{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T15:01:14Z","timestamp":1761490874282,"version":"3.37.3"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2019,10,4]],"date-time":"2019-10-04T00:00:00Z","timestamp":1570147200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Stony Brook Cancer Center"},{"DOI":"10.13039\/100007707","name":"University of California, Davis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007707","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016953","name":"Comprehensive Cancer Center, University of California, Davis","doi-asserted-by":"publisher","award":["NCI P30CA093373"],"award-info":[{"award-number":["NCI P30CA093373"]}],"id":[{"id":"10.13039\/100016953","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,7,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>New chemotherapeutic agents are needed for pancreatic cancer (PC). We have previously shown that phospho-valproic acid (MDC-1112) is effective in cell-line xenografts of PC. Here, we explored whether MDC-1112 is effective in additional clinically relevant animal models of PC and whether MDC-1112 enhances the anticancer effect of clinically used chemotherapeutic agents. MDC-1112 alone strongly reduced patient-derived pancreatic tumor xenograft growth, and extended survival of LSL-KrasG12D\/+; LSL-Trp53R172H\/+; Pdx1-Cre (KPC) mice. In both models, MDC-1112 inhibited STAT3 activation and its downstream signals, including Bcl-xL and cyclin D1. In human PC cell lines, P-V enhanced the growth inhibitory effect of gemcitabine (GEM), Abraxane and 5-FU, but not that of irinotecan. Normal human pancreatic epithelial cells were more resistant to the cytotoxic effects of MDC-1112\/GEM combination. Furthermore, MDC-1112 enhanced GEM\u2019s effect on colony formation, apoptosis, cell migration, and cell invasion. In vivo, MDC-1112 and GEM, given alone, reduced patient-derived pancreatic tumor xenograft growth by 58% and 87%, respectively; whereas MDC-1112\/GEM combination reduced tumor growth by 94%, inducing tumor stasis. In conclusion, MDC-1112 should be further explored as a potential agent to be used in combination with GEM for treating PC.<\/jats:p>","DOI":"10.1093\/carcin\/bgz170","type":"journal-article","created":{"date-parts":[[2019,10,2]],"date-time":"2019-10-02T11:17:51Z","timestamp":1570015071000},"page":"927-939","source":"Crossref","is-referenced-by-count":5,"title":["Phospho-valproic acid (MDC-1112) reduces pancreatic cancer growth in patient-derived tumor xenografts and KPC mice: enhanced efficacy when combined with gemcitabine"],"prefix":"10.1093","volume":"41","author":[{"given":"Dingyuan","family":"Luo","sequence":"first","affiliation":[{"name":"Department of Nutrition, University of California, Davis, One Shields Ave, Davis, CA, USA"},{"name":"Department of Thyroid Surgery, Guangzhou, China"},{"name":"Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew G","family":"Digiovanni","sequence":"additional","affiliation":[{"name":"Department of Nutrition, University of California, Davis, One Shields Ave, Davis, CA, USA"},{"name":"Departments of Family, Population and Preventive Medicine, Stony Brook, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ran","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Nutrition, University of California, Davis, One Shields Ave, Davis, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph F","family":"Lacomb","sequence":"additional","affiliation":[{"name":"Departments of Family, Population and Preventive Medicine, Stony Brook, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennie L","family":"Williams","sequence":"additional","affiliation":[{"name":"Departments of Family, Population and Preventive Medicine, Stony Brook, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Basil","family":"Rigas","sequence":"additional","affiliation":[{"name":"Medicine, Stony Brook University, Stony Brook, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6460-7165","authenticated-orcid":false,"given":"Gerardo G","family":"Mackenzie","sequence":"additional","affiliation":[{"name":"Department of Nutrition, University of California, Davis, One Shields Ave, Davis, CA, USA"},{"name":"Departments of Family, Population and Preventive Medicine, Stony Brook, NY, USA"},{"name":"University of California, Davis Comprehensive Cancer Center, Sacramento, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,10,4]]},"reference":[{"key":"2021031108490445500_CIT0001","doi-asserted-by":"crossref","first-page":"2913","DOI":"10.1158\/0008-5472.CAN-14-0155","article-title":"Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States","volume":"74","author":"Rahib","year":"2014","journal-title":"Cancer Res."},{"key":"2021031108490445500_CIT0002","doi-asserted-by":"crossref","first-page":"16022","DOI":"10.1038\/nrdp.2016.22","article-title":"Pancreatic cancer","volume":"2","author":"Kleeff","year":"2016","journal-title":"Nat. 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