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l-asparaginase

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https://www.readbyqxmd.com/read/29447943/novel-mutant-of-escherichia-coli-asparaginase-ii-to-reduction-of-the-glutaminase-activity-in-treatment-of-acute-lymphocytic-leukemia-by-molecular-dynamics-simulations-and-qm-mm-studies
#1
Noeman Ardalan, Sako Mirzaie, Abbas Akhavan Sepahi, Ramazan Ali Khavari-Nejad
L-Asparaginases (ASNase) belong to a family of amidohydrolases, have both asparaginase and glutaminase activity. Acute lymphocytic leukemia (ALL) is an outrageous disease worldwide. Bacterial ASNase has been used for the treatment of ALL. Glutaminase activity of enzyme causes some side effect and it is not essential for anticancer activity. The aim of this study was engineering of Escherichia coli asparaginase II to find a mutant with reduced glutaminase activity by molecular docking, molecular dynamics (MD) and QM-MM (Quantum mechanics molecular dynamics) simulations...
March 2018: Medical Hypotheses
https://www.readbyqxmd.com/read/29434187/glutamine-metabolism-regulates-flip-expression-and-sensitivity-to-trail-in-triple-negative-breast-cancer-cells
#2
Marta Mauro-Lizcano, Abelardo López-Rivas
Glutamine plays an important role in the metabolism of tumor cells through its contribution to redox homeostasis, bioenergetics, synthesis of macromolecules, and signaling. Triple-negative breast cancers (TNBC) are highly metastatic and associated with poor prognosis. TNBC cells show a marked dependence on extracellular glutamine for growth. Herein we demonstrate that TNBC cells are markedly sensitized to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis upon glutamine deprivation...
February 12, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29414946/asparagine-bioavailability-governs-metastasis-in-a-model-of-breast-cancer
#3
Simon R V Knott, Elvin Wagenblast, Showkhin Khan, Sun Y Kim, Mar Soto, Michel Wagner, Marc-Olivier Turgeon, Lisa Fish, Nicolas Erard, Annika L Gable, Ashley R Maceli, Steffen Dickopf, Evangelia K Papachristou, Clive S D'Santos, Lisa A Carey, John E Wilkinson, J Chuck Harrell, Charles M Perou, Hani Goodarzi, George Poulogiannis, Gregory J Hannon
Using a functional model of breast cancer heterogeneity, we previously showed that clonal sub-populations proficient at generating circulating tumour cells were not all equally capable of forming metastases at secondary sites. A combination of differential expression and focused in vitro and in vivo RNA interference screens revealed candidate drivers of metastasis that discriminated metastatic clones. Among these, asparagine synthetase expression in a patient's primary tumour was most strongly correlated with later metastatic relapse...
February 7, 2018: Nature
https://www.readbyqxmd.com/read/29406798/successful-treatment-of-adolescents-and-young-adults-with-philadelphia-negative-acute-lymphoblastic-leukemia-by-novel-l-asparaginase-intensified-induction-therapy-and-cord-blood-transplantation-a-single-center-decade-report
#4
Akira Kojima, Kazunari Yamada, Koichi Kajiwara, Yuichi Takeuchi, Marina Matsui, Masao Tsukada, Kanichi Iwama, Yasuji Kozai, Hideki Kodo
A novel induction therapy, including intensive L-asparaginase, was designed in 2007 for patients aged <45 years with Philadelphia-negative acute lymphoblastic leukemia (ALL). We analyzed seven de novo cases and one case of recurrence who received this treatment. The median age was 21 years (range: 16-35 years). Four patients had T-ALL and the others had B-ALL. All the patients achieved complete remission and proceeded to cord blood transplantation. In the median 72-month follow-up, there were no cases of observed mortality or recurrence...
February 6, 2018: Journal of Adolescent and Young Adult Oncology
https://www.readbyqxmd.com/read/29406239/coagulopathic-side-effect-of-l-asparginase-on-fibrinogen-level-in-childhood-acute-lymphoblastic-leukemia-during-induction-phase
#5
Alauldeen Mudhafar Zubair Alqasim, Raji Hussein Al-Hadithi, Aseel Nashaat Al-Khalidi
BACKGROUND: L - asparaginase is chemotherapeutic agent commonly used in treatment of Acute Lymphoblastic Leukemia. Thromboembolic and to a lesser extent bleeding events are serious complications associated with administration of this drug during the induction phase in ALL especially in children resulting from reduced synthesis of proteins such as Antithrombin & fibrinogen. OBJECTIVE: Evaluation of the coagulopathic side effect of L - asparaginase during the induction phase in treatment of ALL in children by measuring fibrinogen levels before & after administration of this drug...
February 1, 2018: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/29394970/remission-rate-of-acute-lymphoblastic-leukemia-all-in-adolescents-and-young-adults-aya
#6
Anita Vallacha, Ghulam Haider, Wiky Raja, Dinesh Kumar
OBJECTIVE: To determine the remission rate in adolescent and young adult (AYA) patients with acute lymphoblastic leukemia (ALL). STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Department of Oncology, Jinnah Postgraduate Medical Centre (JPMC), Karachi from January, 2016 to March, 2017. METHODOLOGY: Adolescent and young adult (AYA) patients aged 15-39 years, newly diagnosed with acute lymphoblastic leukemia from January, 2016 to March, 2017...
February 2018: Journal of the College of Physicians and Surgeons—Pakistan: JCPSP
https://www.readbyqxmd.com/read/29393741/intestinal-lymphoma-in-dogs-84-cases-1997-2012
#7
Naoko Sogame, Rebecca Risbon, Kristine E Burgess
OBJECTIVE To describe signalment, clinicopathologic features, and outcomes of dogs with confirmed primary intestinal lymphoma and assess factors associated with survival times in these patients. DESIGN Retrospective case series. ANIMALS 84 client-owned dogs. PROCEDURES Medical records from 7 veterinary institutions were retrospectively reviewed to identify dogs with primary intestinal lymphoma. Data collected included signalment, clinical signs, anatomic location of tumors, diagnostic procedures, treatment, outcome, and dates of diagnosis and death...
February 15, 2018: Journal of the American Veterinary Medical Association
https://www.readbyqxmd.com/read/29368155/nk-t-cell-lymphoma-updates-in-therapy
#8
REVIEW
Ritsuro Suzuki
PURPOSE OF REVIEW: Extranodal NK/T cell lymphoma (ENKL), nasal type, is a highly aggressive lymphoma which used to show a poor clinical outcome. Expression of P-glycoprotein on lymphoma cells of ENKL is a major reason for the refractoriness to conventional chemotherapy containing anthracycline. However, recent innovative approaches have improved the outcome and prognosis of ENKL. The purpose of this review is to summarize the proceedings of treatment. RECENT FINDINGS: Concurrent chemoradiotherapy containing platinum and several drugs including L-asparaginase, methotrexate, and alkylators shows excellent outcomes for the limited-stage ENKL...
January 24, 2018: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/29360413/low-incidence-of-osteonecrosis-in-childhood-acute-lymphoblastic-leukemia-treated-with-all-97-and-all-02-study-of-japan-association-of-childhood-leukemia-study-group
#9
Kenichi Sakamoto, Toshihiko Imamura, Kentaro Kihira, Koji Suzuki, Hisashi Ishida, Hiromi Morita, Miyako Kanno, Takeshi Mori, Hidefumi Hiramatsu, Kousaku Matsubara, Kiminori Terui, Yoshihiro Takahashi, So-Ichi Suenobu, Daiichiro Hasegawa, Yoshiyuki Kosaka, Koji Kato, Akiko Moriya-Saito, Atsushi Sato, Hirohide Kawasaki, Keiko Yumura-Yagi, Junichi Hara, Hiroki Hori, Keizo Horibe
Purpose Osteonecrosis (ON) is a serious complication of the treatment of childhood acute lymphoblastic leukemia (ALL); however, data relating to ON in Asian pediatric patients with ALL are scarce. Therefore, we performed a retrospective analysis of cohorts of Japanese patients with ALL to clarify the incidence, clinical characteristics, and risk factors of ON. Patients and Methods The incidence and characteristics of ON were determined in patients with ALL (n = 1,662) enrolled in two studies from the Japan Association of Childhood Leukemia Study (JACLS) group (n = 635 and n = 1,027 patients treated with the ALL-97 and ALL-02 protocols, respectively)...
January 23, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29350496/venoocclusive-disease-due-to-chemotherapy-for-pediatric-acute-lymphoblastic-leukemia-is-associated-with-increased-levels-of-plasminogen-activator-inhibitor-1
#10
Margherita Mauro, Graziella Saggiorato, Maria Teresa Sartori, Giuseppe Gallo, Massimiliano De Bortoli, Elisa Bonetti, Ada Zaccaron, Virginia Vitale, Rita Balter, Matteo Chinello, Simone Cesaro
We describe three cases of sinusoidal obstruction syndrome/venoocclusive disease (SOS) in pediatric patients with acute lymphoblastic leukemia (ALL). All three episodes occurred during or just after the induction or reinduction phase of treatment based on prednisone/dexamethasone, vincristine, daunorubicin, and pegylated-l-asparaginase. SOS episodes were categorized as mild/moderate and resolved in 7, 10, and 16 days using supportive measures or defibrotide therapy. In all three episodes, the clinical diagnosis of SOS was associated with a significant increase in plasminogen-activator inhibitor-1 (PAI-1) that reduced with patient clinical improvement...
January 19, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29343523/a-novel-l-asparaginase-with-low-l-glutaminase-coactivity-is-highly-efficacious-against-both-t-and-b-cell-acute-lymphoblastic-leukemias-in-vivo
#11
Hien Anh Nguyen, Ying Su, Jenny Yu Zhang, Aleksandar Antanasijevic, Michael Caffrey, Amanda M Schalk, Li Liu, Damiano Rondelli, Annie Oh, Dolores L Mahmud, Maarten C Bosland, Andre Kajdacsy-Balla, Sofie Peirs, Tim Lammens, Veerle Mondelaers, Barbara De Moerloose, Steven Goossens, Michael J Schlicht, Kasim K Kabirov, Alexander V Lyubimov, Bradley J Merrill, Yogen Saunthararajah, Pieter Van Vlierberghe, Arnon Lavie
Acute lymphoblastic leukemia (ALL) is the most common type of pediatric cancer, although about 4 of every 10 cases occur in adults. The enzyme drug L-asparaginase serves as a cornerstone of ALL therapy and exploits the asparagine-dependency of ALL cells. In addition to hydrolyzing the amino acid L-asparagine, all FDA-approved L-asparaginases also have significant L-glutaminase coactivity. Since several reports suggest that L-glutamine depletion correlates with many of the side effects of these drugs, enzyme variants with reduced L-glutaminase coactivity might be clinically beneficial if their anti-leukemic activity would be preserved...
January 17, 2018: Cancer Research
https://www.readbyqxmd.com/read/29328996/acute-and-sub-acute-neurological-toxicity-in-children-treated-for-acute-lymphoblastic-leukemia
#12
REVIEW
Natalia C Millan, Analía Pastrana, Myriam R Guitter, Pedro A Zubizarreta, María S Monges, María S Felice
Eighty percent of children with acute lymphoblastic leukemia (ALL) survive with current treatments. Neurotoxicity is an infrequent adverse event. We describe clinical presentations of neurological toxicity, phases of treatment when these adverse events were more frequent and patients ́ outcome. From January-1995 to December-2015, 1379 ALL cases were admitted. Neurotoxicity was diagnosed in 49 patients (3.6%) and classified according to neurological syndromes. Medical records, laboratory-tests and images were reviewed...
February 2018: Leukemia Research
https://www.readbyqxmd.com/read/29316436/oncogenic-kras-regulates-amino-acid-homeostasis-and-asparagine-biosynthesis-via-atf4-and-alters-sensitivity-to-l-asparaginase
#13
Dana M Gwinn, Alex G Lee, Marcela Briones-Martin-Del-Campo, Crystal S Conn, David R Simpson, Anna I Scott, Anthony Le, Tina M Cowan, Davide Ruggero, E Alejandro Sweet-Cordero
KRAS is a regulator of the nutrient stress response in non-small-cell lung cancer (NSCLC). Induction of the ATF4 pathway during nutrient depletion requires AKT and NRF2 downstream of KRAS. The tumor suppressor KEAP1 strongly influences the outcome of activation of this pathway during nutrient stress; loss of KEAP1 in KRAS mutant cells leads to apoptosis. Through ATF4 regulation, KRAS alters amino acid uptake and asparagine biosynthesis. The ATF4 target asparagine synthetase (ASNS) contributes to apoptotic suppression, protein biosynthesis, and mTORC1 activation...
January 8, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29299118/identification-of-a-cytogenetic-and-molecular-subgroup-of-acute-myeloid-leukemias-showing-sensitivity-to-l-asparaginase
#14
Salvatore Nicola Bertuccio, Salvatore Serravalle, Annalisa Astolfi, Annalisa Lonetti, Valentina Indio, Anna Leszl, Andrea Pession, Fraia Melchionda
L-Asparaginase (L-Asp) is an enzyme that catalyzes the hydrolysis of L-asparagine to L-aspartic acid, and its depletion induces leukemic cell death. L-Asp is an important component of treatment regimens for Acute Lymphoblastic Leukemia (ALL). Sensitivity to L-Asp is due to the absence of L-Asparagine synthetase (ASNS), the enzyme that catalyzes the biosynthesis of L-asparagine. ASNS gene is located on 7q21.3, and its increased expression in ALLs correlates with L-Asp resistance. Chromosome 7 monosomy (-7) is a recurrent aberration in myeloid disorders, particularly in adverse-risk Acute Myeloid Leukemias (AMLs) and therapy-related myeloid neoplasms (t-MN), that leads to a significant downregulation of the deleted genes, including ASNS...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29279817/multi-level-statistical-optimization-of-l-asparaginase-from-bacillus-subtilis-vuvd001
#15
Rajeswara Reddy Erva, T C Venkateswarulu, Bangaraiah Pagala
Physical and chemical factors influencing the anti-leukemic l-asparaginase enzyme production by Bacillus subtilis VUVD001 were optimized using multi-stage optimization on the basis of preliminary experimental outcomes obtained by conventional one-factor-at-a-time approach using shake flasks. Process variables namely carbon, nitrogen sources, pH and temperature were taken into consideration during response surface methodology (RSM) optimization. The finest enzyme activity of 0.51 IUml-1 obtained by OFAT method was enhanced by 3...
January 2018: 3 Biotech
https://www.readbyqxmd.com/read/29236701/anti-leukemic-activity-of-bortezomib-and-carfilzomib-on-b-cell-precursor-all-cell-lines
#16
Kazuya Takahashi, Takeshi Inukai, Toshihiko Imamura, Mio Yano, Chihiro Tomoyasu, David M Lucas, Atsushi Nemoto, Hiroki Sato, Meixian Huang, Masako Abe, Keiko Kagami, Tamao Shinohara, Atsushi Watanabe, Shinpei Somazu, Hiroko Oshiro, Koshi Akahane, Kumiko Goi, Jiro Kikuchi, Yusuke Furukawa, Hiroaki Goto, Masayoshi Minegishi, Shotaro Iwamoto, Kanji Sugita
Prognosis of childhood acute lymphoblastic leukemia (ALL) has been dramatically improved. However, prognosis of the cases refractory to primary therapy is still poor. Recent phase 2 study on the efficacy of combination chemotherapy with bortezomib (BTZ), a proteasome inhibitor, for refractory childhood ALL demonstrated favorable clinical outcomes. However, septic death was observed in over 10% of patients, indicating the necessity of biomarkers that could predict BTZ sensitivity. We investigated in vitro BTZ sensitivity in a large panel of ALL cell lines that acted as a model system for refractory ALL, and found that Philadelphia chromosome-positive (Ph+) ALL, IKZF1 deletion, and biallelic loss of CDKN2A were associated with favorable response...
2017: PloS One
https://www.readbyqxmd.com/read/29229487/proteomics-reveals-key-proteins-participating-in-growth-difference-between-fall-dormant-and-non-dormant-alfalfa-in-terminal-buds
#17
Hongqi Du, Yinghua Shi, Defeng Li, Wenna Fan, Yanhua Wang, Guoqiang Wang, Chengzhang Wang
To explore the molecular mechanism of growth differences between fall dormant (FD) and non-FD alfalfa, we conducted iTRAQ-based quantitative proteomics on terminal buds of Maverick (FD) and Cuf101 (non-FD) cultivars, identified differential abundance protein species (DAPS) and verified expression profiling of the corresponding mRNA by qRT-PCR. A total of 3872 protein species were annotated. Of the 90 DAPS, 56 and 34 were respectively up- and down-accumulated in Maverick, compared to Cuf101. They were grouped into 35 functional categories and enriched in seven pathways...
December 8, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/29198332/optimization-and-purification-of-l-asparaginase-from-fungi-a-systematic-review
#18
REVIEW
Paula Monteiro Souza, Marcela Medeiros de Freitas, Samuel Leite Cardoso, Adalberto Pessoa, Eliete Neves Silva Guerra, Pérola Oliveira Magalhães
The purpose of this systematic review was to identify the available literature of the l-asparaginase producing fungi. This study followed the Preferred Reporting Items for Systematic Reviews. The search was conducted on five databases: LILACS, PubMed, Science Direct, Scopus and Web of Science up until July 20th, 2016, with no time or language restrictions. The reference list of the included studies was crosschecked and a partial gray literature search was undertaken. The methodology of the selected studies was evaluated using GRADE...
December 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/29175524/characterization-of-l-asparaginase-from-marine-derived-aspergillusnigerakv-mkbu-its-antiproliferative-activity-and-bench-scale-production-using-industrial-waste
#19
Anjana K Vala, Bhumi Sachaniya, Dushyant Dudhagara, Haresh Z Panseriya, Haren Gosai, Rakesh Rawal, Bharti P Dave
L-asparaginase (LA), an enzyme with anticancer activities, produced by marine-derived Aspergillusniger was subjected to purification and characterization. The purified enzyme was observed to have molecular weight ∼90KDa. The enzyme retained activity over a wide range of pH, i.e. pH 4-10. The enzyme was quite stable in temperature range 20-40°C. Tween 80 and Triton X-100 were observed to enhance LA activity while inhibition of LA activity was observed in presence of heavy metals. The values for Km was found to be 0...
November 23, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29159986/l-asparaginase-isolated-from-streptomyces-ansochromogenes-promotes-th1-profile-and-activates-cd8-t-cells-in-human-pbmc-an-in-vitro-investigation
#20
Glêzia Renata da Silva Lacerda, Cristiane Moutinho Lagos de Melo, Ana Karine de Araújo Soares, Leyllane Rafael Moreira, Marília Cavalcanti Coriolano, Gláucia Manoella de Souza Lima, Thiago Henrique Napoleão, Virgínia Maria Barros de Lorena, Leonor Alves de Oliveira da Silva, Silene Carneiro do Nascimento
AIMS: A new L-asparaginase produced by Streptomyces ansochromogenes UFPEDA 3420 actinobacteria was used in this study against human lymphocyte cultures to evaluate the immunological profile induced by this enzyme. METHODS AND RESULTS: Cultures of lymphocytes were stimulated with S. ansochromogenes L-asparaginase and cytotoxicity, cell viability, cell stimulation and cytokine production were analyzed. This new S. ansochromogenes L-asparaginase induced activation and proliferation of the TCD8(+) lymphocyte subset and produced higher TNF-α, IFN-γ, IL-2 and IL-10 levels in a 24 hour assay...
November 21, 2017: Journal of Applied Microbiology
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