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        Pathologic basis of the sonographic differences between thyroid cancer and noninvasive follicular thyroid neoplasm with papillary-like nuclear features

        Grace C. H. Yang,Karen O. Fried 대한초음파의학회 2018 ULTRASONOGRAPHY Vol.37 No.2

        Ultrasonography is pivotal in triage thyroid biopsy in the era after the identification of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). This pictorial essay illustrates the pathologic basis of the sonographic features that distinguish NIFTP from thyroid cancers. In this study, we present the correlations of ultrasonography to ×1 histopathology to assess shape and margin characteristics. Markedly hypoechoic nodules correlate to microfollicular/solid nodules, while isoechoic/hyperechoic thyroid nodules correlate to normofollicular/macrofollicular nodules. The ultrasound findings of NIFTP and minimally invasive encapsulated thyroid cancers are similar. Both are well-circumscribed, oval-to-round nodules with regular margins. Blurred or microlobulated margins indicate infiltrating tumors, while lobulated margins are characteristic of expansile tumors. Overtly invasive encapsulated tumors are characterized by oval-to-round nodules with irregular or lobulated margins. The ultrasound findings for infiltrative thyroid cancers show at least one of the following malignant features: marked hypoechoicity, taller-than-wide shape, microcalcifications, and blurred or microlobulated margins.

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        Autophagic UVRAG Promotes UV-Induced Photolesion Repair by Activation of the CRL4<sup>DDB2</sup> E3 Ligase

        Yang, Y.,He, S.,Wang, Q.,Li, F.,Kwak, M.J.,Chen, S.,O'Connell, D.,Zhang, T.,Pirooz, S.,Jeon, Y.,Chimge, N.O.,Frenkel, B.,Choi, Y.,Aldrovandi, Grace M.,Oh, B.H.,Yuan, Z.,Liang, C. Cell Press 2016 Molecular cell Vol.62 No.4

        <P>UV-induced DNA damage, a major risk factor for skin cancers, is primarily repaired by nucleotide excision repair (NER). UV radiation resistance-associated gene (UVRAG) is a tumor suppressor involved in autophagy. It was initially isolated as a cDNA partially complementing UV sensitivity in xeroderma pigmentosum (XP), but this was not explored further. Here we show that UVRAG plays an integral role in UV-induced DNA damage repair. It localizes to photolesions and associates with DDB1 to promote the assembly and activity of the DDB2-DDB1-Cul4A-Roc1 (CRL4(DDB2)) ubiquitin ligase complex, leading to efficient XPC recruitment and global genomic NER. UVRAG depletion decreased substrate handover to XPC and conferred UV-damage hypersensitivity. We confirmed the importance of UVRAG for UV-damage tolerance using a Drosophila model. Furthermore, increased UV-signature mutations in melanoma correlate with reduced expression of UVRAG. Our results identify UVRAG as a regulator of CRL4(DDB2)-mediated NER and suggest that its expression levels may influence melanoma predisposition.</P>

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