尖锐湿疣患者细胞免疫功能及局部角质形成细胞凋亡的研究
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摘要
第一部分尖锐湿疣患者外周血Th1/Th2细胞因子及局部NK细胞变化的研究
目的通过对尖锐湿疣(CA)患者外周血Th1/Th2细胞因子水平及CA皮损内CD4、CD8、CD16、CD57的检测,探讨细胞免疫功能对CA发病的影响。方法采用流式细胞仪和细胞内细胞因子染色(ICCS)法检测40例CA患者和20例正常对照者外周血CD4+T淋巴细胞内Th1/Th2细胞因子(IL-2、IL-12、IFN-γ和IL-4)水平,同时采用免疫组织化学方法对CA皮损及正常对照者包皮环切组织CD4、CD8、CD16及CD57的表达进行检测,并将结果进行统计学分析。结果CA患者外周血IL-2+、IL-12+、IFN-γ+-CD4+T细胞百分率均显著低于正常对照组,IL-4+-CD4+T细胞百分率稍高于正常对照组,但差异无统计学意义,Th1/Th2比值显著低于正常对照组,说明在CA发病过程中存在Th1向Th2漂移。疣体组织中CD4+T细胞、CD8+T细胞均增高,但CD4+/CD8+比值低于对照组织,CD16、CD57表达较正常组织中少,说明皮损局部存在NK细胞减少。结论CA患者存在外周血Th1/Th2失衡及皮损局部细胞免疫功能下降,可能是导致CA发生及长期不愈的原因之一。
第二部分尖锐湿疣患者皮损Fas表达与角质形成细胞凋亡的研究
目的探讨尖锐湿疣(CA)患者皮损角质形成细胞Fas表达与凋亡的关系。方法对28例CA皮损和20例正常对照者包皮环切组织分别采用免疫组织化学方法(SP法)检测角质形成细胞Fas抗原的表达,末端脱氧核苷酸转移酶介导的dUTP缺口末端标记技术(TUNEL)检测细胞凋亡。结果28例CA患者中有23例(82.14%)表皮角质形成细胞Fas染色阳性,20例正常上皮中有3例呈弱阳性表达(15.00%),CA皮损Fas指数显著高于正常上皮,但CA皮损与正常上皮凋亡指数无明显差异。结论CA皮损存在Fas的过表达,但CA皮损Fas的过表达并未引起角质形成细胞凋亡的相应增多。
第三部分5-氨基酮戊酸光动力疗法治疗尖锐湿疣临床疗效观察
目的探讨5-氨基酮戊酸(ALA)光动力疗法(PDT)治疗尖锐湿疣的疗效。方法将60例尖锐湿疣患者随机分为两组,A组30例采用ALA-PDT进行治疗,B组30例采用CO2激光进行治疗,观察两组患者的疗效、不良反应、术后创面愈合过程等,并于治疗后1、3、6个月进行随访,以观察复发情况。结果光动力治疗组四次治疗后痊愈22例(73.33%),其中一次治疗后痊愈5例(16.67%),两次治疗后痊愈8例(26.67%),3次治疗后痊愈6例(20.00%),4次治疗后痊愈3例(10.00%),治愈所需平均次数为2.21次。显效4例(13.33%),进步2例(16.67%),无效2例(16.67%),有效率为86.67%。治疗过程中及治疗结束后无明显不良反应发生,患者耐受良好。术后创面愈合时间平均6.82天,随访6个月复发率为23.33%。CO2激光治疗组治疗结束后全部痊愈,术后创面愈合时间为9.15天,随访6个月复发率为63.33%。结论虽然CO2激光治疗CA痊愈率高于ALA-PDT,但是ALA-PDT治疗后CA复发率明显下降,而且与CO2激光治疗相比,其不良反应发生率低,因此ALA-PDT治疗CA具有简单、有效、耐受性好、复发率低的优势,可望成为治疗CA的良好方法。
Part I Th1/Th2 cytokines in CD4+T cells in peripheral blood and natural killer in lesions of condyloma acuminatum
Objective To investigate the role of Th1/Th2 cytokines in CD4+T cells in peripheral blood and natural killers in lesions in the pathogenesis of condyloma acuminatum. Methods The levels of Th1/Th2 cytokines (IL-2, IL-12 ,and IL-4) in CD4+T cells in peripheral blood of 40 cases of condyloma acuminatum and 20 cases of normal controls were tested by flow cytometry and ICCS. At the same time, the expression of CD4, CD8, CD16, CD57 molecules in condyloma acuminatum leisions and normal prepuce was detected by immunohistochemistry. Results The percentage of IL-2+, IL-12+, IFN-γ+-CD4+T cells in peripheral blood of condyloma acuminatum was significantly lower than that in normal controls (P<0.01). The percentage of Il-4+-CD4+ T cells in peripheral blood of condyloma acuminatum was not significantly higher than that in normal controls. The ratio of Th1/Th2 was remarkedly lower in peripheral blood of the patients with condyloma acunimatum than in the controls. The expression of CD4 and CD8 in lesions of condyloma acunimatum was higher than that in normal controls, but the ratio of CD4/CD8 was lower in condyloma acunimatum. The expression of CD16 and CD57 was significantly lower than that in normal controls. It was suggested that the number of natural killers was less in lesions of condyloma acunimatum than that in controls. Conclusion Th1/Th2 is imbalance in condyloma acuminatum. Th1 type cytokines are inhibited, and Th2 type cytokines are relatively enhanced, so Th1/Th2 shifts to Th2. The shift of Th1 to Th2 and the suppression of cell-mediated immunity may be the pathogens of condyloma acuminata.
Part II Fas expression and apoptosis of keratinocyte in condyloma acuminatum
Objective To investigate the correlation between keratinocyte Fas expression and apoptosis in condyloma acuminatum. Methods The expression of keratinocyte Fas antigen and apoptosis in 28 ases of CA and 20 normal controls was detected respectively with immunohistochemical staining (SP method) and terminal deoxynucleotidyl transferase-mediated dUTP nick endlabeling. Results The keratinocyte Fas index in CA was significantly higher than that in normal controls, and the keratinocyte apoptosis index in CA was not significantly different from that in normal controls. Conclusion There is Fas over-expression in CA epithelium, which doesn’t cause the increase in cell apoptosis.
Part III 5-aminolevulinic acid photodynamic therapy for condyloma acuminatum
Objective To investigate the effect of photodynamic therapy (PDT) with topical 5-aminolaevulinic acid (ALA) on condylomata acuminata(CA). Methods 60 patients with CA were randomly divided into two groups. One group was treated with 10% ALA solution under occlusive dressing followed by irradiation with He-Ne laser at 100mW. The other group was treated with CO2 laser. Results ALA-PDT achieved completed response in 22 of 30 patients (73.33%) after 1～4 times treatment.In 5 patients (16.67%) complete response was found after one ALA-PDT treatment, 8 patients (26.67%) required two treatments, 6 (20.00%) needed three and 3 (10.00%) needed four treatments before the lesions disappered completely. The complete remission was 30 of 30 (100.00%) for CO2 laser treatment. After 6 months of follow-up, recurrence rate was 23.33% and 63.33% for ALA-PDT and CO2 laser, respectively. No scar formed. Conclusion The cure rate with CO2 laser was higher than that with ALA-PDT. However, the recurrence rate with ALA-PDT was lower than that with CO2 laser and ALA-PDT was much better than CO2 laser on side effects. Compared with conventional therapies, topical ALA-PDT is a simple, effective, safe and well-tolerated treatment for condylomata acuminata that is associated with a low recurrence rate. It is expected that ALA-PDT could be a better therapy methods for CA.
目的通过对尖锐湿疣(CA)患者外周血Th1/Th2细胞因子水平及CA皮损内CD4、CD8、CD16、CD57的检测,探讨细胞免疫功能对CA发病的影响。方法采用流式细胞仪和细胞内细胞因子染色(ICCS)法检测40例CA患者和20例正常对照者外周血CD4+T淋巴细胞内Th1/Th2细胞因子(IL-2、IL-12、IFN-γ和IL-4)水平,同时采用免疫组织化学方法对CA皮损及正常对照者包皮环切组织CD4、CD8、CD16及CD57的表达进行检测,并将结果进行统计学分析。结果CA患者外周血IL-2+、IL-12+、IFN-γ+-CD4+T细胞百分率均显著低于正常对照组,IL-4+-CD4+T细胞百分率稍高于正常对照组,但差异无统计学意义,Th1/Th2比值显著低于正常对照组,说明在CA发病过程中存在Th1向Th2漂移。疣体组织中CD4+T细胞、CD8+T细胞均增高,但CD4+/CD8+比值低于对照组织,CD16、CD57表达较正常组织中少,说明皮损局部存在NK细胞减少。结论CA患者存在外周血Th1/Th2失衡及皮损局部细胞免疫功能下降,可能是导致CA发生及长期不愈的原因之一。
第二部分尖锐湿疣患者皮损Fas表达与角质形成细胞凋亡的研究
目的探讨尖锐湿疣(CA)患者皮损角质形成细胞Fas表达与凋亡的关系。方法对28例CA皮损和20例正常对照者包皮环切组织分别采用免疫组织化学方法(SP法)检测角质形成细胞Fas抗原的表达,末端脱氧核苷酸转移酶介导的dUTP缺口末端标记技术(TUNEL)检测细胞凋亡。结果28例CA患者中有23例(82.14%)表皮角质形成细胞Fas染色阳性,20例正常上皮中有3例呈弱阳性表达(15.00%),CA皮损Fas指数显著高于正常上皮,但CA皮损与正常上皮凋亡指数无明显差异。结论CA皮损存在Fas的过表达,但CA皮损Fas的过表达并未引起角质形成细胞凋亡的相应增多。
第三部分5-氨基酮戊酸光动力疗法治疗尖锐湿疣临床疗效观察
目的探讨5-氨基酮戊酸(ALA)光动力疗法(PDT)治疗尖锐湿疣的疗效。方法将60例尖锐湿疣患者随机分为两组,A组30例采用ALA-PDT进行治疗,B组30例采用CO2激光进行治疗,观察两组患者的疗效、不良反应、术后创面愈合过程等,并于治疗后1、3、6个月进行随访,以观察复发情况。结果光动力治疗组四次治疗后痊愈22例(73.33%),其中一次治疗后痊愈5例(16.67%),两次治疗后痊愈8例(26.67%),3次治疗后痊愈6例(20.00%),4次治疗后痊愈3例(10.00%),治愈所需平均次数为2.21次。显效4例(13.33%),进步2例(16.67%),无效2例(16.67%),有效率为86.67%。治疗过程中及治疗结束后无明显不良反应发生,患者耐受良好。术后创面愈合时间平均6.82天,随访6个月复发率为23.33%。CO2激光治疗组治疗结束后全部痊愈,术后创面愈合时间为9.15天,随访6个月复发率为63.33%。结论虽然CO2激光治疗CA痊愈率高于ALA-PDT,但是ALA-PDT治疗后CA复发率明显下降,而且与CO2激光治疗相比,其不良反应发生率低,因此ALA-PDT治疗CA具有简单、有效、耐受性好、复发率低的优势,可望成为治疗CA的良好方法。
Part I Th1/Th2 cytokines in CD4+T cells in peripheral blood and natural killer in lesions of condyloma acuminatum
Objective To investigate the role of Th1/Th2 cytokines in CD4+T cells in peripheral blood and natural killers in lesions in the pathogenesis of condyloma acuminatum. Methods The levels of Th1/Th2 cytokines (IL-2, IL-12 ,and IL-4) in CD4+T cells in peripheral blood of 40 cases of condyloma acuminatum and 20 cases of normal controls were tested by flow cytometry and ICCS. At the same time, the expression of CD4, CD8, CD16, CD57 molecules in condyloma acuminatum leisions and normal prepuce was detected by immunohistochemistry. Results The percentage of IL-2+, IL-12+, IFN-γ+-CD4+T cells in peripheral blood of condyloma acuminatum was significantly lower than that in normal controls (P<0.01). The percentage of Il-4+-CD4+ T cells in peripheral blood of condyloma acuminatum was not significantly higher than that in normal controls. The ratio of Th1/Th2 was remarkedly lower in peripheral blood of the patients with condyloma acunimatum than in the controls. The expression of CD4 and CD8 in lesions of condyloma acunimatum was higher than that in normal controls, but the ratio of CD4/CD8 was lower in condyloma acunimatum. The expression of CD16 and CD57 was significantly lower than that in normal controls. It was suggested that the number of natural killers was less in lesions of condyloma acunimatum than that in controls. Conclusion Th1/Th2 is imbalance in condyloma acuminatum. Th1 type cytokines are inhibited, and Th2 type cytokines are relatively enhanced, so Th1/Th2 shifts to Th2. The shift of Th1 to Th2 and the suppression of cell-mediated immunity may be the pathogens of condyloma acuminata.
Part II Fas expression and apoptosis of keratinocyte in condyloma acuminatum
Objective To investigate the correlation between keratinocyte Fas expression and apoptosis in condyloma acuminatum. Methods The expression of keratinocyte Fas antigen and apoptosis in 28 ases of CA and 20 normal controls was detected respectively with immunohistochemical staining (SP method) and terminal deoxynucleotidyl transferase-mediated dUTP nick endlabeling. Results The keratinocyte Fas index in CA was significantly higher than that in normal controls, and the keratinocyte apoptosis index in CA was not significantly different from that in normal controls. Conclusion There is Fas over-expression in CA epithelium, which doesn’t cause the increase in cell apoptosis.
Part III 5-aminolevulinic acid photodynamic therapy for condyloma acuminatum
Objective To investigate the effect of photodynamic therapy (PDT) with topical 5-aminolaevulinic acid (ALA) on condylomata acuminata(CA). Methods 60 patients with CA were randomly divided into two groups. One group was treated with 10% ALA solution under occlusive dressing followed by irradiation with He-Ne laser at 100mW. The other group was treated with CO2 laser. Results ALA-PDT achieved completed response in 22 of 30 patients (73.33%) after 1～4 times treatment.In 5 patients (16.67%) complete response was found after one ALA-PDT treatment, 8 patients (26.67%) required two treatments, 6 (20.00%) needed three and 3 (10.00%) needed four treatments before the lesions disappered completely. The complete remission was 30 of 30 (100.00%) for CO2 laser treatment. After 6 months of follow-up, recurrence rate was 23.33% and 63.33% for ALA-PDT and CO2 laser, respectively. No scar formed. Conclusion The cure rate with CO2 laser was higher than that with ALA-PDT. However, the recurrence rate with ALA-PDT was lower than that with CO2 laser and ALA-PDT was much better than CO2 laser on side effects. Compared with conventional therapies, topical ALA-PDT is a simple, effective, safe and well-tolerated treatment for condylomata acuminata that is associated with a low recurrence rate. It is expected that ALA-PDT could be a better therapy methods for CA.
引文
1. Trottier H, Franco EL. Human papillomavirus and cervical cancer: burden of illness and basis for prevention. Am J Manag Care, 2006, 12(17 suppl): s462-472
2. Katch KD. Valvovaginal human papilloma virus infections clinical implications and management. Am J Gynecol, 2000, 5: 183
3.龚向东,叶顺章,张君炎等. 1991～2001年我国性病流行病学分析.中华皮肤科杂志, 2002, 35(3): 178-182
4. Villa LL, Costa RL, Petta CA, et al. High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up. Br J Cancer, 2006, 95(11): 1459-66
5. Yu HC, Cho BH, Chung MJ et al. A case of giant condylomata acuminata involving anus after renal transplantation. Clin Nephrol, 2003, 59(3): 235-236
6. von Krogh G, Dahlman-Ghozlan K, Syrijanen S. Potential human papillomavirus reactivation following topical corticosteriod therapy of genital lichen sclerosus and erosive lichen planus. J Eur Acad Dermatol Venereol, 2002, 162(2): 103-133
7. Vandepapeliere P, Barrasso R, Meijer CJ et al. Randomized controlled trial of an adjuvanted human papillomavirus (HPV) type 6 L2E7 vaccine: infection of external anogenital warts with multiple HPV types and failure of therapeutic vaccination. J Infect Dis, 2005, 192(2): 2099-2107
8.王光超.皮肤病及性病学.第一版.北京:北京科学出版社,2002.361-362
9. Underwood MR, Shewchuk LM, Hassell AM et al. Searching for antiviral drugs for human papillomaviruses. Antivir Ther, 2000, 5(4): 229-242
10.Beutner KR, Tying S. Human papillomavirus and human disease. Am J Med, 1997, 102(5A): 9-15
11.Moscicki AB. Impact of HPV infection in adolescent populations. J Adolesc Health, 2005, 37(6 Suppl): S3-9
12.Woodman CB, Collins S, Winter H et al. Natural history of cervical human papillomavirus infection in young women: a longitudinal cohort study. Lancet, 2001, 357(33): 1831-1836
13.Trottier H, Franco EL. Human papillomavirus and cervical cancer: burden of illness and basis for prevention. Am J Manag Care, 2006, 12(17Suppl): s462-472
14.Kim KH, Greenfield W, Shotts E et al. Detection of Human Papillomavirus Type 16-Specific T Lymphocytes Using a Recombinant Vaccinia Virus-Based ELISPOT Assay. Clin Vaccine Immunol, 2007, (Epub ahead of print)
15.Waldrop SL, Pitcher CJ, Peterson DM et al. Determination of antigen-specific memory/effector CD4+T cell frequencies by flow cytometry. J Clin Invest, 1997, 99:1739-1750
16.Pala P, Hussell T, Openshaw PJM et al. Floe cytometric measurement of intracellular cytokines. J Immunol Methods, 2000, 243: 107-124
17.Sander B, Andersson J, Andersson U. Assessment of cytokines by immumofluorescence and the paraformaldehyde-saponin procedure. Immumol Rev, 1991, 119:65-93
18.Andersson PO, Olsson A, Wadenvik H. Reduced transforming growth factor-beta1 production by mononuclear cells from patients with active chronic idiopathic thrombocytopenic purpura. Br J Haematol, 2002, 116(4): 862-867
19.孟泽,李晓军.免疫学检验的热点与难点.临床检验杂志,2000,18(1):60
20.Neurath MF, Finotto S, Glimcher LH. The role of Th1/Th2 polarization in mucosal immunity. Nat Med, 2002, 8: 567-573
21.Torres KC, Dutra WO, gollob KJ. Endogenous IL-4 and IFN-γare essentialfor expression of Th2, but not Th1 cytokine message during the early differentiation of human CD4+ T helper cells. Human Immunol, 2004, 65(1): 1328-1335
22.Murakami H, Ogawara H, Hiroshi H. Th1/Th2 cells in patiens with multiple myeloma. Hematology, 2004, 9(1):41-45
23.Kobayashi A, Miaskowski C, Wallhagen M, et al. Recent development in understanding the immune response to human papilloma virus infection and cervical neoplasia. Oncol Nurs Forum, 2000, 27(4): 643-651
24.郭红卫,钱起丰,吴志华.尖锐湿疣患者Th1/Th2细胞因子检测.中华皮肤科杂志. 2003, 36: 256-257
25.龚非力.基础免疫学.第一版.武汉:湖北科学技术出版社,1998.24-173
26.朱讯.免疫学新进展.第一版.北京:人民卫生出版社,2002.255-294
27.Biron CA, Brossay L. NK cells and NKT cells in innate defense against viral infections. Curr Opin Immunol, 2001, 13: 458-464
28.Luo D, Vermijlen D, Ahishali B et al. MHC class I expression protects colon carcinoma cells from cytolysis and apoptosis by hepatic NK(pit) cells by blocking perforin/granzyme pathway. Comparative Hepatology, 2002, 1: 1-9
29.王玉坤,王克玉,郭淑兰等. NK细胞与尖锐湿疣转归关系研究.中国麻风皮肤病杂志, 2003, 19(5): 442-443
30.杨春莉,裘宇容.流式细胞仪对系统性红斑狼疮患者的T细胞亚群及NK细胞检测.第一军医大学学报, 2000, 20(3):274
31.Wei LH, Kuo ML, Chen CA et al. Interleukin-6 in cervical cancer: the relationship with vascular endothelial growth factor. Gynecol Oncol, 2001, 82(1): 49-56
32.殷缨,张盈华,张利朝等.恶性肿瘤患者T细胞亚群与红细胞免疫功能的变化及其相关性分析.实用癌症杂志,2001,16(2):171-173
1. Irmler M, Thome M, Hahne M et al. Inhibition of death receptor signals by cellular FLIP. Nature, 1997, 388(6638): 190-195
2. Tjalma WA, Weyler JJ, Bogers JJ etal. The importance of biological factors(bcl22, bax, p53, PCNA, MIHPV and angiogenesis) in invasive cervical cancer. Eur J Obstet Gynecol Reprod Biol, 2001, 97(2):223-230
3. Duttagupta C, Sengupta S, Roy M et al. Oncogenic human papillomavirus(HPV) infection and uteine cervical cancer:a screening strategy in the perspective of rural India1. European J Cancer Prevention, 2002, 11(8): 447-456
4. Vaux DL, Korsmeyer SJ. Cell death in development[J]. cell,1999,96:245-254
5.吴人亮,李娜萍.细胞凋亡、胀亡和坏死-关于细胞死亡的新认识.中华病理学杂志, 2002, 31: 455-456
6. Patel T, Gores GJ. Apoptosis and hepatobiliary disease. Hpatology, 1995, 21: 1725-1741
7. Green DR. Apoptotic pathways: paper wraps stone blunts scissors. Cell, 2000, 102(1):1-4
8. Yew DT, Ping Li, Liu WK. Fas and activated caspase 8 in normal, Alzheimer and multiple infarct brains. Neurosci Lett, 2004, 367(1):113-117
9. Xu B, Bulfone-Paus S, Aoyama K et al. Role of Fas/Fas ligand-mediated apoptosis in murine contact hypersensitivity. Int J Immunopharmacol, 2003, 3(7): 927-938
10.Roaquet N, Allemand I, Molina T et al. Fas-dependent apoptosisis impaired by SV40 T-antigen in transgenic liver. Oncogene, 1995, 11(6): 1061-1067
11.Nguyen ML, Blaho JA. Apoptosis during herpes simplex virus infection. Adv Virus Res, 2007, 69:67-97
12.Rieux-Laucat F, Le Deist F, Hivroz C et al. Mutations in Fas associated with human lymphoproliferative syndrome and autoimmunity. Science, 1995, 268(5215): 1347-1349
13.Gavrieli Y, Sherman Y, Ben-Sasson SA. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol, 1992, 119: 493-501
14.Guan DW, Ohshima T, Kondo T. Immunohistochemical study on Fas and Fas ligand in skin wound healing. J Histochem, 2000, 32: 85-91
15.Berthou C, Michel L, Soulie A et al. Acquisition of granzyme B and Fas ligand proteins by human keratinocytes contributes to epidermal cell defense. J Immunol, 1997, 159: 5293-5300
16.项彤,陈兴平.尖锐湿疣组织中的细胞凋亡与caspase-3和bcl-2蛋白的检测.中国皮肤性病学杂志, 2006, 20(8): 471-473
17.Isacson C, Kessis TD, Hedrick L et al. Both cell proliferation and apoptosis increases with Lesion grade in cervical neoplasia but not correlate with human papillomavirus type. Cancel Res, 1996, 56(4): 669-674)
18.Allen SM, Florell SR, Hanks AN et al. Survivin expression in mouse skin prevents papilloma regression and promotes chemical-induced tumor progression. Cancer Res, 2003, 63: 567-572
19.Lanham S, Herber AT, Watt P et al. HPV detection and measurement of HPV-16,telomerase, and survivin transcripts in colposcopy clinic patients. J Clin Pathol, 2001, 54(4): 304-308
20.Michael F, Elka A, David O et al. Immunohistochemical Localization of Survivin in Benign Cervical Mucosa, Cervical Dysplasia, and InvasiveSquamous Cell Carcinoma. Am J Clin Pathol. 2002, 117(5): 738-744
21.Fan G, Ma X, Wong PY et al. p53 dephosphorylation and p21 (cipl/wafl) translocation correlation with caspase-3 activation in TGF-betal-induced apoptosis of HuH27 cell. Apoptosis, 2004, 9(2): 211-221
22.Leverrier S, Bergamaschi D, Ghali L et al. Role of HPV E6 proteins in preventing UVB-induced release of pro-apoptotic factors from the mitochondria. Apoptosis, 2007, 12(3): 549-560
23.Kabsch K, Mossadegh N, Kohl A et al. The HPV-16 E5 protein inhibits TRAIL- and FasL-mediated apoptosis in human keratinocytes raft cultures. Intervirology, 2004, 47(1): 48-56
1. Sonnex C, Lacey CJ. The treatment of human papillomavirus lesions of the lower genital tract. Best Pract Res Clin Obstet Gynaecol, 2001, 15: 801–816
2. Kennedy JC, Pottier RH, Pross DC. Photodynamic therapy with endogenous protoporphyrin IX: basic principles and present clinical experience. J Phtotochem Photobical B Biol, 1990, 6: 143-148
3.张林,虞乐华.光动力疗法作用机制的研究进展.激光杂志, 2003, 24: 91-93
4. Kalka K, Merk H, Mukhtar H. Photodynamic therapy in dermatology. J Am Acad Dermatol, 2000, 42(3): 389-413
5. Talor EL, Brown SB. The advantage of aminolevulinic acid photodynamic therapy in dermatology. J Dermatol Treat, 2002, 13(Suppl. 1): S3-11
6. Britton JER, Goulden V, Stables M, et al. Ivestigation of the use of the pulsed dye laser in the treatment of Bowen’s disease using
5-aminolaevulinic acid phototherapy. Br J Dermatol, 2005, 153: 780-784
7. Karrer B. Baumler W, Abels C, et al. Long-pulse dye laser for photodynamic therapy: in vitro and in vivo. Lasers Surg Med, 1999, 25: 51-59
8. Oieinick NI, Evans HH. The photobiology of photodynamic therapy cellular targets and mechanisms. Radiat Res, 1998, 50 (5): 146-156
9. Gastano AP, Demidova TN, Hamblin MR. Mechanisms in photodynamic therapy. Part one. Photosensitizers, photochemistry and cellular localization. Photodiagn Photodyn Ther, 2004, 1: 279-293
10.Gastano AP, Demidova TN, Hamblin MR. Mechanisms in photodynamic therapy. Part two. Cellular signaling, cell metabolism and modes of cell death. Photodiagn Photodyn Ther, 2005, 2: 1-23
11.Gastano AP, Demidova TN, Hamblin MR. Mechanisms in photodynamic therapy. Part three. Photosensitizer pharmacokinetics, biodistribution, tumor localization and modes of tumor destruction. Photodiagn Photodyn Ther, 2005, 2: 91-106)
12.Szpringer E, Lutnicki K, Marciniak A. et al. Photodynamic therapy - mechanism and employment. Ann Univ Mariae Curie Sklodowska[Med], 2004, 59(2): 498-502
13.Kalka K, Merk H, Mukhtar H. Photodynamic therapy in dermatology. J Am Acad Dermatol, 2000, 42(3): 389-413
14.Gaulloer JM, Berg K, Peng Q, et al. 5-aminolevulinic acid esters to improve photodynamic therapy on cells in culture. Cncer Res, 1997, 57: 1481-1486
15.Bunke A, Derbe A, Schmid H et al. Degradation mechanism and stability of 5-aminolevulinic acid. J Pharm Sci, 2000, 89: 1335-1341
16.Maria CD, Robert JC. Photosensitized singlet oxygen and its applications. Coordination Chemistry Reviews,2002,233-234:351-371
17.Mullooly VM, Abramson AL, Shikowitz MJ. Dihematoporphyrin-ether induced photosensitivity in laryngeal papilloma patients. Laser Surg Med, 1990,10: 349-356
18.李晓原,去径平,谭润初等.温热疗法与Ar+离子激光联合对小鼠s180肉瘤DNA含量的影响研究.中国医学物理学杂志, 1999, 16: 151-153
19.Fink-Puches R, Hofer A, Smolle J, et al. Primary clinical responses and long-term follow-up of solar keratoses treated with topically applied 5-aminolevulinic acid and irradiation by different wave bands of light. J Photochem Photobiol B Biol, 1997,41: 145-151
20.Kennedy JC, Ottier RH. Endogenous protoporphyrin IX, a clinical useful photosensitizer for photodynamic therapy. J Photochem Photobiol B Biol, 1992, 14: 275-292
21.Brancaleon L, Moseley H. Lasers and non-laser light sources for photodynamic therapy. Lasers Med Sci, 2002, 17: 173-186
22.Selvasekar CR, Birbeck N, Mcmillan T et al. Photodynamic therapy and the alimentary track. Aliment Pharmacal Ther, 2001,15: 899-915
23.Ceburkov O, Gollnick H. Photodynamic therapy in dermatology. Eur J Dermatol, 2000, 10: 568-576
24.Szeimies RM, Abels C, Fritsch C et al. Wavelength dependency of photodynamic effects after sensitization with 5-aminolevulinic acid in vitro and in vivo. J Invest Dermatol, 1995, 105: 672-677
25.Dougherty TJ. An update on photodynamic therapy applications. J Clin Laser Med Surg. 2002, 20: 3-7
26.Yow CM, Wong CK, Huang Z et al. Study of the efficacy and mechanism of ALA-mediated photodynamic therapy on human hepatocellular carcinoma cell. Liver Int, 2007, 27(2): 201-208
27.Ibbotson SH. Topical 5-aminolaevulinic acid photodynamic therapy for the treatment of skin conditions other than non-melanoma skin cancer. Br J Dermatol, 2002: 146: 178-188
28.Britton JE, Goulden V, Stables G et al. Investigation of the use of the pulsed dye laser in the treatment of Bowen's disease using 5-aminolaevulinic acid phototherapy. Br J Dermatol, 2005, 153(4): 780-784
29.Alexiades-Armenakes M, Geronemus RG. Laser-mediated photodynamic therapy of actinic keratoses. Arch Dermatol, 2003, 139(10): 1313-1320
30.Szeimies RM. Methyl aminolevulinate-photodynamic therapy for basal cell carcinoma. Dermatol Clin, 2007, 25(1): 89-94
31.Head CS, Luu Q, Sarcarze J et al. Photodynamic therapy and tumor imaging of hypericin-treated squamous cell carcinoma. World J Surg Oncol. 2006, 4: 87
32.Blume JE, Oseroff AR. Aminolevulinic acid photodynamic therapy for skin cancers. Dermatol Clin, 2007, 25(1): 5-14
33.Alexiades-Armenakes M. Long-pulsed dye laser-mediated photodynamic therapy combined with topical therapy for mild to severe comedonal, inflammatory, or cystic acne. J Drugs Dermatol, 2006, 5(1):45-55
34.Calzavara-Pinton PG, Venturini M, Sala R. A comprehensive overview of photodynamic therapy in the treatment of superficial fungal infections of the skin. J Photochem Photobiol B, 2005, 78(1):1-6
35.Edstrom DW, Hedblad MA, Ros AM. Flashlamp pulsed dye laser and argon-pumped dye laser in the treatment of port-wine stains: a clinical and histological comparison. Br J Dermatol, 2002, 146: 285-289
36.Hillemanns P, Unch M, Dannecker C et al. Photodynamic therapy of vulvar intraepithelial neoplasia using 5-aminovulinic acid. Int J Cancer, 2000, 85: 649-653
37.Ross EV, Romero R, Kollias N et al. Selectivity of protoporphyrin IX fluorescence for condylo-mata after topical application of 5-aminolaevulinic acid: implications for photodynamic treatment. Br J Dermatol, 1997, 137: 736–742
38.Itkin A, Gilchrest BA. delta-Aminolevulinic acid and blue light photodynamic therapy for treatment of multiple basal cell carcinomas in two patients with nevoid basal cell carcinoma syndrome. Dermatol Surg, 2004, 30(7): 1054-1061
39.Varma S, Wilson H, Kurwa HA et al. Bowen’s disease, solar keratoses and superficial basal cell carcinomas treated by photodynamic therapy usinga large-field incoherent light source. Br J Dermatol, 2001, 144: 567-574
40.杨文彪,衍坤.尖锐湿疣及HPV亚临床感染病损的组织病理及免疫组织改变.临床皮肤科杂志, 1993, 22(6):298
41.吴阶平.泌尿外科.第一版.济南:山东科学技术出版社, 2003. 412
42.Fehr MK, Hornung R, Degen A et al. Photodynamic therapy of vulvar and vaginal condyloma and intraepithelial neoplasia using topically applied 5-aminolvulinic acid. Lasers Surg Med, 2002, 30: 273-279
43.李迎新,董霞,邵文艾等.光动力学疗法对I型单纯疱疹病毒灭活作用的实验研究.中国激光医学杂志, 2004, 13(4): 228-231
1. Katch KD. Valvovaginal human papilloma virus infections clinical implications and management. Am J Gynecol, 2000, 5: 183
2.龚向东,叶顺章,张君炎等. 1991～2001年我国性病流行病学分析.中华皮肤科杂志, 2002, 35(3): 178-182
3. Van Regenmortel MHV, Fauquet CM, Ishop DHL. Virus Taxonomy. New York: Academic Press, 2000
4. Villa LL, Costa RL, Petta CA et al. High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up. Br J Cancer, 2006, 95(11): 1459-1466
5. Moscicki AB. Impact of HPV infection in adolescent populations. J Adolesc Health, 2005, 37(6 Suppl): S3-9
6. Sedlacek TV. Advances in the diagnosis and treatment of human papillomavirus infections. Clin Obstet Gynecol, 1999, 42: 206-220
7.王丽华,王玉坤,赵东等.尖锐湿疣局部细胞免疫功能状态与人乳头瘤病毒型的相关性研究.中国麻风皮肤病杂志, 2004, 20(3): 242-244
8.杨文彪,衍坤.尖锐湿疣及HPV亚临床感染病损的组织病理及免疫组织改变.临床皮肤科杂志, 1993, 22(6):298
9.吴阶平.泌尿外科.第一版.济南:山东科学技术出版社, 2003. 412
10.张菊,陈中灿,白玉杰等.复发尖锐湿疣患者感染人乳头瘤病毒基因型的荧光偏振检测.临床检验杂志, 2004, 22(4): 244-245
11.Speich N, Schmitt C, Bollmann R et al. Human papillomavirus study of 2916 cytological samples by PCR and DNA sequencing: genotype spectrum of patients from the west German area. J Mcd Michobiol, 2004, 53(pt2): 125-128
12.钱恒林.尖锐湿疣与HLA-A、B位点相关性研究.中华皮肤科杂志, 1996, 25(2): 102-103
13.张庆瑞,谷丽红,杨德荣等.尖锐湿疣患者与HLA抗原及HLA单倍体.中华皮肤科杂志, 1996, 29(3): 192-193
14.Konya J, Dillner J. Immunity to oncogenic human papilloma virus. Adv Cancer Res, 2001, 82: 205-238
15.Perez LA. Genital HPV: links to cervical cancer, treatment, and prevention. Clin Lab Sci, 2001, 14(3): 183-186
16.Habel LA, Van Den Eeden Sk, Sherman KJ et al. Risk factors for incident and recurrent condylomata acuminata among women, a population-based study. Sex Transim Dis, 1998, 25:285-292
17.Svare EI, Kjaer SK, Worm AM et al. Risk factors for genital HPV DNA in men resemble those found in women: a study of male attendees at a Danish STD clinic. Sex Transm Infect, 2002, 78(3): 215-218
18.Winer RL, Lee SK, Hughes JP, et al. Genital human papilloma virus infection: incidence and risk factors in a cohort of female university students. Am J Epidemiol, 2003, 157(3): 218-226
19.Bjekic M, Vlajinac H. Effect of alcohol consumption on recurrence ofvenereal diseases. MedPregl, 2000, 53: 600-602
20.田洪青,杜东红,陈树民.尖锐湿疣发病和复发的危险因素研究现状.国外医学皮肤性病学分册, 2002, 28: 303-305
21.王琳,张广富.尖锐湿疣发病和复发危险因素的问卷调查.中国皮肤性病学杂志, 2005, 19(10): 615-617
22.De la Fuente SG, Ludwig KA, Mantyh CR. Preoperative immune status determines anal condyloma recurrence after surgical excision. Dis Colon Rectum, 2003, 46(3): 367-373
23.Silverberg MJ, Ahdieh L, Munoz A et al. The impact of HIV infection and immunodeficiency on human papilloma virus type 6 or 11 infection and on genital warts. Sex Transm Dis, 2002, 29(8): 427-435
24.梁伶.复发性尖锐湿疣诱发因素的探讨.广西医科大学学报, 2001, 18(3): 369-371
25.王书才,王琳,崔卫国.清洁度变化与阴道内尖锐湿疣复发的关系.中国卫生检验杂志, 2003, 13(5): 659.
26.车雅敏,王家璧,左亚刚等.人乳头瘤病毒DNA载量与尖锐湿疣复发的相关性.中国医学科学院学报, 2004, 26(5): 558-561
27.Coleman N, Birley HDL, Renton AM et al. Immunological events in regressing genital warts. Am J Clin Pathol, 1994, 102(6): 768-774
28.Kobayashi A, Miaskowski C, Wallhagen M et al. Recent development in understanding the immune response to human papilloma virus infection and cervical neoplasia. Oncol Nurs Forum, 2000, 27(4): 643-651
29.Azim AA, Said A, Swelim MM et al. Local expression of tumor necrosis factor-alpha and interleukin-4 mRNA in different types of warts. Egypt J Immunol, 2004, 11(1): 15-21
30.Arrese J, Paguet P, Claessens N et al. Dermal dendritic cells in anogenitalwarty lesionslesions unresponsive to an immune–response modifier. J Cutan Pathol, 2001, 28: 131- 134
31.Kikuchi K, Kusama K. Dendritic cells in human squamous cell carcinomal of the oral cavity. Anticancer Res, 2002, 22: 545-557
32.曹育春,陈兴平,徐祖森等. S100+朗格罕斯细胞与尖锐湿疣复发的相关性研究.中华皮肤科杂志, 2005, 38(7): 446-447
33.Johan SA, Erik JC, Reel A et al. HIV, sexaually transmitted diseases and gynaecologic disorders in women: increased risk for gential herpes and warts among HIV-infected prostitutes in Amsterdam. AIDS, 1995, 91(9):1071-1078
34.Teunissen MB, Koomen CW, de Waal Malefyt R et al. IL-17 and IFN-r synergize in the enhancement of proinflammatory cytokines production by human keratinocytes. J Invest Dermatol, 1998, 111(4): 645-649
35.Li L, Zhou ZG, Zeng K et al. Changes in peripheral blood Th1/Th2 cell balance in patients with condyloma acuminatum. Di Yi Jun Yi Da Xue Xue Bao, 2003 Jul, 23(7): 737-739
36.Liu H, Tu Y, Lin N et al. The expression of Fas/FasL in peripheral blood lymphocytes and the level of IL-2 in serum of patients with condyloma acuminata. J Tongji Med Univ, 2001, 21(2): 171-173
37.李振,曾耀英,蔡小嫦等.尖锐湿疣患者外周血自然杀伤细胞活性的研究.中国皮肤性病学杂志, 2003, 17(3): 145-147
1. Scheinfeld N, Lehman DS. An evidence-based review of medical and surgical treatments of genital warts. Dermatol Online J. 2006 ,12(3): 5-6
2. Garland SM. Imiquimod. Curr Opin Infect Dis, 2003, 31(2): 178-179
3. Vilata JJ, Badia X. ESCCRIM group. Effectiveness, satisfaction and compliance with imiquimod in the treatment of external anogenital warts. Int J STD AIDS, 2003, 14(1): 11-17
4. Eklind J, Tartler U, Masche J, et al. Imiquimod to treat different cancers of the epidermis. Dermatol Surg, 2003, 29(8): 890-896
5. Syed TA. A review of the ap plications of imiquimod: a novel immune response modifier. Expert Opin Pharmacother, 2001, 2(5): 877-882
6. Gupta AK, Browne M, Bluhm R. Imiquimod: a review[J]. J Cutan Med Surg, 2002, 6(6): 554-560
7.任光圆,晏春根,谢青. Toll样受体:免疫治疗的新靶位.中国新药与临床杂志,2004, 23: 718-723
8. Vilata JJ, Sierra X. Efficacy of imiquimod 5% cream in treating genital and perianal warts. Ann Dermatol Venereol, 2002; 129: s322
9. Kono T, Kondo S, Pastore S, et al. Effects of novel topical immunodulator, imiquimod, on keratinocyte cytokine gene expression. Lymphokine Cytokine Res, 1994, 13(2): 72-76
10.Suzaki H, Wang B, Shivji GM, et al. Imiquimod, a topical immune response modifier, induces migration of Langerhans cells. J Invest Dermatol, 2000, 114(1): 135-
11.骆丹,缪旭,吉玺等.咪喹莫特对朗格汉斯细胞及角质形成细胞细胞因子mRNA表达及分泌水平的影响.中华微生物学和免疫学杂志, 2006, 26(3): 274-278
12.吉玺,骆丹,缪旭等. 5%咪喹莫特乳膏对小鼠皮肤3种细胞因子mRNA表达的影响.临床皮肤科杂志, 2006, 35(1): 9-11
13.Kreuter A, Brockmeyer NH, Weissenorn SJ, et al. 5% imiquimod suppositories decrease the DNA load of intra-anal HPV types 6 and 11 in HIV-infected men after surgical ablation of condylomata acuminata. Arch Dermatol. 2006, 142(2): 243-244
14.倪文琼,屈卫东,陈晨等.咪喹莫特乳膏对尖锐湿疣组织HPV载量的影响.中国麻风皮肤病杂志. 2006, 22(2): 131-132
15.顾恒,曾凡钦,郭在培.咪喹莫特乳膏治疗尖锐湿疣随机、双盲、多中心研究.中华皮肤科杂志,2003, 36(9): 501-504
16.More RA, Edwards JE, Hopwood J, et al. Imiquimod for the treatment of genital warts: a quantitative systematic review. BMC Infect Dis, 2001,1:3-4
17.阎乎玲,彭振辉,谭升顺等. 5%咪喹莫特乳膏治疗尖锐湿疣的临床研究.陕西医学杂志. 2006, 35(6): 666-667
18.Vexiau D, Decuypere L, Moyse D, et al. Efficacy and safety of 5% imiquimod cream in external genital warts: a 6 month follow-up evaluation. AnnDermatol Venereol. 2005, 132(11 Pt 1): 845-51
19.Garland SM, Waddell R, Mindel A, et al. An open-label phase II pilot study investigating the optimal duration of imiquimod 5% cream for the treatment of external genital warts in women Int J STD AIDS. 2006 ,17(7): 448-52
20.Chang CH, Chen TH, Hsu RC, et al. The prevalence of HPV-18 and variants of E6 gene isolated from cervical cancer patients in Taiwan. J Clin Virol, 2005, 32: 33-37
21.Palker TJ, Monteior JM, Martin MM, et al. Antibody, cytokine and cytotoxic T lymphocyte responses in chimpanzees immunized with human papillomavirus virus-like particles Vaccine.2001, 19: 3733-3743
22.Koutsky LA, Ault KA, Wheeher CM, et al. A controlled trial of a human papillomavirus type 16 vaccine N Engl J. 2002, 347(21): 1645-1651
23.Berry JM, Palefsky JM. A review of human papilloma virus vaccines: from basic science to clinical trials. Front Biosci, 2003, 8: 833-345
24.Frazer I. Vaccines for papilloma virus infection. Virus Res, 2002, 89(21): 271-274
25.Tobery TW, Smith JF, Kuklin N,et al. Effect of vaccine delivery system on the induction of HPV16L1-specific humoral and cell-mediated immune responses in immunized rhesus macapques. Vaccine, 2003, 21(13-14): 1539-1547
26.Dasilva DM, Velders MP, Tudolf MP, et al. Papillomavirus virus-like-particles as anticancer vaccines. Curr Opin Mo Ther, 1999, 1:82-88
27.Gamett GP, Waddel lHC. Public health paradoxes and the epidemiological impact of an HPV vaccine. J Clin Viro, 2000, 19: 101-111
28.Harro CD, Pang YY, Roden RB, et al. Safety and immunogenicity trial in adult volunteers of a human papilloma virus 16 L1 virus-like particle vaccine.J Natl Cancer Inst, 2001, 93: 284-287
29.Pinto LA, Edwards J, Castle PE, et al. Cellula rimmune responses to human papilloma virus(HPV)-16L1 in healthy volunteers immunized with recombinant HPV-16 L1 virus-like particles. J Infect Dis, 2003, 188: 327-338
30.Widdice LE, Kahn JA. Using the new HPV vaccines in clinical practice. Cleve Clin J Med. 2006, 73(10): 929-35
31.Villa LL, Costa RL, Petta CA, et al. High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up. Br J Cancer, 2006, 95(11): 1459-1466
32.Velders MP, Markiewicz M, Eiben GL, et al. CD4 T cell matters in tumor immunity. Int Rev Immunol, 2003, 22: 113-140
33.Michel N, Osen W, Gissmann L, et al. Enhanced immunogenicity of HPV 16 E7 fusion proteinin DNA vaccination. Virology, 2002, 294(1): 47-59
34.Berzofsky JA, Ahlers JD, Belyakov IM. Strategies for designing and optimizing new generation vaccines. Nat Rev Immunol, 2001, 1: 209-219
35.Peng S, Ji H, Trimble C, et al. Development of a DNA vaccine targeting human papilloma virus type 16 oncoprotein E6. J Virol, 2004, 78: 8468-8476
36.Garcia F, Petry KU, Muderspach L, et al. ZYC101a for treatment of high-grade cervical intraepithelial neoplasia: a randomized controlled trial. Obstet Gynecol, 2004, 103:317-326
37.Lacey CJ, Thompson HS, Monteiro EF, et al. PhaseⅡa safety and immunogenicity of a therapeutic vaccine, TA-GW, in persons with genital warts. J Infect Dis, 1999, 179: 612-618
38.Vandepapeliere P, Barrasso R, Meijer CJ, et al. Randomized controlled trial of an adjuvanted human papillomavirus (HPV) type 6 L2E7 vaccine: infection of external anogenital warts with multiple HPV types and failure oftherapeutic vaccination. J Infect Dis. 2005, 192(12): 2099-2107
39.de Jong A, O'Neill T, Khan AY, et al. Enhancement of human papillomavirus (HPV) type 16 E6 and E7-specific T-cell immunity in healthy volunteers through vaccination with TA-CIN, an HPV16L2E7E6 fusion protein vaccine. Vaccine, 2002, 20(29-30): 3456-3464
40.Zwaveling S, MotaFerreira SC, Nouta J, et al. Established human papilloma virus type16-expressing tumor are effectively eradicated following vaccination with long peptides. J Immunol, 2002, 169: 350-358
41.Kim TW, Hung CF, Ling M, e al. Enhancing DNA vaccine potency by coadministration of DNA encoding antiapoptotic proteins. J Clin Invest, 2003, 112: 109-117
42.Lin CW, Lee JY, Tsao YP, et al. Oral vaccination with recombinant Liseria monocytogenes expressiong human papilloma virus type 16 E7 can cause tumor growth in mice to regress. Int J Cancer, 2002, 102:629-637
2. Katch KD. Valvovaginal human papilloma virus infections clinical implications and management. Am J Gynecol, 2000, 5: 183
3.龚向东,叶顺章,张君炎等. 1991～2001年我国性病流行病学分析.中华皮肤科杂志, 2002, 35(3): 178-182
4. Villa LL, Costa RL, Petta CA, et al. High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up. Br J Cancer, 2006, 95(11): 1459-66
5. Yu HC, Cho BH, Chung MJ et al. A case of giant condylomata acuminata involving anus after renal transplantation. Clin Nephrol, 2003, 59(3): 235-236
6. von Krogh G, Dahlman-Ghozlan K, Syrijanen S. Potential human papillomavirus reactivation following topical corticosteriod therapy of genital lichen sclerosus and erosive lichen planus. J Eur Acad Dermatol Venereol, 2002, 162(2): 103-133
7. Vandepapeliere P, Barrasso R, Meijer CJ et al. Randomized controlled trial of an adjuvanted human papillomavirus (HPV) type 6 L2E7 vaccine: infection of external anogenital warts with multiple HPV types and failure of therapeutic vaccination. J Infect Dis, 2005, 192(2): 2099-2107
8.王光超.皮肤病及性病学.第一版.北京:北京科学出版社,2002.361-362
9. Underwood MR, Shewchuk LM, Hassell AM et al. Searching for antiviral drugs for human papillomaviruses. Antivir Ther, 2000, 5(4): 229-242
10.Beutner KR, Tying S. Human papillomavirus and human disease. Am J Med, 1997, 102(5A): 9-15
11.Moscicki AB. Impact of HPV infection in adolescent populations. J Adolesc Health, 2005, 37(6 Suppl): S3-9
12.Woodman CB, Collins S, Winter H et al. Natural history of cervical human papillomavirus infection in young women: a longitudinal cohort study. Lancet, 2001, 357(33): 1831-1836
13.Trottier H, Franco EL. Human papillomavirus and cervical cancer: burden of illness and basis for prevention. Am J Manag Care, 2006, 12(17Suppl): s462-472
14.Kim KH, Greenfield W, Shotts E et al. Detection of Human Papillomavirus Type 16-Specific T Lymphocytes Using a Recombinant Vaccinia Virus-Based ELISPOT Assay. Clin Vaccine Immunol, 2007, (Epub ahead of print)
15.Waldrop SL, Pitcher CJ, Peterson DM et al. Determination of antigen-specific memory/effector CD4+T cell frequencies by flow cytometry. J Clin Invest, 1997, 99:1739-1750
16.Pala P, Hussell T, Openshaw PJM et al. Floe cytometric measurement of intracellular cytokines. J Immunol Methods, 2000, 243: 107-124
17.Sander B, Andersson J, Andersson U. Assessment of cytokines by immumofluorescence and the paraformaldehyde-saponin procedure. Immumol Rev, 1991, 119:65-93
18.Andersson PO, Olsson A, Wadenvik H. Reduced transforming growth factor-beta1 production by mononuclear cells from patients with active chronic idiopathic thrombocytopenic purpura. Br J Haematol, 2002, 116(4): 862-867
19.孟泽,李晓军.免疫学检验的热点与难点.临床检验杂志,2000,18(1):60
20.Neurath MF, Finotto S, Glimcher LH. The role of Th1/Th2 polarization in mucosal immunity. Nat Med, 2002, 8: 567-573
21.Torres KC, Dutra WO, gollob KJ. Endogenous IL-4 and IFN-γare essentialfor expression of Th2, but not Th1 cytokine message during the early differentiation of human CD4+ T helper cells. Human Immunol, 2004, 65(1): 1328-1335
22.Murakami H, Ogawara H, Hiroshi H. Th1/Th2 cells in patiens with multiple myeloma. Hematology, 2004, 9(1):41-45
23.Kobayashi A, Miaskowski C, Wallhagen M, et al. Recent development in understanding the immune response to human papilloma virus infection and cervical neoplasia. Oncol Nurs Forum, 2000, 27(4): 643-651
24.郭红卫,钱起丰,吴志华.尖锐湿疣患者Th1/Th2细胞因子检测.中华皮肤科杂志. 2003, 36: 256-257
25.龚非力.基础免疫学.第一版.武汉:湖北科学技术出版社,1998.24-173
26.朱讯.免疫学新进展.第一版.北京:人民卫生出版社,2002.255-294
27.Biron CA, Brossay L. NK cells and NKT cells in innate defense against viral infections. Curr Opin Immunol, 2001, 13: 458-464
28.Luo D, Vermijlen D, Ahishali B et al. MHC class I expression protects colon carcinoma cells from cytolysis and apoptosis by hepatic NK(pit) cells by blocking perforin/granzyme pathway. Comparative Hepatology, 2002, 1: 1-9
29.王玉坤,王克玉,郭淑兰等. NK细胞与尖锐湿疣转归关系研究.中国麻风皮肤病杂志, 2003, 19(5): 442-443
30.杨春莉,裘宇容.流式细胞仪对系统性红斑狼疮患者的T细胞亚群及NK细胞检测.第一军医大学学报, 2000, 20(3):274
31.Wei LH, Kuo ML, Chen CA et al. Interleukin-6 in cervical cancer: the relationship with vascular endothelial growth factor. Gynecol Oncol, 2001, 82(1): 49-56
32.殷缨,张盈华,张利朝等.恶性肿瘤患者T细胞亚群与红细胞免疫功能的变化及其相关性分析.实用癌症杂志,2001,16(2):171-173
1. Irmler M, Thome M, Hahne M et al. Inhibition of death receptor signals by cellular FLIP. Nature, 1997, 388(6638): 190-195
2. Tjalma WA, Weyler JJ, Bogers JJ etal. The importance of biological factors(bcl22, bax, p53, PCNA, MIHPV and angiogenesis) in invasive cervical cancer. Eur J Obstet Gynecol Reprod Biol, 2001, 97(2):223-230
3. Duttagupta C, Sengupta S, Roy M et al. Oncogenic human papillomavirus(HPV) infection and uteine cervical cancer:a screening strategy in the perspective of rural India1. European J Cancer Prevention, 2002, 11(8): 447-456
4. Vaux DL, Korsmeyer SJ. Cell death in development[J]. cell,1999,96:245-254
5.吴人亮,李娜萍.细胞凋亡、胀亡和坏死-关于细胞死亡的新认识.中华病理学杂志, 2002, 31: 455-456
6. Patel T, Gores GJ. Apoptosis and hepatobiliary disease. Hpatology, 1995, 21: 1725-1741
7. Green DR. Apoptotic pathways: paper wraps stone blunts scissors. Cell, 2000, 102(1):1-4
8. Yew DT, Ping Li, Liu WK. Fas and activated caspase 8 in normal, Alzheimer and multiple infarct brains. Neurosci Lett, 2004, 367(1):113-117
9. Xu B, Bulfone-Paus S, Aoyama K et al. Role of Fas/Fas ligand-mediated apoptosis in murine contact hypersensitivity. Int J Immunopharmacol, 2003, 3(7): 927-938
10.Roaquet N, Allemand I, Molina T et al. Fas-dependent apoptosisis impaired by SV40 T-antigen in transgenic liver. Oncogene, 1995, 11(6): 1061-1067
11.Nguyen ML, Blaho JA. Apoptosis during herpes simplex virus infection. Adv Virus Res, 2007, 69:67-97
12.Rieux-Laucat F, Le Deist F, Hivroz C et al. Mutations in Fas associated with human lymphoproliferative syndrome and autoimmunity. Science, 1995, 268(5215): 1347-1349
13.Gavrieli Y, Sherman Y, Ben-Sasson SA. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol, 1992, 119: 493-501
14.Guan DW, Ohshima T, Kondo T. Immunohistochemical study on Fas and Fas ligand in skin wound healing. J Histochem, 2000, 32: 85-91
15.Berthou C, Michel L, Soulie A et al. Acquisition of granzyme B and Fas ligand proteins by human keratinocytes contributes to epidermal cell defense. J Immunol, 1997, 159: 5293-5300
16.项彤,陈兴平.尖锐湿疣组织中的细胞凋亡与caspase-3和bcl-2蛋白的检测.中国皮肤性病学杂志, 2006, 20(8): 471-473
17.Isacson C, Kessis TD, Hedrick L et al. Both cell proliferation and apoptosis increases with Lesion grade in cervical neoplasia but not correlate with human papillomavirus type. Cancel Res, 1996, 56(4): 669-674)
18.Allen SM, Florell SR, Hanks AN et al. Survivin expression in mouse skin prevents papilloma regression and promotes chemical-induced tumor progression. Cancer Res, 2003, 63: 567-572
19.Lanham S, Herber AT, Watt P et al. HPV detection and measurement of HPV-16,telomerase, and survivin transcripts in colposcopy clinic patients. J Clin Pathol, 2001, 54(4): 304-308
20.Michael F, Elka A, David O et al. Immunohistochemical Localization of Survivin in Benign Cervical Mucosa, Cervical Dysplasia, and InvasiveSquamous Cell Carcinoma. Am J Clin Pathol. 2002, 117(5): 738-744
21.Fan G, Ma X, Wong PY et al. p53 dephosphorylation and p21 (cipl/wafl) translocation correlation with caspase-3 activation in TGF-betal-induced apoptosis of HuH27 cell. Apoptosis, 2004, 9(2): 211-221
22.Leverrier S, Bergamaschi D, Ghali L et al. Role of HPV E6 proteins in preventing UVB-induced release of pro-apoptotic factors from the mitochondria. Apoptosis, 2007, 12(3): 549-560
23.Kabsch K, Mossadegh N, Kohl A et al. The HPV-16 E5 protein inhibits TRAIL- and FasL-mediated apoptosis in human keratinocytes raft cultures. Intervirology, 2004, 47(1): 48-56
1. Sonnex C, Lacey CJ. The treatment of human papillomavirus lesions of the lower genital tract. Best Pract Res Clin Obstet Gynaecol, 2001, 15: 801–816
2. Kennedy JC, Pottier RH, Pross DC. Photodynamic therapy with endogenous protoporphyrin IX: basic principles and present clinical experience. J Phtotochem Photobical B Biol, 1990, 6: 143-148
3.张林,虞乐华.光动力疗法作用机制的研究进展.激光杂志, 2003, 24: 91-93
4. Kalka K, Merk H, Mukhtar H. Photodynamic therapy in dermatology. J Am Acad Dermatol, 2000, 42(3): 389-413
5. Talor EL, Brown SB. The advantage of aminolevulinic acid photodynamic therapy in dermatology. J Dermatol Treat, 2002, 13(Suppl. 1): S3-11
6. Britton JER, Goulden V, Stables M, et al. Ivestigation of the use of the pulsed dye laser in the treatment of Bowen’s disease using
5-aminolaevulinic acid phototherapy. Br J Dermatol, 2005, 153: 780-784
7. Karrer B. Baumler W, Abels C, et al. Long-pulse dye laser for photodynamic therapy: in vitro and in vivo. Lasers Surg Med, 1999, 25: 51-59
8. Oieinick NI, Evans HH. The photobiology of photodynamic therapy cellular targets and mechanisms. Radiat Res, 1998, 50 (5): 146-156
9. Gastano AP, Demidova TN, Hamblin MR. Mechanisms in photodynamic therapy. Part one. Photosensitizers, photochemistry and cellular localization. Photodiagn Photodyn Ther, 2004, 1: 279-293
10.Gastano AP, Demidova TN, Hamblin MR. Mechanisms in photodynamic therapy. Part two. Cellular signaling, cell metabolism and modes of cell death. Photodiagn Photodyn Ther, 2005, 2: 1-23
11.Gastano AP, Demidova TN, Hamblin MR. Mechanisms in photodynamic therapy. Part three. Photosensitizer pharmacokinetics, biodistribution, tumor localization and modes of tumor destruction. Photodiagn Photodyn Ther, 2005, 2: 91-106)
12.Szpringer E, Lutnicki K, Marciniak A. et al. Photodynamic therapy - mechanism and employment. Ann Univ Mariae Curie Sklodowska[Med], 2004, 59(2): 498-502
13.Kalka K, Merk H, Mukhtar H. Photodynamic therapy in dermatology. J Am Acad Dermatol, 2000, 42(3): 389-413
14.Gaulloer JM, Berg K, Peng Q, et al. 5-aminolevulinic acid esters to improve photodynamic therapy on cells in culture. Cncer Res, 1997, 57: 1481-1486
15.Bunke A, Derbe A, Schmid H et al. Degradation mechanism and stability of 5-aminolevulinic acid. J Pharm Sci, 2000, 89: 1335-1341
16.Maria CD, Robert JC. Photosensitized singlet oxygen and its applications. Coordination Chemistry Reviews,2002,233-234:351-371
17.Mullooly VM, Abramson AL, Shikowitz MJ. Dihematoporphyrin-ether induced photosensitivity in laryngeal papilloma patients. Laser Surg Med, 1990,10: 349-356
18.李晓原,去径平,谭润初等.温热疗法与Ar+离子激光联合对小鼠s180肉瘤DNA含量的影响研究.中国医学物理学杂志, 1999, 16: 151-153
19.Fink-Puches R, Hofer A, Smolle J, et al. Primary clinical responses and long-term follow-up of solar keratoses treated with topically applied 5-aminolevulinic acid and irradiation by different wave bands of light. J Photochem Photobiol B Biol, 1997,41: 145-151
20.Kennedy JC, Ottier RH. Endogenous protoporphyrin IX, a clinical useful photosensitizer for photodynamic therapy. J Photochem Photobiol B Biol, 1992, 14: 275-292
21.Brancaleon L, Moseley H. Lasers and non-laser light sources for photodynamic therapy. Lasers Med Sci, 2002, 17: 173-186
22.Selvasekar CR, Birbeck N, Mcmillan T et al. Photodynamic therapy and the alimentary track. Aliment Pharmacal Ther, 2001,15: 899-915
23.Ceburkov O, Gollnick H. Photodynamic therapy in dermatology. Eur J Dermatol, 2000, 10: 568-576
24.Szeimies RM, Abels C, Fritsch C et al. Wavelength dependency of photodynamic effects after sensitization with 5-aminolevulinic acid in vitro and in vivo. J Invest Dermatol, 1995, 105: 672-677
25.Dougherty TJ. An update on photodynamic therapy applications. J Clin Laser Med Surg. 2002, 20: 3-7
26.Yow CM, Wong CK, Huang Z et al. Study of the efficacy and mechanism of ALA-mediated photodynamic therapy on human hepatocellular carcinoma cell. Liver Int, 2007, 27(2): 201-208
27.Ibbotson SH. Topical 5-aminolaevulinic acid photodynamic therapy for the treatment of skin conditions other than non-melanoma skin cancer. Br J Dermatol, 2002: 146: 178-188
28.Britton JE, Goulden V, Stables G et al. Investigation of the use of the pulsed dye laser in the treatment of Bowen's disease using 5-aminolaevulinic acid phototherapy. Br J Dermatol, 2005, 153(4): 780-784
29.Alexiades-Armenakes M, Geronemus RG. Laser-mediated photodynamic therapy of actinic keratoses. Arch Dermatol, 2003, 139(10): 1313-1320
30.Szeimies RM. Methyl aminolevulinate-photodynamic therapy for basal cell carcinoma. Dermatol Clin, 2007, 25(1): 89-94
31.Head CS, Luu Q, Sarcarze J et al. Photodynamic therapy and tumor imaging of hypericin-treated squamous cell carcinoma. World J Surg Oncol. 2006, 4: 87
32.Blume JE, Oseroff AR. Aminolevulinic acid photodynamic therapy for skin cancers. Dermatol Clin, 2007, 25(1): 5-14
33.Alexiades-Armenakes M. Long-pulsed dye laser-mediated photodynamic therapy combined with topical therapy for mild to severe comedonal, inflammatory, or cystic acne. J Drugs Dermatol, 2006, 5(1):45-55
34.Calzavara-Pinton PG, Venturini M, Sala R. A comprehensive overview of photodynamic therapy in the treatment of superficial fungal infections of the skin. J Photochem Photobiol B, 2005, 78(1):1-6
35.Edstrom DW, Hedblad MA, Ros AM. Flashlamp pulsed dye laser and argon-pumped dye laser in the treatment of port-wine stains: a clinical and histological comparison. Br J Dermatol, 2002, 146: 285-289
36.Hillemanns P, Unch M, Dannecker C et al. Photodynamic therapy of vulvar intraepithelial neoplasia using 5-aminovulinic acid. Int J Cancer, 2000, 85: 649-653
37.Ross EV, Romero R, Kollias N et al. Selectivity of protoporphyrin IX fluorescence for condylo-mata after topical application of 5-aminolaevulinic acid: implications for photodynamic treatment. Br J Dermatol, 1997, 137: 736–742
38.Itkin A, Gilchrest BA. delta-Aminolevulinic acid and blue light photodynamic therapy for treatment of multiple basal cell carcinomas in two patients with nevoid basal cell carcinoma syndrome. Dermatol Surg, 2004, 30(7): 1054-1061
39.Varma S, Wilson H, Kurwa HA et al. Bowen’s disease, solar keratoses and superficial basal cell carcinomas treated by photodynamic therapy usinga large-field incoherent light source. Br J Dermatol, 2001, 144: 567-574
40.杨文彪,衍坤.尖锐湿疣及HPV亚临床感染病损的组织病理及免疫组织改变.临床皮肤科杂志, 1993, 22(6):298
41.吴阶平.泌尿外科.第一版.济南:山东科学技术出版社, 2003. 412
42.Fehr MK, Hornung R, Degen A et al. Photodynamic therapy of vulvar and vaginal condyloma and intraepithelial neoplasia using topically applied 5-aminolvulinic acid. Lasers Surg Med, 2002, 30: 273-279
43.李迎新,董霞,邵文艾等.光动力学疗法对I型单纯疱疹病毒灭活作用的实验研究.中国激光医学杂志, 2004, 13(4): 228-231
1. Katch KD. Valvovaginal human papilloma virus infections clinical implications and management. Am J Gynecol, 2000, 5: 183
2.龚向东,叶顺章,张君炎等. 1991～2001年我国性病流行病学分析.中华皮肤科杂志, 2002, 35(3): 178-182
3. Van Regenmortel MHV, Fauquet CM, Ishop DHL. Virus Taxonomy. New York: Academic Press, 2000
4. Villa LL, Costa RL, Petta CA et al. High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up. Br J Cancer, 2006, 95(11): 1459-1466
5. Moscicki AB. Impact of HPV infection in adolescent populations. J Adolesc Health, 2005, 37(6 Suppl): S3-9
6. Sedlacek TV. Advances in the diagnosis and treatment of human papillomavirus infections. Clin Obstet Gynecol, 1999, 42: 206-220
7.王丽华,王玉坤,赵东等.尖锐湿疣局部细胞免疫功能状态与人乳头瘤病毒型的相关性研究.中国麻风皮肤病杂志, 2004, 20(3): 242-244
8.杨文彪,衍坤.尖锐湿疣及HPV亚临床感染病损的组织病理及免疫组织改变.临床皮肤科杂志, 1993, 22(6):298
9.吴阶平.泌尿外科.第一版.济南:山东科学技术出版社, 2003. 412
10.张菊,陈中灿,白玉杰等.复发尖锐湿疣患者感染人乳头瘤病毒基因型的荧光偏振检测.临床检验杂志, 2004, 22(4): 244-245
11.Speich N, Schmitt C, Bollmann R et al. Human papillomavirus study of 2916 cytological samples by PCR and DNA sequencing: genotype spectrum of patients from the west German area. J Mcd Michobiol, 2004, 53(pt2): 125-128
12.钱恒林.尖锐湿疣与HLA-A、B位点相关性研究.中华皮肤科杂志, 1996, 25(2): 102-103
13.张庆瑞,谷丽红,杨德荣等.尖锐湿疣患者与HLA抗原及HLA单倍体.中华皮肤科杂志, 1996, 29(3): 192-193
14.Konya J, Dillner J. Immunity to oncogenic human papilloma virus. Adv Cancer Res, 2001, 82: 205-238
15.Perez LA. Genital HPV: links to cervical cancer, treatment, and prevention. Clin Lab Sci, 2001, 14(3): 183-186
16.Habel LA, Van Den Eeden Sk, Sherman KJ et al. Risk factors for incident and recurrent condylomata acuminata among women, a population-based study. Sex Transim Dis, 1998, 25:285-292
17.Svare EI, Kjaer SK, Worm AM et al. Risk factors for genital HPV DNA in men resemble those found in women: a study of male attendees at a Danish STD clinic. Sex Transm Infect, 2002, 78(3): 215-218
18.Winer RL, Lee SK, Hughes JP, et al. Genital human papilloma virus infection: incidence and risk factors in a cohort of female university students. Am J Epidemiol, 2003, 157(3): 218-226
19.Bjekic M, Vlajinac H. Effect of alcohol consumption on recurrence ofvenereal diseases. MedPregl, 2000, 53: 600-602
20.田洪青,杜东红,陈树民.尖锐湿疣发病和复发的危险因素研究现状.国外医学皮肤性病学分册, 2002, 28: 303-305
21.王琳,张广富.尖锐湿疣发病和复发危险因素的问卷调查.中国皮肤性病学杂志, 2005, 19(10): 615-617
22.De la Fuente SG, Ludwig KA, Mantyh CR. Preoperative immune status determines anal condyloma recurrence after surgical excision. Dis Colon Rectum, 2003, 46(3): 367-373
23.Silverberg MJ, Ahdieh L, Munoz A et al. The impact of HIV infection and immunodeficiency on human papilloma virus type 6 or 11 infection and on genital warts. Sex Transm Dis, 2002, 29(8): 427-435
24.梁伶.复发性尖锐湿疣诱发因素的探讨.广西医科大学学报, 2001, 18(3): 369-371
25.王书才,王琳,崔卫国.清洁度变化与阴道内尖锐湿疣复发的关系.中国卫生检验杂志, 2003, 13(5): 659.
26.车雅敏,王家璧,左亚刚等.人乳头瘤病毒DNA载量与尖锐湿疣复发的相关性.中国医学科学院学报, 2004, 26(5): 558-561
27.Coleman N, Birley HDL, Renton AM et al. Immunological events in regressing genital warts. Am J Clin Pathol, 1994, 102(6): 768-774
28.Kobayashi A, Miaskowski C, Wallhagen M et al. Recent development in understanding the immune response to human papilloma virus infection and cervical neoplasia. Oncol Nurs Forum, 2000, 27(4): 643-651
29.Azim AA, Said A, Swelim MM et al. Local expression of tumor necrosis factor-alpha and interleukin-4 mRNA in different types of warts. Egypt J Immunol, 2004, 11(1): 15-21
30.Arrese J, Paguet P, Claessens N et al. Dermal dendritic cells in anogenitalwarty lesionslesions unresponsive to an immune–response modifier. J Cutan Pathol, 2001, 28: 131- 134
31.Kikuchi K, Kusama K. Dendritic cells in human squamous cell carcinomal of the oral cavity. Anticancer Res, 2002, 22: 545-557
32.曹育春,陈兴平,徐祖森等. S100+朗格罕斯细胞与尖锐湿疣复发的相关性研究.中华皮肤科杂志, 2005, 38(7): 446-447
33.Johan SA, Erik JC, Reel A et al. HIV, sexaually transmitted diseases and gynaecologic disorders in women: increased risk for gential herpes and warts among HIV-infected prostitutes in Amsterdam. AIDS, 1995, 91(9):1071-1078
34.Teunissen MB, Koomen CW, de Waal Malefyt R et al. IL-17 and IFN-r synergize in the enhancement of proinflammatory cytokines production by human keratinocytes. J Invest Dermatol, 1998, 111(4): 645-649
35.Li L, Zhou ZG, Zeng K et al. Changes in peripheral blood Th1/Th2 cell balance in patients with condyloma acuminatum. Di Yi Jun Yi Da Xue Xue Bao, 2003 Jul, 23(7): 737-739
36.Liu H, Tu Y, Lin N et al. The expression of Fas/FasL in peripheral blood lymphocytes and the level of IL-2 in serum of patients with condyloma acuminata. J Tongji Med Univ, 2001, 21(2): 171-173
37.李振,曾耀英,蔡小嫦等.尖锐湿疣患者外周血自然杀伤细胞活性的研究.中国皮肤性病学杂志, 2003, 17(3): 145-147
1. Scheinfeld N, Lehman DS. An evidence-based review of medical and surgical treatments of genital warts. Dermatol Online J. 2006 ,12(3): 5-6
2. Garland SM. Imiquimod. Curr Opin Infect Dis, 2003, 31(2): 178-179
3. Vilata JJ, Badia X. ESCCRIM group. Effectiveness, satisfaction and compliance with imiquimod in the treatment of external anogenital warts. Int J STD AIDS, 2003, 14(1): 11-17
4. Eklind J, Tartler U, Masche J, et al. Imiquimod to treat different cancers of the epidermis. Dermatol Surg, 2003, 29(8): 890-896
5. Syed TA. A review of the ap plications of imiquimod: a novel immune response modifier. Expert Opin Pharmacother, 2001, 2(5): 877-882
6. Gupta AK, Browne M, Bluhm R. Imiquimod: a review[J]. J Cutan Med Surg, 2002, 6(6): 554-560
7.任光圆,晏春根,谢青. Toll样受体:免疫治疗的新靶位.中国新药与临床杂志,2004, 23: 718-723
8. Vilata JJ, Sierra X. Efficacy of imiquimod 5% cream in treating genital and perianal warts. Ann Dermatol Venereol, 2002; 129: s322
9. Kono T, Kondo S, Pastore S, et al. Effects of novel topical immunodulator, imiquimod, on keratinocyte cytokine gene expression. Lymphokine Cytokine Res, 1994, 13(2): 72-76
10.Suzaki H, Wang B, Shivji GM, et al. Imiquimod, a topical immune response modifier, induces migration of Langerhans cells. J Invest Dermatol, 2000, 114(1): 135-
11.骆丹,缪旭,吉玺等.咪喹莫特对朗格汉斯细胞及角质形成细胞细胞因子mRNA表达及分泌水平的影响.中华微生物学和免疫学杂志, 2006, 26(3): 274-278
12.吉玺,骆丹,缪旭等. 5%咪喹莫特乳膏对小鼠皮肤3种细胞因子mRNA表达的影响.临床皮肤科杂志, 2006, 35(1): 9-11
13.Kreuter A, Brockmeyer NH, Weissenorn SJ, et al. 5% imiquimod suppositories decrease the DNA load of intra-anal HPV types 6 and 11 in HIV-infected men after surgical ablation of condylomata acuminata. Arch Dermatol. 2006, 142(2): 243-244
14.倪文琼,屈卫东,陈晨等.咪喹莫特乳膏对尖锐湿疣组织HPV载量的影响.中国麻风皮肤病杂志. 2006, 22(2): 131-132
15.顾恒,曾凡钦,郭在培.咪喹莫特乳膏治疗尖锐湿疣随机、双盲、多中心研究.中华皮肤科杂志,2003, 36(9): 501-504
16.More RA, Edwards JE, Hopwood J, et al. Imiquimod for the treatment of genital warts: a quantitative systematic review. BMC Infect Dis, 2001,1:3-4
17.阎乎玲,彭振辉,谭升顺等. 5%咪喹莫特乳膏治疗尖锐湿疣的临床研究.陕西医学杂志. 2006, 35(6): 666-667
18.Vexiau D, Decuypere L, Moyse D, et al. Efficacy and safety of 5% imiquimod cream in external genital warts: a 6 month follow-up evaluation. AnnDermatol Venereol. 2005, 132(11 Pt 1): 845-51
19.Garland SM, Waddell R, Mindel A, et al. An open-label phase II pilot study investigating the optimal duration of imiquimod 5% cream for the treatment of external genital warts in women Int J STD AIDS. 2006 ,17(7): 448-52
20.Chang CH, Chen TH, Hsu RC, et al. The prevalence of HPV-18 and variants of E6 gene isolated from cervical cancer patients in Taiwan. J Clin Virol, 2005, 32: 33-37
21.Palker TJ, Monteior JM, Martin MM, et al. Antibody, cytokine and cytotoxic T lymphocyte responses in chimpanzees immunized with human papillomavirus virus-like particles Vaccine.2001, 19: 3733-3743
22.Koutsky LA, Ault KA, Wheeher CM, et al. A controlled trial of a human papillomavirus type 16 vaccine N Engl J. 2002, 347(21): 1645-1651
23.Berry JM, Palefsky JM. A review of human papilloma virus vaccines: from basic science to clinical trials. Front Biosci, 2003, 8: 833-345
24.Frazer I. Vaccines for papilloma virus infection. Virus Res, 2002, 89(21): 271-274
25.Tobery TW, Smith JF, Kuklin N,et al. Effect of vaccine delivery system on the induction of HPV16L1-specific humoral and cell-mediated immune responses in immunized rhesus macapques. Vaccine, 2003, 21(13-14): 1539-1547
26.Dasilva DM, Velders MP, Tudolf MP, et al. Papillomavirus virus-like-particles as anticancer vaccines. Curr Opin Mo Ther, 1999, 1:82-88
27.Gamett GP, Waddel lHC. Public health paradoxes and the epidemiological impact of an HPV vaccine. J Clin Viro, 2000, 19: 101-111
28.Harro CD, Pang YY, Roden RB, et al. Safety and immunogenicity trial in adult volunteers of a human papilloma virus 16 L1 virus-like particle vaccine.J Natl Cancer Inst, 2001, 93: 284-287
29.Pinto LA, Edwards J, Castle PE, et al. Cellula rimmune responses to human papilloma virus(HPV)-16L1 in healthy volunteers immunized with recombinant HPV-16 L1 virus-like particles. J Infect Dis, 2003, 188: 327-338
30.Widdice LE, Kahn JA. Using the new HPV vaccines in clinical practice. Cleve Clin J Med. 2006, 73(10): 929-35
31.Villa LL, Costa RL, Petta CA, et al. High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up. Br J Cancer, 2006, 95(11): 1459-1466
32.Velders MP, Markiewicz M, Eiben GL, et al. CD4 T cell matters in tumor immunity. Int Rev Immunol, 2003, 22: 113-140
33.Michel N, Osen W, Gissmann L, et al. Enhanced immunogenicity of HPV 16 E7 fusion proteinin DNA vaccination. Virology, 2002, 294(1): 47-59
34.Berzofsky JA, Ahlers JD, Belyakov IM. Strategies for designing and optimizing new generation vaccines. Nat Rev Immunol, 2001, 1: 209-219
35.Peng S, Ji H, Trimble C, et al. Development of a DNA vaccine targeting human papilloma virus type 16 oncoprotein E6. J Virol, 2004, 78: 8468-8476
36.Garcia F, Petry KU, Muderspach L, et al. ZYC101a for treatment of high-grade cervical intraepithelial neoplasia: a randomized controlled trial. Obstet Gynecol, 2004, 103:317-326
37.Lacey CJ, Thompson HS, Monteiro EF, et al. PhaseⅡa safety and immunogenicity of a therapeutic vaccine, TA-GW, in persons with genital warts. J Infect Dis, 1999, 179: 612-618
38.Vandepapeliere P, Barrasso R, Meijer CJ, et al. Randomized controlled trial of an adjuvanted human papillomavirus (HPV) type 6 L2E7 vaccine: infection of external anogenital warts with multiple HPV types and failure oftherapeutic vaccination. J Infect Dis. 2005, 192(12): 2099-2107
39.de Jong A, O'Neill T, Khan AY, et al. Enhancement of human papillomavirus (HPV) type 16 E6 and E7-specific T-cell immunity in healthy volunteers through vaccination with TA-CIN, an HPV16L2E7E6 fusion protein vaccine. Vaccine, 2002, 20(29-30): 3456-3464
40.Zwaveling S, MotaFerreira SC, Nouta J, et al. Established human papilloma virus type16-expressing tumor are effectively eradicated following vaccination with long peptides. J Immunol, 2002, 169: 350-358
41.Kim TW, Hung CF, Ling M, e al. Enhancing DNA vaccine potency by coadministration of DNA encoding antiapoptotic proteins. J Clin Invest, 2003, 112: 109-117
42.Lin CW, Lee JY, Tsao YP, et al. Oral vaccination with recombinant Liseria monocytogenes expressiong human papilloma virus type 16 E7 can cause tumor growth in mice to regress. Int J Cancer, 2002, 102:629-637