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https://www.readbyqxmd.com/read/27934981/novel-dna-sensor-system-for-highly-sensitive-and-quantitative-retrovirus-detection-using-virus-encoded-integrase-as-a-biomarker
#1
Jing Wang, Jiangnan Liu, Jonas Thomsen, Denis Selnihhin, Marianne S Hede, Freja C M Kirsebom, Oskar Franch, Søren Fjelstrup, Magnus Stougaard, Yi-Ping Ho, Finn Skou Pedersen, Birgitta R Knudsen
In the current study we describe a novel DNA sensor system that allows the detection of single catalytic DNA integration events mediated by retrovirus encoded integrase (IN) present in viral particles. This is achieved by rolling circle amplification mediated conversion of enzymatic reactions happening within nanometer dimensions to directly detectable micrometer sized DNA products. The system utilizes the unique integration reaction of IN to generate a surface anchored nicked DNA circle that serves as a substrate for rolling circle amplification and allows for specific, quantitative and sensitive detection of purified recombinant IN or virus particles with a detection limit of less than 30 virus particles per μL of sample...
December 9, 2016: Nanoscale
https://www.readbyqxmd.com/read/27934882/stable-knockdown-of-creb-hif-1-and-hif-2-by-replication-competent-retroviruses-abrogates-the-responses-to-hypoxia-in-hepatocellular-carcinoma
#2
D Shneor, R Folberg, J Pe'er, A Honigman, S Frenkel
The fast proliferation of tumor cells develops faster than the vasculature, resulting, in most malignant tumors, in generation of hypoxic regions. Hypoxia renders solid tumors resistant to radiation and chemotherapeutics while providing opportunities for tumor-selective therapies targeting tumor hypoxia. Here we exploit two properties of tumors: propagation of tumor cells and ongoing generation of hypoxic regions to construct a system that preferentially leads to the death of tumor cells and thus hinders tumor growth...
December 9, 2016: Cancer Gene Therapy
https://www.readbyqxmd.com/read/27932374/discontinuation-of-dasatinib-or-nilotinib-in-chronic-myeloid-leukemia-interim-analysis-of-the-stop-2g-tki-study
#3
Delphine Rea, Franck E Nicolini, Michel Tulliez, François Guilhot, Joelle Guilhot, Agnès Guerci-Bresler, Martine Gardembas, Valérie Coiteux, Gaelle Guillerm, Laurence Legros, Gabriel Etienne, Jean-Michel Pignon, Bruno Villemagne, Martine Escoffre-Barbe, Jean-Christophe Ianotto, Aude Charbonnier, Hyacinthe Johnson-Ansah, Marie-Pierre Noel, Philippe Rousselot, François-Xavier Mahon
STOP 2G-TKI is a multicenter observational study designed to evaluate 2(nd) generation (2G)-tyrosine kinase inhibitor (TKI) discontinuation in chronic myeloid leukemia (CML). Patients receiving 1(st) or subsequent line dasatinib or nilotinib who stopped therapy after at least 3 years of TKI treatment and in molecular response 4.5 (MR4.5) with undetectable BCR-ABL1 transcripts for the 2 preceding years at least were eligible for inclusion. This interim analysis reports outcomes of 60 patients with a minimum follow-up of 12 months (median 47, range; 12-65)...
December 8, 2016: Blood
https://www.readbyqxmd.com/read/27932188/successful-single-lung-transplant-for-severe-lung-graft-versus-host-disease-two-years-after-sibling-allograft-for-acute-lymphoblastic-leukemia-a-case-report
#4
M R Irhimeh, M Musk, J P Cooney
Bone marrow transplantation (BMT) has been performed as a successful life-saving treatment for hematological and neoplastic diseases. Despite the predictable long-term survival rates in BMT, pulmonary complications reduce the survival rates significantly mainly because of chronic graft-versus-host disease (GVHD). This report briefly discusses a successful lung transplantation case for severe lung GVHD after allograft for acute lymphoblastic leukemia. This case report supports the scarce evidence in the literature for the importance of lung transplantation as a therapeutic option for patients who develop respiratory failure secondary to BMT...
November 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27932186/late-graft-rejection-in-association-with-t-large-granular-lymphocyte-expansion-of-recipient-origin-after-human-leukocyte-antigen-haploidentical-stem-cell-transplantation-a-case-report
#5
N Nakagawa, H Yamazaki, G Aoki, Y Kondo, S Nakao
BACKGROUND: Large granular lymphocyte (LGL) expansion occasionally occurs after allogeneic stem cell transplantation (allo-SCT), and is thought to be a good prognostic sign that is associated with a lower relapse rate. However, there have been no reports of late graft failure (LGF) due to graft rejection in association with oligoclonal LGL expansion. We herein report a case of LGF associated with the transient expansion of recipient-derived T-LGL after allo-SCT. CASE REPORT: A 65-year-old man underwent peripheral blood stem cell transplantation (PBSCT) from his human leukocyte antigen (HLA)-haploidentical son for the treatment of acute myeloid leukemia, which had evolved from a myelodysplastic syndrome (MDS)...
November 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27932034/oncogenic-retinoic-acid-receptor-%C3%AE-promotes-human-colorectal-cancer-growth-through-simultaneously-regulating-p21-transcription-and-gsk3%C3%AE-%C3%AE-catenin-signaling
#6
Gui-Li Huang, Wei Zhang, Hong-Yue Ren, Pan Zhou, Yun Chen, Qing-Xi Chen, Dong-Yan Shen
Retinoic acid receptor α (RARα) plays important roles in the progression of several cancers such as leukemia, breast cancer, and lung cancer. In this study, we demonstrated that RARα protein was frequently overexpressed in human CRC specimens and CRC cell lines. RARα knockdown decreased cell survival, proliferation, and colony formation in vitro and tumorigenic potential in nude mice. Specifically, RARα knockdown inhibited cell cycle progression at G1 phase through upregulation of cell cycle inhibitor p21, and downregulation of cyclinD1...
December 5, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27931239/mcl-1-inhibition-provides-a-new-way-to-suppress-breast-cancer-metastasis-and-increase-sensitivity-to-dasatinib
#7
Adelaide I J Young, Andrew M K Law, Lesley Castillo, Sabrina Chong, Hayley D Cullen, Martin Koehler, Sebastian Herzog, Tilman Brummer, Erinna F Lee, Walter D Fairlie, Morghan C Lucas, David Herrmann, Amr Allam, Paul Timpson, D Neil Watkins, Ewan K A Millar, Sandra A O'Toole, David Gallego-Ortega, Christopher J Ormandy, Samantha R Oakes
BACKGROUND: Metastatic disease is largely resistant to therapy and accounts for almost all cancer deaths. Myeloid cell leukemia-1 (MCL-1) is an important regulator of cell survival and chemo-resistance in a wide range of malignancies, and thus its inhibition may prove to be therapeutically useful. METHODS: To examine whether targeting MCL-1 may provide an effective treatment for breast cancer, we constructed inducible models of BIMs2A expression (a specific MCL-1 inhibitor) in MDA-MB-468 (MDA-MB-468-2A) and MDA-MB-231 (MDA-MB-231-2A) cells...
December 8, 2016: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/27930641/should-treatment-of-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-be-intensive-intensive-treatment-is-not-necessary-at-least-in-induction
#8
Sabina Chiaretti
No abstract text is available yet for this article.
November 2016: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/27930640/should-treatment-of-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-be-intensive-intensive-treatment-is-the-best-treatment-for-these-patients
#9
Nicholas J Short, Elias Jabbour
No abstract text is available yet for this article.
November 2016: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/27930631/cd19-targeted-car-t-cells-as-novel-cancer-immunotherapy-for-relapsed-or-refractory-b-cell-acute-lymphoblastic-leukemia
#10
Marco L Davila, Renier J Brentjens
Immunotherapy has demonstrated significant potential for the treatment of patients with chemotherapy-resistant hematologic malignancies and solid tumors. One type of immunotherapy involves the adoptive transfer of T cells that have been genetically modified with a chimeric antigen receptor (CAR) to target a tumor. These hybrid proteins are composed of the antigen-binding domains of an antibody fused to T-cell receptor signaling machinery. CAR T cells that target CD19 recently have made the jump from the laboratory to the clinic, and the results have been remarkable...
October 2016: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/27930389/therapy-related-myeloid-neoplasms
#11
Arnold Ganser, Michael Heuser
PURPOSE OF REVIEW: Advances in the genetic characterization of patients with therapy-related myeloid neoplasms (t-MNs) have changed our understanding of the pathogenesis of these diseases. In addition, extensive sequencing studies have identified recurrent mutations with diagnostic and prognostic impact. Thus, the revised version of the WHO classification combines therapy-related myelodysplastic syndromes (t-MDS) and therapy-related acute myeloid leukemia (t-AML) in the one entity of t-MNs because of their similar pathogenesis, rapid progression from t-MDS to t-AML, and their equally poor prognosis...
December 7, 2016: Current Opinion in Hematology
https://www.readbyqxmd.com/read/27930388/should-patients-with-acute-myeloid-leukemia-and-measurable-residual-disease-be-transplanted-in-first-complete-remission
#12
Francesco Buccisano, Roland B Walter
PURPOSE OF REVIEW: Measurable ('minimal') residual disease in acute myeloid leukemia during first complete morphologic remission (MRD CR1) identifies patients with particularly high relapse risk and short survival. Here, we examine the evidence regarding optimal postremission treatment strategy for such patients. RECENT FINDINGS: With chemotherapy alone or chemotherapy/autologous hematopoietic cell transplantation (HCT), disease recurrence appears inevitable in patients with MRD CR1...
December 7, 2016: Current Opinion in Hematology
https://www.readbyqxmd.com/read/27930382/ym155-induces-apoptosis-in-p53-deficient-t-acute-lymphoblastic-leukemia-cells-independent-of-survivin-inhibition
#13
Leilane Sales, Graziella R de Sousa, Guilherme Á Ferreira-Silva, Angel M Castro-Gamero, Marisa Ionta, Jaqueline C de Oliveira
T-acute lymphoblastic leukemia (T-ALL) is an aggressive hematological cancer that arises from the malignant transformation of T-cell progenitors. Despite the significant progress in current treatment, challenges remain the lifelong morbidity after current chemotherapy regimens and postrelapse survival. In addition, patients with T-ALL have inferior outcomes compared with those with B-cell precursor; consequently, novel therapeutic approaches are still necessary to improve the outcome in this cohort. YM155 is an imidazolium derivative originally discovered as a suppressant of survivin expression...
December 7, 2016: Anti-cancer Drugs
https://www.readbyqxmd.com/read/27928132/improved-fret-biosensor-for-the-measurement-of-bcr-abl-activity-in-chronic-myeloid-leukemia-cells
#14
Mika Horiguchi, Mari Fujioka, Takeshi Kondo, Yoichiro Fujioka, Xinxin Li, Kosui Horiuchi, Aya O Satoh, Prabha Nepal, Shinya Nishide, Asuka Nanbo, Takanori Teshima, Yusuke Ohba
Although the co-development of companion diagnostics with molecular targeted drugs is desirable, truly efficient diagnostics are limited to diseases in which chromosomal translocations or overt mutations are clearly correlated with drug efficacy. Moreover, even for such diseases, few methods are available to predict whether drug administration is effective for each individual patient whose disease is expected to respond to the drug(s). We have previously developed a biosensor based on the principle of Förster resonance energy transfer (FRET) to measure the activity of the tyrosine kinase BCR-ABL and its response to drug treatment in patient-derived chronic myeloid leukemia cells...
December 8, 2016: Cell Structure and Function
https://www.readbyqxmd.com/read/27927772/anti-thymocyte-globulin-as-graft-versus-host-disease-prevention-in-the-setting-of-allogeneic-peripheral-blood-stem-cell-transplantation-a-review-from-the-acute-leukemia-working-party-of-the-european-society-for-blood-and-marrow-transplantation
#15
Frédéric Baron, Mohamad Mohty, Didier Blaise, Gérard Socié, Myriam Labopin, Jordi Esteve, Fabio Ciceri, Sebastian Giebel, Norbert Claude Gorin, Bipin N Savani, Christoph Schmid, Arnon Nagler
Allogeneic hematopoietic stem cell transplantation is increasingly used as treatment for patients with life threatening blood diseases. Their curative potential is largely based on immune-mediated graft-versus-leukemia effects caused by donor T cells contained in the graft. Unfortunately, donor T cells are also the cause of graft-versus-host disease. The vast majority of HLA-matched allogeneic hematopoietic stem cell transplantations are nowadays carried out with peripheral blood stem cells (PBSC) as stem cell source...
December 7, 2016: Haematologica
https://www.readbyqxmd.com/read/27927769/integration-of-b-cell-receptor-induced-erk1-2-phosphorylation-and-mutations-of-sf3b1-gene-refines-prognosis-in-treatment-naive-chronic-lymphocytic-leukemia
#16
Chiara Cavallini, Carlo Visco, Santosh Putta, Davide Rossi, Elda Mimiola, Norman Purvis, Ornella Lovato, Omar Perbellini, Erika Falisi, Monica Facco, Livio Trentin, Maria G Romanelli, Gianpietro Semenzato, Achille Ambrosetti, Gianluca Gaidano, Giovanni Pizzolo, Alessandra Cesano, Maria T Scupoli
No abstract text is available yet for this article.
December 7, 2016: Haematologica
https://www.readbyqxmd.com/read/27927767/t-cells-in-chronic-lymphocytic-leukemia-display-dysregulated-expression-of-immune-checkpoints-and-activation-markers
#17
Marzia Palma, Giusy Gentilcore, Kia Heimersson, Fariba Mozaffari, Barbro Näsman-Glaser, Emma Young, Richard Rosenquist, Lotta Hansson, Anders Österborg, Håkan Mellstedt
Chronic lymphocytic leukemia is characterized by impaired immune functions largely due to profound T cell defects. T cell functions also depend on co-signaling receptors, inhibitory or stimulatory, known as immune checkpoints, including cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and programmed death-1 (PD-1). Here we analyzed the T cell phenotype focusing on immune checkpoints and activation markers in chronic lymphocytic leukemia patients (n=80) with different clinical characteristics and compared to healthy controls...
December 7, 2016: Haematologica
https://www.readbyqxmd.com/read/27927766/phase-1-dose-finding-study-of-rebastinib-dcc-2036-in-patients-with-relapsed-chronic-myeloid-leukemia-and-acute-myeloid-leukemia
#18
Jorge Cortes, Moshe Talpaz, Hedy P Smith, David S Snyder, Jean Khoury, Kapil N Bhalla, Javier Pinilla-Ibarz, Richard Larson, David Mitchell, Scott C Wise, Thomas J Rutkoski, Bryan D Smith, Daniel L Flynn, Hagop M Kantarjian, Oliver Rosen, Richard A Van Etten
Available tyrosine kinase inhibitors for chronic myeloid leukemia bind in an ATP-binding pocket and are affected by evolving mutations that confer resistance. Rebastinib was identified as a switch control inhibitor of BCR-ABL1 and FLT3 and may be active against resistant mutations. A Phase 1, first in human, single-agent study investigated rebastinib in relapsed or refractory chronic or acute myeloid leukemia. Primary objectives were to investigate the safety of rebastinib and establish the maximum tolerated dose (MTD) and recommended Phase 2 dose...
December 7, 2016: Haematologica
https://www.readbyqxmd.com/read/27927646/bcr-abl-specific-t-cell-therapy-in-ph-all-patients-on-tyrosine-kinase-inhibitors
#19
Patrizia Comoli, Sabrina Basso, Giovanni Riva, Patrizia Barozzi, Ilaria Guido, Antonella Gurrado, Giuseppe Quartuccio, Laura Rubert, Ivana Lagreca, Daniela Vallerini, Fabio Forghieri, Monica Morselli, Paola Bresciani, Angela Cuoghi, Ambra Paolini, Elisabetta Colaci, Roberto Marasca, Antonio Cuneo, Lorenzo Iughetti, Tommaso Trenti, Franco Narni, Robin Foà, Marco Zecca, Mario Luppi, Leonardo Potenza
While the emergence of bone marrow-resident (p190)BCR-ABL-specific T lymphocytes has been correlated with hematologic and cytogenetic remissions in patients with Philadelphia chromosome positive, acute lymphoblastic leukemia (Ph+ ALL) undergoing maintenance tyrosine-kinase inhibitor treatment, little is known about the possibility of culturing these cells ex vivo and employing them in T-cell therapy strategies. We investigated the feasibility of expanding/priming (p190)BCR-ABL-specific T cells in vitro by stimulation with dendritic cells pulsed with (p190)BCR-ABL peptides derived from the BCR-ABL junctional region and alternative splicing, and of adoptively administering them to patients with relapsed disease...
December 7, 2016: Blood
https://www.readbyqxmd.com/read/27927023/novel-strategies-for-improving-hematopoietic-reconstruction-after-allogeneic-hematopoietic-stem-cell-transplantation-or-intensive-chemotherapy
#20
Frédéric Baron, Arnon Nagler
High-dose conditioning regimens for allogeneic hematopoietic cell transplantation (allo-HCT) as well as intensive poly-chemotherapy for acute myeloid leukemia (AML) induce prolonged periods of neutropenia. The duration of the neutropenia is particularly long following umbilical cord blood transplantation (UCBT). Areas covered: After briefly reviewing the impact of hematopoietic growth factors administration to hasten hematologic reconstitution after allo-HCT or intensive AML chemotherapy, this article summarizes recent approaches that have been investigated to prompt hematologic reconstruction after UCBT or intensive AML chemotherapy...
December 8, 2016: Expert Opinion on Biological Therapy
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