跳到主要內容

臺灣博碩士論文加值系統

(3.235.120.150) 您好!臺灣時間:2021/07/31 15:17
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

我願授權國圖
: 
twitterline
研究生:楊淵傑
研究生(外文):Yuan-Chieh Yang
論文名稱:人類胃幹細胞於胃癌致癌機制之研究
論文名稱(外文):Human Gastric Stem Cells in Carcinogenesis Studies
指導教授:吳登強
指導教授(外文):Deng-Chyang Wu
學位類別:博士
校院名稱:高雄醫學大學
系所名稱:醫學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2009
畢業學年度:97
語文別:中文
論文頁數:151
中文關鍵詞:幹細胞胃癌幽門螺旋桿菌
外文關鍵詞:stem cellgastric cancerHelicobacter pylori
相關次數:
  • 被引用被引用:0
  • 點閱點閱:269
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
許多的證據顯示,癌症的發生可能來自幹細胞的特化,而此種特化可能是致癌因子突變或基因表現之異常所造成。於是,胃上皮幹細胞的取得及培養,對胃癌致癌機制之探討,是極其重要的。
胃上皮組織具有很高的細胞新陳代謝率,一般認為這類組織需相當數量之幹細胞來維持細胞數之恆定。然而至目前為止,有關人類胃幹細胞之分離與體外培養卻未有正式的論文發表。從以往的組織學觀察中可知,不分化(undifferentiated)之人類胃前驅細胞(progenitor)又可稱為多潛能小顆粒細胞(pluripotent mini-granule cell),其位於pit與gland compartments間之isthmus區域,主要功能可持續性的補充及再生胃上皮細胞。為進行胃組織再生或分化機制之探討及建立本土細胞株供胃癌致癌及抑癌機制之研究,分離胃幹細胞及建立體外培養模式是有其必要性的。在我們研究中,主要以胃內視鏡採集胃黏膜組織,進行胃幹細胞之分離與培養,在已進行的56例組織檢體中,共有118個生長能力較好的細胞株被分離,其中Clone KMU-GI2(GI2)的分析,結果顯示其具多項幹細胞之特性,如有較長的生長期(CPDL=37)、於培養過程中能觀察到不同分化型態的細胞(epithelial-like cells, glial-like cells, neuron-like cells)、能表現Oct-4抗原等。另外於GI2之次代培養中,我們分離出了自然轉型(spontaneous transformed)之細胞株GI2CS-(KMU-CSN; CSN),特別的是此株細胞經一段時間之培養後(cpdl=132),得到另一細胞株KMU-CS12(CS12),其於染色體核型之分析中,已發現第十二對染色體出現異常,並且可於裸鼠移植實驗中證實CS12細胞株已具有致癌性(tumorigenic)。本研究論文主要以前述之細胞株(GI2, CSN, CS12)為實驗材料,並分成三部分來探討,第一部份為“自人類胃部組織分離與定性具幹細胞特性之胃上皮細胞株”,此部分除了探討GI2細胞株的分離方法及培養方式,也以特定的分子標誌進行免疫染色、cpdl的計算、細胞型態的觀察等,分析此細胞株之特性。第二部分“人類胃幹/前軀細胞於胃幽門螺旋桿菌致癌機制之應用”,主要將GI2細胞株應用於胃幽門螺旋桿菌(Helicobacter pylori; Hp)致癌機制之探討上,實驗中我們發現在致癌物N-methyl-N’-nitro -N- nitrosoguanidine(MNNG)及特定Hp的刺激及感染下,GI2細胞株有端粒脢表現量上升的現象。第三部分“ 衍自胃上皮幹細胞之轉形細胞株其特性與胃癌致癌機制相關性之分析”,此部分,我們除了對衍自GI2之轉型株CSN及可於裸鼠生成腫瘤之CS12細胞株進行特性分析外,也以Spectral karyotyping(SKY)確定CS12之第12對染色體異常主要為其長臂多了一段DNA複製自第7對染色體短臂,另外我們將細胞染色體核型變化前後(CSN v.s. CS12)以Microarray進行基因表現的比較,結果顯示有1145個基因表現量上升,890基因表現量下降。經分析後,我們發現位於第七對染色體短臂中之HOXA基因組(HOXA4,5,7,9,13)有明顯高度表現的現象,而這些分子可能於CS12致癌機制中扮演重要角色。
我們相信此人類胃細胞株及其轉型株的建立,不僅於胃癌致癌機制分析及抗癌藥物研究上,提供一個極佳的實驗材料外,更有助胃幹細胞特性及其分化機制之探討。特別的是,由於CS12轉形自幹細胞,我們的實驗間接引證了幹細胞致癌理論,而CS12細胞株是否就是Gastric cancer stem cells,則值得進一步實驗探討與證明。
Cancer has been described as disorganized organogenesis, since a wealth of studies point out the similarity between carcinogenesis and organogenesis. The close link underlying the two seemingly different events is suggested to be tissue stem cells. Therefore, it is important to understand what tissue stem cells are and how they behave under different conditions, which may help to unravel the mystery of carcinogenesis.
Gastric epithelium is a high turn-over tissue, in which stem cells are assumed to be robust. Accordingly, it is an ideal tissue for stem cell study. From histology study, the undifferentiated cells resided in the gastric corpal isthmus were suggested to be the putative gastric stem/progenitor cells, also called pluripotent mini-granule cells. As the study how the putative human gastric stem/progenitor cells may contribute to gastric carcinogenesis, an in vitro model of cultured gastric stem/progenitor cells would be a useful model for further dissection. In my study, I used the gastric specimens obtained by endoscopic biopsy to isolate gastric stem/ progenitor cells. From 56 human specimens, 118 cell clones were isolated. Among them, KMU-GI2 (GI2) showed many characteristics of gastric stem cells, including a high cumulative population doubling level (CPDL=37), a capacity to give rise to cells with different morphology, including epithelial cells, glial cells and neuron cells, and expression of Oct-4. In addition, we isolated a spontaneously transformed subclone, named GI2CS- (KMU-CSN; CSN). After long-term culture (CPDL=132), a subclone, named KMU-CS12 (CS12), in CSN cell was tumorigenic and showed an abnormality in chromosome 12 by karyotyping. With both of normal and transformed gastric epithelial cell clones at hand (GI2, CSN, CS12), it is possible to study how the specific genetic abnormality can contribute to gastric carcinogenesis.
My thesis is comprised of 3 parts. The first part is to show how I isolated and cultured the gastric stem/progenitor cell like-cell clones (KMU-GI2) from human gastric specimens and my approach to characterize their gastric stem/progenitor cells properties, including cumulative population doubling level (cpdl), cell morphology and immunocytochemistry. The second part is to show how this GI2 interacts with carcinogenic environmental cues, like N-methyl-N’-nitro -N- nitrosoguanidine (MNNG) and Helicobacter pylori (Hp), and evaluate their responses. This study was assumed to simulate how stem cells would behave under similar conditions. We found telomerase in the study cells was highly activated under these noxious stimuli, and this increment was correlated with human clinical findings. The third part is to evaluate how transformed gastric stem/progenitor cells can recapitulate carcinogenesis. By Spectral karyotyping (SKY), we confirmed there was an extra fragment, replicated from the short arm of chromosome 7, on chromosome 12 in CS12 clone, which appeared to be tumorigenic in nude mice. There were 1145 genes up-regulated and 890 gene down-regulated by this genetic abnormality, detected by microarray. According to the array data, the HOXA genes, located in chromosome 7, were focused. Further analysis revealed HOXA 4, 5, 7, 9, 13 were significantly over-expressed and this effect might be attributed to the tumorigenecity we observed.
With the creation of in vitro gastric stem/progenitor cell line, a model to approach carcinogenesis and built a preclinical system to test the possible anti-cancer therapy has been established. This study also alludes gastric cancer may derive from transformed gastric stem cells and provides a great chance to further increase our understanding of gastric cancer stem cells.
目錄 ……………………………………………………………… 1
中文摘要 ………………………………………………………… 3
英文摘要 ………………………………………………………… 6
第一章、序論
一、成體幹細胞……………………………………………… 9
二、胃癌與胃幽門螺旋桿菌………………………………… 16
三、癌幹細胞………………………………………………… 23
第二章、自人類胃部組織分離具幹細胞特性之胃上皮細胞株
一、前言……………………………………………………… 27
二、研究材料與方法………………………………………… 32
三、研究結果………………………………………………… 41
四、圖表……………………………………………………… 46
五、討論……………………………………………………… 58
第三章、胃幹/前軀細胞於胃幽門螺旋桿菌致癌機制之應用
一、前言……………………………………………………… 61
二、研究材料與方法………………………………………… 64
三、研究結果………………………………………………… 72
四、圖表……………………………………………………… 74
五、討論……………………………………………………… 79
第四章、胃上皮幹細胞之轉形細胞株於胃癌致癌機制之分析
一、前言……………………………………………………… 83
二、研究材料與方法………………………………………… 86
三、研究結果………………………………………………… 92
四、圖表……………………………………………………… 96
五、討論……………………………………………………… 107
第五章、結語……………………………………………………… 111
第六章、參考文獻………………………………………………… 114
第七章、歷年論文著作…………………………………………… 129
附錄、主要論文著作…………………………………………….. 132
1.Alison MR, Poulsom R, Forbes S & Wright NA. An introduction to stem cells. J Pathol 2002 197 419-423.
2.Gearhart J. New potential for human embryonic stem cells. Science 1998 282 1061-1062.
3.Lee KD, Kuo TK, Whang-Peng J, Chung YF, Lin CT, Chou SH, Chen JR, Chen YP & Lee OK. In vitro hepatic differentiation of human mesenchymal stem cells. Hepatology 2004 40 1275-1284.
4.Trosko JE & Chang CC. Stem cell theory of carcinogenesis. Toxicol Lett 1989 49 283-295.
5.Chang CC, Trosko JE, el-Fouly MH, Gibson-D''Ambrosio RE & D''Ambrosio SM. Contact insensitivity of a subpopulation of normal human fetal kidney epithelial cells and of human carcinoma cell lines. Cancer Res 1987 47 1634-1645.
6.Grueterich M & Tseng SC. Human limbal progenitor cells expanded on intact amniotic membrane ex vivo. Arch Ophthalmol 2002 120 783-790.
7.Kao CY, Nomata K, Oakley CS, Welsch CW & Chang CC. Two types of normal human breast epithelial cells derived from reduction mammoplasty: phenotypic characterization and response to SV40 transfection. Carcinogenesis 1995 16 531-538.
8.Matic M, Evans WH, Brink PR & Simon M. Epidermal stem cells do not communicate through gap junctions. J Invest Dermatol 2002 118 110-116.
9.Trosko JE & Chang CC. Isolation and characterization of normal adult human epithelial pluripotent stem cells. Oncol Res 2003 13 353-357.
10.Chang CC, Sun W, Cruz A, Saitoh M, Tai MH & Trosko JE. A human breast epithelial cell type with stem cell characteristics as target cells for carcinogenesis. Radiat Res 2001 155 201-207.
11.Yoder MC, Mead LE, Prater D, Krier TR, Mroueh KN, Li F, Krasich R, Temm CJ, Prchal JT & Ingram DA. Redefining endothelial progenitor cells via clonal analysis and hematopoietic stem/progenitor cell principals. Blood 2007 109 1801-1809.
12.Yamada Y, Yokoyama SI, Wang XD, Fukuda N & Takakura N. Cardiac stem cells in brown adipose tissue express CD133 and induce bone marrow non-hematopoietic cells to differentiate into cardiomyocytes. Stem Cells 2007.
13.Pittenger M, Vanguri P, Simonetti D & Young R. Adult mesenchymal stem cells: potential for muscle and tendon regeneration and use in gene therapy. J Musculoskelet Neuronal Interact 2002 2 309-320.
14.Vaananen HK. Mesenchymal stem cells. Ann Med 2005 37 469-479.
15.Pansky A, Roitzheim B & Tobiasch E. Differentiation potential of adult human mesenchymal stem cells. Clin Lab 2007 53 81-84.
16.Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, Reyes M, Lenvik T, Lund T, Blackstad M, Du J, Aldrich S, Lisberg A, Low WC, Largaespada DA & Verfaillie CM. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 2002 418 41-49.
17.Kolf CM, Cho E & Tuan RS. Mesenchymal stromal cells. Biology of adult mesenchymal stem cells: regulation of niche, self-renewal and differentiation. Arthritis Res Ther 2007 9 204.
18.Tatematsu M, Tsukamoto T & Inada K. Stem cells and gastric cancer: role of gastric and intestinal mixed intestinal metaplasia. Cancer Sci 2003 94 135-141.
19.Sepulveda AR & Graham DY. Role of Helicobacter pylori in gastric carcinogenesis. Gastroenterol Clin North Am 2002 31 517-535, x.
20.Watanabe T, Tada M, Nagai H, Sasaki S & Nakao M. Helicobacter pylori infection induces gastric cancer in mongolian gerbils. Gastroenterology 1998 115 642-648.
21.Hansson LE, Engstrand L, Nyren O, Evans DJ, Jr., Lindgren A, Bergstrom R, Andersson B, Athlin L, Bendtsen O & Tracz P. Helicobacter pylori infection: independent risk indicator of gastric adenocarcinoma. Gastroenterology 1993 105 1098-1103.
22.Parsonnet J, Vandersteen D, Goates J, Sibley RK, Pritikin J & Chang Y. Helicobacter pylori infection in intestinal- and diffuse-type gastric adenocarcinomas. J Natl Cancer Inst 1991 83 640-643.
23.Nomura A, Stemmermann GN, Chyou PH, Kato I, Perez-Perez GI & Blaser MJ. Helicobacter pylori infection and gastric carcinoma among Japanese Americans in Hawaii. N Engl J Med 1991 325 1132-1136.
24.Forman D, Newell DG, Fullerton F, Yarnell JW, Stacey AR, Wald N & Sitas F. Association between infection with Helicobacter pylori and risk of gastric cancer: evidence from a prospective investigation. Bmj 1991 302 1302-1305.
25.Schistosomes, liver flukes and Helicobacter pylori. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Lyon, 7-14 June 1994. IARC Monogr Eval Carcinog Risks Hum 1994 61 1-241.
26.NIH Consensus Conference. Helicobacter pylori in peptic ulcer disease. NIH Consensus Development Panel on Helicobacter pylori in Peptic Ulcer Disease. Jama 1994 272 65-69.
27.Marshall BJ & Warren JR. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet 1984 1 1311-1315.
28.Suerbaum S & Michetti P. Helicobacter pylori infection. N Engl J Med 2002 347 1175-1186.
29.Dobrilla G, Benvenuti S, Amplatz S & Zancanella L. Chronic gastritis, intestinal metaplasia, dysplasia and Helicobacter pylori in gastric cancer: putting the pieces together. Ital J Gastroenterol 1994 26 449-458.
30.Stemmermann GN. Intestinal metaplasia of the stomach. A status report. Cancer 1994 74 556-564.
31.Shimizu N, Inada K, Nakanishi H, Tsukamoto T, Ikehara Y, Kaminishi M, Kuramoto S, Sugiyama A, Katsuyama T & Tatematsu M. Helicobacter pylori infection enhances glandular stomach carcinogenesis in Mongolian gerbils treated with chemical carcinogens. Carcinogenesis 1999 20 669-676.
32.Sugiyama A, Maruta F, Ikeno T, Ishida K, Kawasaki S, Katsuyama T, Shimizu N & Tatematsu M. Helicobacter pylori infection enhances N-methyl-N-nitrosourea-induced stomach carcinogenesis in the Mongolian gerbil. Cancer Res 1998 58 2067-2069.
33.Tokieda M, Honda S, Fujioka T & Nasu M. Effect of Helicobacter pylori infection on the N-methyl-N''-nitro-N-nitrosoguanidine-induced gastric carcinogenesis in mongolian gerbils. Carcinogenesis 1999 20 1261-1266.
34.Loogna P, Franzen L, Sipponen P & Domellof L. Helicobacter pylori, N-methyl-N''-nitro-N''-nitrosoguanidine, and bile modulate gastric cell kinetics in experimental cancer. Virchows Arch 2001 439 653-660.
35.Chan AO, Luk JM, Hui WM & Lam SK. Molecular biology of gastric carcinoma: from laboratory to bedside. J Gastroenterol Hepatol 1999 14 1150-1160.
36.Hiyama K, Ishioka S, Shirotani Y, Inai K, Hiyama E, Murakami I, Isobe T, Inamizu T & Yamakido M. Alterations in telomeric repeat length in lung cancer are associated with loss of heterozygosity in p53 and Rb. Oncogene 1995 10 937-944.
37.Rogan EM, Bryan TM, Hukku B, Maclean K, Chang AC, Moy EL, Englezou A, Warneford SG, Dalla-Pozza L & Reddel RR. Alterations in p53 and p16INK4 expression and telomere length during spontaneous immortalization of Li-Fraumeni syndrome fibroblasts. Mol Cell Biol 1995 15 4745-4753.
38.Hiyama E, Yokoyama T, Tatsumoto N, Hiyama K, Imamura Y, Murakami Y, Kodama T, Piatyszek MA, Shay JW & Matsuura Y. Telomerase activity in gastric cancer. Cancer Res 1995 55 3258-3262.
39.Jong HS, Park YI, Kim S, Sohn JH, Kang SH, Song SH, Bang YJ & Kim NK. Up-regulation of human telomerase catalytic subunit during gastric carcinogenesis. Cancer 1999 86 559-565.
40.Kuniyasu H, Domen T, Hamamoto T, Yokozaki H, Yasui W, Tahara H & Tahara E. Expression of human telomerase RNA is an early event of stomach carcinogenesis. Jpn J Cancer Res 1997 88 103-107.
41.Markert CL. Neoplasia: a disease of cell differentiation. Cancer Res 1968 28 1908-1914.
42.Till JE. Stem cells in differentiation and neoplasia. J Cell Physiol Suppl 1982 1 3-11.
43.Potter VR. Phenotypic diversity in experimental hepatomas: the concept of partially blocked ontogeny. The 10th Walter Hubert Lecture. Br J Cancer 1978 38 1-23.
44.Sawyers CL, Denny CT & Witte ON. Leukemia and the disruption of normal hematopoiesis. Cell 1991 64 337-350.
45.Hogge DE, Shannon KM, Kalousek DK, Schonberg S, Schaffner V, Zoger S, Eaves CJ & Eaves AC. Juvenile monosomy 7 syndrome: evidence that the disease originates in a pluripotent hemopoietic stem cell. Leuk Res 1987 11 705-709.
46.Fialkow PJ. Clonal origin of human tumors. Biochim Biophys Acta 1976 458 283-321.
47.Pathak S. Organ- and tissue-specific stem cells and carcinogenesis. Anticancer Res 2002 22 1353-1356.
48.Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ & Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A 2003 100 3983-3988.
49.Marx J. Cancer research. Mutant stem cells may seed cancer. Science 2003 301 1308-1310.
50.Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J & Dirks PB. Identification of a cancer stem cell in human brain tumors. Cancer Res 2003 63 5821-5828.
51.Dalerba P, Dylla SJ, Park IK, Liu R, Wang X, Cho RW, Hoey T, Gurney A, Huang EH, Simeone DM, Shelton AA, Parmiani G, Castelli C & Clarke MF. Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci U S A 2007 104 10158-10163.
52.Collins AT, Berry PA, Hyde C, Stower MJ & Maitland NJ. Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res 2005 65 10946-10951.
53.O''Brien CA, Pollett A, Gallinger S & Dick JE. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 2007 445 106-110.
54.Hermann PC, Huber SL, Herrler T, Aicher A, Ellwart JW, Guba M, Bruns CJ & Heeschen C. Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell 2007 1 313-323.
55.Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, Wicha M, Clarke MF & Simeone DM. Identification of pancreatic cancer stem cells. Cancer Res 2007 67 1030-1037.
56.Ma S, Chan KW, Hu L, Lee TK, Wo JY, Ng IO, Zheng BJ & Guan XY. Identification and characterization of tumorigenic liver cancer stem/progenitor cells. Gastroenterology 2007 132 2542-2556.
57.Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C & De Maria R. Identification and expansion of human colon-cancer-initiating cells. Nature 2007 445 111-115.
58.Reya T, Morrison SJ, Clarke MF & Weissman IL. Stem cells, cancer, and cancer stem cells. Nature 2001 414 105-111.
59.Dean M, Fojo T & Bates S. Tumour stem cells and drug resistance. Nat Rev Cancer 2005 5 275-284.
60.Jordan CT, Guzman ML & Noble M. Cancer stem cells. N Engl J Med 2006 355 1253-1261.
61.Nomura S, Kaminishi M, Sugiyama K, Oohara T & Esumi H. Clonal analysis of isolated single fundic and pyloric gland of stomach using X-linked polymorphism. Biochem Biophys Res Commun 1996 226 385-390.
62.Modlin IM, Kidd M, Lye KD & Wright NA. Gastric stem cells: an update. Keio J Med 2003 52 134-137.
63.Karam SM & Leblond CP. Dynamics of epithelial cells in the corpus of the mouse stomach. I. Identification of proliferative cell types and pinpointing of the stem cell. Anat Rec 1993 236 259-279.
64.Karam SM & Leblond CP. Dynamics of epithelial cells in the corpus of the mouse stomach. II. Outward migration of pit cells. Anat Rec 1993 236 280-296.
65.Karam SM & Leblond CP. Dynamics of epithelial cells in the corpus of the mouse stomach. III. Inward migration of neck cells followed by progressive transformation into zymogenic cells. Anat Rec 1993 236 297-313.
66.Karam SM & Leblond CP. Dynamics of epithelial cells in the corpus of the mouse stomach. V. Behavior of entero-endocrine and caveolated cells: general conclusions on cell kinetics in the oxyntic epithelium. Anat Rec 1993 236 333-340.
67.Karam SM. Dynamics of epithelial cells in the corpus of the mouse stomach. IV. Bidirectional migration of parietal cells ending in their gradual degeneration and loss. Anat Rec 1993 236 314-332.
68.Nomura S, Esumi H, Job C & Tan SS. Lineage and clonal development of gastric glands. Dev Biol 1998 204 124-135.
69.Karam SM, Straiton T, Hassan WM & Leblond CP. Defining epithelial cell progenitors in the human oxyntic mucosa. Stem Cells 2003 21 322-336.
70.Terano A, Ivey KJ, Stachura J, Sekhon S, Hosojima H, McKenzie WN, Jr., Krause WJ & Wyche JH. Cell culture of rat gastric fundic mucosa. Gastroenterology 1982 83 1280-1291.
71.Sanders MJ, Amirian DA, Ayalon A & Soll AH. Regulation of pepsinogen release from canine chief cells in primary monolayer culture. Am J Physiol 1983 245 G641-646.
72.Rutten MJ, Dempsey PJ, Solomon TE & Coffey RJ, Jr. TGF-alpha is a potent mitogen for primary cultures of guinea pig gastric mucous epithelial cells. Am J Physiol 1993 265 G361-369.
73.Chew CS. Parietal cell culture: new models and directions. Annu Rev Physiol 1994 56 445-461.
74.Boland CR, Kraus ER, Scheiman JM, Black C, Deshmukh GD & Dobbins WO, 3rd. Characterization of mucous cell synthetic functions in a new primary canine gastric mucous cell culture system. Am J Physiol 1990 258 G774-787.
75.Basque JR, Chailler P, Perreault N, Beaulieu JF & Menard D. A new primary culture system representative of the human gastric epithelium. Exp Cell Res 1999 253 493-502.
76.Tommeras K, Chen Y, Rhedin M, Cabero JL & Mardh S. Proliferation and differentiation of cells from explants of fetal rat stomach. Acta Physiol Scand 1997 159 155-161.
77.De Flora S, Izzotti A, D''Agostini F & Balansky RM. Mechanisms of N-acetylcysteine in the prevention of DNA damage and cancer, with special reference to smoking-related end-points. Carcinogenesis 2001 22 999-1013.
78.Hata R & Senoo H. L-ascorbic acid 2-phosphate stimulates collagen accumulation, cell proliferation, and formation of a three-dimensional tissuelike substance by skin fibroblasts. J Cell Physiol 1989 138 8-16.
79.Miller LR, Jacobson ED & Johnson LR. Effect of pentagastrin on gastric mucosal cells grown in tissue culture. Gastroenterology 1973 64 254-267.
80.Gilbert SF & Migeon BR. D-valine as a selective agent for normal human and rodent epithelial cells in culture. Cell 1975 5 11-17.
81.Lin TM, Tsai JL, Lin SD, Lai CS & Chang CC. Accelerated growth and prolonged lifespan of adipose tissue-derived human mesenchymal stem cells in a medium using reduced calcium and antioxidants. Stem Cells Dev 2005 14 92-102.
82.Chang CC, Tsai JL, Kuo KK, Wang KH, Chiang CH, Kao AP, Tai MH & Trosko JE. Expression of Oct-4, alpha fetoprotein and vimentin, and lack of gap-junctional intercellular communication as common phenotypes of human adult liver stem cells and hepatoma cells Proc Am Assoc Cancer Res 2004 45 642.
83.Donovan PJ. High Oct-ane fuel powers the stem cell. Nat Genet 2001 29 246-247.
84.Pesce M, Gross MK & Scholer HR. In line with our ancestors: Oct-4 and the mammalian germ. Bioessays 1998 20 722-732.
85.Trosko JE. From adult stem cells to cancer stem cells: Oct-4 Gene, cell-cell communication, and hormones during tumor promotion. Ann N Y Acad Sci 2006 1089 36-58.
86.Kayahara T, Sawada M, Takaishi S, Fukui H, Seno H, Fukuzawa H, Suzuki K, Hiai H, Kageyama R, Okano H & Chiba T. Candidate markers for stem and early progenitor cells, Musashi-1 and Hes1, are expressed in crypt base columnar cells of mouse small intestine. FEBS Lett 2003 535 131-135.
87.Smith J, Ladi E, Mayer-Proschel M & Noble M. Redox state is a central modulator of the balance between self-renewal and differentiation in a dividing glial precursor cell. Proc Natl Acad Sci U S A 2000 97 10032-10037.
88.Chepda T, Cadau M, Girin P, Frey J & Chamson A. Monitoring of ascorbate at a constant rate in cell culture: effect on cell growth. In Vitro Cell Dev Biol Anim 2001 37 26-30.
89.Studer L, Csete M, Lee SH, Kabbani N, Walikonis J, Wold B & McKay R. Enhanced proliferation, survival, and dopaminergic differentiation of CNS precursors in lowered oxygen. J Neurosci 2000 20 7377-7383.
90.el-Fouly MH, Trosko JE & Chang CC. Scrape-loading and dye transfer. A rapid and simple technique to study gap junctional intercellular communication. Exp Cell Res 1987 168 422-430.
91.Trosko JE, Chang CC, Wilson MR, Upham B, Hayashi T & Wade M. Gap junctions and the regulation of cellular functions of stem cells during development and differentiation. Methods 2000 20 245-264.
92.Pinkus GS & Kurtin PJ. Epithelial membrane antigen--a diagnostic discriminant in surgical pathology: immunohistochemical profile in epithelial, mesenchymal, and hematopoietic neoplasms using paraffin sections and monoclonal antibodies. Hum Pathol 1985 16 929-940.
93.Tai MH, Chang CC, Kiupel M, Webster JD, Olson LK & Trosko JE. Oct4 expression in adult human stem cells: evidence in support of the stem cell theory of carcinogenesis. Carcinogenesis 2005 26 495-502.
94.Linning KD, Tai MH, Madhukar BV, Chang CC, Reed DN, Jr., Ferber S, Trosko JE & Olson LK. Redox-mediated enrichment of self-renewing adult human pancreatic cells that possess endocrine differentiation potential. Pancreas 2004 29 e64-e76.
95.Okano H. Adult neural stem cells and central nervous system repair. Ernst Schering Res Found Workshop 2006 215-228.
96.Ratti A, Fallini C, Cova L, Fantozzi R, Calzarossa C, Zennaro E, Pascale A, Quattrone A & Silani V. A role for the ELAV RNA-binding proteins in neural stem cells: stabilization of Msi1 mRNA. J Cell Sci 2006 119 1442-1452.
97.Nagata H, Akiba Y, Suzuki H, Okano H & Hibi T. Expression of Musashi-1 in the rat stomach and changes during mucosal injury and restitution. FEBS Lett 2006 580 27-33.
98.Vaira D, Miglioli M, Mule P, Holton J, Menegatti M, Vergura M, Biasco G, Conte R, Logan RP & Barbara L. Prevalence of peptic ulcer in Helicobacter pylori positive blood donors. Gut 1994 35 309-312.
99.Lin JT, Wang JT, Wang TH, Wu MS, Lee TK & Chen CJ. Helicobacter pylori infection in a randomly selected population, healthy volunteers, and patients with gastric ulcer and gastric adenocarcinoma. A seroprevalence study in Taiwan. Scand J Gastroenterol 1993 28 1067-1072.
100.Clyne M, Dolan B & Reeves EP. Bacterial factors that mediate colonization of the stomach and virulence of Helicobacter pylori. FEMS Microbiol Lett 2007 268 135-143.
101.Kabir S. The Current Status of Helicobacter pylori Vaccines: A Review. Helicobacter 2007 12 89-102.
102.Kameshima H, Yagihashi A, Yajima T, Kobayashi D, Denno R, Hirata K & Watanabe N. Helicobacter pylori infection: augmentation of telomerase activity in cancer and noncancerous tissues. World J Surg 2000 24 1243-1249.
103.Light Cycler TeloTAGGG hTERT quantification kit. The fastest way to telomerase quantification. In Biochemica, pp 12-13: Roche Molecular Biochemicals, 2000.
104.Tahara E. Molecular biology of gastric cancer. World J Surg 1995 19 484-488; discussion 489-490.
105.Tahara E. Molecular aspects of invasion and metastasis of stomach cancer. Verh Dtsch Ges Pathol 2000 84 43-49.
106.Hanahan D & Weinberg RA. The hallmarks of cancer. Cell 2000 100 57-70.
107.Sun W, Kang KS, Morita I, Trosko JE & Chang CC. High susceptibility of a human breast epithelial cell type with stem cell characteristics to telomerase activation and immortalization. Cancer Res 1999 59 6118-6123.
108.Tahara E. Genetic pathways of two types of gastric cancer. IARC Sci Publ 2004 327-349.
109.Ue T, Yokozaki H, Kitadai Y, Yamamoto S, Yasui W, Ishikawa T & Tahara E. Co-expression of osteopontin and CD44v9 in gastric cancer. Int J Cancer 1998 79 127-132.
110.Barranco SC, Townsend CM, Jr., Casartelli C, Macik BG, Burger NL, Boerwinkle WR & Gourley WK. Establishment and characterization of an in vitro model system for human adenocarcinoma of the stomach. Cancer Res 1983 43 1703-1709.
111.Sekiguchi M, Sakakibara K & Fujii G. Establishment of cultured cell lines derived from a human gastric carcinoma. Jpn J Exp Med 1978 48 61-68.
112.Park JG, Frucht H, LaRocca RV, Bliss DP, Jr., Kurita Y, Chen TR, Henslee JG, Trepel JB, Jensen RT, Johnson BE & et al. Characteristics of cell lines established from human gastric carcinoma. Cancer Res 1990 50 2773-2780.
113.Yang YC, Wang SW, Hung HY, Chang CC, Wu IC, Huang YL, Lin TM, Tsai JL, Chen A, Kuo FC, Wang WM & Wu DC. Isolation and characterization of human gastric cell lines with stem cell phenotypes. J Gastroenterol Hepatol 2007 22 1460-1468.
114.Davidson JM, Gorringe KL, Chin SF, Orsetti B, Besret C, Courtay-Cahen C, Roberts I, Theillet C, Caldas C & Edwards PA. Molecular cytogenetic analysis of breast cancer cell lines. Br J Cancer 2000 83 1309-1317.
115.Taketani T, Taki T, Ono R, Kobayashi Y, Ida K & Hayashi Y. The chromosome translocation t(7;11)(p15;p15) in acute myeloid leukemia results in fusion of the NUP98 gene with a HOXA cluster gene, HOXA13, but not HOXA9. Genes Chromosomes Cancer 2002 34 437-443.
116.Wong KF, So CC & Kwong YL. Chronic myelomonocytic leukemia with t(7;11)(p15;p15) and NUP98/HOXA9 fusion. Cancer Genet Cytogenet 1999 115 70-72.
117.Kwong YL & Pang A. Low frequency of rearrangements of the homeobox gene HOXA9/t(7;11) in adult acute myeloid leukemia. Genes Chromosomes Cancer 1999 25 70-74.
118.Hatano Y, Miura I, Nakamura T, Yamazaki Y, Takahashi N & Miura AB. Molecular heterogeneity of the NUP98/HOXA9 fusion transcript in myelodysplastic syndromes associated with t(7;11)(p15;p15). Br J Haematol 1999 107 600-604.
119.Borrow J, Shearman AM, Stanton VP, Jr., Becher R, Collins T, Williams AJ, Dube I, Katz F, Kwong YL, Morris C, Ohyashiki K, Toyama K, Rowley J & Housman DE. The t(7;11)(p15;p15) translocation in acute myeloid leukaemia fuses the genes for nucleoporin NUP98 and class I homeoprotein HOXA9. Nat Genet 1996 12 159-167.
120.Eklund EA. The role of HOX genes in malignant myeloid disease. Curr Opin Hematol 2007 14 85-89.
121.Frohling S, Scholl C, Bansal D & Huntly BJ. HOX gene regulation in acute myeloid leukemia: CDX marks the spot? Cell Cycle 2007 6 2241-2245.
122.Zakany J & Duboule D. The role of Hox genes during vertebrate limb development. Curr Opin Genet Dev 2007 17 359-366.
123.Calvo R, West J, Franklin W, Erickson P, Bemis L, Li E, Helfrich B, Bunn P, Roche J, Brambilla E, Rosell R, Gemmill RM & Drabkin HA. Altered HOX and WNT7A expression in human lung cancer. Proc Natl Acad Sci U S A 2000 97 12776-12781.
124.Chen KN, Gu ZD, Ke Y, Li JY, Shi XT & Xu GW. Expression of 11 HOX genes is deregulated in esophageal squamous cell carcinoma. Clin Cancer Res 2005 11 1044-1049.
125.Goodman FR & Scambler PJ. Human HOX gene mutations. Clin Genet 2001 59 1-11.
126.Gu ZD, Chen XM, Zhang W, Gu J & Chen KN. [Expression of 39 HOX genes in esophageal cancer cell lines]. Zhonghua Wei Chang Wai Ke Za Zhi 2007 10 365-367.
127.Huang T, Chesnokov V, Yokoyama KK, Carr BI & Itakura K. Expression of the Hoxa-13 gene correlates to hepatitis B and C virus associated HCC. Biochem Biophys Res Commun 2001 281 1041-1044.
128.Kawazoe Y, Sekimoto T, Araki M, Takagi K, Araki K & Yamamura K. Region-specific gastrointestinal Hox code during murine embryonal gut development. Dev Growth Differ 2002 44 77-84.
129.Ota T, Choi KB, Gilks CB, Leung PC & Auersperg N. Cell type- and stage-specific changes in HOXA7 protein expression in human ovarian folliculogenesis: possible role of GDF-9. Differentiation 2006 74 1-10.
130.Ota T, Gilks CB, Longacre T, Leung PC & Auersperg N. HOXA7 in epithelial ovarian cancer: interrelationships between differentiation and clinical features. Reprod Sci 2007 14 605-614.
131.Raman V, Martensen SA, Reisman D, Evron E, Odenwald WF, Jaffee E, Marks J & Sukumar S. Compromised HOXA5 function can limit p53 expression in human breast tumours. Nature 2000 405 974-978.
132.Rossi Degl''Innocenti D, Castiglione F, Buccoliero AM, Bechi P, Taddei GL, Freschi G & Taddei A. Quantitative expression of the homeobox and integrin genes in human gastric carcinoma. Int J Mol Med 2007 20 621-629.
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關期刊