{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T04:06:40Z","timestamp":1790050000542,"version":"4.0.1"},"reference-count":41,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2004,11,1]],"date-time":"2004-11-01T00:00:00Z","timestamp":1099267200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2004,11,1]],"date-time":"2004-11-01T00:00:00Z","timestamp":1099267200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["clinical-colorectal-cancer.com","clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Clinical Colorectal Cancer"],"published-print":{"date-parts":[[2004,11]]},"DOI":"10.3816\/ccc.2004.n.026","type":"journal-article","created":{"date-parts":[[2008,9,10]],"date-time":"2008-09-10T21:05:48Z","timestamp":1221080748000},"page":"268-274","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":29,"title":["A Phase II Trial of ISIS 3521 in Patients with Metastatic Colorectal Cancer"],"prefix":"10.3816","volume":"4","author":[{"given":"John L.","family":"Marshall","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven G.","family":"Eisenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Hanfelt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. Andrew","family":"Dorr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorraya","family":"El-Ashry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Oberst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yair","family":"Fuxman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon","family":"Holmlund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shakun","family":"Malik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.3816\/CCC.2004.n.026_bib1","doi-asserted-by":"crossref","first-page":"1912","DOI":"10.1126\/science.1075762","article-title":"The protein kinase complement of the human genome","volume":"298","author":"Manning","year":"2002","journal-title":"Science"},{"key":"10.3816\/CCC.2004.n.026_bib2","doi-asserted-by":"crossref","unstructured":"Blume-Jensen P, Hunter T. Oncogenic kinase signaling. Nature 200; 411:355-365.","DOI":"10.1038\/35077225"},{"key":"10.3816\/CCC.2004.n.026_bib3","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.1038\/sj.onc.1201725","article-title":"Loss of protein kinase C function induces an apoptotic response","volume":"16","author":"Whelan","year":"1998","journal-title":"Oncogene"},{"key":"10.3816\/CCC.2004.n.026_bib4","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1038\/334661a0","article-title":"The molecular heterogeneity of protein kinase C and its implications for cellular regulation","volume":"334","author":"Nishizuka","year":"1988","journal-title":"Nature"},{"key":"10.3816\/CCC.2004.n.026_bib5","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/0163-7258(93)90070-T","article-title":"The potential of protein kinase C as a target for anticancer treatment","volume":"59","author":"Basu","year":"1993","journal-title":"Pharmacol Ther"},{"key":"10.3816\/CCC.2004.n.026_bib6","first-page":"213","article-title":"Protein kinase C isoenzymes: regulation and function","volume":"27","author":"Blobe","year":"1996","journal-title":"Cancer Surv"},{"key":"10.3816\/CCC.2004.n.026_bib7","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/bjc.1992.209","article-title":"Towards selective pharmacological modulation of protein kinase C\u2013opportunities for the development of novel antineoplastic agents","volume":"66","author":"Gescher","year":"1992","journal-title":"Br J Cancer"},{"key":"10.3816\/CCC.2004.n.026_bib8","first-page":"205","article-title":"Altered protein kinase C activity in biopsies of human colonic adenomas and carcinomas","volume":"51","author":"Kopp","year":"1991","journal-title":"Cancer Res"},{"key":"10.3816\/CCC.2004.n.026_bib9","first-page":"6413","article-title":"Alterations in murine keratinocyte differentiation induced by activated rasHa genes are mediated by protein kinase C-alpha","volume":"54","author":"Dlugosz","year":"1994","journal-title":"Cancer Res"},{"key":"10.3816\/CCC.2004.n.026_bib10","doi-asserted-by":"crossref","first-page":"1906","DOI":"10.1172\/JCI117872","article-title":"MCF-7 breast cancer cells transfected with protein kinase C-alpha exhibit altered expression of other protein kinase C isoforms and display a more aggressive neoplastic phenotype","volume":"95","author":"Ways","year":"1995","journal-title":"J Clin Invest"},{"key":"10.3816\/CCC.2004.n.026_bib11","doi-asserted-by":"crossref","first-page":"11762","DOI":"10.1073\/pnas.91.24.11762","article-title":"Inhibition of protein kinase C-alpha expression in mice after systemic administration of phosphorothioate antisense oligodeoxynucleotides","volume":"91","author":"Dean","year":"1994","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.3816\/CCC.2004.n.026_bib12","first-page":"395","article-title":"Antisense oligonucleotide inhibitors for the treatment of cancer: 2. Toxicological properties of phosphorothioate oligodeoxynucleotides","volume":"12","author":"Henry","year":"1997","journal-title":"Anticancer Drug Des"},{"key":"10.3816\/CCC.2004.n.026_bib13","doi-asserted-by":"crossref","first-page":"3586","DOI":"10.1200\/JCO.1999.17.11.3586","article-title":"Phase I evaluation of ISIS 3521, an antisense oligodeoxynucleotide to protein kinase Calpha, in patients with advanced cancer","volume":"17","author":"Nemunaitis","year":"1999","journal-title":"J Clin Oncol"},{"key":"10.3816\/CCC.2004.n.026_bib14","first-page":"3357","article-title":"Phase I study of an antisense oligonucleotide to protein kinase C-alpha (ISIS 3521\/CGP 64128A) in patients with cancer","volume":"5","author":"Yuen","year":"1999","journal-title":"Clin Cancer Res"},{"key":"10.3816\/CCC.2004.n.026_bib15","first-page":"383","article-title":"Antisense oligonucleotide inhibitors for the treatment of cancer: 1. Pharmacokinetic properties of phosphorothioate oligodeoxynucleotides","volume":"12","author":"Geary","year":"1997","journal-title":"Anticancer Drug Des"},{"key":"10.3816\/CCC.2004.n.026_bib16","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1200\/JCO.1996.14.4.1320","article-title":"Phase I trial of an antisense oligonucleotide OL (1) p53 in hematologic malignancies","volume":"14","author":"Bishop","year":"1996","journal-title":"J Clin Oncol"},{"key":"10.3816\/CCC.2004.n.026_bib17","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/0167-4781(90)90031-V","article-title":"Specific regulation of gene expression by antisense, sense and antigene nucleic acids","volume":"1049","author":"Helene","year":"1990","journal-title":"Biochim Biophys Acta"},{"key":"10.3816\/CCC.2004.n.026_bib18","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1146\/annurev.pa.36.040196.000543","article-title":"Progress in antisense oligonucleotide therapeutics","volume":"36","author":"Crooke","year":"1996","journal-title":"Annu Rev Pharmacol Toxicol"},{"key":"10.3816\/CCC.2004.n.026_bib19","first-page":"325","article-title":"Patent review: therapeutic applications for antisense oligonucleotides 1999-2000","volume":"2","author":"Orr","year":"2000","journal-title":"Curr Opin Mol Ther"},{"key":"10.3816\/CCC.2004.n.026_bib20","first-page":"3499","article-title":"Inhibition of growth of human tumor cell lines in nude mice by an antisense of oligonucleotide inhibitor of protein kinase C-alpha expression","volume":"56","author":"Dean","year":"1996","journal-title":"Cancer Res"},{"key":"10.3816\/CCC.2004.n.026_bib21","doi-asserted-by":"crossref","first-page":"16416","DOI":"10.1016\/S0021-9258(17)34023-1","article-title":"Inhibition of protein kinase C-alpha expression in human A549 cells by antisense oligonucleotides inhibits induction of intercellular adhesion molecule 1 (ICAM-1) mRNA by phorbol esters","volume":"269","author":"Dean","year":"1994","journal-title":"J Biol Chem"},{"key":"10.3816\/CCC.2004.n.026_bib22","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1002\/ijc.2910430519","article-title":"A derivative of staurosporine (CGP 41 251) shows selectivity for protein kinase C inhibition and in vitro anti-proliferative as well as in vivo anti-tumor activity","volume":"43","author":"Meyer","year":"1989","journal-title":"Int J Cancer"},{"key":"10.3816\/CCC.2004.n.026_bib23","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/S0026-895X(25)09212-0","article-title":"Treatment of glioblastoma U-87 by systemic administration of an antisense protein kinase Calpha phosphorothioate oligodeoxynucleotide","volume":"50","author":"Yazaki","year":"1996","journal-title":"Mol Pharmacol"},{"key":"10.3816\/CCC.2004.n.026_bib24","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1089\/ard.1994.4.99","article-title":"In vivo toxicological effects of rel A antisense phosphorothioates in CD-1 mice","volume":"4","author":"Sarmiento","year":"1994","journal-title":"Antisense Res Dev"},{"key":"10.3816\/CCC.2004.n.026_bib25","first-page":"409","article-title":"Toxicological and pharmacokinetic properties of chemically modified antisense oligonucleotide inhibitors of PKC-alpha and C-raf kinase","volume":"12","author":"Henry","year":"1997","journal-title":"Anticancer Drug Des"},{"key":"10.3816\/CCC.2004.n.026_bib26","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1089\/ard.1994.4.201","article-title":"Complement activation and hemodynamic changes following intravenous administration of phosphorothioate oligonucleotides in the monkey","volume":"4","author":"Galbraith","year":"1994","journal-title":"Antisense Res Dev"},{"key":"10.3816\/CCC.2004.n.026_bib27","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1089\/oli.1.1997.7.473","article-title":"Evaluation of the toxicity of ISIS 2302, a phosphorothioate oligonucleotide, in a 4-week study in CD-1mice","volume":"7","author":"Henry","year":"1997","journal-title":"Antisense Nucleic Acid Drug Dev"},{"key":"10.3816\/CCC.2004.n.026_bib28","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1089\/oli.1.1997.7.503","article-title":"Inhibition of coagulation by a phosphorothioate oligonucleotide","volume":"7","author":"Henry","year":"1997","journal-title":"Antisense Nucleic Acid Drug Dev"},{"key":"10.3816\/CCC.2004.n.026_bib29","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1016\/S0022-3565(24)36667-4","article-title":"Activation of the alternative pathway of complement by a phosphorothioate oligonucleotide: potential mechanism of action","volume":"281","author":"Henry","year":"1997","journal-title":"J Pharmacol Exp Ther"},{"key":"10.3816\/CCC.2004.n.026_bib30","doi-asserted-by":"crossref","first-page":"2227","DOI":"10.1200\/JCO.1999.17.7.2227","article-title":"Phase I clinical\/pharmacokinetic and pharmacodynamic trial of the c-raf-1 antisense oligonucleotide ISIS 5132 (CGP 69846A)","volume":"17","author":"Stevenson","year":"1999","journal-title":"J Clin Oncol"},{"key":"10.3816\/CCC.2004.n.026_bib31","first-page":"1214","article-title":"Phase I trial of ISIS 5132, an antisense oligonucleotide inhibitor of c-raf-1, administered by 24-hour weekly infusion to patients with advanced cancer","volume":"7","author":"Rudin","year":"2001","journal-title":"Clin Cancer Res"},{"key":"10.3816\/CCC.2004.n.026_bib32","first-page":"1626","article-title":"A phase I trial of c-Raf kinase antisense oligonucleotide ISIS 5132 administered as a continuous intravenous infusion in patients with advanced cancer","volume":"6","author":"Cunningham","year":"2000","journal-title":"Clin Cancer Res"},{"key":"10.3816\/CCC.2004.n.026_bib33","first-page":"3977","article-title":"c-raf-1 depletion and tumor responses in patients treated with the c-raf-1 antisense oligodeoxynucleotide ISIS 5132 (CGP 69846A)","volume":"5","author":"O'Dwyer","year":"1999","journal-title":"Clin Cancer Res"},{"key":"10.3816\/CCC.2004.n.026_bib34","doi-asserted-by":"crossref","first-page":"2194","DOI":"10.1016\/S0959-8049(01)00286-6","article-title":"Phase II trial with ISIS 5132 in patients with small-cell (SCLC) and non-small cell (NSCLC) lung cancer. A European Organization for Research and Treatment of Cancer (EORTC) Early Clinical Studies Group report","volume":"37","author":"Coudert","year":"2001","journal-title":"Eur J Cancer"},{"key":"10.3816\/CCC.2004.n.026_bib35","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1097\/00001622-199411000-00010","article-title":"Antisense oligodeoxynucleotides","volume":"6","author":"Stein","year":"1994","journal-title":"Curr Opin Oncol"},{"key":"10.3816\/CCC.2004.n.026_bib36","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1056\/NEJM199602013340508","article-title":"Antisense-oligonucleotide therapy","volume":"334","author":"Askari","year":"1996","journal-title":"N Engl J Med"},{"key":"10.3816\/CCC.2004.n.026_bib37","first-page":"44a","article-title":"A phase II trial with antisense oligonucleotide ISIS 3521\/Cgp 64128a in patients (pts) with metastatic breast cancer (MBC): ECOG Trial 3197","volume":"20","author":"Gradishar","year":"2001","journal-title":"Proc Am Soc Clin Oncol"},{"key":"10.3816\/CCC.2004.n.026_bib38","first-page":"309a","article-title":"Phase I\/II trial of ISIS 3521, an antisense inhibitor of PKC-alpha, with carboplatin and paclitaxel in non-small cell lung cancer","volume":"20","author":"Yuen","year":"2001","journal-title":"Proc Am Soc Clin Oncol"},{"key":"10.3816\/CCC.2004.n.026_bib39","first-page":"332a","article-title":"Multicenter phase II trial of an antisense inhibitor of H-ras (ISIS 2503) in advanced non-smalllung cancer (NSCLC)","volume":"20","author":"Dang","year":"2001","journal-title":"Proc Am Soc Clin Oncol"},{"key":"10.3816\/CCC.2004.n.026_bib40","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1124\/mol.60.6.1296","article-title":"Inhibition of potentially anti-apoptotic proteins by antisense protein kinase C-alpha (Isis 3521) and antisense bcl-2 (G3139) phosphorothioate oligodeoxynucleotides: relationship to the decreased viability of T24 bladder and PC3 prostate cancer cells","volume":"60","author":"Benimetskaya","year":"2001","journal-title":"Mol Pharmacol"},{"key":"10.3816\/CCC.2004.n.026_bib41","first-page":"393","article-title":"Technology evaluation: ISIS-3521","volume":"1","author":"Li","year":"1999","journal-title":"Curr Opin Mol Ther"}],"container-title":["Clinical Colorectal Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S153300281170127X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S153300281170127X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T22:58:07Z","timestamp":1761519487000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S153300281170127X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,11]]},"references-count":41,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2004,11]]}},"alternative-id":["S153300281170127X"],"URL":"https:\/\/doi.org\/10.3816\/ccc.2004.n.026","relation":{},"ISSN":["1533-0028"],"issn-type":[{"value":"1533-0028","type":"print"}],"subject":[],"published":{"date-parts":[[2004,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"A Phase II Trial of ISIS 3521 in Patients with Metastatic Colorectal Cancer","name":"articletitle","label":"Article Title"},{"value":"Clinical Colorectal Cancer","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.3816\/CCC.2004.n.026","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2004 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}