不同CO_2压力状态对卵巢癌SKOV_3细胞增殖、侵袭力影响的实验研究
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
近十年,腹腔镜技术已经取得令人瞩目的成就,同时,腹腔镜恶性肿瘤手术的安全性问题也越来越受到关注。临床上已有腹腔镜肿瘤外科手术后穿刺孔和腹膜肿瘤种植率高于开腹手术、残余肿瘤生长迅速等病例报道。以二氧化碳(carbon dioxide,C02)建立人工气腹是腹腔镜与传统妇科手术方式的主要病理生理差异。但临床报道腹腔镜的相关并发症多与手术操作失误有关,且关于C02与恶性肿瘤细胞的生长和转移关系的细胞学及动物实验报道的结论并不完全一致,甚至有相悖。本研究拟通过模拟实际腹腔镜操作环境,建立不同C02压力梯度,系统观察其对卵巢癌SKOV3细胞体外、体内生长及粘附、转移特性的影响并探讨相关机制,初步评估腹腔镜C02气腹用于妇科恶性肿瘤的安全性。
     第一部份不同CO2压力状态对卵巢癌SKOV3细胞体外增殖能力的影响
     【目的】通过观察模拟腹腔镜实际操作时的不同C02压力、作用不同时间对卵巢癌SKOV3细胞体外生长、增殖能力的影响,评估C02人工气腹对恶性卵巢肿瘤细胞体外生长、增殖的直接作用并探讨相关机制。
In the last decade of the 20th century, laparoscopic areas have gained remarkable achievements. The advantages of minimally invasive surgery—including less pain, quicker recovery, and shorter hospitalization time—have been realized in patients with intra-abdominal malignancies. However, more and more concerns about the safety of laparoscopy treatment have been aroused. A few clinical trials have reported that port site tumor metastases (PSM) and higher peritoneal tumor metastasis (PTM), rapidly growth rate of residual carcinoma in laparoscopic procedures than opening procedures. Compared with traditional operative procedures, the main pathologicphysiolic difference between the two methods is cause by pnemumoperitoneum with carbon dioxide (C02). On the other hand, most of the complications are related with improper manipulation. Furthermore, no consistent conclusion of the in vitro and in vivo experiments about C02 and the proliferation, adhesion and invasion of carcinoma has been drawn.
     Therefore, this research is aimed to systematically observe the influences of different C02 pressure models to imitating realistic laparoscopic manipulation situation on the proliferate, adhesive and
引文
[1]. Gil-Moreno A, Puig O, Perez-Benavente MA, et al. Total laparoscopic radical hysterectomy (type II-III) with pelvic lympHadenectomy in early invasive cervical cancer[J]. J Minim Invasive Gynecol. 2005;12(2):113-20
    [2]. Holub Z, Jabor A, Bartos P, et al. Laparoscopic surgery in women with endometrial cancer: the learning curve[J]. Eur J Obstet Gynecol Reprod Biol. 2003;107(2):195-200
    [3]. Kosugi C, Ono M, Saito N, et al. Port site recurrence diagnosed by positron emission tomograpHy after laparoscopic surgery for colon cancer. Hepatogastroenterology[J]. 2005;52(65):1440-3
    [4]. Izumi K, Ishikawa K, Shiroshita H, et al. MorpHological changes in hepatic vascular endothelium after carbon dioxide pneumoperitoneum in a murine model.Surg Endosc[J]. 2005,19:554-558
    [5]. Wittich P, Mearadji A, Marquet RL,et al.Increased tumor growth after high pressure pneumoperitoneum with helium and air[J]. J Laparoendosc Adv Surg Tech A,2004,14:205-208
    [6]. Curet MJ. Port site metastases[J]. Am J Surg,2004,187:705-712
    [7]. Zayyan KS, Christie-Brown JS, Van Noorden S, et al. Rapid flow carbon dioxide laparoscopy disperses cancer cells into the peritoneal cavity but not the port sites in a new rat model[J]. Surg Endosc. 2003;17(2):273-7.
    [8]. The Clinical Outcomes of Surgical Therapy Study Group(2004).A comparison of laparoscopically assisted and open colectomy for colon cancer[J]. N Engl J Med,2004,350:2050–2059.
    [9]. Lacy AM, Garcia-Valdecasas JC, Delgado S,et al. Laparoscopy-assisted colectomy versus open colectomy for treatment of non-metastatic colon cancer: a randomised trial[J]. Lancet,2002,359:2296–2229.
    [10]. Hirabayashi Y, Yamaguchi K, Shiraishi N, etal. Development of port site metastasis after pneumoperitoneum[J]. Surg Endosc,2002,16: 864-868.Schmeding M, Schwalbach P, Reinshagen S,etal. Helium pneumoperitoneum reduces tumor recurrence after curative laparoscopic liver resection in rats in a tumor-bearing small animal model[J]. Surg Endosc,2003,17:951-959
    [12]. Schafer M, Krahenbuhl L. Effect of laparoscopy on intraabdominal blood flow[J]. Surgery,2001,129:385–389.
    [13]. Schmandra TC, Kim ZG, Gutt CN. Effect of insulation gas and intraabdominal pressure on portal venous flow during pneumoperitoneum in the rat[J]. Surg Endosc,2001,15:405–408.
    [14]. Ost MC, Tan BJ, Lee B, et al.Urological laparoscopy: basic pHysiological considerations and immunological consequences[J]. J Urol,2005,174:1183-1188.
    [15]. 刘国礼. 现代微创外科学[M].北京,科学出版社,2003 年第 1 版,40-42.
    [16]. 司徒镇强,吴军政. 细胞的生存环境. 细胞培养[M]. 西安,世界图书出版社, 第一版,2004 年,19.
    [17]. 张爱容,孔北华. 纯二氧化碳气体环境对卵巢癌细胞株生长增殖的影响[A]中国优秀硕、博士学位论文.二氧化碳气腹环境对卵巢癌生长、转移影响的实验研究. 2004,12-26.
    [18]. 徐春阳,粱志清,熊光武. 二氧化碳人工气腹对子宫内膜癌细胞体外生长的影响[J].中华妇产科杂志,2003,38:766-767.
    [19]. 蒋宇林,冷金花,郎景和.体外模拟二氧化碳气腹环境对卵巢癌细胞凋亡的影响[J].中华妇产科杂志,2004,39:634-635.
    [20]. Molinas CR, Binda MM, Carmeliet P, et al. Role of vascular endothelial growth factor receptor 1 in basal adhesion formation and in carbon dioxide pneumoperitoneum-enhanced adhesion formation after laparoscopic surgery in mice[J]. Fertil Steril. 2004,82:1149-1153.
    [21]. Tan BJ, Dy JS, Chiu PY, et al. Effects of pneumoperitoneal gases andpressures on transitional cell carcinoma adhesion, growth, apoptosis and necrosis: an in vitro study[J]. J Urol. 2005,174:1463-7.
    [1]. Karadag A, Fedarko NS, Fisher LW. et al.Dentin matrix protein 1 enhances invasion potential of colon cancer cells by bridging matrix metallo proteinase 9 to integrins and CD44[J]. Cancer Res. 2005,24:11545-11552.
    [2]. 司徒镇强,吴军政.细胞培养[M].西安,世界图书出版社, 第一版,2004 年216-218.
    [3]. Jacobi CA, Bonjer HJ, Puttick MI,et al. Oncologic implications of laparoscopic and open surgery[J]. Surg Endosc,2002;16:441–445.
    [4]. Nestler G, Schulz HU, Tautenhahn J,et al. Effects of the angiogenesis inhibitor angiostatin on the growth of CC531 colon carcinoma cells in vitro and in a laparoscopic animal model of peritoneal carcinomatosis[J]. Int J Colorectal Dis. 2005,5:1-7.
    [5]. Ridgway PF, Ziprin P, Jones TL,et al. Laparoscopic staging of pancreatic tumors induces increased invasive capacity in vitro[J]. Surg Endosc, 2003,2:306-310.
    [6]. Curet MJ. Port site metastases[J]. Am J Surg, 2004,6:705-712.
    [7]. Ferrara N, Kerbel RS. Angiogenesis as a therapeutic target[J]. Nature, 2005,7070:967-74.
    [8]. Ezzat S, Asa SL.The molecular pathogenetic role of cell adhesion in endocrine neoplasia[J].J Clin Pathol,2005,11:1121-1125.
    [9]. Ribatti D, Marimpietri D, Pastorino F, et al.Angiogenesis in neuroblastoma[J]. Ann N Y Acad Sci. 2004,1028:133-142.
    [10]. Ferrara N. VEGF as a therapeutic target in cancer.Oncology[J],2005,69 Suppl 3:11-16.
    [11]. Carmeliet P. VEGF as a key mediator of angiogenesis in cancer[J].Oncology,2005,69 Suppl 3:4-10.
    [12]. Kerr DJ. Targeting angiogenesis in cancer: clinical development of bevacizumab[J].Nat Clin Pract Oncol,2004,1:39-43.
    [13]. Nishida N, Yano H, Komai K, et al. Vascular endothelial growth factor C and vascular endothelial growth factor receptor 2 are related closely to the prognosis of patients with ovarian carcinoma[J]. Cancer, 2004, 6: 1364-1374.
    [14]. Ueda M, Terai Y, Kanda K,et al. Tumor angiogenesis and molecular target therapy in ovarian carcinomas[J]. Hum Cell,2005,1:1-16.
    [15]. Nguyen TH. Mechanisms of metastasis[J].Clin Dermatol,2004,3:209-216
    [16]. Li VW, Li WW, Talcott KE, et al. Imiquimod as an antiangiogenic agent[J].J Drugs Dermatol,2005,6:708-717.
    [17]. Yoshizaki T, Sato H, Furukawa M. Recent advances in the regulation of matrix metalloproteinase 2 activation: from basic research to clinical implication[J].Oncol Rep,2002,3:607-611.
    [18]. Ozalp S, Tanir HM, Yalcin OT, et al. Prognostic value of matrix metalloproteinase-9 (gelatinase-B) expression in epithelial ovarian tumors[J].Eur J Gynaecol Oncol,2003,5:417-420.
    [19]. Manenti L, Paganoni P, Floriani I,et al. Expression levels of vascular endothelial growth factor, matrix metalloproteinases 2 and 9 and tissue inhibitor of metalloproteinases 1 and 2 in the plasma of patients with ovarian carcinoma[J].Eur J Cancer,2003,13: 1948-1956.
    [20]. Ridgway PF, Smith A, Ziprin P, et al. Pneumoperitoneum augmented tumorinvasiveness is abolished by matrix metalloproteinase blockade[J]. Surg Endosc,2002,3:533-536.
    [21]. Beng JT, Jun SD, Pui YC, et al.Effects of pneumoperitoneal gases and pressures on transitional cell carcinoma adhesion, growth, apoptosis and necrosis: an in vitro study[J]. J Urol, 2005,174:1463-1467.
    [22]. Molinas CR, Campo R, Dewerchin M, et al. Role of vascular endothelial growth factor and placental growth factor in basal adhesion formation and in carbon dioxide pneumoperitoneum enhanced adhesion formation after laparoscopic surgery in transgenic mice[J]. Fertil Steril, 2003,80 Suppl 2:803-811.
    [23]. Wong YT, Shah PC, Birkett DH, et al. Peritoneal pH during laparoscopy is dependent on ambient gas environment: helium and nitrous oxide do not cause peritoneal acidosis[J].Surg Endosc,2005,1:60-64
    [24]. Vosseler S, Mirancea N, Bohlen P, et al. Angiogenesis inhibition by vascular endothelial growth factor receptor-2 blockade reduces stromal matrix metalloproteinase expression, normalizes stromal tissue, and reverts epithelial tumor pHenotype in surface heterotransplants[J].Cancer Res,2005,4:1294-1305.
    [1]. 刘彦. 妇科腹腔镜的应用进展[M]. 上海医学, 2005, 3:180-181.
    [2]. Jacobi CA, Bonjer HJ, Puttick MI, et al. Oncologic implications of laparoscopic and open surgery[J]. Surg Endosc, 2002,16:441–445.
    [3]. Neuhaus S. J, Watson D. I. Pneumoperitoneum and peritoneal surface changes[J]. Surg Endosc, 2004, 18: 1316–1322.
    [4]. Suematsu T, Shiromizu A, Yamaguchi K, et al. Convenient murine pneumoperitoneal model for the study of laparoscopic cancer surgery[J]. Surg Laparosc Endosc Percutan Tech, 1999,9: 279–281.
    [5]. 周坤,葛海燕.腹腔镜技术与术后肿瘤转移. 重庆医学[J],2005,34(3):442-445.
    [6]. Wu J S, Brasfield EB, Guo LW, et al. Implantation of colon cancer at rocar sites is increased by low pressure pneumoperitoneum[J]. Surgery,1997,122:1-6.
    [7]. Bouvy ND, Marquet RL, Hamming J F, et al. Laparoscopic surgery in the rat: beneficial effect on body weight and tumor take[J]. Surg Endosc, 1996,10:490-497.
    [8]. Gupta A, Wat son I, Ellis T, et al. Tumour implantation following laparoscopy using different insufflation gases[J]. ANZ J Surg, 2002, 72:254-259.
    [9]. Jacobi CA, Sabat R, Bvohm B, et al. Pnemumoperitoneum with carbon dioxide stimulates growth of malignant colonic cells[J]. Surgery, 1997, 121:72-76.
    [10]. Jacobi CA, Ordemann J, Boham B, et al. Inhibition of peritoneal tumor cell growth and implantation in laparoscopic surgery in a rat model[J]. Am J Surg, 1997, 174:359-366.
    [11]. 蒋宇林,冷金花,郎景和.体外模拟二氧化碳气腹环境对卵巢癌细胞凋亡的影响[J].中华妇产科杂志,2004,39:634-635.
    [12]. Binda MM, Carmeliet P, et al. Role of vascular endothelial growth factor receptor 1 in basal adhesion formation and in carbon dioxide pneumoperitoneum enhanced adhesion formation after laparoscopic surgery in mice[J]. Fertil Steril. 2004,82:1149-1153.
    [13]. Tan BJ, Dy JS, Chiu PY, et al. Effects of pneumoperitoneal gases and pressures on transitional cell carcinoma adhesion, growth, apoptosis and necrosis: an in vitro study[J]. J Urol. 2005,174:1463-1467.
    [14]. Neuhaus S.J, Watson D.I. Pneumoperitoneum and peritoneal surface changes[J]. Surg Endosc, 2004, 18: 1316-1322.
    [15]. Volz J, Koster S, Spacek Z, et al. Characteristic alterations of the peritoneum after carbon dioxide pneumoperitoneum[J]. Surg Endosc, 1999, 13: 611-617.
    [16]. Bergstro M, Falk MP, Holmdahl L. CO2 promotes plasminogen activator inhibitor type 1 expression in human mesothelial cells[J]. Surg Endosc, 2003, 17: 1818-1822.
    [17]. Wong YT, Shah PC, Birkett DH, et al. Peritoneal pH during laparoscopy is dependent on ambient gas environment: Helium and nitrous oxide do not cause peritoneal acidosis[J]. Surg Endosc, 2005, 19: 60–64.
    [18]. 唐 均 英 , 姚 珍 微 . CO2 气 腹 对 腹 腔 内 环 境 的 影 响 [J]. 中 国 内 镜 杂志,2005,11:1273-1275.
    [19]. Lee SW, Feingold DL, Carter JJ, et al. Peritoneal macropHage and blood monocyte functions after open and laparoscopic- assisted cecectomy in rats[J]. Surg Endosc, 2003, 17: 62-68.
    [20]. Whelan RL, Franklin M, Holubar SD, et al. Postoperative cell mediated immune response is better preserved after laparoscopic vs open colorectal resection in humans[J]. Surg Endosc, 2003, 17(6): 972-977.
    [21]. Buunen M, Gholghesaei M, Veldkamp R. Stress response to laparoscopic surgery: a review[J]. Surg Endosc. 2004, 18:1022-1028.
    [22]. Ziprin P, Ridgway PF, Peck DH, et al. Laparoscopic-type environment enhances mesothelial cell fibrinolytic activity in vitro via a down-regulation of plasminogen activator inhibitor-1 activity[J]. Surg, 2003,134:758-765.
    1 Volz J, Koster S, Spacek Z, et al. Characteristic alterations of the peritoneum after carbon dioxide pneumoperitoneum[J]. Surg Endosc 1999;13(6):611.
    2 Mouton WG , Bessell JR , Pfitzner J , et al . A randomized controlled trial to determine the effects of humidified carbon dioxide insufflation during thoracoscopy[J]. Surg Endosc 1999;13(2):382.
    3 Volz J, Koster S, Weiss M, et al. PathopHysiologic features of a pneumoperitoneum at laparoscopy: a swine model[J]. Am J Obstet Gynecol 1998;174(1):132.
    4 West MA, Hackam DJ, Baker J, et al. Mechanism of decreased in vitro murine macropHage cytokine release after exposure to carbon dioxide: relevance to laparoscopic surgery[J]. Ann Surg 1997;226(2):179.
    5 Neuhaus SJ, Watson DI, Ellis T, et al. Metabolic and immunological consequences of laparoscopy with helium or carbon dioxide insufflation – a randomized clinical study[J]. ANZ J Surg 2001; 71(8); 447
    6 Ziprin p, Ridgwayb P.F,Peck D.H..Laparoscopic enhancement of tumour cell binding to the peritoneum is inhibited by anti-intercellular adhesion molecule-1 monoclonal antibody[J].Surg Endosc. 2003 ;17(11):1812.
    7 Yamsguchi K,Hirabayashi Y,Suematsu T. Hyaluronic acid secretion during carbon dioxide pneumoperitoneum and its association with port-site metastasis in a murine model[J]. Surg Endosc. 2001 ;15(1):59.
    8 Bouvy ND, Marquet RL, Hamming JF, et al. Laparoscopic surgery in the rat. Beneficial effect on body weight and tumor take[J]. Surg Endosc 1996;10(5):490
    9 Bouvy ND , Marquet RL , Jeekel J, et al. Laparoscopic surgery is associated with less tumour growth stimulation than conventional surgery: an experimental study[J]. Br J Surg 1997;36(6);84:358
    10 Brune IB, Wilke W, Hensler T, et al. Normal T lympHocyte and monocyte function after minimally invasive surgery[J]. Surg Endosc 1998;12(3):1020
    11 Evrard S, Falkenrodt A, Park A, et al. Influence of CO2 pneumoperitoneum on systemic and peritoneal cell-mediated immunity[J]. World J Surg 1997;21(4):353.
    12 Jacobi CA, Wenger F, Opitz, et al. Immunologic changes during minimally invasive surgery[J].Dig Surg. 2002;19(6):459. Review
    13 Jacobi CA,Sterzel A,Braumann C,etal.The impact of conventional and laparoscopic colon resection (CO2 or helium) on intraperitoneal adhesion formation in a rat peritonitis model[J].Surg Endosc. 2001 Apr;15(4):380.
    14 Heel KA, Hall JC. Peritoneal defenses and peritoneum-associated lympHoid tissue[J]. Br J Surg 1996;83(8):1031.
    15 Rofe AM, Bourgeois CS, Coyle P. Beneficial effects of endotoxin treatment on metabolism in tumour-bearing rats[J]. Immunol Cell Biol 1992;70(1):1.
    16 Rofe AM, Bourgeois CS, Washington JM. Metabolic consequences of methotrexate therapy in tumour-bearing rats[J]. Immunol Cell Biol.1994;72(1):43.
    17 Mathew G, Watson DI, Ellis T, et al. The role of peritoneal immunity and the tumour-bearing state on the development of wound and peritoneal metastases after laparoscopy[J]. Aust NZ J Surg 1999;69(1):14.
    18 Mathew G, Watson DI, Ellis T, etal.The effect of laparoscopy on the movement of tumor cells and metastasis to surgical wounds[J]. Surg Endosc. 1997;11(12):1163.
    19 Bouvy ND,Marquet RL,Jeekel H,etal.Impact of gas(less) laparoscopy and laparotomy on peritoneal tumor growth and abdominal wall metastases[J].Ann Surg. 1996;224(6):694
    20 Brundell S,Ellis T,DoddT,etal.Hematogenous spread as a mechanism for the generation of abdominal wound metastases following laparoscopy. Surg Endosc. 2002 Feb;16(2):292.
    21 Lee SW, Southall JC, Gleason NR,etal.Time course of differences in lympHocyte proliferation rates after laparotomy vs CO(2) insufflation[J]. Surg Endosc. 2000;14(2):145.
    22 Jacobi CA, Wenger F, Sabat R, et al. The impact of laparoscopy with carbon dioxide versus helium on immunologic function and tumor growth in a rat model[J]. Dig Surg 1998;15(2):110.
    23 Mathew G, Watson DI, Rofe AM, Baigrie CF, Ellis T, Jamieson GG. Wound metastases following laparoscopic and open surgery for abdominal cancer in a rat model[J]. Br J Surg 1996;83(6):1087.
    24 Murthy SM, Goldschmidt RA, Rao LN, Ammirati M, Buchmann T, Scanlon EF. The influence of surgical trauma on experimental metastasis[J]. Cancer 1999;86(5):770.
    25 Nathan CF. Secretory products of macropHages[J]. J Clin Invest 1987;79(9):319.
    26 Nduka CC, Coates P, Poland N, Kalu P, Davies R, Mansfield AO, Darzi A.Intraoperative modulation of the metastatic cascade by carbon dioxide pneumoperitoneum[J]. Br J Surg 1997;84(6):1613.(Abstract)
    27 West MA, Baker J, Bellingham J. Kinetics of decreased LPS-stimulated cytokine release by macropHages exposed to CO2[J]. J Surg Res 1996;63(1):269.
    28 West MA, Hackam DJ, Baker J, Rodriguez JL, Bellingham J, Rotstein OD. Mechanism of decreased in vitro murine macropHage cytokine release after exposure to carbon dioxide: relevance to laparoscopic surgery[J]. Ann Surg 1997;226(1):179.
    29 陈旭 ,黄锐 ,刘彦,等。不同气腹环境对大鼠系统免疫功能的影响 中国内镜杂志[J]2003; 9(10):31.
    30 Fujii K,Izumi k,sonoda K,etal.Less impaired cell-mediated immune response in the murine peritoneal cavity after CO(2) pneumoperitoneum[J]. Surg Today. 2003;33(11):833.
    31 Romeo C,Impellizzeri P,antonuccio P,etal.Peritoneal macropHage activity after laparoscopy or laparotomy. J Pediatr Surg. 2003 Jan;38(1):97;
    32 Gupta A,Watson DI.Effect of laparoscopy on immune function[J]. Br J Surg. 2001;88(10):1296.
    33 Lee SW,Feingold DL,Carter JJ,etal.Peritoneal macropHage and blood monocyte functions after open and laparoscopic-assisted cecectomy in rats[J]. Surg Endosc. 2003;17(12):19962.
    34 Whelan RL, Franklin M, Holubar SD,etal.Postoperative cell mediated immune response is better preserved after laparoscopic vs open colorectal resection in humans[J]. Surg Endosc. 2003;17(6):972.
    35 Carter JJ,Whelan RL.The immunologic consequences of laparoscopy in oncology[J]. Surg Oncol Clin N Am. 2001;10(3):655.

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700