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1.
Nucleic Acids Res ; 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34718734

RESUMO

Liquid-liquid phase separation (LLPS) is critical for assembling membraneless organelles (MLOs) such as nucleoli, P-bodies, and stress granules, which are involved in various physiological processes and pathological conditions. While the critical role of RNA in the formation and the maintenance of MLOs is increasingly appreciated, there is still a lack of specific resources for LLPS-related RNAs. Here, we presented RPS (http://rps.renlab.org), a comprehensive database of LLPS-related RNAs in 20 distinct biomolecular condensates from eukaryotes and viruses. Currently, RPS contains 21,613 LLPS-related RNAs with three different evidence types, including 'Reviewed', 'High-throughput' and 'Predicted'. RPS provides extensive annotations of LLPS-associated RNA properties, including sequence features, RNA structures, RNA-protein/RNA-RNA interactions, and RNA modifications. Moreover, RPS also provides comprehensive disease annotations to help users to explore the relationship between LLPS and disease. The user-friendly web interface of RPS allows users to access the data efficiently. In summary, we believe that RPS will serve as a valuable platform to study the role of RNA in LLPS and further improve our understanding of the biological functions of LLPS.

2.
Cancer Cell ; 39(11): 1479-1496.e18, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34653364

RESUMO

Small cell lung cancer (SCLC) is an aggressive malignancy that includes subtypes defined by differential expression of ASCL1, NEUROD1, and POU2F3 (SCLC-A, -N, and -P, respectively). To define the heterogeneity of tumors and their associated microenvironments across subtypes, we sequenced 155,098 transcriptomes from 21 human biospecimens, including 54,523 SCLC transcriptomes. We observe greater tumor diversity in SCLC than lung adenocarcinoma, driven by canonical, intermediate, and admixed subtypes. We discover a PLCG2-high SCLC phenotype with stem-like, pro-metastatic features that recurs across subtypes and predicts worse overall survival. SCLC exhibits greater immune sequestration and less immune infiltration than lung adenocarcinoma, and SCLC-N shows less immune infiltrate and greater T cell dysfunction than SCLC-A. We identify a profibrotic, immunosuppressive monocyte/macrophage population in SCLC tumors that is particularly associated with the recurrent, PLCG2-high subpopulation.

3.
Nucleic Acids Res ; 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34570216

RESUMO

As an increasing number of noncoding RNAs (ncRNAs) have been suggested to encode short bioactive peptides in cancer, the exploration of ncRNA-encoded small peptides (ncPEPs) is emerging as a fascinating field in cancer research. To assist in studies on the regulatory mechanisms of ncPEPs, we describe here a database called SPENCER (http://spencer.renlab.org). Currently, SPENCER has collected a total of 2806 mass spectrometry (MS) data points from 55 studies, covering 1007 tumor samples and 719 normal samples. Using an MS-based proteomics analysis pipeline, SPENCER identified 29 526 ncPEPs across 15 different cancer types. Specifically, 22 060 of these ncPEPs were experimentally validated in other studies. By comparing tumor and normal samples, the identified ncPEPs were divided into four expression groups: tumor-specific, upregulated in cancer, downregulated in cancer, and others. Additionally, since ncPEPs are potential targets for neoantigen-based cancer immunotherapy, SPENCER also predicted the immunogenicity of all the identified ncPEPs by assessing their MHC-I binding affinity, stability, and TCR recognition probability. As a result, 4497 ncPEPs curated in SPENCER were predicted to be immunogenic. Overall, SPENCER will be a useful resource for investigating cancer-associated ncPEPs and may boost further research in cancer.

4.
Clin Cancer Res ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34526363

RESUMO

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.

5.
Comput Struct Biotechnol J ; 19: 3077-3086, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34136106

RESUMO

The secreting function of pituitary adenomas (PAs) plays a critical role in making the treatment strategies. However, Magnetic Resonance Imaging (MRI) analysis for pituitary adenomas is labor intensive and highly variable among radiologists. In this work, by applying convolutional neural network (CNN), we built a segmentation and classification model to help distinguish functioning pituitary adenomas from non-functioning subtypes with 3D MRI images from 185 patients with PAs (two centers). Specifically, the classification model adopts the concept of transfer learning and uses the pre-trained segmentation model to extract deep features from conventional MRI images. As a result, both segmentation and classification models obtained high performance in two internal validation datasets and an external testing dataset (for segmentation model: Dice score = 0.8188, 0.8091 and 0.8093 respectively; for classification model: AUROC = 0.8063, 0.7881 and 0.8478, respectively). In addition, the classification model considers the attention mechanism for better model interpretation. Taken together, this work provides the first deep learning-based tumor region segmentation and classification models of PAs, which enables early diagnosis and subtyping PAs from MRI images.

6.
Front Cell Dev Biol ; 9: 686894, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34055810

RESUMO

2'-O-methylations (2'-O-Me or Nm) are one of the most important layers of regulatory control over gene expression. With increasing attentions focused on the characteristics, mechanisms and influences of 2'-O-Me, a revolutionary technique termed Nm-seq were established, allowing the identification of precise 2'-O-Me sites in RNA sequences with high sensitivity. However, as the costs and complexities involved with this new method, the large-scale detection and in-depth study of 2'-O-Me is still largely limited. Therefore, the development of a novel computational method to identify 2'-O-Me sites with adequate reliability is urgently needed at the current stage. To address the above issue, we proposed a hybrid deep-learning algorithm named DeepOMe that combined Convolutional Neural Networks (CNN) and Bidirectional Long Short-term Memory (BLSTM) to accurately predict 2'-O-Me sites in human transcriptome. Validating under 4-, 6-, 8-, and 10-fold cross-validation, we confirmed that our proposed model achieved a high performance (AUC close to 0.998 and AUPR close to 0.880). When testing in the independent data set, DeepOMe was substantially superior to NmSEER V2.0. To facilitate the usage of DeepOMe, a user-friendly web-server was constructed, which can be freely accessed at http://deepome.renlab.org.

7.
Gigascience ; 10(5)2021 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-34018555

RESUMO

BACKGROUND: Multi-region sequencing (MRS) has been widely used to analyze intra-tumor heterogeneity (ITH) and cancer evolution. However, comprehensive analysis of mutational data from MRS is still challenging, necessitating complicated integration of a plethora of computational and statistical approaches. FINDINGS: Here, we present MesKit, an R/Bioconductor package that can assist in characterizing genetic ITH and tracing the evolutionary history of tumors based on somatic alterations detected by MRS. MesKit provides a wide range of analysis and visualization modules, including ITH evaluation, metastatic route inference, and mutational signature identification. In addition, MesKit implements an auto-layout algorithm to generate phylogenetic trees based on somatic mutations. The application of MesKit for 2 reported MRS datasets of hepatocellular carcinoma and colorectal cancer identified known heterogeneous features and evolutionary patterns, together with potential driver events during cancer evolution. CONCLUSIONS: In summary, MesKit is useful for interpreting ITH and tracing evolutionary trajectory based on MRS data. MesKit is implemented in R and available at https://bioconductor.org/packages/MesKit under the GPL v3 license.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Biópsia , Humanos , Mutação , Filogenia
8.
Aging (Albany NY) ; 13(6): 7758-7766, 2021 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-33735836

RESUMO

The recent outbreak of COVID-19 in the world is currently a big threat to global health and economy. Convalescent plasma has been confirmed effective against the novel corona virus in preliminary studies. In this paper, we first described the therapeutic schedule, antibody detection method, indications, contraindications of the convalescent plasmas and reported the effectiveness of convalescent plasma therapy by a retrospective cohort study.


Assuntos
COVID-19/terapia , Anticorpos Antivirais/sangue , COVID-19/virologia , Humanos , Imunização Passiva , Estudos Retrospectivos , SARS-CoV-2/imunologia , SARS-CoV-2/isolamento & purificação
9.
Nucleic Acids Res ; 49(D1): D1405-D1412, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33021671

RESUMO

Distinguishing the few disease-related variants from a massive number of passenger variants is a major challenge. Variants affecting RNA modifications that play critical roles in many aspects of RNA metabolism have recently been linked to many human diseases, such as cancers. Evaluating the effect of genetic variants on RNA modifications will provide a new perspective for understanding the pathogenic mechanism of human diseases. Previously, we developed a database called 'm6AVar' to host variants associated with m6A, one of the most prevalent RNA modifications in eukaryotes. To host all RNA modification (RM)-associated variants, here we present an updated version of m6AVar renamed RMVar (http://rmvar.renlab.org). In this update, RMVar contains 1 678 126 RM-associated variants for 9 kinds of RNA modifications, namely m6A, m6Am, m1A, pseudouridine, m5C, m5U, 2'-O-Me, A-to-I and m7G, at three confidence levels. Moreover, RBP binding regions, miRNA targets, splicing events and circRNAs were integrated to assist investigations of the effects of RM-associated variants on posttranscriptional regulation. In addition, disease-related information was integrated from ClinVar and other genome-wide association studies (GWAS) to investigate the relationship between RM-associated variants and diseases. We expect that RMVar may boost further functional studies on genetic variants affecting RNA modifications.


Assuntos
Bases de Dados Genéticas , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Neoplasias/genética , Processamento Pós-Transcricional do RNA , RNA Neoplásico/genética , Processamento Alternativo , Gráficos por Computador , Humanos , Internet , MicroRNAs/genética , MicroRNAs/metabolismo , Anotação de Sequência Molecular , Neoplasias/metabolismo , Neoplasias/patologia , Polimorfismo de Nucleotídeo Único , RNA Circular/genética , RNA Circular/metabolismo , RNA Neoplásico/classificação , RNA Neoplásico/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Software , Transcriptoma
10.
Comput Struct Biotechnol J ; 18: 3361-3367, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33294132

RESUMO

Cancer staging provides a common language that is used to describe the severity of an individual's cancer, which plays a critical role in optimizing cancer treatment. Recursive partitioning analysis (RPA) is the most widely accepted method for cancer staging. Despite its widespread use, to date, only limited tools have been developed to implement the RPA algorithm for cancer staging. Moreover, most of the available tools can be accessed only from command lines and also lack visualization, making them difficult for clinical investigators without programing skills to use. Therefore, we developed a web server called autoRPA that is dedicated to supporting the construction of prognostic staging models and performance comparisons among different staging models. Based on the RPA algorithm and log-rank test statistics, autoRPA can establish a decision-making tree from survival data and provide clinicians an intuitive method to further prune the decision tree. Moreover, autoRPA can evaluate the contribution of each submitted covariate that is involved in the grouping process and help identify factors that significantly contribute to cancer staging. Four indicators, including hazard consistency, hazard discrimination, percentage of variation explained, and sample size balance, are introduced to validate the performance of the designed staging models. In addition, autoRPA can also be used to compare the performance of different prognostic staging models using a standard bootstrap evaluation method. The web server of autoRPA is freely available at http://rpa.renlab.org.

11.
Front Cell Dev Biol ; 8: 593661, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33240890

RESUMO

High-throughput sequencing technologies have identified millions of genetic mutations in multiple human diseases. However, the interpretation of the pathogenesis of these mutations and the discovery of driver genes that dominate disease progression is still a major challenge. Combining functional features such as protein post-translational modification (PTM) with genetic mutations is an effective way to predict such alterations. Here, we present PTMsnp, a web server that implements a Bayesian hierarchical model to identify driver genetic mutations targeting PTM sites. PTMsnp accepts genetic mutations in a standard variant call format or tabular format as input and outputs several interactive charts of PTM-related mutations that potentially affect PTMs. Additional functional annotations are performed to evaluate the impact of PTM-related mutations on protein structure and function, as well as to classify variants relevant to Mendelian disease. A total of 4,11,574 modification sites from 33 different types of PTMs and 1,776,848 somatic mutations from TCGA across 33 different cancer types are integrated into the web server, enabling identification of candidate cancer driver genes based on PTM. Applications of PTMsnp to the cancer cohorts and a GWAS dataset of type 2 diabetes identified a set of potential drivers together with several known disease-related genes, indicating its reliability in distinguishing disease-related mutations and providing potential molecular targets for new therapeutic strategies. PTMsnp is freely available at: http://ptmsnp.renlab.org.

12.
Clin Cancer Res ; 26(18): 4947-4957, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32527942

RESUMO

PURPOSE: Immune checkpoint inhibitor therapy is emerging as the promising option for patients with advanced hepatocellular carcinoma. We aimed to investigate the heterogeneity of different tumor nodules of the same patient with multifocal hepatocellular carcinomas in response to immunotherapy and its molecular mechanisms. EXPERIMENTAL DESIGN: We attained 45 surgical tumor samples including 33 small and 12 large nodules from 12 patients with multifocal hepatocellular carcinoma and evaluated genomic and immune heterogeneity among tumors through whole-genome sequencing and RNA sequencing. IHC was performed to validate the expression of immune markers. The responses to anti-programmed cell death protein-1 (PD-1) therapy in patients with multifocal hepatocellular carcinoma were evaluated. RESULTS: The small and large tumors within the same patient presented with similar genomic characteristics, indicating their same genomic origin. We further found the small tumors had higher immune cell infiltration including more CD8+ T cells, M1 macrophages, and monocytes as compared with large tumors. Besides, the expression of interferon signature predictive of response to anti-PD-1 therapy was significantly upregulated in the small tumors. Moreover, the immune pathways were more vigorous along with less active proliferation pathways in the small tumors. In keeping with this, we found that small nodules were more sensitive to anti-PD-1 therapy than large nodules in patients with multifocal hepatocellular carcinoma. CONCLUSIONS: The small tumors in patients with multifocal hepatocellular carcinoma had higher immune cell infiltration and upregulation of immune pathways as compared with the large tumors, which can partially explain the different responses of small and large tumors in the same case to anti-PD-1 therapy.

13.
Ann Palliat Med ; 9(3): 1030-1036, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32434362

RESUMO

BACKGROUND: Seborrheic alopecia (SA) is a common dermatological disease with a long disease course, and treatment for this disease usually exhibits slow effects. Currently, Western medicine treatments have shown some effects; however, they also have certain limitations. In recent years, Chinese medicine has made breakthroughs in treating SA. The efficacy of plum blossom needle acupuncture with qi-invigorating superficies-consolidating therapy for SA was observed, and its clinical effects were investigated in this study. METHODS: A total of 87 patients with SA treated at the First Affiliated Hospital of Guangzhou University of Chinese Medicine from September 2018 to September 2019 were enrolled as the research subjects. They were divided into a Western medicine group and a Chinese medicine group by the random number table method. The 43 patients in the Western medicine group were treated with conventional Western medicine, and the 44 patients in the Chinese medicine group were treated with a comprehensive traditional Chinese medicine regimen of plum blossom needling with qi-invigorating superficies-consolidating therapy. The treatment effects, changes in estradiol (E2) and testosterone (T) levels, and scores for various body signs (hair growth and hair loss) of the two groups before and after treatment were compared. RESULTS: The difference in total effective rate between the Chinese medicine group and the Western medicine group (95.45% vs. 81.40%) was statistically significant (P<0.05). After treatment, the T levels of both groups were lower than before treatment, and the E2 levels of both groups were higher than before treatment; the difference between the two groups was statistically significant (P<0.05). After treatment, the hair growth and hair loss scores of the two groups were lower than those before treatment, and those of the Chinese medicine group were lower than those of the Western medicine group; the differences were statistically significant (P<0.05). CONCLUSIONS: Plum blossom needle acupuncture combined with qi-invigorating superficies-consolidating therapy is significantly effective for treating patients with SA. It can effectively adjust the patient's hormone levels, improve hair loss, and promote hair growth. It has the advantages of simplicity, tolerability, and low cost. It cures the cause of the disease and is worth promoting.


Assuntos
Terapia por Acupuntura , Prunus domestica , Alopecia/terapia , Flores , Humanos , Qi
14.
Nat Med ; 26(2): 259-269, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32042191

RESUMO

Developmental processes underlying normal tissue regeneration have been implicated in cancer, but the degree of their enactment during tumor progression and under the selective pressures of immune surveillance, remain unknown. Here we show that human primary lung adenocarcinomas are characterized by the emergence of regenerative cell types, typically seen in response to lung injury, and by striking infidelity among transcription factors specifying most alveolar and bronchial epithelial lineages. In contrast, metastases are enriched for key endoderm and lung-specifying transcription factors, SOX2 and SOX9, and recapitulate more primitive transcriptional programs spanning stem-like to regenerative pulmonary epithelial progenitor states. This developmental continuum mirrors the progressive stages of spontaneous outbreak from metastatic dormancy in a mouse model and exhibits SOX9-dependent resistance to natural killer cells. Loss of developmental stage-specific constraint in macrometastases triggered by natural killer cell depletion suggests a dynamic interplay between developmental plasticity and immune-mediated pruning during metastasis.


Assuntos
Adenocarcinoma/imunologia , Adenocarcinoma/patologia , Sistema Imunitário/fisiologia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Metástase Neoplásica , Animais , Brônquios/metabolismo , Diferenciação Celular , Linhagem da Célula , Análise por Conglomerados , Bases de Dados Genéticas , Progressão da Doença , Endoderma/metabolismo , Feminino , Humanos , Hidrogéis/química , Células Matadoras Naturais/metabolismo , Pulmão/patologia , Camundongos , Fenótipo , Alvéolos Pulmonares/metabolismo , Regeneração , Transdução de Sinais
15.
Autophagy ; 16(4): 626-640, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31204567

RESUMO

Seeing is believing. The direct observation of GFP-Atg8 vacuolar delivery under confocal microscopy is one of the most useful end-point measurements for monitoring yeast macroautophagy/autophagy. However, manually labelling individual cells from large-scale sets of images is time-consuming and labor-intensive, which has greatly hampered its extensive use in functional screens. Herein, we conducted a time-course analysis of nitrogen starvation-induced autophagy in wild-type and knockout mutants of 35 AuTophaGy-related (ATG) genes in Saccharomyces cerevisiae and obtained 1,944 confocal images containing > 200,000 cells. We manually labelled 8,078 autophagic and 18,493 non-autophagic cells as a benchmark dataset and developed a new deep learning tool for autophagy (DeepPhagy), which exhibited superior accuracy in recognizing autophagic cells compared to other existing methods, with an area under the curve (AUC) value of 0.9710 from 10-fold cross-validations. We further used DeepPhagy to automatically analyze all the images and quantitatively classified the autophagic phenotypes of the 35 atg knockout mutants into 3 classes. The high consistency in our computational and biochemical results indicated the reliability of DeepPhagy for measuring autophagic activity. Moreover, we used DeepPhagy to analyze 3 additional types of autophagic phenotypes, including the targeting of Atg1-GFP to the vacuole, the vacuolar delivery of GFP-Atg19, and the disintegration of autophagic bodies indicated by GFP-Atg8, all with satisfying accuracies. Taken together, our study not only enables the GFP-Atg8 fluorescence assay to become a quantitative measurement for analyzing autophagic phenotypes in S. cerevisiae but also demonstrates that deep learning-based methods could potentially be applied to different types of autophagy.Abbreviations: Ac: accuracy; ALP: alkaline phosphatase; ALR: autophagic lysosomal reformation; ATG: AuTophaGy-related; AUC: area under the curve; CNN: convolutional neural network; Cvt: cytoplasm-to-vacuole targeting; DeepPhagy: deep learning for autophagy; fc_2: second fully connected; GFP: green fluorescent protein; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3 beta; HAT: histone acetyltransferase; HemI: Heat map Illustrator; JRE: Java Runtime Environment; KO: knockout; LRN: local response normalization; MCC: Mathew Correlation Coefficient; OS: operating system; PAS: phagophore assembly site; PC: principal component; PCA: principal component analysis; PPI: protein-protein interaction; Pr: precision; QPSO: Quantum-behaved Particle Swarm Optimization; ReLU: rectified linear unit; RF: random forest; ROC: receiver operating characteristic; ROI: region of interest; SD: systematic derivation; SGD: stochastic gradient descent; Sn: sensitivity; Sp: specificity; SRG: seeded region growing; t-SNE: t-distributed stochastic neighbor embedding; 2D: 2-dimensional; WT: wild-type.


Assuntos
Proteínas Relacionadas à Autofagia/metabolismo , Autofagia/fisiologia , Aprendizado Profundo , Proteínas de Saccharomyces cerevisiae/metabolismo , Lisossomos/metabolismo , Fagossomos/metabolismo , Transporte Proteico/fisiologia , Receptores de Superfície Celular/metabolismo , Reprodutibilidade dos Testes , Saccharomyces cerevisiae/metabolismo
16.
Nucleic Acids Res ; 48(D1): D789-D796, 2020 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-31665503

RESUMO

The early detection of cancer holds the key to combat and control the increasing global burden of cancer morbidity and mortality. Blood-based screenings using circulating DNAs (ctDNAs), circulating RNA (ctRNAs), circulating tumor cells (CTCs) and extracellular vesicles (EVs) have shown promising prospects in the early detection of cancer. Recent high-throughput gene expression profiling of blood samples from cancer patients has provided a valuable resource for developing new biomarkers for the early detection of cancer. However, a well-organized online repository for these blood-based high-throughput gene expression data is still not available. Here, we present BBCancer (http://bbcancer.renlab.org/), a web-accessible and comprehensive open resource for providing the expression landscape of six types of RNAs, including messenger RNAs (mRNAs), long noncoding RNAs (lncRNAs), microRNAs (miRNAs), circular RNAs (circRNAs), tRNA-derived fragments (tRFRNAs) and Piwi-interacting RNAs (piRNAs) in blood samples, including plasma, CTCs and EVs, from cancer patients with various cancer types. Currently, BBCancer contains expression data of the six RNA types from 5040 normal and tumor blood samples across 15 cancer types. We believe this database will serve as a powerful platform for developing blood biomarkers.


Assuntos
Biomarcadores Tumorais , Bases de Dados de Compostos Químicos , Detecção Precoce de Câncer/métodos , Neoplasias/diagnóstico , RNA/sangue , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica , Humanos
17.
BMC Cancer ; 19(1): 1188, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31805975

RESUMO

BACKGROUND: An extremely rare condition, radiation-induced angiosarcoma is characterized by a poor prognosis, high recurrence rate and lack of effective treatment. Herein, we present a case report of a 48-year-old female patient with radiation-induced abdominal wall angiosarcoma who showed a dramatic response to low-dose apatinib. CASE PRESENTATION: The patient, who was diagnosed with cervical squamous cell carcinoma 20 years ago, had received radiotherapy and chemotherapy after operation. Angiosarcomas of the abdominal wall appeared 9 years later. After repeated surgical operations and intravenous chemotherapy for the angiosarcomas, the patient developed tumor recurrence and pulmonary metastasis. The abdominal wall tumors showed repeated rupture and bleeding, with poor wound healing. On evaluation, laboratory findings detected the negative serum tumor markers CEA, CA 125, CA 15-3 and CA 19-9. Imaging showed multiple subcutaneous nodules and masses in the abdominal wall, accompanied by suspected small subpleural nodule at the lower lobe of the right lung. Immunohistochemistry of previous surgical pathology indicated that CD31, ERG and Vim were positive. The result of whole exome sequencing suggested the mutations of BRAF and HRAS, and the amplification of MYC. Based on the above results, the patient was clinically diagnosed with radiation-induced angiosarcoma of the abdominal wall with pulmonary metastasis. The patient was treated with low-dose apatinib and rejected reoperation or chemotherapy. RESULTS: At the 6-month follow-up visit, the abdominal wall lesions that had previously ruptured stopped bleeding and showed significant shrinkage. Imaging showed that most of the abdominal wall lesions had partially regressed, and some of the lesions on the abdominal wall and the suspected lesion of subpleural nodule at the lower lobe of the right lung had disappeared. CONCLUSIONS: We described this case and reviewed the literature on radiation-related angiosarcoma. Importantly, this case suggests that apatinib may be an effective and sensitive treatment for radiation-induced angiosarcoma even at the lowest dosage, without aggravating the bleeding of lesions.


Assuntos
Neoplasias Abdominais/tratamento farmacológico , Hemangiossarcoma/tratamento farmacológico , Neoplasias Pulmonares/secundário , Neoplasias Induzidas por Radiação/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Piridinas/administração & dosagem , Neoplasias Abdominais/etiologia , Neoplasias Abdominais/genética , Parede Abdominal/patologia , Feminino , Amplificação de Genes , Hemangiossarcoma/etiologia , Hemangiossarcoma/genética , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Pessoa de Meia-Idade , Mutação , Neoplasias Induzidas por Radiação/genética , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Piridinas/uso terapêutico , Resultado do Tratamento
18.
Mater Sci Eng C Mater Biol Appl ; 103: 109711, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31349489

RESUMO

Tendon calcification is a common but intractable problem leading to pain and activity limitation when injury or tendinopathy progresses into the late stage. This is because tendon stem/progenitor cells (TSPCs) can undergo aberrant osteogenic differentiation under inflammatory conditions. This study aims to investigate the effect of curcumin, a natural anti-inflammatory agent, on regulating the differentiation of TSPCs in tendon calcification. With inflammatory stimulation, TSPCs showed higher alkaline phosphatase activity and more frequent formation of mineralized nodules which were verified in the culture system; however, curcumin significantly alleviated these pathological changes. In in vivo function analysis, chitosan microsphere-encapsulated curcumin was delivered to injured sites of rat tendon ectopic calcification model. The inflammation in the tendon tissues of the curcumin group was significantly relieved. Controlled-release curcumin partially rescued tendon calcification and enhanced tendon regeneration in animal model. This study demonstrates that controlled-release curcumin can manipulate the fate decision of TSPCs, and that it promotes the tenogenesis and inhibits the osteogenesis of TSPCs in a pathological microenvironment, which provides a possible new therapeutic strategy for tendon disease.


Assuntos
Tendão do Calcâneo/metabolismo , Calcinose/tratamento farmacológico , Diferenciação Celular/efeitos dos fármacos , Curcumina/farmacologia , Células-Tronco/metabolismo , Tendão do Calcâneo/patologia , Animais , Calcinose/metabolismo , Calcinose/patologia , Curcumina/química , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacologia , Camundongos , Ratos , Células-Tronco/patologia
19.
Gene ; 711: 143925, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31212048

RESUMO

More than 2300 genes have been reported to be involved in spermatogenesis but the functional roles of most genes in male fertility remain to be elucidated. In this study, we explored the function of dipeptidase 3 (Dpep3), a gene predicted to be testis-specific, in male fertility of mice. We showed that Dpep3 is evolutionarily conserved in human and mouse along with other eutherians. Its mRNA was exclusively detected in testicular tissue and expressed in testes from 7 days postpartum. To further explore its role in male fertility, we generated Dpep3 knockout mice (Dpep3-/-) using the CRISPR/Cas9 technology and found that the male Dpep3-/- mice are fertile despite a significant reduction in sperm count. Histology of testis and progression of meiotic prophase I showed no obvious difference between wild-type and Dpep3-/- mice. All these findings indicate that Dpep3 is not essential for male fertility in mice. These findings will help other researchers to avoid research duplication, save their time and resources to focus on the genes that are indispensable for male fertility.


Assuntos
Dipeptidases/genética , Dipeptidases/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Espermatogênese , Testículo/metabolismo , Animais , Sequência Conservada , Técnicas de Inativação de Genes , Humanos , Infertilidade Masculina/genética , Infertilidade Masculina/metabolismo , Masculino , Camundongos , Especificidade de Órgãos , Filogenia , Contagem de Espermatozoides , Motilidade Espermática
20.
Cancer Res ; 79(8): 2076-2083, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30786995

RESUMO

Long noncoding RNAs (lncRNA) have emerged as promising biomarkers in cancer diagnosis, treatment, and prognosis. Recent studies suggest that a large number of coding gene expression microarray probes could be reannotated as lncRNAs. Microarray, once the most cutting-edge high-throughput gene expression technology, has been used for thousands of cancer studies and has brought invaluable resources for studying the functions of lncRNA in cancer development. However, a comprehensive lncRNA resource based on microarray data is still lacking. Here, we present lnCAR (lncRNAs from cancer arrays), a comprehensive open resource for providing expression profiles and prognostic landscape of lncRNAs derived from reannotation of public microarray data. Currently, lnCAR contains 52,300 samples for differential expression analysis and 12,883 samples for survival analysis from 10 cancer types. lnCAR allows users to interactively explore any annotated or novel lncRNAs. We believe lnCAR will serve as a valuable resource for the community focused on lncRNA research in cancer. SIGNIFICANCE: lnCAR, a new interactive tool of reannotated public cancer-related microarray data, provides expression profiles and prognostic landscapes of lncRNAs across thousands of samples and multiple cancer types.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Bases de Dados Genéticas , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante/genética , Software , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Feminino , Humanos , Prognóstico , Taxa de Sobrevida , Interface Usuário-Computador
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