-promising-tool-for-ex-vivo-immunophenotyping
#13
Swati Choudhary, Stefan Barth, Rama S Verma
BACKGROUND: SNAP-tag, a self-labeling protein tag, is commonly used for in vitro and in vivo analysis of bound target proteins. We report the first evidence that SNAP-tag could be used for ex vivo detection of enriched biological markers. METHODS: Proof of concept was established for target c-kit receptor, a pathological and diagnostic marker for a variety of cancers. SNAP-tag conjugates with stem-cell factor (SCF) fusion proteins were designed and their binding and specificity was validated in vitro using flow cytometry and immunostaining...
February 6, 2017: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/28160352/outcomes-of-children-adolescents-and-young-adults-following-allogeneic-stem-cell-transplantation-for-secondary-acute-myeloid-leukemia-and-myelodysplastic-syndromes-the-md-anderson-cancer-center-experience
#14
Ossama M Maher, Jorge Galvez Silva, Jimin Wu, Diane Liu, Laurence J N Cooper, Nidale Tarek, Laura Worth, Dean A Lee, Demetrios Petropoulos, Anna R K Franklin, Patrick Zweidler-Mckay, Robert J Wells, Gabriela Rondon, Richard E Champlin, Priti Tewari
We conducted a retrospective analysis of outcomes for children and young adults with sAML/sMDS who underwent HSCT at our institution. Thirty-two patients (median age 20 years) with sAML (n=24) and sMDS (n=8) received HSCT between 1990 and 2013. The median time from sAML/sMDS diagnosis to HSCT was 4.1 months (range: 1.2-27.2 months). The transplant regimens were primarily busulfan based (n=19). BM was the primary donor source (n=15). Eleven recipients were transplanted with residual disease. At a median follow-up of 62...
February 3, 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28159741/biology-and-relevance-of-human-acute-myeloid-leukemia-stem-cells
#15
Daniel Thomas, Ravindra Majeti
Evidence of human acute myeloid leukemia stem cells (AML LSCs) was first reported nearly two decades ago through the identification of rare subpopulations of engrafting cells in xenotransplantation assays. These AML LSCs were shown to reside at the apex of a cellular hierarchy that initiates and maintains the disease, exhibiting properties of self-renewal, cell cycle quiescence, and chemoresistance. This cancer stem cell model offers an explanation for chemotherapy resistance and disease relapse, and implies that approaches to treatment must eradicate LSCs for cure...
February 3, 2017: Blood
https://www.readbyqxmd.com/read/28159740/the-chronic-myeloid-leukemia-stem-cell-stemming-the-tide-of-persistence
#16
Tessa L Holyoake, David Vetrie
Chronic myeloid leukaemia (CML) is caused by the acquisition of the tyrosine kinase BCR-ABL1 in a haemopoietic stem cell (HSC), transforming it into a leukaemic stem cell (LSC) that self-renews, proliferates and differentiates to give rise to a myeloproliferative disease. While tyrosine kinase inhibitors (TKI) that target the kinase activity of BCR-ABL1 have transformed CML from a once fatal disease to a manageable one for the vast majority of patients, only ~10% of those who present in chronic phase (CP) can discontinue TKI treatment and maintain a therapy-free remission...
February 3, 2017: Blood
https://www.readbyqxmd.com/read/28159738/therapeutic-targeting-of-acute-myeloid-leukemia-stem-cells
#17
Daniel A Pollyea, Craig T Jordan
For over 50 years investigators have considered a malignant stem cell as the potential origin of and a key therapeutic target for acute myeloid leukemia (AML) and other forms of cancer(1-4) The nature and existence of tumor-initiating cells for leukemia and other malignancies has long been the subject of intense and rigorous study; indeed, the promise of the potential to eradicate such cells is clear. However, until recently, deficiencies in our understanding of the nature of these cell populations, coupled with a limited ability to therapeutically exploit their weaknesses, have been limiting factors towards realizing the goal of targeting leukemia stem cells (LSCs)...
February 3, 2017: Blood
https://www.readbyqxmd.com/read/28152889/characterization-of-unplanned-30-day-medical-oncology-readmissions-after-discharge-at-an-academic-medical-center-with-a-comprehensive-cancer-center
#18
Justin Eusebio, Nie Bohlen, Margaret Ruddy, David P Ryan
: 269 Background: Hospital readmission rate is increasingly suggested as a quality care metric. Currently there are no standard criteria for an avoidable readmission in oncology. Although patients with cancer have been identified as being at increased risk of readmission, there has been little to examine the reasons for the oncology patient readmission. The aim was to examine the profiles of patients with an unplanned readmission within 30 days after discharge by an oncology provider and to measure the unplanned 30-day readmission rate...
March 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28143872/musashi-rna-binding-proteins-as-cancer-drivers-and-novel-therapeutic-targets
#19
Alexander E Kudinov, John Karanicolas, Erica A Golemis, Yanis Boumber
Aberrant gene expression that drives human cancer can arise from epigenetic dysregulation. While much attention has focused on altered activity of transcription factors and chromatin-modulating proteins, proteins that act post-transcriptionally can potently affect expression of oncogenic signaling proteins. The RNA-binding proteins (RBPs) Musashi-1 (MSI1) and Musashi-2 (MSI2) are emerging as regulators of multiple critical biological processes relevant to cancer initiation, progression, and drug resistance...
January 31, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28143565/disulfiram-overcomes-bortezomib-and-cytarabine-resistance-in-down-syndrome-associated-acute-myeloid-leukemia-cells
#20
Ranjan Bista, David W Lee, Oliver B Pepper, David O Azorsa, Robert J Arceci, Eiman Aleem
BACKGROUND: Children with Down syndrome (DS) have increased risk for developing AML (DS-AMKL), and they usually experience severe therapy-related toxicities compared to non DS-AMKL. Refractory/relapsed disease has very poor outcome, and patients would benefit from novel, less toxic, therapeutic strategies that overcome resistance. Relapse/resistance are linked to cancer stem cells with high aldehyde dehydrogenase (ALDH) activity. The purpose of the present work was to study less toxic alternative therapeutic agents for relapsed/refractory DS-AMKL...
February 1, 2017: Journal of Experimental & Clinical Cancer Research: CR
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