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1.
Sebastian Mondaca Walid K. Chatila David Bates Jaclyn F. Hechtman Andrea Cercek Neil H. Segal Zsofia K. Stadler Anna M. Varghese Ritika Kundra Marinela Capanu Jinru Shia Nikolaus Schultz Leonard Saltz Rona Yaeger 《Clinical colorectal cancer》2019,18(1):e39-e52
Background
Treatment of advanced anal squamous cell cancer (SCC) is usually with the combination of cisplatin and 5-fluorouracil, which is associated with heterogeneous responses across patients and significant toxicity. We examined the safety and efficacy of a modified schedule, FOLFCIS (leucovorin, fluorouracil, and cisplatin), and performed an integrated clinical and genomic analysis of anal SCC.Patients and Methods
We reviewed all patients with advanced anal SCC receiving first-line FOLFCIS chemotherapy – essentially a FOLFOX (leucovorin, fluorouracil, and oxaliplatin) schedule with cisplatin substituted for oxaliplatin – in our institution between 2007 and 2017, and performed deep sequencing to identify genomic markers of response and key genomic drivers.Results
Fifty-three patients with advanced anal SCC (48 metastatic; 5 unresectable, locally advanced) received first-line FOLFCIS during this period; all were platinum-naive. The response rate was 48% (95% confidence interval [CI], 32.6%-63%). With a median follow-up of 41.6 months, progression-free survival and overall survival were 7.1 months (95% CI, 4.4-8.6 months) and 22.1 months (95% CI, 16.9-28.1 months), respectively. Among all patients with advanced anal SCC that underwent sequencing during the study period, the most frequent genomic alterations consisted of chromosome 3q amplification (51%) and mutations in PIK3CA (29%) and KMT2D (22%). No genomic alteration correlated with response to platinum-containing treatment. Although there were few cases, patients with human papillomavirus-negative anal SCC did not appear to benefit from FOLFCIS, and all harbored distinct genomic profiles with TP53, TERT promoter, and CDKN2A mutations.Conclusions
FOLFCIS appears effective and safe as first-line chemotherapy in patients with advanced anal SCC and represents an alternative treatment option for these patients. 相似文献2.
W. A. A. Tjalma M. Arbyn† J. Paavonen‡ T. R. Van Waes & J. J. Bogers§ 《International journal of gynecological cancer》2004,14(5):751-761
Persistent infection with one of the oncogenic human papillomavirus (HPV) types is a necessity for the development of cervical cancer. By HPV vaccination, cervical cancer could become a very rare disease. Two types of HPV vaccines can be distinguished: (i) therapeutic vaccines which induce cellular immunity targeted against epithelial cells infected with HPV and (ii) prophylactic vaccines inducing virus-neutralizing antibodies protecting against new but not against established infections. At present, several vaccines have been developed and tested in clinical trials. The vaccines are generally well tolerated and highly immunogenic. The current clinical data indicate that prophylactic vaccines are very effective against new persistent infections and the development of cervical intraepithelial lesions. The protection is type specific. However, the follow-up of the vaccination trials is still short. The effect of HPV vaccines on future cancer incidence will only be known after decades of follow-up. This article will address the status of recently terminated phase II and currently running phase III trials with prophylactic HPV vaccines. 相似文献
3.
4.
Bo Sikström M.D. Dan Hellberg M.D. Ph.D. Staffan Nilsson M.D. Ph.D. Christina Brihmer M.D. Ph.D. Per-Anders Mårdh M.D. Ph.D. 《Archives of sexual behavior》1996,25(4):361-372
In a study of 972 women, sexual characteristics of 66 women with a cervical human papillomavirus infection (CHPI) were compared
to the remaining study population. Among a number of sexual variables that were significantly correlated with CHPI were number
of lifetime sexual partners, short partnerships, many recent partners, infidelity, casual travel sex, sexual début abroad,
oral and anal sex, and sexual abuse. In multifactorial analyses four variables remained significantly correlated with CHPI,
i.e., number of lifetime sexual partners, casual travel sex, sexual début abroad, and infidelity. It is concluded that CHPI
shows most of the epidemiological characteristics of a sexually transmitted disease. 相似文献
5.
原位杂交与免疫组化技术在HPV检测中的应用 总被引:5,自引:0,他引:5
目的:对两种HPV检测技术DNA原位杂交和免疫组化染色方法进行对比观察。方法:选取本院外阴尖锐湿疣病例95例,组织经固定、脱水、石蜡包埋、切片,分别采用原位杂交和免疫组化技术进行检测。结果:HPV—DNA阳性率为94.7%(90/95),阳性反应由鳞状上皮表层的空泡细胞核内延伸至棘层中下部近基底层的细胞核内;HPV—Ag阳性率为63.1%(60/95),阳性反应主要位于鳞状上皮表层的空泡细胞核内及角质层内。个别阳性细胞可在棘层出现。结论:原位杂交技术在敏感度、阳性率及阳性强度、背景染色等方面均优于免疫组化方法,为尖锐湿疣的确诊及临床治疗提供更准确、可靠的依据。 相似文献
6.
Kathleen A. Ward Sinead A. McKernan Natalina N. Durnien Wallace W. Dinsmore 《Journal of the European Academy of Dermatology and Venereology》1995,4(2):160-165
Objective Detection of HPV DNA in oral and genital lesions of a heterosexual male. 4 months after oral and vaginal intercourse with a woman with vulvar warts. Passible modes of acquisition of oral HPV infection in the male sexual partner are discussed. Setting Genitourinary Medicine clinic. Methods Polymerase chain reaction amplification of genomic DNA from oral and genital lesions. HPV DNA typing by dot blot hybridization. Results HPV DNA types 6 and 11 were identified in a polypoid tongue lesion and in a penile wart from the male sexual partner. Conclusions The acquisition of oral HPV infection in the male sexual partner may have resulted from genital-oral HPV transfer, either by direct contact with vulvar warts or by digital self-inoculation. 相似文献
7.
核酸原位杂交程序中探针和靶基因的加热变性和杂交为整个程序中最重要的环节,目前国内外最常用的方法是在切片上滴加DNA探针溶液后用盖玻片复盖组织,并加胶泥或其他封固剂封闭玻片四周,变性杂交后需拆除盖玻片,这一操作过程易损坏组织切片或出现干片、脱片。作者针对上述情况,对传统的核酸原位杂交方法中的部分程序加以改良,采用不加盖玻片直接在蒸汽中变性方法,经多次实验证明此方法稳定、可靠、简便,结果满意。 相似文献
8.
目的 将人乳头瘤病毒16型(Human papillomavirus type 16,HPV-16)的晚期表达蛋白E7上的抗原24肽(从第38位氨基酸到第61位氨基6病毒感染防治酸)与人免疫球蛋白G的重链恒定区融合表达,并以此融合蛋白作为抗原,可能为HPV-1提供免疫治疗方法。方法 利用PCR方法分别扩增HPV-16 E7(38-61)24肽的DNA片段和人免疫球蛋白G的重链恒定区DNA片段,并构建到pEV21a表达载体上,转化入E.coli中表达,利用SDS-聚丙烯酰胺凝胶电泳(SDS-PAGE)和蛋白质免疫印迹(Western-blotting)的方法对表达结果进行鉴定。结果 构建的表达载体HPV16E7e/hIgGHCCR-pET21a经酶切鉴定和测序显示序列正确;通过SDS-PAGE和Western-blotting的鉴定,重组融合蛋白Mr约40000,表达量可占菌体蛋白的20%左右。结论 成功构建HPV16-E7的抗原多肽片段和人免疫球蛋白G的重链恒定区的融合蛋白,并可在E.coli中高效表达。 相似文献
9.
本文应用HPV-PCR技术和DNA杂交技术对76例宫颈鳞癌标本进行了HPV-DNA的研究,发现HPV-DNA存在率为90.79%(69/76),主要类型为HPV16和18。多酶切SouthernBlot杂交证实在宫颈癌中92.56%的HPV-DNA发生变异,说明HPV-DNA的基因变异与其致癌作用密切相关。PCR结果证实HPV-E6片段在宫颈癌组织中常可出现,推测可能是致癌的关键片段之一。因此,检测宫颈癌组织中HPV-DNA的完整性、关键基因片段的存在与否,可能对于病变恶变的预测有一定的意义 相似文献
10.
应用地高辛甙元标记人乳头瘤病毒(HPV)-6,11,16和18探针,通过核酸杂交法检测上海地区女性患者HPV的感染。计活检组织标本128例,阴道脱落细胞130例,同时取样34例。斑点杂交结果表明活检组织中四种类型HPV的总阳性率:宫颈癌44%,宫颈间变66.7%,有间变史28.6%,外阴尖锐湿疣63%和慢性宫颈炎5.6%。阴道脱落细胞的各阳性率与之相近,同时取样的检测符合率为91.2%。Southern转移杂交结果提示:宫颈癌以HPV-16型为主,尖锐湿疣中的HPV为6和11型 相似文献