GnRH、LH和黄体细胞对神经胶质瘤细胞C_6生长的影响
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摘要
为了研究小鼠卵巢黄体中弥散性神经内分泌系统(DNES)细胞的存在情况、DNES细胞的来源;GnRH、LH和黄体细胞对神经胶质瘤细胞C_6生长的影响。本试验采用了免疫组化链霉素抗生物素蛋白-过氧化物酶法、免疫组织荧光化学法对小鼠卵巢黄体中是否存在神经内分泌细胞及其来源进行了研究;采用细胞培养法、免疫细胞荧光化学法、HE染色法、MTT比色法、嗜银蛋白分析法、细胞共培养法和计算机图象分析法对黄体细胞和神经胶质瘤细胞C_6的培养及二者的共培养;GnRH、LH和黄体细胞对神经胶质瘤细胞C_6生长的影响进行了深入的研究。主要结果如下:
1.小鼠黄体中部分细胞中含神经元特异性烯醇化酶(NSE)、S100蛋白和催产素(OT)免疫反应阳性产物。根据免疫反应产物呈色的程度不同可分为强阳性、中等阳性和弱阳性三种。这些免疫反应阳性细胞散在或成团分布,多呈圆形、卵圆形,一些细胞具有明显的突起。NSE和S100蛋白均为DNES系统广谱的,共同的细胞标记物,提示小鼠黄体中的免疫反应细胞属DNES细胞。在小鼠次级卵泡的卵泡膜外膜也存在NSE和S100蛋白的表达,提示小鼠卵巢在排卵前就已经开始了神经内分泌化;DNES物质参与了卵泡发育、黄体形成与退化的整个过程。
2.GnRH、LH和黄体细胞对神经胶质瘤细胞C_6的影响。结果显示: 35μg/mL的GnRH和100IU的LH作用24小时后显著抑制神经胶质瘤细胞C_6生长。
3. GnRH、LH和黄体细胞对神经胶质瘤细胞C_6中p21基因、NSE和S100蛋白表达的影响。GnRH可以显著降低p21基因、NSE和S100蛋白的表达;LH可以显著降低p21基因和NSE的表达,而对S100的表达无显著影响。
4.黄体细胞和神经胶质瘤细胞C_6共培养之间的作用。黄体细胞对神经胶质瘤细胞C_6的生长起了一定的抑制作用。
结果提示:小鼠黄体中存在DNES细胞;小鼠黄体细胞对混合共培养的神经胶质瘤细胞C_6的生长有一定的抑制作用。
The distribution properties and source of diffused neuroendocrine system cells in corpus luteum(CL) of mouse during different physiological periods was studied by method of immunohistochemistry streptavidin-peroxidase and immunohistofluorescence in present research; and in order to investigate the effect of GnRH、LH and luteal cell on glioma cell C_6, we used the cell culture in vitro, immunocytefluorescence, HE staining method, MTT assay method, AgNORs analytical method, cell coculture to detect the cell morphous change of leteal cell culture, glioma cell C_6 culture and their coculture; and to research the expression diversity of p21 protein, NSE and S100 protein in glioma cell C_6 when we exert GnRH, LH and luteal cell culture into the culture of glioma cell C_6 or not. All results were analyzed by Jiangsu JieDa cellular morphology Microsoft ware. The main contents and results of this studies are as follows:
1.The immuno-reactive productions of NSE, S100 protein and OT were located in the cytoplasm of part of the luteal cells of mouse during different physiological periods. The positive cells were belonged to three groups of strongly, mid and weekly staining according to the immuno-reaction. Some of the positive cells get together while the others are diffused in the CL. There are various morphological features of the positive cells including oval and triangle and spinal in shapes and some of which have projects. As the NSE, S100 protein are the common markers of neuroendocrine cells, this experiment show that there are a number of neuroendocrine cells in the CL of mouse. This experiment also found that there are expression of NSE, S100 protein in tunica externa of secondary follicle. It could be infer that DNES cells exist in the mouse ovary, and the muose ovary develop neuroendocrine preovulation.DNES markers exert different roles in the process of ovarian follicular development, corpus luteum development and luteolysis. Some cells develop DNES cells during ovary development.
2. The effect of GnRH, LH and luteal cell on glioma cell C_6 in vitro. Results show that 35μg/mL GnRH and 100 IU LH for 24h inhibited the growth of glioma cells.
3. The effect of GnRH, LH and luteal cell on the expression of p21 protein, NSE and S100 protein in glioma cell C_6. The result indicated that the expression of p21 protein, NSE and S100 protein were down regulated dominantly in glioma cells C_6 after GnRH treatment compared with the control group. And also show that the expression of p21 protein and NSE decreased in LH treatment group compared with the control group. However, LH has no different effect on the S100 protein expression in glioma cells compared with the control group.
4. The interaction between luteal cell and glioma cell by means of their coculture. The result show that luteal cell makes a significant inhibition of luteal cells growth after coculture for 24 h.
From the results above, we draw the following conclusions: there are neuroendocrine cells in the CL of mouse; and mouse luteal cells have a remarkably effect on the growth of glioma cells.
1.小鼠黄体中部分细胞中含神经元特异性烯醇化酶(NSE)、S100蛋白和催产素(OT)免疫反应阳性产物。根据免疫反应产物呈色的程度不同可分为强阳性、中等阳性和弱阳性三种。这些免疫反应阳性细胞散在或成团分布,多呈圆形、卵圆形,一些细胞具有明显的突起。NSE和S100蛋白均为DNES系统广谱的,共同的细胞标记物,提示小鼠黄体中的免疫反应细胞属DNES细胞。在小鼠次级卵泡的卵泡膜外膜也存在NSE和S100蛋白的表达,提示小鼠卵巢在排卵前就已经开始了神经内分泌化;DNES物质参与了卵泡发育、黄体形成与退化的整个过程。
2.GnRH、LH和黄体细胞对神经胶质瘤细胞C_6的影响。结果显示: 35μg/mL的GnRH和100IU的LH作用24小时后显著抑制神经胶质瘤细胞C_6生长。
3. GnRH、LH和黄体细胞对神经胶质瘤细胞C_6中p21基因、NSE和S100蛋白表达的影响。GnRH可以显著降低p21基因、NSE和S100蛋白的表达;LH可以显著降低p21基因和NSE的表达,而对S100的表达无显著影响。
4.黄体细胞和神经胶质瘤细胞C_6共培养之间的作用。黄体细胞对神经胶质瘤细胞C_6的生长起了一定的抑制作用。
结果提示:小鼠黄体中存在DNES细胞;小鼠黄体细胞对混合共培养的神经胶质瘤细胞C_6的生长有一定的抑制作用。
The distribution properties and source of diffused neuroendocrine system cells in corpus luteum(CL) of mouse during different physiological periods was studied by method of immunohistochemistry streptavidin-peroxidase and immunohistofluorescence in present research; and in order to investigate the effect of GnRH、LH and luteal cell on glioma cell C_6, we used the cell culture in vitro, immunocytefluorescence, HE staining method, MTT assay method, AgNORs analytical method, cell coculture to detect the cell morphous change of leteal cell culture, glioma cell C_6 culture and their coculture; and to research the expression diversity of p21 protein, NSE and S100 protein in glioma cell C_6 when we exert GnRH, LH and luteal cell culture into the culture of glioma cell C_6 or not. All results were analyzed by Jiangsu JieDa cellular morphology Microsoft ware. The main contents and results of this studies are as follows:
1.The immuno-reactive productions of NSE, S100 protein and OT were located in the cytoplasm of part of the luteal cells of mouse during different physiological periods. The positive cells were belonged to three groups of strongly, mid and weekly staining according to the immuno-reaction. Some of the positive cells get together while the others are diffused in the CL. There are various morphological features of the positive cells including oval and triangle and spinal in shapes and some of which have projects. As the NSE, S100 protein are the common markers of neuroendocrine cells, this experiment show that there are a number of neuroendocrine cells in the CL of mouse. This experiment also found that there are expression of NSE, S100 protein in tunica externa of secondary follicle. It could be infer that DNES cells exist in the mouse ovary, and the muose ovary develop neuroendocrine preovulation.DNES markers exert different roles in the process of ovarian follicular development, corpus luteum development and luteolysis. Some cells develop DNES cells during ovary development.
2. The effect of GnRH, LH and luteal cell on glioma cell C_6 in vitro. Results show that 35μg/mL GnRH and 100 IU LH for 24h inhibited the growth of glioma cells.
3. The effect of GnRH, LH and luteal cell on the expression of p21 protein, NSE and S100 protein in glioma cell C_6. The result indicated that the expression of p21 protein, NSE and S100 protein were down regulated dominantly in glioma cells C_6 after GnRH treatment compared with the control group. And also show that the expression of p21 protein and NSE decreased in LH treatment group compared with the control group. However, LH has no different effect on the S100 protein expression in glioma cells compared with the control group.
4. The interaction between luteal cell and glioma cell by means of their coculture. The result show that luteal cell makes a significant inhibition of luteal cells growth after coculture for 24 h.
From the results above, we draw the following conclusions: there are neuroendocrine cells in the CL of mouse; and mouse luteal cells have a remarkably effect on the growth of glioma cells.
引文
[1] HE X Y, FAN R W. Research progress of functional motility and physiological regulation of mammalian ovaries [J].Sci/Tech information development &economy.2001 (11),5:75-76.
[2] B.Berisha, D.Schams. ovarian function in ruminants[J].Domestic animal endocrinology.2005,29:305- 317.
[3] Alila H W, Hansel W. Origen of different cell types in the bovine corpus luteum as characterized by specific monoclonal antibodies [J].Biol Reprod,1984,31(5):1015-1025.
[4] John A,Marya G,Kirk L,et al. Oxytocin receptor regulation and action in a human granulosa-lutein cell line[J].Biology of Reproduction, 2002, 66(5): 1230-1236.
[5] Spicer L J, Francisco C C. The adipose obese gene product, leptin:evidence of a direct inhibitory role in ovarian function[J].Endocrinology,1997,138:3374-3379.
[6] Harrison G S,Wierman M E,Nett T M,et al. Gonadotropin-releasing hormone and its receptor in normal and malignant cells [J].Endocrine Related Cancer,2004,11:725-748.
[7] McGee1 E A ,Hsueh A J. Initial and cyclic recruitment of ovarian follicles[J]. Endocr Rev, 2000, 21 (2):200-214.
[8] Aufderheide E,Ehrismann R,Ekblom P. Epithelial-mesenchymal Interactions in the development kindney lead to expression of tenascin in the mesenchyme[J].Cell Biol, 1987,105:599.
[9] Donovan P J,Stott D,Cairns L A,et al. Migratory and postmigratory and mouse primordial germ cells behave differently in cuture[J].Cell,1986,44:831.
[10] Stewart T A,Bellve A R. Transcription and promoter usage of the c-myc gene in normal somatic and spermatogenetic cells[J].Science,1984,226:707.
[11]金萱,方廉.原癌基因与卵巢[J].国外医学计划生育分册,2000,19(2):94~102.
[12] Finkel T,Der C J. Activation of ras gene in human tumors does not affect localization, modification,or nucleotide binding properties of P21[J].Cell,1984,37:151.
[13] Papageorge A,Lowy D. Comparative biochemical properties of the P21 ras molecules coded for viral and cellular ras genes[J].Virol,1982,44:509.
[14] Iwaoki Y,Matsuda H, Mutter G L, et al. Differential expression of the proto-oncogene c-abl and c-mos in developing mouse germ cells[J]. Exp cell Res,1993,206(2):212-219.
[15] Zhao X,Singh B,Batten B E. The role of c-mos proto-oncoprotein in mammalian meiotic maturation[J]. Oncogene,1991,6(1):43-49.
[16] Hashimoto N,Watanabe N, Furuta Y,et al. Pathenogenetic actiiation of oocytes in c-mos-deficient mice[J]. Nature,1994, 370(6484):68-71.
[17] Someya A,Harada N,Honda A,et al. Stimulation of DNA replication by treated Fos and Jun proteins in a cell-free extract of xenopus eggs[J]. Biophys Res Commun,1995,208(3):1080- 1091.
[18] Narasimhan V,Hamill O,Cerione RA. The effects of the normal and oncogenic forms of the neu tyrosine kinase and the corresponding forms of an immaoglobulin receptor/neutyrosine kinase fusion protein on Xenopus oocyte maturation[J].FEBS Lett,1992,303(2–3):164-168.
[19] Hashiba Y,Asada Y,Heikinheimo O,et al. Microinjection of antisense C-mos oligonucleotides prevent progression of meiosis in tuman tamster oocytes[J]. Fertility and sterility,2001,76(1): 143-147.
[20] Charlesworth A,Ridge JA,King LA,et al. A novel regulatory element determines the timing of Mos mRNA translation during Xehopus oocyte maturation[J].The EMBO Journal, 2002, 22 (11):2798-2806.
[21]郑莉萍,吴磊,郑月慧.原癌基因c-erbB2、c-myb对小鼠卵母细胞体外成熟的影响[J].生殖与避孕,2005,25(12):712-715. [22郑月慧,方廉,况海斌,等. c-myb对大鼠黄体细胞孕酮和雌二醇生成的影响[J].基础医学与临床,1999,19(2): 65-68.
[23]郑月慧,徐斯凡,况海斌,等. c-myc对大鼠黄体细胞hCG诱导的孕酮和雌二醇生成的影响[J].生殖医学杂志,1998,7(3): 167-170.
[24]郑月慧,钟志胜,方廉,等. c-fos、c-myb和c-erbB2对大鼠卵巢颗粒细胞生孕酮调控关系的研究[J].中国应用生理学杂志,2000,16(3): 268-271.
[25]郑月慧,方廉,况海斌,等. c-ras与大鼠黄体细胞和颗粒细胞生成孕酮的关系[J].生殖医学杂志,2000,9(2):96-99.
[26]郑月慧,金萱,方廉,等. c-erbB2对大鼠黄体细胞hCG诱导的孕酮生成的影响[J].生理学报,2000,52(1):17-21.
[27] Gospodarowicz D, Gospoarowicz F. A technique for the isolation of bovine luteal cells and its application to metabolic studies of luteal cells in vitro[J].Endocrinology,1972,90(6):14-27.
[28] Papaionannou S,Gospodarowicz D. Comparison of the binding of human chorionic gonadotropin to isolated bovine luteal cells and bovine luteal plasma membranes[J]. Endocrinology.1975,97(3):114.
[29] Thomas J P. Mechanism of the rapid antigonadotropic action of prostoglandins in cultured luteal cells[J].Proc Natl Acad Sei.1978,75(3):13-14.
[30] Simmons K R. A simple method for preparting suspensions of luteal cells[J].Proc Soc Exp Biol Mcd.1976,152(3):366.
[31] Glulyas B J. Progesterone production by dispersed monkey (macaca mulatta) luteal cells after exposure to trypsin[J]. Steroids,1980,1:43.
[32] Channing C P,Ledwitz R F. Methods for assessing hormone-mediated differentiation of ovarean cells in culture and in short-term incubations [J].Methods Emzymol,1975, 39: 183 -230.
[33] Pescador N,Stocco D M,Murphu B D. Growth factor modulation of steroidogenic acute regulatory protein and luteinization in the pig ovary[J].Biol Reprod,1999,60:1453-1461.
[34] Meidan R, Girsh E,Blum O,et a1. In vitro differentiation of bouine granulosa cells into small and large luteal-like cells: morphologecal and functional characeritics[J].Biol Reprod,1990,43:913- 921.
[35] Robinson R S, Hammond A J, Mann G E, et al. A novel physiological culture system that mimics luteal angiogenesis [J].Reproduction.2008, 135(3):405-413.
[36] Staszkiewicz J,Skowronski M T,Siawrys G.et al.Expression of proopiomelanocortin, proenkephalin and prodynorphin genes in porcine luteal cells[J].Clin Endocrinol Metab. 2008,93(4):1476-1481.
[37] Viani I, Vottero A, Tassi F.et al. Ghrelin inhibits steroid biosynthesis by cultured granulosa-lutein cells[J].Clin Endocrinol Metab.2008,93(4):1476-1481.
[38] Nishimura R, Komiyama J, Tasaki Y, et al. Hypoxia promotes luteal cell death in bovine corpus luteum[J].Biol Reprod.2008 ,78(3):529-536.
[39] Wen X,Tozer A J,Li D,et al. Human granulosa-lutein cell in vitro production of progesterone, inhibin A,inhibin B,and activin A are dependent on follicular size and not the presence of the oocyte[J].FertilSteril.2008 ,89(5):1406-1413.
[40] Arikan S,Yigit A A. Effects of cholesterol and cAMP on progesterone production in cultured luteal cells isolated from pseudopregnant cat ovaries[J].Anim Reprod Sci.2008 ,6.
[41] Gould V E. Sypnaptophysin:A new and promising panneuroendcrine Marker[J].Arch Pathol Lab Med.1987,11:791.
[42] Lioyd RV. The neuroendocrine and paracrine systems in diagnostic surgical pathology[J].Raven Press,1989:435.
[43]陈代云,李蜀华,成娘.消化道小细胞癌的临床病理研究[J].诊断病理学杂志,1998,1:28.
[44]李维华,许红民,侯宁. 30例肺神经内分泌癌光电镜免疫组化研究[J].中华病理学杂志,1993,22:197.
[45]谭郁彬.弥散性内分泌系统病理研究进展[J].中华病理学杂志,1990,19:81.
[46] Dardick I,et al. Reliability of critera for ultrastruct[J].Pathil.1993,17:37.
[47] Lioyd RV. The neuroendocrine and paracrine systems in diagnostic surgical pathology[J].Raven Press.1989:435.
[48] Herrera G A,et al. Ultrastructural immunolabeling in the evaluation of neuroendocrine neoplasmas, diagnosis and characterization of neuroendocrine neoplasmas[J].Ultrastruct Pathol,1993,17:93.
[49]杨林森,戴益民.原位杂交技术在病理学中的应用[J],国外医学生理:病理科学与临床分册,1988,8:107.
[50] Tavassolia F,Devilee P. World Health Organization classification of tumours Pathology & genetics tumours of the breast and female genital organs[J].Lyon: IARC Press,2003:32-40.
[51]郑益红,路名芝,刘勇.卵巢浆液性乳头状囊腺癌伴神经内分泌分化1例报告[J].实用癌症杂志,2006,1(21):85.
[52] Guppy A E,Nathan P D,Rustin G J. Epithelial ovarian cancer:a review of current management[J].Clin Oncol,2005,17(6):399-411.
[53] Yang X D,Wang S,Meng H Y,et al. The prognosis value of human neuroendocrine clone on colorectal carcinoma [J].Chinese Journal of Surgery,2005 ,43(11):706-709.
[54] Atasoy P,Bozdogan O,Ozturk S,et al.Bcl-2 expression and its correlation with neuroendocrine, differentiation in colon carcinomas[J].Tumori,2004,90(2):233-238.
[55]何松,严桥,陈旭东,等.胃癌细胞中神经内分泌分化与术后生存关系的研究[J].中国肿瘤临床,2007,34(22):1283-1286.
[56] Yao G Y,Zhou J L,Lai M D,et al. Neuroendocrine markers in adenocarcinoma:an investigation of 356 cases [J].World J Gastroenterol,2003,9(4):860-861.
[57] Eyden B,Pandit D,Banerjee S S. Malignant melanoma with neuroendocrine differentiation:clinical,histological,immunohistochemical and ultrastructural features of there cases[J].Histopathology,2005,47:402-409.
[58]向理科,米粲,罗子国,等. 17例骨肉瘤伴神经内分泌分化[J].诊断病理学杂志,2000,7(3):175-177. 59] Huang J,Yao J L,diSant'Agnese P A,et al. Immunohistochemical characterization of neuroendocrine cells in prostate cancer[J].Prostate,2006,66:1125-1135.
[60] Kamiya N,Akakura K,Suzuki H,et al. Pretreatment serum level ofneuron specific enolase(NSE) as a prognostic factor in metastatic prostate cancer patients treated with endocrine therapy[J].European Urology,2003,44(3):309-314.
[61] Ziecik AJ,Bodek G,Bfik A,et a1. Nongonadal LH receptors,their involvement in female reproductivefunction and a new applicable approach[J].Vet J,2005,169(1):75-84.
[62] Ziecik AJ,Derecka K,Gawronska B,et a1.Nongonadal LH/hCG receptor in pig:Functional importance and parallels to human[J].Semin Reprod Med,2001,19(1):19-30.
[63] Shemesh M.Actions of gonadotrophins on the uterus[J].Reproduction,2001,121(6):835-842.
[64] Leuschner C,Hansel W. Targeting breast and prostate cancel though their hormone receptors [J].Biol Reprod,2005,73(5):860-865.
[65] Ji Q,Chen P,Aoyoma C,et a1. Increased expression of human luteinizing hormone/human ehorionic gonadotropin receptor mBNA in human endometrial cancer[J].Mol Cell Probes,2002,16(4):269-275.
[66] Plebani M,Basso D. Clinical evalution of seven tumor market in lung cancer diagnosis:Can any combination improve the results [J].Bri J Cancer,2005,72(1):170-173.
[67] Iny V,Edwards V,Halliday W, et al.“Ployphenotypic”tumors in the central nervous system: problems in nosology and classification[J].Pedictr Patho,1997,17(3):369-389.
[68]王兰兰,柳永和.临床免疫学和免疫检验[M].全国高等医药教材建设研究会规划教材, 2003.5.
[69] Poola I,Graziano S L. Expression of neuron specific enolase. Chromogranin A. synaptophysin and Leu-7 in lung cancer cell lines[J].J Exp Clin Cancer Res,1998,17 (2):165.
[70] Satoh H,Ishikawa K,et al. Cut-off levels of NSE to differentiate SCLC from NSCLC[J]. Oncol Rep,2002,9(30):581-583.
[71] Bonner J A,Sloan J A,Rowland K M,et al. Significanceof neuron-specific enolase levers before and during therapy for small cell lung cancer[J].Clin Cancer Res,2000,6(2):597- 598.
[72] Fizazi K,Cbjean I,Pignon J P,et al. Normal serum neunon specific enolase(NSE) value after the first cycle of chemotherapy, an early predictor of complete response and survival in patients with small lung carcinoma[J].Cancer,2006,82(6):1049-1049.
[73] Stefan K. J Neurosci Lett,1999,261(1-2):124.
[74] ugelkamp D,Schafer B W,Mattei M G,et al. Six S100 genes are clustered an human chromosome 1q21:Identification of two genescoding for the two previously unreported calcium2-binding proteins S100D and S100E[J].Proc Natl Acad Sci.1993,90(14):6547– 6551.
[75] Wicki R,Franz C,Scholl F A,et al. Repression of the candidate tumor suppressor gene S100A2 in breast cancer in mediated by site specific hypermethylation[J].Cell calcium, 1997,22(4):243-254
[76] Glenney J R,KindyM S,Zokas L. Isolation of a new member of theS100 protein family: Amino Acid sequence,Tissue,and subcellular distribution[J].J Cell Biol,1989,108(2):569- 578.
[77] Lee SW,Tomasetto C,Swisshelm K,et al. Down-regulation of a member of the S100 gene family in mammary carcinoma cells and re-expression by azadeoxycytidine treat men[J]. Proc Natl AcadSci,1992,89(6):2504-2508.
[78] Kyriazanos I D,Tachibana M,Dhar DK,et al. Expression and prognostic significance of S100A2 protein in squamous cell carcinoma of the esophagus[J].Oncol Rep,2002,9(3): 503-510.
[79] Watson P H,Leygue E R,Mushy L C. Psoriasin(S100A7) [J].Int J Biochem Cell Biol, 1998,30:567-571.
[80] Tarabykina S,Scott D J.The dimerization interface of the metastasis- associated protein S100A4 (Mts1):in vivo and in vitro studies[J].J Biol Chem,2001,276:24212-242222.
[81] Shebet G V,Lakshmi M S.S100A4(MTS1)calcium binding protein in cancer growth, invasion and metastasis[J].Anticancer Res,1998,l8:24l5-2421.
[82] Schmidt-Hansen B,Klingelhofer J,Grum-Schwensen B,et al. Functional significance ofmetastasis-inducing S100A4 (Mts1) in tumor-stroma interplay [J].J Biol Chem,2004,279: 24498-24504.
[83] Schmidt-Hansen B,Ornas D,GrigorianM,et al. Extracellular S100A4 (mts1) stimulates invasive growth of mouse endothelial cells and modulates MMP-13 matrix metallo protein as eactivity[J].Oncogene,2004,23:5487-5495.
[84] Ambartsumian N,Klingelhofer J,GrigorianM,et al. The metastasis-associated Mts1(S100A4) protein could act as an angiogenic factor[J].Oncogene,2001,20:4685-4695.
[85]Hsieh H L,Schafer B W,Sasaki N,et al. Expression analysis of S100 proteins and RAGE in human tumors using tissue microarrays [J].Biochem Biophys Res Commun,2003,307(2): 375 -381.
[86] Mazzucchelli L. Protein S100A4:too long overlooked by pathologists?[J].Am J Pathol,2002, 160(1):7-3.
[87] SastryM. The three-dimensional structure of Ca2+-bound calcyclin:implications for Ca2+- signal transduction by S100 proteins[J].Structure,1998,6:223-231.
[88] Leygue E,Snell L,Hiller T,et al. Differential expression of psoriasin messenger RNA between in situ and invasive human breast carcinoma[J].Cancer Res, 1996,56(20): 4606- 4609.
[89] Sakaguchi M,Miyazaki M,Inoue Y,et al. Relationship between contact inhibition and intranuclear S100C of normal human fibroblasts[J].J Cell Biol,2000,149(6):1193-1206.
[90] Brewer G. Copper control as an antiangiogenic anticancer therapy:lessons from treating Wilson′s dieases[J].Exp Biol Med,2001,226(3):665-673.
[91] Brewer G,Dick RD,GroverDK,et al. Treatment of metastatic cancer with tetrathiomolybdate, an anticopper antiangiogenic agent [J].Clin Cancer Res,2000,6(1):1-10.
[92] Ilg E C,Schafer B W,Heizmann C W. Expression pattern of S100calcium binding proteins in human tumors[J].Int J Cancer,1996,68(3):325-332.
[93] Hauschild A,Engel G,Brenner W,et al. S100B protein detection in serum is a significant prognostic factor in metastatic melanoma[J].Oncology,1999,56(4):338-344.
[94] Rustandi R R,Baldisseri D M,Weber DJ. Structure of the negative regulatory domain of p53 bound to S100B(betabeta)[J].Nat Struct Biol,2000,7(7):570-574.
[95] Lin J,Blake M,Tang C,et al. Inhibition of p53 transcriptional activity by the S100B calcium binding protein[J].J Biol Chem,2001,276(37):35037-35041.
[96] Choi KC,Auersperg N,Leung P C. Expression and Anti-proliferative effect of second form of gonadotropin-releasing hormone in normal and neoplastic ovarian surface epithelial cells[J].J Clin Endocrinol Metab,2001 86:5075-5078.
[97] Lovas S,Palyi I,Vincze B,et al. Direct anticancer activity of gonadotropin-releasing hormone III[J].J Peptide Res,1998,52:384-389.
[98] Emons G,Weib S,Ortmann O,et al. Luteinizing hormone-releasing hormone(LHRH) might act as a negative autocrine regulator of proliferation of human ovarian cancer[J].Eur J Endoc,2000,142:665-670.
[99] Grundker C, Emons G. GnRH-mechanisms of action: in gnrh analorgues[M].The state of the art at the millennium.Carnforth,1999,95-120.
[100] Arencibia J M,Schally A V. Luteinizing hormone-releasing hormone as an autocrine growth factor in ES-2 ovaria cancer cell line[J].Int J Oncol,2000,16:1009-1013.
[101] Amotz N,Yarkoni S,Marianovsky I,et al. Adenocacinoma cells are targeted by the new GnRH-PE66 chimeric toxin through specific gonadotropin-releasing hormone binding sites[J].J Biological Chemistry,1997,272:11597-11603.
[102] Ziecik A J,Bodek G,Blitek A,et a. Nongonadal LH receptom,their involvement in female reproductive function and a new applicable approach[J],Vet J,2005,169(1)75-84.
[103] Ziecik A J,Derecka K,Gawronska B,et a1.Nongonadal LH/hCG receptom in pig:Functional importance and parallels to human[J].Semin Reprod Med,2001,19(1):19-30.
[104] Shemesh M. Actions of gonadotrophins on the uterus[J].Reproduetion,2001,121(6):835– 842.
[105] Carlson H E,Katie P,Lei Z M,et a1. Presence of luteinizing hormone/human ehorionie gonadotropin receptom in male breast tissuse[J].J Clin Endocrinol Metab, 2004, 89(8): 4119 -4123.
[106] Sibley PE,Harper ME,Joyee BG,et a1. The immunocytochemical detection of protein hormones in human prostatic tissues [J].Prostare,1981,2(2):175-185.
[107] Leuschner C,Hansel W. Targeting breast and prostate cancers through their hormone receptors [J].Biol Reprod,2005,73(5):860-865.
[108] Bose CK. Does hormone replacement thempy prevent epithelial ovarian cancer[J].Reprod Biomed Online,2005,11(1):86-92.
[109] Watanabe A,Kineshita Y,Hosokawa K,et a1. Function of estrogen-related receptor alpha in human endometrial cancer[J].J Clin EndocrinolMetab,2006,91(4):1573-1577.
[110]夏铁安,郭敏..喉癌与垂体分泌的LH、FSH水平关系的初步探讨[J].中华耳鼻咽喉科杂志.1990,25(5):268-269.
[111] http://www.fda.gov/bbs/topics/NEWS/2008/NEW01935.html.
[112]李作生,李保庆. p21和p27基因多态性与肿瘤的相关性[J].国际遗传学杂志,2006,29(4): 317-320.
[113]曹岩,郑永晨. p21基因转染人胃癌细胞对化疗药物敏感性的影响[J].吉林大学学报(医学版),2005,31(5):785-787.
[114]冉志华,冯樱,邱德凯,等.重组细小病毒H21(rhH1Δ/p21)对胃癌细胞HGC27生长抑制作用的研究[J].肿瘤,2007,27(4):251-255.
[115] Ganjavi H,Gee M,Narendran A,et al. Adenovirus-mediated p53 gene therapy in pediatric soft-tissue sarcoma cell lines: sensitization to cisplatin and doxorubicin[J].Cancer Gene Ther,2005,12(4):397-406.
[116] Simon C,Frances R A A,Piouette G,et al. Immunohistochemical localization of the interleukin-1 system in the mouse ovary during follicular growth,ovulation,and luteinization [J].Biology of Reproduction,1994,50:449-457.
[117] Pearse A G E. Embryology of the diffuse neuroendocrine system and its relationships to the common peptides [J].Frederation Proccedings,l987,38(10):2288-2294.
[118]陈树林,蒋田园,雷治海,等.山羊黄体弥散性神经内分泌细胞的分布[J].畜牧与兽医,2007,139(19):16-19.
[119]刘彤华.诊断病理学[M].北京:人民卫生出版社,l995:370-377,1027-1028.
[120]李伟,李光乾,林忠东,等.癫痫患儿血清及脑脊液神经元特异性烯醇化酶和肿瘤坏死子α测定的意义[J].实用儿科临床杂志,2007,22(8):611-613.
[121]陈俊国.新生儿缺氧缺血性脑病血清及脑脊液中神经元特异性烯醇化酶水平变化的临床分析[J].现代中西医结合杂志,2007,16(9):1213-1214.
[122]卿素珠,沈霞芬,陈谊,等.奶山羊周期黄体中催产素的免疫组化定位[J].西北农林科技大学学报,2001,29(2):25-28.
[123] Burke C R,Cardenas H,Mussard M L, et al.Histological and steroidogenic changes in dominant ovarian follicles during oestradiol-induced atresia in heifers[J].Society Reprod Ferti, 2005, 129 (5): 611-620.
[124] Pakarainen T,Zhang F P,Nurmi L,et al.Knockout of luteining hormone receptor abolishes the effects of follicle-stimulating on hormone on preovulatory maturation and ovulation of mouse graafian follicles [J].Mol Endocrinol,2005,19(10):2561-2602.
[125] Rodriguez Dorta N, Cognie Y,Gonzaez F,et a1.Effect of cocuhure with oviduct epithelial cells on viability after transfer of vitrified in vitro produced goat embryos[J].Theriogenology,2007,68(6):908-913.
[126] Qian Y,Shi W Q,Ding J T,et a1.Efects of type and state of coculture cells on in-vitro development of porcine oocytes matured and fertilized in vitro[J].J Assist Reprod Genet,2005,22(6):233-238.
[127] Spandofer SD,Soslow R,Clark R,et a1.Histologic characteristics of the endometrium predicts success when utilizing autologous endometrial cocuhure in patients with lVF failure[J].Assist Reprod Genet,2006,23(4):185-189.
[128] Azadbakht M,Valojerdi M R,Mowla S J.Development of mouse embryos cocultured with polarized or nonpolarized uterine epithelial cells using sequential culture media[J].Anita Reprod Sci,2007,100(1-2):141-157.
[129] Sugiura K,Pendola F L,Eppig J J.Oocyte control of metabolic cooperativity between oocytes and companion granulosa cells:energy metabolism[J].Dev Biol,2005,279(1):20-30.
[130] Gilchrist R B,Lane M,Thompson J G.Oocyte secreted factors:regulators of cumulus cell function and oocyte quality[J].Hum Reprod Update,2008,l4(2):159-177.
[131] Parikh F R,Nadkarni S G,Naik N J,et a1.Cumulus coeuhure and cumulus-aided embryo transfer increases pregnancy rates in patients undergoing in vitro fertilization[J].Fertil Steril,2006,86 (4):839-847.
[132] Ebner T,Moser M,Sommergmber M,et a1.Incomplete denudation of oocytes prior to ICSI enhances embryo quality and blastocyst development[J].Hum Reprod,2006,21(11):2972-2977.
[133] Nottola SA,Heyn R,Camboni A,et a1.Ultrastructural characteristics of human granulosa cells in a cocuhure system for in vitro fertilization[J].Microsc Res Tech,2006,69(6):508-516.
[134] Ge L,Han D,Lan G C,et a1.Factors affecting the in vitro action of cumulus cells on the maturing mouse oocytes[J].Mol Reprod Dev,2008,75(1):136-142.
[135] Tan XW,Ma sF,Yu JN,et a1.Effects of species and cellular activity of oviductal epithelial cells on their dialogue with cocultured mouse embryos[J].Cell Tissue Res,2007,327(1):55-66.
[136] Malekshah AK,Moghaddam AE,Daraka SM.Comparison of conditioned medium and direct coculture of human granulosa ceils on mouse embryo development[J].Indian J Exp Biol,2006,44(3):189-192.
[137] Lange C,Togel F,Ittrich H,et a1.Administered mesenchymal stem cells enhance recovery from ischemia/reperfusion-induced acute renal failure in rats[J].Kidney International,2005,68(4):1613-1617.
[138] Togel F,Hu Z,W eiss K,et a1.Administered mesenchymal stem cells protect against ischemic acuterenal failurethrough differentiation-independent mechanisms[J].Am J Physiol,2005,289(1):31-42.
[139]周涛,许百男,陈德蕙. PC12细胞分化的神经元与离体培养的大鼠原代皮质神经元之间功能性突触的形成[J ].中华神经科杂志, 2005 ,38(3) :183 - 186.
[140] Galli D,Innocenzi A,Staszewsky L,et a1.Mesoangioblasts,vessel associated multipotent stem cells,repair the infarcted heart by multiple cellular mechanisms:A conparison with bone marrow progenitors,fibroblasts,and endothelial cells[J].Arterioscler Thromb Vasc Biol;2005,25(4): 692-697.
[141] Li N,Feugier P,Serrurrier B,et a1.Human mesenchymal stem cells improve ex vivo expansion of adult humanCD34+ peripheral blood progenitor cells and decreasetheir allostimulatory capacity [J]. Exp Hematol,2007,35(3):507-515.
[2] B.Berisha, D.Schams. ovarian function in ruminants[J].Domestic animal endocrinology.2005,29:305- 317.
[3] Alila H W, Hansel W. Origen of different cell types in the bovine corpus luteum as characterized by specific monoclonal antibodies [J].Biol Reprod,1984,31(5):1015-1025.
[4] John A,Marya G,Kirk L,et al. Oxytocin receptor regulation and action in a human granulosa-lutein cell line[J].Biology of Reproduction, 2002, 66(5): 1230-1236.
[5] Spicer L J, Francisco C C. The adipose obese gene product, leptin:evidence of a direct inhibitory role in ovarian function[J].Endocrinology,1997,138:3374-3379.
[6] Harrison G S,Wierman M E,Nett T M,et al. Gonadotropin-releasing hormone and its receptor in normal and malignant cells [J].Endocrine Related Cancer,2004,11:725-748.
[7] McGee1 E A ,Hsueh A J. Initial and cyclic recruitment of ovarian follicles[J]. Endocr Rev, 2000, 21 (2):200-214.
[8] Aufderheide E,Ehrismann R,Ekblom P. Epithelial-mesenchymal Interactions in the development kindney lead to expression of tenascin in the mesenchyme[J].Cell Biol, 1987,105:599.
[9] Donovan P J,Stott D,Cairns L A,et al. Migratory and postmigratory and mouse primordial germ cells behave differently in cuture[J].Cell,1986,44:831.
[10] Stewart T A,Bellve A R. Transcription and promoter usage of the c-myc gene in normal somatic and spermatogenetic cells[J].Science,1984,226:707.
[11]金萱,方廉.原癌基因与卵巢[J].国外医学计划生育分册,2000,19(2):94~102.
[12] Finkel T,Der C J. Activation of ras gene in human tumors does not affect localization, modification,or nucleotide binding properties of P21[J].Cell,1984,37:151.
[13] Papageorge A,Lowy D. Comparative biochemical properties of the P21 ras molecules coded for viral and cellular ras genes[J].Virol,1982,44:509.
[14] Iwaoki Y,Matsuda H, Mutter G L, et al. Differential expression of the proto-oncogene c-abl and c-mos in developing mouse germ cells[J]. Exp cell Res,1993,206(2):212-219.
[15] Zhao X,Singh B,Batten B E. The role of c-mos proto-oncoprotein in mammalian meiotic maturation[J]. Oncogene,1991,6(1):43-49.
[16] Hashimoto N,Watanabe N, Furuta Y,et al. Pathenogenetic actiiation of oocytes in c-mos-deficient mice[J]. Nature,1994, 370(6484):68-71.
[17] Someya A,Harada N,Honda A,et al. Stimulation of DNA replication by treated Fos and Jun proteins in a cell-free extract of xenopus eggs[J]. Biophys Res Commun,1995,208(3):1080- 1091.
[18] Narasimhan V,Hamill O,Cerione RA. The effects of the normal and oncogenic forms of the neu tyrosine kinase and the corresponding forms of an immaoglobulin receptor/neutyrosine kinase fusion protein on Xenopus oocyte maturation[J].FEBS Lett,1992,303(2–3):164-168.
[19] Hashiba Y,Asada Y,Heikinheimo O,et al. Microinjection of antisense C-mos oligonucleotides prevent progression of meiosis in tuman tamster oocytes[J]. Fertility and sterility,2001,76(1): 143-147.
[20] Charlesworth A,Ridge JA,King LA,et al. A novel regulatory element determines the timing of Mos mRNA translation during Xehopus oocyte maturation[J].The EMBO Journal, 2002, 22 (11):2798-2806.
[21]郑莉萍,吴磊,郑月慧.原癌基因c-erbB2、c-myb对小鼠卵母细胞体外成熟的影响[J].生殖与避孕,2005,25(12):712-715. [22郑月慧,方廉,况海斌,等. c-myb对大鼠黄体细胞孕酮和雌二醇生成的影响[J].基础医学与临床,1999,19(2): 65-68.
[23]郑月慧,徐斯凡,况海斌,等. c-myc对大鼠黄体细胞hCG诱导的孕酮和雌二醇生成的影响[J].生殖医学杂志,1998,7(3): 167-170.
[24]郑月慧,钟志胜,方廉,等. c-fos、c-myb和c-erbB2对大鼠卵巢颗粒细胞生孕酮调控关系的研究[J].中国应用生理学杂志,2000,16(3): 268-271.
[25]郑月慧,方廉,况海斌,等. c-ras与大鼠黄体细胞和颗粒细胞生成孕酮的关系[J].生殖医学杂志,2000,9(2):96-99.
[26]郑月慧,金萱,方廉,等. c-erbB2对大鼠黄体细胞hCG诱导的孕酮生成的影响[J].生理学报,2000,52(1):17-21.
[27] Gospodarowicz D, Gospoarowicz F. A technique for the isolation of bovine luteal cells and its application to metabolic studies of luteal cells in vitro[J].Endocrinology,1972,90(6):14-27.
[28] Papaionannou S,Gospodarowicz D. Comparison of the binding of human chorionic gonadotropin to isolated bovine luteal cells and bovine luteal plasma membranes[J]. Endocrinology.1975,97(3):114.
[29] Thomas J P. Mechanism of the rapid antigonadotropic action of prostoglandins in cultured luteal cells[J].Proc Natl Acad Sei.1978,75(3):13-14.
[30] Simmons K R. A simple method for preparting suspensions of luteal cells[J].Proc Soc Exp Biol Mcd.1976,152(3):366.
[31] Glulyas B J. Progesterone production by dispersed monkey (macaca mulatta) luteal cells after exposure to trypsin[J]. Steroids,1980,1:43.
[32] Channing C P,Ledwitz R F. Methods for assessing hormone-mediated differentiation of ovarean cells in culture and in short-term incubations [J].Methods Emzymol,1975, 39: 183 -230.
[33] Pescador N,Stocco D M,Murphu B D. Growth factor modulation of steroidogenic acute regulatory protein and luteinization in the pig ovary[J].Biol Reprod,1999,60:1453-1461.
[34] Meidan R, Girsh E,Blum O,et a1. In vitro differentiation of bouine granulosa cells into small and large luteal-like cells: morphologecal and functional characeritics[J].Biol Reprod,1990,43:913- 921.
[35] Robinson R S, Hammond A J, Mann G E, et al. A novel physiological culture system that mimics luteal angiogenesis [J].Reproduction.2008, 135(3):405-413.
[36] Staszkiewicz J,Skowronski M T,Siawrys G.et al.Expression of proopiomelanocortin, proenkephalin and prodynorphin genes in porcine luteal cells[J].Clin Endocrinol Metab. 2008,93(4):1476-1481.
[37] Viani I, Vottero A, Tassi F.et al. Ghrelin inhibits steroid biosynthesis by cultured granulosa-lutein cells[J].Clin Endocrinol Metab.2008,93(4):1476-1481.
[38] Nishimura R, Komiyama J, Tasaki Y, et al. Hypoxia promotes luteal cell death in bovine corpus luteum[J].Biol Reprod.2008 ,78(3):529-536.
[39] Wen X,Tozer A J,Li D,et al. Human granulosa-lutein cell in vitro production of progesterone, inhibin A,inhibin B,and activin A are dependent on follicular size and not the presence of the oocyte[J].FertilSteril.2008 ,89(5):1406-1413.
[40] Arikan S,Yigit A A. Effects of cholesterol and cAMP on progesterone production in cultured luteal cells isolated from pseudopregnant cat ovaries[J].Anim Reprod Sci.2008 ,6.
[41] Gould V E. Sypnaptophysin:A new and promising panneuroendcrine Marker[J].Arch Pathol Lab Med.1987,11:791.
[42] Lioyd RV. The neuroendocrine and paracrine systems in diagnostic surgical pathology[J].Raven Press,1989:435.
[43]陈代云,李蜀华,成娘.消化道小细胞癌的临床病理研究[J].诊断病理学杂志,1998,1:28.
[44]李维华,许红民,侯宁. 30例肺神经内分泌癌光电镜免疫组化研究[J].中华病理学杂志,1993,22:197.
[45]谭郁彬.弥散性内分泌系统病理研究进展[J].中华病理学杂志,1990,19:81.
[46] Dardick I,et al. Reliability of critera for ultrastruct[J].Pathil.1993,17:37.
[47] Lioyd RV. The neuroendocrine and paracrine systems in diagnostic surgical pathology[J].Raven Press.1989:435.
[48] Herrera G A,et al. Ultrastructural immunolabeling in the evaluation of neuroendocrine neoplasmas, diagnosis and characterization of neuroendocrine neoplasmas[J].Ultrastruct Pathol,1993,17:93.
[49]杨林森,戴益民.原位杂交技术在病理学中的应用[J],国外医学生理:病理科学与临床分册,1988,8:107.
[50] Tavassolia F,Devilee P. World Health Organization classification of tumours Pathology & genetics tumours of the breast and female genital organs[J].Lyon: IARC Press,2003:32-40.
[51]郑益红,路名芝,刘勇.卵巢浆液性乳头状囊腺癌伴神经内分泌分化1例报告[J].实用癌症杂志,2006,1(21):85.
[52] Guppy A E,Nathan P D,Rustin G J. Epithelial ovarian cancer:a review of current management[J].Clin Oncol,2005,17(6):399-411.
[53] Yang X D,Wang S,Meng H Y,et al. The prognosis value of human neuroendocrine clone on colorectal carcinoma [J].Chinese Journal of Surgery,2005 ,43(11):706-709.
[54] Atasoy P,Bozdogan O,Ozturk S,et al.Bcl-2 expression and its correlation with neuroendocrine, differentiation in colon carcinomas[J].Tumori,2004,90(2):233-238.
[55]何松,严桥,陈旭东,等.胃癌细胞中神经内分泌分化与术后生存关系的研究[J].中国肿瘤临床,2007,34(22):1283-1286.
[56] Yao G Y,Zhou J L,Lai M D,et al. Neuroendocrine markers in adenocarcinoma:an investigation of 356 cases [J].World J Gastroenterol,2003,9(4):860-861.
[57] Eyden B,Pandit D,Banerjee S S. Malignant melanoma with neuroendocrine differentiation:clinical,histological,immunohistochemical and ultrastructural features of there cases[J].Histopathology,2005,47:402-409.
[58]向理科,米粲,罗子国,等. 17例骨肉瘤伴神经内分泌分化[J].诊断病理学杂志,2000,7(3):175-177. 59] Huang J,Yao J L,diSant'Agnese P A,et al. Immunohistochemical characterization of neuroendocrine cells in prostate cancer[J].Prostate,2006,66:1125-1135.
[60] Kamiya N,Akakura K,Suzuki H,et al. Pretreatment serum level ofneuron specific enolase(NSE) as a prognostic factor in metastatic prostate cancer patients treated with endocrine therapy[J].European Urology,2003,44(3):309-314.
[61] Ziecik AJ,Bodek G,Bfik A,et a1. Nongonadal LH receptors,their involvement in female reproductivefunction and a new applicable approach[J].Vet J,2005,169(1):75-84.
[62] Ziecik AJ,Derecka K,Gawronska B,et a1.Nongonadal LH/hCG receptor in pig:Functional importance and parallels to human[J].Semin Reprod Med,2001,19(1):19-30.
[63] Shemesh M.Actions of gonadotrophins on the uterus[J].Reproduction,2001,121(6):835-842.
[64] Leuschner C,Hansel W. Targeting breast and prostate cancel though their hormone receptors [J].Biol Reprod,2005,73(5):860-865.
[65] Ji Q,Chen P,Aoyoma C,et a1. Increased expression of human luteinizing hormone/human ehorionic gonadotropin receptor mBNA in human endometrial cancer[J].Mol Cell Probes,2002,16(4):269-275.
[66] Plebani M,Basso D. Clinical evalution of seven tumor market in lung cancer diagnosis:Can any combination improve the results [J].Bri J Cancer,2005,72(1):170-173.
[67] Iny V,Edwards V,Halliday W, et al.“Ployphenotypic”tumors in the central nervous system: problems in nosology and classification[J].Pedictr Patho,1997,17(3):369-389.
[68]王兰兰,柳永和.临床免疫学和免疫检验[M].全国高等医药教材建设研究会规划教材, 2003.5.
[69] Poola I,Graziano S L. Expression of neuron specific enolase. Chromogranin A. synaptophysin and Leu-7 in lung cancer cell lines[J].J Exp Clin Cancer Res,1998,17 (2):165.
[70] Satoh H,Ishikawa K,et al. Cut-off levels of NSE to differentiate SCLC from NSCLC[J]. Oncol Rep,2002,9(30):581-583.
[71] Bonner J A,Sloan J A,Rowland K M,et al. Significanceof neuron-specific enolase levers before and during therapy for small cell lung cancer[J].Clin Cancer Res,2000,6(2):597- 598.
[72] Fizazi K,Cbjean I,Pignon J P,et al. Normal serum neunon specific enolase(NSE) value after the first cycle of chemotherapy, an early predictor of complete response and survival in patients with small lung carcinoma[J].Cancer,2006,82(6):1049-1049.
[73] Stefan K. J Neurosci Lett,1999,261(1-2):124.
[74] ugelkamp D,Schafer B W,Mattei M G,et al. Six S100 genes are clustered an human chromosome 1q21:Identification of two genescoding for the two previously unreported calcium2-binding proteins S100D and S100E[J].Proc Natl Acad Sci.1993,90(14):6547– 6551.
[75] Wicki R,Franz C,Scholl F A,et al. Repression of the candidate tumor suppressor gene S100A2 in breast cancer in mediated by site specific hypermethylation[J].Cell calcium, 1997,22(4):243-254
[76] Glenney J R,KindyM S,Zokas L. Isolation of a new member of theS100 protein family: Amino Acid sequence,Tissue,and subcellular distribution[J].J Cell Biol,1989,108(2):569- 578.
[77] Lee SW,Tomasetto C,Swisshelm K,et al. Down-regulation of a member of the S100 gene family in mammary carcinoma cells and re-expression by azadeoxycytidine treat men[J]. Proc Natl AcadSci,1992,89(6):2504-2508.
[78] Kyriazanos I D,Tachibana M,Dhar DK,et al. Expression and prognostic significance of S100A2 protein in squamous cell carcinoma of the esophagus[J].Oncol Rep,2002,9(3): 503-510.
[79] Watson P H,Leygue E R,Mushy L C. Psoriasin(S100A7) [J].Int J Biochem Cell Biol, 1998,30:567-571.
[80] Tarabykina S,Scott D J.The dimerization interface of the metastasis- associated protein S100A4 (Mts1):in vivo and in vitro studies[J].J Biol Chem,2001,276:24212-242222.
[81] Shebet G V,Lakshmi M S.S100A4(MTS1)calcium binding protein in cancer growth, invasion and metastasis[J].Anticancer Res,1998,l8:24l5-2421.
[82] Schmidt-Hansen B,Klingelhofer J,Grum-Schwensen B,et al. Functional significance ofmetastasis-inducing S100A4 (Mts1) in tumor-stroma interplay [J].J Biol Chem,2004,279: 24498-24504.
[83] Schmidt-Hansen B,Ornas D,GrigorianM,et al. Extracellular S100A4 (mts1) stimulates invasive growth of mouse endothelial cells and modulates MMP-13 matrix metallo protein as eactivity[J].Oncogene,2004,23:5487-5495.
[84] Ambartsumian N,Klingelhofer J,GrigorianM,et al. The metastasis-associated Mts1(S100A4) protein could act as an angiogenic factor[J].Oncogene,2001,20:4685-4695.
[85]Hsieh H L,Schafer B W,Sasaki N,et al. Expression analysis of S100 proteins and RAGE in human tumors using tissue microarrays [J].Biochem Biophys Res Commun,2003,307(2): 375 -381.
[86] Mazzucchelli L. Protein S100A4:too long overlooked by pathologists?[J].Am J Pathol,2002, 160(1):7-3.
[87] SastryM. The three-dimensional structure of Ca2+-bound calcyclin:implications for Ca2+- signal transduction by S100 proteins[J].Structure,1998,6:223-231.
[88] Leygue E,Snell L,Hiller T,et al. Differential expression of psoriasin messenger RNA between in situ and invasive human breast carcinoma[J].Cancer Res, 1996,56(20): 4606- 4609.
[89] Sakaguchi M,Miyazaki M,Inoue Y,et al. Relationship between contact inhibition and intranuclear S100C of normal human fibroblasts[J].J Cell Biol,2000,149(6):1193-1206.
[90] Brewer G. Copper control as an antiangiogenic anticancer therapy:lessons from treating Wilson′s dieases[J].Exp Biol Med,2001,226(3):665-673.
[91] Brewer G,Dick RD,GroverDK,et al. Treatment of metastatic cancer with tetrathiomolybdate, an anticopper antiangiogenic agent [J].Clin Cancer Res,2000,6(1):1-10.
[92] Ilg E C,Schafer B W,Heizmann C W. Expression pattern of S100calcium binding proteins in human tumors[J].Int J Cancer,1996,68(3):325-332.
[93] Hauschild A,Engel G,Brenner W,et al. S100B protein detection in serum is a significant prognostic factor in metastatic melanoma[J].Oncology,1999,56(4):338-344.
[94] Rustandi R R,Baldisseri D M,Weber DJ. Structure of the negative regulatory domain of p53 bound to S100B(betabeta)[J].Nat Struct Biol,2000,7(7):570-574.
[95] Lin J,Blake M,Tang C,et al. Inhibition of p53 transcriptional activity by the S100B calcium binding protein[J].J Biol Chem,2001,276(37):35037-35041.
[96] Choi KC,Auersperg N,Leung P C. Expression and Anti-proliferative effect of second form of gonadotropin-releasing hormone in normal and neoplastic ovarian surface epithelial cells[J].J Clin Endocrinol Metab,2001 86:5075-5078.
[97] Lovas S,Palyi I,Vincze B,et al. Direct anticancer activity of gonadotropin-releasing hormone III[J].J Peptide Res,1998,52:384-389.
[98] Emons G,Weib S,Ortmann O,et al. Luteinizing hormone-releasing hormone(LHRH) might act as a negative autocrine regulator of proliferation of human ovarian cancer[J].Eur J Endoc,2000,142:665-670.
[99] Grundker C, Emons G. GnRH-mechanisms of action: in gnrh analorgues[M].The state of the art at the millennium.Carnforth,1999,95-120.
[100] Arencibia J M,Schally A V. Luteinizing hormone-releasing hormone as an autocrine growth factor in ES-2 ovaria cancer cell line[J].Int J Oncol,2000,16:1009-1013.
[101] Amotz N,Yarkoni S,Marianovsky I,et al. Adenocacinoma cells are targeted by the new GnRH-PE66 chimeric toxin through specific gonadotropin-releasing hormone binding sites[J].J Biological Chemistry,1997,272:11597-11603.
[102] Ziecik A J,Bodek G,Blitek A,et a. Nongonadal LH receptom,their involvement in female reproductive function and a new applicable approach[J],Vet J,2005,169(1)75-84.
[103] Ziecik A J,Derecka K,Gawronska B,et a1.Nongonadal LH/hCG receptom in pig:Functional importance and parallels to human[J].Semin Reprod Med,2001,19(1):19-30.
[104] Shemesh M. Actions of gonadotrophins on the uterus[J].Reproduetion,2001,121(6):835– 842.
[105] Carlson H E,Katie P,Lei Z M,et a1. Presence of luteinizing hormone/human ehorionie gonadotropin receptom in male breast tissuse[J].J Clin Endocrinol Metab, 2004, 89(8): 4119 -4123.
[106] Sibley PE,Harper ME,Joyee BG,et a1. The immunocytochemical detection of protein hormones in human prostatic tissues [J].Prostare,1981,2(2):175-185.
[107] Leuschner C,Hansel W. Targeting breast and prostate cancers through their hormone receptors [J].Biol Reprod,2005,73(5):860-865.
[108] Bose CK. Does hormone replacement thempy prevent epithelial ovarian cancer[J].Reprod Biomed Online,2005,11(1):86-92.
[109] Watanabe A,Kineshita Y,Hosokawa K,et a1. Function of estrogen-related receptor alpha in human endometrial cancer[J].J Clin EndocrinolMetab,2006,91(4):1573-1577.
[110]夏铁安,郭敏..喉癌与垂体分泌的LH、FSH水平关系的初步探讨[J].中华耳鼻咽喉科杂志.1990,25(5):268-269.
[111] http://www.fda.gov/bbs/topics/NEWS/2008/NEW01935.html.
[112]李作生,李保庆. p21和p27基因多态性与肿瘤的相关性[J].国际遗传学杂志,2006,29(4): 317-320.
[113]曹岩,郑永晨. p21基因转染人胃癌细胞对化疗药物敏感性的影响[J].吉林大学学报(医学版),2005,31(5):785-787.
[114]冉志华,冯樱,邱德凯,等.重组细小病毒H21(rhH1Δ/p21)对胃癌细胞HGC27生长抑制作用的研究[J].肿瘤,2007,27(4):251-255.
[115] Ganjavi H,Gee M,Narendran A,et al. Adenovirus-mediated p53 gene therapy in pediatric soft-tissue sarcoma cell lines: sensitization to cisplatin and doxorubicin[J].Cancer Gene Ther,2005,12(4):397-406.
[116] Simon C,Frances R A A,Piouette G,et al. Immunohistochemical localization of the interleukin-1 system in the mouse ovary during follicular growth,ovulation,and luteinization [J].Biology of Reproduction,1994,50:449-457.
[117] Pearse A G E. Embryology of the diffuse neuroendocrine system and its relationships to the common peptides [J].Frederation Proccedings,l987,38(10):2288-2294.
[118]陈树林,蒋田园,雷治海,等.山羊黄体弥散性神经内分泌细胞的分布[J].畜牧与兽医,2007,139(19):16-19.
[119]刘彤华.诊断病理学[M].北京:人民卫生出版社,l995:370-377,1027-1028.
[120]李伟,李光乾,林忠东,等.癫痫患儿血清及脑脊液神经元特异性烯醇化酶和肿瘤坏死子α测定的意义[J].实用儿科临床杂志,2007,22(8):611-613.
[121]陈俊国.新生儿缺氧缺血性脑病血清及脑脊液中神经元特异性烯醇化酶水平变化的临床分析[J].现代中西医结合杂志,2007,16(9):1213-1214.
[122]卿素珠,沈霞芬,陈谊,等.奶山羊周期黄体中催产素的免疫组化定位[J].西北农林科技大学学报,2001,29(2):25-28.
[123] Burke C R,Cardenas H,Mussard M L, et al.Histological and steroidogenic changes in dominant ovarian follicles during oestradiol-induced atresia in heifers[J].Society Reprod Ferti, 2005, 129 (5): 611-620.
[124] Pakarainen T,Zhang F P,Nurmi L,et al.Knockout of luteining hormone receptor abolishes the effects of follicle-stimulating on hormone on preovulatory maturation and ovulation of mouse graafian follicles [J].Mol Endocrinol,2005,19(10):2561-2602.
[125] Rodriguez Dorta N, Cognie Y,Gonzaez F,et a1.Effect of cocuhure with oviduct epithelial cells on viability after transfer of vitrified in vitro produced goat embryos[J].Theriogenology,2007,68(6):908-913.
[126] Qian Y,Shi W Q,Ding J T,et a1.Efects of type and state of coculture cells on in-vitro development of porcine oocytes matured and fertilized in vitro[J].J Assist Reprod Genet,2005,22(6):233-238.
[127] Spandofer SD,Soslow R,Clark R,et a1.Histologic characteristics of the endometrium predicts success when utilizing autologous endometrial cocuhure in patients with lVF failure[J].Assist Reprod Genet,2006,23(4):185-189.
[128] Azadbakht M,Valojerdi M R,Mowla S J.Development of mouse embryos cocultured with polarized or nonpolarized uterine epithelial cells using sequential culture media[J].Anita Reprod Sci,2007,100(1-2):141-157.
[129] Sugiura K,Pendola F L,Eppig J J.Oocyte control of metabolic cooperativity between oocytes and companion granulosa cells:energy metabolism[J].Dev Biol,2005,279(1):20-30.
[130] Gilchrist R B,Lane M,Thompson J G.Oocyte secreted factors:regulators of cumulus cell function and oocyte quality[J].Hum Reprod Update,2008,l4(2):159-177.
[131] Parikh F R,Nadkarni S G,Naik N J,et a1.Cumulus coeuhure and cumulus-aided embryo transfer increases pregnancy rates in patients undergoing in vitro fertilization[J].Fertil Steril,2006,86 (4):839-847.
[132] Ebner T,Moser M,Sommergmber M,et a1.Incomplete denudation of oocytes prior to ICSI enhances embryo quality and blastocyst development[J].Hum Reprod,2006,21(11):2972-2977.
[133] Nottola SA,Heyn R,Camboni A,et a1.Ultrastructural characteristics of human granulosa cells in a cocuhure system for in vitro fertilization[J].Microsc Res Tech,2006,69(6):508-516.
[134] Ge L,Han D,Lan G C,et a1.Factors affecting the in vitro action of cumulus cells on the maturing mouse oocytes[J].Mol Reprod Dev,2008,75(1):136-142.
[135] Tan XW,Ma sF,Yu JN,et a1.Effects of species and cellular activity of oviductal epithelial cells on their dialogue with cocultured mouse embryos[J].Cell Tissue Res,2007,327(1):55-66.
[136] Malekshah AK,Moghaddam AE,Daraka SM.Comparison of conditioned medium and direct coculture of human granulosa ceils on mouse embryo development[J].Indian J Exp Biol,2006,44(3):189-192.
[137] Lange C,Togel F,Ittrich H,et a1.Administered mesenchymal stem cells enhance recovery from ischemia/reperfusion-induced acute renal failure in rats[J].Kidney International,2005,68(4):1613-1617.
[138] Togel F,Hu Z,W eiss K,et a1.Administered mesenchymal stem cells protect against ischemic acuterenal failurethrough differentiation-independent mechanisms[J].Am J Physiol,2005,289(1):31-42.
[139]周涛,许百男,陈德蕙. PC12细胞分化的神经元与离体培养的大鼠原代皮质神经元之间功能性突触的形成[J ].中华神经科杂志, 2005 ,38(3) :183 - 186.
[140] Galli D,Innocenzi A,Staszewsky L,et a1.Mesoangioblasts,vessel associated multipotent stem cells,repair the infarcted heart by multiple cellular mechanisms:A conparison with bone marrow progenitors,fibroblasts,and endothelial cells[J].Arterioscler Thromb Vasc Biol;2005,25(4): 692-697.
[141] Li N,Feugier P,Serrurrier B,et a1.Human mesenchymal stem cells improve ex vivo expansion of adult humanCD34+ peripheral blood progenitor cells and decreasetheir allostimulatory capacity [J]. Exp Hematol,2007,35(3):507-515.