Effect of Serum Insulin2Like Growth Factor-1 on Nutritional Status of Cancerous Cachexia of Mice_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

1. Department of General S urgery ,Tong j i Hos pi tal of Tong j i Medical Col lege , Huaz hong Uni versi t y of Science and Technology , Wuhan 430030 ,China;;
2. Department of General S urgery , The People’s Hos pi tal of Zhongshan Ci t y , Guang dong Province ,Zhongshan 528403 , ChinaCorres ponding A uthor : WU Yi-ping , E-mai l : y pw u@t j h. t jmu. edu. cn;

Corresponding author：

Keywords：

Insulin2like growth factor ,Cancerous cachexia ,Cytokine ,Nut rition【Foundation item】Hubei Research Project for Natural Science (No.2002AB129)

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Objective 　To investigate the relationship between the level of serum-insulin like growth factor-1
( IGF-1) and the nut ritional status of cancerous cachexia. Methods 　Colon cancer CT-26 cells were implanted subcutaneously to 30 liver2specified IGF-1 gene deleted (L ID) C57BL/ 6 mice to establish cancerous cachexia model and the
other 30 C57BL/ 6 mice were included as cont rol group. The serum levels of IGF-1 , cytokine TNF-αand IL-6 , blood
glucose , albumin and t riglyceride were detected respectively on day 14 , 18 and 22 af ter the plantation of tumor. The
body weight of mice , tumor weight and the weight af ter tumor removed in two group s were measured respectively.
Results 　Af ter the plantation , the levels of IGF-1 in L ID group at different times were all significantly lower than
those in cont rol group ( P lt; 0. 05) . The serum levels of TNF-α, IL-6 , blood glucose and t riglyceride were ascending
gradually over time ( P lt; 0. 05) , but weight s af ter tumor removed and the level of albumin were descending in two
group s ( P lt; 0. 05) . Compared with the cont rol group , the serum levels of IL-6 , TNF-α, blood glucose and t riglyceride in L ID tumor-bearing mice were all significantly higher at different time point s ( P lt; 0. 05) . On day 18 and 22 ,
the weight s af ter tumor removed and the amount of ingestion in L ID group were significantly lower than those in the
cont rol group ( P lt; 0. 05) . Conclusion 　Compared with the low level of IGF-1 in cancerous cachexia , normal level of
serum IGF-1 may represent lower degree of cancerous cachexia2related cytokines and better nut ritional state , which
may provide a novel idea of the therapy of cancerous cachexia.

Citation： Z HA NG Shan ,CH EN Guoqing,TANG Hongbo,MA Shihui,REN Yuping,WU Yiping .. Effect of Serum Insulin2Like Growth Factor-1 on Nutritional Status of Cancerous Cachexia of Mice. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2008, 15(2): 112-115. doi: Copy

1.	Ma G,Alexandar HR.Prevalence and pathophysiology of cancer cachexia[A].In:Bruera E,Portenoy RK,eds.Topics in Palliative Care,Vol.2[M].New York:Oxford University Press,1998:91-129.
2.	MacDonald N,Easson AM,Mazurak VC,et al.Understanding and managing cancer cachexia[J].J Am Coll Surg,2003; 197(1):143.
3.	吴毅平,Yakar S,LeRoith D.循环中胰岛素样生长因子-1水平调节结肠癌的生长和转移研究[J].中华实验外科杂志,2004; 21(5):598.
4.	Yu H,Rohan T.Role of the insulin-like growth factor family in cancer development and progression[J].J Natl Cancer Inst,2000; 92(18):1472.
5.	吴毅平,Yakar S,LeRoith D.肝特异性胰岛素样生长因子-1基因缺失鼠结肠癌肝转移模型的建立[J].华中科技大学学报(医学版),2004; 33(3):300.
6.	周伟,江志伟,姜军,等.一种癌性恶病质动物模型的建立[J].中华实验外科杂志,2004; 21(4):490.
7.	Tisdale MJ.Cancer cachexia:metabolic alterations and clinical manifestations[J].Nutrition,1997; 13(1):1.
8.	Dewys WD,Begg C,Lavin PT,et al.Prognostic effect of weight loss prior to chemotherapy in cancer patients.Eastern Cooperative Oncology Group[J].Am J Med,1980; 69(4):491.
9.	Darling G,Fraker DL,Jensen JC,et al.Cachectic effects of recombinant human tumor necrosis factor in rats[J].Cancer Res,1990; 50(13):4008.
10.	Bossola M,Muscaritoli M,Bellantone R,et al.Serum tumour necrosis factor-alpha levels in cancer patients are discontinuous and correlate with weight loss[J].Eur J Clin Invest,2000; 30(12):1107.
11.	Strassmann G,Fong M,Kenney JS,et al.Evidence for the involvement of interleukin 6 in experimental cancer cachexia[J].J Clin Invest,1992; 89(5):1681.
12.	Lambert CP,Sullivan DH,Freeling SA,et al.Effects of testosterone replacement and/or resistance exercise on the composition of megestrol acetate stimulated weight gain in elderly men:a randomized controlled trial[J].J Clin Endocrinol Metab,2002; 87(5):2100.
13.	Binnerts A,Wilson JH,Lamberts SW.The effects of human growth hormone administration in elderly adults with recent weight loss[J].J Clin Endocrinol Metab,1988; 67(6):1312.
14.	Yakar S,Liu JL,Stannard B,et al.Normal growth and development in the absence of hepatic insulin-like growth factor Ⅰ[J].Proc Natl Acad Sci USA,1999; 96(13):7324.
15.	Plata-Salamán CR.Central nervous system mechanisms contributing to the cachexia-anorexia syndrome[J].Nutrition,2000; 16(10):1009.
16.	Mantovani G,Macciò A,Esu S,et al.Medroxyprogesterone acetate reduces the production of cytokines and serotonin involved in anorexia/cachexia and emesis by peripheral blood mononuclear cells of cancer patients[J].Biochem Soc Trans,1997; 25(2):296S.
17.	Yoshikawa T,Noguchi Y,Doi C,et al.Insulin resistance in patients with cancer:relationships with tumor site,tumor stage,body-weight loss,acute-phase response,and energy expenditure[J].Nutrition,2001; 17(7-8):590.
18.	Hotamisligil GS,Peraldi P,Budavari A,et al.IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha-and obesity-induced insulin resistance[J].Science,1996; 271(5249):665.
19.	Holroyde CP,Gabuzda TG,Putnam RC,et al.Altered glucose metabolism in metastatic carcinoma[J].Cancer Res,1975; 35(12):3710.
20.	Clark RP,Schuenke M,Keeton SM,et al.Effects of growth hormone and insulin-like growth factor Ⅰ on muscle in mouse models of human growth disorders[J].Horm Res,2006; 66(Suppl 1):26.

1. Ma G,Alexandar HR.Prevalence and pathophysiology of cancer cachexia[A].In:Bruera E,Portenoy RK,eds.Topics in Palliative Care,Vol.2[M].New York:Oxford University Press,1998:91-129.
2. MacDonald N,Easson AM,Mazurak VC,et al.Understanding and managing cancer cachexia[J].J Am Coll Surg,2003; 197(1):143.
3. 吴毅平,Yakar S,LeRoith D.循环中胰岛素样生长因子-1水平调节结肠癌的生长和转移研究[J].中华实验外科杂志,2004; 21(5):598.
4. Yu H,Rohan T.Role of the insulin-like growth factor family in cancer development and progression[J].J Natl Cancer Inst,2000; 92(18):1472.
5. 吴毅平,Yakar S,LeRoith D.肝特异性胰岛素样生长因子-1基因缺失鼠结肠癌肝转移模型的建立[J].华中科技大学学报(医学版),2004; 33(3):300.
6. 周伟,江志伟,姜军,等.一种癌性恶病质动物模型的建立[J].中华实验外科杂志,2004; 21(4):490.
7. Tisdale MJ.Cancer cachexia:metabolic alterations and clinical manifestations[J].Nutrition,1997; 13(1):1.
8. Dewys WD,Begg C,Lavin PT,et al.Prognostic effect of weight loss prior to chemotherapy in cancer patients.Eastern Cooperative Oncology Group[J].Am J Med,1980; 69(4):491.
9. Darling G,Fraker DL,Jensen JC,et al.Cachectic effects of recombinant human tumor necrosis factor in rats[J].Cancer Res,1990; 50(13):4008.
10. Bossola M,Muscaritoli M,Bellantone R,et al.Serum tumour necrosis factor-alpha levels in cancer patients are discontinuous and correlate with weight loss[J].Eur J Clin Invest,2000; 30(12):1107.
11. Strassmann G,Fong M,Kenney JS,et al.Evidence for the involvement of interleukin 6 in experimental cancer cachexia[J].J Clin Invest,1992; 89(5):1681.
12. Lambert CP,Sullivan DH,Freeling SA,et al.Effects of testosterone replacement and/or resistance exercise on the composition of megestrol acetate stimulated weight gain in elderly men:a randomized controlled trial[J].J Clin Endocrinol Metab,2002; 87(5):2100.
13. Binnerts A,Wilson JH,Lamberts SW.The effects of human growth hormone administration in elderly adults with recent weight loss[J].J Clin Endocrinol Metab,1988; 67(6):1312.
14. Yakar S,Liu JL,Stannard B,et al.Normal growth and development in the absence of hepatic insulin-like growth factor Ⅰ[J].Proc Natl Acad Sci USA,1999; 96(13):7324.
15. Plata-Salamán CR.Central nervous system mechanisms contributing to the cachexia-anorexia syndrome[J].Nutrition,2000; 16(10):1009.
16. Mantovani G,Macciò A,Esu S,et al.Medroxyprogesterone acetate reduces the production of cytokines and serotonin involved in anorexia/cachexia and emesis by peripheral blood mononuclear cells of cancer patients[J].Biochem Soc Trans,1997; 25(2):296S.
17. Yoshikawa T,Noguchi Y,Doi C,et al.Insulin resistance in patients with cancer:relationships with tumor site,tumor stage,body-weight loss,acute-phase response,and energy expenditure[J].Nutrition,2001; 17(7-8):590.
18. Hotamisligil GS,Peraldi P,Budavari A,et al.IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha-and obesity-induced insulin resistance[J].Science,1996; 271(5249):665.
19. Holroyde CP,Gabuzda TG,Putnam RC,et al.Altered glucose metabolism in metastatic carcinoma[J].Cancer Res,1975; 35(12):3710.
20. Clark RP,Schuenke M,Keeton SM,et al.Effects of growth hormone and insulin-like growth factor Ⅰ on muscle in mouse models of human growth disorders[J].Horm Res,2006; 66(Suppl 1):26.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Effect of Serum Insulin2Like Growth Factor-1 on Nutritional Status of Cancerous Cachexia of Mice

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