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Michael O Childress, José A Ramos-Vara, Audrey Ruple
OBJECTIVE To determine the effect of prednisone omission from a multidrug chemotherapy protocol on outcome in dogs with peripheral nodal lymphomas. DESIGN Single-center, nonblinded, parallel-group, randomized, controlled trial. ANIMALS 40 client-owned dogs with a histopathologically confirmed diagnosis of peripheral nodal lymphoma and an expected survival time of > 4 weeks with treatment. PROCEDURES Treatment consisted of a combination of L-asparaginase, cyclophosphamide, doxorubicin, vincristine, and prednisone (L-CHOP) or an identical protocol except for the omission of prednisone (L-CHO)...
November 1, 2016: Journal of the American Veterinary Medical Association
Kosuke Toda, Kenji Kawada, Masayoshi Iwamoto, Susumu Inamoto, Takehiko Sasazuki, Senji Shirasawa, Suguru Hasegawa, Yoshiharu Sakai
A number of clinical trials have shown that KRAS mutations of colorectal cancer (CRC) can predict a lack of responses to anti-epidermal growth factor receptor-based therapy. Recently, there have been several studies to elucidate metabolism reprogramming in cancer. However, it remains to be investigated how mutated KRAS can coordinate the metabolic shift to sustain CRC tumor growth. In this study, we found that KRAS mutation in CRC caused alteration in amino acid metabolism. KRAS mutation causes a marked decrease in aspartate level and an increase in asparagine level in CRC...
October 17, 2016: Neoplasia: An International Journal for Oncology Research
Saleh A Mohamed, Mohamed F Elshal, Taha A Kumosani, Alia M Aldahlawi, Tasneem A Basbrain, Fauziah A Alshehri, Hani Choudhry
Escherichia coli-derived L-asparaginases have been used in the treatment of acute lymphoblastic leukemia (ALL), however, clinical hypersensitivity reactions and silent inactivation due to antibodies against E. coli-asparaginase, lead to inactivation of these preparations in most cases.Therefore, this study was aimed to investigate the cytotoxicity and antitumor effects ofa novel L-asparaginaseenzyme, isolated from Phaseolus vulgaris seeds (P-Asp) on the ALL cell line (Jurkat). The immunogenicity of the enzyme was also evaluated in-vivo and results were compared to commercially available enzymes of microbial sources...
October 14, 2016: International Journal of Environmental Research and Public Health
W L Wan, J Wang, M X Zhu, W Zhang, X Y Ke
OBJECTIVE: To investigate prognostic factors of the T-cell non-Hodgkin's lymphoma (T-NHL), and to study the clinical efficacy of CHOPE plus L-asparaginase(L-ASP) regimen for T-NHL. METHODS: Retrospective analyses were made of 61 T-NHL patients who were treated from July 2007 to August 2013. Randomly divided into two groups CHOPE and CHOPE+L group(Based on CHOPE, added with L-ASP on the 1st, 3rd, 5th, 7th, 9th and 11th day). RESULTS: Of the 61 patients evaluatd with the median survival was 22 (3-65) months,the complete remission rate was 52...
October 18, 2016: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
A Cacace, M Sboarina, T Vazeille, P Sonveaux
Cancer cells can use a variety of metabolic substrates to fulfill the bioenergetic and biosynthetic needs of their oncogenic program. Besides bioenergetics, cancer cell metabolism also directly influences genetic, epigenetic and signaling events associated with tumor progression. Many cancer cells are addicted to glutamine, and this addiction is observed in oxidative as well as in glycolytic cells. Although both oxidative and bioreductive glutamine metabolism can contribute to cancer progression and glutamine can further serve to generate peptides (including glutathione) and proteins, we report that glutamine promotes the proliferation of cancer cells independently of its use as a metabolic fuel or as a precursor of glutathione...
October 17, 2016: Oncogene
P Pardes-Chavanes, M Afanetti, C Boyer, M Poirée
Intracerebral hemorrhage (ICH) remains a cause of death in hematologic malignancies. Asparaginase represents a key agent in the treatment of acute lymphoblastic leukemia (ALL). The toxicity of asparaginase includes coagulopathy such as thrombotic or bleeding tendency. We report a case of fatal cerebral hemorrhage in a 12-year-old girl treated for ALL. Cerebral hemorrhage occurred after three injections of L-asparaginase. The patient presented with hypofibrinogenemia (0.36g/L), associated with thrombocytopenia (24,000/mm(3))...
October 12, 2016: Archives de Pédiatrie: Organe Officiel de la Sociéte Française de Pédiatrie
Archana Vimal, Awanish Kumar
Allosterism has emerged as an innovative and significant mode of drug discovery. It facilitates the targeting of an allosteric site that is unique and more specific. A relatively new approach to allosteric regulation is the morpheein model, a concerted dissociative model that describes the equilibrium of alternate quaternary structure assemblies, whose architectures are dictated by alternate conformations in the dissociated state. It is involved in various biological phenomena, including enzyme regulation. One such enzyme is l-asparaginase, which is exploited by pathogenic microbes to cause infectious disease in humans...
October 11, 2016: Drug Discovery Today
Joy Benadiba, Celia Rosilio, Marielle Nebout, Vera Heimeroth, Zouhour Neffati, Alexandra Popa, Didier Mary, Emmanuel Griessinger, Véronique Imbert, Nicolas Sirvent, Jean-François Peyron
Iron is an essential nutrient, acting as a catalyst for metabolic reactions that are fundamental to cell survival and proliferation. Iron complexed to transferrin is delivered to the metabolism after endocytosis via the CD71 surface receptor. We found that transformed cells from a murine PTEN-deficient T-cell lymphoma model and from T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/T-LL) cell lines overexpress CD71. As a consequence, the cells developed an addiction toward iron whose chelation by deferoxamine (DFO) dramatically affected their survival to induce apoptosis...
October 13, 2016: Leukemia & Lymphoma
Mousumee Panigrahi, Trupti Rekha Swain, Rabindra Kumar Jena, Ashutosh Panigrahi
OBJECTIVES: The objective of this study was to evaluate any abnormal change in plasma glucose levels in patients treated with L-asparaginase (L-Asp)-based chemotherapy regimen in patients of acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: This retrospective, hospital-based study was conducted in patients of ALL, admitted to the Clinical Haematology Department of a tertiary care hospital of Odisha from August 2014 to July 2015. Indoor records of 146 patients on multi-centered protocol-841 were evaluated for any alteration in plasma glucose level, time of onset of hypo/hyperglycemia, and persistence of plasma glucose alteration...
September 2016: Indian Journal of Pharmacology
Karen Einsfeldt, Isis Cavalcante Baptista, Juliana Christina Castanheira Vicente Pereira, Roberta Eitler Bruno, Fabiana Vieira Mello, Isabele Campos Costa-Amaral, Elaine Sobral da Costa, Maria Cecília Menks Ribeiro, Marcelo Gerardin Poirot Land, Tito Lívio Moitinho Alves, Ariane Leites Larentis, Rodrigo Volcan Almeida
[This corrects the article DOI: 10.1371/journal.pone.0156692.].
2016: PloS One
Babasaheb D Yadav, Amy L Samuels, Julia E Wells, Rosemary Sutton, Nicola C Venn, Katerina Bendak, Denise Anderson, Glenn M Marshall, Catherine H Cole, Alex H Beesley, Ursula R Kees, Richard B Lock
Relapse in pediatric T-cell acute lymphoblastic leukemia (T-ALL) remains a significant clinical problem and is thought to be associated with clonal selection during treatment. In this study we used an established pre-clinical model of induction therapy to increase our understanding of the effect of engraftment and chemotherapy on clonal selection and acquisition of drug resistance in vivo. Immune-deficient mice were engrafted with patient diagnostic specimens and exposed to a repeated combination therapy consisting of vincristine, dexamethasone, L-asparaginase and daunorubicin...
August 11, 2016: Oncotarget
Hadeel A Khalil, Tarek S Belal, Ahmed F El-Yazbi, Dalia A Hamdy
BACKGROUND: Vincristine (VCR), an antineoplastic agent, is a key component in the treatment of acute lymphoblastic leukemia, lymphomas, rhabdomyosarcoma, neuroblastoma, and Wilms' tumor diseases. Recently, high incidence of hyperlipidemia was reported to be associated with allogenic hematopoietic stem cell transplantation and VCR/L-asparaginase therapy. The aim of this study is to test the effects of incremental increase in lipoproteins levels on vincristine disposition in rat. METHOD: To study VCR pharmacokinetics and protein binding, rats (n = 25) were assigned to three groups, normal lipidemic (NL), intermediate (IHL) and extreme hyperlipidemic (HL)...
2016: Lipids in Health and Disease
Noura El-Ahmady El-Naggar, Sahar F Deraz, Hoda M Soliman, Nehal M El-Deeb, Sara M El-Ewasy
L-asparaginase is an important enzyme as therapeutic agents used in combination with other drugs in the treatment of acute lymphoblastic leukemia. A newly isolated actinomycetes strain, Streptomyces sp. NEAE-82, was potentially producing extracellular L-asparaginase, it was identified as Streptomyces fradiae NEAE-82, sequencing product was deposited in the GenBank database under accession number KJ467538. L-asparaginase was purified from the crude enzyme using ammonium sulfate precipitation, dialysis and ion exchange chromatography using DEAE Sepharose CL-6B...
2016: Scientific Reports
Yoshinori Goto, Ryosei Nishimura, Atsushi Nohara, Shintaro Mase, Toshihiro Fujiki, Hitoshi Irabu, Rie Kuroda, Raita Araki, Yasuhiro Ikawa, Hideaki Maeba, Akihiro Yachie
A 10-year-old girl developed L-asparaginase (ASP)-associated pancreatitis during chemotherapy for acute lymphocytic leukemia. Her symptoms showed alleviation with continuous regional arterial infusion of protease inhibitor and systemic somatostatin analog therapy. She had intermittent and marked hypertriglyceridemia, an initial trigger for pancreatitis, probably as a side effect of ASP and steroids. However, we considered the pancreatitis to have developed mainly because of factors other than hypertriglyceridemia as lipoprotein analysis confirmed chylomicron levels to be nearly undetectable...
August 2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Jing Jia, Yuqin Song, Ningjing Lin, Weiping Liu, Lingyan Ping, Wen Zheng, Xiaopei Wang, Yan Xie, Meifeng Tu, Chen Zhang, Zhitao Ying, Lijuan Deng, Ning Ding, Jun Zhu
Extranodal natural killer (NK)/T cell lymphoma-associated hemophagocytic syndrome (HPS) (NK/T-LAHS) is a heterogeneous and life-threatening disease, which warrants investigation of its risk factors and clinical features. We retrospectively analyzed the clinical records of 202 patients with extranodal NK/T cell lymphoma and compared the characteristics and survival of extranodal NK/T cell lymphoma patients with and without HPS. The cumulative incidence of NK/T-LAHS was 11.4 % (23/202). In a multivariate logistic regression model, younger age (p = 0...
September 6, 2016: Annals of Hematology
Bao-Hua Yu, Ruo-Hong Shui, Wei-Qi Sheng, Chao-Fu Wang, Hong-Fen Lu, Xiao-Yan Zhou, Xiong-Zeng Zhu, Xiao-Qiu Li
PURPOSE: To investigate the clinicopathological features, survival and prognostic factors of primary intestinal extranodal natural killer/T-cell lymphoma, nasal type (PI-ENKTCL). METHODS: Clinical and histological characteristics of PI-ENKTCL cases were retrospectively evaluated. Immunohistochemical phenotype and status of Epstein-Barr virus (EBV) and T-cell receptor (TCR) gene rearrangement were examined. The overall survival and prognostic parameters were also analyzed...
2016: PloS One
Ahmet Ulu, Suleyman Koytepe, Burhan Ates
We prepared biodegradable P(MAA-co-MMA)-starch composite as carrier matrix for the immobilization of l-asparaginase (l-ASNase), an important chemotherapeutic agent in acute lymphoblastic leukemia. Chemical characteristics and thermal stability of the prepared composites were determined by FT-IR, TGA, DTA and, DSC, respectively. Also, biodegradability measurements of P(MAA-co-MMA)-starch composites were carried out to examine the effects of degradation of the starch. Then, l-ASNase was immobilized on the P(MAA-co-MMA)-starch composites...
November 20, 2016: Carbohydrate Polymers
Raheel Altaf Raja, Kjeld Schmiegelow, Ditte Nørbo Sørensen, Thomas Leth Frandsen
BACKGROUND: l-Asparaginase is an important drug for treatment of childhood acute lymphoblastic leukemia (ALL), but is associated with serious toxicities, including pancreatitis and hypertriglyceridemia (HTG). Asparaginase-associated pancreatitis (AAP) is a common reason for stopping asparaginase treatment. The aim of this study was to explore if HTG or early elevations in pancreatic enzymes were associated with the subsequent development of AAP. METHOD: Children (1...
August 24, 2016: Pediatric Blood & Cancer
Nikolaos E Labrou, Magdy Mohamed Muharram
l-Asparaginases (l-ASNase, E.C. catalyze the conversion of l-asparagine to l-aspartic acid and ammonia. In the present work, a new form of l-ASNase from a strain of Erwinia carotovora (EcaL-ASNase) was cloned, expressed in Escherichia coli as a soluble protein and characterized. The enzyme was purified to homogeneity by a single-step procedure comprising ion-exchange chromatography. The properties of the recombinant enzyme were investigated employing kinetic analysis and molecular modelling and the kinetic parameters (Km, kcat) were determined for a number of substrates...
October 2016: Enzyme and Microbial Technology
Dok Hyun Yoon, Seok Jin Kim, Seong Hyun Jeong, Dong-Yeop Shin, Sung Hwa Bae, Junshik Hong, Seong Kyu Park, Ho-Young Yhim, Deok-Hwan Yang, Hyewon Lee, Hye Jin Kang, Mark Hong Lee, Hyeon-Seok Eom, Jae-Yong Kwak, Jae Hoon Lee, Cheolwon Suh, Won Seog Kim
We designed a new treatment protocol incorporating concurrent administration of L-asparaginase (to reduce the probability of systemic progression during concurrent chemoradiotherapy (CCRT)) plus high-dose methotrexate to consolidation chemotherapy to intensify the regimen for treating localized extranodal NK/T cell lymphoma, nasal type (ENKTL). CCRT comprised radiation (36-44 Gy) with weekly cisplatin (30 mg/m2) and tri-weekly L-asparaginase (4 000 IU). Chemotherapy-MIDLE (methotrexate 3 g/m2 on day 1, etoposide 100 mg/m2 and Ifosfamide 1 000 mg/m2 on days 2-3, dexamethasone 40 mg on days 1-4, and L-asparaginase 6 000 IU/m2 on days 4, 6, 8, 10)-was repeated every 28 days for two cycles...
August 16, 2016: Oncotarget
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