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Duc Dat Le, Duc Hung Nguyen, Bing Tian Zhao, Jeong Ah Kim, Seok Kyu Kim, Byung Sun Min, Jae Sue Choi, Mi Hee Woo
Four undescribed 23,24-O-isopropylidene-19(18 → 17)-abeo-28-noroleanane-derived spirocyclic triterpenoids and an undescribed 28-noroleanane-derived spirocyclic triterpenoid, together with five known 28-noroleanane-derived spirocyclic triterpenoids, were isolated and identified. In addition, three undescribed iridoid glucosides and four known ones were also identified. All the isolates were identified using spectroscopic techniques, and the absolute configurations of 28-noroleanane-derived spirocyclic triterpenoids were determined by CD method for the first time...
June 18, 2018: Phytochemistry
Shuang Ma, Lian-He Yang, Catherine Luedke, Kimberly Ingersoll, Endi Wang
No abstract text is available yet for this article.
June 19, 2018: British Journal of Haematology
Deyan Chen, Chunhong Feng, Xiaoyan Tian, Nan Zheng, Zhiwei Wu
The promyelocytic leukemia (PML) protein, also known as TRIM19, functions as a major organizer of PML nuclear bodies (NBs) in most mammalian cells and plays important roles in antiviral activities against both DNA and RNA viruses. In this study, we found that the downregulation of PML rendered HeLa cells more susceptible to infection by enterovirus 71 (EV71), and the overexpression of the PMLIII or PMLIV isoforms inhibited viral protein expression and resulted in viral titers that were 2-3 log units lower than those in the control...
2018: Frontiers in Immunology
Tomoo Osumi, Shin-Ichi Tsujimoto, Moe Tamura, Meri Uchiyama, Kazuhiko Nakabayashi, Kohji Okamura, Masanori Yoshida, Daisuke Tomizawa, Akihiro Watanabe, Hiroyuki Takahashi, Tsukasa Hori, Shohei Yamamoto, Kazuko Hamamoto, Masahiro Migita, Hiroko Ogata-Kawata, Toru Uchiyama, Hiroe Kizawa, Hitomi Ueno-Yokohata, Ryota Shirai, Masafumi Seki, Kentaro Ohki, Junko Takita, Takeshi Inukai, Seishi Ogawa, Toshio Kitamura, Kimikazu Matsumoto, Kenichiro Hata, Nobutaka KIyokawa, Susumu Goyama, Motohiro Kato
Translocations of retinoic acid receptor-α (RARA), typically PML-RARA, are a genetic hallmark of acute promyelocytic leukemia (APL). However, because a small fraction of APL lack translocations of RARA, we focused here on APL cases without RARA translocation to elucidate the molecular etiology of RARA-negative APL. We performed whole-genome sequencing, PCR, and FISH for five APL cases without RARA translocations. Four of five RARA-negative APL cases had translocations involving retinoic acid receptor-β (RARB) translocations, and TBL1XR1-RARB was identified as an in-frame fusion in three cases; one case had an RARB rearrangement detected by FISH, although the partner gene could not be identified...
June 19, 2018: Cancer Research
B Song, Y-J Tang, W-G Zhang, C-C Wan, Y Chen, L-J Zhang
OBJECTIVE: Extracellular signal-regulated kinase (ERK)/mitogen activated protein kinase (MAPK) signaling pathway is widely involved in cell proliferation and invasion regulation. Enhanced expression or function of ERK1 is important for leukemia. Abnormal down-regulation of microRNA (miR)-143 is correlated with leukemia pathogenesis, indicating possible tumor-suppressing role. Bioinformatics analysis showed the existence of complementary binding sites between miR-143 and ERK1. This study aims to investigate whether the miR-143 plays a role in mediating ERK1 expression and proliferation and apoptosis of leukemia cells...
June 2018: European Review for Medical and Pharmacological Sciences
Christine Bellanné-Chantelot, Barbara Schmaltz-Panneau, Caroline Marty, Odile Fenneteau, Isabelle Callebaut, Séverine Clauin, Aurélie Docet, Gandhi-Laurent Damaj, Thierry Leblanc, Isabelle Pellier, Cécile Stoven, Sylvie Souquere, Iléana Antony-Debré, Blandine Beaupain, Nathalie Aladjidi, Vincent Barlogis, Frédéric Bauduer, Philippe Bensaid, Odile Boespflug-Tanguy, Claire Berger, Yves Bertrand, Liana Carausu, Claire Fieschi, Claire Galambrun, Aline Schmidt, Hubert Journel, Françoise Mazingue, Brigitte Nelken, Thuan Chong Quah, Eric Oksenhendler, Marie Ouachée, Marlène Pasquet, Véronique Saada, Felipe Suarez, Gérard Pierron, William Vainchenker, Isabelle Plo, Jean Donadieu
Congenital neutropenias (CN) are rare heterogeneous genetic disorders with about 25% of patients without known genetic defects. Using whole-exome sequencing, we identified a heterozygous mutation in the SRP54 gene, encoding the signal recognition particle (SRP) 54 GTPase protein, in 3 sporadic cases and one autosomal dominant family. We subsequently sequenced the SRP54 gene in 66 probands from the French CN registry. In total, we identified 23 mutated cases (16 sporadic, 7 familial) with seven distinct germline SRP54 mutations including a recurrent in-frame deletion (Thr117del) in 14 cases...
June 18, 2018: Blood
Alyse N Steves, Adam Turry, Brittany Gill, Danielle Clarkson-Townsend, Joshua M Bradner, Ian Bachli, W Michael Caudle, Gary W Miller, Anthony W S Chan, Charles A Easley
Per- and polyfluoroalkyl substances (PFASs) represent a highly ubiquitous group of synthetic chemicals used in products ranging from water and oil repellents and lubricants to firefighting foam. These substances can enter and accumulate in multiple tissue matrices in up to 100% of people assessed. Though animal models strongly identify these compounds as male reproductive toxicants, with exposed rodents experiencing declines in sperm count, alterations in hormones, and DNA damage in spermatids, among other adverse outcomes, human studies report conflicting conclusions as to the reproductive toxicity of these chemicals...
June 18, 2018: Systems Biology in Reproductive Medicine
Mohammadreza Sharifi, Mahdi Fasihi-Ramandi, Abdolkarim Sheikhi, Abbas Moridnia, Maryam Saneipour
MicroRNAs (miRNAs) involved in regulation of the genes. The CCAAT/enhancer-binding protein-α ( CEBPα ) is a crucial transcription factor for normal hematopoiesis and cell cycle that frequently disrupted in human acute myeloid leukemia (AML). The miR-182 up-regulation in several malignant diseases such as AML was reported, in the other hand bioinformatics analysis revealed CEBPα targeted by miR-182.miR-182-5p inhibition in human acute promyelocytic leukemia (APL) cell line was performed by using locked nucleic acid (LNA) and subsequently miR-182-5p and CEBPα expression, apoptosis, necrosis and cell proliferation were measured...
March 2018: Molecular Biology Research Communications
Shuyuan Liu, Jinhua Wan, Yunyuan Kong, Yonglu Zhang, Lagen Wan, Zhanglin Zhang
The cullin-RING ligase (CRL)-NEDD8 pathway maintains essential cellular processes, including cell cycle progression, apoptosis, autophagy, DNA repair, antigen processing and signal transduction. Growing evidence demonstrates that the alteration of the CRL-NEDD8 pathway in some cancers constitutes an attractive target for therapeutic intervention, but the roles of CRL-NEDD8 pathway in acute promyelocytic leukemia (APL) is still unclear. In the present study, we found that ATRA could decrease the expression of NEDD8-activating enzyme E1 (NAE1) and inhibit the neddylation of cullin1 and cullin3 in the APL cell line NB4...
2018: International Journal of Medical Sciences
Lianlian Li, Yong Wang, Xiaoyu Zhang, Guanhua Song, Qiang Guo, Zhiyong Zhang, Yutao Diao, Haipeng Yin, Hongyan Liu, Guosheng Jiang
All-trans retinoic acid (ATRA) has been used for the treatment of acute promyelocytic leukemia (APL). However, its molecular mechanisms of action are unclear. Ubiquitin-specific protease 48 (USP48) is a deubiquitinase enzyme that can post-translationally remove ubiquitin molecules from substrates. In the present study, the role of USP48 in ATRA-induced differentiation of APL cells was studied. The expression of USP48 decreased following ATRA treatment. Functionally, overexpression of USP48 using electroporation-mediated delivery inhibited the proliferation of APL cells and promoted ATRA-mediated differentiation...
June 13, 2018: International Journal of Oncology
Peter Geon Kim, Kelly Bridgham, Evan C Chen, Mahesh K Vidula, Olga Pozdnyakova, Andrew M Brunner, Amir T Fathi
The use of all-trans retinoic acid (ATRA) combined with arsenic trioxide (ATO) with or without cytotoxic chemotherapy is highly effective in acute promyelocytic leukemia (APL) but incident chronic adverse events (AEs) after initiation of therapy are not well understood. We retrospectively analyzed adult patients with newly diagnosed APL from 2004 through 2014 to identify incident AEs following treatment and contributing risk factors. Cardiac and neurologic AEs were more common and characterized in detail. Cardiac AEs such as the development of coronary artery disease (CAD), arrhythmias, and heart failure had a cumulative incidence of 6...
2018: Leukemia Research Reports
Daria Gaut, Joshua Sasine, Gary Schiller
Although rare, secondary clonal hematologic neoplasia may occur after successful therapy for acute promyelocytic leukemia (APL). These secondary clonal events may be considered therapy-related, but may also be due to an underlying background of clonal hematopoiesis from which both malignancies may develop. In this manuscript, we describe two patients with secondary clones after APL therapy characterized in one patient by deletion of chromosome 11q23 and, in the other, by monosomy of chromosome 7, and also provide a review of all secondary clonal disorders described after APL therapy...
2018: Leukemia Research Reports
Carmen Winters, Andy I Chen, Stephen Moore, Elie Traer, Jennifer Dunlap
Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia defined by a balanced translocation between chromosomes 15 and 17 resulting in fusion of the promyelocytic leukemia gene (PML) on chromosome 15 with the retinoic acid receptor-alpha gene (RARα) on chromosome 17. APL often presents with pancytopenia and is associated with a life threatening coagulopathy making prompt diagnosis and initiation of therapy critical. We report an unusual case of APL in a 59 year old female without peripheral blood abnormalities or diffuse marrow involvement...
2018: Leukemia Research Reports
Christopher A Miller, Christopher Tricarico, Zachary L Skidmore, Geoffrey L Uy, Yi-Shan Lee, Anjum Hassan, Michelle D O'Laughlin, Heather Schmidt, Ling Tian, Eric J Duncavage, Malachi Griffith, Obi L Griffith, John S Welch, Lukas D Wartman
No abstract text is available yet for this article.
June 12, 2018: Blood Advances
András Demjén, Róbert Alföldi, Anikó Angyal, Márió Gyuris, László Hackler, Gábor J Szebeni, János Wölfling, László G Puskás, Iván Kanizsai
The synthesis and in vitro cytotoxic characteristics of new imidazo[1,2-b]pyrazole-7-carboxamides were investigated. Following a hit-to-lead optimization exploiting 2D and 3D cultures of MCF-7 human breast, 4T1 mammary gland, and HL-60 human promyelocytic leukemia cancer cell lines, a 67-membered library was constructed and the structure-activity relationship (SAR) was determined. Seven synthesized analogues exhibited sub-micromolar activities, from which compound 63 exerted the most significant potency with a remarkable HL-60 sensitivity (IC50  = 0...
June 10, 2018: Archiv der Pharmazie
Christian Hoischen, Shamci Monajembashi, Klaus Weisshart, Peter Hemmerich
The promyelocytic leukemia ( pml ) gene product PML is a tumor suppressor localized mainly in the nucleus of mammalian cells. In the cell nucleus, PML seeds the formation of macromolecular multiprotein complexes, known as PML nuclear bodies (PML NBs). While PML NBs have been implicated in many cellular functions including cell cycle regulation, survival and apoptosis their role as signaling hubs along major genome maintenance pathways emerged more clearly. However, despite extensive research over the past decades, the precise biochemical function of PML in these pathways is still elusive...
2018: Frontiers in Oncology
Hong-Hu Zhu, De-Pei Wu, Xin Du, Xi Zhang, Lin Liu, Jun Ma, Zong-Hong Shao, Han-Yun Ren, Jian-Da Hu, Kai-Lin Xu, Jing-Wen Wang, Yong-Ping Song, Mei-Yun Fang, Juan Li, Xiao-Yan Yan, Xiao-Jun Huang
BACKGROUND: Intravenous arsenic trioxide plus all-trans retinoic acid (ATRA) without chemotherapy is the standard of care for non-high-risk acute promyelocytic leukaemia (white blood cell count ≤10 × 109 per L), resulting in cure in more than 95% of cases. However, a pilot study of treatment with oral arsenic realgar-Indigo naturalis formula (RIF) plus ATRA without chemotherapy, which has a more convenient route of administration than the standard intravenous regimen, showed high efficacy...
June 5, 2018: Lancet Oncology
Francesco Lo-Coco, Laura Cicconi
No abstract text is available yet for this article.
June 5, 2018: Lancet Oncology
Abhishek A Singh, Francesca Petraglia, Angela Nebbioso, Guoqiang Yi, Mariarosaria Conte, Sergio Valente, Amit Mandoli, Lucia Scisciola, Rik Lindeboom, Hinri Kerstens, Eva M Janssen-Megens, Farzin Pourfarzad, Ehsan Habibi, Kim Berentsen, Bowon Kim, Colin Logie, Simon Heath, Albertus T J Wierenga, Laura Clarke, Paul Flicek, Joop H Jansen, Taco Kuijpers, Marie Laure Yaspo, Veronique Della Valle, Olivier Bernard, Ivo Gut, Edo Vellenga, Hendrik G Stunnenberg, Antonello Mai, Lucia Altucci, Joost H A Martens
Epigenomic alterations have been associated with both pathogenesis and progression of cancer. Here, we analyzed the epigenome of two high-risk APL (hrAPL) patients and compared it to non-high-risk APL cases. Despite the lack of common genetic signatures, we found that human hrAPL blasts from patients with extremely poor prognosis display specific patterns of histone H3 acetylation, specifically hyperacetylation at a common set of enhancer regions. In addition, unique profiles of the repressive marks H3K27me3 and DNA methylation were exposed in high-risk APLs...
May 22, 2018: Oncotarget
Nathaniel J Buteyn, Kavin Fatehchand, Ramasamy Santhanam, Huiqing Fang, Gino M Dettorre, Shalini Gautam, Bonnie K Harrington, Sally E Henderson, Giovanna Merchand-Reyes, Xiaokui Mo, Don M Benson, William E Carson, Sumithira Vasu, John C Byrd, Jonathan P Butchar, Susheela Tridandapani
Acute myeloid leukemia (AML) remains a significant health problem, with poor outcomes despite chemotherapy and bone-marrow transplants. Although one form of AML, acute promyelocytic leukemia (APL), is successfully treated with all-trans retinoic acid (ATRA), this drug is seemingly ineffective against all other forms of AML. Here, we show that ATRA upregulates CD38 expression on AML blasts to sufficient levels that promote antibody-mediated fratricide following the addition of anti-CD38 Daratumumab. The combination of ATRA plus Daratumumab induced Fc-dependent conjugate formation and cytotoxicity among AML blasts in vitro...
June 2, 2018: International Immunology
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