CpG ODN, Toll like receptor (TLR)-9 agonist, inhibits metastatic colon adenocarcinoma in a murine hepatic tumor model

Ik Yong Kim, Xiaohong Yan, Samer Tohme, Aqeel Ahmed, Carlos Cordon-Cardo, H. M.C. Shantha Kumara, Soo Ki Kim, Richard L. Whelan

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)284-290
Number of pages7
JournalJournal of Surgical Research
Volume174
Issue number2
DOIs
Publication statusPublished - 2012 May 15

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Toll-Like Receptor 9
Colon
Adenocarcinoma
Liver
Neoplasms
Neoplasm Metastasis
Confidence Intervals
Spleen
Growth
Weights and Measures
Control Groups
Oligodeoxyribonucleotides
Liver Neoplasms
Portal Vein
Tumor Burden
Intraperitoneal Injections
Colonic Neoplasms
Immunity

All Science Journal Classification (ASJC) codes

  • Surgery

Cite this

Kim, Ik Yong ; Yan, Xiaohong ; Tohme, Samer ; Ahmed, Aqeel ; Cordon-Cardo, Carlos ; Shantha Kumara, H. M.C. ; Kim, Soo Ki ; Whelan, Richard L. / CpG ODN, Toll like receptor (TLR)-9 agonist, inhibits metastatic colon adenocarcinoma in a murine hepatic tumor model. In: Journal of Surgical Research. 2012 ; Vol. 174, No. 2. pp. 284-290.
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title = "CpG ODN, Toll like receptor (TLR)-9 agonist, inhibits metastatic colon adenocarcinoma in a murine hepatic tumor model",
abstract = "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.",
author = "Kim, {Ik Yong} and Xiaohong Yan and Samer Tohme and Aqeel Ahmed and Carlos Cordon-Cardo and {Shantha Kumara}, {H. M.C.} and Kim, {Soo Ki} and Whelan, {Richard L.}",
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CpG ODN, Toll like receptor (TLR)-9 agonist, inhibits metastatic colon adenocarcinoma in a murine hepatic tumor model. / Kim, Ik Yong; Yan, Xiaohong; Tohme, Samer; Ahmed, Aqeel; Cordon-Cardo, Carlos; Shantha Kumara, H. M.C.; Kim, Soo Ki; Whelan, Richard L.

In: Journal of Surgical Research, Vol. 174, No. 2, 15.05.2012, p. 284-290.

Research output: Contribution to journalArticle

TY - JOUR

T1 - CpG ODN, Toll like receptor (TLR)-9 agonist, inhibits metastatic colon adenocarcinoma in a murine hepatic tumor model

AU - Kim, Ik Yong

AU - Yan, Xiaohong

AU - Tohme, Samer

AU - Ahmed, Aqeel

AU - Cordon-Cardo, Carlos

AU - Shantha Kumara, H. M.C.

AU - Kim, Soo Ki

AU - Whelan, Richard L.

PY - 2012/5/15

Y1 - 2012/5/15

N2 - 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.

AB - 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.

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