口腔黏膜下纤维性变癌变的危险因素及以Survivin为靶向的致病机制研究
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摘要
背景与目的
口腔黏膜下纤维性变(oral submucous fibrosis,OSF)是一种具有癌变倾向的口腔黏膜疾病。印度、孟加拉国、巴基斯坦等南亚、东南亚地区及我国湖南、台湾、海南等地为OSF高发区,这与当地居民喜好咀嚼槟榔有关。OSF的癌变率可高达7～13%,且近年来有逐渐上升的趋势。OSF癌变是多因素综合作用的结果,其发病机制目前尚无明确定论。鉴于此,有必要对OSF癌变发病机制作进一步研究。
我们首先从流行病学的角度,采用Logistic回归分析探讨OSF癌变的危险因素,为预防和治疗提供依据。接着,选择Survivin及其相关分子为代表,从分子生物学的角度,以细胞凋亡受阻、细胞周期紊乱为切入点来探讨OSF癌变的发病机制,为早期诊断与治疗提供理论依据。
方法
首先,对病例组42例OSF癌变患者和对照组40例OSF未癌变者进行多因素Logistic回归分析,研究OSF癌变与年龄等13个相关因素之间的数量关系。接着,在10例正常口腔黏膜上皮组织、40例OSF上皮组织(早期10例、中期15例、晚期15例)以及42例OSF癌变组织中,采用免疫组化、RT-PCR及Western blotting先分别检测Survivin的表达,再应用免疫组化及Western blotting检测p-Survivin的表达,然后应用Western blotting分别检测Cyclin B1、p34~(cdc2)和p-p34~(cdc2)的表达。最后,利用免疫共沉淀分析p34~(cdc2)激酶与Survivin的相关性。
结果
1.Logistic回归结果提示,引入回归方程的4个因素为:年龄、嚼槟榔持续时间、吸烟持续时间、是否合并白斑(oral leukoplakia,OLK)或扁平苔藓(oral lichen planus,OLP)。
2.免疫组化及RT-PCR结果表明:正常口腔黏膜上皮中无Survivin阳性表达;OSF组Survivin阳性表达率为47.5%(19/40),其中早期为30.0%(3/10),中期为46.7%(7/15),晚期为60.0%(9/15);OSF癌变组阳性率高达95.2%(40/42)。Survivin在OSF癌变组中阳性率高于OSF组,差异有统计学意义(P＜0.01);而OSF早、中、晚期三组间Survivin阳性表达率虽逐渐增高,但其差异并无统计学意义(P＞0.05)。Western blotting证实了上述结果。Survivin mRNA的表达与OSF癌变患者的年龄、肿瘤大小、肿瘤部位及临床TNM分期均无明显相关。
3.免疫组化结果提示:p-Survivin在正常口腔黏膜上皮中无阳性表达;OSF组p-Survivin阳性表达率为50.0%(20/40),其中早期为30.0%(3/10),中期为46.7%(7/15),晚期为66.7%(10/15);OSF癌变组阳性率高达97.6%(41/42)。OSF癌变组中p-Survivin阳性表达率高于OSF组,差异有统计学意义(P＜0.01);p-Survivin的表达率在OSF早、中、晚期三组之间相比差异无统计学意义(P＞0.05)。Western blotting结果与免疫组化检测的结果基本吻合。
4.Western blotting分析表明:正常口腔黏膜上皮中Cyclin B1表达极弱,未检测到p34~(cdc2)和p-p34~(cdc2)的阳性表达;Cyclin B1、p34~(cdc2)和p-p34~(cdc2)的表达在OSF早、中和晚期组织中表达逐渐增强;OSF癌变组织中Cyclin B1、p34~(cdc2)和p-p34~(cdc2)的表达最强。Cyclin B1、p34~(cdc2)和p-p34~(cdc2)在OSF组中阳性表达高于正常口腔黏膜组,差异有统计学意义(P＜0.05);而这些G_2/M期分子在OSF癌变组中的阳性表达高于OSF组,差异有统计学意义(P＜0.05);但在OSF早、中、晚期三组之间相比则差异无统计学意义(P＞0.05)。
5.免疫共沉淀实验证实了p34~(cdc2)与Survivin的结合。
结论
1.年龄、嚼槟榔持续时间、吸烟持续时间、是否合并OLK或OLP与OSF癌变密切相关,可能是OSF癌变的危险因素。
2.Survivin在OSF及其癌变组织中的过度表达与OSF癌变密切相关。Survivin在其中参与了细胞凋亡的抑制和有丝分裂的干扰,对癌变具有促进作用,这可能是OSF癌变过程中的一个重要分子机制。Survivin对OSF及其癌变的早期诊断和治疗具有重要的临床意义,有望成为诊断标志物及治疗靶。
3.细胞周期G_2/M期重要激酶p34~(cdc2)-Cyclin B1复合物促进Survivin Thr34位的磷酸化,进一步说明Survivin在OSF癌变中具有功能活性。
4.从细胞周期的角度证实了Cyclin B1、p34~(cdc2)在OSF及其癌变组织中的过表达引起的细胞周期G_2/M检测点紊乱可能是OSF癌变过程中另一重要的分子机制。
Background and Objectives
Oral submucous fibrosis(OSF),a kind of oral mucosa diseases,is regarded as the precancerous condition of oral squamous cell carcinoma (OSCC).It is predominantly seen in South and Southeast Asia,including India,Bangladesh,Pakistan and Taiwan.On the Chinese mainland,OSF is common in Hunan Province and Hainan Province.Its distribution is associated with chewing betel quid(BQ).The malignant transformation rate of OSF is 7～13%depending on the different study population mainly in India and Taiwan,and it is expected to rise in recent years.As far as we know,the carcinogenesis of OSF is a complex and multi-step process that results from multiple environmental factors and genetic susceptibility. However,its pathogenesis remains unclear.In view of this,the exact mechanisms of the malignant transformation of OSF needs to be investigated further.
First of all,from the epidemiological point of view we used logistic regression analysis to investigate the risk factors for carcinogenesis of OSF so as to provide the evidence for treatment and self-prevention. Secondly,we chose Survivin and its related molecules as the delegates in our study.From the perspective of molecular biology,we explored the pathogenesis of the carcinogenesis of OSF reined to two aspects of blocked apoptosis and cell cycle disorders,which could provide a theoretical basis for early diagnosis and treatment.
Methods
Firstly,a case-control study was performed between 42 patients with OSCC originating from OSF and 40 patients with OSF.The numeral relationship between the 13 interrelated factors and malignant transformation of oral submucous fibrosis was studied by the multivariate logistic regression analysis.Secondly,the expression of Survivin was analyzed by immunohistochemical SP method,reverse transcription polymerase chain reaction(RT-PCR) and Western blotting assay in 10 cases of normal oral mucosal epithelium,40 cases of OSF epithelium(10 cases of early stage,15 cases of moderately advanced stage,and 15 cases of advanced stage) and 42 cases of OSCC originating from OSF, respectively.Thirdly,we used immunohistochemical SP method and Western blotting assay to detect the expression of p-Survivin in those tissues,respectively.Fourthly,Western blotting assay was used to examine the expressions of Cyclin B1、p34~(cdc2)and p-p34~(cdc2) in the tissues, respectively.Finally,Co-immunoprecipitation was used to confirm the relationship between the p34~(cdc2) and Survivin.
Results
1.Logistic regression analysis indicated that the four factors including age,duration of BQ chewing,duration of cigarette smoking, and OSF accompanied by oral leukoplakia(OLK) or oral lichen planus(OLP) entered the logistic regression equation.
2.The results of immunohistochemical SP method and RT-PCR showed that Survivin was not detected in normal oral mucosal epithelium; the rate of Survivin detection in OSCC originating from OSF(95.2%, 40/42) was significantly higher than that in OSF(47.5%,19/40)(P＜0.01); no statistically significant difference was found in the rates of Survivin expression among the early stage(30%,3/10),the moderately advanced stage(46.7%,7/15)and the advanced stage(60.0%,9/15) of OSF(P＞0.05).Western blotting analysis further confirmed the phase expression of Survivn protein in carcinogenesis of OSF.For patients with OSCC originating from OSF,Survivin mRNA expression was not correlated to age,tumor size,tumor location or TNM stage.
3.The results of immunohistochemical SP method showed that the expression of p-Survivin was negative in normal oral mucosal epithelium; the positive staining rate of p-Survivin in OSCC originating from OSF (97.6%,41/42) was significantly higher than that in OSF(50.0%,20/40) (P＜0.01);however,the rate of p-Survivin detection showed no significant difference among the early stage(30.0%,3/10),the moderately advanced stage(46.7%,7/15) and the advanced stage(66.7%,10/15)of OSF(P＞0.05).Western blotting analysis showed gradually increasing expression of p-Survivin protein as the stage of OSF increased,which was consistent with the results of immunohistochemical SP method.
4.Western blotting analysis indicated that p34~(cdc2) and p-p34~(cdc2) were not detected in normal oral mucosal epithelium;the expression of Cyclin B1 was very weak in normal oral mucosal epithelium;there were gradually increasing expressions of Cyclin B1,p34~(cdc2) and p-p34~(cdc2) as the stage of OSF increased;the expressions of Cyclin B1,p34~(cdc2) and p-p34~(cdc2) in OSF group were significantly higher than those in normal group(P＜0.05);the expressions of these molecules showed significant diferent(P＜0.05) between the OSF and the OSCC originating from OSF, but there was no significant difference among the early stage,the moderately advanced stage and the advanced stage of OSF(P＞0.05).
5.Co-immunoprecipitation assay confirmed the combination of p34~(cdc2) and Survivin.
Conclusions
1.This study identified that age,duration of BQ chewing,duration of cigarette smoking,and presence of OLK or OLP may be the risk factors in carcinogenesis of OSF.
2.The over-expression of Survivin in OSF and OSCC originating from OSF is closely associated with malignant transformation of OSF. Survivin,as a promoting factor in carcinogenesis of OSF,takes part in the inhibition of apoptosis and mitotic interference in the course,which may be an important molecular mechanism in the carcinogenesis process of OSF.Survivin may be helpful in early diagnosis and therapy of carcinogenesis of OSF and may provide an index for diagnosis as well as a target for treatment.
3.P34~(cdc2)-Cyclin B1 complexes,the important kinase of G_2/M phase transition in cell cycle,could promote Survivin Thr34 phosphorylation.It further validates that Survivin has functional activity in malignant transformation of OSF.
4.From the perspective of the cell cycle,it was confirmed that cell cycle G_2/M checkpoint disorder resulted from the over-expression of Cyclin B1 and p34~(cdc2) in OSF and OSCC originating from OSF,which may be another important molecular mechanism in the carcinogenesis process of OSF.
口腔黏膜下纤维性变(oral submucous fibrosis,OSF)是一种具有癌变倾向的口腔黏膜疾病。印度、孟加拉国、巴基斯坦等南亚、东南亚地区及我国湖南、台湾、海南等地为OSF高发区,这与当地居民喜好咀嚼槟榔有关。OSF的癌变率可高达7～13%,且近年来有逐渐上升的趋势。OSF癌变是多因素综合作用的结果,其发病机制目前尚无明确定论。鉴于此,有必要对OSF癌变发病机制作进一步研究。
我们首先从流行病学的角度,采用Logistic回归分析探讨OSF癌变的危险因素,为预防和治疗提供依据。接着,选择Survivin及其相关分子为代表,从分子生物学的角度,以细胞凋亡受阻、细胞周期紊乱为切入点来探讨OSF癌变的发病机制,为早期诊断与治疗提供理论依据。
方法
首先,对病例组42例OSF癌变患者和对照组40例OSF未癌变者进行多因素Logistic回归分析,研究OSF癌变与年龄等13个相关因素之间的数量关系。接着,在10例正常口腔黏膜上皮组织、40例OSF上皮组织(早期10例、中期15例、晚期15例)以及42例OSF癌变组织中,采用免疫组化、RT-PCR及Western blotting先分别检测Survivin的表达,再应用免疫组化及Western blotting检测p-Survivin的表达,然后应用Western blotting分别检测Cyclin B1、p34~(cdc2)和p-p34~(cdc2)的表达。最后,利用免疫共沉淀分析p34~(cdc2)激酶与Survivin的相关性。
结果
1.Logistic回归结果提示,引入回归方程的4个因素为:年龄、嚼槟榔持续时间、吸烟持续时间、是否合并白斑(oral leukoplakia,OLK)或扁平苔藓(oral lichen planus,OLP)。
2.免疫组化及RT-PCR结果表明:正常口腔黏膜上皮中无Survivin阳性表达;OSF组Survivin阳性表达率为47.5%(19/40),其中早期为30.0%(3/10),中期为46.7%(7/15),晚期为60.0%(9/15);OSF癌变组阳性率高达95.2%(40/42)。Survivin在OSF癌变组中阳性率高于OSF组,差异有统计学意义(P＜0.01);而OSF早、中、晚期三组间Survivin阳性表达率虽逐渐增高,但其差异并无统计学意义(P＞0.05)。Western blotting证实了上述结果。Survivin mRNA的表达与OSF癌变患者的年龄、肿瘤大小、肿瘤部位及临床TNM分期均无明显相关。
3.免疫组化结果提示:p-Survivin在正常口腔黏膜上皮中无阳性表达;OSF组p-Survivin阳性表达率为50.0%(20/40),其中早期为30.0%(3/10),中期为46.7%(7/15),晚期为66.7%(10/15);OSF癌变组阳性率高达97.6%(41/42)。OSF癌变组中p-Survivin阳性表达率高于OSF组,差异有统计学意义(P＜0.01);p-Survivin的表达率在OSF早、中、晚期三组之间相比差异无统计学意义(P＞0.05)。Western blotting结果与免疫组化检测的结果基本吻合。
4.Western blotting分析表明:正常口腔黏膜上皮中Cyclin B1表达极弱,未检测到p34~(cdc2)和p-p34~(cdc2)的阳性表达;Cyclin B1、p34~(cdc2)和p-p34~(cdc2)的表达在OSF早、中和晚期组织中表达逐渐增强;OSF癌变组织中Cyclin B1、p34~(cdc2)和p-p34~(cdc2)的表达最强。Cyclin B1、p34~(cdc2)和p-p34~(cdc2)在OSF组中阳性表达高于正常口腔黏膜组,差异有统计学意义(P＜0.05);而这些G_2/M期分子在OSF癌变组中的阳性表达高于OSF组,差异有统计学意义(P＜0.05);但在OSF早、中、晚期三组之间相比则差异无统计学意义(P＞0.05)。
5.免疫共沉淀实验证实了p34~(cdc2)与Survivin的结合。
结论
1.年龄、嚼槟榔持续时间、吸烟持续时间、是否合并OLK或OLP与OSF癌变密切相关,可能是OSF癌变的危险因素。
2.Survivin在OSF及其癌变组织中的过度表达与OSF癌变密切相关。Survivin在其中参与了细胞凋亡的抑制和有丝分裂的干扰,对癌变具有促进作用,这可能是OSF癌变过程中的一个重要分子机制。Survivin对OSF及其癌变的早期诊断和治疗具有重要的临床意义,有望成为诊断标志物及治疗靶。
3.细胞周期G_2/M期重要激酶p34~(cdc2)-Cyclin B1复合物促进Survivin Thr34位的磷酸化,进一步说明Survivin在OSF癌变中具有功能活性。
4.从细胞周期的角度证实了Cyclin B1、p34~(cdc2)在OSF及其癌变组织中的过表达引起的细胞周期G_2/M检测点紊乱可能是OSF癌变过程中另一重要的分子机制。
Background and Objectives
Oral submucous fibrosis(OSF),a kind of oral mucosa diseases,is regarded as the precancerous condition of oral squamous cell carcinoma (OSCC).It is predominantly seen in South and Southeast Asia,including India,Bangladesh,Pakistan and Taiwan.On the Chinese mainland,OSF is common in Hunan Province and Hainan Province.Its distribution is associated with chewing betel quid(BQ).The malignant transformation rate of OSF is 7～13%depending on the different study population mainly in India and Taiwan,and it is expected to rise in recent years.As far as we know,the carcinogenesis of OSF is a complex and multi-step process that results from multiple environmental factors and genetic susceptibility. However,its pathogenesis remains unclear.In view of this,the exact mechanisms of the malignant transformation of OSF needs to be investigated further.
First of all,from the epidemiological point of view we used logistic regression analysis to investigate the risk factors for carcinogenesis of OSF so as to provide the evidence for treatment and self-prevention. Secondly,we chose Survivin and its related molecules as the delegates in our study.From the perspective of molecular biology,we explored the pathogenesis of the carcinogenesis of OSF reined to two aspects of blocked apoptosis and cell cycle disorders,which could provide a theoretical basis for early diagnosis and treatment.
Methods
Firstly,a case-control study was performed between 42 patients with OSCC originating from OSF and 40 patients with OSF.The numeral relationship between the 13 interrelated factors and malignant transformation of oral submucous fibrosis was studied by the multivariate logistic regression analysis.Secondly,the expression of Survivin was analyzed by immunohistochemical SP method,reverse transcription polymerase chain reaction(RT-PCR) and Western blotting assay in 10 cases of normal oral mucosal epithelium,40 cases of OSF epithelium(10 cases of early stage,15 cases of moderately advanced stage,and 15 cases of advanced stage) and 42 cases of OSCC originating from OSF, respectively.Thirdly,we used immunohistochemical SP method and Western blotting assay to detect the expression of p-Survivin in those tissues,respectively.Fourthly,Western blotting assay was used to examine the expressions of Cyclin B1、p34~(cdc2)and p-p34~(cdc2) in the tissues, respectively.Finally,Co-immunoprecipitation was used to confirm the relationship between the p34~(cdc2) and Survivin.
Results
1.Logistic regression analysis indicated that the four factors including age,duration of BQ chewing,duration of cigarette smoking, and OSF accompanied by oral leukoplakia(OLK) or oral lichen planus(OLP) entered the logistic regression equation.
2.The results of immunohistochemical SP method and RT-PCR showed that Survivin was not detected in normal oral mucosal epithelium; the rate of Survivin detection in OSCC originating from OSF(95.2%, 40/42) was significantly higher than that in OSF(47.5%,19/40)(P＜0.01); no statistically significant difference was found in the rates of Survivin expression among the early stage(30%,3/10),the moderately advanced stage(46.7%,7/15)and the advanced stage(60.0%,9/15) of OSF(P＞0.05).Western blotting analysis further confirmed the phase expression of Survivn protein in carcinogenesis of OSF.For patients with OSCC originating from OSF,Survivin mRNA expression was not correlated to age,tumor size,tumor location or TNM stage.
3.The results of immunohistochemical SP method showed that the expression of p-Survivin was negative in normal oral mucosal epithelium; the positive staining rate of p-Survivin in OSCC originating from OSF (97.6%,41/42) was significantly higher than that in OSF(50.0%,20/40) (P＜0.01);however,the rate of p-Survivin detection showed no significant difference among the early stage(30.0%,3/10),the moderately advanced stage(46.7%,7/15) and the advanced stage(66.7%,10/15)of OSF(P＞0.05).Western blotting analysis showed gradually increasing expression of p-Survivin protein as the stage of OSF increased,which was consistent with the results of immunohistochemical SP method.
4.Western blotting analysis indicated that p34~(cdc2) and p-p34~(cdc2) were not detected in normal oral mucosal epithelium;the expression of Cyclin B1 was very weak in normal oral mucosal epithelium;there were gradually increasing expressions of Cyclin B1,p34~(cdc2) and p-p34~(cdc2) as the stage of OSF increased;the expressions of Cyclin B1,p34~(cdc2) and p-p34~(cdc2) in OSF group were significantly higher than those in normal group(P＜0.05);the expressions of these molecules showed significant diferent(P＜0.05) between the OSF and the OSCC originating from OSF, but there was no significant difference among the early stage,the moderately advanced stage and the advanced stage of OSF(P＞0.05).
5.Co-immunoprecipitation assay confirmed the combination of p34~(cdc2) and Survivin.
Conclusions
1.This study identified that age,duration of BQ chewing,duration of cigarette smoking,and presence of OLK or OLP may be the risk factors in carcinogenesis of OSF.
2.The over-expression of Survivin in OSF and OSCC originating from OSF is closely associated with malignant transformation of OSF. Survivin,as a promoting factor in carcinogenesis of OSF,takes part in the inhibition of apoptosis and mitotic interference in the course,which may be an important molecular mechanism in the carcinogenesis process of OSF.Survivin may be helpful in early diagnosis and therapy of carcinogenesis of OSF and may provide an index for diagnosis as well as a target for treatment.
3.P34~(cdc2)-Cyclin B1 complexes,the important kinase of G_2/M phase transition in cell cycle,could promote Survivin Thr34 phosphorylation.It further validates that Survivin has functional activity in malignant transformation of OSF.
4.From the perspective of the cell cycle,it was confirmed that cell cycle G_2/M checkpoint disorder resulted from the over-expression of Cyclin B1 and p34~(cdc2) in OSF and OSCC originating from OSF,which may be another important molecular mechanism in the carcinogenesis process of OSF.
引文
[1]邱蔚六,郑家伟.应重视口腔颌面部恶性肿瘤的综合序列治疗.中国口腔颌面外科杂志,2005,3(3):179-182.
[2]Scully C,Bagan JV,Hopper C,et al.Oral cancer:current and future diagnostic techniques.Am J Dent,2008,21(4):199-209.
[3]Scully C.Oral precancer:preventive and medical approaches to management.Eur J Cancer B Oral Oncol,1995,31B(1):16-26.
[4]Schepman K,der Meij E,Smeele L,et al.Concomitant leukoplakia in patients with oral squamous cell carcinoma.Oral Dis,1999,5(3):206-209.
[5]Gonzalez-Moles MA,Scully C,Gil-Montoya JA.Oral lichen planus:controversies surrounding malignant transformation.Oral Dis,2008,14(3):229-243.
[6]Pindborg JJ,Sirsat SM.Oral submucous fibrosis.Oral Surg Oral Med Oral Pathol 1966,22(6):764-779.
[7]Zhang X,Reichart PA.A review of betel quid chewing,oral cancer and precancer in Mainland China.Oral Oncol,2007,43(5):424-430.
[8]雷荣昌,翦新春.咀嚼槟榔等生活习惯与口腔黏膜下的纤维性变.中固临床康复,2005,9(23):24-25.
[9]Pindborg JJ,Murti PR,Bhonsle RB,et al.Oral submucous fibrosis as a precancerous condition.Scand J Dent Res,1984,92(3):224-229.
[10]Gupta PC,Sinor PN,Bhonsle RB,et al.Oral submucous fibrosis in India:a new epidemic? Natl Med J India,1998,11(3):113-116.
[11]Lee CH,Ko YC,Huang HL,et al.The precancer risk of betel quid chewing,tobacco use and alcohol consumption in oral leukoplakia and oral submucous fibrosis in southern Taiwan.Br J Cancer,2003,88(3):366-372.
[12]Murti PR,Bhonsle RB,Pindborg JJ,et al.Malignant transformation rate in oral submucous fibrosis over a 17-year period.Community Dent Oral Epidemiol,1985,13(6):340-341.
[13]Pindborg JJ,Poulsen HE,Zachariah J.Oral epithelial changes in thirty Indians with oral cancer and submucous fibrosis.Cancer,1967,20(7):1141-1146.
[14]翦新春,沈子华,刘蜀凡,等.口腔黏膜下纤维性变(附二例报告).临床口腔医学杂志,1985,1(1):12-13.
[15]高义军,凌天牖,尹晓敏,等.口腔黏膜下纤维性变癌变的回顾性研究.临床口腔医学杂志,2005,21(2):119-120.
[16]翦新春,彭解英,唐瞻贵,等.口腔黏膜下纤维性变癌变(附三例报告).华西口腔医学杂志,2000,18(2):130-131.
[17]邱蔚六主审,张志愿主编.口腔颌面肿瘤学.济南:山东科技出版社,2004.
[18]Pindborg JJ,Reichart PA,Smith CJ,et al.Histological typing of cancer and precancer of the oral mucosa(WHO).2nd edn.New York:Berlin Heidelberg Springer,1997.
[19]Tilakaratne WM,Klinikowski ME Saku T,et al.Oral submucous fibrosis:review on aetiology and pathogenesis.Oral Oncol,2006,42(6):561-568.
[20]Auluck A,Rosin MP,Zhang L,et al.Oral submucous fibrosis,a clinically benign but potentially malignant disease:report of 3 cases and review of the literature.J Can Dent Assoc,2008,74(8):735-740.
[21]Jacob B J,Straif K,Thomas G,et al.Betel quid without tobacco as a risk factor for oral precancers.Oral Oncol,2004,40(7):697-704.
[22]Lee CH,Ko YC,Huang HL,et al.The precancer risk of betel quid chewing,tobacco use and alcohol consumption in oral leukoplakia and oral submucous fibrosis in southern Taiwan.Br J Cancer,2003,88(3):366-372.
[23]Yang SC,Lin SC,Chiang WF,et al.Areca nut extract treatment elicits the fibroblastoid morphological changes,actin re-organization and signaling activation in oral keratinocytes.J Oral Pathol Med,2003,32(10):600-605.
[24]蔺琳,凌天牖.槟榔碱在口腔黏膜纤维性变及癌变发病机制中的作用.临床 口腔医学杂志,2006,22(2):124-126.
[25]高义军,凌天牖.口腔黏膜下纤维性变发病机制的研究进展.临床口腔医学杂志,2004 20(8):502-504.
[26]Harvey W,Scutt A,Meghji S,et al.Stimulation of human buccal mucosa fibroblasts in vitro by betel-nut alkaloids.Arch Oral Biol,1986,31(1):45-49.
[27]Rajalalitha P,Vali S.Molecular pathogenesis of oral submucous fibrosis--a collagen metabolic disorder.J Oral Pathol Med,2005,34(6):321-328.
[28]Pereira AL,Veras SS,Silveira E J,et al.The role of matrix extracellular proteins and metalloproteinases in head and neck carcinomas:an updated review.Braz J Otorhinolaryngol,2005,71(1):81-86.
[29]Shieh DH,Chiang LC,Shieh TY.Augmented mRNA expression of tissue inhibitor of metalloproteinase-1 in buccal mucosal fibroblasts by arecoline and safrole as a possible pathogenesis for oral submucous fibrosis.Oral Oncol,2003,39(7):728-735.
[30]曾曙光,周磊,陈伟良,等.舌鳞癌与其颈淋巴结转移癌组织中iNOS与COX-2的表达差异.中山大学学报(医学科学版),2006,27(2):157-160.
[31]尹晓敏,高义军,彭解英,等.环氧合酶-2在口腔黏膜下纤维性变癌变过程中作用研究.中国医学工程,2006,14(3):234-236,240.
[32]Jeng JH,Tsai CL,Hahn LJ,et al.Arecoline cytotoxicity on human oral mucosal fibroblasts related to cellular thiol and esterase activities.Food Chem Toxicol,1999,37(7):751-756.
[33]Hsu H J,Chang KL,Yang YH,et al.The effects of arecoline on the release of cytokines using cultured peripheral blood mononuclear cells from patients with oral mucous diseases.Kaohsiung J Med Sci,2001,17(4):175-182.
[34]冯云枝,凌天牖.槟榔提耳义物对人类口腔黏膜上皮角朊细胞分泌内皮素的影响.临床口腔医学杂志,2001,17(3):215-216.
[35]李霞,凌天牖.槟榔提取物对口腔黏膜角朊细胞分泌肿瘤坏死因子α的影响.临床口腔医学杂志,2004,20(10):590-592.
[36]尹晓敏,黄琰,高义军,等.长沙地区2749例体检者咀嚼槟榔及口腔黏膜下 纤维性变患病情况调查分析.实用预防医学,2007,14(3):715-716.
[37]Zhang X,Li C,Liao Q,et al.Areca chewing in Xiangtan,Hunan province,China:interviews with chewers.J Oral Pathol Med,2008,37(7):423-429.
[38]Oliver AJ,Helfrick JF,Gard D.Primary oral squamous cell carcinoma:a review of 92 cases.J Oral Maxillofac Surg,1996,54(8):949-954;discussion 955.
[39]Pinholt EM,Rindum J,Pindborg JJ.Oral cancer:a retrospective study of 100Danish cases.Br J Oral Maxillofac Surg,1997,35(2):77-80.
[40]Ko YC,Huang YL,Lee CH,et al.Betel quid chewing,cigarette smoking and alcohol consumption related to oral cancer in Taiwan.J Oral Pathol Med,1995,24(10):450-453.
[41]周曾同.口腔白斑、红斑和黑斑的诊断与治疗.中华口腔医学杂志,2006,41(8):502-505.
[42]孙正,宫芸芸,黄洁.白斑癌变危险因素与口腔白斑病分期体系的关系.中华口腔医学杂志,2001,36(5):364-366.
[43]Chung CH,Yang YH,Wang TY,et al.Oral precancerous disorders associated with areca quid chewing,smoking,and alcohol drinking in southern Taiwan.J Oral Pathol Med,2005,34(8):460-466.
[44]Gonzalez-Moles MA,Scully C,Gil-Montoya JA.Oral lichen planus:controversies surrounding malignant transformation.Oral Dis,2008,14(3):229-243.
[45]翦新春,周晌辉,马文涛,等.口腔黏膜下纤维性变癌变病例临床体征的分析研究.华西口腔医学杂志,2005,23(增刊):146-148.
[46]郑家伟,李金忠,钟来平,等.口腔鳞状细胞癌临床流行病学研究现状.中国口腔颌面外科杂志,2007,5(2):83-90.
[1]Ambrosini G,Adida C,Altieri DC.A novel anti-apoptosis gene,survivin,expressed in cancer and lymphoma.Nat Med,1997,3(8):917-921.
[2]Altieri DC.Validating survivin as a cancer therapeutic target.Nat Rev Cancer, 2003, 3(1): 46-54.
[3] Conway EM, Pollefeyt S, Cornelissen J, et al. Three differentially expressed survivin cDNA variants encode proteins with distinct antiapoptotic functions. Blood, 2000, 95(4):1435-1442.
[4] Temme A, Rieger M, Reber F, et al. Localization, dynamics, and function of survivin revealed by expression of functional survivinDsRed fusion proteins in the living cell. Mol Biol Cell, 2003, 14(1):78-92.
[5] Skoufias DA, Mollinari C, Lacroix FB, et al. Human survivin is a kinetochore-associated passenger protein. J Cell Biol, 2000, 151(7):1575-1582.
[6] Tamm I, Wang Y, Sausville E, et al. IAP Family protein Survivin inhibits caspases , and anticancer drugs. Cancer Res, 1998, 58 (23): 5315-5320.
[7] Verdecia MA, Huang H, Dutil E, et al. Structure of the human anti-apoptotic protein survivin reveals a dimeric arrangement. Nat Struct Biol, 2000, 7(7):602-608.
[8] Muchmore SW, Chen J, Jakob C, et al. Crystal structure and mutagenic analysis of the inhibitor-of-apoptosis protein survivin. Mol Cell, 2000, 6(1): 173-182.
[9] Verhagen AM , Ekort PG, Pakusch M ,et al. Identification of DIABLO ,a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins. Cell, 2000, 102 (1):43-53.
[10] Mitza A, Mcguirk M , Hockenberry TN , et al. Human survivin is negatively regulated by wild type p53 and participates in p53 depend apoptotic pathway. Oncogene , 2002 ,21 (17):2613-2622.
[11] Altieri DC, Marchisio PC. Survivin apoptosis: an interloper between cell death and cell proliferation in cancer. Lab Invest, 1999, 79(11): 1327-1333.
[12] Li F, Ambrosini G, Chu EY, et al. Control of apoptosis and mitotic spindle checkpoint by survivin. Nature, 1998, 396(6711):580-584.
[13] Fortugno P , Wall NR , Giodini A , et al . Survivin exisis in immunochemically distinct subcellular pools and is involved in spindle microtubule function. Cell Soi, 2002,115 (3):575-585.
[14] Beardmore VA. Ahonen LJ. Gorbsky GJ, et al. Survivin dynamics increases at centromeres during G2/M phase transition and is regulated by microtubule-attachment and Aurora B kinase activity. J Cell Sci, 2004 , 117(Pt 18):4033-4042.
[15] Velculescu VE, Madden SL, Zhang L, et al. Analysis of human transcriptomes. Nat Genet, 1999,23(4):387-388.
[16] Ikeguchi M, Ueta T, Yamane Y, et al. Inducible nitric oxide synthase and survivin messenger RNA expression in hepatocellular carcinoma. Clin Cancer Res, 2002, 8(10):3131-3136.
[17] Ikeguchi M, Kaibara N. survivin messenger RNA expression is a good prognostic biomarker for oesophageal carcinoma. Br J Cancer, 2002, 87(8):883-887.
[18] Monzo M, Rosell R, Felip E, et al. A novel Anti-apoptosis gene: re-expression of survivin messenger RNA as apoptosis marker in non-small-cell lung cancers. J Clin Oncol 1999,17(7): 2100-2104.
[19] LuCD, Altieri DC,Tanigawa N, et al. Expression of a novel anti-apoptosis gene, survivin, correlated with tumor cell apoptosis and p53 accumulation in gastric carcinomas. Cancer Res, 1998, 58(9): 1808-1812.
[20] Tanaka K, Iwamoto S, Gon G, et al. Expression of survivin and its relationship to loss of apoptosis in breast carcinomas. Clin Cancer Res, 2000, 6(1): 127-134.
[21] Kamihira S, Yamada Y, Hirakata Y, et al. Aberrant expression of caspase cascade regulatory genes in adult T-cell leukaemia: survivin is an important determinant for prognosis. Br J Haematol, 2001, 114(1):63-69.
[22] Kawasaki H, Altieri DC, Lu CD et al. Inhibition of apoptosis by survivin predicts shorter survival rates in colorectal cancer. Cancer Res, 1998, 58(22):5071-5074.
[23] Altieri DC. New wirings in the survivin networks. Oncogene, 2008, 27(48): 6276-6284.
[24] Altieri DC. Survivin, cancer networks and pathway-directed drug discovery. Nat Rev Cancer, 2008, 8(1 ):61-70.
[25] Chang CC, Heller JD, Kuo J, et al. Tetra-O-methyl nordihydroguaiaretic acid induces growth arrest and cellular apoptosis by inhibiting Cdc2 and survivin expression. Proc Natl Acad Sci U S A, 2004, 101(36): 13239-13244.
[26]Wall NR,O'Connor DS,Plescia J,et al.Suppression of survivin phosphorylation on Thr34 by flavopiridol enhances tumor cell apoptosis.Cancer Res,2003,63(1):230-235.
[27]Pennati M,Folini M,Zaffaroni N.Targeting survivin in cancer therapy.Expert Opin Ther Targets,2008,12(4):463-476.
[28]Andersen MH,Svane IM,Becker JC,et al.The universal character of the tumor-associated antigen survivin.Clin Cancer Res,2007,13(20):5991-5994.
[29]Tolcher AW,Mita A,Lewis LD,et al.Phase I and pharmacokinetic study of YM155,a small-molecule inhibitor of survivin.J Clin Oncol,2008,26(32):5198-5203.
[30]Lopez RA,Goodman AB,Rhodes M,et al.The anticancer activity of the transcription inhibitor terameprocol(meso-tetra-O-methyl nordihydroguaiaretic acid) formulated for systemic administration.Anticancer Drugs,2007,18(8):933-939.
[31]Molckovsky A,Siu LL.First-in-class,first-in-human phase I results of targeted agents:Highlights of the 2008 American Society of Clinical Oncology meeting.J Hematol Oncol,2008,1(1):20.
[32]许春姣,彭解英,刘蜀儿,等.内皮素.1(ET-1)在口腔黏膜下纤维性变中的表达水平.临床口腔医学杂志,1999,15(1):41-44.
[33]冯云枝,凌天牖.槟榔提取物抑制人类口腔黏膜成纤维细胞生长的实验研究.临床口腔医学杂志,2006,18(3):222-223.
[34]胡延佳,翦新春,彭解英,等.口腔黏膜下纤维性变中MMP-2基因的表达及意义.临床口腔医学杂志,2007,23(3):178-180.
[35]尹晓敏,高义军,彭解英,等.环氧合酶-2在口腔黏膜下纤维性变癌变过程中作用研究.中国医学工程,2006,14(3):234-236,240.
[36]高义军,凌天牖,尹晓敏,等.槟榔碱对口腔角质形成细胞端粒酶逆转录酶表达的影响.实用口腔医学杂志,2007,23(3):360-364.
[37]Lo Muzio L,Pannone G,Leonardi R,et al.Survivin,a potential early predictor of tumor progression in the oral mucosa.J Dent Res,2003,82(11):923-928.
[38]Tanaka C,Uzawa K,Shibahara T,et al.Expression of an inhibitor of apoptosis, survivin,in oral carcinogenesis.J Dent Res,2003,82(8):607-611.
[39]秦红霞.Survivin在人口腔黏膜白斑和鳞状细胞癌中表达的研究.医药论坛杂志,2004,25(17):11-13,16.
[40]Engels K,Knauer S,Metzler D,et al.Dynamic intracellular survivin in oral squamous cell carcinoma:underlying molecular mechanism and potential as an early prognostic marker.J Pathol,2007,211(5):532-540.
[41]Lo Muzio L,Pannone G,Staibano S,et al.Survivin expression in oral squamous cell carcinoma.Br J Cancer,2003,89(12):2244-2248.
[42]Lo Muzio L,Staibano S,Pannone G,et al.Expression of the apoptosis inhibitor survivin in aggressive squamous cell carcinoma.Exp Mol Pathol,2001,70(3):249-254.
[43]Shinozawa I,Inokuchi K,Wakabayashi I,et al.Disturbed expression of the anti-apoptosis gene,survivin,and EPR-1 in hematological malignancies.Leuk Res,2000,24(11):965-970.
[44]卓贤露,冯红超,宋宇峰.口腔鳞癌组织中Survivin的表达与血管生成的关.临床口腔医学杂志,2004,20(4):207-209.
[45]Kim MJ,Lim KY,Kim JW,et al.Stage and mRNA expression of survivin in lymph node as prognostic indicators in patients with oral squamous cell carcinoma.Cancer Lett,2005,224(2):253-261.
[46]Marioni G,Bedogni A,Giacomelli L,et al.Survivin expression is significantly higher in pN+ oral and oropharyngeal primary squamous cell carcinomas than in pNO carcinomas.Acta Otolaryngol,2005,125(11):1218-1223.
[47]Lo Muzio L,Farina A,Rubini C,et al.Survivin as prognostic factor in squamous cell carcinoma of the oral cavity.Cancer Lett,2005,225(1):27-33.
[48]刘艳梅,黄建华,冯德云,等.口腔鳞癌组织中Survivin蛋白的表达及与血管生成的关系.癌症,2005,24(11):1354-1357.
[49]Lin CY,Hung HC,Kuo RC,et al.Survivin expression predicts poorer prognosis in patients with areca quid chewing-related oral squamous cell carcinoma in Taiwan.Oral Oncol,2005,41(6):645-654.
[50]Jane C,Nerurkar AV,Shirsat NV,et al.Increased survivin expression in high-grade oral squamous cell carcinoma:a study in Indian tobacco chewers,J Oral Pathol Med,2006,35(10):595-601.
[51]Lo Muzio L,D'Angelo M,Procaccini M,et al.Expression of cell cycle markers and human papillomavirus infection in oral squamous cell carcinoma:use of fuzzy neural networks.Int J Cancer,2005,115(5):717-723.
[52]Lo Muzio L,Campisi G,Giovannelli L,et al.HPV DNA and survivin expression in epithelial oral carcinogenesis:a relationship? Oral Oncol,2004,40(7):736-741.
[53]Campisi G,Di Fede O,Giovannelli L,et al.Use of fuzzy neural networks in modeling relationships of HPV infection with apoptotic and proliferation markers in potentially malignant oral lesions.Oral Oncol,2005,41(10):994-1004.
[54]杨成,丁涛,张汉东.HPV与Survivin在口腔上皮组织中致癌作用研究.临床口腔医学杂志,2005,21(7):401-403.
[55]Wang L,Zhang GM,Feng ZH.Down-regulation of survivin expression reversed multidrug resistance in adriamycin-resistant HL-60/ADR cell line.Acta Pharmacol Sin,2003,24(12):1235-1240.
[56]Freier K,Pungs S,Sticht C,et al.High survivin expression is associated with favorable outcome in advanced primary oral squamous cell carcinoma after radiation therapy.Int J Cancer,2007,120(4):942-946.
[57]闫琳,陈伟强,梁永钜,等.沉默survivin基因介导口腔表皮癌细胞KB及KBv200凋亡的比较研究.癌症,2006,25(8):933-940.
[58]Jiang G,Li J,Zeng Z,et al.Lentivirus-mediated gene therapy by suppressing survivin in BALB/c nude mice bearing oral squamous cell carcinoma.Cancer Biol Ther,2006,5(4):435-440.
[59]Satake K,Takagi E,Ishii A,et al.Anti-tumor effect of vitamin A and D on head and neck squamous cell carcinoma.Auris Nasus Larynx,2003,30(4):403-412.
[60]Li F,Ling X.Survivin study:an update of "what is the next wave"? J Cell Physiol,2006,208(3):476-486.
[1] Lee AM, Messing RO. Protein kinases and addiction. Ann N Y Acad Sci, 2008,1141:22-57.
[2] Sefton BM. Overview of protein phosphorylation. Curr Protoc Cell Biol. 2001,Chapter 14:Unit 14.1. Review
[3] Hlavacek WS, Faeder JR, Blinov ML, et al. Rules for modeling signal-transduction systems. Sci STKE, 2006, 2006(344):re6.
[4] Chong PK, Lee H, Kong JW, et al. Phosphoproteomics, oncogenic signaling and cancer research. Proteomics. 2008, 8(21):4370-4382.
[5] de la Fuente van Bentem S, Mentzen WI, de la Fuente A, et al. Towards functional phosphoproteomics by mapping differential phosphorylation events in signaling networks. Proteomics, 2008, 8(21):4453-4465.
[6] Preisinger C, von Kriegsheim A, Matallanas D, et al. Proteomics and phosphoproteomics for the mapping of cellular signalling networks. Proteomics, 2008, 8(21 ):4402-4415.
[7] Eyers P. Survivin(g) phosphorylation?: Survivin phosphorylation, mitosis and apoptosis. Cell Cycle. 2009 Jan 15;8(2). [Epub ahead of print]
[8] O'Connor DS, Grossman D, Plescia J, et al. Regulation of apoptosis at cell division by p34cdc2 phosphorylation of survivin. Proc Natl Acad Sci U S A, 2000, 97(24):13103-13107.
[9] Delacour-Larose M, Thi MN, Dimitrov S, et al. Role of survivin phosphorylation by aurora B in mitosis. Cell Cycle, 2007 ,6(15): 1878-1885.
[10] Dohi T, Xia F, Altieri DC. Compartmentalized phosphorylation of IAP by protein kinase A regulates cytoprotection. Mol Cell, 2007, 27(1): 17-28.
[11] Wall NR, O'Connor DS, Plescia J, et al. Suppression of survivin phosphorylation on Thr34 by flavopiridol enhances tumor cell apoptosis. Cancer Res,2003,63(1):230-235.
[12] O'Connor DS, Wall NR, Porter AC, et al. A p34(cdc2) survival checkpoint in cancer. Cancer Cell, 2002, 2(1):43-54.
[13]Wheatley SP, Barrett RM, Andrews PD, et al. Phosphorylation by aurora-B negatively regulates survivin function during mitosis. Cell Cycle, 2007,6(10):1220-1230.
[14] Honda R, Korner R, Nigg EA. Exploring the functional interactions between Aurora B, INCENP, and survivin in mitosis. Mol Biol Cell, 2003, 14(8):3325-3341.
[15] Dohi T, Xia F, Altieri DC. Compartmentalized phosphorylation of IAP by protein kinase A regulates cytoprotection. Mol Cell, 2007, 27(1): 17-28.
[16] Altieri DC. Validating survivin as a cancer therapeutic target. Nat Rev Cancer, 2003,3(1):46-54.
[17]曾益新.肿瘤学(第二版). 北京: 人民卫生出版社, 2003年.
[18] Bowers LM, Shapland EB, Ryan KR. Who's in charge here? Regulating cell cycle regulators. Curr Opin Microbiol, 2008,11(6):547-552.
[19] Csikasz-Nagy A, Novak B, Tyson JJ. Reverse engineering models of cell cycle regulation. Adv Exp Med Biol, 2008, 641:88-97.
[20] van den Heuvel S. Cell-cycle regulation. WormBook, 2005 , 21:1-16.
[21] Malumbres M. Cyclins and related kinases in cancer cells. J BUON, 2007 ,12 (Suppl1):S45-52.
[22] Yu Y, Kovacevic Z, Richardson DR. Tuning cell cycle regulation with an iron key. Cell Cycle, 2007 ,6(16):1982-1994.
[23] Calonge TM, O'Connell MJ. Turning off the G2 DNA damage checkpoint. DNA Repair (Amst), 2008,7(2):136-140.
[24] Miyazaki T, Arai S. Two distinct controls of mitotic cdkl/cyclin Bl activity requisite for cell growth prior to cell division. Cell Cycle, 2007,6(12): 1419-1425.
[25] Galaktionov K, Beach D. Specific activation of cdc25 tyrosine phosphatases by B-type cyclins: evidence for multiple roles of mitotic cyclins. Cell, 1991,67(6):1181-1194.
[26] Pines J, Hunter T. The differential localization of human cyclins A and B is due to a cytoplasmic retention signal in cyclin B. EMBO J, 1994,13(16):3772-3781.
[27] Francis D. The G2/M transition in eukaryotes. SEB Exp Biol Ser, 2008,59:81-98.
[28] Stark GR, Taylor WR. Control of the G2/M transition. Mol Biotechnol, 2006 ,32(3):227-248.
[29] Kaufmann W K, Paules R S. DNA damage and cell cycle checkpoints, FASEB J, 1996,10(2):238-247.
[30] Stark GR, Taylor WR. Analyzing the G2/M checkpoint. Methods Mol Biol, 2004, 280:51-82.
[31] Badie C, Banrhis J, Sobczak-Thepot J, et al. p53-dependent G2 arrest associated with a decrease in cyclins A2 and B1 levels in a human carcinoma cell line. Br J Cancer, 2000, 82(3):642-650.
[32] Southern SA, McDicken IW, Herrington CS. Evidence for keratinocyte immortalization in high-grade squanlous intraepithelial lesions of the cervix infected with high-risk human papillomavimses . Lab Invest, 2000,80(4):539-544.
[33] Sofia JC, Jang SJ, Khufi FR, et al. Overexpression of cyclin Bl in early-stage non-small cell lung cancer and its clinical implication. Cancer Res. 2000, 60(15):4000-4004.
[34] Banerjee SK, Weston AP, Zoubine MN, et al. Expression of cdc2 and cyclin Bl in Helicobacter pylori-associated gastric MALT and MALT lymphoma: relationship to cell death, proliferation, and transformation. Am J Pathol,2000,156(1): 217-225.
[35] NozoeT, Korenaga D, Kabashima, et al. Significance of cyclin Bl expression as an independent prognostic indicator of patients with squamous cell carcinoma of the esophagus. Clin Cancer Res, 2002, 8(3): 817-822.
[36] Dang Y, Sui L, Watanabe Y, et al. Clinical relevance of cyclin B1 over-expression in laryngeal squamous cell carcinoma. Cancer Lett, 2002, 177(1): 13-19.
[37] Hassan KA, El-Naggar AK, Sofia JC, et al. Clinical significance of cyclin B1 protein expression in squamous cell carcinoma of the tongue. Clin Cancer Res,2001, 7(8): 2458-2462.
[38] Lo Muzio L, Pannone G, Leonardi R, et al. Survivin, a potential early predictor of tumor progression in the oral mucosa. J Dent Res, 2003, 82: 923-928.
[39] Wall NR, O'Connor DS, Plescia J, et al. Suppression of survivin phosphorylation on Thr34 by flavopiridol enhances tumor cell apoptosis. Cancer Res, 2003, 63(1): 230-235.
[40]Salz W,Eisenberg D,Plescia J,et al.A survivin gene signature predicts aggressive tumor behavior.Cancer Res,2005,65(9):3531-3534.
[41]Zhang M,Latham DE,Delaney MA,et al.Survivin mediates resistance to antiandrogen therapy in prostate cancer.Oncogene,2005,24(15):2474-2482.
[42]Kaldis P,Aleem E.Cell cycle sibling rivalry:Cdc2 vs.Cdk2.Cell Cycle,2005,4(11):1491-1494.
[43]Malumbres M,Hunt SL,Sotillo R,et al.Driving the cell cycle to cancer.Adv Exp Med Biol,2003,532:1-11.
[44]陈新,周健.细胞周期调控蛋白P34cdc2与cyclin B1在头颈部鳞癌中的预测价值.国外医学口腔医学分册,2005,32(6):428-430.
[45]Wada S,Yue L,Furuta I.Prognostic significance of p34cdc2 expression in tongue squamous cell carcinoma.Oral Oncol,2004,40(2):164-169.
[46]Pannone G,Bufo P,Serpico R,et al.Survivin phosphorylation and M-phase promoting factor in oral carcinogenesis.Histol Histopathol,2007,22(11):1241-1249.
[47]Kushner J,Bradley G,Young B,et al.Aberrant expression of cyclin A and cyclin B1 proteins in oral carcinoma.J Oral Pathol Med,1999,28(2):77-81.
[48]Ruchaud S,Carmena M,Earnshaw WC.Chromosomal passengers:conducting cell division.Nat Rev Mol Cell Biol,2007,8(10):798-812.
[49]Li F,Yang J,Ramnath N,et al.Nuclear or cytoplasmic expression of survivin:what is the significance? Int J Cancer,2005,114(4):509-512.
[50]Engels K,Knauer S,Metzler D,et al.Dynamic intracellular survivin in oral squamous cell carcinoma:underlying molecular mechanism and potential as an early prognostic marker.J Pathol,2007,211(5):532-540.
[51]Stauber RH,Mann W,Knauer SK.Nuclear and cytoplasmic survivin:molecular mechanism,prognostic,and therapeutic potential.Cancer Res,2007,67(13):5999-6002.
[1]Sidransky D.Emerging molecular markers of cancer.Nat Rev Cancer,2002,2(3):210-219.
[2]Leethanakul C,Knezevic V,Patel V,et al.Gene discovery in oral squamous cell carcinoma through the Head and Neck Cancer Genome Anatomy Project:confirmation by microarray analysis.Oral Oncol,2003,39(3):248-258.
[3]Odani T,Ito D,Li MH,et al.Gene expression profiles of oral leukoplakia and carcinoma:genome-wide comparison analysis using oligonucleotide microarray technology.Int J Oncol,2006,28(3):619-624.
[4]周曾同,陶疆,张庆华,等.白斑癌变相关基因的表达谱研究.临床口腔医学杂志,2003,19(8):491-494.
[5]Shimada K,Uzawa K,Kato M,et al.Aberrant expression of RAB1A in human tongue cancer.Br J Cancer,2005,92(10):1915-1921.
[6]Makitie AA,Pintor Dos Reis P,Arora S,et al.Molecular characterization of salivary gland malignancy using the Smgb-Tag transgenic mouse model.Lab Invest,2005,85(8):947-961.
[7]Leivo I,Jee KJ,Heikinheimo K,et al.Characterization of gene expression in major types of salivary gland carcinomas with epithelial differentiation.Cancer Genet Cytogenet,2005,156(2):104-113.
[8]Yasumoto J,Kirita T,Takahashi A,et al.Apoptosis-related gene expression after hyperthermia in human tongue squamous cell carcinoma cells harboring wild-type or mutated-type p53.Cancer Lett,2004,204(1):41-51.
[9]Higo M,Uzawa K,Kouzu Y,et al.Identification of candidate radioresistant genes in human squamous cell carcinoma cells through gene expression analysis using DNA microarrays. Oncol Rep, 2005,14(5):1293-1298.
[10] Tsai WC, Tsai ST, Ko JY, et al. The mRNA profile of genes in betel quid chewing oral cancer patients. Oral Oncol, 2004,40(4):418-426.
[11] O'Donnell RK, Kupferman M, Wei SJ, et al. Gene expression signature predicts lymphatic metastasis in squamous cell carcinoma of the oral cavity.Oncogene, 2005, 24(7): 1244-1251.
[12] Roepman P, Wessels LF, Kettelarij N, et al. An expression profile for diagnosis of lymph node metastases from primary head and neck squamous cell carcinomas. Nat Genet, 2005, 37(2): 182-186.
[13] Gires O, Mack B, Rauch J, et al. CK8 correlates with malignancy in leukoplakia and carcinomas of the head and neck. Biochem Biophys Res Commun, 2006, 343(1):252-259.
[14] He QY, Chen J, Kung HF, et al. Identification of tumor-associated proteins in oral tongue squamous cell carcinoma by proteomics. Proteomics, 2004, 4(1):271-278.
[15] Chen J, He QY, Yuen AP, et al. Proteomics of buccal squamous cell carcinoma: the involvement of multiple pathways in tumorigenesis.Proteomics, 2004,4(8):2465-2475.
[16] Nakashima D, Uzawa K, Kasamatsu A, et al. Protein expression profiling identifies maspin and stathmin as potential biomarkers of adenoid cystic carcinoma of the salivary glands. Int J Cancer, 2006, 118(3):704-713.
[17] An J, Sun JY, Yuan Q, et al. Proteomics analysis of differentially expressed metastasis-associated proteins in adenoid cystic carcinoma cell lines of human salivary gland. Oral Oncol, 2004, 40 (4):400-408.
[1]Altieri DC.Validating survivin as a cancer therapeutic target.Nat Rev Cancer,2003,3(1):46-54.
[2]Conway EM,Pollefeyt S,Cornelissen J,et al.Three differentially expressed survivin cDNA variants encode proteins with distinct antiapoptotic functions.Blood,2000,95(4):1435-1442.
[3]Altieri DC,Marchisio PC.Survivin apoptosis:an interloper between cell death and cell proliferation in cancer.Lab Invest,1999,79(11):1327-1333.
[4]Downer MC,Moles DR,Palmer S,et al.A systematic review of test performance in screening for oral cancer and precancer.Oral Oncol,2004,40(3):264-273.
[5]Lo Muzio L,Pannone G,Leonardi R,et al.Survivin,a potential early predictor of tumor progression in the oral mucosa.J Dent Res,2003,82(11):923-928.
[6]Shinozawa I,Inokuchi K,Wakabayashi I,et al.Disturbed expression of the antiapoptosis gene,surviving,and EPR-1 in hematological malignancies.Leuk Res,2000,24(11):965-970.
[7]卓贤露,冯红超,宋宇峰.口腔鳞癌组织中Survivin的表达与血管生成的关系.临床口腔医学杂志,2004,20(4):207-209.
[8]Kim MJ,Lim KY,Kim JW,et al.Stage and mRNA expression of survivin in lymph node as prognostic indicators in patients with oral squamous cell carcinoma.Cancer Lett,2005,224(2):253-261.
[9]Marioni G,Bedogni A,Giacomelli L,et al.Survivin expression is significantly higher in pN+ oral and oropharyngeal primary squamous cell carcinomas than in pN0 carcinomas.Acta Otolaryngol,2005,125(11):1218-1223.
[10]Lo Muzio L,Farina A,Rubini C,et al.Survivin as prognostic factor in squamous cell carcinoma of the oral cavity.Cancer Lett,2005,225(1):27-33.
[11]刘艳梅,黄建华,冯德云,等.口腔鳞癌组织中Survivin蛋白的表达及与血管生成的关系.癌症,2005,24(11):1354-1357.
[12]Lin CY,Hung HC,Kuo RC,et al.Survivin expression predicts poorer prognosis in patients with areca quid chewing-related oral squamous cell carcinoma in Taiwan.Oral Oncol,2005,41(6):645-654.
[13]Jane C,Nerurkar AV,Shirsat NV,et al.Increased survivin expression in high-grade oral squamous cell carcinoma:a study in Indian tobacco chewers.J Oral Pathol Med,2006,35(10):595-601.
[14]Lo Muzio L,D'Angelo M,Procaccini M,et al.Expression of cell cycle markers and human papillomavirus infection in oral squamous cell carcinoma:use of fuzzy neural networks.Int J Cancer,2005,115(5):717-723.
[15]Lo Muzio L,Campisi G,Giovannelli L,et al.HPV DNA and survivin expression in epithelial oral carcinogenesis:a relationship? Oral Oncol,2004,40(7):736-741.
[16]Campisi G,Di Fede O,Giovannelli L,et al.Use of fuzzy neural networks in modeling relationships of HPV infection with apoptotic and proliferation markers in potentially malignant oral lesions.Oral Oncol,2005,41(10):994-1004.
[17]Engels K,Knauer S,Metzler D,et al.Dynamic intracellular surviving in oral squamous cell carcinoma:underlying molecular mechanism and potential as an early prognostic marker.J Pathol,2007,211(5):532-540.
[18]Freier K,Pungs S,Sticht C,et al.High survivin expression is associated with favorable outcome in advanced primary oral squamous cell carcinoma after radiation therapy.Int J Cancer,2007,120(4):942-946.
[19]闫琳,陈伟强,梁永钜,等.survivin基因介导口腔表皮癌细胞KB及KBv200凋亡的比较研究.癌症,2006,25(8):933-940.
[20]Jiang G,Li J,Zeng Z,et al.Lentivirus-mediated gene therapy by suppressing survivin in BALB/c nude mice bearing oral squamouscell carcinoma.Cancer Biol Ther,2006,5(4):435-440.
[21]Li F,Ling X.Survivin study:an update of "what is the next wave"? J Cell Physiol,2006,208(3):476-486.
[2]Scully C,Bagan JV,Hopper C,et al.Oral cancer:current and future diagnostic techniques.Am J Dent,2008,21(4):199-209.
[3]Scully C.Oral precancer:preventive and medical approaches to management.Eur J Cancer B Oral Oncol,1995,31B(1):16-26.
[4]Schepman K,der Meij E,Smeele L,et al.Concomitant leukoplakia in patients with oral squamous cell carcinoma.Oral Dis,1999,5(3):206-209.
[5]Gonzalez-Moles MA,Scully C,Gil-Montoya JA.Oral lichen planus:controversies surrounding malignant transformation.Oral Dis,2008,14(3):229-243.
[6]Pindborg JJ,Sirsat SM.Oral submucous fibrosis.Oral Surg Oral Med Oral Pathol 1966,22(6):764-779.
[7]Zhang X,Reichart PA.A review of betel quid chewing,oral cancer and precancer in Mainland China.Oral Oncol,2007,43(5):424-430.
[8]雷荣昌,翦新春.咀嚼槟榔等生活习惯与口腔黏膜下的纤维性变.中固临床康复,2005,9(23):24-25.
[9]Pindborg JJ,Murti PR,Bhonsle RB,et al.Oral submucous fibrosis as a precancerous condition.Scand J Dent Res,1984,92(3):224-229.
[10]Gupta PC,Sinor PN,Bhonsle RB,et al.Oral submucous fibrosis in India:a new epidemic? Natl Med J India,1998,11(3):113-116.
[11]Lee CH,Ko YC,Huang HL,et al.The precancer risk of betel quid chewing,tobacco use and alcohol consumption in oral leukoplakia and oral submucous fibrosis in southern Taiwan.Br J Cancer,2003,88(3):366-372.
[12]Murti PR,Bhonsle RB,Pindborg JJ,et al.Malignant transformation rate in oral submucous fibrosis over a 17-year period.Community Dent Oral Epidemiol,1985,13(6):340-341.
[13]Pindborg JJ,Poulsen HE,Zachariah J.Oral epithelial changes in thirty Indians with oral cancer and submucous fibrosis.Cancer,1967,20(7):1141-1146.
[14]翦新春,沈子华,刘蜀凡,等.口腔黏膜下纤维性变(附二例报告).临床口腔医学杂志,1985,1(1):12-13.
[15]高义军,凌天牖,尹晓敏,等.口腔黏膜下纤维性变癌变的回顾性研究.临床口腔医学杂志,2005,21(2):119-120.
[16]翦新春,彭解英,唐瞻贵,等.口腔黏膜下纤维性变癌变(附三例报告).华西口腔医学杂志,2000,18(2):130-131.
[17]邱蔚六主审,张志愿主编.口腔颌面肿瘤学.济南:山东科技出版社,2004.
[18]Pindborg JJ,Reichart PA,Smith CJ,et al.Histological typing of cancer and precancer of the oral mucosa(WHO).2nd edn.New York:Berlin Heidelberg Springer,1997.
[19]Tilakaratne WM,Klinikowski ME Saku T,et al.Oral submucous fibrosis:review on aetiology and pathogenesis.Oral Oncol,2006,42(6):561-568.
[20]Auluck A,Rosin MP,Zhang L,et al.Oral submucous fibrosis,a clinically benign but potentially malignant disease:report of 3 cases and review of the literature.J Can Dent Assoc,2008,74(8):735-740.
[21]Jacob B J,Straif K,Thomas G,et al.Betel quid without tobacco as a risk factor for oral precancers.Oral Oncol,2004,40(7):697-704.
[22]Lee CH,Ko YC,Huang HL,et al.The precancer risk of betel quid chewing,tobacco use and alcohol consumption in oral leukoplakia and oral submucous fibrosis in southern Taiwan.Br J Cancer,2003,88(3):366-372.
[23]Yang SC,Lin SC,Chiang WF,et al.Areca nut extract treatment elicits the fibroblastoid morphological changes,actin re-organization and signaling activation in oral keratinocytes.J Oral Pathol Med,2003,32(10):600-605.
[24]蔺琳,凌天牖.槟榔碱在口腔黏膜纤维性变及癌变发病机制中的作用.临床 口腔医学杂志,2006,22(2):124-126.
[25]高义军,凌天牖.口腔黏膜下纤维性变发病机制的研究进展.临床口腔医学杂志,2004 20(8):502-504.
[26]Harvey W,Scutt A,Meghji S,et al.Stimulation of human buccal mucosa fibroblasts in vitro by betel-nut alkaloids.Arch Oral Biol,1986,31(1):45-49.
[27]Rajalalitha P,Vali S.Molecular pathogenesis of oral submucous fibrosis--a collagen metabolic disorder.J Oral Pathol Med,2005,34(6):321-328.
[28]Pereira AL,Veras SS,Silveira E J,et al.The role of matrix extracellular proteins and metalloproteinases in head and neck carcinomas:an updated review.Braz J Otorhinolaryngol,2005,71(1):81-86.
[29]Shieh DH,Chiang LC,Shieh TY.Augmented mRNA expression of tissue inhibitor of metalloproteinase-1 in buccal mucosal fibroblasts by arecoline and safrole as a possible pathogenesis for oral submucous fibrosis.Oral Oncol,2003,39(7):728-735.
[30]曾曙光,周磊,陈伟良,等.舌鳞癌与其颈淋巴结转移癌组织中iNOS与COX-2的表达差异.中山大学学报(医学科学版),2006,27(2):157-160.
[31]尹晓敏,高义军,彭解英,等.环氧合酶-2在口腔黏膜下纤维性变癌变过程中作用研究.中国医学工程,2006,14(3):234-236,240.
[32]Jeng JH,Tsai CL,Hahn LJ,et al.Arecoline cytotoxicity on human oral mucosal fibroblasts related to cellular thiol and esterase activities.Food Chem Toxicol,1999,37(7):751-756.
[33]Hsu H J,Chang KL,Yang YH,et al.The effects of arecoline on the release of cytokines using cultured peripheral blood mononuclear cells from patients with oral mucous diseases.Kaohsiung J Med Sci,2001,17(4):175-182.
[34]冯云枝,凌天牖.槟榔提耳义物对人类口腔黏膜上皮角朊细胞分泌内皮素的影响.临床口腔医学杂志,2001,17(3):215-216.
[35]李霞,凌天牖.槟榔提取物对口腔黏膜角朊细胞分泌肿瘤坏死因子α的影响.临床口腔医学杂志,2004,20(10):590-592.
[36]尹晓敏,黄琰,高义军,等.长沙地区2749例体检者咀嚼槟榔及口腔黏膜下 纤维性变患病情况调查分析.实用预防医学,2007,14(3):715-716.
[37]Zhang X,Li C,Liao Q,et al.Areca chewing in Xiangtan,Hunan province,China:interviews with chewers.J Oral Pathol Med,2008,37(7):423-429.
[38]Oliver AJ,Helfrick JF,Gard D.Primary oral squamous cell carcinoma:a review of 92 cases.J Oral Maxillofac Surg,1996,54(8):949-954;discussion 955.
[39]Pinholt EM,Rindum J,Pindborg JJ.Oral cancer:a retrospective study of 100Danish cases.Br J Oral Maxillofac Surg,1997,35(2):77-80.
[40]Ko YC,Huang YL,Lee CH,et al.Betel quid chewing,cigarette smoking and alcohol consumption related to oral cancer in Taiwan.J Oral Pathol Med,1995,24(10):450-453.
[41]周曾同.口腔白斑、红斑和黑斑的诊断与治疗.中华口腔医学杂志,2006,41(8):502-505.
[42]孙正,宫芸芸,黄洁.白斑癌变危险因素与口腔白斑病分期体系的关系.中华口腔医学杂志,2001,36(5):364-366.
[43]Chung CH,Yang YH,Wang TY,et al.Oral precancerous disorders associated with areca quid chewing,smoking,and alcohol drinking in southern Taiwan.J Oral Pathol Med,2005,34(8):460-466.
[44]Gonzalez-Moles MA,Scully C,Gil-Montoya JA.Oral lichen planus:controversies surrounding malignant transformation.Oral Dis,2008,14(3):229-243.
[45]翦新春,周晌辉,马文涛,等.口腔黏膜下纤维性变癌变病例临床体征的分析研究.华西口腔医学杂志,2005,23(增刊):146-148.
[46]郑家伟,李金忠,钟来平,等.口腔鳞状细胞癌临床流行病学研究现状.中国口腔颌面外科杂志,2007,5(2):83-90.
[1]Ambrosini G,Adida C,Altieri DC.A novel anti-apoptosis gene,survivin,expressed in cancer and lymphoma.Nat Med,1997,3(8):917-921.
[2]Altieri DC.Validating survivin as a cancer therapeutic target.Nat Rev Cancer, 2003, 3(1): 46-54.
[3] Conway EM, Pollefeyt S, Cornelissen J, et al. Three differentially expressed survivin cDNA variants encode proteins with distinct antiapoptotic functions. Blood, 2000, 95(4):1435-1442.
[4] Temme A, Rieger M, Reber F, et al. Localization, dynamics, and function of survivin revealed by expression of functional survivinDsRed fusion proteins in the living cell. Mol Biol Cell, 2003, 14(1):78-92.
[5] Skoufias DA, Mollinari C, Lacroix FB, et al. Human survivin is a kinetochore-associated passenger protein. J Cell Biol, 2000, 151(7):1575-1582.
[6] Tamm I, Wang Y, Sausville E, et al. IAP Family protein Survivin inhibits caspases , and anticancer drugs. Cancer Res, 1998, 58 (23): 5315-5320.
[7] Verdecia MA, Huang H, Dutil E, et al. Structure of the human anti-apoptotic protein survivin reveals a dimeric arrangement. Nat Struct Biol, 2000, 7(7):602-608.
[8] Muchmore SW, Chen J, Jakob C, et al. Crystal structure and mutagenic analysis of the inhibitor-of-apoptosis protein survivin. Mol Cell, 2000, 6(1): 173-182.
[9] Verhagen AM , Ekort PG, Pakusch M ,et al. Identification of DIABLO ,a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins. Cell, 2000, 102 (1):43-53.
[10] Mitza A, Mcguirk M , Hockenberry TN , et al. Human survivin is negatively regulated by wild type p53 and participates in p53 depend apoptotic pathway. Oncogene , 2002 ,21 (17):2613-2622.
[11] Altieri DC, Marchisio PC. Survivin apoptosis: an interloper between cell death and cell proliferation in cancer. Lab Invest, 1999, 79(11): 1327-1333.
[12] Li F, Ambrosini G, Chu EY, et al. Control of apoptosis and mitotic spindle checkpoint by survivin. Nature, 1998, 396(6711):580-584.
[13] Fortugno P , Wall NR , Giodini A , et al . Survivin exisis in immunochemically distinct subcellular pools and is involved in spindle microtubule function. Cell Soi, 2002,115 (3):575-585.
[14] Beardmore VA. Ahonen LJ. Gorbsky GJ, et al. Survivin dynamics increases at centromeres during G2/M phase transition and is regulated by microtubule-attachment and Aurora B kinase activity. J Cell Sci, 2004 , 117(Pt 18):4033-4042.
[15] Velculescu VE, Madden SL, Zhang L, et al. Analysis of human transcriptomes. Nat Genet, 1999,23(4):387-388.
[16] Ikeguchi M, Ueta T, Yamane Y, et al. Inducible nitric oxide synthase and survivin messenger RNA expression in hepatocellular carcinoma. Clin Cancer Res, 2002, 8(10):3131-3136.
[17] Ikeguchi M, Kaibara N. survivin messenger RNA expression is a good prognostic biomarker for oesophageal carcinoma. Br J Cancer, 2002, 87(8):883-887.
[18] Monzo M, Rosell R, Felip E, et al. A novel Anti-apoptosis gene: re-expression of survivin messenger RNA as apoptosis marker in non-small-cell lung cancers. J Clin Oncol 1999,17(7): 2100-2104.
[19] LuCD, Altieri DC,Tanigawa N, et al. Expression of a novel anti-apoptosis gene, survivin, correlated with tumor cell apoptosis and p53 accumulation in gastric carcinomas. Cancer Res, 1998, 58(9): 1808-1812.
[20] Tanaka K, Iwamoto S, Gon G, et al. Expression of survivin and its relationship to loss of apoptosis in breast carcinomas. Clin Cancer Res, 2000, 6(1): 127-134.
[21] Kamihira S, Yamada Y, Hirakata Y, et al. Aberrant expression of caspase cascade regulatory genes in adult T-cell leukaemia: survivin is an important determinant for prognosis. Br J Haematol, 2001, 114(1):63-69.
[22] Kawasaki H, Altieri DC, Lu CD et al. Inhibition of apoptosis by survivin predicts shorter survival rates in colorectal cancer. Cancer Res, 1998, 58(22):5071-5074.
[23] Altieri DC. New wirings in the survivin networks. Oncogene, 2008, 27(48): 6276-6284.
[24] Altieri DC. Survivin, cancer networks and pathway-directed drug discovery. Nat Rev Cancer, 2008, 8(1 ):61-70.
[25] Chang CC, Heller JD, Kuo J, et al. Tetra-O-methyl nordihydroguaiaretic acid induces growth arrest and cellular apoptosis by inhibiting Cdc2 and survivin expression. Proc Natl Acad Sci U S A, 2004, 101(36): 13239-13244.
[26]Wall NR,O'Connor DS,Plescia J,et al.Suppression of survivin phosphorylation on Thr34 by flavopiridol enhances tumor cell apoptosis.Cancer Res,2003,63(1):230-235.
[27]Pennati M,Folini M,Zaffaroni N.Targeting survivin in cancer therapy.Expert Opin Ther Targets,2008,12(4):463-476.
[28]Andersen MH,Svane IM,Becker JC,et al.The universal character of the tumor-associated antigen survivin.Clin Cancer Res,2007,13(20):5991-5994.
[29]Tolcher AW,Mita A,Lewis LD,et al.Phase I and pharmacokinetic study of YM155,a small-molecule inhibitor of survivin.J Clin Oncol,2008,26(32):5198-5203.
[30]Lopez RA,Goodman AB,Rhodes M,et al.The anticancer activity of the transcription inhibitor terameprocol(meso-tetra-O-methyl nordihydroguaiaretic acid) formulated for systemic administration.Anticancer Drugs,2007,18(8):933-939.
[31]Molckovsky A,Siu LL.First-in-class,first-in-human phase I results of targeted agents:Highlights of the 2008 American Society of Clinical Oncology meeting.J Hematol Oncol,2008,1(1):20.
[32]许春姣,彭解英,刘蜀儿,等.内皮素.1(ET-1)在口腔黏膜下纤维性变中的表达水平.临床口腔医学杂志,1999,15(1):41-44.
[33]冯云枝,凌天牖.槟榔提取物抑制人类口腔黏膜成纤维细胞生长的实验研究.临床口腔医学杂志,2006,18(3):222-223.
[34]胡延佳,翦新春,彭解英,等.口腔黏膜下纤维性变中MMP-2基因的表达及意义.临床口腔医学杂志,2007,23(3):178-180.
[35]尹晓敏,高义军,彭解英,等.环氧合酶-2在口腔黏膜下纤维性变癌变过程中作用研究.中国医学工程,2006,14(3):234-236,240.
[36]高义军,凌天牖,尹晓敏,等.槟榔碱对口腔角质形成细胞端粒酶逆转录酶表达的影响.实用口腔医学杂志,2007,23(3):360-364.
[37]Lo Muzio L,Pannone G,Leonardi R,et al.Survivin,a potential early predictor of tumor progression in the oral mucosa.J Dent Res,2003,82(11):923-928.
[38]Tanaka C,Uzawa K,Shibahara T,et al.Expression of an inhibitor of apoptosis, survivin,in oral carcinogenesis.J Dent Res,2003,82(8):607-611.
[39]秦红霞.Survivin在人口腔黏膜白斑和鳞状细胞癌中表达的研究.医药论坛杂志,2004,25(17):11-13,16.
[40]Engels K,Knauer S,Metzler D,et al.Dynamic intracellular survivin in oral squamous cell carcinoma:underlying molecular mechanism and potential as an early prognostic marker.J Pathol,2007,211(5):532-540.
[41]Lo Muzio L,Pannone G,Staibano S,et al.Survivin expression in oral squamous cell carcinoma.Br J Cancer,2003,89(12):2244-2248.
[42]Lo Muzio L,Staibano S,Pannone G,et al.Expression of the apoptosis inhibitor survivin in aggressive squamous cell carcinoma.Exp Mol Pathol,2001,70(3):249-254.
[43]Shinozawa I,Inokuchi K,Wakabayashi I,et al.Disturbed expression of the anti-apoptosis gene,survivin,and EPR-1 in hematological malignancies.Leuk Res,2000,24(11):965-970.
[44]卓贤露,冯红超,宋宇峰.口腔鳞癌组织中Survivin的表达与血管生成的关.临床口腔医学杂志,2004,20(4):207-209.
[45]Kim MJ,Lim KY,Kim JW,et al.Stage and mRNA expression of survivin in lymph node as prognostic indicators in patients with oral squamous cell carcinoma.Cancer Lett,2005,224(2):253-261.
[46]Marioni G,Bedogni A,Giacomelli L,et al.Survivin expression is significantly higher in pN+ oral and oropharyngeal primary squamous cell carcinomas than in pNO carcinomas.Acta Otolaryngol,2005,125(11):1218-1223.
[47]Lo Muzio L,Farina A,Rubini C,et al.Survivin as prognostic factor in squamous cell carcinoma of the oral cavity.Cancer Lett,2005,225(1):27-33.
[48]刘艳梅,黄建华,冯德云,等.口腔鳞癌组织中Survivin蛋白的表达及与血管生成的关系.癌症,2005,24(11):1354-1357.
[49]Lin CY,Hung HC,Kuo RC,et al.Survivin expression predicts poorer prognosis in patients with areca quid chewing-related oral squamous cell carcinoma in Taiwan.Oral Oncol,2005,41(6):645-654.
[50]Jane C,Nerurkar AV,Shirsat NV,et al.Increased survivin expression in high-grade oral squamous cell carcinoma:a study in Indian tobacco chewers,J Oral Pathol Med,2006,35(10):595-601.
[51]Lo Muzio L,D'Angelo M,Procaccini M,et al.Expression of cell cycle markers and human papillomavirus infection in oral squamous cell carcinoma:use of fuzzy neural networks.Int J Cancer,2005,115(5):717-723.
[52]Lo Muzio L,Campisi G,Giovannelli L,et al.HPV DNA and survivin expression in epithelial oral carcinogenesis:a relationship? Oral Oncol,2004,40(7):736-741.
[53]Campisi G,Di Fede O,Giovannelli L,et al.Use of fuzzy neural networks in modeling relationships of HPV infection with apoptotic and proliferation markers in potentially malignant oral lesions.Oral Oncol,2005,41(10):994-1004.
[54]杨成,丁涛,张汉东.HPV与Survivin在口腔上皮组织中致癌作用研究.临床口腔医学杂志,2005,21(7):401-403.
[55]Wang L,Zhang GM,Feng ZH.Down-regulation of survivin expression reversed multidrug resistance in adriamycin-resistant HL-60/ADR cell line.Acta Pharmacol Sin,2003,24(12):1235-1240.
[56]Freier K,Pungs S,Sticht C,et al.High survivin expression is associated with favorable outcome in advanced primary oral squamous cell carcinoma after radiation therapy.Int J Cancer,2007,120(4):942-946.
[57]闫琳,陈伟强,梁永钜,等.沉默survivin基因介导口腔表皮癌细胞KB及KBv200凋亡的比较研究.癌症,2006,25(8):933-940.
[58]Jiang G,Li J,Zeng Z,et al.Lentivirus-mediated gene therapy by suppressing survivin in BALB/c nude mice bearing oral squamous cell carcinoma.Cancer Biol Ther,2006,5(4):435-440.
[59]Satake K,Takagi E,Ishii A,et al.Anti-tumor effect of vitamin A and D on head and neck squamous cell carcinoma.Auris Nasus Larynx,2003,30(4):403-412.
[60]Li F,Ling X.Survivin study:an update of "what is the next wave"? J Cell Physiol,2006,208(3):476-486.
[1] Lee AM, Messing RO. Protein kinases and addiction. Ann N Y Acad Sci, 2008,1141:22-57.
[2] Sefton BM. Overview of protein phosphorylation. Curr Protoc Cell Biol. 2001,Chapter 14:Unit 14.1. Review
[3] Hlavacek WS, Faeder JR, Blinov ML, et al. Rules for modeling signal-transduction systems. Sci STKE, 2006, 2006(344):re6.
[4] Chong PK, Lee H, Kong JW, et al. Phosphoproteomics, oncogenic signaling and cancer research. Proteomics. 2008, 8(21):4370-4382.
[5] de la Fuente van Bentem S, Mentzen WI, de la Fuente A, et al. Towards functional phosphoproteomics by mapping differential phosphorylation events in signaling networks. Proteomics, 2008, 8(21):4453-4465.
[6] Preisinger C, von Kriegsheim A, Matallanas D, et al. Proteomics and phosphoproteomics for the mapping of cellular signalling networks. Proteomics, 2008, 8(21 ):4402-4415.
[7] Eyers P. Survivin(g) phosphorylation?: Survivin phosphorylation, mitosis and apoptosis. Cell Cycle. 2009 Jan 15;8(2). [Epub ahead of print]
[8] O'Connor DS, Grossman D, Plescia J, et al. Regulation of apoptosis at cell division by p34cdc2 phosphorylation of survivin. Proc Natl Acad Sci U S A, 2000, 97(24):13103-13107.
[9] Delacour-Larose M, Thi MN, Dimitrov S, et al. Role of survivin phosphorylation by aurora B in mitosis. Cell Cycle, 2007 ,6(15): 1878-1885.
[10] Dohi T, Xia F, Altieri DC. Compartmentalized phosphorylation of IAP by protein kinase A regulates cytoprotection. Mol Cell, 2007, 27(1): 17-28.
[11] Wall NR, O'Connor DS, Plescia J, et al. Suppression of survivin phosphorylation on Thr34 by flavopiridol enhances tumor cell apoptosis. Cancer Res,2003,63(1):230-235.
[12] O'Connor DS, Wall NR, Porter AC, et al. A p34(cdc2) survival checkpoint in cancer. Cancer Cell, 2002, 2(1):43-54.
[13]Wheatley SP, Barrett RM, Andrews PD, et al. Phosphorylation by aurora-B negatively regulates survivin function during mitosis. Cell Cycle, 2007,6(10):1220-1230.
[14] Honda R, Korner R, Nigg EA. Exploring the functional interactions between Aurora B, INCENP, and survivin in mitosis. Mol Biol Cell, 2003, 14(8):3325-3341.
[15] Dohi T, Xia F, Altieri DC. Compartmentalized phosphorylation of IAP by protein kinase A regulates cytoprotection. Mol Cell, 2007, 27(1): 17-28.
[16] Altieri DC. Validating survivin as a cancer therapeutic target. Nat Rev Cancer, 2003,3(1):46-54.
[17]曾益新.肿瘤学(第二版). 北京: 人民卫生出版社, 2003年.
[18] Bowers LM, Shapland EB, Ryan KR. Who's in charge here? Regulating cell cycle regulators. Curr Opin Microbiol, 2008,11(6):547-552.
[19] Csikasz-Nagy A, Novak B, Tyson JJ. Reverse engineering models of cell cycle regulation. Adv Exp Med Biol, 2008, 641:88-97.
[20] van den Heuvel S. Cell-cycle regulation. WormBook, 2005 , 21:1-16.
[21] Malumbres M. Cyclins and related kinases in cancer cells. J BUON, 2007 ,12 (Suppl1):S45-52.
[22] Yu Y, Kovacevic Z, Richardson DR. Tuning cell cycle regulation with an iron key. Cell Cycle, 2007 ,6(16):1982-1994.
[23] Calonge TM, O'Connell MJ. Turning off the G2 DNA damage checkpoint. DNA Repair (Amst), 2008,7(2):136-140.
[24] Miyazaki T, Arai S. Two distinct controls of mitotic cdkl/cyclin Bl activity requisite for cell growth prior to cell division. Cell Cycle, 2007,6(12): 1419-1425.
[25] Galaktionov K, Beach D. Specific activation of cdc25 tyrosine phosphatases by B-type cyclins: evidence for multiple roles of mitotic cyclins. Cell, 1991,67(6):1181-1194.
[26] Pines J, Hunter T. The differential localization of human cyclins A and B is due to a cytoplasmic retention signal in cyclin B. EMBO J, 1994,13(16):3772-3781.
[27] Francis D. The G2/M transition in eukaryotes. SEB Exp Biol Ser, 2008,59:81-98.
[28] Stark GR, Taylor WR. Control of the G2/M transition. Mol Biotechnol, 2006 ,32(3):227-248.
[29] Kaufmann W K, Paules R S. DNA damage and cell cycle checkpoints, FASEB J, 1996,10(2):238-247.
[30] Stark GR, Taylor WR. Analyzing the G2/M checkpoint. Methods Mol Biol, 2004, 280:51-82.
[31] Badie C, Banrhis J, Sobczak-Thepot J, et al. p53-dependent G2 arrest associated with a decrease in cyclins A2 and B1 levels in a human carcinoma cell line. Br J Cancer, 2000, 82(3):642-650.
[32] Southern SA, McDicken IW, Herrington CS. Evidence for keratinocyte immortalization in high-grade squanlous intraepithelial lesions of the cervix infected with high-risk human papillomavimses . Lab Invest, 2000,80(4):539-544.
[33] Sofia JC, Jang SJ, Khufi FR, et al. Overexpression of cyclin Bl in early-stage non-small cell lung cancer and its clinical implication. Cancer Res. 2000, 60(15):4000-4004.
[34] Banerjee SK, Weston AP, Zoubine MN, et al. Expression of cdc2 and cyclin Bl in Helicobacter pylori-associated gastric MALT and MALT lymphoma: relationship to cell death, proliferation, and transformation. Am J Pathol,2000,156(1): 217-225.
[35] NozoeT, Korenaga D, Kabashima, et al. Significance of cyclin Bl expression as an independent prognostic indicator of patients with squamous cell carcinoma of the esophagus. Clin Cancer Res, 2002, 8(3): 817-822.
[36] Dang Y, Sui L, Watanabe Y, et al. Clinical relevance of cyclin B1 over-expression in laryngeal squamous cell carcinoma. Cancer Lett, 2002, 177(1): 13-19.
[37] Hassan KA, El-Naggar AK, Sofia JC, et al. Clinical significance of cyclin B1 protein expression in squamous cell carcinoma of the tongue. Clin Cancer Res,2001, 7(8): 2458-2462.
[38] Lo Muzio L, Pannone G, Leonardi R, et al. Survivin, a potential early predictor of tumor progression in the oral mucosa. J Dent Res, 2003, 82: 923-928.
[39] Wall NR, O'Connor DS, Plescia J, et al. Suppression of survivin phosphorylation on Thr34 by flavopiridol enhances tumor cell apoptosis. Cancer Res, 2003, 63(1): 230-235.
[40]Salz W,Eisenberg D,Plescia J,et al.A survivin gene signature predicts aggressive tumor behavior.Cancer Res,2005,65(9):3531-3534.
[41]Zhang M,Latham DE,Delaney MA,et al.Survivin mediates resistance to antiandrogen therapy in prostate cancer.Oncogene,2005,24(15):2474-2482.
[42]Kaldis P,Aleem E.Cell cycle sibling rivalry:Cdc2 vs.Cdk2.Cell Cycle,2005,4(11):1491-1494.
[43]Malumbres M,Hunt SL,Sotillo R,et al.Driving the cell cycle to cancer.Adv Exp Med Biol,2003,532:1-11.
[44]陈新,周健.细胞周期调控蛋白P34cdc2与cyclin B1在头颈部鳞癌中的预测价值.国外医学口腔医学分册,2005,32(6):428-430.
[45]Wada S,Yue L,Furuta I.Prognostic significance of p34cdc2 expression in tongue squamous cell carcinoma.Oral Oncol,2004,40(2):164-169.
[46]Pannone G,Bufo P,Serpico R,et al.Survivin phosphorylation and M-phase promoting factor in oral carcinogenesis.Histol Histopathol,2007,22(11):1241-1249.
[47]Kushner J,Bradley G,Young B,et al.Aberrant expression of cyclin A and cyclin B1 proteins in oral carcinoma.J Oral Pathol Med,1999,28(2):77-81.
[48]Ruchaud S,Carmena M,Earnshaw WC.Chromosomal passengers:conducting cell division.Nat Rev Mol Cell Biol,2007,8(10):798-812.
[49]Li F,Yang J,Ramnath N,et al.Nuclear or cytoplasmic expression of survivin:what is the significance? Int J Cancer,2005,114(4):509-512.
[50]Engels K,Knauer S,Metzler D,et al.Dynamic intracellular survivin in oral squamous cell carcinoma:underlying molecular mechanism and potential as an early prognostic marker.J Pathol,2007,211(5):532-540.
[51]Stauber RH,Mann W,Knauer SK.Nuclear and cytoplasmic survivin:molecular mechanism,prognostic,and therapeutic potential.Cancer Res,2007,67(13):5999-6002.
[1]Sidransky D.Emerging molecular markers of cancer.Nat Rev Cancer,2002,2(3):210-219.
[2]Leethanakul C,Knezevic V,Patel V,et al.Gene discovery in oral squamous cell carcinoma through the Head and Neck Cancer Genome Anatomy Project:confirmation by microarray analysis.Oral Oncol,2003,39(3):248-258.
[3]Odani T,Ito D,Li MH,et al.Gene expression profiles of oral leukoplakia and carcinoma:genome-wide comparison analysis using oligonucleotide microarray technology.Int J Oncol,2006,28(3):619-624.
[4]周曾同,陶疆,张庆华,等.白斑癌变相关基因的表达谱研究.临床口腔医学杂志,2003,19(8):491-494.
[5]Shimada K,Uzawa K,Kato M,et al.Aberrant expression of RAB1A in human tongue cancer.Br J Cancer,2005,92(10):1915-1921.
[6]Makitie AA,Pintor Dos Reis P,Arora S,et al.Molecular characterization of salivary gland malignancy using the Smgb-Tag transgenic mouse model.Lab Invest,2005,85(8):947-961.
[7]Leivo I,Jee KJ,Heikinheimo K,et al.Characterization of gene expression in major types of salivary gland carcinomas with epithelial differentiation.Cancer Genet Cytogenet,2005,156(2):104-113.
[8]Yasumoto J,Kirita T,Takahashi A,et al.Apoptosis-related gene expression after hyperthermia in human tongue squamous cell carcinoma cells harboring wild-type or mutated-type p53.Cancer Lett,2004,204(1):41-51.
[9]Higo M,Uzawa K,Kouzu Y,et al.Identification of candidate radioresistant genes in human squamous cell carcinoma cells through gene expression analysis using DNA microarrays. Oncol Rep, 2005,14(5):1293-1298.
[10] Tsai WC, Tsai ST, Ko JY, et al. The mRNA profile of genes in betel quid chewing oral cancer patients. Oral Oncol, 2004,40(4):418-426.
[11] O'Donnell RK, Kupferman M, Wei SJ, et al. Gene expression signature predicts lymphatic metastasis in squamous cell carcinoma of the oral cavity.Oncogene, 2005, 24(7): 1244-1251.
[12] Roepman P, Wessels LF, Kettelarij N, et al. An expression profile for diagnosis of lymph node metastases from primary head and neck squamous cell carcinomas. Nat Genet, 2005, 37(2): 182-186.
[13] Gires O, Mack B, Rauch J, et al. CK8 correlates with malignancy in leukoplakia and carcinomas of the head and neck. Biochem Biophys Res Commun, 2006, 343(1):252-259.
[14] He QY, Chen J, Kung HF, et al. Identification of tumor-associated proteins in oral tongue squamous cell carcinoma by proteomics. Proteomics, 2004, 4(1):271-278.
[15] Chen J, He QY, Yuen AP, et al. Proteomics of buccal squamous cell carcinoma: the involvement of multiple pathways in tumorigenesis.Proteomics, 2004,4(8):2465-2475.
[16] Nakashima D, Uzawa K, Kasamatsu A, et al. Protein expression profiling identifies maspin and stathmin as potential biomarkers of adenoid cystic carcinoma of the salivary glands. Int J Cancer, 2006, 118(3):704-713.
[17] An J, Sun JY, Yuan Q, et al. Proteomics analysis of differentially expressed metastasis-associated proteins in adenoid cystic carcinoma cell lines of human salivary gland. Oral Oncol, 2004, 40 (4):400-408.
[1]Altieri DC.Validating survivin as a cancer therapeutic target.Nat Rev Cancer,2003,3(1):46-54.
[2]Conway EM,Pollefeyt S,Cornelissen J,et al.Three differentially expressed survivin cDNA variants encode proteins with distinct antiapoptotic functions.Blood,2000,95(4):1435-1442.
[3]Altieri DC,Marchisio PC.Survivin apoptosis:an interloper between cell death and cell proliferation in cancer.Lab Invest,1999,79(11):1327-1333.
[4]Downer MC,Moles DR,Palmer S,et al.A systematic review of test performance in screening for oral cancer and precancer.Oral Oncol,2004,40(3):264-273.
[5]Lo Muzio L,Pannone G,Leonardi R,et al.Survivin,a potential early predictor of tumor progression in the oral mucosa.J Dent Res,2003,82(11):923-928.
[6]Shinozawa I,Inokuchi K,Wakabayashi I,et al.Disturbed expression of the antiapoptosis gene,surviving,and EPR-1 in hematological malignancies.Leuk Res,2000,24(11):965-970.
[7]卓贤露,冯红超,宋宇峰.口腔鳞癌组织中Survivin的表达与血管生成的关系.临床口腔医学杂志,2004,20(4):207-209.
[8]Kim MJ,Lim KY,Kim JW,et al.Stage and mRNA expression of survivin in lymph node as prognostic indicators in patients with oral squamous cell carcinoma.Cancer Lett,2005,224(2):253-261.
[9]Marioni G,Bedogni A,Giacomelli L,et al.Survivin expression is significantly higher in pN+ oral and oropharyngeal primary squamous cell carcinomas than in pN0 carcinomas.Acta Otolaryngol,2005,125(11):1218-1223.
[10]Lo Muzio L,Farina A,Rubini C,et al.Survivin as prognostic factor in squamous cell carcinoma of the oral cavity.Cancer Lett,2005,225(1):27-33.
[11]刘艳梅,黄建华,冯德云,等.口腔鳞癌组织中Survivin蛋白的表达及与血管生成的关系.癌症,2005,24(11):1354-1357.
[12]Lin CY,Hung HC,Kuo RC,et al.Survivin expression predicts poorer prognosis in patients with areca quid chewing-related oral squamous cell carcinoma in Taiwan.Oral Oncol,2005,41(6):645-654.
[13]Jane C,Nerurkar AV,Shirsat NV,et al.Increased survivin expression in high-grade oral squamous cell carcinoma:a study in Indian tobacco chewers.J Oral Pathol Med,2006,35(10):595-601.
[14]Lo Muzio L,D'Angelo M,Procaccini M,et al.Expression of cell cycle markers and human papillomavirus infection in oral squamous cell carcinoma:use of fuzzy neural networks.Int J Cancer,2005,115(5):717-723.
[15]Lo Muzio L,Campisi G,Giovannelli L,et al.HPV DNA and survivin expression in epithelial oral carcinogenesis:a relationship? Oral Oncol,2004,40(7):736-741.
[16]Campisi G,Di Fede O,Giovannelli L,et al.Use of fuzzy neural networks in modeling relationships of HPV infection with apoptotic and proliferation markers in potentially malignant oral lesions.Oral Oncol,2005,41(10):994-1004.
[17]Engels K,Knauer S,Metzler D,et al.Dynamic intracellular surviving in oral squamous cell carcinoma:underlying molecular mechanism and potential as an early prognostic marker.J Pathol,2007,211(5):532-540.
[18]Freier K,Pungs S,Sticht C,et al.High survivin expression is associated with favorable outcome in advanced primary oral squamous cell carcinoma after radiation therapy.Int J Cancer,2007,120(4):942-946.
[19]闫琳,陈伟强,梁永钜,等.survivin基因介导口腔表皮癌细胞KB及KBv200凋亡的比较研究.癌症,2006,25(8):933-940.
[20]Jiang G,Li J,Zeng Z,et al.Lentivirus-mediated gene therapy by suppressing survivin in BALB/c nude mice bearing oral squamouscell carcinoma.Cancer Biol Ther,2006,5(4):435-440.
[21]Li F,Ling X.Survivin study:an update of "what is the next wave"? J Cell Physiol,2006,208(3):476-486.