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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
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
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
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
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
Archana Vimal, Anubhuti Jha, Awanish Kumar
Salmonella typhimurium is the causative agent of severe human infections and mortality throughout the world. Pacing advent of new resistance mechanisms in this microorganism exists, rendering treatment of infectious disease difficult. Ciprofloxacin is no longer considered the first choice of antimicrobial agent due to the emergence of resistance. Therefore, the need for scenario is to find out novel drug target and its potential inhibitor to fight against this pathogen. The present study was undertaken to find out a novel drug target and its inhibitor for improving the current therapeutic methods for treating Salmonella infections...
November 11, 2017: Microbial Pathogenesis
Jaya Kumar Arjun, Balakrishna Pillai Aneesh, Thulasi Kavitha, Kumarapillai Harikrishnan
OBJECTIVES: To screen soil metagenomic libraries for novel enzymes with enhanced activities. RESULTS: To screen soil metagenomic libraries for novel enzymes with enhanced activities. A novel L-asparaginase was identified from forest soil metagenome and its characteristics were studied. The purified protein had a specific activity of 696 IU mg(-1) and optimum activity at pH 7 and 35 °C. Enhanced enzyme activities were observed in the presence of Mg(2+), Ca(2+) and K(+)...
November 10, 2017: Biotechnology Letters
Maristella Maggi, Steven D Mittelman, Jean Hugues Parmentier, Giorgio Colombo, Massimiliano Meli, Jeannette Marie Whitmire, D Scott Merrell, Julian Whitelegge, Claudia Scotti
L-Asparaginases (ASNases) have been used as first line drugs for paediatric Acute Lymphoblastic Leukaemia (ALL) treatment for more than 40 years. Both the Escherichia coli (EcAII) and Erwinia chrysanthemi (ErAII) type II ASNases currently used in the clinics are characterized by high in vivo instability, short half-life and the requirement of several administrations to obtain a pharmacologically active concentration. Moreover, they are sensitive to proteases (cathepsin B and asparagine endopeptidase) that are over-expressed by resistant leukaemia lymphoblasts, thereby impairing drug activity and pharmacokinetics...
November 3, 2017: Scientific Reports
Jingxu Guo, Alun R Coker, Steve P Wood, Jonathan B Cooper, Shahid Mahmood Chohan, Naeem Rashid, Muhummad Akhtar
L-Asparaginases catalyse the hydrolysis of asparagine to aspartic acid and ammonia. In addition, L-asparaginase is involved in the biosynthesis of amino acids such as lysine, methionine and threonine. These enzymes have been used as chemotherapeutic agents for the treatment of acute lymphoblastic leukaemia and other haematopoietic malignancies since the tumour cells cannot synthesize sufficient L-asparagine and are thus killed by deprivation of this amino acid. L-Asparaginases are also used in the food industry and have potential in the development of biosensors, for example for asparagine levels in leukaemia...
November 1, 2017: Acta Crystallographica. Section D, Structural Biology
R Sindhu, H K Manonmani
l-asparaginase (E.C., an anti-cancer drug has been used in the treatment of acute lymphoblastic leukemia. A novel source of l-asparaginase from Pseudomonas fluorescens was addressed in the present studies. The ANS gene in Pseudomonas fluorescens MTCC 8127 which produces l-asparaginase was cloned and expressed in E. coli BL21 (DE3). The expressed recombinant protein (PfAns) which was purified, showed l-asparaginase activity. The enzyme was further characterized. The pH and temperature optima were found to be 7...
October 25, 2017: Protein Expression and Purification
Chun Qiu, Lin Wang
OBJECTIVE: To analyse the clinical efficacy and its influencing factors of early ENKTL patients received chemotherapy of gemcitabine-L-asparaginase-oxaliplatin (GELOX) scheme and radiotherapy. METHODS: The clinical data of 80 cases of early nasal type NK/T cell lymphoma treated during May 2013 to May 2016 were analyzed retrospectively. The earty ENKTL patients were divided into 3 groups: group I (50 cases) with GELOX after chemotherapy combined with radical radiotherapy, group II (16 cases) with GELOX after other chemotherapy combined radical radiotherapy, group III (14 cases) patients only received GELOX chemotherapy...
October 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
Rajender Jena, Dushyant K Garg, Lipsa Choudhury, Akanksha Saini, Bishwajit Kundu
Heat shock proteins (HSPs) are known to confer protection to the stressed cells by rescuing vital host cell proteins. In the present study we have demonstrated that heterologous expression of N-terminal domain of hyperthermophilic L-asparaginase (NPfA) confers thermotolerance to E. coli. The recombinant expression of NPfA enabled E. coli to demonstrate typical growth behavior at 52°C and survive a thermal shock up to 62°C, both being the highest reported temperatures for growth and heat shock survival. To understand the basis of protection proteome analysis of these cells was carried out which showed that NPfA guards a battery of proteins, especially related to gene regulations and repair, providing definite survival advantage to the stressed cells...
October 16, 2017: International Journal of Biological Macromolecules
Annamária Bakos, Árpád Szomor, Tamás Schneider, Zsófia Miltényi, Imelda Marton, Zita Borbényi, Judit Pammer, László Krenács, Enikő Bagdi, Klára Piukovics
INTRODUCTION: Extranodal natural killer/T (NK/T) cell lymphoma, nasal type (ENKTL) represents a rare subtype of T-cell lymphomas with aggressive clinical behavior according to WHO 2016 classification. AIM: ENKTL has distinctive geographic distribution with higher incidence in Asia and Latin America (10% of all non-Hodgkin lymphoma cases), than in Europe and North America (<1%). ENKTL tipically origins from nasopharynx and upper aerodigestive tract. Anthracycline-based chemotherapy regimens are largely ineffective in the treatment of ENKTL...
October 2017: Orvosi Hetilap
Stefano Giuntini, Evita Balducci, Linda Cerofolini, Enrico Ravera, Marco Fragai, Francesco Berti, Claudio Luchinat
Carbohydrate-based vaccines are among the safest and most effective vaccines and represent potent tools for prevention of life-threatening bacterial infectious diseases, like meningitis and pneumonia. The chemical conjugation of a weak antigen to protein as a source of T-cell epitopes generates a glycoconjugate vaccine that results more immunogenic. Several methods have been used so far to characterize the resulting polysaccharide-protein conjugates. However, a reduced number of methodologies has been proposed for measuring the degree of saccharide conjugation at the possible protein sites...
October 10, 2017: Angewandte Chemie
Brenton G Mar, S Haihua Chu, Josephine D Kahn, Andrei V Krivstov, Richard Koche, Cecilia A Castellano, Jacob L Kotlier, Rebecca L Zon, Marie E McConkey, Jonathan Chabon, Ryan Chappell, Peter V Grauman, James J Hsieh, Scott A Armstrong, Benjamin L Ebert
Mutations in SETD2, encoding the histone 3 lysine 36 trimethyltransferase, are enriched in relapsed acute lymphoblastic leukemia and MLL rearranged acute leukemia. We investigated the impact of SETD2 mutations on chemotherapy sensitivity in isogenic leukemia cell lines and in murine leukemia generated from a conditional knockout of Setd2SETD2 mutations led to resistance to DNA-damaging agents, cytarabine, 6-thioguanine, doxorubicin, and etoposide, but not to a non-DNA damaging agent, L-asparaginase. H3K36me3 localizes components of the DNA damage response pathway and SETD2 mutation impaired the DNA damage response (DDR), blunting apoptosis induced by cytotoxic chemotherapy...
October 10, 2017: Blood
Jasdeep Singh, Mohd Imran Khan, Shiv Pratap Singh Yadav, Ankit Srivastava, Kislay K Sinha, Ashish, Pradeep Das, Bishwajit Kundu
Emergence of Amphotericin B (AmB) resistant Leishmania donovani has posed major therapeutic challenge against the parasite. Consequently, combination therapy aimed at multiple molecular targets, based on proteome wise network analysis has been recommended. In this regard we had earlier identified and proposed L-asparaginase of Leishmania donovani (LdAI) as a crucial metabolic target. Here we report that both LdAI overexpressing axenic amastigote and promastigote forms of L. donovani survives better when challenged with AmB as compared to wild type strain...
September 28, 2017: International Journal for Parasitology, Drugs and Drug Resistance
Dmitry D Zhdanov, Vadim S Pokrovsky, Marina V Pokrovskaya, Svetlana S Alexandrova, Mikhail A Eldarov, Dmitry V Grishin, Marsel M Basharov, Yulia A Gladilina, Olga V Podobed, Nikolai N Sokolov
Rhodospirillum rubrum L-asparaginase mutant E149R, V150P, F151T (RrA) down-regulates telomerase activity due to its ability to inhibit the expression of telomerase catalytic subunit hTERT. The aim of this study was to define the effect of short-term and long-term RrA exposure on proliferation of cancer Jurkat cell line and normal human CD4(+) T lymphocytes. RrA could inhibit telomerase activity in dose- and time-dependent manner in both Jurkat and normal CD4(+) T cells. Continuous RrA exposure of these cells resulted in shortening of telomeres followed by cell cycle inhibition, replicative senescence, and development of apoptosis...
November 2017: Cancer Medicine
Keshu Zhou, Yongping Song, Yanli Zhang, Xudong Wei, Yuewen Fu, Fengkuan Yu, Hu Zhou, Xinjian Liu, Jian Zhou, Baijun Fang
Acute lymphoblastic leukemia (ALL) patients who fail to acquire complete remission (CR) or who relapse after initial response have poor prognosis. At present there is no consensus as to the standard salvage therapy for these patients. In this study, we retrospectively evaluate safety and efficacy of a salvage regimen (CAGLP) consisting of G-CSF, low-dose cytarabine, aclarubicin, l-asparaginase and prednisone. Thirty-six patients were included with primary refractory (n=13) or relapse (n=23). The overall response rate (ORR) and CR rate were 86...
November 2017: Leukemia Research
Suresh Susan Aishwarya, Sellamuthu Iyappan, Kamepali Vijaya Lakshmi, Kandathil Narayanan Rajnish
l-Asparaginase is employed in leukaemic treatment and in processing starchy foods. The in silico analysis of Lactobacillus reuteri DSM 20016 reveals the presence of an l-asparaginase gene with theoretical pI value of 4.99. 3D structure prediction was carried out and one model was selected based on the validation scores of 86.293 for ERRAT, 92.10% for VERIFY 3D and Ramachandran plot. Multiple sequence alignment of the protein sequences of l-asparaginases I and II of Escherichia coli, Erwinia chrysanthemum and Homo sapiens shows their sequence similarity...
October 2017: 3 Biotech
Abbas Ismail, Rosli Md Illias
The excretion of cyclodextrin glucanotransferase (CGTase) into the culture medium offers significant advantages over cytoplasmic expression. However, the limitation of Escherichia coli is its inability to excrete high amount of CGTase outside the cells. In this study, modification of the hydrophobic region of the N1R3 signal peptide using site-saturation mutagenesis improved the excretion of CGTase. Signal peptide mutants designated M9F, V10L and A15Y enhanced the excretion of CGTase three-fold and demonstrated two-fold higher secretion rate than the wild type...
December 2017: Journal of Industrial Microbiology & Biotechnology
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