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https://www.readbyqxmd.com/read/28090796/impact-of-c-rel-inhibition-of-cord-blood-derived-b-t-and-nk-cells
#1
Shirin Fallahi, Seyede Momeneh Mohammadi, Hamid Tayefi Nasrabadi, Alireza Alihemmati, Naser Samadi, Sanaz Gholami, Dariush Shanehbandi, Hojjatollah Nozad Charoudeh
The c-Rel transcription factor is a unique member of the nuclear factor (NF)-κB family that has a role in curtailing the proliferation, differentiation, cytokine production, and overall activity of B- and T-cells. In addition, c-Rel is a key regulator of apoptosis in that it influences the expression of anti-apoptotic genes such as Bcl-2 and Bcl-xL; conversely, inhibition of c-Rel increases cell apoptosis. To better understand the relationship between c-Rel expression and effects on B- and T-cell expansion, the current study evaluated c-Rel expression in cord blood mononuclear cells...
January 16, 2017: Journal of Immunotoxicology
https://www.readbyqxmd.com/read/28089099/clinical-characteristics-and-outcome-of-invasive-fungal-infections-in-pediatric-acute-myeloid-leukemia-patients-in-a-medical-center-in-taiwan
#2
Gu-Lung Lin, Hsiu-Hao Chang, Chun-Yi Lu, Chung-Ming Chen, Meng-Yao Lu, Ping-Ing Lee, Shiann-Tarng Jou, Yung-Li Yang, Li-Min Huang, Luan-Yin Chang
BACKGROUND: Invasive fungal infection (IFI) causes significant morbidity and mortality in patients with hematological malignancies, especially those with acute myeloid leukemia (AML), recurrent acute leukemia, high-risk acute lymphoblastic leukemia, and after allogeneic hematopoietic stem cell transplantation. The study aimed to investigate the clinical characteristics and outcome of IFIs in pediatric AML patients in a medical center in Taiwan. METHODS: We performed retrospective chart reviews...
December 19, 2016: Journal of Microbiology, Immunology, and Infection, Wei Mian Yu Gan Ran za Zhi
https://www.readbyqxmd.com/read/28060797/t-memory-stem-cells-in-health-and-disease
#3
REVIEW
Luca Gattinoni, Daniel E Speiser, Mathias Lichterfeld, Chiara Bonini
T memory stem (TSCM) cells are a rare subset of memory lymphocytes endowed with the stem cell-like ability to self-renew and the multipotent capacity to reconstitute the entire spectrum of memory and effector T cell subsets. Cumulative evidence in mice, nonhuman primates and humans indicates that TSCM cells are minimally differentiated cells at the apex of the hierarchical system of memory T lymphocytes. Here we describe emerging findings demonstrating that TSCM cells, owing to their extreme longevity and robust potential for immune reconstitution, are central players in many physiological and pathological human processes...
January 6, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28058217/review-of-allogeneic-hematopoietic-stem-cell-transplantation-with-reduced-intensity-conditioning-in-solid-tumors-excluding-breast-cancer
#4
REVIEW
Nuri Karadurmus, Ugur Sahin, Bilgin Bahadir Basgoz, Fikret Arpaci, Taner Demirer
Solid tumors in adults constitute a heterogeneous group of malignancy originating from various organ systems. Solid tumors are not completely curable by chemotherapy, even though some subgroups are very chemo-sensitive. Recently, oncologists have focused on the use of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with reduced intensity conditioning (RIC) for the treatment of some refractory solid tumors. After the demonstration of allogeneic graft-versus-leukemia effect in patients with hematological malignancies who received allo-HSCT, investigators evaluated this effect in patients with refractory metastatic solid tumors...
December 24, 2016: World Journal of Transplantation
https://www.readbyqxmd.com/read/28057848/a-pipeline-for-drug-target-identification-and-validation
#5
Eusebio Manchado, Chun-Hao Huang, Nilgun Tasdemir, Darjus F Tschaharganeh, John E Wilkinson, Scott W Lowe
Rapid and affordable tumor profiling has led to an explosion of genomic data that is facilitating the development of new cancer therapies. The potential of therapeutic strategies aimed at inactivating the oncogenic lesions that contribute to the aberrant survival and proliferation of tumor cells has yielded remarkable success in some malignancies such as BRAF-mutant melanoma and BCR-ABL expressing chronic myeloid leukemia. However, the direct inhibition of several well-established oncoproteins in some of these cancers is not possible or produces only transient benefits...
January 5, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/28057845/targeting-the-epithelial-to-mesenchymal-transition-the-case-for-differentiation-based-therapy
#6
Diwakar R Pattabiraman, Robert A Weinberg
Although important strides have been made in targeted therapy for certain leukemias and subtypes of breast cancer, the standard of care for most carcinomas still involves chemotherapy, radiotherapy, surgery, or a combination of these. Two processes serve as obstacles to the successful treatment of carcinomas. First, a majority of deaths from these types of cancers occurs as a result of distant metastases and not the primary tumors themselves. Second, subsets of cells that are able to survive conventional therapy drive the aggressive relapse of the tumors, often in forms that are resistant to treatment...
January 5, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/28054442/markers-and-function-of-human-nk-cells-in-normal-and-pathological-conditions
#7
REVIEW
Genny Del Zotto, Emanuela Marcenaro, Paola Vacca, Simona Sivori, Daniela Pende, Mariella Della Chiesa, Francesca Moretta, Tiziano Ingegnere, Maria Cristina Mingari, Alessandro Moretta, Lorenzo Moretta
Natural killer (NK) cells, the most important effectors of the Innate Lymphoid Cells (ILCs), play a fundamental role in tumor immune-surveillance, defense against viruses and, in general, in innate immune responses. NK cell activation is mediated by several activating receptors and co-receptors able to recognize ligands on virus-infected or tumor cells. To prevent healthy cells from auto-aggression, NK cells are provided with strong inhibitory receptors (KIRs and NKG2A) which recognize HLA class I molecules on target cells and, sensing their level of expression, allow killing of targets underexpressing HLA-class I...
January 5, 2017: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/28045896/a-signature-of-genomic-instability-resulting-from-deficient-replication-licensing
#8
Steven C Pruitt, Maochun Qin, Jianmin Wang, Dimiter Kunnev, Amy Freeland
Insufficient licensing of DNA replication origins has been shown to result in genome instability, stem cell deficiency, and cancers. However, it is unclear whether the DNA damage resulting from deficient replication licensing occurs generally or if specific sites are preferentially affected. To map locations of ongoing DNA damage in vivo, the DNAs present in red blood cell micronuclei were sequenced. Many micronuclei are the product of DNA breaks that leave acentromeric remnants that failed to segregate during mitosis and should reflect the locations of breaks...
January 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28044259/bortezomib-interferes-with-adhesion-of-b-cell-precursor-acute-lymphoblastic-leukemia-cells-through-sparc-up-regulation-in-human-bone-marrow-mesenchymal-stromal-stem-cells
#9
Masaki Iwasa, Yasuo Miura, Aya Fujishiro, Sumie Fujii, Noriko Sugino, Satoshi Yoshioka, Asumi Yokota, Terutoshi Hishita, Hideyo Hirai, Akira Andoh, Tatsuo Ichinohe, Taira Maekawa
The poor prognosis of adults with B cell precursor acute lymphoblastic leukemia (BCP-ALL) is attributed to leukemia cells that are protected by the bone marrow (BM) microenvironment. In the present study, we explored the pharmacological targeting of mesenchymal stromal/stem cells in BM (BM-MSCs) to eliminate chemoresistant BCP-ALL cells. Human BCP-ALL cells (NALM-6 cells) that adhered to human BM-MSCs (NALM-6/Ad) were highly resistant to multiple anti-cancer drugs, and exhibited pro-survival characteristics, such as an enhanced Akt/Bcl-2 pathway and increased populations in the G0 and G2/S/M cell cycle stages...
January 2, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28041846/change-in-ighv-mutational-status-of-cll-suggests-origin-from-multiple-clones
#10
Afaf Osman, Christopher D Gocke, Douglas E Gladstone
BACKGROUND: Fluorescence in situ hybridization and immunoglobulin (Ig) heavy-chain variable-region (IgHV) mutational status are used to predict outcome in chronic lymphocytic leukemia (CLL). Although DNA aberrations change over time, IgHV sequences and mutational status are considered stable. PATIENTS AND METHODS: In a retrospective review, 409 CLL patients, between 2008 and 2015, had IgHV analysis: 56 patients had multiple analyses performed. Seven patients' IgHV results changed: 2 from unmutated to mutated and 5 from mutated to unmutated IgHV sequence...
November 21, 2016: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28027652/melatonin-ameliorates-busulfan-induced-spermatogonial-stem-cell-oxidative-apoptosis-in-mouse-testes
#11
Bo Li, Xin He, Mengru Zhuang, Bowen Niu, Chongyang Wu, Hailong Mu, Furong Tang, Yanhua Cui, Weishuai Liu, Baoyu Zhao, Sha Peng, Guangpeng Li, Jinlian Hua
AIMS: Many men endure immunosuppressive or anticancer treatments that contain alkylating agents prior to the age of sexual maturity, especially the increasing number of preadolescent males who undergo busulfan treatment for myeloablative conditioning prior to hematopoietic stem cell transplantation. Prior to sperm production, there are no sperm available for cryopreservation. Thus, it is necessary to identify a solution to ameliorate the busulfan-induced damage of spermatogonial stem cells (SSCs)...
December 27, 2016: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28026860/pioglitazone-together-with-imatinib-in-chronic-myeloid-leukemia-a-proof-of-concept-study
#12
Philippe Rousselot, Stéphane Prost, Joelle Guilhot, Lydia Roy, Gabriel Etienne, Laurence Legros, Aude Charbonnier, Valérie Coiteux, Pascale Cony-Makhoul, Francoise Huguet, Emilie Cayssials, Jean-Michel Cayuela, Francis Relouzat, Marc Delord, Heriberto Bruzzoni-Giovanelli, Laure Morisset, François-Xavier Mahon, François Guilhot, Philippe Leboulch
BACKGROUND: We recently reported that peroxisome proliferator-activated receptor γ agonists target chronic myeloid leukemia (CML) quiescent stem cells in vitro by decreasing transcription of STAT5. Here in the ACTIM phase 2 clinical trial, we asked whether pioglitazone add-on therapy to imatinib would impact CML residual disease, as assessed by BCR-ABL1 transcript quantification. METHODS: CML patients were eligible if treated with imatinib for at least 2 years at a stable daily dose, having yielded major molecular response (MMR) but not having achieved molecular response 4...
December 27, 2016: Cancer
https://www.readbyqxmd.com/read/28003281/dnmt3a-in-leukemia
#13
Lorenzo Brunetti, Michael C Gundry, Margaret A Goodell
DNA methylation is an epigenetic process involved in development, aging, and cancer. Although the advent of new molecular techniques has enhanced our knowledge of how DNA methylation alters chromatin and subsequently affects gene expression, a direct link between epigenetic marks and tumorigenesis has not been established. DNMT3A is a de novo DNA methyltransferase that has recently gained relevance because of its frequent mutation in a large variety of immature and mature hematologic neoplasms. DNMT3A mutations are early events during cancer development and seem to confer poor prognosis to acute myeloid leukemia (AML) patients making this gene an attractive target for new therapies...
December 21, 2016: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28002788/tianshengyuan-1-tsy-1-regulates-cellular-telomerase-activity-by-methylation-of-tert-promoter
#14
Weibo Yu, Xiaotian Qin, Yusheng Jin, Yawei Li, Chintda Santiskulvong, Victor Vu, Gang Zeng, Zuofeng Zhang, Michelle Chow, Jianyu Rao
Telomere and Telomerase have recently been explored as anti-aging and anti-cancer drug targets with only limited success. Previously we showed that the Chinese herbal medicine Tianshengyuan-1 (TSY-1), an agent used to treat bone marrow deficiency, has a profound effect on stimulating Telomerase activity in hematopoietic cells. Here, the mechanism of TSY-1 on cellular Telomerase activity was further investigated using HL60, a promyelocytic leukemia cell line, normal peripheral blood mononuclear cells, and CD34+ hematopoietic stem cells derived from umbilical cord blood...
December 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27992855/amplified-detection-of-leukemia-cancer-cells-using-an-aptamer-conjugated-gold-coated-magnetic-nanoparticles-on-a-nitrogen-doped-graphene-modified-electrode
#15
Seyyed Mehdi Khoshfetrat, Masoud A Mehrgardi
The increasing demands for early, accurate and ultrasensitive diagnosis of cancers demonstrate the importance of the development of new amplification strategies or diagnostic technologies. In the present study, an aptamer-based electrochemical biosensor for ultrasensitive and selective detection of leukemia cancer cells has been introduced. The thiolated sgc8c aptamer was immobilized on gold nanoparticles-coated magnetic Fe3O4 nanoparticles (Apt-GMNPs). Ethidium bromide (EB), intercalated into the stem of the aptamer hairpin, provides the read-out signal for the quantification of the leukemia cancer cells...
December 12, 2016: Bioelectrochemistry
https://www.readbyqxmd.com/read/27983886/graft-versus-host-disease-in-adolescents-and-young-adults-15-24-years-old-after-allogeneic-hematopoietic-stem-cell-transplantation-for-acute-leukemia-in-first-complete-remission
#16
Marguerite Vignon, Annalisa Andreoli, Nathalie Dhédin, Etienne Lengliné, Emeline Masson, Marie Robin, Clémence Granier, Jérôme Larghero, Marie-Hélène Schlageter, Régis Peffault de Latour, Gérard Socié, Nicolas Boissel
PURPOSE: Adolescents and young adults (AYAs) with cancer are a unique group of patients in terms of disease incidence and biology, outcome, and psychosocial needs. This study aims to correlate the risk of graft-versus-host disease (GvHD) and age in a population of children and young adults with acute leukemia undergoing hematopoietic stem cell transplantation (HSCT) in first complete remission (CR). METHODS: We analyzed the outcome of 153 consecutive children (<15 years), AYAs (15-24 years), and adults (25-35 years) with lymphoblastic or myeloid acute leukemia in first CR who underwent HSCT with matched donors after myeloablative conditioning...
December 16, 2016: Journal of Adolescent and Young Adult Oncology
https://www.readbyqxmd.com/read/27980223/extracellular-atp-induces-apoptosis-through-p2x7r-activation-in-acute-myeloid-leukemia-cells-but-not-in-normal-hematopoietic-stem-cells
#17
Valentina Salvestrini, Stefania Orecchioni, Giovanna Talarico, Francesca Reggiani, Cristina Mazzetti, Francesco Bertolini, Elisa Orioli, Elena Adinolfi, Francesco Di Virgilio, Annalisa Pezzi, Michele Cavo, Roberto M Lemoli, Antonio Curti
Recent studies have shown that high ATP levels exhibit direct cytotoxic effects on several cancer cells types. Among the receptors engaged by ATP, P2X7R is the most consistently expressed by tumors. P2X7R is an ATP-gated ion channel that could drive the opening of a non-selective pore, triggering cell-death signal. We previously demonstrated that acute myeloid leukemia (AML) cells express high level of P2X7R. Here, we show that P2X7R activation with high dose ATP induces AML blast cells apoptosis. Moreover, P2X7R is also expressed on leukemic stem/progenitor cells (LSCs) which are sensitive to ATP-mediated cytotoxicity...
December 13, 2016: Oncotarget
https://www.readbyqxmd.com/read/27960078/dormancy-stems-the-tide-of-chemotherapy
#18
Deepali Pal, Olaf Heidenreich, Josef Vormoor
In this issue of Cancer Cell, Ebinger et al. describe rare, non-cycling blasts in acute lymphoblastic leukemia that combine the phenotypes of dormancy, stemness, and chemo-resistance. This novel in vivo model for dormant blasts will facilitate the dissection of the niche and the development of therapies targeting the leukemic microenvironment.
December 12, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27956388/autophagy-a-key-mechanism-of-oncogenesis-and-resistance-in-leukemia
#19
Patrick Auberger, Alexandre Puissant
Autophagy is a lysosomal pathway involved in degradation of intracellular material. It appears as an adaptation mechanism that is essential for cellular homeostasis in response to various stress conditions. Over the past decade, many studies have linked alteration of autophagy with cancer initiation and progression, autoimmune, inflammatory, metabolic, and degenerative diseases. This review highlights recent findings on the impact of autophagy on leukemic transformation of normal hematopoietic stem cells and summarizes its role on leukemic cell response to chemotherapy...
December 12, 2016: Blood
https://www.readbyqxmd.com/read/27956387/targeting-sphingosine-kinase-1-induces-mcl1-dependent-cell-death-in-acute-myeloid-leukemia
#20
Jason A Powell, Alexander C Lewis, Wenying Zhu, John Toubia, Melissa R Pitman, Craig T Wallington-Beddoe, Paul A B Moretti, Diana Iarossi, Saumya E Samaraweera, Nik Cummings, Hayley S Ramshaw, Daniel Thomas, Andrew H Wei, Angel F Lopez, Richard J D'Andrea, Ian D Lewis, Stuart M Pitson
Acute myeloid leukemia (AML) is an aggressive malignancy where despite improvements in conventional chemotherapy and bone marrow transplantation, overall survival remains poor. Sphingosine kinase 1 (SPHK1) generates the bioactive lipid sphingosine 1-phosphate (S1P) and has established roles in tumor initiation, progression and chemotherapy resistance in a wide range of cancers. The role and targeting of SPHK1 in primary AML, however, has not been previously investigated. Here we show that SPHK1 is overexpressed and constitutively activated in primary AML patient blasts but not in normal mononuclear cells...
December 12, 2016: Blood
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