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研究生:鍾元強
研究生(外文):Yuan-Chang Chung
論文名稱:C反應蛋白、介白質-6及血管生成素在大腸直腸癌之表現及其對預後之重要性
論文名稱(外文):Expressions and Prognostic Significances of C-reactive Protein, Interleukin-6 and Angiopoietins in Colorectal carcinoma
指導教授:許宗雄許宗雄引用關係
指導教授(外文):Tzong-Hsiung Hseu
學位類別:博士
校院名稱:國立清華大學
系所名稱:生命科學系
學門:生命科學學門
學類:生物學類
論文種類:學術論文
論文出版年:2005
畢業學年度:94
語文別:中文
論文頁數:118
中文關鍵詞:大腸直腸癌C反應蛋白介白質-6血管生成素預後因子
外文關鍵詞:Colorectal carcinomaC-reactive proteinInterleukin-6AngiopoietinsPrognostic factor
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大腸直腸癌的發生在台灣近年來有急遽之上升,但是其五年存活率在這三十年來則未見有大幅度之進步。手術切除是處理大腸直腸癌之基本原則,但是術後是否要搭配化療治療,在第二期之大腸直腸癌之病人而言,目前仍是莫衷一是。主要原因就是因為現在真正被證實有預估預後好壞之獨立因子,最重要的依據是癌症期數。倘若如果可以找出更多其他有效之預後因子,加以利用評估手術後之病人,以選擇適合接受化療或放射治療之病例,應可增加大腸直腸癌病人之存活率。
C反應蛋白是由肝細胞在對發炎時進行反應所製造出來的急性相蛋白,在過去曾有人報告它是一種癌症預後預測因子。而在本研究中發現有三分之一大腸直腸癌病人其C反應蛋白質會明顯上升,而且和腫瘤大小、淋巴結或肝轉移有明顯相關。有較高之C反應蛋白之病人,其預後較差。但是它卻不是可預測病人存活率之預後因子。而C反應蛋白之產生係經由細胞激素介白質-1、介白質-6及腫瘤壞死因子之調控。因此本研究另外對大腸直腸癌病人常見之不同細胞激素加以研究,發現大腸直腸癌病人之介白質-6及介白質-8確實是比正常人高。而介白質-6及介白質-2升高之程度又和腫瘤進展之期數有相關性。但只有介白質-6之高低和病人之存活率有所相關。所以我們再針對血清介白質-6之產生與大腸直腸癌之病人之相關性做一分析研究,結果是血清中介白質-6之高低的確調控著CRP之產生,而較高之介白質-6也和腫瘤大小、肝臟轉移和腫瘤發生之期別有著顯著之關連性,但利用多變數回歸分析法則發現血清中之介白質-6本身卻非有效判斷預後之獨立因子。但因血清中介白質-6有可能由身體其他之單核球、上皮細胞、吞噬細胞、纖維母細胞所產生,分析起來較複雜。而由癌上皮組織中產生之介白質-6或許更能表示癌症本身之介白質-6之角色,因此我們再以免疫組織染色之方式檢測癌組織內介白質-6之表現程度,結果發現癌組織內介白質-6和病人術前癌胚抗原高低有關,另外與腫瘤分期及血管受癌之侵襲有關。經過統計後,介白質-6在組織中之表現可以被認定是一有效之預後因子。為探討為何癌組織中介白質-6對大腸直腸癌之表現扮演著何種角色。我們利用大腸癌細胞株(SW480)做細胞黏連,菌落形成、趨化性及侵襲性等之實驗。發現介白質-6對細胞之增生影響不大,但對細胞之菌落形成、黏連性、趨化性及侵襲性具有促進之能力。但是當介白質-6之量太高時,反而會抑制癌侵襲之能力,表示介白質-6若在體內作用時應有自動迴饋抑制癌細胞之功能。至於細胞激素在體內促進大腸直腸癌之進展事實上也和血管新生作用有關,介白質-6與血管內皮細胞生長因子之關係十分密切。但另一調控血管新生作用因子,血管生成素-1,2(Ang-1,2)也十分重要。根據我們的研究,發現腫瘤有無過度表現Ang和預後有關。Ang-1,2之過度表現均會引導微小血管密度值上升。而Ang-2和淋巴結轉移、靜脈癌侵襲、術前高CEA有關。但只有Ang-2表現與否和病人之存活有關,而且也是一有效之預後預後因子。
經由以上之研究我們可以找出大腸直腸癌之有效預後預測因子是癌組織內介白質-6及血管生成素-2,其他如血清內C反應蛋白及介白質-6之表現則未如預期無法擔任有效之預後因子,而介白質-6會促進癌細胞之菌落形成、黏連性、趨化性及侵襲性,且具有一迴饋抑制之機轉。這因子在因此大腸直腸癌之進展扮演了一重要角色,而影響了存活率。未來可能應可以利用介白質-6之特性來有效治療及追蹤大腸直腸癌之病人。
Colorectal carcinoma (CRC) represents a disease with a high incidence and mortality in Traiwan. There is no doubt that the only for cure is in patients who are candidates for radical resection of primary tumors and isolated metastatic disease. However, the long-term survival after surgical intervention has remained unchanged during the past 30 years. At present, anatomical TNM staging system of CRC is regarded as the most important prognostic factor to predict the survival of CRC. Systemic chemotherapy for CRC is routinely given to the patients in stage III or IV of CRC to decrease the recurrent rate and metastasis. However, in the case of stage II of CRC, considerable controversy exists regarding the relative benefit of treament. Some analyses had suggested that adjuvant chemotherapy was helpful; others had not. The conflicting results are in part related to the result of residual occult viable tumor cells whose bulk is below the threshold of detection of current radiological, laboratory or pathological intervention, which have metastasized prior to primary tumor resection. To identify the patients with high risk of recurrence and metastasis needs another independent prognostic factors except staging classification. New biological or molecular factors, which affect the long-term survival of patients of CRC, are classified as probable prognostic factors. Long-term survival might be improved by evaluating these factors to select proper cases for further chemotherapy.
C-reactive protein (CRP) is synthesized in hepatocyte. It belongs to the family of acute-phase protein, the concentration of which changes in response to inflammatory process. The serum level of CRP is frequently elevated in cancer patients and was found to be an indicator of the malignant potential of tumor as well as a predictor of the prognosis. In our study, one-third of patients had increased CRP levels and this was associated with larger tumor size, lymph node or liver metastasis and advanced cancerous stage. High CRP levels were related to the poor survival of CRC. However, multivariate analysis indicated that CRP was not an independent prognostic to predict survival. The changes of CRP are upregulated by cytokines, such as interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor (TNF). So we investigated whether cytokines play a role in the development or progression of CRC. In this study, we demonstrated that levels of IL-6 and IL-8 were significantly higher in patients than in controls. The serum concentrations of IL-2 and IL-6 were correlated with cancerous staging. Only the levels of IL-6 were found to be associated with patient survival. In addition, high levels of IL-6 (>12pg/ml) were correlated with large tumor size, elevated serum CRP levels and liver metastases. Although serum IL-6 correlated with survive, it still was not an independent prognostic indicator. Because serum IL-6 is produced by several kinds of cells, such as monocytes, macrophages, fibroblast and tumor cells, we designed another experiment to evaluate the protein expression in the cancerous cells of CRC. By immunohistochemical examination, the actual role of IL-6 expressed in cancerous tissues could be demonstrated. The results showed tissue expressions of IL-6 associated with higher preoperative CEA level, tumor staging and venous invasion by cancer. Futhermore, tissue expression of IL-6 correlated with the survival of patients with CRC, and could be regarded as independent prognostic factor by multivariate analyses. Thereafter, different concentrations of IL-6 were added to cancerous cell lines to clarify the changes of biological behaviors of CRC. IL-6 did not affect the proliferation of the colon cancer significantly. It increased the abilities of clonogenic growth, adhesion, chemotaxis and invasion in CRC, especially in the dosage of 10~50ng/ml. But IL-6 proceeded to a reciprocal inhibition of these potentials after the dosage increasing to 100ng/ml, which represented an autocrine-like feedback effect. Cytokines could promote tumor angiogenesis and IL-6 had been reported to be associated with the functions of vascular endothelial growth factor. So, angiopoietins (Angs) were also investigated in this thesis. We found both Ang-1 and Ang-2 were associated with increasing of microvascular density. However, only Ang-2 was correlated with lymph node metastasis, venous invasion by cancer and elevation of preoperative CEA levels. The overexpression of Ang-2 was associated with the poor survival of patients with CRC and could be a useful prognostic factor to predict patient survival.
According to our results, tissue expressions of IL-6 and Ang-2 were recognized as independent prognostic factors. Serum CRP and IL-6 were not effective prognostic factors. Elevation of IL-6 could enhance clonogenic growth, adhesion, chemotaxis and invasion abilities of CRC and reciprocal inhibitions were also demonstrated. IL-6 played an important role in the progression of CRC and it could be a useful factor in the treatment and follow-up of the patients with CRC.
論文目錄
中文摘要 ……………………………………… I
英文摘要 ……………………………………… III
總目錄 ………………………………………… 1
表目錄 ………………………………………… 4
圖目錄 ………………………………………… 5
縮寫名詞總覽 ………………………………… 6

第一章 緒論
第一節 大腸直腸癌發生及其預後因子 ……………… 7
第二節 C反應蛋白與癌症之關係 ………………… 9
第三節 細胞激素介白質-6與癌症之關係 …………… 10
第四節 血管生成素與癌症之關係 ………………… 13
第五節 本論文研究之重點 ………………………… 14

第二章 C反應蛋白及各種細胞激素與大腸直腸癌之進展及預後相關性
本章中文摘要 …………………………………… 18
本章英文摘要……………………………………… 19
第一節 前言 ……………………………………… 20
第二節 研究材料與方法 …………………………… 22
第三節 結果 ……………………………………… 24
第四節 討論 ……………………………………… 26
第五節 結論 ……………………………………… 29
第三章 血清中介白質-6與大腸直腸癌之進展及預後之相關性
本章中文摘要 ……………………………………… 37
本章英文摘要 ……………………………………… 37
第一節 前言 ……………………………………… 38
第二節 研究材料與方法 …………………………… 39
第三節 結果 ……………………………………… 40
第四節 討論 ……………………………………… 41
第五節 結論 ……………………………………… 42

第四章 癌組織內介白質-6及其接受體之表現與大腸直腸癌之進展及預後之相關性
本章中文摘要 ……………………………………… 46
本章英文摘要 ……………………………………… 46
第一節 前言 ……………………………………… 47
第二節 研究材料與方法 …………………………… 48
第三節 結果 ……………………………………… 50
第四節 討論 ……………………………………… 51
第五節 結論 ……………………………………… 53

第五章 介白質-6對於大腸直腸癌細胞株之細胞黏連、趨化性及侵襲性所扮演之角色
本章中文摘要 …………………………………… 59
本章英文摘要 …………………………………… 59
第一節 前言 …………………………………… 60
第二節 研究材料與方法 …………………………… 61
第三節 結果 …………………………………… 64
第四節 討論 …………………………………… 65
第五節 結論 …………………………………… 66

第六章 血管生成素之表現與大腸直腸癌進展與預後之相關性
本章中文摘要 …………………………………… 79
本章英文摘要 …………………………………… 79
第一節 前言 ……………………………………… 80
第二節 研究材料與方法 …………………………… 82
第三節 結果 …………………………………… 84
第四節 討論 …………………………………… 85
第五節 結論 …………………………………… 87

第七章 總結與展望 ……………………………… 95

參考文獻 …………………………………………… 96
發表之相關論文……………………………………… 118

表目錄
表1-1 TNM大腸直腸癌分期(病理分類) …………………………………………… 16
表2-1 大腸直腸癌病人之臨床特性………………………………………………… 31
表2-2 大腸直腸癌病患在高及低C反應蛋白組中其臨床病理特徵之表現………………… 32
表2-3 172名大腸直腸癌病患與預後有關之因子其單變數及多變數分析表……… 33
表2-4 血漿中細胞激素之值與大腸直腸癌病人之期數分析及存活率之相關性…… 33
表2-5 164個大腸直腸癌病患之可能預後評估因子之單變數及多變數分析之結果 34
表3-1 大腸直腸癌病人在高及低介白質-6組織臨床病理特性之比較……………… 43
表3-2 在不同主要變數中血清介白質-6之濃度變化表……………………………… 44
表3-3 大腸直腸癌病人利用單及多變數分析其潛在因子與預後之相關性……………… 45
表4-1 大腸直腸癌病人組織中IL-6之表現與臨床病理特徵之比較………………… 54
表4-2 大腸直腸癌病人組織中IL-6R之表現與臨床病理特徵之比較……………… 55
表4-3 IL-6(+)與IL-6R(+)在癌組織內表現之相關表 ……………………………… 56
表4-4 以單變數及多變數分析評估160個大腸直腸癌病人可能之預後因 ……………… 56
表5-1 外加IL-6後之SW480之生物特性之改變…………………………………… 68
表6-1 臨床病理特性與血管生成素-1之表現之相關表……………………………… 88
表6-2 臨床病理特性與血管生成素-2之表現之相關表……………………………… 89
表6-3 血管生成素-1及-2在癌組織內表現之相關表 ……………………………… 90
表6-4 大腸直腸癌之潛在影響因子之單及多變數分析表…………………………… 90

圖目錄
圖1-1 大腸直腸癌TNM分期圖……………………………………………………… 17
圖1-2 IL-6及IL-6R作用之機轉……………………………………………………… 17
圖2-1 大腸直腸癌患者,高及低之C反應蛋白組別之病患術後存活率圖………… 35
圖2-2 不同IL-6值之大腸直腸癌患者之術後存活率圖 …………………………… 36
圖4-1 IL-6在大腸直腸癌組織中之免疫組織染色圖………………………………… 57
圖4-2 IL-6R在大腸直腸癌組織中之免疫組織染色圖 …………………………… 57
圖4-3 大腸直腸癌組織是否顯示IL-6 之病人術後存活率圖 ……………………… 58
圖5-1 各種不同之大腸直腸癌細胞株圖 …………………………………………… 69
圖5-2 評估侵襲性及趨化性所使用之改良型Boyden盒圖 ………………………… 70
圖5-3 外加IL-6於不同細胞株其細胞增殖圖 ……………………………………… 71
圖5-4 外加IL-6R於不同細胞株其細胞增殖圖……………………………………… 72
圖5-5 外加IL-6於SW480細胞,於不同時間其上清液中IL-6之濃度圖………… 73
圖5-6 在不同濃度IL-6外加於SW480細胞,進行菌落生長形成之變化圖………… 74
圖5-7 SW480細胞株在不同IL-6濃度下之菌落形成之情形 ……………………… 75
圖5-8 外加不同濃度之IL-6對SW480之黏連性之影響 ………………………… 76
圖5-9 外加不同濃度之IL-6對SW480之趨化性之影響…………………………… 77
圖5-10 外加不同濃度之IL-6對SW480之侵襲性之影響 ………………………… 78
圖6-1 血管生成素在大腸直腸癌中免疫組織染色圖……………………………… 91
圖6-2 血管生成素-1及2之表現與微小血管密度之相關分析圖…………………… 92
圖6-3 血管生成素-2之表現與否與存活率之相關圖 ……………………………… 93
圖6-4 分析血管生成素-1及2共同表現與存活率之相關圖………………………… 94
Ahmad SA, Liu W, Jung YD, et al. The effects of angiopoietin-1 and -2 on tumor growth and angiogenesis in human colon cancer. Cancer Res 2001; 61:1255-1259.
Ahmad SA, Liu W, Jung YD. Differential expression of angiopoietin-1 and angiopoietin-2 in colon carcinoma. Cancer 2001; 92:1138-1143.
Akira S, Taga T, and Kishimoto T. Interleukin-6 in biology and medicine. Adv Immunol 1993; 54:1-78.
Asahara T, Chen D, Takahashi, et al. Tie-2 receptor ligands , angiopoietin-1 and angiopoietin-2 modulate VEGF – induced postnatal neovascularization. Cir Res 1998; 83:233-240.
Ashizawa T, Okada R, Suzuki Y, et al. Clinical signficance of interleukin-6 in the spread of gastric cancer: role of IL-6 as a prognostic factor. Gastric Cancer. 2005; 8: 124-31.
Astler VB, Coller FA. The prognostic significance of direct extension of carcinoma of the colon and rectum. Ann Surg 1954; 139: 846-54.
Audero E, Cascone I, Zanon I, et al. Expression of angiopoietin-1 in human glioblastomas regulates tumor-induced angiogenesis. Arterioscler Thromb Vascu Biol 2001; 21:536-541.
Baffet G, Braciak TA, Fletcher RG, et al. Autocrine activity of interleukin-6 secreted by hepatocellular carcinoma cell lines. Mol Biol Med. 1991; 8: 141-56.
Balkwill F and Mantovani A. Inflammation and cancer: back to virchow ? Lancet 2001; 357: 539-45.
Baumann H, Richards C, Gauldie J. Interaction among hepatocyte regulation of acute phase plasma protein in human hepatoma (Hep G2) cells. J Immunol 1987; 139:4122-4128.
Blay JY, Negrier S, Combarey V, et al. Serum level of interleukin-6 as a prognostic factor in metastatic renal cell carcinoma. Cancer Res 1992;53:3317-22
Bleinerg H, Rougier P, Wilke HJ(ed5), Management of colorectal cancer. London: Mosby 1998.
Blume- Jesen P and Hunter T. Oncogenic kinase signaling. Nature 2001; 411: 355-65.
Castell JV, Geiger T, Vicet G, et al. Plasma clearance, organ distribution and target cells of interleukin-6 /hepatocyte-stimulating factor in the rat. Eur J Biochem 1988;177:357-61.
Castell JV, Gomes-Lechon MJ, David M, et al. Acute phase response of human hepatocyte: regulation of acute-phase protein synthesis by interleukin-6. Hepatology 1991; 12:1179-1186.
Chae Jk, Kim I, Lim ST, et al. Coadministration of angiopoietin-1 and vascular endothelial growth factor enhances collateral vascularization. Arterioscler Thromb Vascu Biol 2000; 20:2573-2578.
Chau GY, Wu CW, Lui WY, et al. Serum interleukin-10 but not interleukin-6 is related to clinical outcome in patients with resectable hepatocellular carcinoma. Ann Surg 2000; 231:552-8.
Chen RH, Chang MC, Su YH, et al. Interleukin-6 inhibits transforming growth factor-beta induced apoptosis through the PI3K/AKT and signal transducers and activators of transcriptor 3 pathway. J Biol Chem 1998; 274: 23013-9.
Chung YC, Chang YF. Serum interleukin-6 levels reflect the disease status of colorectal cancer. J Surg Oncol 2003; 83: 222-6.
Chung YC, Hou YC, Pan ACH. Endoglin (CD105) expression in the development of hemorrhoids. Euro J Clin Invest 2004; 34: 107-12.
Colotta F, Dower SK, SIM JE, et al. The type II “decoy” receptor: novel regulatory pathway for interleukin-1. Immunol Today 1994; 15:562-6.
Compton C, Fenoglio-Preiser CM, Pettigrew N, et al. American Joint Committee on Cancer Prognostic Factors Consensus Conference: Colorectal Working Group. Cancer 2000; 88: 1739-57.
Cos S, Fernandez R, Guezmes A, et al. Influence of melatonin on invasive and metastatic properties of MCF-7 human breast cancer cells. Cancer Res 1998; 58: 4383-90.
Currie MJ, Gunningham SP, Tumer K, et al. Expression of the angiopoietins and their receptor Tie-2 in human renal clear cell carcinomas; regulation by the von Hippel – Lindau gene and hypoxia. J Path 2002; 198:502-510.
Dankbar B, Padro T, Leo R, et al. Vascular endothelial growth factor in interleukin-6 in paracrine tumor-stromal cell interactions in multiple myeloma. Blood 2000; 95: 2630-6.
Davis S, Aldrich TH, Jones PF, et al. Isolation of angiopoietin-1, a ligand for the TIE 2 receptor, by secrection – trap expression cloning. Cell 1996; 87:1161-1169.
DeVita F, Romano C, Orditura M, et al. Interleukin-6 serum level correlates with survival in advanced gastrointestinal cancer patients but is not an independent progrostic indicator. J Inter Cytok Res 2001; 21:45-52.
Dinarello CA: Biological basis for IL-1 in disease. Blood 1996; 87:2095-147.
Douillard JY, Benonouna J, Vavasseur F, et al. Phase I trial of interleukin-2 and high-dose arginin butyrate in metastatic colorectal cancer. Cancer Immunol Immunother 2000; 49:56-61.
Dowdall JF, Winter DC, Andrews E, et al. Soluble interleukin-6 receptor (SIL-6R) mediates colonic tumor cell adherence to vascular endothelium: a mechanism for metastatic initiation ? J Surg Res 2002; 107:1-6.
Dukes CE. The spread of cancer of rectum. Br J Surg 1930; 12: 643-8.
Dumont DJ, Fong GH, Puri MC, et al. Vascularization of the mouse embryo: A study of flk-1, tek, tie and vascular endothelial growth factor expression during development. Dev Dyn 1995; 203: 80-92.
Dumont DJ, Gradwohl G, Fong GH, et al. Dominant-negative and targeted null mutation in the endothelial receptor tyrosine kinase, tek , reveal a critical role in vaculogenesis of the embryo. Genes Dev 1994; 8: 1897-1909.
Dvorak HF. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med. 1986; 315: 1650-9.
Eggert A, Ikegaki N, Kwiatkowski J, et al. High level expression of angiogenic factors is associated with advanced tumor stage in human neuroblastoma. Clin Cancer Res 2000; 6:1900-1908.
Ethier S. Growth factor synthesis and human breast cancer progression. J Natl Cancer Inst 1995; 87:964-72.
Etoh T, Inoue H, Tanaka S, et al. Argiopoictin-2 is related to tumor angiogenesis in gastric carcinoma: possible in vivo regulation via proteases. Cancer Res 2001; 61:2145-2153.
Fabbri M, Ridolfi R, Maltoni R, et al. Tumor infiltrating lymphocyte and continuous infusion interleukin-2 after metastasectomy in 61 patients with melanoma, colorectal cancer and renal carcinoma. Tumori 2000; 86:46-52.
Falconer JS, Fearon KCH, Ross JA, et al. Acute-phase protein response and survival in pancreatic cancer. Cancer 1995; 75:2077-2082.
Fearon KCH, McMillan DC, Preson T, et al. Elevated circulating interleukin-6 is associated with an acute phase response but reduced fixed hepatic protein synthesis in patients with cancer. Ann Surg 1991; 231:26-31.
Fiedler W, Kruger W, Laack E, et al. A clinical trial of edrecolomab, interleukin-2 and GM-CSF in patients with advanced colorectal cancer. Oncol Rep 2001; 8:225-31.
Fisher RI, Coltman J CA, Doroshow JH, et al. Metastatic renal cell cancer treated with interleukin-2 and lymphokine-activated killer cells: a phase II clinical trial. Ann Intern Med 1988; 108:518-23.
Folkman J. D more PA: Blood vessel formation: what is its molecular basis ? Cell 1996; 87:1153-1155
Fong G H, Rossant J, Gertsenstein M, et al. Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature 1995; 376:66-70
Freedman VH, Shin SI. Cellular tumorigenicity in nude mice: correlation with cell growth in semisolid medium. Cell 1974; 3: 355-9.
Fukada T, Hibi M, Yamanaka Y, et al. Two signals are necessary for cell proliferation induced by a cytokine receptor gp130; involvement of STAT3 in antiapoptosis. Immunity 1996; 5: 449-60.
Gelin J, Moldawer LL, Lonnroch C, et al. Role of endogenous tumor necrosis factor alpha and interleukin-1 for experimental tumor growth and the development of cancer cachexia. Cancer Res 1991; 51:415-421.
Goode V, Schmidt T, Kimmina S, et al. Analysis of blood vessel maturation processes during cyclic ovarian angiogenesis. Lab Invest 1998; 78: 1385-94.
Gruss HJ, Pinto A, Duyster J, et al. Hodgkin’s disease: a tumor with disturbed immunological pathways. Immunol Today 1997; 18: 156-63.
Gurleyik E, Gurleyik G, Unalmiser S. Accuracy of serum C-reactive protein measurements in diagnosis of acute appendicitis compared with surgeon’s clinical impression. Dis Colon Rectum 1995; 38:127-124.
Hanahan D, Folkman J. Patterns and emerging mechanism of the angiogenic switch during tumorigenesis. Cell 1996; 86:353-364.
Hangai M, Moon YS, Kitaya N. Systemically expressed soluble Tie-2 inhibit intraocular neovascularization. Human Gene Ther 2001; 12: 1311-21.
Hannhan D, Weinbeg RA. The hallmarks of cancer. Cell 2000; 100: 57-70.
Hart IR, Goode NT, Wilson RE. Molecular aspects of the metastatic cascade. Biochem Biophys Acta. 1989; 989: 65-84.
Hart IR, Saini A. Biology of tumor metastasis. Lancet. 1992; 339: 1453-1467.
Hashimoto K, Ikeda Y, Korenaga D, et al. The impact of preoperative serum C-reactive protein on the prognosis of patients with hepatocellular carcinoma. Cancer 2005; 103: 1856-64.
Hatzi E, Murphy C, Zoephel A. N-myc oncogene overexpression down-regulates IL-6; evidence that IL-6 inhibits angiogenesis and suppresses neuroblastoma tumor growth. Oncogene 2002; 21: 3552-61.
Hawighorst T, Skobe M, Streit M, et al. Activation of the tie 2 receptor by angiopoietin-1 enhances tumor vessel maturation and impairs squamous cell carcinoma growth. Am J Path 2002; 160:1381-1392.
Hayer AJ, Huang WQ, Yu J, et al. Expression and function of angiopoietin-1 in breast cancer. Br J Cancer 2000; 83:1154-1160.
Hayes AJ, Huang WQ, Mallah J, et al. Angiopoietin-1 and its receptor Tie-2 participate in the regulation of capillary-like tubule formation and survival of endothelial cells. Microvas Res 1999; 58:224-237.
Heinrich PC, Castell JV, Andus T. Interleukin-6 and the acute phase response. Biochem J 1990; 265:621-636.
Hermanek P. Evaluation of new prognostic factor in oncology. Virch Arch Pathol 1995; 427: 335-6.
Hermanek P, Hutter RVP, Sobin LH. Prognostic grouping; the next step in tumor classification. J Cancer Res Clin Oncol 1990; 116: 513-6.
Hermanek P, Sobin LH. Colorectal carcinoma. In: Prognostic Factors in Cancer. Berlin: Springer-Verlag 1999.
Hernandez A, Thomas R, Smith F, et al. Butyrate sensitizes human colon cancer cells to TRAIL-mediated apoptosis. Surgery 2001; 130:265-72.
Hirano T, Akira S, Taga T, et al. Biological and clinical aspect of interleukin-6. Immunol Today 1990; 11:443-9.
Hirano T, Ishihara K, Hibi H. Roles of STAT3 in mediating the cell growth, differentiation and survival signals relayed through the IL-6 family of cytokine receptor. Oncogene 2000; 19: 2548-56.
Hobday TJ, Erlichman C. Colorectal cancer In: UICC: Prognostic Factors in Cancer, 2nd edu. New York: Wiley. 2001.
Hobisch A, Rogatsch H, Hittmair A, et al. Immunohistocheuical localization of interleukin-6 and its receptor in benign, premalignant and malignant prostate tissure. J Pathol 2000; 191: 239-44.
Holash J, Maisonpierre PC, Compton D, et al. Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF. Science 1999; 284:1994-1998.
Holash J, Wiegand SJ, Yancopoulos GD. New model of tumor angiogenesis: dynamic balance between vessel regression and growth mediated by angiopoieitins and VEGF. Oncogene 1999; 18:5356-5362.
Hu RH, Lee PH, Yu SC. Secrection of acute-phase proteins before and after hepatocellular carcinoma resection. J Formos Med Assoc 1999; 98: 85-91.
Huang SP, Wu MS, Shun CT, et al. Interleukin-6 increases vascular endothelial growth factor and angiogenesis in gastric cancer, J Biomed Sci 2004; 11: 517-27.
Jeha S, Luo XN, Beran M, et al. Antisense RNA inhibition of phosphoprotein p18 expression abrogates the transformed phenotype of leukemic cells. Cancer Res 1996; 56: 1445-50.
Jothy S, Munro SB, LeDuy L, et al. Adhesion or anti-adhesion in cancer: what matters more? Cancer Metastasis Rev. 1995; 14: 363-376.
Joussen AM, Poulaki V, Tsujikawa A, et al. Suppression of diabetic retinopathy with angiopeietin-1. Am J Pathol 2002; 160:1683-1693.
Kato MT, Hofland LJ, VanGrevenstein WMU, et al. Influence of proinflammatroy cytokines on the adhesion of human colon carcinoma cells to lung microvascular endothelium. Int J Cancer. 2004; 112: 943-50.
Kawano M, Hirano T, Matsuda T, et al. Autocrine generation and requirement of BSF-2/ IL-6 for human multiple myeloma. Nature 1988; 332: 83-5.
Kinoshita T, Ito H and Miki C. Serum interleukin-6 level reflects the tumor proliferetive activity in patients with colorectal cancer. Cancer 1999; 85:2526-31.
Kirnbauer R, Kock A, Schwarz T, et al. TNF-b2, B cell differentiation factor 2 or hybridoma growth factor (IL-6) is expressed and released by human epidermal cells and epidermoid carcinoma cells. J Immunol 1989; 142:1922-8.
Köbel M, Budianto D, Schmitt WD, et al. Influence of various cytokines on adhesion and migration of the colorectal adenocarcinoma cell line HRT-18. Oncology 2005; 68: 33-9.
Komoda H, Tanaka Y, Honda M, et al. Interleukin-6 level in colorectal cancer tissues. World J Surg 1998; 22:895-8.
Kuper H, Adami HO and Trichopoulos D. Infections as a major preventable cause of human cancer. J Inter Med 2000; 248: 171-83.
Kyriakos M. The Presidents cancer, the Dukes classification and confusion. Arch Path Labor Med 1985; 109: 1063-6.
Lafreniere R, Rosenberg SA. Adoptive immunotherapy of murine hepatic metastases with lymphokine-activated killer cells and recombinant interleukin-2 can mediate regression of both immunogenic and non-immunogenic sarcoma and an adenocarinoma. J Immunol 1985; 135:4273-80.
Lahm H, Suardet L, Laurent PL, et al. Growth regulation and co-stimulation of human colorectal cancer cell lines by insulin-like growth factor I, II and transforming growth factor. Br J Cancer 1992; 65: 341-6.
Lauta VM. Interleukin-6 and the network of several cytokines in multiple myeloma: an overview of clinical and experimental data. Cytokine 2001; 16: 79-86.
Le J, Vilcek J. Interleukin-6: a multifunctional cytokine regulating immune reactions and the acute phase protein response. Lab Invest 1989; 61:1588-600.
Legouffe E, Rodriguez C, Picot MC, et al. C-reactive protein serum level is a valuable and simple prognostic marker in non-Hodgkin’s lymphoma. Leuk Lymphoma 1998; 31:351-357.
Maisonpierre DC, Suri C, Jones PF, et al. Angropoietin-2, a natural antagonist for Tie-2 that disrupts in vivo angiogenesis. Science (Washington DC) 1997; 277:55-60.
Marotovani A. The chemokine system: redundancy for robust output. Immunol Today 1999; 20:254-7.
McMillan DC, Graham AF, Smith J, et al. Interleukin-6, neutrophil and the acute phase protein response in colorectal cancer patients. Euro J Surg Oncol 1994; 20:151-154.
McMillan DC, Wotherspoon HA, Fearon KCH, et al. A prospective study of tumor recurrence and acute-phase response after apparently curative colorectal surgery. Am J Surg 1995; 170:319-322.
Miki S, Iwano M, Miki Y. Interleukin-6 functions as an autocrine growth factor in renal cell carcinoma. FEBS Lett 1989; 250:607-610.
Mitsuhashi N, Shimizu H, Ohtsuka M, et al. Angiopoietin and Tie-2 expression in angiogenesis and proliferation of human hepatocellular carcinoma. Hepatology 2003; 37:1105-1113.
Mitsutake N, Namba H, Takahara K, et al. Tie-2 and angiopoietin-1 expression in human thyroid tumors. Thyroid 2002; 12:95-99.
Moran DM, Mayers N, Koniaris LG, et al. Interleukin-6 inhibit cell proliferation in a rat model of hepatocellular carcinoma. Liver International 2005; 25: 445-57.
Motro B, Itin A, Sachs L, et al. Pattern of interleukin-6 gene expression in vivo suggests a role for this cytokine in angiogenesis. Proc Natl Acad Sci USA 1990; 87:3092-6.
Muzio M. Signaling by proteolysis: death receptors induce apoptosis. Int J Clin Lab Res 1998; 28:141-7.
Nakashima J, Jachibana M, Horiguchi Y. et al. Serum interleukin-6 as prognostic factor in patrents with prostate cancer. Clin Cancer Res 2000; 6:2702-6.
Naylor MS, Stamp GWH, Foulkes WD, et al. Tumor necrosis factor and its receptors in human ovarian cancer. J Clin Invest 1993; 91:2194-2206.
Nicolson GL. Organ specificity of tumor metastasis: role of preferential adhesion, invasion and growth of malignant cells at specific secondary sites. Cancer Metastasis Rev 1988; 7: 143-188.
NIH Consensus Conference. Adjuvant therapy for patients with colon and rectal cancer. JAMA 1990; 264: 1444-50.
Nikiteas NI, Tzanakis N, Gazouli M, et al. Serum IL-6, TNF alpha and CRP levels in Greek colorectal cancer patients: prognostic implications. World J Gastroenterol 2005; 11: 1639-43.
Nozoe T, Matsumata T, Kitamura M, Sugimachi K. Significance of preoperative elevation of serum C-reactive protein as an indicator for prognosis in colorectal cancer. Am J Surg 1998; 176:335-338.
Nozoe T, Matsumate T, Sugimachi K. Preoperative elevation of serum C-reactive protein is related to impaired immunity in patients with colorectal cancer. Am J Clin Oncol 2000; 23:263-266.
Nozoe T, Saeki H, Sugimachi K. Significance of preoperative elevation of serum C-reactive protein as an indicator of prognosis in esophageal carcinoma. Am J Surg 2001; 182:197-201.
Ochiumi T, Tanaka S, Oka S, et al. Clinical significance of angiopoietin-2 expression at the deepest invasive tumor site of advanced colorectal carcinoma. Int J Oncol 2004; 24:539-549.
Oka M, Hirose K, Lizuka N, et al. Cytokine mRNA expression patterns in human esophageal cancer cell line. J Interferon Cytokine Res. 1995; 15: 1005-9.
Oka M, Lizuka N, Yamamoto K, et al. The influence of interleukin-6 on the growth of human esophageal cacner cell line. J Interferon Cytokine Res 1996; 16: 1001-6.
Old LJ. Immunotherapy for cancer. Sci Am 1996; 275: 136-43.
Papapetropoulos A, Fulton D, Mahboubi K, et al. Angiopoietin-1 inhibits endothelial cell apoptosis via the Akt / surviving pathway. J Biol Chem 2000; 275:9102-9105.
Papapetropoulos A, Guillermo GC, Dengler TJ, et al. Direct action of angiopoietin-1 on human endothelium: evidence for network stabilization, cell survival and interaction with other angiogenic growth factors. Lab Investig 1999; 79:213-223.
Pekarek L, Starr BA, Toledano AY, et al. Inhibition of tumor growth by elimination of granulocytes. J Exp Med. 1995; 181:435-40.
Pieter S, Martijn S, Kees DL. In vitro Ig-synthesis and proliferation activity in multiple myeloma are stimulated by different growth factors. Br J Haematol 1991; 79:589-94.
Plante M, Rubin SC, Wang G Y, et al. Interleuki-6 level in serum and ascites as prognostic factor in patients with epithelial ovarian cancer. Cancer 1994; 73:1882-8.
Pomyje J, Zinvy JH, Stopka T, et al. Angiopoietin-1, angiopoietin-2 and Tie-2 in tumor and non-tumor tissues during growth of experimental melanoma. Melanoma Res 2001; 11:639-643.
Qiu Y, Robinson D, Pretlow TG, et al. Etk/Bmx, a tyrosine kinase with pleekstrin-homology domain, is an effecter of PI3K and is involved in IL-6 induced neuroendocrine differentiation of prostate cancer cells. Proct Natl Acad Sci USA. 1998; 95: 3644-9.
Ramadori G, Christ G. Cytokines and the hepatic acute-phase response. Semin Liver Dis 1999; 19:141-55.
Ray PS, Esfrada-Hernandez T, Sasaki H, et al. Early effects of hypoxia/reoxygenation on VEGF, ang-1, ang-2 and their receptors in the rat myocardium: implication of myocardial angiogenesis. Mo1 Cell Biochem 2000; 213:145-153.
Risau W. Mechanism of angiogenesis. Nature 1997; 386:671-674.
Rodriguez-Sanjuan JC, Martin-Parra JI, Seco I, et al. C-reactive protein and leukocyte count in the diagnosis of acute appendicitis in children. Dis Colon Rectum 1999; 42:1325-1329.
Romagnanis. The Th1/Th2 paradigm. Immunol Today. 1997; 18:263-6.
Saito S, Kasai Y, Nomoto S, et al. Polymorphism of tumor necrosis factor in esophageal, gastric or colorectal carcinoma. Hepatogastroenterology 2001; 48:468-70.
Sato TN, Tozawa Y, Deutsch U, et al. Distinct roles of the receptor tyrosine kinase Tie-1 and Tie-2 in blood vessel formation. Nature 1995; 376:70-74.
Scambia G, Testa U, Benedetti PP, et al. Prognostic significance of interleukin-6 serum level in patients with ovarian cancer. Br J Cancer 1995;71: 954-6.
Schnerder MR, Hoeflich A, Fischer JR, et al. Interleukin-6 stimulates clonogenic growth of primary and metastatic hunan colon carcinoma cells. Cancer Lett 2000; 151:31-8.
Sfiligoi C, DcLuca A, Cascone I, et al. Angiopoietin-2 expression in breast cancer correlated with lymph node invasion and short survival. Int J Cancer 2003; 103:466-474.
Shalaby F, Rossant J, Yamaguchi TP, et al. Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature 1995; 376:62-66.
Shim WS, Teh M, Mack P et al. Inhibition of angiopoietin-1 expression in tumor cells by an antisense RNA approach inhibited xenograft tumor growth in immunodeficient mice. Int J Cancer 2001; 94:6-15.
Shin SI, Freedman VH, Risser R, et al. Tumorigenicity of virus-transformed cells in nude mice is correlated specifically with anchorage independent growth in vitro. Proc Natl Acad Sci USA 1975; 72: 4435-9.
Socher SH, Martinez D, Craig JB, et al. Tumor necrosis factor not detectable in patients with clinical cancer cachexia. J Natl Cancer Inst 1988; 80:595-8.
Staal van den Brekel AJ, Dentener MA, Schols AMWJ, et al. Increased resting energy expenditure and weight loss are related to a systemic inflammatory response in lung cancer patients. J Clin Oncol 1995; 13:2600--2605.
Stamatiadis AP, Manouras AJ, Triantos GN, et al. Combination of serum carcino-embryonic antigen and C-reactive protein-a useful test in preoperative staging of colorectal cancer. Eur J Surg Oncol 1992; 18:41-43.
Stoeltzing O, Ahmad SA, Liu W, et al. Angiopoietin-1 inhibits vascular permeability, angiogenesis and growth of hepatic colon cancer tumors. Cancer Res 2003; 63:3370-3377.
Suematsue S. Generation of plasmacytomas with the chromosomal translocation in interleukin-6 transgenic mice. Proc Natl Acad Sci USA 1992; 89:232-6.
Suri C, Jones PF, Patan S, et al. Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis. Cell 1996; 87:1171-1180.
Suri C, McClain J, Thurston G, et al. Increased vascularization in mice overexpressing angiopoietin-1. Science (Washington DC) 1998; 282:468-471.
Taga T. The signal transducer gp130 is shared by interleukin-6 family of hematopoietic and neurotropic cytokine. Ann Med 1997; 29: 63-72.
Takizawa H, Ohtosh T, Ohtak, et al. Growth inhibition of human lung cancer cell line by interleukin-6 in vitro: a possible role in tumor growth via an autocrine mechanism. Cancer Res 1993; 53:4175-81.
Tanaka F, Isikawa S, Yanagihara K, et al. Expression of angiopoietins and its clinical significance in non-small cell lung cancer. Cancer Res 2002; 62:7124-7129.
Tang DG, Honn KV. Adhesion molecules and tumor metastasis: an update. Invasion Metastasis 1994; 14: 109-122.
Tanner J, Tosato G. Impairment of natural killer functions by interleukin-6 increases lymphoblastoid cell tumorigenicity in athymic mice. J Clin Invest 1991; 88:239-47.
Thun MJ, Namboodiri MM, Heath CW Jr. Aspirin use and reduced risk of colon cancer. N Engl J Med 1991; 325: 1593-6.
Thurston G, Rudge JS, Joffe E, et al. Angiopoietin-1 protects the adult vasculature against plasma leakage. Nat Med 2000; 6:460-3.
Thurston G, Suri C, Smith K, et al. Leakage-resistant blood vessels in mice transgenically overexpressing angiopoietin-1. Science (Washington DC) 1999; 286:2511-2514.
Tian S, Hayer AJ, Metheny-Barlow LJ, et al. Stabilization of breast cancer xenograft tumor neovasculature by angiopoietin-1. Br J Cancer 2002; 86:645-651.
Tsukamoto T, Kumamoto Y, Miyao N, et al. Interleukin-6 in metastatic renal cell carcinoma. J Urology 1992; 148:1778-82.
Ueda T, Shimada E, Urakawa T. Serum levels of cytokines in patients with colorectal cancer: possible involvement of IL-6 and IL-8 in hematogenous metastasis J Gastroenterol 1994; 29:423-9.
Van Roy F, Mareel M. Tumor invasion: effects of cell adhesion and motility. Trends Cell Biol 1994; 14: 109-122.
Vita FD, Romano C, Orditura M, et al. Interleukin-6 serum level correlates with survival in advanced gastrointestinal cancer patients but is not an independent prognostic indicator. J Interferon Cytokine Res 2001; 21:45-53.
Waldman TA. T cell receptors for cytokines: targets for immunotherapy of leukemia/ lymphoma. Ann Oncol 2000; 11: 101-6.
Watson JM, Sensintaffar JL, Bere K, et al. Constitutive production of IL-6 by ovarian cancer cell lines and by primary ovarian tumor culture. Cancer Res 1990; 50:6959-65.
Wei LH, Kuo ML, Chen CA, et al. Interleukin-6 promotes cervical tumor growth by VEGF dependent angiogenesis via STAT3 pathway. Oncogene 2003; 22: 1517-27.
Weinstein PS, Skinner M, Sipe JD, et al. Acute phase proteins or tumor makers: the role of SAA, SAP, CRP and CEA as indicators of metastasis in a broad spectrum of neoplastic disease. Scand J Immunol 1984; 19:193-198.
Wigmore SJ, McMahon AJ, Sturgeon CM, et al. Acute phase protein response, survival and tumor recurrence in patients with colorectal cancer. Br J Surg 2001; 88:255-260.
Wu CW, Rang SR, Chao MF, et al. Serum interleukin-6 levels reflect disease status of gastric cancer. Am J Gastroenterology 1996; 91:1417-22.
Yanagawa H, Sone S, Takahashi Y, et al. Serum levels of interleukin-6 in patients with lung cancer. Br J Cancer 1995; 71:1095-8.
Zhang G T, Adachi I. Serum interleukin-6 levels correlate to tumor progression and prognosis in metastatic breast carcinoma. Anticancer Res 1999; 19:1427-32.
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