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https://www.readbyqxmd.com/read/29677511/an-integrated-genome-wide-crispra-approach-to-functionalize-lncrnas-in-drug-resistance
#1
Assaf C Bester, Jonathan D Lee, Alejandro Chavez, Yu-Ru Lee, Daphna Nachmani, Suhani Vora, Joshua Victor, Martin Sauvageau, Emanuele Monteleone, John L Rinn, Paolo Provero, George M Church, John G Clohessy, Pier Paolo Pandolfi
Resistance to chemotherapy plays a significant role in cancer mortality. To identify genetic units affecting sensitivity to cytarabine, the mainstay of treatment for acute myeloid leukemia (AML), we developed a comprehensive and integrated genome-wide platform based on a dual protein-coding and non-coding integrated CRISPRa screening (DICaS). Putative resistance genes were initially identified using pharmacogenetic data from 760 human pan-cancer cell lines. Subsequently, genome scale functional characterization of both coding and long non-coding RNA (lncRNA) genes by CRISPR activation was performed...
April 19, 2018: Cell
https://www.readbyqxmd.com/read/29676445/systematic-patient-involvement-for-homebased-outpatient-administration-of-complex-chemotherapy-in-acute-leukemia-and-lymphoma
#2
Katrine S Fridthjof, Peter Kampmann, Anne Dünweber, Jette S Gørløv, Connie Nexø, Lone S Friis, Kristina H Nørskov, Pernille C Welinder, Claus Moser, Lars Kjeldsen, Tom Møller
Based on experience with comprehensive patient involvement, we present data from implementation of portable, programmable infusion pumps (PPP) for home-based chemotherapy administration in patients with acute leukaemia and in lymphoma patients receiving (carmustine, etoposide, cytarabine, melphalan) BEAM regimen. Data from 84 patients, receiving 177 cycles of PPP administered chemotherapy, showed convincing safety with minor equipment errors encountered and with high patient satisfaction. In-hospital days could be reduced with 52% out of a total of 1197 treatment days...
April 20, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29668607/successful-treatment-of-high-risk-myelodysplastic-syndrome-with-decitabine-based-chemotherapy-followed-by-haploidentical-lymphocyte-infusion-a-case-report-and-literature-review
#3
Yuanyuan Ma, Jianliang Shen, Li-Xin Wang
RATIONALE: The current therapy for elderly patients with high-risk myelodysplastic syndromes (MDSs) remains unsatisfactory. Decitabine, which has been approved to treat MDS, cannot eliminate malignant clones of MDS. PATIENT CONCERNS: A 68-year-old woman presented with multiple divergent bleeding points in the subcutaneous tissue of the limb. Two years earlier, she had been diagnosed with invasive ductal carcinoma of the left breast and had undergone left modified radical mastectomy and local radiation therapy...
April 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29668549/epigenetic-therapy-in-a-patient-with-down-syndrome-and-refractory-acute-myeloid-leukemia
#4
Kerri Becktell, Kerri Houser, Michael J Burke
Acute myeloid leukemia (AML) associated with Down syndrome (DS-AML) is a unique entity of AML with superior treatment response and overall survival compared with children with non-DS-AML. Despite good outcomes in DS-AML, those who relapse or have refractory disease have poor survival. Successful treatment of these patients is challenged by increased incidence of treatment-related toxicities often encountered with high-dose chemotherapy. Here we report the experience of epigenetic modifying agents (decitabine and vorinostat) followed by fludarabine, cytarabine, and granulocyte colony stimulating growth factor for a child with refractory DS-AML...
April 17, 2018: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29665909/-complete-remission-rate-and-adverse-ractions-of-three-different-chemotherapy-regimens-in-the-treatment-of-adult-patients-with-newly-diagnosed-non-m3-aml
#5
Peng Lin, Wei Wang, Wei-Bo Huang, Ming-Wei Li, Xiao-Na Yang, Hai-Ying Yao
OBJECTIVE: To compare the complete remission rate (CRR) and adverse reaction of the 3 different chemotherapy regimens (daunorubicin, idarubicin, imported idarubicin combined with cytarabine) for the treatment of adult patients with newly diagnosed non-M3 acute myeloid leukemia (AML). METHODS: Seventy-one adult patients with newly diagnosed non-M3 AML were divided into 3 groups: 17 cases treated with daunorubicin plus cytarabine as group A, 24 cases treated with idarubicin plus cytarabine as group B, 30 cases treated with the imported idarubicin plus cytarabine as group C...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29660836/final-results-of-a-phase-2-open-label-study-of-indisulam-idarubicin-and-cytarabine-in-patients-with-relapsed-or-refractory-acute-myeloid-leukemia-and-high-risk-myelodysplastic-syndrome
#6
Rita Assi, Hagop M Kantarjian, Tapan M Kadia, Naveen Pemmaraju, Elias Jabbour, Nitin Jain, Naval Daver, Zeev Estrov, Taisuke Uehara, Takashi Owa, Jorge E Cortes, Gautam Borthakur
BACKGROUND: Indisulam possesses anticancer properties through down-regulation of various cell-cycle checkpoint molecules, thereby blocking the phosphorylation of retinoblastoma protein and inducing p53 and p21. Indisulam exhibits synergy with nucleoside analogs and topoisomerase inhibitors. METHODS: The authors designed a phase 2 study of indisulam in combination with idarubicin and cytarabine in patients who had relapsed/refractory acute myeloid leukemia AML and high-risk myelodysplastic syndrome...
April 16, 2018: Cancer
https://www.readbyqxmd.com/read/29658620/impact-of-economic-sanctions-on-access-to-noncommunicable-diseases-medicines-in-the-islamic-republic-of-iran
#7
Mehrnaz Kheirandish, Vida Varahrami, Abbas Kebriaeezade, Abdol Majid Cheraghali
Background: It has been argued that economic sanctions and the economic crisis have adversely affected access to drugs. Aim: To assess the impact of economic sanctions on the Iranian banking system in 2011 and Central Bank in 2012 on access to and use of drugs for noncommunicable diseases (NCDs). Methods: An interrupted time series study assessed the effects of sanctions on drugs for diabetes (5 drug groups), asthma (5 drug groups), cancer (14 drugs) and multiple sclerosis (2 drugs)...
April 5, 2018: Eastern Mediterranean Health Journal, la Revue de Santé de la Méditerranée Orientale
https://www.readbyqxmd.com/read/29650946/a-rare-case-of-relapsed-pediatric-acute-promyelocytic-leukemia-with-skin-involvement-by-myeloid-sarcoma
#8
Nathalia Silva Araújo, Claudio José Dos Santos Júnior, Vitória Mikaelly da Silva Gomes, Luiz Arthur Calheiros Leite, Luana Novaes Bomfim, Amanda Katielly Firmino da Silva Gusmão, Maria Jordana Rocha Gomes Alves, Cyndi Myrelle da Silva Barros Romão, Arthur Moacir Costa Sampaio Batinga, Maria Rosa da Silva, Célio Fernando de Sousa Rodrigues
BACKGROUND Acute promyelocytic leukemia (APL) is a very rare leukemia in children. Extramedullary involvement by APL has been reported in between 3-5% of cases, mainly associated with cases of relapse. A rare case of relapse of APL in a 9-year-old child is presented with skin involvement with myeloid sarcoma. CASE REPORT A 9-year-old male child was admitted to the Oncology Service of the hospital complaining of fever, progressive fatigue, oral petechiae with severe bleeding in the oral cavity. Bone marrow examination showed some promyelocytes...
April 13, 2018: American Journal of Case Reports
https://www.readbyqxmd.com/read/29645075/results-of-second-salvage-therapy-in-673-adults-with-acute-myelogenous-leukemia-treated-at-a-single-institution-since-2000
#9
Hagop M Kantarjian, Courtney D DiNardo, Graciela M Nogueras-Gonzalez, Tapan M Kadia, Elias Jabbour, Carlos E Bueso-Ramos, Susan M O'Brien, Marina Konopleva, Nitin B Jain, Naval G Daver, Elizabeth J Shpall, Richard E Champlin, Aron Simkins, Guillermo Garcia-Manero, Michael J Keating, Xuelin Huang, Jorge E Cortes, Sherry A Pierce, Farhad Ravandi, Emil J Freireich
BACKGROUND: The prognosis is poor for patients who have relapsed-refractory acute myelogenous leukemia (AML). Most published reports analyzed results from therapies in first-salvage AML or in studies that were conducted before 2000. Several novel agents and strategies are being tested for potential approval as treatment for patients with relapsed-refractory AML in second salvage. Therefore, it is important to establish the historic results of anti-AML therapies in this setting in the modern era...
April 12, 2018: Cancer
https://www.readbyqxmd.com/read/29623713/-active-substances-from-marine-organisms-in-clinical-trials-and-practice
#10
Jana Rudá-Kučerová, D Mareček
Oceans cover a large part of our planet and they are a home for an enormous amount of species. A lot of them are still waiting to be discovered by man, much like the chemicals they synthesize. Marine pharmacology concerns itself with the study of these chemicals and their potential use in medicine. Origin in marine species is for the most part the only thing this large and diverse group of substances have in common, so the spectrum of possible applications is quite wide. Many of these substances have a unique mechanism of action, offering new therapeutic possibilities...
2018: Ceská a Slovenská Farmacie
https://www.readbyqxmd.com/read/29616840/decitabine-in-combination-with-g-csf-low-dose-cytarabine-and-aclarubicin-is-as-effective-as-standard-dose-chemotherapy-in-the-induction-treatment-for-patients-aged-from-55-to-69-years-old-with-newly-diagnosed-acute-myeloid-leukemia
#11
Jiayu Huang, Ming Hong, Yu Zhu, Huihui Zhao, Xiaoyan Zhang, Yujie Wu, Yun Lian, Xiaoli Zhao, Jianyong Li, Sixuan Qian
We retrospectively studied 87 patients aged from 55 to 69 years old with acute myeloid leukemia (AML) who received decitabine in combination with G-CSF, low-dose cytarabine and aclarubicin (DCAG) or standard dose chemotherapy as induction therapy. Patients receiving DCAG had a similar overall response rate (ORR) (p = .6105) and complete remission (CR) rate (p = .3615) compared to those undergoing standard induction. The median overall survival (OS) and relapse-free survival (RFS) was also similar between the two groups although more 'older' (aged from 60 to 69 years old) and 'unfit' patients underwent DCAG regimen...
April 4, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29615003/role-of-cytarabine-in-paediatric-acute-promyelocytic-leukemia-treated-with-the-combination-of-all-trans-retinoic-acid-and-arsenic-trioxide-a-randomized-controlled-trial
#12
Li Zhang, Yao Zou, Yumei Chen, Ye Guo, Wenyu Yang, Xiaojuan Chen, Shuchun Wang, Xiaoming Liu, Min Ruan, Jiayuan Zhang, Tianfeng Liu, Fang Liu, Benquan Qi, Wenbin An, Yuanyuan Ren, Lixian Chang, Xiaofan Zhu
BACKGROUND: The combination of all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) has been suggested to be safe and effective for adult acute promyelocytic leukaemia (APL). As of 2010, the role of cytarabine (Ara-C) in APL was controversial. The aim of this study was to test the efficacy and safety of ATRA and ATO in paediatric APL patients. Also, we assessed whether Ara-C could be omitted in ATO and ATRA- based trials in children. METHODS: We performed a randomized controlled trial in paediatric APL patients (≤14 years of age) in our hospital from May 2010 to December 2016...
April 3, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29607465/sirolimus-enhances-remission-induction-in-patients-with-high-risk-acute-myeloid-leukemia-and-mtorc1-target-inhibition
#13
Margaret T Kasner, Rosemarie Mick, Grace R Jeschke, Matthew Carabasi, Joanne Filicko-O'Hara, Neal Flomenberg, Noelle V Frey, Elizabeth O Hexner, Selina M Luger, Alison W Loren, James K Mangan, John L Wagner, Mark Weiss, Martin Carroll, Alexander E Perl
Background Mammalian Target of Rapamycin Complex 1 (mTORC1) inhibitors enhance chemotherapy response in acute myelogenous leukemia (AML) cells in vitro. However whether inhibiting mTORC1 enhances clinical response to AML chemotherapy remains controversial. We previously optimized measurement of mTORC1's kinase activity in AML blasts during clinical trials using serial phospho-specific flow cytometry of formaldehyde-fixed whole blood or marrow specimens. To validate mTORC1 as a therapeutic target in AML, we performed two clinical trials combining an mTORC1 inhibitor (sirolimus) and MEC (mitoxantrone, etoposide, cytarabine) in patients with relapsed, refractory, or untreated high-risk AML...
April 2, 2018: Investigational New Drugs
https://www.readbyqxmd.com/read/29603737/clinical-presentation-and-magnetic-resonance-imaging-findings-in-11-dogs-with-eosinophilic-meningoencephalitis-of-unknown-aetiology
#14
T J A Cardy, I Cornelis
OBJECTIVES: To describe the clinical presentation, MRI findings and outcome in dogs with eosinophilic meningoencephalitis of unknown origin. MATERIALS AND METHODS: Dogs were included in this retrospective study if they had complete medical records, complete neurological examination, MR imaging, cerebellomedullary cerebrospinal fluid sample consistent with eosinophilic pleocytosis and negative infectious disease testing. RESULTS: Eleven dogs were included with a median age of 22·0 months (range 7·6 to 92·0 months)...
March 30, 2018: Journal of Small Animal Practice
https://www.readbyqxmd.com/read/29574395/acute-myeloid-leukemia-induction-with-cladribine-outcomes-by-age-and-leukemia-risk
#15
Martin W Schoen, Susan K Woelich, James T Braun, Dhinesh V Reddy, Mark J Fesler, Paul J Petruska, Carl E Freter, Jack M Lionberger
Acute myeloid leukemia (AML) induction traditionally includes seven days of cytarabine and three days of an anthracycline (7 + 3). Because of evidence of increased efficacy of cladribine combined with this regimen, we conducted a retrospective analysis of 107 AML patients treated with idarubicin, cytarabine and cladribine (IAC) at our institution. Complete remission (CR) occurred in 71%, with overall response of 79%. One-year survival overall was 59%, with 47% (27/57) among patients ≥60 years old and 72% (36/50) in those <60 (Relative Risk [RR] 1...
March 6, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29574276/cxcr4-mediated-signaling-regulates-autophagy-and-influences-acute-myeloid-leukemia-cell-survival-and-drug-resistance
#16
Xiaojia Hu, Shuang Mei, Wenfang Meng, Shihang Xue, Lejian Jiang, Yang Yang, Lanlan Hui, Ye Chen, Min-Xin Guan
CXCR4 surface expression is considered an independent prognostic factor for disease relapse and survival in acute myeloid leukemia (AML) patients. Herein, we investigated targetable autophagy-related mechanisms of CXCR4 for AML therapy. Our experiments show that activation of CXCR4 signaling in AML cells increases autophagic activity and decreases cytarabine-induced apoptosis. Accordingly, combined use of autophagy inhibitors significantly increased the sensitivity of AML cells to cytarabine in vitro and in vivo...
March 21, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29567781/a-novel-regimen-for-relapsed-refractory-adult-acute-myeloid-leukemia-using-a-kmt2a-partial-tandem-duplication-targeted-therapy-results-of-phase-1-study-nci-8485
#17
Alice S Mims, Anjali Mishra, Shelley Orwick, James Blachly, Rebecca B Klisovic, Ramiro Garzon, Alison R Walker, Steven M Devine, Katherine J Walsh, Sumithira Vasu, Susan Whitman, Guido Marcucci, Daniel Jones, Nyla A Heerema, Gerard Lozanski, Michael A Caligiuri, Clara D Bloomfield, John C Byrd, Richard Piekarz, Michael R Grever, William Blum
KMT2A partial tandem duplication occurs in approximately 5-10% of patients with acute myeloid leukemia and is associated with adverse prognosis. KMT2A wild type is epigenetically silenced in KMT2A partial tandem duplication; re-expression can be induced with DNA methyltransferase and/or histone deacetylase inhibitors in vitro, sensitizing myeloid blasts to chemotherapy. We hypothesized that epigenetic silencing of KMT2A wildtype contributes to KMT2A partial tandem duplication-associated leukemogenesis and pharmacologic re-expression activates apoptotic mechanisms important for chemo-response...
March 22, 2018: Haematologica
https://www.readbyqxmd.com/read/29565169/biochemical-and-histological-changes-produced-by-sweeteners-and-cytarabine-in-the-brain-of-young-rats
#18
Ernestina Hernández García, Norma Osnaya Brizuela, Armando Valenzuela Peraza, David Calderón Guzmán, Maribel Ortiz Herrera, Hugo Juárez Olguín, Gerardo Barragán Mejía, Daniel Santamaría Del Ángel, Alberto Rojas Ochoa
OBJECTIVE: The aim of this study was to evaluate the effect of splenda and stevia on dopamine and 5-HIAA levels, and some biomarkers of oxidative stress in the presence of cytarabine. METHODS: Forty-eight young male Wistar rats each with a weight of 80 g (four weeks of age), distributed in six groups of eight animals each, were treated as follows: group 1, control (NaCl 0.9% vehicle); group 2, cytarabine (0.6 g/kg); group 3, stevia (0.6 g/kg); group 4, cytarabine + stevia; group 5, splenda; and group 6, cytarabine + splenda...
February 13, 2018: Nutrición Hospitalaria: Organo Oficial de la Sociedad Española de Nutrición Parenteral y Enteral
https://www.readbyqxmd.com/read/29559562/adjuvant-treatment-for-pole-proofreading-domain-mutant-cancers-sensitivity-to-radiotherapy-chemotherapy-and-nucleoside-analogs
#19
Inge C Van Gool, Emily Rayner, Elisabeth M Osse, Remi A Nout, Carien L Creutzberg, Ian Tomlinson, David N Church, Vincent T H B M Smit, Niels de Wind, Tjalling Bosse, Mark Drost
PURPOSE: Pathogenic POLE proofreading domain mutations are found in many malignancies where they are associated with ultramutation and favorable prognosis. The extent to which this prognosis depends on their sensitivity to adjuvant treatment is unknown, as is the optimal therapy for advanced-staged or recurrent POLE-mutant cancers. EXPERIMENTAL DESIGN: We examined the recurrence-free survival of women with POLE-mutant and POLE-wild-type endometrial cancers (ECs) in the observation arm of the randomized PORTEC-1 EC trial (N=245 patients with stage I EC for analysis)...
March 20, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29558212/combination-of-bleomycin-and-cytosine-arabinoside-chemotherapy-for-relapsed-canine-lymphoma
#20
Karen Batschinski, Nikolaos Dervisis, Barbara Kitchell, Rebecca Newman, Todd Erfourth
A retrospective study was performed to evaluate response rate, time to progression, and toxicity of a bleomycin and cytosine arabinoside (Bleo/Cytarabine) combination protocol for dogs with relapsed lymphoma (LSA). Dogs diagnosed with LSA and previously treated with chemotherapy were included in the study. A total of 20 dogs met the inclusion criteria, and 19 were evaluable for response. Bleomycin was administered subcutaneously on days 1 and 8 and cytosine arabinoside was administered subcutaneously on days 1-5 of a 21-day cycle...
March 20, 2018: Journal of the American Animal Hospital Association
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