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Amino Acid Therapy

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https://www.readbyqxmd.com/read/29345570/the-role-of-ampk-mtor-modulators-in-therapy-of-acute-myeloid-leukemia
#1
Dora Visnjic, Vilma Dembitz, Hrvoje Lalic
Differentiation therapy of acute promyelocytic leukemia with all-trans retinoic acid represents the most successful pharmacological therapy of acute myeloid leukemia (AML). Numerous studies demonstrate that drugs that inhibit mechanistic target of rapamycin (mTOR) and activate AMP-kinase (AMPK) have beneficial effects in promoting differentiation and blocking proliferation of AML. Most of these drugs are already in use for other purposes; rapalogs as immunosuppressants, biguanides as oral antidiabetics, and 5-amino-4-imidazolecarboxamide ribonucleoside (AICAr, acadesine) as an exercise mimetic...
January 16, 2018: Current Medicinal Chemistry
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
#2
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/29343185/exploring-protein-protein-intermolecular-recognition-between-meprin-%C3%AE-and-endogenous-protease-regulator-cystatinc-coupled-with-pharmacophore-elucidation
#3
Ankur Chaudhuri, Sampa Biswas, Sibani Chakraborty
Meprins are a group of zinc metalloproteases of the astacin family which play pivotal role in several physiological and pathologocal diseases. The inhibition of the meprins by various inhibitors; macromolecular and small molecules are crucial in the control of several diseases. Human cystatinC, an amyloidogenic protein is reported to be an endogenous inhibitor of meprin-α. In this computational study, we elucidate a rational model for meprinα-cystatinC complex by using protein-protein docking. The complex model as well as the unbound form was evaluated by molecular dynamics simulation...
January 17, 2018: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29337987/identification-of-a-noncanonical-function-for-ribose-5-phosphate-isomerase-a-promotes-colorectal-cancer-formation-by-stabilizing-and-activating-%C3%AE-catenin-via-a-novel-c-terminal-domain
#4
Yu-Ting Chou, Jeng-Kai Jiang, Muh-Hwa Yang, Jeng-Wei Lu, Hua-Kuo Lin, Horng-Dar Wang, Chiou-Hwa Yuh
Altered metabolism is one of the hallmarks of cancers. Deregulation of ribose-5-phosphate isomerase A (RPIA) in the pentose phosphate pathway (PPP) is known to promote tumorigenesis in liver, lung, and breast tissues. Yet, the molecular mechanism of RPIA-mediated colorectal cancer (CRC) is unknown. Our study demonstrates a noncanonical function of RPIA in CRC. Data from the mRNAs of 80 patients' CRC tissues and paired nontumor tissues and protein levels, as well as a CRC tissue array, indicate RPIA is significantly elevated in CRC...
January 16, 2018: PLoS Biology
https://www.readbyqxmd.com/read/29337187/metabolomics-reveals-that-dietary-xenoestrogens-alter-cellular-metabolism-induced-by-palbociclib-letrozole-combination-cancer-therapy
#5
Benedikt Warth, Philipp Raffeiner, Ana Granados, Tao Huan, Mingliang Fang, Erica M Forsberg, H Paul Benton, Laura Goetz, Caroline H Johnson, Gary Siuzdak
Recently, the palbociclib/letrozole combination therapy was granted accelerated US FDA approval for the treatment of estrogen receptor (ER)-positive breast cancer. Since the underlying metabolic effects of these drugs are yet unknown, we investigated their synergism at the metabolome level in MCF-7 cells. As xenoestrogens interact with the ER, we additionally aimed at deciphering the impact of the phytoestrogen genistein and the estrogenic mycotoxin zearalenone. A global metabolomics approach was applied to unravel metabolite and pathway modifications...
January 10, 2018: Cell Chemical Biology
https://www.readbyqxmd.com/read/29337163/utility-of-ultra-deep-sequencing-for-detection-of-varicella-zoster-virus-antiviral-resistance-mutations
#6
Mélanie Mercier-Darty, David Boutolleau, Raphaël Lepeule, Christophe Rodriguez, Sonia Burrel
We report the first application of ultra-deep sequencing (UDS) to varicella-zoster virus (VZV) genotypic antiviral testing in a case of acyclovir-resistant VZV infection initially detected by Sanger sequencing within a deeply immunocompromised heart transplant recipient. As added-value compared to Sanger analysis, UDS revealed complex dynamics of viral population under antiviral pressure. Varicella-zoster virus (VZV) is a ubiquitous human herpesvirus affecting populations worldwide. VZV is commonly acquired in youth whose primary infection usually manifests as benign varicella (chickenpox)...
January 11, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29336493/n-terminal-cu-binding-motifs-xxx-zzz-his-atcun-and-xxx-his-and-their-derivatives-chemistry-biology-and-medicinal-applications
#7
Peter Faller, Paulina Gonzalez, Karolina Bossak, Ewelina Stefaniak, Christelle Hureau, Laurent Raibaut, Wojciech Bal
Peptides and proteins with N-terminal amino acid sequences NH2-Xxx-His (XH) and NH2-Xxx-Zzz-His (XZH) form well established high affinity CuII-complexes. Key examples are Asp-Ala-His (in serum albumin) and Gly-His-Lys, the wound healing factor. This opens a straightforward way to add a high affinity CuII-binding site to almost any peptide or protein, by chemical or recombinant approaches. Thus, these motifs, NH2-Xxx-Zzz-His in particular, have been used to equip peptides and proteins with a multitude of functions based on the redox activity of Cu, including nuclease, protease, glycosidase, or oxygen activation, useful in anticancer or antimicrobial drugs...
January 16, 2018: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29335813/organic-acidurias-in-adults-late-complications-and-management
#8
Ali Tunç Tuncel, Nikolas Boy, Marina A Morath, Friederike Hörster, Ulrike Mütze, Stefan Kölker
Organic acidurias (synonym, organic acid disorders, OADs) are a heterogenous group of inherited metabolic diseases delineated with the implementation of gas chromatography/mass spectrometry in metabolic laboratories starting in the 1960s and 1970s. Biochemically, OADs are characterized by accumulation of mono-, di- and/or tricarboxylic acids ("organic acids") and corresponding coenzyme A, carnitine and/or glycine esters, some of which are considered toxic at high concentrations. Clinically, disease onset is variable, however, affected individuals may already present during the newborn period with life-threatening acute metabolic crises and acute multi-organ failure...
January 15, 2018: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/29334665/i-7ab-inhibited-the-growth-of-tnbc-cells-via-targeting-hdac3-and-promoting-the-acetylation-of-p53
#9
Mei Yang, Xuefei Dang, Yue Tan, Meixing Wang, Xiaojing Li, Gang Li
Triple negative breast cancer (TNBC) is a heterogenous disease with high aggressive and poor outcome. The lack of biomarkers and targeted therapies makes it a challenge for the treatment of TNBC. Histone deacetylase inhibitors (HDACis) are emerging as novel anti-tumor agents in many types of human cancers. In this study, we found that I-7ab, a novel HDACi, inhibited the cell viability of TNBC cells and induced the cell apoptosis. Mechanistically, I-7ab specifically decreased the expression of HDAC3 and promoted the acetylation of p53 at both Lys373 and Lys382 amino acids...
January 12, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29334372/pharmacological-blockade-of-asct2-dependent-glutamine-transport-leads-to-antitumor-efficacy-in-preclinical-models
#10
Michael L Schulte, Allie Fu, Ping Zhao, Jun Li, Ling Geng, Shannon T Smith, Jumpei Kondo, Robert J Coffey, Marc O Johnson, Jeffrey C Rathmell, Joe T Sharick, Melissa C Skala, Jarrod A Smith, Jordan Berlin, M Kay Washington, Michael L Nickels, H Charles Manning
The unique metabolic demands of cancer cells underscore potentially fruitful opportunities for drug discovery in the era of precision medicine. However, therapeutic targeting of cancer metabolism has led to surprisingly few new drugs to date. The neutral amino acid glutamine serves as a key intermediate in numerous metabolic processes leveraged by cancer cells, including biosynthesis, cell signaling, and oxidative protection. Herein we report the preclinical development of V-9302, a competitive small molecule antagonist of transmembrane glutamine flux that selectively and potently targets the amino acid transporter ASCT2...
January 15, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29331379/effect-of-histidine-on-sorafenib-induced-vascular-damage-analysis-using-novel-medaka-fish-model
#11
Yoko Shinagawa-Kobayashi, Kenya Kamimura, Ryo Goto, Kohei Ogawa, Ryosuke Inoue, Takeshi Yokoo, Norihiro Sakai, Takuro Nagoya, Akira Sakamaki, Satoshi Abe, Soichi Sugitani, Masahiko Yanagi, Koichi Fujisawa, Yoshizu Nozawa, Naoto Koyama, Hiroshi Nishina, Makoto Furutani-Seiki, Isao Sakaida, Shuji Terai
BACKGROUND: Sorafenib (SFN) is an anti-angiogenic chemotherapeutic that prolongs survival of patients with hepatocellular carcinoma (HCC); its side effects, including vascular damages such as hand-foot syndrome (HFS), are a major cause of therapy discontinuation. We previously reported that maintenance of peripheral blood flow by intake of dried bonito broth (DBB) significantly prevented HFS and prolonged the administration period. The amino acids contained in DBB probably contribute to its effects, but the mechanism has not been clarified...
January 10, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29330550/a-metabolomics-pilot-study-on-desmoid-tumors-and-novel-drug-candidates
#12
Kelly A Mercier, Mushriq Al-Jazrawe, Raymond Poon, Zachery Acuff, Benjamin Alman
Desmoid tumors (aggressive fibromatosis) are locally invasive soft tissue tumors that lack the ability to metastasize. There are no directed therapies or standard treatment plan, and chemotherapeutics, radiation, and surgery often have temporary effects. The majority of desmoid tumors are related to T41A and S45F mutations of the beta-catenin encoding gene (CTNNB1). Using broad spectrum metabolomics, differences were investigated between paired normal fibroblast and desmoid tumor cells from affected patients...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29329981/molecular-cloning-and-characterization-of-leucine-aminopeptidase-gene-from-taenia-pisiformis
#13
Shaohua Zhang, Xuepeng Cai, Xuenong Luo, Shuai Wang, Aijiang Guo, Junling Hou, Run Wu
Leucine aminopeptidase (LAP, EC: 3.4.11.1) is an important metalloexopeptidase that catalyze the hydrolysis of amino-terminal leucine residues from polypeptides and proteins. In this study, a full length of cDNA encoding leucine aminopeptidase of Taenia pisiformis (TpLAP) was cloned by rapid amplification of cDNA-ends using the polymerase chain reaction (RACE-PCR) method. The full-length cDNA of the TpLAP gene is 1823 bp and contains a 1569 bp ORF encoding 533 amino acids with a putative mass of 56.4 kDa...
January 9, 2018: Experimental Parasitology
https://www.readbyqxmd.com/read/29328422/l%C3%A2-mimosine-induces-caspase%C3%A2-9%C3%A2-mediated-apoptosis-in-human-osteosarcoma-cells
#14
Yiwen Xu, Lin Cai
L-mimosine is a rare plant amino acid extracted from Mimosa or Leucaena spp., and it has been reported to exhibit antitumor activity in a number of types of cancer. However, the underlying mechanisms remain to be clarified. In the present study, the effect of L‑mimosine was investigated in human osteosarcoma cells. A Cell Counting Kit‑8 assay and flow cytometry were used for toxicity detection. Hoechst staining and transmission electron microscopy (TEM), in addition to western blot analysis, were used for the examination of the associated mechanisms...
January 9, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29325609/the-cag-polyglutamine-repeat-diseases-a-clinical-molecular-genetic-and-pathophysiologic-nosology
#15
Colleen A Stoyas, Albert R La Spada
Throughout the genome, unstable tandem nucleotide repeats can expand to cause a variety of neurologic disorders. Expansion of a CAG triplet repeat within a coding exon gives rise to an elongated polyglutamine (polyQ) tract in the resultant protein product, and accounts for a unique category of neurodegenerative disorders, known as the CAG-polyglutamine repeat diseases. The nine members of the CAG-polyglutamine disease family include spinal and bulbar muscular atrophy (SBMA), Huntington disease, dentatorubral pallidoluysian atrophy, and six spinocerebellar ataxias (SCA 1, 2, 3, 6, 7, and 17)...
2018: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/29323879/malaria-derived-gpi-anchor-enhances-anti-pfs25-functional-antibodies-that-block-malaria-transmission
#16
Neeraj Kapoor, Ivana Vanjak, James Rozzelle, Aym Berges, Wei Chan, Gang Yin, Cuong Tran, Aaron K Sato, Alexander R Steiner, Thao P Pham, Ashley J Birkett, Carole Long, Jeff Fairman, Kazutoyo Miura
Malaria, one of the most common vector borne human diseas-es, is a major world health issue. In 2015 alone, more than 200 million people were infected with malaria, out of which, 429,000 died. Even though artemisinin-based combination therapies (ACT) are highly effective at treating malaria infections, novel efforts towards development of vaccines to prevent transmission are still needed. Pfs25, a post-fertilization stage parasite surface antigen, is a leading transmission-blocking vaccine (TBV) candidate. It is postulated that Pfs25 anchors to the cell membrane using a glycosylphosphatidyl-inositol (GPI) linker, which itself possesses proinflammatory properties...
January 11, 2018: Biochemistry
https://www.readbyqxmd.com/read/29323428/enteral-nutrition-in-the-management-of-crohn-s-disease-reviewing-mechanisms-of-actions-and-highlighting-potential-venues-for-enhancing-the-efficacy
#17
REVIEW
Moftah H Alhagamhmad
Crohn's disease (CD) is a chronic condition that affects the gut and has adverse effects on growth and development. There is a global increase in the incidence and prevalence rates, and several factors are believed to contribute to this rise, including dietary habits. In contrast, the use of enteral nutrition (EN) as an exclusive source of nutrition is increasingly becoming the preferred induction treatment of pediatric CD patients in part to address the nutrition complications. However, EN therapy is considered less effective in adults with CD...
January 11, 2018: Nutrition in Clinical Practice
https://www.readbyqxmd.com/read/29321311/herpes-simplex-virus-1-mutant-with-point-mutations-in-ul39-is-impaired-for-acute-viral-replication-in-mice-establishment-of-latency-and-explant-induced-reactivation
#18
Heba H Mostafa, Thornton W Thompson, Adam J Konen, Steve D Haenchen, Joshua G Hilliard, Stuart J Macdonald, Lynda A Morrison, David J Davido
In the process of generating HSV-1 mutants in the viral regulatory gene encoding infected cell protein 0 (ICP0), we isolated a viral mutant, termed KOS-NA, that was severely impaired for acute replication in the eyes and trigeminal ganglia (TG) of mice, defective in establishing a latent infection, and reactivated poorly from explanted TG. To identify the secondary mutation(s) responsible for the impaired phenotypes of this mutant, we sequenced the KOS-NA genome and noted that it contained two nonsynonymous mutations in UL39, which encodes the large subunit of ribonucleotide reductase, ICP6...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29318540/identification-of-proteolytic-cleavage-sites-of-epha2-by%C3%A2-membrane-type-1-matrix-metalloproteinase-on-the%C3%A2-surface-of-cancer-cells
#19
Keiji Kikuchi, Hiroko Kozuka-Hata, Masaaki Oyama, Motoharu Seiki, Naohiko Koshikawa
Proteolytic cleavage of membrane proteins can alter their functions depending on the cleavage sites. We recently demonstrated that membrane type 1 matrix metalloproteinase (MT1-MMP ) converts the tumor suppressor EphA2 into an oncogenic signal transducer through EphA2 cleavage. The cleaved EphA2 fragment that remains at the cell surface may be a better target for cancer therapy than intact EphA2. To analyze the cleavage site(s) of EphA2, we purified the fragments from tumor cells expressing MT1-MMP and Myc- and 6× His-tagged EphA2 by two-step affinity purification ...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29318516/cloning-and-expression-of-h-influenzae-49247-iga-protease-in-e-coli
#20
Honglian Wang, Xia Zhong, Jianchun Li, Menglian Zhu, Lu Wang, Xingli Ji, Junming Fan, Li Wang
IgA protease is secreted by various mucosal pathogenic bacteria which can cleave human immunoglobulin A1 (IgA1) in its hinge region. In addition to be considered as a virulence factor, it's reported that IgA protease can also be used for IgA nephropathy (IgAN) treatment. Our previous study identified bacteria H. influenzae 49247 expressed high activity of IgA protease with promised application in IgAN therapy. In this study, we cloned the IgA protease gene of H. influenzae 49247 with degenerate primers. Alignment analysis indicated that H...
January 9, 2018: Molecular Biotechnology
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