{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T01:01:14Z","timestamp":1792717274534,"version":"4.5.0"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2014,1,1]],"date-time":"2014-01-01T00:00:00Z","timestamp":1388534400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Mol Biotechnol"],"published-print":{"date-parts":[[2014,5]]},"DOI":"10.1007\/s12033-013-9725-x","type":"journal-article","created":{"date-parts":[[2013,12,31]],"date-time":"2013-12-31T17:43:20Z","timestamp":1388511800000},"page":"421-428","source":"Crossref","is-referenced-by-count":83,"title":["Addition of Valproic Acid to CHO Cell Fed-Batch Cultures Improves Monoclonal Antibody Titers"],"prefix":"10.1007","volume":"56","author":[{"given":"William C.","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiuyi","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ngan B.","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas V.","family":"Healy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rashmi","family":"Kshirsagar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Ryll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao-Ming","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2014,1,1]]},"reference":[{"issue":"2","key":"9725_CR1","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1007\/s00253-010-2798-6","volume":"88","author":"O Kramer","year":"2010","unstructured":"Kramer, O., Klausing, S., & Noll, T. (2010). Methods in mammalian cell line engineering: From random mutagenesis to sequence-specific approaches. Applied Microbiology and Biotechnology, 88(2), 425\u2013436.","journal-title":"Applied Microbiology and Biotechnology"},{"issue":"3","key":"9725_CR2","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1007\/s00253-011-3758-5","volume":"93","author":"JY Kim","year":"2012","unstructured":"Kim, J. Y., Kim, Y. G., & Lee, G. M. (2012). CHO cells in biotechnology for production of recombinant proteins: Current state and further potential. Applied Microbiology and Biotechnology, 93(3), 917\u2013930.","journal-title":"Applied Microbiology and Biotechnology"},{"issue":"5","key":"9725_CR3","doi-asserted-by":"crossref","first-page":"466","DOI":"10.4161\/mabs.2.5.12720","volume":"2","author":"F Li","year":"2010","unstructured":"Li, F., Vijayasankaran, N., Shen, A. Y., Kiss, R., & Amanullah, A. (2010). Cell culture processes for monoclonal antibody production. mAbs, 2(5), 466\u2013479.","journal-title":"mAbs"},{"issue":"6","key":"9725_CR4","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1002\/bit.21839","volume":"100","author":"MJ Allen","year":"2008","unstructured":"Allen, M. J., Boyce, J. P., Trentalange, M. T., Treiber, D. L., Rasmussen, B., Tillotson, B., et al. (2008). Identification of novel small molecule enhancers of protein production by cultured mammalian cells. Biotechnology and Bioengineering, 100(6), 1193\u20131204.","journal-title":"Biotechnology and Bioengineering"},{"issue":"1","key":"9725_CR5","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S1389-1723(01)80114-6","volume":"91","author":"C Liu","year":"2001","unstructured":"Liu, C., Chu, I., & Hwang, S. (2001). Pentanoic acid, a novel protein synthesis stimulant for Chinese Hamster Ovary (CHO) cells. Journal of Bioscience and Bioengineering, 91(1), 71\u201375.","journal-title":"Journal of Bioscience and Bioengineering"},{"issue":"1\u20132","key":"9725_CR6","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/S0022-1759(00)00308-2","volume":"247","author":"Y Mimura","year":"2001","unstructured":"Mimura, Y., Lund, J., Church, S., Dong, S., Li, J., Goodall, M., et al. (2001). Butyrate increases production of human chimeric IgG in CHO-K1 cells whilst maintaining function and glycoform profile. Journal of Immunological Methods, 247(1\u20132), 205\u2013216.","journal-title":"Journal of Immunological Methods"},{"issue":"1","key":"9725_CR7","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1002\/bit.21726","volume":"100","author":"Z Jiang","year":"2008","unstructured":"Jiang, Z., & Sharfstein, S. T. (2008). Sodium butyrate stimulates monoclonal antibody over-expression in CHO cells by improving gene accessibility. Biotechnology and Bioengineering, 100(1), 189\u2013194.","journal-title":"Biotechnology and Bioengineering"},{"issue":"6","key":"9725_CR8","first-page":"1036","volume":"17","author":"MK Jeon","year":"2007","unstructured":"Jeon, M. K., & Lee, G. M. (2007). Correlation between enhancing effect of sodium butyrate on specific productivity and mRNA transcription level in recombinant Chinese hamster ovary cells producing antibody. Journal of Microbiology and Biotechnology, 17(6), 1036\u20131040.","journal-title":"Journal of Microbiology and Biotechnology"},{"issue":"1\u20133","key":"9725_CR9","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1023\/A:1014088919546","volume":"36","author":"V Hendrick","year":"2001","unstructured":"Hendrick, V., Winnepenninckx, P., Abdelkafi, C., Vandeputte, O., Cherlet, M., Marique, T., et al. (2001). Increased productivity of recombinant tissular plasminogen activator (t-PA) by butyrate and shift of temperature: A cell cycle phases analysis. Cytotechnology, 36(1\u20133), 71\u201383.","journal-title":"Cytotechnology"},{"issue":"2","key":"9725_CR10","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.jbiotec.2009.09.008","volume":"145","author":"A Kantardjieff","year":"2010","unstructured":"Kantardjieff, A., Jacob, N. M., Yee, J. C., Epstein, E., Kok, Y. J., Philp, R., et al. (2010). Transcriptome and proteome analysis of Chinese hamster ovary cells under low temperature and butyrate treatment. Journal of Biotechnology, 145(2), 143\u2013159.","journal-title":"Journal of Biotechnology"},{"key":"9725_CR11","first-page":"125","volume":"301","author":"W Doerfler","year":"2006","unstructured":"Doerfler, W. (2006). De novo methylation, long-term promoter silencing, methylation patterns in the human genome, and consequences of foreign DNA insertion. Current Topics in Microbiology and Immunology, 301, 125\u2013175.","journal-title":"Current Topics in Microbiology and Immunology"},{"issue":"24","key":"9725_CR12","doi-asserted-by":"crossref","first-page":"3156","DOI":"10.1038\/sj.onc.1204339","volume":"20","author":"MR Rountree","year":"2001","unstructured":"Rountree, M. R., Bachman, K. E., Herman, J. G., & Baylin, S. B. (2001). DNA methylation, chromatin inheritance, and cancer. Oncogene, 20(24), 3156\u20133165.","journal-title":"Oncogene"},{"issue":"9","key":"9725_CR13","first-page":"2723","volume":"31","author":"S Sarkar","year":"2011","unstructured":"Sarkar, S., Abujamra, A. L., Loew, J. E., Forman, L. W., Perrine, S. P., & Faller, D. V. (2011). Histone deacetylase inhibitors reverse CpG methylation by regulating DNMT1 through ERK signaling. Anticancer Research, 31(9), 2723\u20132732.","journal-title":"Anticancer Research"},{"issue":"1","key":"9725_CR14","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1002\/bit.21882","volume":"101","author":"G Backliwal","year":"2008","unstructured":"Backliwal, G., Hildinger, M., Kuettel, I., Delegrange, F., Hacker, D. L., & Wurm, F. M. (2008). Valproic acid: A viable alternative to sodium butyrate for enhancing protein expression in mammalian cell cultures. Biotechnology and Bioengineering, 101(1), 182\u2013189.","journal-title":"Biotechnology and Bioengineering"},{"issue":"15","key":"9725_CR15","doi-asserted-by":"crossref","first-page":"e96","DOI":"10.1093\/nar\/gkn423","volume":"36","author":"G Backliwal","year":"2008","unstructured":"Backliwal, G., Hildinger, M., Chenuet, S., Wulhfard, S., De Jesus, M., & Wurm, F. M. (2008). Rational vector design and multi-pathway modulation of HEK 293E cells yield recombinant antibody titers exceeding 1\u00a0g\/L by transient transfection under serum-free conditions. Nucleic Acids Research, 36(15), e96.","journal-title":"Nucleic Acids Research"},{"issue":"2\u20133","key":"9725_CR16","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.jbiotec.2010.05.003","volume":"148","author":"S Wulhfard","year":"2010","unstructured":"Wulhfard, S., Baldi, L., Hacker, D. L., & Wurm, F. (2010). Valproic acid enhances recombinant mRNA and protein levels in transiently transfected Chinese hamster ovary cells. Journal of Biotechnology, 148(2\u20133), 128\u2013132.","journal-title":"Journal of Biotechnology"},{"issue":"11","key":"9725_CR17","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1038\/nbt1030","volume":"22","author":"AJ Chirino","year":"2004","unstructured":"Chirino, A. J., & Mire-Sluis, A. (2004). Characterizing biological products and assessing comparability following manufacturing changes. Nature Biotechnology, 22(11), 1383\u20131391.","journal-title":"Nature Biotechnology"},{"issue":"1","key":"9725_CR18","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1128\/MCB.10.1.401","volume":"10","author":"MG Pallavicini","year":"1990","unstructured":"Pallavicini, M. G., DeTeresa, P. S., Rosette, C., Gray, J. W., & Wurm, F. M. (1990). Effects of methotrexate on transfected DNA stability in mammalian cells. Molecular and Cellular Biology, 10(1), 401\u2013404.","journal-title":"Molecular and Cellular Biology"},{"issue":"3","key":"9725_CR19","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/0014-5793(95)01328-8","volume":"377","author":"C Gandor","year":"1995","unstructured":"Gandor, C., Leist, C., Fiechter, A., & Asselbergs, F. A. (1995). Amplification and expression of recombinant genes in serum-independent Chinese hamster ovary cells. FEBS Letters, 377(3), 290\u2013294.","journal-title":"FEBS Letters"},{"issue":"5","key":"9725_CR20","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1002\/btpr.436","volume":"26","author":"YM Huang","year":"2010","unstructured":"Huang, Y. M., Hu, W., Rustandi, E., Chang, K., Yusuf-Makagiansar, H., & Ryll, T. (2010). Maximizing productivity of CHO cell-based fed-batch culture using chemically defined media conditions and typical manufacturing equipment. Biotechnology Progress, 26(5), 1400\u20131410.","journal-title":"Biotechnology Progress"},{"issue":"10","key":"9725_CR21","doi-asserted-by":"crossref","first-page":"2523","DOI":"10.1002\/bit.24511","volume":"109","author":"R Kshirsagar","year":"2012","unstructured":"Kshirsagar, R., McElearney, K., Gilbert, A., Sinacore, M., & Ryll, T. (2012). Controlling trisulfide modification in recombinant monoclonal antibody produced in fed-batch cell culture. Biotechnology and Bioengineering, 109(10), 2523\u20132532.","journal-title":"Biotechnology and Bioengineering"},{"issue":"3\u20134","key":"9725_CR22","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.jbiotec.2010.04.004","volume":"147","author":"Y Yang","year":"2010","unstructured":"Yang, Y., Mariati, Chusainow, J., & Yap, M. G. (2010). DNA methylation contributes to loss in productivity of monoclonal antibody-producing CHO cell lines. Journal of Biotechnology, 147(3\u20134), 180\u2013185.","journal-title":"Journal of Biotechnology"},{"issue":"3","key":"9725_CR23","doi-asserted-by":"crossref","first-page":"296","DOI":"10.3390\/pr1030296","volume":"1","author":"F Wurm","year":"2013","unstructured":"Wurm, F. (2013). CHO quasispecies: Implications for manufacturing processes. Processes, 1(3), 296\u2013311.","journal-title":"Processes"},{"issue":"8","key":"9725_CR24","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1038\/nbt.2624","volume":"31","author":"NE Lewis","year":"2013","unstructured":"Lewis, N. E., Liu, X., Li, Y., Nagarajan, H., Yerganian, G., O\u2019Brien, E., et al. (2013). Genomic landscapes of Chinese hamster ovary cell lines as revealed by the Cricetulus griseus draft genome. Nature Biotechnology, 31(8), 759\u2013765.","journal-title":"Nature Biotechnology"},{"issue":"6","key":"9725_CR25","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1002\/bit.22348","volume":"103","author":"M Gawlitzek","year":"2009","unstructured":"Gawlitzek, M., Estacio, M., Furch, T., & Kiss, R. (2009). Identification of cell culture conditions to control N-glycosylation site-occupancy of recombinant glycoproteins expressed in CHO cells. Biotechnology and Bioengineering, 103(6), 1164\u20131175.","journal-title":"Biotechnology and Bioengineering"},{"issue":"1","key":"9725_CR26","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1023\/A:1008080432681","volume":"29","author":"D Lamotte","year":"1999","unstructured":"Lamotte, D., Buckberry, L., Monaco, L., Soria, M., Jenkins, N., Engasser, J. M., et al. (1999). Na-butyrate increases the production and alpha2,6-sialylation of recombinant interferon-gamma expressed by alpha2,6-sialyltransferase engineered CHO cells. Cytotechnology, 29(1), 55\u201364.","journal-title":"Cytotechnology"},{"issue":"1","key":"9725_CR27","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1002\/1097-0290(20001005)70:1<25::AID-BIT4>3.0.CO;2-Q","volume":"70","author":"DC Andersen","year":"2000","unstructured":"Andersen, D. C., Bridges, T., Gawlitzek, M., & Hoy, C. (2000). Multiple cell culture factors can affect the glycosylation of Asn-184 in CHO-produced tissue-type plasminogen activator. Biotechnology and Bioengineering, 70(1), 25\u201331.","journal-title":"Biotechnology and Bioengineering"}],"container-title":["Molecular Biotechnology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s12033-013-9725-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s12033-013-9725-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s12033-013-9725-x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,6,2]],"date-time":"2019-06-02T02:34:38Z","timestamp":1559442878000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s12033-013-9725-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,1,1]]},"references-count":27,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2014,5]]}},"alternative-id":["9725"],"URL":"https:\/\/doi.org\/10.1007\/s12033-013-9725-x","relation":{},"ISSN":["1073-6085","1559-0305"],"issn-type":[{"value":"1073-6085","type":"print"},{"value":"1559-0305","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,1,1]]}}}