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Soluble AXL as a marker of disease progression and survival in melanoma.

可溶性AXL作为黑色素瘤疾病进展和生存的标志物。

  • 影响因子:3.02
  • DOI:10.1371/journal.pone.0227187
  • 作者列表:"Flem-Karlsen K","Nyakas M","Farstad IN","McFadden E","Wernhoff P","Jacobsen KD","Flørenes VA","Mælandsmo GM
  • 发表时间:2020-01-09
Abstract

:Receptor tyrosine kinase AXL is a one-pass transmembrane protein upregulated in cancers and associated with lower survival and therapy resistance. AXL can be cleaved by the A Disintegrin and Metalloproteinases (ADAM)10 and ADAM17, yielding a soluble version of the protein. Elevated soluble AXL (sAXL) has been reported to be associated with disease progression in hepatocellular carcinoma, renal cancer, neurofibromatosis type 1 and inflammatory diseases. In the present work, we analyzed sAXL levels in blood from melanoma patients and showed that sAXL increases with disease progression. Additionally, increased sAXL levels were found correlated with shorter two-year survival in stage IV patients treated with ipilimumab. Furthermore, we showed that sAXL levels were related to the percentage of cells expressing AXL in resected melanoma lymph node metastases. This finding was verified in vitro, where sAXL levels in the cell media corresponded to AXL expression in the cells. AXL inhibition using the small-molecular inhibitor BGB324 reduced sAXL levels, while the cellular expression was elevated through increased protein stability. Our findings signify that quantification of sAXL blood levels is a simple and easily assessable method to determine cellular AXL levels and should be further evaluated for its use as a biomarker of disease progression and treatment response.

摘要

: 受体酪氨酸激酶AXL是一种在癌症中上调的单向跨膜蛋白,与较低的生存率和治疗耐药性相关。AXL可以被A去整合素和金属蛋白酶 (ADAM)10 和ADAM17 切割,产生可溶性的蛋白。可溶性AXL升高 (sAXL) 已被报道与肝细胞癌、肾癌、 1 型神经纤维瘤病和炎症性疾病的疾病进展相关。在目前的工作中,我们分析了黑色素瘤患者血液中的sAXL水平,并显示sAXL随疾病进展而增加。此外,在接受ipilimumab治疗的IV期患者中,发现sAXL水平升高与缩短的两年生存率相关。此外,我们发现sAXL水平与切除的黑色素瘤淋巴结转移灶中表达AXL的细胞百分比相关。这一发现在体外得到验证,其中细胞培养基中的sAXL水平与细胞中的AXL表达相对应。使用小分子抑制剂BGB324 的AXL抑制降低了sAXL水平,而细胞表达通过增加蛋白稳定性而升高。我们的研究结果表明,sAXL血液水平的定量是确定细胞AXL水平的一种简单且易于评估的方法,应进一步评估其作为疾病进展和治疗反应的生物标志物的用途。

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DOI:10.1111/ced.14003
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影响因子:2.93
发表时间:2020-01-01
DOI:10.1016/j.jaad.2019.04.067
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METHODS:BACKGROUND:Human papillomavirus (HPV) infections are associated with common dermatologic and nondermatologic diseases. Although HPV vaccines are well established as preventive measures for genital warts and cervical neoplasia, their use as therapeutic agents deserves greater attention. OBJECTIVE:To evaluate the use of HPV vaccine(s) as a treatment modality for cutaneous and/or mucosal disease. METHODS:A primary literature search using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted in January 2019 by using the PubMed and Cochrane databases. RESULTS:A total of 63 articles with 4439 patients were included. The majority of patients with cutaneous warts, recurrent respiratory papillomatosis, and squamous and basal cell carcinomas were successfully treated with HPV vaccination. Preliminary data on patients with pre-existing anogenital warts, cervical intraepithelial neoplasia, anal intraepithelial neoplasia, and vulvar intraepithelial neoplasia is promising. LIMITATIONS:This review was limited by the lack of controls, patients' previous HPV vaccination status, and publication bias. CONCLUSION:The commercially available three-dose, quadrivalent HPV vaccine is a potential therapeutic option for the treatment of cutaneous warts, recurrent respiratory papillomatosis, and squamous and basal cell carcinomas. Noncommercially available HPV vaccines demonstrate therapeutic response for treating anogenital warts, cervical intraepithelial neoplasia, anal intraepithelial neoplasia, and vulvar intraepithelial neoplasia. The vaccine's efficacy as an adjunct therapy for HPV-associated cutaneous and/or mucosal disease warrants further exploration.

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影响因子:0.96
发表时间:2020-01-01
DOI:10.1097/DAD.0000000000001459
作者列表:["Lang UE","Love NR","Cheung C","McCalmont TH","Kim J"]

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皮肤肿瘤方向

皮肤肿瘤是发生在皮肤的细胞增生性疾病,是一种常见病。发生于皮内或皮下组织的新生物,种类很多,临床上分良性肿瘤和恶性肿瘤。恶性肿瘤可以不断增殖,引起转移,威胁生命,称为皮肤癌。

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