BACKGROUND: Colorectal liver metastases (mets) are often refractory to conventional therapies. CpG oligodeoxynucleotide 1826 (CpG), a Toll like receptor (TLR)-9 agonist, inhibits murine tumor growth by augmenting Th1 immunity. The impact of CpG on metastatic colon tumors is unknown. The purpose of this study was to determine the effect of CpG on the growth of hepatic colon cancer mets. METHODS: Two studies with separate control groups were performed using 40 Balb/C mice (study A, CpG 50 μg/dose; study B, 100 μg/dose; n = 9-11/subgroup). Tumors were induced via portal vein injection of 2 × 10(4) CT26 colon tumor cells. After surgery, the mice were randomized; test groups were given 14 daily intraperitoneal (i.p.) CpG injections (50 or 100 μg/dose) while the control group received i.p. saline. On d 21 mice were sacrificed, the livers and spleens excised and weighed and the mets counted (reported as median ± 95% confidence interval [CI]) and histologically assessed. RESULTS: The CpG mice had significantly fewer hepatic mets/mouse (study A, median two nodules, 95% CI, 0-3; study B, 0 nodules, 95% CI 0-0) than the control mice (study A, 6 nodules, 95% CI, 3-9, P = 0.002; Study B, 6 nodules, 95% CI, 3-9, P < 0.001). In study B, there were no mets in 9/11 CpG mice (versus 2/10 for CpG 50 μg and 0/19 for control mice). The mean liver/spleen weights of the CpG mice in both studies were significantly greater than in control mice. Histologically, high mitotic rates were noted in control mets while fewer tumor cells and histiocytic and lymphocytic infiltrates were found in CpG livers. CONCLUSIONS: CpG inhibited liver tumor growth in this model (100 μg/dose more than 50 μg/dose). CpG was associated with increased liver and spleen weights not related to tumor burden. Increased lymphocytic and histiocytic infiltrates were noted in CpG-treated tumor nodules.
BACKGROUND:Colorectal liver metastases (mets) are often refractory to conventional therapies. CpG oligodeoxynucleotide 1826 (CpG), a Toll like receptor (TLR)-9 agonist, inhibits murinetumor growth by augmenting Th1 immunity. The impact of CpG on metastatic colon tumors is unknown. The purpose of this study was to determine the effect of CpG on the growth of hepatic colon cancer mets. METHODS: Two studies with separate control groups were performed using 40 Balb/C mice (study A, CpG 50 μg/dose; study B, 100 μg/dose; n = 9-11/subgroup). Tumors were induced via portal vein injection of 2 × 10(4) CT26 colon tumor cells. After surgery, the mice were randomized; test groups were given 14 daily intraperitoneal (i.p.) CpG injections (50 or 100 μg/dose) while the control group received i.p. saline. On d 21 mice were sacrificed, the livers and spleens excised and weighed and the mets counted (reported as median ± 95% confidence interval [CI]) and histologically assessed. RESULTS: The CpG mice had significantly fewer hepatic mets/mouse (study A, median two nodules, 95% CI, 0-3; study B, 0 nodules, 95% CI 0-0) than the control mice (study A, 6 nodules, 95% CI, 3-9, P = 0.002; Study B, 6 nodules, 95% CI, 3-9, P < 0.001). In study B, there were no mets in 9/11 CpG mice (versus 2/10 for CpG 50 μg and 0/19 for control mice). The mean liver/spleen weights of the CpG mice in both studies were significantly greater than in control mice. Histologically, high mitotic rates were noted in control mets while fewer tumor cells and histiocytic and lymphocytic infiltrates were found in CpG livers. CONCLUSIONS: CpG inhibited liver tumor growth in this model (100 μg/dose more than 50 μg/dose). CpG was associated with increased liver and spleen weights not related to tumor burden. Increased lymphocytic and histiocytic infiltrates were noted in CpG-treated tumor nodules.
Authors: Keith I Block; Charlotte Gyllenhaal; Leroy Lowe; Amedeo Amedei; A R M Ruhul Amin; Amr Amin; Katia Aquilano; Jack Arbiser; Alexandra Arreola; Alla Arzumanyan; S Salman Ashraf; Asfar S Azmi; Fabian Benencia; Dipita Bhakta; Alan Bilsland; Anupam Bishayee; Stacy W Blain; Penny B Block; Chandra S Boosani; Thomas E Carey; Amancio Carnero; Marianeve Carotenuto; Stephanie C Casey; Mrinmay Chakrabarti; Rupesh Chaturvedi; Georgia Zhuo Chen; Helen Chen; Sophie Chen; Yi Charlie Chen; Beom K Choi; Maria Rosa Ciriolo; Helen M Coley; Andrew R Collins; Marisa Connell; Sarah Crawford; Colleen S Curran; Charlotta Dabrosin; Giovanna Damia; Santanu Dasgupta; Ralph J DeBerardinis; William K Decker; Punita Dhawan; Anna Mae E Diehl; Jin-Tang Dong; Q Ping Dou; Janice E Drew; Eyad Elkord; Bassel El-Rayes; Mark A Feitelson; Dean W Felsher; Lynnette R Ferguson; Carmela Fimognari; Gary L Firestone; Christian Frezza; Hiromasa Fujii; Mark M Fuster; Daniele Generali; Alexandros G Georgakilas; Frank Gieseler; Michael Gilbertson; Michelle F Green; Brendan Grue; Gunjan Guha; Dorota Halicka; William G Helferich; Petr Heneberg; Patricia Hentosh; Matthew D Hirschey; Lorne J Hofseth; Randall F Holcombe; Kanya Honoki; Hsue-Yin Hsu; Gloria S Huang; Lasse D Jensen; Wen G Jiang; Lee W Jones; Phillip A Karpowicz; W Nicol Keith; Sid P Kerkar; Gazala N Khan; Mahin Khatami; Young H Ko; Omer Kucuk; Rob J Kulathinal; Nagi B Kumar; Byoung S Kwon; Anne Le; Michael A Lea; Ho-Young Lee; Terry Lichtor; Liang-Tzung Lin; Jason W Locasale; Bal L Lokeshwar; Valter D Longo; Costas A Lyssiotis; Karen L MacKenzie; Meenakshi Malhotra; Maria Marino; Maria L Martinez-Chantar; Ander Matheu; Christopher Maxwell; Eoin McDonnell; Alan K Meeker; Mahya Mehrmohamadi; Kapil Mehta; Gregory A Michelotti; Ramzi M Mohammad; Sulma I Mohammed; D James Morre; Vinayak Muralidhar; Irfana Muqbil; Michael P Murphy; Ganji Purnachandra Nagaraju; Rita Nahta; Elena Niccolai; Somaira Nowsheen; Carolina Panis; Francesco Pantano; Virginia R Parslow; Graham Pawelec; Peter L Pedersen; Brad Poore; Deepak Poudyal; Satya Prakash; Mark Prince; Lizzia Raffaghello; Jeffrey C Rathmell; W Kimryn Rathmell; Swapan K Ray; Jörg Reichrath; Sarallah Rezazadeh; Domenico Ribatti; Luigi Ricciardiello; R Brooks Robey; Francis Rodier; H P Vasantha Rupasinghe; Gian Luigi Russo; Elizabeth P Ryan; Abbas K Samadi; Isidro Sanchez-Garcia; Andrew J Sanders; Daniele Santini; Malancha Sarkar; Tetsuro Sasada; Neeraj K Saxena; Rodney E Shackelford; H M C Shantha Kumara; Dipali Sharma; Dong M Shin; David Sidransky; Markus David Siegelin; Emanuela Signori; Neetu Singh; Sharanya Sivanand; Daniel Sliva; Carl Smythe; Carmela Spagnuolo; Diana M Stafforini; John Stagg; Pochi R Subbarayan; Tabetha Sundin; Wamidh H Talib; Sarah K Thompson; Phuoc T Tran; Hendrik Ungefroren; Matthew G Vander Heiden; Vasundara Venkateswaran; Dass S Vinay; Panagiotis J Vlachostergios; Zongwei Wang; Kathryn E Wellen; Richard L Whelan; Eddy S Yang; Huanjie Yang; Xujuan Yang; Paul Yaswen; Clement Yedjou; Xin Yin; Jiyue Zhu; Massimo Zollo Journal: Semin Cancer Biol Date: 2015-12 Impact factor: 15.707