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leukemia AND treatment

Yuhua Ding, Huihui Xu, Luyang Li, Yibiao Yuan, Yong Xu
Diabetic retinopathy (DR) is one of the most devastating complications of diabetes mellitus. When exposed to high glucose (HG), retinal epithelial cells undergo profound alterations both morphologically and functionally in a well-conserved process known as epithelial-to-mesenchymal transition (EMT). The mechanism governing HG-induced EMT in retinal epithelial cells is not completely understood. Here we report that treatment with 25 mM glucose led to EMT in retinal pigmented epithelial cells (RPE) characterized by a simultaneous down-regulation of E-Cadherin (encoded by CDH1) and up-regulation of alpha smooth muscle actin (encoded by ACTA2)...
December 13, 2018: Biochemical and Biophysical Research Communications
Rik A Brooimans, Vincent H J van der Velden, Nancy Boeckx, Jennita Slomp, Frank Preijers, Jeroen G Te Marvelde, Ngoc M Van, Antoinette Heijs, Erik Huys, Bronno van der Holt, Georgine E de Greef, Angele Kelder, Gerrit Jan Schuurhuis
Flow-cytometric detection of now termed measurable residual disease (MRD) in acute myeloid leukemia (AML) has proven to have an independent prognostic impact. In a previous multicenter study we developed protocols to accurately define leukemia-associated immunophenotypes (LAIPs) at diagnosis. It has, however, not been demonstrated whether the use of the defined LAIPs in the same multicenter setting results in a high concordance between centers in MRD assessment. In the present paper we evaluated whether interpretation of list-mode data (LMD) files, obtained from MRD assessment of previously determined LAIPs during and after treatment, could reliably be performed in a multicenter setting...
November 27, 2018: Leukemia Research
Jing Wang, Changpei Gan, Irene A Retmana, Rolf W Sparidans, Wenlong Li, Maria C Lebre, Jos H Beijnen, Alfred H Schinkel
Quizartinib, a second-generation FLT3 inhibitor, is in clinical development for the treatment of acute myeloid leukemia. We studied its pharmacokinetic interactions with the multidrug efflux transporters ABCB1 and ABCG2 and the multidrug metabolizing enzyme CYP3A, using in vitro transport assays and knockout and transgenic mouse models. Quizartinib was transported by human ABCB1 in vitro, and by mouse (m)Abcb1 and mAbcg2 in vivo. Upon oral administration, the brain accumulation of quizartinib was 6-fold decreased by mAbcb1 and 2-fold by mAbcg2 (together: 12-fold)...
December 12, 2018: International Journal of Pharmaceutics
Qun Luo, Wanglong Deng, Haiwei Wang, Huiyong Fan, Ji Zhang
Bromodomain-containing 4 (BRD4) has been considered as an important requirement for disease maintenance and an attractive therapeutic target for cancer therapy. This protein can be targeted by JQ1, a selective small-molecule inhibitor. However, few studies have investigated whether BRD4 influenced acute promyelocytic leukemia (APL), and whether BRD4 had interaction with promyelocytic leukemia-retinoic acid receptor α (PML/RARα) fusion protein to some extent. Results from cell viability assay, cell cycle analysis, and Annexin-V/PI analysis indicated that JQ1 inhibited the growth of NB4 cells, an APL-derived cell line, and induced NB4 cell cycle arrest at G1 and apoptosis...
December 2018: Frontiers of Medicine
Arnon P Kater, Sabina Kersting, Yvette van Norden, Julie Dubois, Johan A Dobber, Clemens H Mellink, Ludo M Evers, Fransien Croon-de Boer, John Schreurs, Ellen van der Spek, Hein Visser, Cecile Idink, Shulamiet Wittebol, Mels Hoogendoorn, Sanne H Tonino, Mehrdad Mobasher, Mark-David Levin
Early data on venetoclax-containing regimens for the treatment of chronic lymphocytic leukemia (CLL) show promising results with deep remissions, but are hampered by potential risk for tumor lysis syndrome (TLS). Whether optimal duration of venetoclax treatment can be guided by minimal residual disease (MRD) is currently unknown. To study whether TLS risk can be mitigated in an unfit population by introducing preinduction, and whether MRD-guided duration of venetoclax treatment is a feasible and efficacious approach, we performed the Dutch-Belgian Cooperative Trial Group for Hemato-oncology (HOVON) 139/GIVE trial...
December 26, 2018: Blood Advances
Atif A Ahmed, Divya S Vundamati, Midhat S Farooqi, Erin Guest
Precision oncologic medicine is an emerging approach for cancer treatment that has recently taken giant steps in solid clinical practice. Recent advances in molecular diagnostics that can analyze the individual tumor's variability in genes have provided greater understanding and additional strategies to treat cancers. Although tumors can be tested by several molecular methods, the use of next-generation sequencing (NGS) has greatly facilitated our understanding of pediatric cancer and identified additional therapeutic opportunities...
December 13, 2018: High-throughput
Arash Soltani, Seyed Isaac Hashemy, Farnaz Zahedi Avval, Anvar Soleimani, Houshang Rafatpanah, Seyed Abdorahim Rezaee, Renate Griffith, Baratali Mashkani
Human T-cell lymphotropic virus type 1 (HTLV-1) infection is linked to adult T-cell leukemia-lymphoma (ATLL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and several other disorders. ATLL occurs in approximately 5% of the 15-20 million people infected by HTLV-1 in the world. In general, ATLL is resistant to chemotherapy, which underlines the need for new and effective therapeutic strategies. Previous studies highlighted the role of viral enzymes, responsible for viral replication, and regulatory proteins such as Tax and HBZ in the progression of HTLV-1-associated diseases...
January 2019: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Zahra Payandeh, Armina Alagheband Bahrami, Reyhaneh Hoseinpoor, Yousef Mortazavi, Masoumeh Rajabibazl, Azam Rahimpour, Amir Hossein Taromchi, Saeed Khalil
B-lymphocyte antigen CD20 (called CD20) is known as an activated-glycosylated phosphoprotein which is expressed on the surface of all B-cells. CD20 is involved in the regulation of trans-membrane Ca2+ conductance and also play critical roles in cell-cycle progression during human B cell proliferation and activation. The appearance of monoclonal antibody (mAb) technology provided an effective field for targeted therapy in treatment of a variety of diseases such as cancer, and autoimmune diseases. Anti-CD20 is one of important antibodies which could be employed in treatment of several diseases...
January 2019: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Jinfeng Xiang, Gang Wang, Tian Xia, Zhixin Chen
Mutation of PHF6 has been identified in Börjeson-Forssman-Lehmann syndrome and some types of subsets of childhood leukemia. However, the molecular function and the relationship of PHF6 mutation with glucocorticoid drug resistance during T-ALL treatment remains elusive. Here we report the influence of PHF6 expression on the drug response of T-ALL to prednisolone, and the underlying mechanism of this. Through sanger sequencing and western blotting assays, we identified two T-ALL cell lines with wild-type PHF6 expression, including SIL-ALL and CCRF-CEM, and two T-ALL cell lines without PHF6 expression, including TALL-1 and HPB-ALL, due to the nonsense and frameshift mutations in the coding region of PHF6...
January 2019: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Qun Li, Wei Song, Jianmin Wang
Increasing evidence has suggested the involvement of long non-coding RNA (lncRNA) taurine upregulated gene 1 (TUG1) in chemoresistance of cancer treatment. However, its function and molecular mechanisms in acute myeloid leukemia (AML) chemoresistance are still not well elucidated. In the present study, we investigate the functional role of TUG1 in Adriamycin (ADR) resistance of AML and discover the underlying molecular mechanism. Our study revealed that TUG1 was up-regulated in ADR-resistant AML tissues and cells...
January 2019: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Qiuju Zhao, Shihao Zhao, Jinling Li, Huiwu Zhang, Cheng Qian, He Wang, Jianjun Liu, Yuqi Zhao
Acute lymphoblastic leukemia (ALL) is characterized by abnormal lymphoblasts accumulation in the bone marrow and blood. Despite great efforts have been made in exploring novel therapeutic method, the prognosis of children with ALL is still unsatisfied. Glucocorticoid (GC) resistance is a great obstacle for the clinical treatment of ALL. Therefore, it is essential to investigate the molecular mechanism underlying the GC resistance. According to previous reports, long noncoding RNAs (lncRNAs) are involved in drug resistance of various human cancers...
January 2019: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Yan-Lai Tang, Xi Sun, Li-Bin Huang, Xiao-Jian Liu, Ge Qin, Li-Na Wang, Xiao-Li Zhang, Zhi-Yong Ke, Jie-Si Luo, Cong Liang, Chun-Jin Peng, Wen-Yan Tang, Yu Li, Wenlin Huang, Xue-Qun Luo, Wuguo Deng
MLL-rearranged leukemia is an aggressive malignancy associated with poor outcome, which is refractory to conventional treatment. Melatonin has been proven to exert anti-tumor activity, but the effect of melatonin on MLL-r leukemia and the underlying mechanism remain poorly understood. In this study, melatonin inhibited cell proliferation and induced apoptosis by activating the caspase-dependent apoptotic pathway in MLL-r leukemia cells. Mechanistic investigations revealed that melatonin suppressed the expression of hTERT by abrogating the binding activity of RBFOX3 to the hTERT promoter...
December 10, 2018: Cancer Letters
Anne-Sofie Skou, Steen Ø Olsen, Lars H Nielsen, Heidi Glosli, Kirsi Jahnukainen, Marianne Jarfelt, Guðmundur K Jónmundsson, Johan Malmros, Karsten Nysom, Henrik Hasle
BACKGROUND: As more children survive acute myeloid leukemia (AML) it is increasingly important to assess possible late effects of the intensive treatment. Hearing loss has only sporadically been reported in survivors of childhood AML. We assessed hearing status in survivors of childhood AML treated with chemotherapy alone according to 3 consecutive NOPHO-AML trials. PROCEDURE: A population-based cohort of children treated according to the NOPHO-AML-84, NOPHO-AML-88, and NOPHO-AML-93 trials included 137 eligible survivors among whom 101 (74%) completed a questionnaire and 99 (72%) had otologic and audiologic examination performed including otoscopy (72%), pure tone audiometry (70%), and tympanometry (60%)...
January 2019: Journal of Pediatric Hematology/oncology
Jean-Baptiste Vulsteke, Dries Deeren
Mucormycosis is an aggressive invasive fungal infection that occurs rarely in immunocompetent but frequently in immunocompromised patients. We present a case of a 68-year old patient with cutaneous mucormycosis due to Rhizopus pusillus. He was initially hospitalized for invasive pulmonary aspergillosis and diabetes mellitus secondary to acute graft-versus-host treatment with glucocorticoids after allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia. Treatment with liposomal amphotericin B and posaconazole was initiated but the patient developed septic shock with multiple organ failure and died 5 days later...
December 13, 2018: Transplant Infectious Disease: An Official Journal of the Transplantation Society
Silin Zhang, Yunhe Xiong, Yixian Zhang, Hongmei Zhao
Interactions between the tumor cells and bone marrow (BM) microenvironment promote survival, growth, and chemoresistance of acute myeloid leukemia (AML). The mTOR pathway plays a key role in mediating the AML-BM microenvironment interactions. Here, we report the anti-AML activity of a natural monomer extracted from the Chinese medicinal herb Evodia rutaecarpa, dihydroevocarpine. Our results showed that dihydroevocarpine-induced cytotoxicity, apoptosis, and G0/G1 arrest in AML cells, and inhibited the tumor growth in an AML xenograft model...
December 12, 2018: Journal of Cellular Physiology
Tingting Wang, Lizhang Chen, Tubao Yang, Lesan Wang, Lijuan Zhao, Senmao Zhang, Ziwei Ye, Letao Chen, Zan Zheng, Jiabi Qin
Prior studies on the association between fertility treatment and childhood cancer risk have generated inconsistent results. We performed a systematic review and meta-analysis of observation studies to summarize the evidence regarding the relation of fertility treatment with childhood cancer risk. A systematic literature search of several databases was conducted through April 2018 to identify relevant studies. The outcomes of interest included overall cancer, haematological malignancies, neural tumours, other solid tumours, and eight specific cancers...
December 13, 2018: International Journal of Cancer. Journal International du Cancer
Gregory S Calip, Kellyn M Moran, Karen I Sweiss, Pritesh R Patel, Zhaoju Wu, Sruthi Adimadhyam, Todd A Lee, Naomi Y Ko, John G Quigley, Brian C-H Chiu
BACKGROUND: Granulocyte colony-stimulating factors (G-CSFs), which are used for the prevention of complications from chemotherapy-related neutropenia, are linked to the risk of developing second primary myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). The objective of this study was to examine the correlation between using a specific G-CSF agent and the risk of MDS/AML among older patients with non-Hodgkin lymphoma (NHL). METHODS: This was a retrospective cohort study of adults aged >65 years who were diagnosed with first primary NHL between 2001 and 2011...
December 12, 2018: Cancer
Sedigheh Eskandari, Razieh Yazdanparast
Tyrosine kinase inhibitor (TKI)-based therapy has created promising results among much chronic myeloid leukemia (CML) patients. Imatinib as a relatively specific inhibitor of Bcr-Abl is at present one of the undisputed therapeutic agent for newlydiagnosed patients with CML. However, the occurrence of imatinib-resistance enlightens the urgent need to identify other therapeutic agents against CML. Juglone (5-hydroxy-2-methyl-1, 4-naphthoquinone) exerts cytotoxic effects against various human cancer cell lines...
December 11, 2018: Journal of Cellular Biochemistry
Tomasz Sacha, Giuseppe Saglio
Nilotinib, a second-generation tyrosine kinase inhibitor, was designed to overcome resistance of a wide range of BCR-ABL mutants to imatinib. When used in the first-line treatment in newly diagnosed  chronic myeloid leukemia (CML), it induces faster and deeper molecular responses in higher than imatinib percentage of patients. Treatment-free remission after achievement of sustained deep molecular response represents an emerging treatment goal for a proportion of patients with CML in chronic phase. The pharmacologic properties, and the role of nilotinib in the current treatment of CML in the context of considered optimal end point of therapy including the discontinuation trial and durable treatment-free remission achievement is discussed in the article...
December 14, 2018: Future Oncology
J Prinz, Y d'Hargues, P Gödel, A Shimabukuro-Vornhagen, M Kochanek, B Böll
BACKGROUND: The development of chimeric antigen receptor (CAR) T‑cells has shown promising results in relapsed/refractory B‑cell acute lymphoblastic leukemia/lymphoma (B-ALL) and diffuse large cell B‑cell lymphoma. Complications, especially cytokine release syndrome (CRS) and CAR T‑cell related encephalopathy syndrome (CRES), can be life threatening. The management of both plays a key role in CAR T‑cell therapy. OBJECTIVES: Diagnosis, clinical presentation and development of complications in the treatment with CAR T‑cells...
December 13, 2018: Medizinische Klinik, Intensivmedizin und Notfallmedizin
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