RESUMO
An accurate tool enabling early diagnosis of hepatocellular carcinoma (HCC) is clinically important, given that early detection of HCC markedly improves survival. We aimed to investigate the molecular markers underlying early progression of HCC that can be detected in precancerous lesions. We designed a gene selection strategy to identify potential driver genes by integrative analysis of transcriptome and clinicopathological data of human multistage HCC tissues, including precancerous lesions, low- and high-grade dysplastic nodules. The gene selection process was guided by detecting the selected molecules in both HCC and precancerous lesion. Using various computational approaches, we selected 10 gene elements as a candidate and, through immunohistochemical staining, showed that barrier to autointegration factor 1 (BANF1), procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3 (PLOD3), and splicing factor 3b subunit 4 (SF3B4) are HCC decision markers with superior capability to diagnose early-stage HCC in a large cohort of HCC patients, as compared to the currently popular trio of HCC diagnostic markers: glypican 3, glutamine synthetase, and heat-shock protein 70. Targeted inactivation of BANF1, PLOD3, and SF3B4 inhibits in vitro and in vivo liver tumorigenesis by selectively modulating epithelial-mesenchymal transition and cell-cycle proteins. Treatment of nanoparticles containing small-interfering RNAs of the three genes suppressed liver tumor incidence as well as tumor growth rates in a spontaneous mouse HCC model. We also demonstrated that SF3B4 overexpression triggers SF3b complex to splice tumor suppressor KLF4 transcript to nonfunctional skipped exon transcripts. This contributes to malignant transformation and growth of hepatocyte through transcriptional inactivation of p27Kip1 and simultaneously activation of Slug genes. CONCLUSION: The findings suggest molecular markers of BANF1, PLOD3, and SF3B4 indicating early-stage HCC in precancerous lesion, and also suggest drivers for understanding the development of hepatocarcinogenesis. (Hepatology 2018;67:1360-1377).
Assuntos
Carcinoma Hepatocelular/metabolismo , Proteínas de Ligação a DNA/metabolismo , Neoplasias Hepáticas/metabolismo , Proteínas Nucleares/metabolismo , Pró-Colágeno-Lisina 2-Oxoglutarato 5-Dioxigenase/metabolismo , Fatores de Processamento de RNA/metabolismo , Animais , Biomarcadores Tumorais/metabolismo , Western Blotting , Carcinogênese/metabolismo , Carcinoma Hepatocelular/patologia , Humanos , Imuno-Histoquímica , Fator 4 Semelhante a Kruppel , Fígado/metabolismo , Fígado/patologia , Neoplasias Hepáticas/patologia , Camundongos , Ratos , Análise Serial de Tecidos/métodosRESUMO
Polymer vesicles are being extensively studied to emulate self-assembly in biological systems and also use them in a variety of biological and industrial applications. This study demonstrates a novel strategy to prepare polymer vesicles in a pure aqueous medium by driving the micelle-to-vesicle transition with metallic nanoparticles. We synthesized poly(2-amino-2-hydroxyethyl aspartamide) (PAHA) substituted with octadecyl chains, which could form micelle-like self-aggregates in the aqueous medium and chemically bind with platinum precursors. Then, in situ polymerization of Pt nanoparticles within the PAHA self-aggregates generated polymer vesicles that possess nanoparticles within bilayers, because of the increase of the hydrophilic mass ratio to total mass of PAHA, f (w). This new strategy to prepare polymer vesicles would greatly serve to facilitate the control of self-assembly and ultimately improve the functionality of a wide array of polymer vesicles.
RESUMO
Primary adenocarcinoma of the appendix is a rare malignancy that constitutes < 0.5% of all gastrointestinal neoplasms. Moreover, primary signet ring cell carcinoma of the appendix is an exceedingly rare entity. We have encountered 15 cases of primary appendiceal cancer among 3389 patients who underwent appendectomy over the past 18 years. In the present report, we describe a rare case of primary signet ring cell carcinoma of the appendix with ovarian metastases and unresectable peritoneal dissemination occurring in a 67-year-old female patient. She underwent appendectomy and bilateral salpingo-oophorectomy with a laparoscopy procedure. She then received palliative systemic chemotherapy with 12 cycles of oxaliplatin, 5-flurorouracil, and leucovorin (FOLFOX-4). The patient currently is well without progression of disease 12 mo after beginning chemotherapy.
Assuntos
Neoplasias do Apêndice/patologia , Carcinoma de Células em Anel de Sinete/secundário , Neoplasias Ovarianas/secundário , Neoplasias Peritoneais/secundário , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apendicectomia , Neoplasias do Apêndice/terapia , Carcinoma de Células em Anel de Sinete/terapia , Quimioterapia Adjuvante , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Ovarianas/terapia , Ovariectomia , Neoplasias Peritoneais/terapia , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
OBJECTIVE: The purpose of our study was to evaluate whether MRI can discriminate between extraaxial neurofibromas and neurilemmomas. MATERIALS AND METHODS: MR images of 52 patients with a pathologically proven extraaxial neurofibroma or neurilemmoma were retrospectively reviewed by observers who were unaware of the surgical results, regarding the presence or absence of individual imaging criteria. MRI findings in 12 patients with a localized neurofibroma and 40 patients with a neurilemmoma were compared using the chi-square test or Fisher's exact test. RESULTS: MRI findings suggestive of neurofibroma (p < 0.05) were a target sign on T2-weighted images (58% in neurofibromas vs 15% in neurilemmomas), central enhancement (75% vs 8%), and a combination of both findings (63% vs 3%). MRI findings suggestive of a neurilemmoma (p < 0.05) were a fascicular appearance on T2-weighted images (25% vs 63%), a thin hyperintense rim on T2-weighted images (8% vs 58%), a combination of both findings (8% vs 48%), and diffuse enhancement (13% vs 67%). No significant difference was seen between neurofibromas and neurilemmomas for a centrally entering and exiting nerve (42% in neurofibromas vs 23% in neurilemmomas), a peripherally entering and exiting nerve (58% vs 77%), a cystic area (38% vs 64%), a low-signal margin (100% vs 100%), peripheral enhancement (13% vs 26%), or a target sign on contrast-enhanced images (11% vs 31%). CONCLUSION: MRI shows features helpful for differentiating extraaxial neurofibromas from neurilemmomas; however, no single finding or combination of findings allows definitive differentiation.