Microwave hyperthermia represses human papillomavirus oncoprotein activity and induces cell death due to cell stress in 3D tissue models of anogenital precancers and cancers.
Microwave hyperthermia represses human papillomavirus oncoprotein activity and induces cell death due to cell stress in 3D tissue models of anogenital precancers and cancers.
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DOI：
10.1016/j.ebiom.2023.104577
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发表时间：
2023-05
期刊：
影响因子：
11.1
通讯作者：
Graham SV
中科院分区：
文献类型：
--
作者：
Conley MJ;Epifano I;Kirk A;Stevenson A;Graham SV
热疗是一种广为接受的癌症疗法。微波提供了一种非常精确、有针对性的热疗方法，目前用于治疗由皮肤感染性人乳头瘤病毒 (HPV) 引起的足底疣。其他感染肛门生殖器粘膜的 HPV 基因型会导致尖锐湿疣或癌前病变或宫颈癌。对于这些与 HPV 相关的病态病变，目前缺乏有效的非消融疗法。在体外培养的三维 HPV 阳性宫颈肿瘤组织和由 HPV 感染的正常永生化角质形成细胞形成的组织中研究了微波治疗的分子后果。量化向组织传递的微波能量。使用定量逆转录酶 PCR 来量化 mRNA 表达。使用免疫组织化学和荧光免疫染色来评估蛋白质表达。微波能量沉积在治疗部位诱导持续的局部细胞死亡。 HPV 癌蛋白 E6 和 E7 水平下调，同时细胞生长/增殖减少以及细胞凋亡/自噬诱导。 HSP70 表达证实了体温过高，并伴有翻译应激的诱导。数据表明，微波治疗可抑制肿瘤细胞增殖，并允许 HPV 感染细胞恢复自然凋亡。精准微波传输为治疗 HPV 阳性肛门生殖器癌前病变和癌症提供了一种潜在的新疗法。资金来自于 .
Hyperthermia is a well-accepted cancer therapy. Microwaves provide a very precise, targeted means of hyperthermia and are currently used to treat plantar warts caused by cutaneous-infective human papillomaviruses (HPVs). Other HPV genotypes infecting the anogenital mucosa cause genital warts or preneoplastic lesions or cervical cancer. Effective, non-ablative therapies for these morbid HPV-associated lesions are lacking. The molecular consequences of microwave treatment were investigated in in vitro cultured three-dimensional HPV-positive cervical tumour tissues, and tissues formed from HPV-infected normal immortalised keratinocytes. Microwave energy delivery to tissues was quantified. Quantitative reverse transcriptase PCR was used to quantify mRNA expression. Immunohistochemistry and fluorescence immunostaining was used to assess protein expression. Microwave energy deposition induced sustained, localised cell death at the treatment site. There was a downregulation in levels of HPV oncoproteins E6 and E7 alongside a reduction in cellular growth/proliferation and induction of apoptosis/autophagy. HSP70 expression confirmed hyperthermia, concomitant with induction of translational stress. The data suggest that microwave treatment inhibits tumour cell proliferation and allows the natural apoptosis of HPV-infected cells to resume. Precision microwave delivery presents a potential new treatment for treating HPV-positive anogenital precancerous lesions and cancers. Funding was through an grant (ID# 92138-556187), a grant (TCS/19/11) and core support from (MC_ UU_12014) core funding for the .
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HPV介导的p53降解所需的E6/E6AP/p53复合物的结构。
影响因子：
64.8
作者：
Martinez-Zapien D;Ruiz FX;Poirson J;Mitschler A;Ramirez J;Forster A;Cousido-Siah A;Masson M;Vande Pol S;Podjarny A;Travé G;Zanier K
通讯作者：
Zanier K
影响因子：
6.4
作者：
de Martel C;Plummer M;Vignat J;Franceschi S
通讯作者：
Franceschi S
影响因子：
8.4
作者：
Dudley GB;Richert R;Stiegman AE
通讯作者：
Stiegman AE
影响因子：
4.6
作者：
Jentsch, Marcel;Snyder, Petra;Loewer, Alexander
通讯作者：
Loewer, Alexander
影响因子：
5.4
作者：
JEON, S;ALLENHOFFMANN, BL;LAMBERT, PF
通讯作者：
LAMBERT, PF