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Clin Cancer Res ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34526363


PURPOSE: Targeted therapy and immunotherapy are transforming the treatment approach for intrahepatic cholangiocarcinoma (ICC). However, little is known about the intertumor heterogeneity (ITH) of multifocal ICC and its impacts on patient response to these treatments. We aimed to characterize the immunogenomic and epigenomic heterogeneity of multifocal ICC to guide treatment decision making. EXPERIMENTAL DESIGN: We obtained 66 tumor samples from 16 patients with multifocal ICC and characterized the tumor and immune heterogeneity using whole-exome sequencing, bulk and single-cell RNA sequencing, methylation microarray, and multiplex immunostaining. Patients were divided into high- or low-ITH groups according to the median ITH index. Two independent cohorts were used to validate findings. Responses to anti-PD-1 therapy were assessed. RESULTS: Multifocal ICC presented considerable intertumor genomic, transcriptional, and epigenomic heterogeneity within a patient in high ITH group. The immune profile among multiple tumors within a patient was relatively less heterogeneous in high- or low-ITH group, and consistent responses of multiple tumors to anti-PD-1 immunotherapy were observed. Unsupervised clustering of immune markers identified one low and one high immune subtype, with higher immune cell infiltration, closer tumor-immune cell interactions, and upregulated IFN-signature expression in high-immune subtype. Determining expression levels of CD8B and ICOS facilitated this immune classification and prediction of patient prognosis. Finally, promoter DNA methylation contributed to different immune profiles of two subtypes by regulating immune-gene expression. CONCLUSIONS: There is comprehensive heterogeneity in the genome, transcriptome, and epigenome of multifocal ICC. On the basis of the less heterogeneous immune profile of ICC, we suggest an immune classification that stratifies patients' prognosis and may support personalized immunotherapy.

Polymers (Basel) ; 11(1)2019 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-30960069


A solution for forecasting the dissolved gases in oil-immersed transformers has been proposed based on the wavelet technique and least squares support vector machine. In order to optimize the hyper-parameters of the constructed wavelet LS-SVM regression, the imperialist competition algorithm was then applied. In this study, the assessment of prediction performance is based on the squared correlation coefficient and mean absolute percentage error methods. According to the proposed method, this novel procedure was applied to a simulated case and the experimental results show that the dissolved gas contents could be accurately predicted using this method. Besides, the proposed approach was compared to other prediction methods such as the back propagation neural network, the radial basis function neural network, and generalized regression neural network. By comparison, it was inferred that this method is more effective than previous forecasting methods.

Biomaterials ; 53: 1-11, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25890701


The antimicrobial peptide piscidin (PCD)-1 has been reported to have antibacterial and immunomodulatory functions. Here, we investigated the anti-neuropathic properties of PCD-1, in order to determine its potential as a compound to alleviate pain. Treatment with PCD-1 suppressed the inflammatory proteins COX-2 and iNOS in murine macrophage (RAW264.7) and microglial (BV2) cell lines stimulated by lipopolysaccharide (LPS). For studies of the effect of PCD-1 in vivo, mononeuropathy in rats was induced by chronic constriction injury (CCI), and the resulting anti-nociceptive behaviors were compared between CCI controls and CCI rats given intrathecal injections of PCD-1. Much like gabapentin, PCD-1 exerts anti-nociceptive effects against thermal hyperalgesia, with a median effective dose (ED50) of 9.5 µg in CCI rats. In CCI rats, PCD-1 exerted effects against mechanical and cold allodynia, thermal hyperalgesia, and weight-bearing deficits. Furthermore, CCI-mediated activation of microglia and astrocytes in the dorsal horn of the lumbar spinal cord were decreased by PCD-1. In addition, PCD-1 suppressed up-regulation of interleukin-1ß (IL-1ß) and phosphorylated mammalian target of rapamycin (phospho-mTOR) in CCI rats. Finally, CCI-induced down-regulation of transforming growth factor-ß1 (TGF-ß1) in rats was attenuated by injection of PCD-1. Taken together, the present findings demonstrate that the marine antimicrobial peptide PCD-1 has anti-nociceptive effects, and thus may have potential for development as an alternative pain-alleviating agent.

Analgésicos/uso terapêutico , Peptídeos Catiônicos Antimicrobianos/farmacologia , Proteínas de Peixes/farmacologia , Sequência de Aminoácidos , Animais , Peptídeos Catiônicos Antimicrobianos/química , Astrócitos/efeitos dos fármacos , Linhagem Celular , Ciclo-Oxigenase 2/metabolismo , Proteínas de Peixes/química , Interleucina-1beta/metabolismo , Masculino , Camundongos , Microglia/efeitos dos fármacos , Dados de Sequência Molecular , Óxido Nítrico Sintase Tipo II/metabolismo , Ratos , Ratos Wistar , Serina-Treonina Quinases TOR/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Regulação para Cima/efeitos dos fármacos
Nan Fang Yi Ke Da Xue Xue Bao ; 31(12): 1981-4, 2011 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-22200695


OBJECTIVE: Based on a simple deconvolution model of multi-layer interfaces, the reasons of wave number variation of the interfacial echo signal were analyzed to explore a method for feature recognition of the superficial soft tissue interfaces. The interfacial echo signal data were decomposed and reconstructed by Mallat multisolution analysis, with the number of the reconstructed interface signal as the feature. The results showed that the deconvolution model was effective for extracting the interface echo signal features in the superficial soft tissue and allowed identification and location of tissue defects.

Tecido Conjuntivo/diagnóstico por imagem , Transferência de Energia/fisiologia , Modelos Teóricos , Pele/diagnóstico por imagem , Tela Subcutânea/diagnóstico por imagem , Animais , Simulação por Computador , Interpretação de Imagem Assistida por Computador , Espalhamento de Radiação , Suínos , Ultrassonografia