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1.
J Biomed Opt ; 25(3): 1-17, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32170857

RESUMO

SIGNIFICANCE: Detection and characterization of circulating tumor cells (CTCs), a key determinant of metastasis, are critical for determining risk of disease progression, understanding metastatic pathways, and facilitating early clinical intervention. AIM: We aim to demonstrate label-free imaging of suspected melanoma CTCs. APPROACH: We use a linear-array-based photoacoustic tomography system (LA-PAT) to detect melanoma CTCs, quantify their contrast-to-noise ratios (CNRs), and measure their flow velocities in most of the superficial veins in humans. RESULTS: With LA-PAT, we successfully imaged suspected melanoma CTCs in patients in vivo, with a CNR >9. CTCs were detected in 3 of 16 patients with stage III or IV melanoma. Among the three CTC-positive patients, two had disease progression; among the 13 CTC-negative patients, 4 showed disease progression. CONCLUSIONS: We suggest that LA-PAT can detect suspected melanoma CTCs in patients in vivo and has potential clinical applications for disease monitoring in melanoma.

2.
Cancer Imaging ; 20(1): 12, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32000852

RESUMO

BACKGROUND: We developed a computational model integrating clinical data and imaging features extracted from contrast-enhanced computed tomography (CECT) images, to predict lymph node (LN) metastasis in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: This retrospective study included 159 patients with PDAC (118 in the primary cohort and 41 in the validation cohort) who underwent preoperative contrast-enhanced computed tomography examination between 2012 and 2015. All patients underwent surgery and lymph node status was determined. A total of 2041 radiomics features were extracted from venous phase images in the primary cohort, and optimal features were extracted to construct a radiomics signature. A combined prediction model was built by incorporating the radiomics signature and clinical characteristics selected by using multivariable logistic regression. Clinical prediction models were generated and used to evaluate both cohorts. RESULTS: Fifteen features were selected for constructing the radiomics signature based on the primary cohort. The combined prediction model for identifying preoperative lymph node metastasis reached a better discrimination power than the clinical prediction model, with an area under the curve of 0.944 vs. 0.666 in the primary cohort, and 0.912 vs. 0.713 in the validation cohort. CONCLUSIONS: This pilot study demonstrated that a noninvasive radiomics signature extracted from contrast-enhanced computed tomography imaging can be conveniently used for preoperative prediction of lymph node metastasis in patients with PDAC.

3.
Int J Biol Macromol ; 149: 1084-1097, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32035151

RESUMO

This study presented the first purification and characterization of a hepatoprotective polysaccharide (PNPS-0.5 M) from the residue of Panax notoginseng (Burk.) F.H. Chen. This polysaccharide included a backbone of (4 â†’ 1)-linked GalA and branches of (1→)-linked Araf, (1→)-linked Rhap, and (5 â†’ 1)-linked Araf and had an extremely high molecular weight (2600 kDa). We investigated the hepatoprotective effects of PNPS-0.5 M on mice with alcoholic liver damage (ALD). After administration of PNPS-0.5 M, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), and hepatic malondialdehyde (MDA) were reduced to normal. In contrast, hepatic levels of alcohol dehydrogenase (ADH) and the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were elevated to normal. Further investigations indicated that PNPS-0.5 M activated Nrf2 signaling as a protective mechanism against Cyp2e1 toxicity in ALD mice. Meanwhile, it strengthened the ADH pathway and suppressed the CAT pathway of alcohol metabolism to prevent peroxide accumulation, thereby ameliorating ALD. In the present study, we describe a novel acidic polysaccharide from P. notoginseng with hepatoprotective activity that facilitates the development and utilization of P. notoginseng resources.

4.
Molecules ; 25(2)2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31941038

RESUMO

(1) Background: Flavonoids are the primary medicinal ingredient of Saussurea involucrate, which have significant antioxidant capacity. Optimizing the extraction of Saussurea involucrate flavonoids (SIFs) and exploring the ability to block melanin deposition caused by reactive oxygen can greatly promote the development of S. involucrate whitening products. (2) Methods: Ultrasonic extraction process was optimized using the Box-Behnken design (BBD) and response surface methodology (RSM). Then, the effect of SIFs on antioxidant activity and anti-deposition of melanin, and genes related to the melanin synthesis are studied. (3) Results: The optimal extraction procedures are as follows: the extraction time, ethanol content, and solvent ratio (v/w) are 64 min, 54%, and 54:1, respectively. The reducing activity and scavenging rates of 2,2-diphenyl-1-picrylhydrazyl (DPPH), superoxide anion, hydroxyl radical, and ABTS+ were promoted as more S. involucrate flavonoid extract was added. The SIFs extract induced a decrease in the melanin synthesis by inhibiting the human melanoma A375 cell tyrosinase activity. SIFs also depress expression of melanin synthesis related genes. (4) Conclusions: the highest SIFs content was obtained by using 54% ethanol and 54:1 solvent ratio (v/w) for 64 min. The extract of SIFs exhibited good ability of antioxidant and anti-deposition of melanin in human melanocytes.

5.
Mol Genet Genomic Med ; 8(3): e1115, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31958216

RESUMO

BACKGROUND: The aim of this research was to investigate the retinal transcriptome changes in long-term streptozotocin (STZ)-induced rats' retinas using RNA sequencing (RNA-seq), to explore the molecular mechanisms of diabetic retinopathy (DR), and to identify novel targets for the treatment of DR by comparing the gene expression profile we obtained. METHODS: In this study, 6 healthy male SD rats were randomly divided into wild-type (WT) group and streptozotocin (STZ)-induced group, 3 rats each group. After 6 months, 3 normal retina samples and 3 DM retina samples (2 retinas from the same rat were considered as 1 sample) were tested and differentially expressed genes (DEGs) were measured by RNA-seq technology. Then, we did Gene Ontology (GO) enrichment analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis and validated the results of RNA-seq through qRT-PCR. RESULTS: A total of 118 DEGs were identified, of which 72 were up-regulated and 46 were down-regulated. The enriched GO terms showed that 3 most significant enrichment terms were binding (molecular function), cell part (cellular component), and biological regulation (biological process). The results of the KEGG pathway analysis revealed a significant enrichment in cell adhesion molecules, PI3K-Akt signaling pathway, and allograft rejection, etc. CONCLUSION: Our research has identified specific DEGs and also speculated their potential functions, which will provide novel targets to explore the molecular mechanisms of DR.

6.
Aging (Albany NY) ; 12(1): 866-883, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31915310

RESUMO

Epithelial-to-mesenchymal transition (EMT) is important in tumor invasiveness and metastasis. We aimed to determine prognostic value of six key EMT markers (CDH1, CDH2, SNAI1, SNAI2, VIM, TWIST1) in clear cell renal cell carcinoma (ccRCC). A total of 533 ccRCC patients with RNASeq data from The Cancer Genome Atlas (TCGA) cohort were included for analysis. Gene expression of these EMT markers was compared between tumor and normal tissues based on Oncomine database and TCGA cohort. Their correlations with progression-free survival (PFS) and overall survival (OS) were also examined in both TCGA cohort and FUSCC (Fudan University Shanghai Cancer Center) cohort. Cox proportional hazards regression model and Kaplan-Meier plot were used to assess the relative factors. Functional enrichment analyses were utilized to describe biologic function annotations and significantly involved hallmarks pathways of each gene. We found that Epithelial marker, CDH1 expression was lower, while mesenchymal markers (CDH2, SNAI1, VIM, TWIST1) expression was higher in ccRCC primary tumors. In the TCGA cohort, we found that patients with higher expression of VIM, TWIST1 or lower expression of CDH1 had worse prognosis. Further, in the FUSCC cohort, we confirmed the predictive ability of mesenchymal markers and epithelial marker expression in PFS and OS of ccRCC patients. After generating Cox regression models, EMT markers (CDH1, SNAI1, VIM, and TWIST1) were independent prognostic factors of both PFS and OS in ccRCC patients. Our preliminary EMT prediction model can facilitate further screening of EMT biomarkers and cast a better understanding of EMT gene function in ccRCC.

7.
Cancer Res ; 80(2): 319-333, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31690668

RESUMO

The tumorigenic role and underlying mechanisms of lipid accumulation, commonly observed in many cancers, remain insufficiently understood. In this study, we identified an AMP-activated protein kinase (AMPK)-GATA-binding protein 3 (GATA3)-enoyl-CoA hydratase short-chain 1 (ECHS1) pathway that induces lipid accumulation and promotes cell proliferation in clear cell renal cell carcinoma (ccRCC). Decreased expression of ECHS1, which is responsible for inactivation of fatty acid (FA) oxidation and activation of de novo FA synthesis, positively associated with ccRCC progression and predicted poor patient survival. Mechanistically, ECHS1 downregulation induced FA and branched-chain amino acid (BCAA) accumulation, which inhibited AMPK-promoted expression of GATA3, a transcriptional activator of ECHS1. BCAA accumulation induced activation of mTORC1 and de novo FA synthesis, and promoted cell proliferation. Furthermore, GATA3 expression phenocopied ECHS1 in predicting ccRCC progression and patient survival. The AMPK-GATA3-ECHS1 pathway may offer new therapeutic approaches and prognostic assessment for ccRCC in the clinic. SIGNIFICANCE: These findings uncover molecular mechanisms underlying lipid accumulation in ccRCC, suggesting the AMPK-GATA3-ECHS1 pathway as a potential therapeutic target and prognostic biomarker.

8.
J Cell Biochem ; 121(2): 1552-1562, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31512789

RESUMO

OBJECTIVE: Serine palmitoyltransferase, long chain base subunit 1 (SPTLC1) catalyzes the first step in sphingolipid synthesis and has been implicated in the progression of various cancers. However, its role in clear cell renal cell carcinoma (ccRCC) remains unclear. Here, we investigated the expression and prognostic value of SPTLC1 in ccRCC. METHODS: Three ccRCC patient cohorts were studied. ccRCC and adjacent normal kidney tissue samples were obtained from 183 patients at the Fudan University Shanghai Cancer Center (FUSCC) and subjected to immunohistochemical staining and quantitative reverse-transcription polymerase chain reaction to evaluate SPTLC1 protein and messenger RNA (mRNA) expression. Two validation cohorts consisting of mRNA and clinicopathological data sets from patients with ccRCC were obtained from the Cancer Genome Atlas (TCGA, n = 429) and Oncomine (n = 178) databases. Associations between low and high SPTLC1 mRNA and protein expression and survival were evaluated using the Kaplan-Meier method and log-rank test. Independent prognostic factors were identified using univariate and multivariate Cox regression analysis. RESULTS: SPTLC1 mRNA or protein were expressed at significantly lower levels in ccRCC tissues compared with normal kidney tissues in all three patient cohorts (P < .001). Low SPTLC1 expression was significantly associated with shorter overall survival in the FUSCC (P = .041) and Oncomine (P < .001) cohorts, and was significantly associated with shorter overall survival (P < .0001) and progression-free survival (P < .001) in the TCGA cohort. Bioinformatics analysis identified 10 genes significantly coregulated with SPTLC1 in ccRCC, most of which contributed to sphingomyelin metabolism (SPTLC2, SPTLC3, SPTSSA, SPTSSB, ORMDL1, ORMDL2, ORMDL3, ZDHHC9, GOLGA7B, and KDSR). Functional enrichment analysis predicted that SPTLC1 and its network play significant roles in inflammatory, hypoxia, and interferon gamma responses, and in allograft rejection pathways. CONCLUSION: Low SPTLC1 expression is significantly associated with disease progression and poor survival in patients with ccRCC, suggesting that SPTLC1 may function as a tumor suppressor. Thus, SPTLC1 could be a potential new biomarker and/or therapeutic target for ccRCC.

9.
J Exp Med ; 217(2)2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-31699823

RESUMO

All hematopoietic lineages are derived from a limited pool of hematopoietic stem cells (HSCs). Although the mechanisms underlying HSC self-renewal have been extensively studied, little is known about the role of protein glutamylation and deglutamylation in hematopoiesis. Here, we show that carboxypeptidase CCP3 is most highly expressed in BM cells among CCP members. CCP3 deficiency impairs HSC self-renewal and hematopoiesis. Deubiquitinase BAP1 is a substrate for CCP3 in HSCs. BAP1 is glutamylated at Glu651 by TTLL5 and TTLL7, and BAP1-E651A mutation abrogates BAP1 glutamylation. BAP1 glutamylation accelerates its ubiquitination to trigger its degradation. CCP3 can remove glutamylation of BAP1 to promote its stability, which enhances Hoxa1 expression, leading to HSC self-renewal. Bap1E651A mice produce higher numbers of LT-HSCs and peripheral blood cells. Moreover, TTLL5 and TTLL7 deficiencies sustain BAP1 stability to promote HSC self-renewal and hematopoiesis. Therefore, glutamylation and deglutamylation of BAP1 modulate HSC self-renewal and hematopoiesis.

10.
Oral Oncol ; 101: 104512, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31869689

RESUMO

OBJECTIVES: This study aimed to explore the value of preoperative radiotherapy in the comprehensive treatment of locally advanced nasal cavity and paranasal sinus squamous cell carcinomas (LA-NPSCCs). MATERIALS: This retrospective study included 140 patients with stage III-IVB NPSCCs treated with pre-/postoperative radiotherapy plus surgery. The complete resection rate, pathologic complete response (pCR) rate, and orbital content retention rate were calculated. The overall survival (OS), local control (LC), distance metastasis free survival (DMFS) and disease-free survival (DFS) between treatment groups were evaluated. RESULTS: With a median follow-up of 92.3 months, the 5-year OS, LC, DMFS, and DFS of entire cohort were 62.0%, 65.5%, 85.4%, and 57.8%, respectively. The preoperative radiotherapy group achieved similar LC, DFS, DMFS, and OS rates compared to postoperative radiotherapy group, despite higher rates of stage IV and orbital content/apex invasion. The preoperative radiotherapy resulted in significantly improved complete resection rate (93.3% vs 38.0%, p < 0.001). In the preoperative radiotherapy group, one third of patients achieved pathologic complete response. The pCR subgroup achieved statistically higher 5-year OS, LC, DFS (p < 0.05), but similar 5-year DMFS (p > 0.05) compared to non-pCR subgroup. The actual orbital content retention rate in preoperative radiotherapy group was 85.7%, superior to 58.3% in postoperative radiotherapy group (p = 0.049). CONCLUSION: On the basis of multimodality therapy becoming standard paradigm for LA-NPSCCs, preoperative radiotherapy significantly improved complete resection rate and orbital content retention rate. Therefore, preoperative radiotherapy followed by surgery might be desirable for LA-NPSCCs, especially for those with organ preservation intention.

11.
Front Oncol ; 9: 879, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31824835

RESUMO

Objective: To investigate the association between tumor PD-L1 expression and patient survival to determine whether PD-L1 represents an independent prognostic feature for patients with non-metastatic clear cell renal cell carcinoma (RCC). Patients and Methods: The tissue bank of the Fudan University Shanghai Cancer Center was queried to identity tissue samples of patients treated with radical nephrectomy, for non-metastatic sporadic clear cell RCC (ccRCC) between 2008 and 2015. Real-time polymerase chain reaction and immunohistochemistry staining was performed to detect the expression level of PD-L1 in paired cancer tissue and paracancerous tissue. Results: Three-hundred-and-thirty patients were enrolled in this study, with a mean age of 55.0 years at surgery and a mean tumor size of 5.2 cm. Two-hundred-and-forty-two (73.3%) and 88 (26.7%) patients showed a high and low expression of PD-L1 mRNA, respectively, while 254 patients had positive PD-L1 immunohistochemistry staining. Two-hundred-and-ninety-two patients had consistent results for mRNA and the PD-L1 protein based on these different detection methods. Patients with high PD-L1 expression were more likely to exhibit adverse pathologic features including an advanced T stage (P = 0.002) and lymph node metastasis (P = 0.044). The Kaplan-Meier curves of PFS and OS stratified by PD-L1 expression had a statistically significant difference. PD-L1 expression maintained a significant predictive role for PFS and OS in the multivariate cox model. Conclusions: Our data suggests that PD-L1 correlates with prognosis in RCC and targeting the PD-1/PD-L1 pathway should be considered in the treatment of RCC patients.

12.
Med Sci Monit ; 25: 9458-9470, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31825950

RESUMO

BACKGROUND The serine peptidase inhibitor Kazal type 13 (SPINK13) gene has tumor suppressor activity, but its role in renal cell carcinoma (RCC) remains unknown. This study aimed to investigate mRNA expression of SPINK13 in clear cell renal cell carcinoma (CCRCC) in human tissue and to use bioinformatics data to investigate the role of SPINK13 expression as a clinicopathological and prognostic biomarker for patients with CCRCC. MATERIAL AND METHODS Patients with CCRCC (N=533) with available RNA sequence data from The Cancer Genome Atlas (TCGA)-CCRCC database were analyzed with patients who had a tissue diagnosis of CCRCC (N=305) at the Fudan University Shanghai Cancer Center (FUSCC). Differential transcriptional and proteome expression profiles were obtained from the ONCOMINE cancer microarray database, TCGA, and the Human Protein Atlas (HPA) database. Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) measured SPINK13 mRNA expression in 305 samples of CCRCC tissue from the FUSCC. The effects of clinicopathological parameters on progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier and log-rank test. RESULTS Transcriptional and proteome expression of SPINK13 were significantly increased CCRCC tissue samples. Increased SPINK13 mRNA expression was significantly associated with reduced PFS and OS in 838 patients with CCRCC patients from the two independent cohorts, the FUSCC and the TCGA-CCRCC cohorts (p<0.01). Gene set enrichment analysis (GSEA) showed that SPINK13 expression was involved in complement, apical junction, epithelial-mesenchymal transition (EMT), glycolysis, hypoxia, and inflammation signaling pathways. CONCLUSIONS Increased expression of SPINK13 was associated with poor prognosis in patients with CCRCC.

13.
Radiat Oncol ; 14(1): 225, 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31831042

RESUMO

PURPOSE: The purpose of this study was to determine the associations between pathological complete remission (pCR) and clinical outcomes in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) who received preoperative radiotherapy or chemoradiotherapy in a phase 3 clinical study. METHODS: A total of 222 newly diagnostic stage III/IVM0 HNSCC patients were randomly assigned to a preoperative concurrent chemoradiotherapy group (n = 104) or preoperative radiotherapy alone group (n = 118). Over a mean follow-up of 59 months, 72 patients were defined as non-responders to preoperative therapy and subsequently underwent resection of the primary lesion with or without neck dissection. The relationship between the pathological tumor response of the primary lesion and treatment prognosis was analyzed. Kaplan-Meier and Cox regression multivariate analyses were performed to evaluate the impact of pCR on local control (LC), overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS). RESULTS: Among the 72 non-responders, 25 patients, 10 in the chemotherapy group and 15 in the radiotherapy group, achieved pCR. The 5-year LC, OS, PFS, and DMFS of pCR patients and non-pCR patients were 93.2% vs. 67.7% (p = 0.007), 83.3% vs. 39.7% (p = 0.0006), 76.1% vs. 44.0% (p = 0.009), and 90.4% vs. 56.3% (p = 0.005), respectively. In multivariate analysis, pCR is also an independent prognostic factor in prognosis, with statistically significant differences. CONCLUSION: pCR after preoperative radiotherapy or concurrent chemoradiotherapy is a good prognostic factor in locally advanced HNSCC. TRIAL REGISTRATION: Number:ChiCTR-TRC-114004322 Date:05 Mar, 2014.

14.
J Cell Biochem ; 2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31886567

RESUMO

Increasing evidence has shown that Rad50, a protein involved in the DNA damage repair process, significantly correlated with tumor prognosis. This study focused on Rad50 expression in tumor samples and its prognostic value for patients with prostate cancer (PCa). In this study, significantly elevated Rad50 expression in PCa tissues compared to normal tissues (P < .01). Five independent Oncomine databases validated significant differential expression of Rad50 (P < .001). Hence, 80 patients with PCa from Fudan University Shanghai Cancer Center (FUSCC) and 351 patients with PCa with available protein expression data from The Cancer Genome Atlas (TCGA) were included to investigate the survival benefit. Univariate and multivariate Cox regression analyses were performed to investigate the significance of clinicopathological factors on disease-free survival (DFS) and overall survival (OS). Kaplan-Meier analysis indicated that elevated Rad50 protein expression levels significantly correlated with unfavorable DFS (P = .005) in the FUSCC cohort and poorer OS (P = .04) in TCGA cohort. Furthermore, coregulation analysis of proteins indicated that 76 coregulated proteins were associated with Rad50, while 11 most highly involved hub proteins, including Rad50, MRE11A, DUT, POLR3A, MCM3AP, RECQL, PNPT1, RANBP3, DDX1, SNRPB, and UGN, were significantly coregulated in the protein-protein interaction network. Functional enrichment analysis consecutively indicated significant functions and signaling pathways including DNA replication, spliceosome, DNA geometric change, homologous recombination, and G2M checkpoint. This study first reveals that elevated Rad50 expression is significantly associated with aggressive progression and poor survival for patients with PCa. Together, these data suggest that Rad50 may act as an oncoprotein, guide the molecular diagnosis, and may shed light on novel individual therapeutic strategies for progressive PCa patients.

15.
Sci Rep ; 9(1): 20034, 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31882989

RESUMO

Resistance of cancer cells to chemotherapy is a significant clinical concern and mechanisms regulating cell death in cancer therapy, including apoptosis, autophagy or necrosis, have been extensively investigated over the last decade. Accordingly, the identification of medicinal compounds against chemoresistant cancer cells via new mechanism of action is highly desired. Autophagy is important in inducing cell death or survival in cancer therapy. Recently, novel autophagy activators isolated from natural products were shown to induce autophagic cell death in apoptosis-resistant cancer cells in a calcium-dependent manner. Therefore, enhancement of autophagy may serve as additional therapeutic strategy against these resistant cancers. By computational docking analysis, biochemical assays, and advanced live-cell imaging, we identified that neferine, a natural alkaloid from Nelumbo nucifera, induces autophagy by activating the ryanodine receptor and calcium release. With well-known apoptotic agents, such as staurosporine, taxol, doxorubicin, cisplatin and etoposide, utilized as controls, neferine was shown to induce autophagic cell death in a panel of cancer cells, including apoptosis-defective and -resistant cancer cells or isogenic cancer cells, via calcium mobilization through the activation of ryanodine receptor and Ulk-1-PERK and AMPK-mTOR signaling cascades. Taken together, this study provides insights into the cytotoxic mechanism of neferine-induced autophagy through ryanodine receptor activation in resistant cancers.

16.
Aging (Albany NY) ; 11(24): 12057-12079, 2019 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-31850854

RESUMO

Clear cell renal cell carcinoma (ccRCC) is one of the most common cancers worldwide. Despite intense efforts to elucidate its pathogenesis, the molecular mechanisms and genetic characteristics of this cancer remain unknown. In this study, three expression profile data sets (GSE15641, GSE16441 and GSE66270) were integrated to identify candidate genes that could elucidate functional pathways in ccRCC. Expression data from 63 ccRCC tumors and 54 normal samples were pooled and analyzed. The GSE profiles shared 379 differentially expressed genes (DEGs), including 249 upregulated genes, and 130 downregulated genes. A protein-protein interaction network (PPI) was constructed and analyzed using STRING and Cytoscape. Functional and signaling pathways of the shared DEGs with significant p values were identified. Kaplan-Meier plots of integrated expression scores were used to analyze survival outcomes. These suggested that FN1, ICAM1, CXCR4, TYROBP, EGF, CAV1, CCND1 and PECAM1/CD31 were independent prognostic factors in ccRCC. Finally, to investigate early events in renal cancer, we screened for the hub genes CCND1 and PECAM1/CD31. In summary, integrated bioinformatics analysis identified candidate DEGs and pathways in ccRCC that could improve our understanding of the causes and underlying molecular events of ccRCC. These candidate genes and pathways could be therapeutic targets for ccRCC.

17.
J Transl Med ; 17(1): 363, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31703694

RESUMO

BACKGROUND: Growing evidence has demonstrated immune reactivity as a confirmed important carcinogenesis and therapy efficacy for clear cell renal cell carcinoma (ccRCC). Aquaporin 9 (AQP9) is involved in many immune-related signals; however, its role in ccRCC remains to be elucidated. This study investigated AQP9 expression in tumor tissues and defined the prognostic value in ccRCC patients. METHODS: A total of 913 ccRCC patients with available RNA-sequence data from the Cancer Genome Atlas (TCGA) database and Fudan University Shanghai Cancer Center (FUSCC) were consecutively recruited in analyses. Differential transcriptional and proteome expression profiles were obtained and validated using multiple datasets. A partial likelihood test from Cox regression analysis was developed to address the influence of independent factors on progression-free survival (PFS) and overall survival (OS). The Kaplan-Meier method and log-rank test were performed to assess survival. Receiver operating characteristic (ROC) curves were used to describe binary classifier value of AQP9 using area under the curve (AUC) score. Functional enrichment analyses and immune infiltration analysis were used to describe significantly involved hallmark pathways of hub genes. RESULTS: Significantly elevated transcriptional and proteomic AQP9 expressions were found in ccRCC samples. Increased AQP9 mRNA expression was significantly associated with advanced clinicopathological parameters and correlated with shorter PFS and OS in TCGA and FUSCC cohorts (p < 0.001). ROC curves suggested the significant diagnostic and prognostic ability of AQP9 (PFS, AUC = 0.823; OS, AUC = 0.828). Functional annotations indicated that AQP9 is involved in the most significant hallmarks including complement, coagulation, IL6/JAK-STAT3, inflammatory response and TNF-alpha signaling pathways. CONCLUSION: Our study revealed that elevated AQP9 expression was significantly correlated with aggressive progression, poor survival and immune infiltrations in ccRCC patients, and we validated its prognostic value in a real-world cohort. These data suggest that AQP9 may act as an oncogene and a promising prognostic marker in ccRCC.

18.
Medicine (Baltimore) ; 98(44): e17663, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689778

RESUMO

RATIONALE: Postoperative delirium is extremely rare in young women and in minimally invasive endoscopic surgeries in gynecology and obstetrics. It greatly affects both physicians and patients. This report presents a special case of postoperative delirium after hysteroscopy in a young woman and a literature review of the associated etiology, diagnosis, and treatment. PATIENT CONCERNS: A 39-year-old woman was admitted to the gynecology ward following irregular vaginal bleeding for 3 months and an intrauterine space-occupying lesion for 1 week. Hysteroscopy, endometrial polypectomy, and fractional curettage procedures were successfully performed; however, the patient became unresponsive after surgery. DIAGNOSIS: Postoperative delirium. INTERVENTIONS: Sedatives and vasoactive medicines, such as dexmedetomidine, midazolam, and dopamine were administered for maintenance treatment. OUTCOMES: The patients gradually regained consciousness. LESSONS: Physicians should attach importance and improvise effective clinical management strategies for postoperative delirium based on clinical specialty characteristics and related guidelines.


Assuntos
Delírio do Despertar/etiologia , Histeroscopia/efeitos adversos , Adulto , Feminino , Humanos
19.
Med Sci Monit ; 25: 8984-8994, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31769434

RESUMO

BACKGROUND This study aimed to evaluate the factors associated with a survival benefit for patients with metastatic renal cell carcinoma (mRCC) treated with sunitinib, with and without cytoreductive nephrectomy (CN). MATERIAL AND METHODS This retrospective clinical study included 118 patients with mRCC who were treated with CN and sunitinib (CN-sunitinib) (N=70) and with sunitinib-alone (N=48). Categorical clinicopathological variables were compared with hypothesis tests using contingency tables and a chi-squared test. Independent indicators for progression-free survival (PFS) and overall survival (OS) were analyzed with univariate and multivariate Cox regression models. The Kaplan-Meier method and log-rank test were used to evaluate patient survival. RESULTS The median PFS and OS for the 118 patients were 8.38 and 15.48 months, respectively. There were no significant differences between the CN-sunitinib group and the sunitinib-alone group for either PFS (7.2 months vs. 11.6 months; P=0.525) or OS (16.7 months vs. 15.2 months; P=0.839). Stratification of patients based on clinicopathological characteristics showed that CN was significantly associated with reduced PFS and OS for patients with lymph node metastasis (PFS, P<0.001; OS, P<0.001) and high International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk scores (PFS, P=0.003; OS, P=0.011). However, CN was associated with a significant survival benefit for patients with low levels of serum C-reactive protein (CRP<10 mg/L) (PFS, P=0.026; OS, P=0.007). CONCLUSIONS Sunitinib-alone without CN improved the survival of patients with mRCC who had high IMDC risk scores or lymph node metastasis. CN and sunitinib resulted in significantly improved survival in patients with low serum CRP.

20.
Curr Med Sci ; 39(5): 825-830, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31612403

RESUMO

To explore the feasibility and superiority of iodine delivery rate (IDR) and tube voltage determined by patients' body mass index (BMI) in coronary CT angiography (CCTA), a total of 1567 patients undertaking CCTA during Feb. and Dec. 2016 were enrolled and divided into two groups. In the control group, the IDR and tube voltage were fixed, while in the experimental group, the IDR and tube voltage were determined by patients' BMI. The volume of iodinated contrast media (ICM), extravasation rate, extravasation volume, extravasation recovery interval, incidence rate of adverse reactions, effective dose (ED) and image quality of the two groups were compared. The experiments demonstrated that the ICM volume, extravasation rate, extravasation volume, extravasation recovery interval, incidence of adverse reactions and ED were lower or shorter in the experimental group than in the control group, and the differences were statistically significant (all P<0.05). However, there were no significant differences in the mean CT value, image noise, signal to noise ratio and contrast to noise ratio between the two groups (all P<0.05), which were consistent with the diagnosticians' subjective evaluation outcomes. Our findings suggested that in CCTA, it is feasible to determine the IDR and tube voltage based on patients' BMI; low tube voltage and IDR are superior to the fixed tube voltage and IDR and are worthy of clinical promotion.


Assuntos
Angiografia por Tomografia Computadorizada/métodos , Meios de Contraste/farmacocinética , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Extravasamento de Materiais Terapêuticos e Diagnósticos/diagnóstico por imagem , Iodo/farmacocinética , Índice de Massa Corporal , Doença da Artéria Coronariana/sangue , Extravasamento de Materiais Terapêuticos e Diagnósticos/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão Sinal-Ruído
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