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Sökning: (L773:1569 8041 OR L773:0923 7534) srt2:(2015-2019) > (2016)

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  • Sand, M., et al. (författare)
  • Next-generation sequencing of the basal cell carcinoma miRNome and a description of novel microRNA candidates under neoadjuvant vismodegib therapy : an integrative molecular and surgical case study
  • 2016
  • Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 27:2, s. 332-338
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: MicroRNAs (miRNAs) have been identified as key players in posttranscriptional gene regulation and have a significant impact on basal cell carcinoma (BCC) development. The Sonic hedgehog pathway inhibitor vismodegib has been approved for oral therapy of metastatic or advanced BCC. Here, a high-throughput miRNA sequencing analysis was carried out to identify differentially expressed miRNAs and possible novel miRNA candidates in vismodegib-treated BCC tissue. Additionally, we described our surgical experience with neoadjuvant oral vismodegib therapy. Patients and methods: A punch biopsy (4 mm) from a patient with an extensive cranial BCC under oral vismodegib therapy and a corresponding nonlesional epithelial skin biopsy were harvested. Total RNA was isolated, after which a sequencing cDNA library was prepared, and cluster generation was carried out, which was followed by an ultra-high-throughput miRNA sequencing analysis to indicate the read number of miRNA expression based on miRBase 21. In addition to the identification of differentially expressed miRNAs from RNA sequencing data, additional novel miRNA candidates were determined with a tool for identifying new miRNA sequences (miRDeep2). Results: We identified 33 up-regulated miRNAs (fold change >= 2) and 39 potentially new miRNA candidates (miRDeep scores 0-43.6). A manual sequence analysis of the miRNA candidates on the genomic locus of chromosome 1 with provisional IDs of chr1_1913 and chr1_421 was further carried out and rated as promising (chr1_1913) and borderline (chr1_421). Histopathology revealed skip lesions in clinically healthy appearing skin at the tumor margins, which were the cause of seven re-excisions by micrographic controlled surgery to achieve tumor-free margins. Conclusion: miRNA sequencing revealed novel miRNA candidates that need to be further confirmed in functional Dicer knockout studies. Clinically, on the basis of our surgical experience described here, neoadjuvant vismodegib therapy in BCC appears to impede histopathologic evaluations with effects on surgical therapy. Thus, larger studies are necessary, but are not preferable at this time if other options are available.
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  • Scelo, G, et al. (författare)
  • International cancer seminars : a focus on kidney cancer.
  • 2016
  • Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 27:8, s. 1382-5
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent years have seen important advances in our understanding of the etiology, biology and genetics of kidney cancer. To summarize important achievements and identify prominent research questions that remain, a workshop was organized by IARC and the US NCI. A series of 'difficult questions' were formulated, which should be given future priority in the areas of population, genomic and clinical research.
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  • Resultat 11-20 av 43

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