Effect of Human Growth Hormone on Growth Situation and Hematopoietic Function in Rats under Chemotherapy_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

ZHANG Yi ¹ , CHEN Jiayong ¹ , LIANG Daoming ¹ , YUAN Yong ¹ , ZHOU Dong ¹ , WU Xiaoting ²

1.Department of Emergency, The Second Affiliated Hospital of Kunming Medical College, Kunming 650101, China;;
2.Surgery Center of Gastroenterology， West China Hospital， Sichuan University， Chengdu 610041， China;

Corresponding author：

Keywords：

Human growth hormone; Chemotherapy; Hematopoietic function; Growth situation

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Objective To investigate the effect of recombinant human growth hormone (hGH) on growth situation and bone marrow hematopoietic function in rats under chemotherapy. Methods A total of 136 10-week-old SD rats were included in the study. The rats were randomly assigned into five groups: normal control group (n=8), normal saline control group (NS group, n=32), human growth hormone group (hGH group, n=32), chemotherapeutic drug treated group (CT group, n=32), and chemotherapeutic drug plus hGH treated group (CT+hGH group, n=32). The body weight, bone marrow differential count, and the expression of proliferating cell nuclear antigen (PCNA) in bone marrow were measured before treatment and weekly in four weeks after treatment. Results Weight loss occurred in both CT group and CT+hGH group (P＜0.05), but the weight loss in CT+hGH group was significantly smaller (P＜0.05) on day 7 after treatment. In myeloid morphology, myeloid cell was hypoplastic excessively in CT group, and it was hypoplastic obviously in CT+hGH group on day 7 after treatment. Day 14, weight gain appeared in CT+hGH group, while weight loss remained in CT group; In myeloid morphology, myeloid cell was hyperplastic actively excessively in CT+hGH group, and myeloid karyote count was increased significantly in CT+hGH group (P＜0.05). Day 7, 14 and 21, PCNA positive cells count in CT group was lower than that in hGH group and CT+hGH group (P＜0.05). There was no significant different of every index among normal control group, NS group, and hGH group (P gt;0.05), except weight between normal control group and hGH group on day 7 (P＜0.05). Conclusion hGH has a protective effect on myeloid hematopoietic function and growth situation in rats after intraperitoneal chemotherapy.

Citation： ZHANG Yi,CHEN Jiayong,LIANG Daoming,YUAN Yong,ZHOU Dong,WU Xiaoting. Effect of Human Growth Hormone on Growth Situation and Hematopoietic Function in Rats under Chemotherapy. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2009, 16(12): 958-963. doi: Copy

1.	Fahlke J, Ridwelski K, Schmidt C, et al. A multicentre phase Ⅱ study of docetaxel plus cisplatin for the treatment of advanced gastric cancer [J]. Chemotherapy, 2007; 53(6): 454-460.
2.	Hofmann MA, Gabriel V, Milling A, et al. High-dose platinum combination therapy in pretreated patients with disseminated melanoma [J]. Chemotherapy, 2007; 53(6): 422-428.
3.	Shimonov M, Hayat H, Chaitchik S, et al. Combined systemic chronotherapy and hepatic artery infusion for the treatment of metastatic colorectal cancer confined to the liver [J]. Chemotherapy, 2005; 51（2-3）: 111-115.
4.	Bozzeti F, Gavazzi C, Mariani L, et al. Artificicial nutrition in cancer patients: which route, what composition [J]. World J Sury, 1999; 23(6): 577-583.
5.	Vara-Thorbeck R, Guerrero JA, Ruiz-Requena E, et al. Can the use of growth hormone reduced the postoperative fatigue syndrome? [J]. World J Surg, 1996; 20(1): 81-87.
6.	杨澄宇, 李伟明, 骆曦图. 应用重组人生长激素改善高龄病人术后疲劳综合征的临床研究 [J]. 肠外与肠内营养， 2003； 10(3): 160-162.
7.	祁晓平, 黎介寿, 陈彻. 人生长激素对人结肠癌细胞LS-174-T增殖周期的影响 [J]. 肠内与肠外营养, 2001； 8(1): 8-10.
8.	Tacke J, Bolder U, Herrmann A, et al. Long-term risk of gastrointestinal tumor recurrence after postoperative treatment with recombinant human growth hormone [J]. JPEN J Parenter Enteral Nutr， 2000; 24(3): 140-144.
9.	Swerdlow AJ, Higgins CD, Adlard P, et al. Risk of cancer in patients treated with human pituitary growth hormone in the UK, 1959-85: a cohort study [J]. Lancet, 2002; 360(9329): 273-277.
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11.	陈嘉勇, 张捷, 谭晶, 等. 胃结肠癌患者术后生长激素应用的价值评估 [J]. 中国普外基础与临床杂志, 1999; 6(6): 365-367.
12.	陈嘉勇, 甘平, 梁道明, 等. 重组人生长激素在体外对人直肠癌细胞株HR8348增殖的影响 [J]. 中国普外基础与临床杂志, 2003; 10(4): 362-365.
13.	陈嘉勇, 梁道明, 甘平, 等. 重组人生长激素对胃癌细胞生长的影响 [J]. 中华普通外科杂志, 2004; 19(12): 741-743.
14.	陈嘉勇, 梁道明, 甘平, 等. 人生长激素在体外对人胃癌细胞的作用 [J]. 中华实验外科杂志, 2004; 21(5): 521-523.
15.	Ng B, Wolf RF, Weksler B, et al. Growth hormone administration preserves lean body mass in sarcoma-bearing rats treated with doxorubicin [J]. Cancer Res, 1993; 53(22): 5483-5486.
16.	Sirohi B, Powles R, Morgan G, et al. Use of physiological doses of human growth hormone in haematological patients receiving intensive chemotherapy promotes haematopoietic recovery: a double-blind randomized, placebo-controlled study [J]. Bone Marrow Transplant， 2007; 39(2): 115-120.
17.	Murphy WJ, Tsarfaty G, Longo DL. Growth hormone exerts hematopoietic growth-promoting effects in vivo and partially counteracts the myelosuppressive effects of azidothymidine [J]. Blood, 1992; 80(6): 1443-1447.
18.	Carlo-Stella C, Di Nicola M, Milani R， et al. Age- and irradiation-associated loss of bone marrow hematopoietic function in mice is reversed by recombinant human growth hormone [J]. Exp Hematol， 2004; 32(2): 171-178.
19.	Carlo-Stella C, Di Nicola M, Milani R, et al. Use of recombinant human growth hormone (rhGH) plus recombinant human granulocyte colony-stimulating factor (rhG-CSF) for the mobilization and collection of CD34+ cells in poor mobilizers [J]. Blood， 2004; 103(9): 3287-3295.
20.	Golde DW, Bersch N, Li CH. Growth hormone: Species-specific stimulation of erythropoiesis in vitro [J]. Science， 1977; 196（4294）: 1112-1113.
21.	Merchav S, Tatarsky I, Hochberg Z. Enhancement of human granulopoiesis in vitro by biosynthetic insulin-like growth factor Ⅰ/somatomedin C and human growth hormone [J]. J Clin Invest， 1988; 81（3）: 791-797.
22.	Tian ZG, Woody MA. Sun R, et al. Recombinant human growth hormone promotes hematopoietic reconstitution after syngeneic bone marrow transplantation in mice [J]. Stem Cells, 1998； 16(3): 193-199.
23.	Jones JI, Clemmons DR. Insulin-like growth factors and their binding proteins: biological actings [J]. Endocr Rev, 1995； 16(1): 30-34.
24.	Tsarfaty G, Longo DL, Murphy WJ. Human insulin-like gr-owth factor Ⅰ exerts hematopoietic growth-promoting effects after in vivo administration [J]. Exp Hematol， 1994； 22（13）: 1273-1277.
25.	Conzemius MG, Graham JC, Haynes JS, et al. Effects of treatment with growth hormone and somatostatin on efficacy of diammine [1, 1-cyclobutane dicarboxylato (2-)-0,0’]-(SP-4-2) in athymic rats with osteosarcoma [J]. Am J Vet Res, 2000； 61(6): 646-650.

1. Fahlke J, Ridwelski K, Schmidt C, et al. A multicentre phase Ⅱ study of docetaxel plus cisplatin for the treatment of advanced gastric cancer [J]. Chemotherapy, 2007; 53(6): 454-460.
2. Hofmann MA, Gabriel V, Milling A, et al. High-dose platinum combination therapy in pretreated patients with disseminated melanoma [J]. Chemotherapy, 2007; 53(6): 422-428.
3. Shimonov M, Hayat H, Chaitchik S, et al. Combined systemic chronotherapy and hepatic artery infusion for the treatment of metastatic colorectal cancer confined to the liver [J]. Chemotherapy, 2005; 51（2-3）: 111-115.
4. Bozzeti F, Gavazzi C, Mariani L, et al. Artificicial nutrition in cancer patients: which route, what composition [J]. World J Sury, 1999; 23(6): 577-583.
5. Vara-Thorbeck R, Guerrero JA, Ruiz-Requena E, et al. Can the use of growth hormone reduced the postoperative fatigue syndrome? [J]. World J Surg, 1996; 20(1): 81-87.
6. 杨澄宇, 李伟明, 骆曦图. 应用重组人生长激素改善高龄病人术后疲劳综合征的临床研究 [J]. 肠外与肠内营养， 2003； 10(3): 160-162.
7. 祁晓平, 黎介寿, 陈彻. 人生长激素对人结肠癌细胞LS-174-T增殖周期的影响 [J]. 肠内与肠外营养, 2001； 8(1): 8-10.
8. Tacke J, Bolder U, Herrmann A, et al. Long-term risk of gastrointestinal tumor recurrence after postoperative treatment with recombinant human growth hormone [J]. JPEN J Parenter Enteral Nutr， 2000; 24(3): 140-144.
9. Swerdlow AJ, Higgins CD, Adlard P, et al. Risk of cancer in patients treated with human pituitary growth hormone in the UK, 1959-85: a cohort study [J]. Lancet, 2002; 360(9329): 273-277.
10. Fiebig HH, Dengler W, Hendriks HR. No evidence of tumor growth stimulation in human tumors in vitro following treatment with recombinant human growth hormone [J]. Anticancer Drugs, 2000; 11(8): 659-664.
11. 陈嘉勇, 张捷, 谭晶, 等. 胃结肠癌患者术后生长激素应用的价值评估 [J]. 中国普外基础与临床杂志, 1999; 6(6): 365-367.
12. 陈嘉勇, 甘平, 梁道明, 等. 重组人生长激素在体外对人直肠癌细胞株HR8348增殖的影响 [J]. 中国普外基础与临床杂志, 2003; 10(4): 362-365.
13. 陈嘉勇, 梁道明, 甘平, 等. 重组人生长激素对胃癌细胞生长的影响 [J]. 中华普通外科杂志, 2004; 19(12): 741-743.
14. 陈嘉勇, 梁道明, 甘平, 等. 人生长激素在体外对人胃癌细胞的作用 [J]. 中华实验外科杂志, 2004; 21(5): 521-523.
15. Ng B, Wolf RF, Weksler B, et al. Growth hormone administration preserves lean body mass in sarcoma-bearing rats treated with doxorubicin [J]. Cancer Res, 1993; 53(22): 5483-5486.
16. Sirohi B, Powles R, Morgan G, et al. Use of physiological doses of human growth hormone in haematological patients receiving intensive chemotherapy promotes haematopoietic recovery: a double-blind randomized, placebo-controlled study [J]. Bone Marrow Transplant， 2007; 39(2): 115-120.
17. Murphy WJ, Tsarfaty G, Longo DL. Growth hormone exerts hematopoietic growth-promoting effects in vivo and partially counteracts the myelosuppressive effects of azidothymidine [J]. Blood, 1992; 80(6): 1443-1447.
18. Carlo-Stella C, Di Nicola M, Milani R， et al. Age- and irradiation-associated loss of bone marrow hematopoietic function in mice is reversed by recombinant human growth hormone [J]. Exp Hematol， 2004; 32(2): 171-178.
19. Carlo-Stella C, Di Nicola M, Milani R, et al. Use of recombinant human growth hormone (rhGH) plus recombinant human granulocyte colony-stimulating factor (rhG-CSF) for the mobilization and collection of CD34+ cells in poor mobilizers [J]. Blood， 2004; 103(9): 3287-3295.
20. Golde DW, Bersch N, Li CH. Growth hormone: Species-specific stimulation of erythropoiesis in vitro [J]. Science， 1977; 196（4294）: 1112-1113.
21. Merchav S, Tatarsky I, Hochberg Z. Enhancement of human granulopoiesis in vitro by biosynthetic insulin-like growth factor Ⅰ/somatomedin C and human growth hormone [J]. J Clin Invest， 1988; 81（3）: 791-797.
22. Tian ZG, Woody MA. Sun R, et al. Recombinant human growth hormone promotes hematopoietic reconstitution after syngeneic bone marrow transplantation in mice [J]. Stem Cells, 1998； 16(3): 193-199.
23. Jones JI, Clemmons DR. Insulin-like growth factors and their binding proteins: biological actings [J]. Endocr Rev, 1995； 16(1): 30-34.
24. Tsarfaty G, Longo DL, Murphy WJ. Human insulin-like gr-owth factor Ⅰ exerts hematopoietic growth-promoting effects after in vivo administration [J]. Exp Hematol， 1994； 22（13）: 1273-1277.
25. Conzemius MG, Graham JC, Haynes JS, et al. Effects of treatment with growth hormone and somatostatin on efficacy of diammine [1, 1-cyclobutane dicarboxylato (2-)-0,0’]-(SP-4-2) in athymic rats with osteosarcoma [J]. Am J Vet Res, 2000； 61(6): 646-650.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Effect of Human Growth Hormone on Growth Situation and Hematopoietic Function in Rats under Chemotherapy

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