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1.
Aging (Albany NY) ; 122020 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-32039833

RESUMO

The lncRNA tumor suppressor candidate 8 (TUSC8) plays a critical role in the development of several cancers. However, the biological functions and underlying molecular mechanisms of TUSC8 with respect to breast cancer remain largely unclear. Here, we found that TUSC8 was significantly down-regulated in breast cancer tissues and its high expression predicted better prognosis of breast cancer patients. Functionally, knock-down of TUSC8 drastically promoted the proliferation, migration and invasion of breast cancer cells in vitro and facilitated tumorigenicity and metastasis in vivo. Mechanistically, the results of luciferase reporter, RIP and RNA pull-down assays proved that TUSC8 functioned as molecular sponge for miR-190b-5p. Furthermore, we showed that TUSC8 served as a competing endogenous RNA (ceRNA) of myosin regulatory light chain interacting protein (MYLIP) through competitively binding with miR-190b-5p and suppressed breast cancer metastasis through regulating the expression of epithelial-mesenchymal transition (EMT) related markers. Clinically, the receiver operating characteristic curve (ROC) analyses revealed that the combination usage of TUSC8 and MYLIP might become novel promising diagnostic biomarkers for breast cancer. Taken together, these results suggested that TUSC8 inhibited breast cancer growth and metastasis via miR-190b-5p/MYLIP axis, providing us new insights into developing potential therapeutic targets for breast cancer patients.

2.
Biomark Med ; 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31904263

RESUMO

Aim: Fatty acid synthase (FASN), a key enzyme for de novo synthesis of fatty acids, has been identified as an oncogene in some tumor types; however, the function of FASN in gastric cancer (GC) is poorly elucidated. Method: Integrative bioinformatics analyses were performed to unveil the role of FASN in tumor progression and cancer-associated immunology of GC. Result: FASN was overexpressed in the GC tissues and correlated with an inferior survival outcome, and largely contributed to the carcinogenesis of GC. Moreover, FASN expression was closely associated with the immune-infiltrating levels of CD8+ T, CD4+ T, neutrophils, macrophages and dendritic cells. Conclusion: FASN was closely associated with GC and may be involved in the tumorigenesis and cancer-immune interactions, and could be a promising prognostic and therapeutic biomarker in GC.

3.
Anal Chem ; 92(2): 1842-1849, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31859488

RESUMO

Recently, the rapid development and application of mass spectrometry (MS)-based technologies have markedly improved the comprehensive proteomic characterization of global proteome and protein post-translational modifications (PTMs). However, the current conventional approach for global proteomic analysis is often carried out separately from PTM analysis. In our study, we developed an integrated workflow for multiplex analysis of global, glyco-, and phospho-proteomics using breast cancer patient-derived xenograft (PDX) tumor samples. Our approach included the following steps: trypsin-digested tumor samples were enriched for phosphopeptides through immobilized metal ion affinity chromatography (IMAC), followed by enrichment of glycopeptides through mixed anion exchange (MAX) method, and then the flow-through peptides were analyzed for global proteomics. Our workflow demonstrated an increased identification of peptides and associated proteins in global proteome, as compared to those using the peptides without PTM depletion. In addition to global proteome, the workflow identified phosphopeptides and glycopeptides from the PTM enrichment. We also found a subset of glycans with unique distribution profiles in the IMAC flow-through, as compared to those enriched directly using the MAX method. Our integrated workflow provided an effective platform for simultaneous global proteomic and PTM analysis of biospecimens.

4.
Anal Chem ; 92(2): 1680-1686, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31859482

RESUMO

Aberrant glycosylation has been shown to associate with disease progression, and with glycoproteins representing the major protein component of biological fluids this makes them attractive targets for disease monitoring. Leveraging glycoproteomic analysis via mass spectrometry (MS) could provide the insight into the altered glycosylation patterns that relate to disease progression. However, investigation of large sample cohorts requires rapid, efficient, and highly reproducible sample preparation. To address the limitation, we developed a high-throughput method for characterizing glycans, glycosites, and intact glycopeptides (IGPs) derived from N-linked glycoproteins. We combined disparate peptide enrichment strategies (i.e., hydrophilic and hydrophobic) and a liquid handling platform allowing for a high throughput and rapid enrichment of IGP in a 96-well plate format. The C18/MAX-Tip workflow reduced sample processing time and facilitated the selective enrichment of IGPs from complex samples. Furthermore, our approach enabled the analysis of deglycosylated peptides and glycans from enriched IGPs following PNGase F digest. Following development and optimization of the C18/MAX-Tip methodology using the standard glycoprotein, fetuin, we investigated normal urine samples to obtain N-linked glycoprotein information. Together, our method enables a high-throughput enrichment of glycan, glycosites, and IGPs from biological samples.

5.
J Orthop Surg Res ; 14(1): 446, 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31847866

RESUMO

BACKGROUND: Poly(vinyl alcohol) (PVA) hydrogels have been widely used in synthetic cartilage materials. However, limitations of PVA hydrogels such as poor biomechanics and limited cell ingrowth remain challenges in this field. METHODS: This work aimed to design novel nano-hydroxyapatite (nano-HA)/poly(vinyl alcohol) (PVA) hydrogels coated with a poly(lactic-co-glycolic acid) (PLGA)/nano-HA/PVA scaffold to counter the limitations of PVA hydrogels. The core, comprising nano-HA/PVA hydrogel, had the primary role of bearing the mechanical load. The peripheral structure, composed of PLGA/nano-HA/PVA, was designed to favor interaction with surrounding cartilage. RESULTS: The double-layer HA/PVA hydrogel coated with PLGA/HA/PVA scaffold was successfully prepared using a two-step molding method, and the mechanical properties and biocompatibility were characterized. The mechanical properties of the novel PLGA/HA/PVA scaffold modified HA/PVA hydrogel were similar to those of native cartilage and showed greater sensitivity to compressive stress than to tensile stress. Rabbit chondrocytes were seeded in the composites to assess the biocompatibility and practicability in vitro. The results showed that the peripheral component comprising 30 wt% PLGA/5 wt% HA/15 wt% PVA was most conducive to rabbit chondrocyte adhesion and proliferation. CONCLUSIONS: The study indicated that the double-layer HA/PVA hydrogel coated with PLGA/HA/PVA scaffold has the potential for cartilage repair.

6.
Cytojournal ; 16: 16, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31516538

RESUMO

Background: The large-scale National Lung Cancer Screening Trial demonstrated an increased detection of early-stage lung cancers using low-dose computed tomography scan in the screening population. It also demonstrated a 20% reduction of lung cancer-related deaths in these patients. Aims: Although both solid and subsolid lung nodules are evaluated in studies, subsolid and partially calcified lung nodules are often overlooked. Materials and Methods: We reviewed transthoracic fine-needle aspiration (FNA) cases from lung nodule patients in our clinics and correlated cytological diagnoses with radiologic characteristics of lesions. A computer search of the pathology archive was performed over a period of 12 months for transthoracic FNAs, including both CT- and ultrasound-guided biopsies. Results: A total of 111 lung nodule cases were identified. Lesions were divided into three categories: solid, subsolid, and partially calcified nodules according to radiographic findings. Of 111 cases, the average sizes of the solid (84 cases), subsolid (22 cases), and calcified (5 cases) lesions were 1.952 ± 2.225, 1.333 ± 1.827, and 1.152 ± 1.984 cm, respectively. The cytological diagnoses of three groups were compared. A diagnosis of malignancy was made in 64.28% (54 cases) in solid, 22.72% (5 cases) in subsolid, and 20% (1 case) in partially calcified nodules. Among benign lesions, eight granulomatous inflammations were identified, including one case of solid, five cases of subsolid, and two cases of calcified nodules. Conclusions: Our study indicates that solid nodules have the highest risk of malignancy. Furthermore, the cytological evaluation of subsolid and partially calcified nodules is crucial for the accurate diagnosis and appropriate clinical management of lung nodule patients.

7.
Curr Res Transl Med ; 67(4): 123-128, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31492588

RESUMO

Carbamoyl phosphate synthetase-1 (CPS1), the first rate-limiting mitochondrial enzyme in the urea cycle, regulates proliferation and differentiation during tumor progression. However, the detailed function of CPS1 in glioblastoma Multiforme (GBM) is still unclear. Here, we highlight mechanisms for CPS1 upregulation and the effects of upregulated CPS1 on GBM tumorigenesis. The transcriptome data from several public databases, such as Oncomine and GEPIA, revealed that CPS1 transcriptional level was significantly upregulated in GBM tissues and cells. Moreover, CPS1 was hypomethylated in GBM tissues. The Wanderer database, linked to the Cancer Genome Atlas (TCGA), showed the association between CPS1 expression or its methylation values and the clinicopathological parameters in GBM patients. Our work fully demonstrated that CPS1 expression was upregulated in GBM and this gene could be used as a potential diagnostic and prognosis indicator for GBM.

8.
Front Oncol ; 9: 683, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31403034

RESUMO

Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (EBV+ DLBCL) is a rare type of lymphoma with a high incidence in elderly patients, poor drug response, and unfavorable prognosis. Despite advances in genomic profiling and precision medicine in DLBCL, EBV+ DLBCL remain poorly characterized and understood. We include 236 DLBCL patients for EBV-encoded mRNA (EBER) in situ hybridization detection and analyzed 9 EBV+ and 6 EBV negative cases by next-generation sequencing (NGS). We then performed fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) to analyze chromosome rearrangements and gene expressions in 22 EBV+ and 30 EBV negative cases. The EBER results showed a 9.3% (22/236) positive rate. The NGS results revealed recurrent alterations in MYC and RHOA, components of apoptosis and NF-κB pathways. The most frequently mutated genes in EBV+ DLBCL were MYC (3/9; 33.3%), RHOA (3/9; 33.3%), PIM1 (2/9; 22.2%), MEF2B (2/9; 22.2%), MYD88 (2/9; 22.2%), and CD79B (2/9; 22.2%) compared with KMT2D (4/6; 66.7%), CREBBP (3/6; 50.0%), PIM1 (2/6; 33.3%), TNFAIP3 (2/6; 33.3%), and BCL2 (2/6; 33.3%) in EBV-negative DLBCL. MYC and KMT2D alterations stood out the most differently mutated genes between the two groups. FISH detection displayed a lower rearrangement rate in EBV+ cohort. Furthermore, KMT2D expression was highly expressed and associated with poor survival in both cohorts. MYC was only overexpressed and related to an inferior prognosis in the EBV+ DLBCL cohort. In summary, we depicted a distinct mutation profile for EBV+ and EBV-negative DLBCL and validated the differential expression of KMT2D and MYC with potential prognostic influence, thereby providing new perspectives into the pathogenesis and precision medicine of DLBCL.

9.
J Knee Surg ; 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31434148

RESUMO

Diffuse-type pigmented villonodular synovitis is a rare benign disease that causes disorders of the knee, including erosion of subchondral bone and cyst formation, with eventual osteoarthritis. The purpose of this study was to evaluate the short-term outcomes of synovectomy and total knee replacement in patients with the diffuse type of pigmented villonodular synovitis. From November 2011 to May 2015, we performed synovectomy and total knee replacement in 28 patients with diffuse pigmented villonodular synovitis diagnosed on the basis of histopathology of biopsy specimens. Clinical data were collected perioperatively and during follow-up for evaluation of surgical efficacy. No intraoperative complications were encountered. Mean operative duration was 73.4 minutes (range: 47-115 minutes); mean estimated blood loss was 223.9 mL (range: 50-600 mL). The mean duration of follow-up was 58.7 months (range: 36-84 months). Mean range of motion improved from 86.1 ± 11.3 degrees (range: 60-100 degrees) to 107 ± 11.4 degrees (range: 90-130 degrees). Average Knee Society clinical scores improved from 38.9 ± 9.5 (range: 17-54) to 84.4 ± 6.1 (range: 75-98); functional scores improved from 48.9 ± 13.1 (range: 25-80) to 84.6 ± 6.1 (range: 75-95; p < 0.05 for both). Postoperative radiographs showed no signs of prosthesis loosening, periprosthetic fractures, or dislocation. The short-term efficacy of synovectomy and total knee replacement in treating patients with diffuse pigmented villonodular synovitis was satisfactory.

10.
Biomark Med ; 13(9): 761-771, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31157548

RESUMO

Aim: p16 and p53 are frequently altered intracellular pathways in cancers. We investigated the aberrant expression of p16 and its relationship with p53 and HPV status in primary non-small-cell lung carcinoma. Patients & methods: Lung tumor tissue microarray (n = 163), immunohistochemical study of p16 and p53, and HPV in-situ hybridization were analyzed. Results: p16 and p53 were detected in 50.7 and 57.3% of adenocarcinoma (ADCs; n = 75), and 35.2 and 63.6% of squamous cell carcinoma (n = 88). HPV was detected in 16 and 10.2% of ADC and squamous cell carcinoma. In ADCs, p16 positive tumors demonstrated a favorable median overall survival time of 60.9 months, compared with p16 negative tumors of 46.9 months (p < 0.05). Furthermore, we did not find significant relationships between p16 expression and HPV status, nor with p53 expression. Conclusion: p16 play an unique role in lung cancer survival. The mechanism of p16 needs to be further studied.

11.
Anal Chem ; 91(9): 5517-5522, 2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-30924636

RESUMO

Mass spectrometry-based urinary proteomics is one of the most attractive strategies to discover proteins for diagnosis, prognosis, monitoring, or prediction of therapeutic responses of urological diseases involving the kidney, prostate, and bladder; however, interfering compounds found in urine necessitate sample preparation strategies that are currently not suitable for urinary proteomics in the clinical setting. Herein, we describe the C4-tip method, comprising a simple, automated strategy utilizing a reverse-phase resin tip-based format and "on-tip" digestion to examine the urine proteome. We first determined the optimal conditions for protein isolation and protease digestion on the C4-tip using the standard protein bovine fetuin. Next, we applied the C4-tip method to urinary proteomics, identifying a total of 813 protein groups using LC-MS/MS, with identified proteins from the C4-tip method displaying a similar distribution of gene ontology (GO) cellular component assignments compared to identified proteins from an ultrafiltration preparation method. Finally, we assessed the reproducibility of the C4-tip method, revealing a high Spearman correlation R-value for shared proteins identified across all tips. Together, we have shown the C4-tip method to be a simple, robust method for high-throughput analysis of the urinary proteome by mass spectrometry in the clinical setting.

12.
Int J Exp Pathol ; 100(1): 32-40, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30912195

RESUMO

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma. Because the prognosis of DLBCL patients varies considerably, there is an urgent need to identify novel prognostic factors. In this study, we investigated the expression levels of the signalling enzyme 3-phosphoinositide-dependent protein kinase-1 (PDK1), the cell cycle regulatory enzyme Polo-like kinase 1 (PLK1) and the transcription factor (c-Myc) in DLBCL tissues and evaluated their clinical and prognostic significance. PDK1, PLK1 and c-Myc were detected by immunohistochemical staining of paraffin-embedded specimens from 152 DLBCL and 48 lymphadenitis patients. Expression levels were correlated with clinicopathological factors. PDK1, PLK1 and c-Myc were more commonly expressed in DLBCL specimens than in lymphadenitis specimens, and the expression of each protein correlated positively with that of the other two molecules. High PDK1, PLK1 and c-Myc expression, high international prognostic index score, high lactate dehydrogenase levels and late Ann Arbor stage were shown to correlate with shorter overall survival time. A multivariate Cox regression model showed that high expression levels of PLK1 and c-Myc were independent prognostic factors for DLBCL. Our findings indicate that PLK1 and c-Myc expression might be promising predictive biomarkers for DLBCL patients.


Assuntos
Proteínas Quinases Dependentes de 3-Fosfoinositídeo/análise , Proteínas de Ciclo Celular/análise , Linfoma Difuso de Grandes Células B/enzimologia , Proteínas Serina-Treonina Quinases/análise , Proteínas Proto-Oncogênicas c-myc/análise , Proteínas Proto-Oncogênicas/análise , Biomarcadores Tumorais/análise , Biópsia , Feminino , Humanos , Imuno-Histoquímica , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco
13.
Gene ; 692: 1-8, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30641222

RESUMO

BACKGROUND: Phosphoribosylaminoimidazole carboxylase (PAICS), a de novo purine metabolic enzyme, has been identified as an oncogene in several tumor types, including breast cancer and prostate cancer. However, the role of PAICS in human lung adenocarcinoma (LADC) requires further study. METHODS: In this research, the effects of PAICS on the occurrence and prognosis of LADC were evaluated using integrative bioinformatics analyses. RESULTS: By employing the bioinformatics analyses of several public databases, PAICS, which is overexpressed in the LADC tissues, was identified as a potential tumor-promoting gene in LADC biology. Several relevant clinical studies indicated that the upregulation of PAICS was statistically correlated with a shorter overall survival time. Moreover, the carcinogenic function of PAICS in LADC was validated by the further protein-protein interactions (PPI) and biological process annotation analysis. Mechanistically, we found that the PAICS methylation level was significantly lower in the LADC tissues compared to the normal lung tissues. Furthermore, using the MEXPRESS web tool, we predicted 15 possible DNA methylation sites in the nucleotide sequences of PAICS, which could explain the alteration in the PAICS expression levels in LADC. CONCLUSIONS: Our work demonstrates that high levels of PAICS are found in LADC and that this gene may be a potential therapeutic target for this subset of lung cancers. Determining the detailed roles of PAICS in LADC biology may provide useful information for further investigations.


Assuntos
Adenocarcinoma de Pulmão/genética , Carboxiliases/genética , Carboxiliases/metabolismo , Neoplasias Pulmonares/genética , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/mortalidade , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Metilação de DNA , Receptores ErbB/genética , Feminino , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Masculino , Prognóstico , Mapas de Interação de Proteínas
14.
Am J Physiol Lung Cell Mol Physiol ; 316(4): L630-L643, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30604627

RESUMO

Lung adenocarcinoma (LUAD) is the most common histological form of lung cancer that is clinically diagnosed. The aim of this study is to explore the novel genes associated with LUAD tumorigenesis. Comprehensive bioinformatics analyses of the data were obtained from several publicly available databases, such as the Gene Expression Omnibus, the Human Protein Atlas project, and the Cancer Cell Line Encyclopedia. The clinical relevance of these novel genes in LUAD was further examined by immunohistochemistry. We identified the overlapping differentially expressed genes (DEGs) in five independent microarray data sets from the Gene Expression Omnibus database ( GSE75037 , GSE85716 , GSE85841 , GSE63459 , and GSE32867 ). Using the criteria of |log (fold change)| ≥ 1 and P value <0.05, 167 genes were preliminarily validated as co-DEGs. Protein-protein interaction network analysis indicated that caveolin 1 (CAV1) and decorin (DCN) levels were significantly reduced and that these genes were the most promising predictive biomarkers for the occurrence and prognosis of LUAD. A cell proliferation assay indicated that overexpressed CAV1 and DCN could significantly inhibit the proliferation rate of A549 and H157 cells. Additionally, these two downregulated candidate genes were further verified by immunohistochemistry conducted on a LUAD tissue array and comprehensive bioinformatics analyses, including those using the Oncomine platform and the Cancer Cell Line Encyclopedia. Our study demonstrates low levels of CAV1 and DCN in LUAD. An understanding of their functional roles in LUAD biology would give us important insights that would be useful in further investigations.

15.
Front Oncol ; 8: 473, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30406035

RESUMO

Marsdenia tenacissima (MT), a traditional Chinese herbal medicine, has long been used for thousands of years to treat asthma, tracheitis, rheumatism, etc. An increasing number of recent studies have focused on the antitumor effects of MT. The effects of MT on cancer are the result of various activated signaling pathways and inhibiting factors and the high expression levels of regulatory proteins. MT can inhibit different cancer types including non-small cell lung cancer (NSCLC), malignant tumors, hepatic carcinoma, and so on. This article mainly focuses on the activities and mechanisms of MT. In addition, the efficacy and toxicity of MT are also discussed. Further studies of MT are required for improved medicinal utilization.

16.
Int J Oncol ; 53(6): 2780-2788, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30320371

RESUMO

Helicase­like transcription factor (HLTF) has been identified as a tumor suppressor gene. The hypermethylation of HTLF is frequently observed in various types of cancer, including colorectal cancer (CRC). However, the mechanisms through which HLTF suppresses CRC progression remain unclear. Thus, the aim of the present study was to explore the biological function of HLTF in CRC cells and the underlying mechanisms. CRC tissues and cells were used to detect the expression of HLTF. Wound­healing and Transwell assays were performed to assess the motility of CRC cells. The results revealed that HLTF expression was significantly associated with the differentiation status, invasion depth, lymph node metastasis and distant metastasis. A low HLTF expression was significantly associated with a poor survival. Furthermore, HTLF knockdown or ectopic overexpression significantly promoted or suppressed the motility of CRC cells, respectively. With regard to the underlying molecular mechanisms, the protein expression of HTLF was upregulated when the CRC cells were stimulated with transforming growth factor (TGF)­ß, and HLTF upregulation induced an increase in SMAD4 and p­SMAD2/3 expression and a decrease in levels of the TGF­ß/SMAD pathway downstream genes, Vimentin and zinc finger e­box binding homeobox 1 (ZEB1). On the whole, the findings of this study suggest that HLTF is negatively associated with the progression of CRC, and its overexpression suppresses the migration and invasion of CRC cells by targeting the TGF­ß/SMAD pathway.


Assuntos
Neoplasias Colorretais/metabolismo , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Transdução de Sinais , Linhagem Celular Tumoral , Movimento Celular , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Células HCT116 , Células HT29 , Humanos , Técnicas In Vitro , Masculino , Invasividade Neoplásica , Metástase Neoplásica , Estadiamento de Neoplasias , Fosforilação , Prognóstico , Proteínas Smad/metabolismo , Análise de Sobrevida , Fator de Crescimento Transformador beta/metabolismo
17.
Neoplasia ; 20(10): 1059-1069, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30227305

RESUMO

Primary central nervous system lymphoma (PCNSL) is a rare and special type of non-Hodgkin lymphoma. The treatment of PCNSL is comprehensive, combining surgery, radiotherapy, and chemotherapy. However, the outcome is poor because of its high invasiveness and rate of recurrence. We analyzed 22 cases of PCNSL using next-generation sequencing (NGS) to detect 64 candidate genes. We used immunohistochemical methods to analyze gene expression in 57 PCNSL samples. NGS showed that recurrent mutations in KMT2D and CD79B, components of the NF-κB pathway, accounted for 65% of total mutations in PCNSL samples. The most frequent mutated gene was PIM1 (77.27%, 17/22), followed by MYD88 (63.64%, 14/22), CD79B (69.09%, 13/22), and KMT2D (50.00%, 11/22). Mutations of the CD79B gene were associated with an inferior progression-free survival (PFS), and GNA13 gene mutations were associated with a shorter PFS and overall survival (OS) in PCNSL patients (P < .05). PIM1 and MYD88 were highly expressed in PCNSL patients and were related to their OS time. MYD88 overexpression might be an independent and poor prognostic predictor of OS time. In summary, we identified highly recurrent genetic lesions in CD79B and KMT2D, components of the NF-κB pathway, in PCNSL and validated the expression of PIM1 and MYD88 related to poor survival, thereby providing novel insights into the pathogenesis and precision medicine of PCNSL.


Assuntos
Neoplasias do Sistema Nervoso Central/genética , Regulação Neoplásica da Expressão Gênica , Linfoma/genética , Mutação , Adolescente , Adulto , Idoso , Antígenos CD79/genética , Neoplasias do Sistema Nervoso Central/mortalidade , Proteínas de Ligação a DNA/genética , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfoma/mortalidade , Masculino , Pessoa de Meia-Idade , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , Proteínas de Neoplasias/genética , Prognóstico , Proteínas Proto-Oncogênicas c-pim-1/genética , Proteínas Proto-Oncogênicas c-pim-1/metabolismo
18.
Sci Technol Adv Mater ; 19(1): 425-442, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29868147

RESUMO

Perovskite solar cells have recently drawn significant attention for photovoltaic applications with a certified power conversion efficiency of more than 22%. Unfortunately, the toxicity of the dissolvable lead content in these materials presents a critical concern for future commercial development. This review outlines some criteria for the possible replacement of lead by less toxic elements, and highlights current research progress in the application of low-lead halide perovskites as optically active materials in solar cells. These criteria are discussed with the aim of developing a better understanding of the physio-chemical properties of perovskites and of realizing similar photovoltaic performance in perovskite materials either with or without lead. Some open questions and future development prospects are outlined for further advancing perovskite solar cells toward both low toxicity and high efficiency.

19.
Genes (Basel) ; 9(1)2018 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-29300342

RESUMO

There is increasing evidence for the contribution of synuclein alpha (SNCA) to the etiology of neurological disorders, such as Parkinson's disease (PD). However, little is known about the detailed role of SNCA in human cancers, especially lung cancers. Here, we evaluated the effects of SNCA on the occurrence and prognosis of lung adenocarcinoma (ADC). Comprehensive bioinformatics analyses of data obtained from the Oncomine platform, the human protein atlas (HPA) project and the cancer cell line encyclopedia (CCLE) demonstrated that SNCA expression was significantly reduced in both ADC tissues and cancer cells. The results of relevant clinical studies indicated that down-regulation of SNCA was statistically correlated with shorter overall survival time and post-progression survival time. Through analysis of datasets obtained from the Gene Expression Omnibus database, significant low levels of SNCA were identified in cisplatin-resistant ADC cells. Moreover, small interfering RNA (siRNA)-mediated knockdown of protein tyrosine kinase 7 (PTK7) elevated the expression of SNCA in the ADC cell lines H1299 and H2009. Our work demonstrates that low levels of SNCA are specifically found in ADC and that this gene may be a potential therapeutic target for this subset of lung cancers. Determination of the role of SNCA in ADC biology would give us some insightful information for further investigations.

20.
Spine (Phila Pa 1976) ; 43(10): E565-E573, 2018 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-29135884

RESUMO

STUDY DESIGN: Retrospective cohort analysis of patients with spinal astrocytoma from multi-institutional data and the literature. OBJECTIVE: To determine the prognostic factors, treatment, and survival of patients. SUMMARY OF BACKGROUND DATA: Our current understanding of the epidemiology, prognosis, and optimal treatment of spinal astrocytoma is limited. The literature is confined to case reports or small institutional case series. METHOD: Patient demographics, tumor characteristics, treatments, and outcomes were extracted. Univariate Kaplan-Meier survival analysis was performed to identify prognostic factors followed by multivariate Cox proportional hazard analysis. Wilcoxon signed-rank test was performed on pre- and postoperational functional status as measured by McCormick score. RESULTS: Ninety-four patients from four institutions and 339 patients from the literature were included. For the multi-institutional cohort, WHO grade IV tumors had shorter progression-free survival (PFS) than those of lower grades, whereas gross total resection (GTR) (hazard ratio [HR]: 0.41, 95% confidence interval [CI]: 0.14-1.27, P = 0.124) trended toward longer PFS when compared to subtotal resection (STR). Age 18 years or older, paresthesia as a presenting symptom, and higher WHO grade were associated with shorter overall survival (OS), whereas thoracic tumor location when compared to cervical tumor location, biopsy when compared to STR, and radiotherapy (HR: 0.42, 95% CI: 0.20-0.88, P = 0.022) were associated with longer OS. For the literature cohort, GTR (HR 0.43, 95% CI: 0.24-0.77, P = 0.005) was associated with longer PFS when compared to STR, whereas higher WHO grade was associated with shorter PFS. Higher WHO grade and recurrence/progression were associated with shorter OS. Postoperative McCormick score was significantly higher than preoperative score (P < 0.001), but subgroup analysis of the change in McCormick score by extent of resection revealed no differences among groups (P = 0.551). CONCLUSION: In patients with spinal astrocytomas, GTR likely resulted in longer PFS when compared to STR. Adjuvant radiotherapy appears to be effective in improving survival outcomes for high-grade tumors. LEVEL OF EVIDENCE: 4.


Assuntos
Astrocitoma/diagnóstico , Astrocitoma/cirurgia , Quimiorradioterapia/tendências , Neoplasias da Medula Espinal/diagnóstico , Neoplasias da Medula Espinal/cirurgia , Adolescente , Adulto , Idoso , Astrocitoma/mortalidade , Quimiorradioterapia/mortalidade , Criança , Pré-Escolar , Estudos de Coortes , Terapia Combinada/mortalidade , Terapia Combinada/tendências , Feminino , Seguimentos , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Neoplasias da Medula Espinal/mortalidade , Taxa de Sobrevida/tendências , Resultado do Tratamento , Adulto Jovem
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