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Cladribine

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https://www.readbyqxmd.com/read/28626781/both-cladribine-and-alemtuzumab-may-effect-ms-via-b-cell-depletion
#1
David Baker, Samuel S Herrod, Cesar Alvarez-Gonzalez, Lukasz Zalewski, Christo Albor, Klaus Schmierer
OBJECTIVE: To understand the efficacy of cladribine (CLAD) treatment in MS through analysis of lymphocyte subsets collected, but not reported, in the pivotal phase III trials of cladribine and alemtuzumab induction therapies. METHODS: The regulatory submissions of the CLAD Tablets Treating Multiple Sclerosis Orally (CLARITY) (NCT00213135) cladribine and Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis, study one (CARE-MS I) (NCT00530348) alemtuzumab trials were obtained from the European Medicine Agency through Freedom of Information requests...
July 2017: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/28624910/clinical-pharmacology-and-clinical-trials-of-ribonucleotide-reductase-inhibitors-is-it-a-viable-cancer-therapy
#2
REVIEW
Mukundan Baskar Mannargudi, Subrata Deb
PURPOSE: Ribonucleotide reductase (RR) enzymes (RR1 and RR2) play an important role in the reduction of ribonucleotides to deoxyribonucleotides which is involved in DNA replication and repair. Augmented RR activity has been ascribed to uncontrolled cell growth and tumorigenic transformation. METHODS: This review mainly focuses on several biological and chemical RR inhibitors (e.g., siRNA, GTI-2040, GTI-2501, triapine, gemcitabine, and clofarabine) that have been evaluated in clinical trials with promising anticancer activity from 1960's till 2016...
June 17, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28599315/reevaluation-of-atr-signaling-in-primary-resting-chronic-lymphocytic-leukemia-cells-evidence-for-pro-survival-or-pro-apoptotic-function
#3
Maxime Beyaert, Eliza Starczewska, Ana Cristina González Pérez, Nicolas Vanlangendonck, Pascale Saussoy, Gaëlle Tilman, Anne De Leener, Marie-Christiane Vekemans, Eric Van Den Neste, Françoise Bontemps
ATM, primarily activated by DNA double-strand breaks, and ATR, activated by single-stranded DNA, are master regulators of the cellular response to DNA damage. In primary chronic lymphocytic leukemia (CLL) cells, ATR signaling is considered to be switched off due to ATR downregulation. Here, we hypothesized that ATR, though expressed at low protein level, could play a role in primary resting CLL cells after genotoxic stress. By investigating the response of CLL cells to UV-C irradiation, a prototypical activator of ATR, we could detect phosphorylation of ATR at Thr-1989, a marker for ATR activation, and also observed that selective ATR inhibitors markedly decreased UV-C-induced phosphorylation of ATR targets, including H2AX and p53...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28596664/bullous-pyoderma-gangrenosum-associated-with-hairy-cell-leukemia-and-its-complete-response-to-cladribine-therapy
#4
Ankur Jain, Deepesh Lad, Gaurav Prakash, Alka Khadwal, Pankaj Malhotra, Amanjit Bal, Nabhajit Mallik, Narendar Kumar, Subhash Varma
Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis seen in association with systemic disorders including hematologic malignancies. Hairy cell leukemia (HCL) however, is an unusual association of PG. We describe a 49-year old lady who presented to our hematology clinic with easy fatiguability and ulcerative skin lesions of 6 months duration. Examination revealed pallor and massive splenomegaly. Indurated, ulcerated lesion with undermined edges and necrotic base was observed on left thigh. Investigations revealed pancytopenia and bone marrow examination identified typical hairy cells...
June 2017: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/28553668/the-clinical-spectrum-of-erdheim-chester-disease-an-observational-cohort-study
#5
Juvianee I Estrada-Veras, Kevin J O'Brien, Louisa C Boyd, Rahul H Dave, Benjamin Durham, Liqiang Xi, Ashkan A Malayeri, Marcus Y Chen, Pamela J Gardner, Jhonell R Alvarado-Enriquez, Nikeith Shah, Omar Abdel-Wahab, Bernadette R Gochuico, Mark Raffeld, Elaine S Jaffe, William A Gahl
Erdheim-Chester Disease (ECD) is a rare, potentially fatal, multi-organ myeloid neoplasm occurring mainly in adults. The diagnosis is established by clinical, radiologic, and histologic findings; ECD tumors contain foamy macrophages that are CD68+, CD163+, CD1a-, and frequently S100-. The purpose of this report is to describe the clinical and molecular variability of ECD. Sixty consecutive ECD patients (45 males, 15 females) were prospectively evaluated at the NIH Clinical Center between 2011 and 2015. Comprehensive imaging and laboratory studies were performed, and tissues were examined for BRAF V600E and MAPK pathway mutations...
February 14, 2017: Blood Advances
https://www.readbyqxmd.com/read/28544144/cladribine-is-a-promising-therapy-for-xanthoma-disseminatum
#6
E Adışen, P Aladağ, E Özlem, M A Gürer
No abstract text is available yet for this article.
May 22, 2017: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/28539531/synergistic-activity-of-an-antimetabolite-drug-and-tyrosine-kinase-inhibitors-against-breast-cancer-cells
#7
Yushan Wu, Dongxing Zhang, Baofan Wu, Yuan Quan, Dongwu Liu, Yanyan Li, Xiuzhen Zhang
Antimetabolite drugs, including the adenosine deaminase inhibitor cladribine, have been shown to induce apoptosis in a variety of cancer cells, and have been widely used in clinical trials of various cancers in conjunction with tyrosine kinase inhibitors (TKIs). Combination treatment with cladribine and gefitinib or dasatinib is expected to have a synergistic inhibitory effect on breast cancer cell growth. Our results demonstrated that the combination treatment had synergistic activity against MCF-7 cells, enhanced G2/M cell arrest and ROS generation, and increased the loss of mitochondrial membrane potential and cell apoptosis...
May 25, 2017: Chemical & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28523957/clinical-case-idelalisib-induced-immunoglobulin-flare
#8
Jan Novak, Martin Havrda, Lubica Gaherova, Jan Spicka, Tomas Kozak
IgM flare is a transient, treatment-induced, increase of monoclonal IgM levels in lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM) patients. Until recently this phenomenon was observed in patients treated with Cladribine and Rituximab. Here we report a case of a heavily pretreated chronic lymphocytic leukemia patient with an atypically high immunoglobulin production who developed clinically significant immunoglobulin flare following Idelalisib treatment.
May 19, 2017: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/28523163/a-single-center-experience-rituximab-plus-cladribine-is-an-effective-and-safe-first-line-therapy-for-unresectable-bronchial-associated-lymphoid-tissue-lymphoma
#9
Zheng Wei, Jing Li, Zhixiang Cheng, Ling Yuan, Peng Liu
BACKGROUND: Bronchial-associated lymphoid tissue (BALT) lymphoma is a relatively rare form of B-cell non-Hodgkin lymphoma (B-NHL). To date, the standard systemic treatment for this disease is still under debate, and few data are accessible for newly diagnosed unresectable BALT lymphoma presented with advanced disease. The combination of rituximab (R) and cladribine (2-CdA) has shown some activity in indolent B-NHL, but its usage has not been tested in disseminated BALT lymphoma so far...
April 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28485619/characteristics-and-treatment-patterns-among-us-patients-with-hairy-cell-leukemia-a-retrospective-claims-analysis
#10
Victoria Divino, Sudeep Karve, Andrew Gaughan, Mitch DeKoven, Guozhi Gao, Kevin B Knopf, Mark C Lanasa
AIM: Describe hairy cell leukemia (HCL) treatment patterns using a large, nationally representative US database. PATIENTS & METHODS: Adults newly diagnosed with HCL (1 January 2006 to 30 June 2014) with continuous health plan enrollment ≥180 days pre- and 90 days post-diagnosis were identified from the QuintilesIMS PharMetrics Plus Health Plan Claims Database. Treatment patterns by line of therapy were assessed over the variable follow-up. RESULTS: Among 749 HCL patients (77...
May 9, 2017: Journal of Comparative Effectiveness Research
https://www.readbyqxmd.com/read/28454364/personalized-therapy-tests-for-the-monitoring-of-chronic-lymphocytic-leukemia-development
#11
Małgorzata Rogalińska, Paweł Góralski, Jerzy Z Błoński, Paweł Robak, Jan Barciszewski, Aneta Koceva-Chyła, Henryk Piekarski, Tadeusz Robak, Zofia M Kilianska
There is individual variation in the course of disease development and response to therapy of patients with chronic lymphocytic leukemia (CLL). Novel treatment options for CLL include a new generation of purine analogs, antibodies and inhibitors of specific cell signaling pathways, which typically induce apoptosis or necrosis. A prospective analysis of patient blood samples revealed that a combination of four tests allowed the most appropriate and effective type of treatment to be selected prior to drug administration, and for the analysis of leukemic cell sensitivity to anticancer drug(s) during disease development...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28440858/treatment-with-disease-modifying-drugs-for-people-with-a-first-clinical-attack-suggestive-of-multiple-sclerosis
#12
REVIEW
Graziella Filippini, Cinzia Del Giovane, Marinella Clerico, Omid Beiki, Miriam Mattoscio, Federico Piazza, Sten Fredrikson, Irene Tramacere, Antonio Scalfari, Georgia Salanti
BACKGROUND: The treatment of multiple sclerosis has changed over the last 20 years. The advent of disease-modifying drugs in the mid-1990s heralded a period of rapid progress in the understanding and management of multiple sclerosis. With the support of magnetic resonance imaging early diagnosis is possible, enabling treatment initiation at the time of the first clinical attack. As most of the disease-modifying drugs are associated with adverse events, patients and clinicians need to weigh the benefit and safety of the various early treatment options before taking informed decisions...
April 25, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28421232/clinical-spectrum-quality-of-life-braf-mutation-status-and-treatment-of-skin-involvement-in-adult-langerhans-cell-histiocytosis
#13
Etienne Crickx, Jean-David Bouaziz, Gwenaël Lorillon, Mathilde de Menthon, Florence Cordoliani, Emmanuell Bugnet, Martine Bagot, Michel Rybojad, Samia Mourah, Abdellatif Tazi
Langerhans cell histiocytosis is a rare histiocytic disorder for which skin involvement and management are poorly described in adults. The aim of this retrospective monocentric study in a national reference centre is to describe the clinical characteristics, quality of life, BRAF mutation status and outcomes of skin involvement in adult patients with Langerhans cell histiocytosis. Twenty-five patients (14 females, mean age 47 years) were included, with a median follow-up of 33 months (range 4-420 months). Patients experienced poor dermatological quality of life despite low body surface involvement...
April 19, 2017: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/28415014/determination-and-quantification-of-intracellular-fludarabine-triphosphate-cladribine-triphosphate-and-clofarabine-triphosphate-by-lc-ms-ms-in-human-cancer-cells
#14
Jean-Yves Puy, Lars Petter Jordheim, Emeline Cros-Perrial, Charles Dumontet, Suzanne Peyrottes, Isabelle Lefebvre-Tournier
Purine nucleoside analogues are widely used in the treatment of haematological malignancies, and their biological activity is dependent on the intracellular accumulation of their triphosphorylated metabolites. In this context, we developed and validated a liquid chromatography tandem mass spectrometry (LC-MS/MS) method to study the formation of 5'-triphosphorylated derivatives of cladribine, fludarabine, clofarabine and 2'-deoxyadenosine in human cancer cells. Br-ATP was used as internal standard. Separation was achieved on a hypercarb column...
May 15, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28344788/lymphoma-development-and-survival-in-refractory-coeliac-disease-type-ii-histological-response-as-prognostic-factor
#15
P Nijeboer, Rlj van Wanrooij, T van Gils, N J Wierdsma, G J Tack, B I Witte, H J Bontkes, O Visser, Cjj Mulder, G Bouma
BACKGROUND: Refractory coeliac disease type II (RCDII) frequently transforms into an enteropathy-associated T-cell lymphoma (EATL) and therefore requires intensive treatment. Current evaluated treatment strategies for RCDII include cladribine (2-CdA) and autologous stem cell transplantation (auSCT). OBJECTIVE: The purpose of this study was to evaluate long-term survival and define clear prognostic criteria for EATL development comparing two treatment strategies...
March 2017: United European Gastroenterology Journal
https://www.readbyqxmd.com/read/28275540/a-rare-breed-wild-type-braf-and-ighv-expression-in-a-29-year-old-lady-with-classical-hairy-cell-leukemia
#16
Aneesha Hossain, Hind Rafei, Amar Jariwala, Khaled El-Shami
The V600 BRAF mutation has been described as a key mutation in the pathogenesis of classical hairy cell leukemia (c-HCL) cases without expression of a mutant immunoglobulin heavy chain (IgHV). Here we present a rare case of c-HCL with neither V600 BRAF mutation nor the aforementioned IgHV variant successfully treated with cladribine and review the current literature on its use in women of childbearing age/pregnancy.
2017: Leukemia Research Reports
https://www.readbyqxmd.com/read/28255849/population-pharmacokinetics-of-cladribine-in-patients-with-multiple-sclerosis
#17
Radojka M Savic, Ana M Novakovic, Marianne Ekblom, Alain Munafo, Mats O Karlsson
PURPOSE: The aims of this study were to characterize the concentration-time course of cladribine (CdA) and its main metabolite 2-chloroadenine (CAde), estimate interindividual variability in pharmacokinetics (PK), and identify covariates explaining variability in the PK of CdA. METHODS: This population PK analysis was based on the combined dataset from four clinical studies in patients with multiple sclerosis (MS): three phase I studies, including one food and one drug-drug interaction study, and one phase III clinical study...
March 2, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28255023/the-clinical-and-molecular-diversity-of-mast-cell-leukemia-with-or-without-associated-hematologic-neoplasm
#18
Mohamad Jawhar, Juliana Schwaab, Manja Meggendorfer, Nicole Naumann, Hans-Peter Horny, Karl Sotlar, Torsten Haferlach, Karla Schmitt, Alice Fabarius, Peter Valent, Wolf-Karsten Hofmann, Nicholas C P Cross, Georgia Metzgeroth, Andreas Reiter
Mast cell leukemia is a rare variant of advanced systemic mastocytosis characterized by at least 20% of mast cells in a bone marrow smear. We evaluated clinical and molecular characteristics of 28 patients with (n=20, 71%) or without an associated hematologic neoplasm. De novo mast cell leukemia was diagnosed in 16 of 28 (57%) patients and secondary mast cell leukemia evolving from other advanced systemic mastocytosis subtypes in 12 of 28 (43%) patients, of which 7 patients progressed while on cytoreductive treatment...
June 2017: Haematologica
https://www.readbyqxmd.com/read/28253394/clinical-and-radiologic-responses-to-cladribine-for-the-treatment-of-erdheim-chester-disease
#19
Gaurav Goyal, Mithun V Shah, Timothy G Call, Mark R Litzow, William J Hogan, Ronald S Go
Importance: While cladribine is best known for the treatment of hairy cell leukemia and other lymphoid cancers, it also has activity against myeloid neoplasms, such as Erdheim-Chester disease (ECD). Objective: To assess the efficacy of cladribine (2-chloro-2'-deoxyadenosine) in the treatment of ECD. Design, Setting, and Participants: This study was a single-institution retrospective medical record review from January 1, 1998, to April 6, 2016, at a tertiary academic medical center...
March 2, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28247189/successful-treatment-of-histiocytic-sarcoma-with-cladribine-and-high-dose-cytosine-arabinoside-in-a-child
#20
Haruko Iwabuchi, Hiroyuki Kawashima, Hajime Umezu, Takayuki Takachi, Masaru Imamura, Akihiko Saitoh, Akira Ogose, Chihaya Imai
Histiocytic sarcoma, a rare hematopoietic neoplasm with evidence of histiocytic differentiation, is often refractory to conventional chemotherapy and radiotherapy, and its prognosis is generally dismal. The optimal management of this malignancy has not been established. We report a case of 8-year-old girl with histiocytic sarcoma involving the left femur. The tumor rapidly responded to a combination of cladribine and high-dose cytosine arabinoside, an aggressive salvage regimen for refractory Langerhans cell histiocytosis, and became impalpable during the first cycle...
February 28, 2017: International Journal of Hematology
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