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Onconase

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https://www.readbyqxmd.com/read/28963346/onconase-dimerization-through-3d-domain-swapping-structural-investigations-and-increase-in-the-apoptotic-effect-in-cancer-cells
#1
Andrea Fagagnini, Andrea Pica, Sabrina Fasoli, Riccardo Montioli, Massimo Donadelli, Marco Cordani, Elena Butturini, Laura Acquasaliente, Delia Picone, Giovanni Gotte
Onconase® (ONC), a protein extracted from the oocytes of the Rana pipiens frog, is a monomeric member of the secretory 'pancreatic-type' RNase superfamily. Interestingly, ONC is the only monomeric ribonuclease endowed with a high cytotoxic activity. In contrast with other monomeric RNases, ONC displays a high cytotoxic activity. In this work, we found that ONC spontaneously forms dimeric traces and that the dimer amount increases about four times after lyophilization from acetic acid solutions. Differently from RNase A (bovine pancreatic ribonuclease) and the bovine seminal ribonuclease, which produce N- and C-terminal domain-swapped conformers, ONC forms only one dimer, here named ONC-D...
November 6, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28053284/microrna-494-and-atf3-the-targets-of-onconase
#2
EDITORIAL
Zbigniew Darzynkiewicz
No abstract text is available yet for this article.
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28035074/activating-transcription-factor-3-is-crucial-for-antitumor-activity-and-to-strengthen-the-antiviral-properties-of-onconase
#3
Anna Vert, Jessica Castro, Marc Ribó, Antoni Benito, Maria Vilanova
Onconase is a ribonuclease that presents both antitumor and antiviral properties linked to its ribonucleolytic activity and represents a new class of RNA-damaging drugs. It has reached clinical trials for the treatment of several cancers and human papilloma virus warts. Onconase targets different RNAs in the cell cytosol but Onconase-treated cells present features that are different from a simple arrest of protein synthesis. We have used microarray-derived transcriptional profiling to identify Onconase-regulated genes in two ovarian cancer cell lines (NCI/ADR-RES and OVCAR-8)...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/27791452/the-growing-impact-of-lyophilized-cell-free-protein-expression-systems
#4
REVIEW
J Porter Hunt, Seung Ook Yang, Kristen M Wilding, Bradley C Bundy
Recently reported shelf-stable, on-demand protein synthesis platforms are enabling new possibilities in biotherapeutics, biosensing, biocatalysis, and high throughput protein expression. Lyophilized cell-free protein expression systems not only overcome cold-storage limitations, but also enable stockpiling for on-demand synthesis and completely sterilize the protein synthesis platform. Recently reported high-yield synthesis of cytotoxic protein Onconase from lyophilized E. coli extract preparations demonstrates the utility of lyophilized cell-free protein expression and its potential for creating on-demand biotherapeutics, vaccines, biosensors, biocatalysts, and high throughput protein synthesis...
July 4, 2017: Bioengineered
https://www.readbyqxmd.com/read/27590062/combination-of-onconase-and-dihydroartemisinin-synergistically-suppresses-growth-and-angiogenesis-of-non-small-cell-lung-carcinoma-and-malignant-mesothelioma
#5
Ruling Shen, Jun Li, Danrong Ye, Qingcheng Wang, Jian Fei
Onconase (Onc) is a cytotoxic ribonuclease derived from leopard frog oocytes or early embryos, and has been applied to the treatment of malignant mesothelioma in clinics. Onc also exhibits effective growth suppression of human non-small-cell lung cancer (NSCLC). Artemisinin (Art) and its derivatives are novel antimalarial drugs that exhibit antitumor and antivirus activities. In this study, we investigated the antitumor effects of combinations of Onc and an Art derivative, dihydroartemisinin (DHA), both in vitro and in vivo Isobologram analyses showed synergistic effects on the proliferation of NSCLC cells under the treatment with Onc and DHA...
October 2016: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/27352327/anti-gliomas-effect-of-chlorotoxin-conjugated-onconase-at-high-dose
#6
Xiaomin Wang, Zhanyun Guo
Malignant gliomas are rarely curable malignant tumors in the central nervous system. Chlorotoxin (CTX) is a peptide derived from scorpion venom, which can selectively target malignant gliomas. Onconase (Onc) is a small cytotoxic ribonuclease derived from frogspawn that exhibits cytotoxicity against some tumor cells. In the present study, we found that CTX-conjugated Onc (CTX-Onc) shows better anti-tumor effect than the physical mixture of CTX and Onc (CTX + Onc) on the nude mice carrying subcutaneous glioblastoma cell-derived tumor...
November 2015: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/26939446/-expression-purification-and-characterization-of-recombinant-onconase-expressed-in-pichia-pastoris
#7
Ganggang Yang, Chengkai Ma, Quanyi Zhang, Shihui Shi, Ze Wang, Zhongyuan Lü, Xuyang Wang, Xiaoya Xu, Qingqing Cui, Jihong Zhang, Ruigang Zhang, Cunshuan Xu
Ranpirnase (onconase, ONC) is a new drug, with weak RNase activity and strong cytotoxicity to various tumor cells in vitro and in vivo. This study is to obtain recombination onconase (rONC) with high bioactivity. Based on the codon preference of Pichia pastoris, we designed and synthesized the gene according to cDNA sequences of ONC and the α mating factor's prepeptide. We screened positive clones after transforming the recombination plasmids into P. pastoris X-33, GSS115 and SMD1168. We screened the best combination of seven different vectors and host strains...
November 2015: Sheng Wu Gong Cheng Xue Bao, Chinese Journal of Biotechnology
https://www.readbyqxmd.com/read/26817512/prognostic-and-therapeutic-implications-of-microrna-in-malignant-pleural-mesothelioma
#8
REVIEW
Anna Truini, Simona Coco, Carlo Genova, Marco Mora, Maria G Dal Bello, Irene Vanni, Angela Alama, Erika Rijavec, Giulia Barletta, Federica Biello, Claudia Maggioni, Francesco Grossi
Malignant Pleural Mesothelioma (MPM) is an aggressive disease characterized by a dismal prognosis, mainly due to late diagnosis. To date, there are very few treatment options available and the refractoriness to the majority of therapeutic strategies, leading to consider MPM a relevant problem in public health. Therefore, the identification of novel prognostic markers and alternative therapeutic strategies remain a top priority. Several efforts have been made in this direction and to date a number of studies have investigated the role of microRNA as biomarkers in MPM, identifying the potential prognostic role of miR-29c* and miR-31...
2016: MicroRNA
https://www.readbyqxmd.com/read/26808536/rational-design-of-a-carrier-protein-for-the-production-of-recombinant-toxic-peptides-in-escherichia-coli
#9
Katia Pane, Lorenzo Durante, Elio Pizzo, Mario Varcamonti, Anna Zanfardino, Valeria Sgambati, Antimo Di Maro, Andrea Carpentieri, Viviana Izzo, Alberto Di Donato, Valeria Cafaro, Eugenio Notomista
Commercial uses of bioactive peptides require low cost, effective methods for their production. We developed a new carrier protein for high yield production of recombinant peptides in Escherichia coli very well suited for the production of toxic peptides like antimicrobial peptides. GKY20, a short antimicrobial peptide derived from the C-terminus of human thrombin, was fused to the C-terminus of Onconase, a small ribonuclease (104 amino acids), which efficiently drove the peptide into inclusion bodies with very high expression levels (about 200-250 mg/L)...
2016: PloS One
https://www.readbyqxmd.com/read/26782924/constitutive-expression-and-anticancer-potency-of-a-novel-immunotoxin-onconase-dv3
#10
Miaonan Sun, Huichun Tang, Yan Gao, Xinxuan Dai, Yue Yuan, Chunmei Zhang, Dejun Sun
Onconase is an RNase of the ribonuclease A superfamily that is purified from the Northern leopard frog (Rana pipiens). It targets several types of malignant tumors, digests cytoplasmic transfer RNA (tRNA), and causes tumor cell apoptosis. Onconase has been employed in clinical trials as an antitumor drug, and has revealed its valuable clinical activity in several types of tumors, particularly pleural mesothelioma. However, its inefficiency in targeting tumor cells and its non‑specific toxicity in normal tissues have diminished its clinical benefits...
April 2016: Oncology Reports
https://www.readbyqxmd.com/read/26605343/a-humanized-anti-cd22-onconase-antibody-drug-conjugate-mediates-highly-potent-destruction-of-targeted-tumor-cells
#11
Tobias Weber, Athanasios Mavratzas, Stefan Kiesgen, Stephanie Haase, Benedikt Bötticher, Evelyn Exner, Walter Mier, Ludger Grosse-Hovest, Dirk Jäger, Michaela A E Arndt, Jürgen Krauss
Antibody-drug conjugates (ADCs) have evolved as a new class of potent cancer therapeutics. We here report on the development of ADCs with specificity for the B-cell lineage specific (surface) antigen CD22 being expressed in the majority of hematological malignancies. As targeting moiety a previously generated humanized anti-CD22 single-chain variable fragment (scFv) derivative from the monoclonal antibody RFB4 was reengineered into a humanized IgG1 antibody format (huRFB4). Onconase (ranpirnase), a clinically active pancreatic-type ribonuclease, was employed as cytotoxic payload moiety...
2015: Journal of Immunology Research
https://www.readbyqxmd.com/read/26380966/cell-free-protein-synthesis-of-a-cytotoxic-cancer-therapeutic-onconase-production-and-a-just-add-water-cell-free-system
#12
Amin S M Salehi, Mark Thomas Smith, Anthony M Bennett, Jacob B Williams, William G Pitt, Bradley C Bundy
Biotherapeutics have many promising applications, such as anti-cancer treatments, immune suppression, and vaccines. However, due to their biological nature, some biotherapeutics can be challenging to rapidly express and screen for activity through traditional recombinant methods. For example, difficult-to-express proteins may be cytotoxic or form inclusion bodies during expression, increasing the time, labor, and difficulty of purification and downstream characterization. One potential pathway to simplify the expression and screening of such therapeutics is to utilize cell-free protein synthesis...
February 2016: Biotechnology Journal
https://www.readbyqxmd.com/read/26137092/rana-catesbeiana-ribonuclease-induces-cell-apoptosis-via-the-caspase-9-3-signaling-pathway-in-human-glioblastoma-dbtrg-gbm8901-and-gbm8401-cell-lines
#13
Jen-Ni Chen, Giou-Teng Yiang, Yi-Fan Lin, Pei-Lun Chou, Tsai-Kun Wu, Wei-Jung Chang, Chinshuh Chen, Yung-Luen Yu
Human glioblastoma multiforme is one of the most aggressive malignant brain tumor types, and the mean survival time of patients with a brain tumor is <2 years when traditional therapies are administered. Thus, numerous studies have focused on the development of novel treatments for brain tumors. Frog ribonucleases, such as Onconase and Rana catesbeiana ribonuclease (RC-RNase), exert antitumor effects on various tumor cells, including cervical cancer, breast cancer, hepatoma, leukemia, pancreatic cancer and prostate cancer cells...
June 2015: Oncology Letters
https://www.readbyqxmd.com/read/25842855/-ribonucleases-as-antiviral-agents
#14
REVIEW
O N Il'inskaia, R Shakh Makhmud
Many ribonucleases (RNases) are able to inhibit the reproduction of viruses in infected cell cultures and laboratory animals, but molecular mechanisms of their antiviral activity remain unclear. The review observes the most known RNases which possess established antiviral effects, actually intracellular RNases (RNase L, MCPIPI protein, eosinophylic RNases) as well as exogenously applied ones (RNase A, BS-RNase, onconase, binase, synthetic RNases). Attention is given on two important but not always obligatory aspects in molecule of RNases, which have antiviral properties: catalytic activity and ability to the dimerization...
September 2014: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/25663909/chlorotoxin-conjugated-onconase-as-a-potential-anti-glioma-drug
#15
Xiaomin Wang, Zhanyun Guo
Gliomas are rarely curable malignant brain tumors arising from normal glial cells. The scorpion-derived small peptide, chlorotoxin (CTX), can selectively bind malignant gliomas. In the present study, a CTX-conjugated onconase (Onc), a small cytotoxic ribonuclease, was prepared as a potential anti-glioma drug. In this conjugate, recombinant CTX was covalently linked with recombinant Onc by reversible disulfide linkage. The chemically conjugated CTX-Onc showed much higher cytotoxicity to the cultured glioma U251 and SHG-44 cells than the physical mixture of CTX and Onc (CTX + Onc)...
March 2015: Oncology Letters
https://www.readbyqxmd.com/read/25533084/onconase-induces-autophagy-sensitizing-pancreatic-cancer-cells-to-gemcitabine-and-activates-akt-mtor-pathway-in-a-ros-dependent-manner
#16
Claudia Fiorini, Marco Cordani, Giovanni Gotte, Delia Picone, Massimo Donadelli
Onconase® (ONC) is a member of the RNase super-family that is secreted in oocytes and early embryos of Rana pipiens. Over the last years, research interest about this small and basic frog RNase, also called ranpirnase, constantly increased because of its high cytotoxicity and anticancer properties. Onconase is currently used in clinical trials for cancer therapy; however, the precise mechanisms determining cytotoxicity in cancer cells have not yet been fully investigated. In the present manuscript, we evaluate the antitumoral property of onconase in pancreatic adenocarcinoma cells and in non-tumorigenic cells as a control...
March 2015: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/25434798/an-egf-receptor-targeting-ranpirnase-diabody-fusion-protein-mediates-potent-antitumour-activity-in-vitro-and-in-vivo
#17
Stefan Kiesgen, Michaela A E Arndt, Christoph Körber, Ulrich Arnold, Tobias Weber, Niels Halama, Armin Keller, Benedikt Bötticher, Anne Schlegelmilch, Nora Liebers, Martin Cremer, Christel Herold-Mende, Gerhard Dyckhoff, Philippe A Federspil, Alexandra D Jensen, Dirk Jäger, Roland E Kontermann, Walter Mier, Jürgen Krauss
Cytotoxic ribonucleases such as the leopard frog derivative Ranpirnase (Onconase(®)) have emerged as a valuable new class of cancer therapeutics. Clinical trials employing single agent Ranpirnase in cancer patients have demonstrated significant clinical activity and surprisingly low immunogenicity. However, dose-limiting toxicity due to unspecific uptake of the RNase into non-cancerous cells is reached at relatively low concentrations of > 1 mg/m(2). We have in the present study generated a dimeric anti-EGFR Ranpirnase-diabody fusion protein capable to deliver two Ranpirnase moieties per molecule to EGFR-positive tumour cells...
February 1, 2015: Cancer Letters
https://www.readbyqxmd.com/read/25303768/genetic-delivery-of-an-immunornase-by-an-oncolytic-adenovirus-enhances-anticancer-activity
#18
Inés Fernández-Ulibarri, Katharina Hammer, Michaela A E Arndt, Johanna K Kaufmann, Dominik Dorer, Sarah Engelhardt, Roland E Kontermann, Jochen Hess, Heike Allgayer, Jürgen Krauss, Dirk M Nettelbeck
Antibody therapy of solid cancers is well established, but suffers from unsatisfactory tumor penetration of large immunoglobulins or from low serum retention of antibody fragments. Oncolytic viruses are in advanced clinical development showing excellent safety, but suboptimal potency due to limited virus spread within tumors. Here, by developing an immunoRNase-encoding oncolytic adenovirus, we combine viral oncolysis with intratumoral genetic delivery of a small antibody-fusion protein for targeted bystander killing of tumor cells (viro-antibody therapy)...
May 1, 2015: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/25179221/designing-hybrid-onconase-nanocarriers-for-mesothelioma-therapy-a-taguchi-orthogonal-array-and-multivariate-component-driven-analysis
#19
Rakesh K Tekade, Susanne R Youngren-Ortiz, Haining Yang, Rahul Haware, Mahavir B Chougule
Onconase (ONC) is a member of a ribonuclease superfamily that has cytostatic activity against malignant mesothelioma (MM). The objective of this investigation was to develop bovine serum albumin (BSA)-chitosan based hybrid nanoformulations for the efficient delivery of ONC to MM while minimizing the exposure to normal tissues. Taguchi orthogonal array L9 type design was used to formulate ONC loaded BSA nanocarriers (ONC-ANC) with a mean particle size of 15.78 ± 0.24 nm (ζ = -21.89 ± 0.11 mV). The ONC-ANC surface was hybridized using varying chitosan concentrations ranging between 0...
October 6, 2014: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/24966023/stability-and-folding-of-amphibian-ribonuclease%C3%A2-a-superfamily-members-in-comparison-with-mammalian-homologues
#20
REVIEW
Ulrich Arnold
Comparative studies on homologous proteins can provide knowledge on how limited changes in the primary structure find their expression in large effects on catalytic activity, stability or the folding behavior. For more than half a century, members of the ribonuclease A superfamily have been the subject of a myriad of studies on protein folding and stability. Both the unfolding and refolding kinetics as well as the structure of several folding intermediates of ribonuclease A have been characterized in detail...
August 2014: FEBS Journal
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