PMID- 17097874 OWN - NLM STAT- MEDLINE DCOM- 20070329 LR - 20121115 IS - 0960-7404 (Print) IS - 0960-7404 (Linking) VI - 15 IP - 2 DP - 2006 Aug TI - Alvocidib (Flavopiridol) suppresses tumor growth in SCID mice with human esophageal cancer xenografts without inducing apoptosis. PG - 107-13 AB - Alvocidib (Flavopiridol, HMR1275) is a potent inhibitor of multiple cyclin-dependent kinases and has been identified recently as an antitumor agent in several cancers. Previous studies have shown that alvocidib could potentially treat esophageal cancer in vitro. This study evaluates alvocidib for its ability to suppress tumor growth in severe combined immunodeficiency (SCID) mice bearing TE8 human esophageal squamous cell carcinoma (SCC) xenografts. Alvocidib treatment of 10mg/kg body weight reduced tumor volume significantly. Immunohistochemistry analysis of alvocidib-treated tumor sections showed significant reductions in cyclin D1, VEGF, and Rb levels. Alvocidib treatment did not cause a marked increase in apoptotic tumor cells by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) analysis, yet hematoxylin and eosin staining revealed tumor necrosis. In vivo investigation of alvocidib treatment confirmed antitumor activity in TE8 esophageal xenografts. These findings suggest that alvocidib could be a useful anti-cancer agent for esophageal cancer. FAU - Sato, Shinsuke AU - Sato S AD - Department of Gastroenterological Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. ssato@maz.miinet.or.jp FAU - Kajiyama, Yoshiaki AU - Kajiyama Y FAU - Sugano, Masahiko AU - Sugano M FAU - Iwanuma, Yoshimi AU - Iwanuma Y FAU - Sonoue, Hiroshi AU - Sonoue H FAU - Matsumoto, Toshiharu AU - Matsumoto T FAU - Tsurumaru, Masahiko AU - Tsurumaru M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20061113 PL - Netherlands TA - Surg Oncol JT - Surgical oncology JID - 9208188 RN - 0 (Antineoplastic Agents) RN - 0 (Flavonoids) RN - 0 (Piperidines) RN - 0 (Retinoblastoma Protein) RN - 0 (Vascular Endothelial Growth Factor A) RN - 136601-57-5 (Cyclin D1) RN - 45AD6X575G (alvocidib) SB - IM MH - Animals MH - Antineoplastic Agents/pharmacology MH - *Apoptosis MH - Cell Line, Tumor MH - Cyclin D1/biosynthesis MH - Esophageal Neoplasms/*drug therapy/*genetics/*pathology MH - Female MH - Flavonoids/*pharmacology MH - Humans MH - Immunohistochemistry MH - In Situ Nick-End Labeling MH - Mice MH - Mice, SCID MH - Necrosis MH - Neoplasm Transplantation MH - Piperidines/*pharmacology MH - Retinoblastoma Protein/biosynthesis MH - Vascular Endothelial Growth Factor A/biosynthesis EDAT- 2006/11/14 09:00 MHDA- 2007/03/30 09:00 CRDT- 2006/11/14 09:00 PHST- 2006/08/27 00:00 [received] PHST- 2006/10/02 00:00 [accepted] PHST- 2006/11/14 09:00 [pubmed] PHST- 2007/03/30 09:00 [medline] PHST- 2006/11/14 09:00 [entrez] AID - S0960-7404(06)00052-1 [pii] AID - 10.1016/j.suronc.2006.10.001 [doi] PST - ppublish SO - Surg Oncol. 2006 Aug;15(2):107-13. doi: 10.1016/j.suronc.2006.10.001. Epub 2006 Nov 13.