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1.
Medicine (Baltimore) ; 103(14): e37642, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38579086

RESUMO

Pyroptosis is a programmed cell death, which has garnered increasing attention because it relates to the immune and therapy response. However, few studies focus on the application of pyroptosis-related genes (PRGs) in predicting osteosarcoma (OS) patients' prognoses. In this study, the gene expression and clinical information of OS patients were downloaded from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. Based on these PRGs and unsupervised clustering analysis, all OS samples can be classified into 2 clusters. The 8 key differential expressions for PRGs (LAG3, ITGAM, CCL2, TLR4, IL2RA, PTPRC, FCGR2B, and CD5) were established through the univariate Cox regression and utilized to calculate the risk score of all samples. According to the 8-gene signature, OS samples can be divided into high and low-risk groups and correlation analysis can be performed using immune cell infiltration and immune checkpoints. Finally, we developed a nomogram to improve the PRG-predictive model in clinical application. We verified the predictive performance using receiver operating characteristic (ROC) and calibration curves. There were significant differences in survival, immune cell infiltration and immune checkpoints between the low and high-risk groups. A nomogram was developed with clinical indicators and the risk scores were effective in predicting the prognosis of patients with OS. In this study, a prognostic model was constructed based on 8 PRGs were proved to be independent prognostic factors of OS and associated with tumor immune microenvironment. These 8 prognostic genes were involved in OS development and may serve as new targets for developing therapeutic drugs.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Humanos , Prognóstico , Piroptose , Nomogramas , Osteossarcoma/genética , Neoplasias Ósseas/genética , Microambiente Tumoral
2.
Int J Oncol ; 64(3)2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38275102

RESUMO

Increasing evidence suggests that pseudogenes play crucial roles in various cancers, yet their functions and regulatory mechanisms in glioma pathogenesis remain enigmatic. In the present study, a novel pseudogene was identified, UBDP1, which is significantly upregulated in glioblastoma and positively correlated with the expression of its parent gene, UBD. Additionally, high levels of these paired genes are linked with a poor prognosis for patients. In the present study, clinical samples were collected followed by various analyses including microarray for long non­coding RNAs, reverse transcription­quantitative PCR, fluorescence in situ hybridization and western blotting. Cell lines were authenticated and cultured then subjected to various assays for proliferation, migration, and invasion to investigate the molecular mechanisms. Bioinformatic tools identified miRNA targets, and luciferase reporter assays validated these interactions. A tumor xenograft model in mice was used for in vivo studies. In vitro and in vivo studies have demonstrated that UBDP1, localized in the cytoplasm, functions as a tumor­promoting factor influencing cell proliferation, migration, invasion and tumor growth. Mechanistic investigations have indicated that UBDP1 exerts its oncogenic effects by decoying miR­6072 from UBD mRNA, thus forming a competitive endogenous RNA network, which results in the enhanced oncogenic activity of UBD. The present findings offered new insights into the role of pseudogenes in glioma progression, suggesting that targeting the UBDP1/miR­6072/UBD network may serve as a potential therapeutic strategy for glioma patients.


Assuntos
Neoplasias Encefálicas , Glioma , MicroRNAs , RNA Longo não Codificante , Animais , Humanos , Camundongos , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Glioma/patologia , Hibridização in Situ Fluorescente , MicroRNAs/genética , MicroRNAs/metabolismo , Pseudogenes/genética , RNA Longo não Codificante/genética
4.
J Hematol Oncol ; 16(1): 121, 2023 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-38104104

RESUMO

Brain metastases signify a deleterious milestone in the progression of several advanced cancers, predominantly originating from lung, breast and melanoma malignancies, with a median survival timeframe nearing six months. Existing therapeutic regimens yield suboptimal outcomes; however, burgeoning insights into the tumor microenvironment, particularly the immunosuppressive milieu engendered by tumor-brain interplay, posit immunotherapy as a promising avenue for ameliorating brain metastases. In this review, we meticulously delineate the research advancements concerning the microenvironment of brain metastases, striving to elucidate the panorama of their onset and evolution. We encapsulate three emergent immunotherapeutic strategies, namely immune checkpoint inhibition, chimeric antigen receptor (CAR) T cell transplantation and glial cell-targeted immunoenhancement. We underscore the imperative of aligning immunotherapy development with in-depth understanding of the tumor microenvironment and engendering innovative delivery platforms. Moreover, the integration with established or avant-garde physical methodologies and localized applications warrants consideration in the prevailing therapeutic schema.


Assuntos
Neoplasias Encefálicas , Melanoma , Humanos , Microambiente Tumoral , Imunoterapia/métodos , Neoplasias Encefálicas/tratamento farmacológico , Melanoma/terapia , Encéfalo , Imunoterapia Adotiva/métodos
6.
Neurosurg Focus ; 54(6): E6, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37283401

RESUMO

OBJECTIVE: Language-related networks have been recognized in functional maintenance, which has also been considered the mechanism of plasticity and reorganization in patients with cerebral malignant tumors. However, the role of interhemispheric connections (ICs) in language restoration remains unclear at the network level. Navigated transcranial magnetic stimulation (nTMS) and diffusion tensor imaging fiber tracking data were used to identify language-eloquent regions and their corresponding subcortical structures, respectively. METHODS: Preoperative image-based IC networks and nTMS mapping data from 30 patients without preoperative and postoperative aphasia as the nonaphasia group, 30 patients with preoperative and postoperative aphasia as the glioma-induced aphasia (GIA) group, and 30 patients without preoperative aphasia but who developed aphasia after the operation as the surgery-related aphasia group were investigated using fully connected layer-based deep learning (FC-DL) analysis to weight ICs. RESULTS: GIA patients had more weighted ICs than the patients in the other groups. Weighted ICs between the left precuneus and right paracentral lobule, and between the left and right cuneus, were significantly different among these three groups. The FC-DL approach for modeling functional and structural connectivity was also tested for its potential to predict postoperative language levels, and both the achieved sensitivity and specificity were greater than 70%. Weighted IC was reorganized more in GIA patients to compensate for language loss. CONCLUSIONS: The authors' method offers a new perspective to investigate brain structural organization and predict functional prognosis.


Assuntos
Afasia , Neoplasias Encefálicas , Aprendizado Profundo , Glioma , Humanos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Imagem de Tensor de Difusão/métodos , Mapeamento Encefálico/métodos , Glioma/cirurgia , Estimulação Magnética Transcraniana/métodos , Idioma , Prognóstico , Afasia/diagnóstico por imagem , Afasia/etiologia
7.
Front Oncol ; 12: 841682, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35311152

RESUMO

Background: Here, we describe an innovative oncoplastic technique for small to medium volume breasts with a tumor in the lower quadrant and this technique could provide sufficient tissue to avoid visible defects after tumor removal and help reshape the natural shape of the breast. Methods: A detailed procedure for the folding flap technique is described step by step. Then, the results of a retrospective analysis of patients treated using this technique, including complications and disease recurrence rate, between January 2017 and November 2021 are reported. Aesthetic outcomes were evaluated on a 5-point scale proposed by the Paris Breast Center. Results: A total of 52 patients underwent surgery with the folding flap technique, The average operation time was 98.4 min (range, 75-120 min), and the mean bleeding volume was 56.5 mL (range, 20-100 mL). A margin-positive result was confirmed in 1 patient who underwent re-excision. Short-term postoperative complications were observed in 7 patients, including 4 with fat liquefaction, 2 with seroma, and 1 with skin redness and swelling. No flap necrosis was observed. The median follow-up time was 28.6 months (range, 9-58 months), and 2 patients experienced local recurrence. The mean aesthetic score was 4.7 points, with 36 patients scoring 5 points and 26 patients scoring 4 points, respectively. Conclusions: The folding flap technique, as an innovative and favorable oncoplastic technique for treating small- to medium-volume breasts with a tumor in the lower quadrant, could retain sufficient tissue to fill the residual cavity after the operation while improving the aesthetic outcome of the breast.

8.
Ann Transl Med ; 9(20): 1561, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34790767

RESUMO

BACKGROUND: Glioblastoma (GBM) is one of the most common and malignant primary brain tumors in adults, with high mortality rates and limited treatment. Based on bioinformatic analyses, this study aimed to identify biomarkers and relevant molecular pathways that may serve as potential targets for the treatment of GBM. METHODS: Expression profiles were downloaded from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database; nine GBM samples and three normal samples were extracted from the GSE104267 dataset. Differentially-expressed messenger RNA (mRNA) and long non-coding RNA (lncRNA) were screened from the preprocessed dataset. The clusterProfiler package in R was used to perform a biological process (BP) analysis of gene ontology (GO), and a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed separately in upregulated and downregulated groups. A competing endogenous RNA (ceRNA) network was constructed using Cytoscape. Based on data downloaded from The Cancer Genome Atlas (TCGA), Kaplan-Meier (K-M) survival curves were established. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to evaluate IL10RB antisense RNA 1 (IL10RB-AS1) expression in GBM tissue compared with that in normal brain tissue. RESULTS: A total of 253 differentially-expressed genes (DEGs) were obtained. Based on BP and KEGG enrichment annotation analyses, 11 lncRNA-related pathways were identified through function prediction analysis. A competing endogenous RNA (ceRNA) subnetwork, including 21 nodes and 29 regulatory pairs, was then constructed. Based on the clinical data of GBM in TCGA, one survival-related DEG, IL10RB-AS1, was identified using the log-rank statistical test. K-M survival curves of IL10RB-AS1 and expression levels of IL10RB-AS1 in both GBM and normal brain tissue were obtained. CONCLUSIONS: Through the combination of bioinformatic analyses, one survival-related differentially-expressed lncRNA, IL10RB-AS1, was identified. This, along with several related signaling pathways and ceRNA systems that were elucidated in GBM have potential prognostic value and might offer new possibilities for the treatment of GBM.

9.
Cancer Sci ; 112(8): 3150-3162, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34097336

RESUMO

Glioma is one of the most commonly diagnosed intracranial malignancies. The molecular mechanism underlying the development of glioma is still largely unknown. In this study, we present the first report concerning the function and mechanism of cyclin-dependent kinase-like 3 (CDKL3) in the development and prognosis of glioma. It is shown that CDKL3 was upregulated in glioma tissues and could independently predict poor prognosis of patients. Silencing CDKL3 in glioma cells could inhibit cell proliferation and migration and induce cell apoptosis and cell cycle arrest, whereas the overexpression of CDKL3 promoted cell proliferation. The in vivo experiments also indicated that knockdown of CDKL3 significantly suppressed tumor growth of glioma. Gene expression profiling of CDKL3 knockdown U87 cells identified RRM2 as a potential target of CDKL3, which was proved to have direct interaction with CDKL3. Given similar effects on glioma development with CDKL3, knockdown of RRM2 could rescue the effects of CDKL3 overexpression on glioma cells. Moreover, knockdown of CDKL3 or RRM2 suppressed the activity of JNK signaling, whereas CDKL3 overexpression produced the opposite effect. In conclusion, our results identified CDKL3 as a promotor for glioma, probably through the regulation of RRM2 and activation of the JNK signalling pathway, highlighting the significance of CDKL3 as a promising therapeutic target of glioma.


Assuntos
Neoplasias Encefálicas/patologia , Glioma/patologia , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Ribonucleosídeo Difosfato Redutase/genética , Regulação para Cima , Animais , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Glioma/genética , Glioma/metabolismo , Humanos , Sistema de Sinalização das MAP Quinases , Masculino , Camundongos , Transplante de Neoplasias , Prognóstico , Ribonucleosídeo Difosfato Redutase/metabolismo , Análise de Sobrevida
10.
J Int Med Res ; 48(10): 300060520924256, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33021413

RESUMO

OBJECTIVE: Patients receiving carbon-ion radiation therapy and astronauts exploring outer space are inevitably exposed to heavy ion radiation. The aim of this study was to develop radioprotectors to minimize the injuries induced by carbon ion radiation. METHODS: Heat-killed Salmonella Typhimurium (HKST) was administered to mice by gavage prior to irradiation with a 12C6+ heavy ion accelerator. Hematoxylin and eosin staining and immunofluorescence TdT-mediated dUTP Nick-End Labeling staining were used to assess the radioprotective effect of HKST on organ damage and levels of apoptosis, respectively, in mice. To investigate the mechanism underlying the radioprotective effect of HKST, levels of the pro-apoptotic proteins BAX and caspase 3 as well as interferon-regulatory factor (IRF) 3/7 in the femur, testis and intestine were assessed using immunofluorescence. RESULTS: Injuries induced by carbon ion radiation were significantly eased by pretreatment with HKST. Both apoptosis and high expression levels of pro-apoptotic proteins induced by heavy ion radiation were inhibited by HKST pretreatment. The radioprotective effect of HKST was associated with stimulation of Toll-like receptor signaling mediated by enhanced IRF3 and IRF7 signaling. CONCLUSION: HKST was an effective radioprotector alleviating damage to multiple organs caused by heavy ion radiation.


Assuntos
Temperatura Alta , Salmonella typhimurium , Animais , Apoptose , Carbono , Humanos , Masculino , Camundongos , Testículo
11.
Front Oncol ; 10: 634, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32547937

RESUMO

Objective: Surgical removal of anterior clinoidal meningiomas (ACMs) remains a challenge because of its complicated relationship with surrounding meninges, major arteries and cranial nerves. This study aims to define the meningeal structures around the anterior clinoid process (ACP) and its surgical implications. Methods: Five dry skulls and 19 cadavers were used in the anatomical study. Cadavers were prepared as transverse, coronal, and sagittal plastinated sections, and the meningeal architecture around the ACP was studied with dissecting and confocal microscopies. The database of meningiomas in one single center was retrospectively reviewed, and the patients with ACMs were collected for clinical analysis. Results: The superior, lateral, medial surfaces, and the tip of ACP were covered by different layers and types of meninges. The ACMs were classified into four main types based on the sites of origin, possible extending pathways following meningeal dura. In the retrospective cohort of 131 ACMs, the percentage of types I, IIa, IIb, III, and IV were 42.0% (55/131), 19.8% (26/131), 9.2% (12/131), 16.8% (22/131), and 12.2% (16/131), respectively. We found that types IIa and I had higher chances for achieving Simpson grade 1-2 resection (92.3 and 85.4%, respectively), followed by type III (54.5%) and type IV (31.3%), while type IIb showed little chance of Simpson grade 1-2 resection. Univariate and multivariate analyses revealed ACM classification and tumor size (<3 cm) to be independent risk factors for achieving more extensive resection. Conclusion: The meningeal architecture around the ACP may guide and determine the origin and extension of ACMs. The classification based on the meningeal architecture helps to understand surgical anatomy as well as predicting surgical outcomes.

12.
BMC Med Genet ; 21(1): 56, 2020 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-32188434

RESUMO

BACKGROUND: The prognosis of the glioblastoma (GBM) is dismal. This study aims to select an optimal RNA signature for prognostic prediction of GBM patients. METHODS: For the training set, the long non-coding RNA (lncRNA) and mRNA expression profiles of 151 patients were downloaded from the TCGA. Differentially expressed mRNAs (DEGs) and lncRNAs (DE-lncRNAs) were identified between good prognosis and bad prognosis patients. Optimal prognostic mRNAs and lncRNAs were selected respectively, by using univariate Cox proportional-hazards (PH) regression model and LASSO Cox-PH model. Subsequently, four prognostic scoring models were built based on expression levels or expression status of the selected prognostic lncRNAs or mRNAs, separately. Each prognostic model was applied to the training set and an independent validation set. Function analysis was used to uncover the biological roles of these prognostic DEGs between different risk groups classified by the mRNA-based signature. RESULTS: We obtained 261 DEGs and 33 DE-lncRNAs between good prognosis and bad prognosis patients. A panel of eight mRNAs and a combination of ten lncRNAs were determined as predictive RNAs by LASSO Cox-PH model. Among the four prognostic scoring models using the eight-mRNA signature or the ten-lncRNA signature, the one based on the expression levels of the eight mRNAs showed the greatest predictive power. The DEGs between different risk groups using the eight prognostic mRNAs were functionally involved in calcium signaling pathway, neuroactive ligand-receptor interaction pathway, and Wnt signaling pathway. CONCLUSION: The eight-mRNA signature has greater prognostic value than the ten-lncRNA-based signature for GBM patients based on bioinformatics analysis.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Encefálicas/diagnóstico , Glioblastoma/diagnóstico , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Transcriptoma , Adulto , Idoso , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidade , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Glioblastoma/genética , Glioblastoma/mortalidade , Humanos , Masculino , Análise em Microsséries , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes , Taxa de Sobrevida
13.
J Neurol Surg B Skull Base ; 80(Suppl 4): S358-S359, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31750061

RESUMO

Tumors located in the craniocervical junction region are significantly challenging for surgical resection. We shared our experience of a meningioma at craniocervical junction resected through far lateral approach in a 68-year-old female. The patient presented with intermittent headache with discomfort in the neck and shoulders for 3 years without any positive signs. Magnetic resonance imaging (MRI) revealed a tumor of 3.6 cm × 3.0 cm × 2.5 cm lying at the ventral side of medulla oblongata, with T1 hypointensity, T2 hyperintensity, and a significant enhancement on T1-contrast image. The far lateral approach on the right side was planned to resect the tumor with a park-bench position. The patient underwent a standard craniotomy using a lazy S -shaped incision. The transposition of vertebral artery was performed carefully therein, followed by removal of part of the arches of atlas and axis. After exposure of the tumor, vertebral artery (VA) and posterior inferior cerebellar artery (PICA) adhesive to the lesion could be seen operatively. Truncating the supplying blood vessels of the tumor was taken as the first step, followed by resecting the tumor mass in a piecemeal manner. While preserving VA, PICA, posterior nerves, medulla oblongata, and cervical cord, gross-total resection was achieved under the careful operation. The patient tolerated the procedure well without any neurological deficits. Histological examination confirmed the tumor as a meningioma (World Health Organization [WHO] grade I). Postoperative MRI scan depicted complete resection of the tumor. The patient remained symptom free without any evidence of recurrence during the follow-up period of 1 year. Informed consent was obtained from the patient. The link to the video can be found at: https://youtu.be/i9H-wS4fF10 .

14.
Onco Targets Ther ; 12: 4351-4357, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31213850

RESUMO

Background: Circ-SHPRH is a novel circular RNA which was down-regulated in various cancer tissues. Several recent studies hinted that circ-SHPRH might function as a diagnostic and prognostic biomarker for solid cancers. This meta-analysis was performed to determine the diagnostic and prognostic roles of circ-SHPRH for these solid cancers. Methods: Publications were searched in PubMed, MEDLINE, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang database. Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic curve (SROC) (AUC) with 95% confidence interval (95% CI) were calculated to evaluate the diagnostic value of circ-SHPRH. Pooled hazard ratio (HR) with 95% CI was applied to assess the prognostic value of circ-SHPRH. Results: Nine eligible studies, including 4 for diagnosis and 5 for prognosis, were included in this meta-analysis. Pooled sensitivity, specificity, PLR, NLR, DOR, and AUC were 0.79 (95% CI: 0.73-0.84), 0.75 (95% CI: 0.69-0.81), 3.20 (95% CI: 2.53-4.06), 0.28 (95% CI: 0.22-0.36), 11.27 (95% CI: 7.57-16.79), and 0.84 (95% CI: 0.80-0.87), respectively. Pooled HR indicated that low circ-SHPRH expression was significantly associated with poor overall survival (OS) (low vs high, HR=2.22, 95% CI: 1.60-3.09). Conclusion: The results of this meta-analysis indicate that circ-SHPRH might be an important diagnostic and prognostic biomarker for various solid cancers.

15.
Clin Neurol Neurosurg ; 171: 168-173, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29920451

RESUMO

OBJECTIVE: The aim of the present study is to investigate the expression profiles of circular RNAs (circRNAs) in IDH-wild type (IDH-wt) glioblastoma and explore the differences in circRNAs expression between IDH-wt glioblastoma and adjacent normal brain. PATIENTS AND METHODS: circRNA expression profiles were detected by circRNA microarray in three matched pairs of IDH-wt glioblastoma and adjacent normal brain. qRT-PCR was used to verify the differential expression of circRNAs from microarray analysis. Bioinformatics analysis was used to analyze potential functions of the differentially expressed circRNAs in IDH-wt glioblastoma. RESULTS: Compared with the adjacent normal brain tissues, 254 circRNAs were upregulated and 361 circRNAs were downregulated in IDH-wt glioblastoma with a ≥1.5-fold change. A total of 12 differentially expressed circRNAs were randomly selected and validated a good correlation of results from circRNA-seq with qRT-PCR. Gene Ontology (GO) analysis revealed the differentially expressed circRNAs possibly involved in cell division, DNA damage repair, cytoskeleton, and protein ubiquitination. 46 and 50 miRNAs were predicted to be adsorbed by the top 10 upregulated circRNAs and top 10 downregulated circRNAs, respectively. CONCLUSION: Differential expression of circRNAs may be associated with IDH-wt glioblastoma development and progression, and these circRNAs can be identified as biomarkers for prognosis prediction and targets for treatment.


Assuntos
Biomarcadores/sangue , Glioblastoma/genética , MicroRNAs/sangue , RNA/sangue , Idoso , Biologia Computacional/métodos , Regulação para Baixo , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , RNA Circular , RNA Mensageiro/metabolismo , Regulação para Cima
16.
Clin Neurol Neurosurg ; 169: 92-97, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29642043

RESUMO

OBJECTIVE: Cytoplasmic polyadenylation element binding protein 4 (CPEB4) is a regulator of gene expression at transcriptional level and has been reported to be associated with biological malignancy in cancers. However, little was known about the correlation between CPEB4 and glioblastoma cell proliferation and the prognostic significance in patients. Our aim was to investigate the functional role and prognostic value of CPEB4 in glioblastoma. PATIENTS AND METHODS: We determined the expression of CPEB4 protein using immunohistochemistry in tissue microarrays containing 278 glioma patients (including 98 primary glioblastomas) and evaluated its association with pathological grades and clinical outcome by univariate and multivariate analyses. And then, lentiviral-mediated RNAi targeting CPEB4 was utilized to study the role of CPEB4 in glioblastoma cell proliferation. RESULTS: In our cohort, CPEB4 expression was positively related to glioma pathological grade (p < 0.01) and elevated in glioblastoma (p < 0.01). High expression of CPEB4 was associated with significantly poor prognosis, and could be identified as an independent risk factor for overall survival (OS) and progression-free survival (PFS) of glioblastoma patients (hazard ratio (HR) = 1.730, p = 0.014 and HR = 1.877, p = 0.004, respectively). In vitro studies further showed that downregulation of CPEB4 significantly reduced the growth rate of T98G and U251 cells comparing with the controls. CONCLUSION: Our study indicated that increased expression of CPEB4 in primary glioblastoma is a novel biomarker for predicting poor outcome of patients and suppression of CPEB4 inhibit tumor cell proliferation, suggesting a potential therapeutic target for glioblastoma.


Assuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/metabolismo , Proliferação de Células/fisiologia , Glioblastoma/diagnóstico , Glioblastoma/metabolismo , Proteínas de Ligação a RNA/biossíntese , Idoso , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Estudos de Coortes , Feminino , Seguimentos , Glioblastoma/genética , Células HEK293 , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas de Ligação a RNA/genética , Taxa de Sobrevida/tendências , Resultado do Tratamento
17.
Stem Cell Res Ther ; 9(1): 101, 2018 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-29650044

RESUMO

BACKGROUND: White smoke inhalation (WSI) is an uncommon but potentially deadly cause of acute lung injury and acute respiratory distress syndrome for which no effective pharmaceutical treatment has been developed. This study aimed to determine the protective effects of human amnion-derived mesenchymal stem cells (hAMSCs) against WSI-induced lung injury in rats. METHODS: hAMSCs were injected into rats via the tail vein 4 h after WSI. At 1, 3, 7, 14, and 28 days after cell injection, hAMSCs labeled with PKH26 in lung, heart, liver, and kidney tissues were observed by fluorescence microscopy. The lung injury score was determined by hematoxylin and eosin staining. Lung fibrosis was assessed by Masson's trichrome staining. The computed tomography (CT) score was assessed by CT scanning. The wet/dry weight ratio was calculated. The levels of interleukin (IL)-1ß, IL-6, and IL-10 were determined by enzyme-linked immunosorbent assays. The expression of surfactant protein (SP)-A, SP-C, and SP-D was measured by Western blotting. RESULTS: The injected hAMSCs were primarily distributed in the lung tissues in WSI-induced rats. Compared with the model and phosphate-buffered saline (PBS) group, hAMSC treatment led to reduced lung injury, lung fibrosis, CT score, and inflammation levels in WSI-induced mice. hAMSC treatment also resulted in increased cell retention in the lung, partial pressure of oxygen (PaO2), and PaO2/fraction of inspired oxygen (FiO2) levels, and pulmonary SP-A, SP-C, and SP-D expression compared with that in the model and PBS group. CONCLUSIONS: hAMSCs are a potential cell-based therapy for WSI-induced lung injury.


Assuntos
Lesão Pulmonar/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Lesão por Inalação de Fumaça/terapia , Adulto , Âmnio/citologia , Animais , Células Cultivadas , Feminino , Humanos , Interleucinas/genética , Interleucinas/metabolismo , Pulmão/metabolismo , Pulmão/patologia , Células-Tronco Mesenquimais/citologia , Gravidez , Proteínas Associadas a Surfactantes Pulmonares/genética , Proteínas Associadas a Surfactantes Pulmonares/metabolismo , Ratos
18.
Clin Neurol Neurosurg ; 164: 132-137, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29223793

RESUMO

OBJECTIVE: G-protein-coupled receptors 65 (GPR65), identified as an acid-sensing receptor, is overexpressed in several malignancies and promote tumor development. Our aim was to investigate the expression and prognostic value of GPR65 in glioblastoma. MATERIALS AND METHODS: We determined the expression of GPR65 protein using immunohistochemistry in tissue microarrays containing 11 Grade I, 107 Grade II, 47 Grade III, and 102 Grade IV gliomas and 16 normal brains. Then we evaluated its association with pathological grades, prognosis, and recurrence. The Cancer Genome Atlas (TCGA) group (N=528) was further employed to examine transcriptional level of GPR65 in glioblastoma and the correlation between GPR65 expression and clinical outcome. RESULTS: In our cohort, GPR65 expression was positively related to glioma pathological grade (p<0.01) and elevated in glioblastoma (p<0.01). High expression of GPR65 was associated with significantly short overall survival (OS) (p=0.013) and progression-free survival (PFS) (p=0.029), and could be identified as an independent risk factor for OS of glioblastoma patients (Hazard Ratio [HR]=1.596, p=0.037). As an aiding evidence, increased GPR65 mRNA expression was also found in TCGA glioblastoma group (p<0.001) and its high level predicted a poor clinical outcome (OS, p=0.003; PFS, p=0.001). CONCLUSION: Our findings suggest that GPR65 is overexpressed in glioblastoma and its high expression predicts unfavorable clinical outcome for patients. Targeting GPR65 may serve as a potential therapy for treating glioblastoma.


Assuntos
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Regulação Neoplásica da Expressão Gênica , Glioblastoma/genética , Glioblastoma/patologia , Receptores Acoplados a Proteínas G/genética , Adulto , Neoplasias Encefálicas/metabolismo , Estudos de Coortes , Bases de Dados Genéticas/tendências , Feminino , Glioblastoma/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Receptores Acoplados a Proteínas G/biossíntese
19.
Int J Surg ; 42: 164-169, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28476543

RESUMO

BACKGROUND: According to previously studies, nosocomial infections (NIs) surveillance could effectively reduce infection rates. As NIs surveillance systems have been implemented in some hospitals for several years, their impact on NIs need to be explored. Therefore, the purpose of this review is to evaluate the tendency of NI rates during the surveillance period and the impact of surveillance on NI rates. METHODS: A systematic literature search of the PubMed database to identify papers that evaluated effect of surveillance on NIs, all kinds of NIs occurred during hospitalization or discharged were included. Exclude articles investigated the surveillance combined with other infection control measures. RESULTS: Twenty-five articles were included. NI rates had different levels of reduction during surveillance period, the reduction were not limited by state, department, surveillance system, and NI type. Continuous surveillance had a positive impact on NI, OR/RR were ranged from 0.43 to 0.95. CONCLUSION: Participation in NI surveillance is associated with reducing infection rates, though RCTs need to further prove the effective role of surveillance. Hospitals may consider to perform NIs surveillance systems according to its own conditions.


Assuntos
Infecção Hospitalar/epidemiologia , Humanos
20.
Biomed Res Int ; 2017: 3519745, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28393074

RESUMO

Our previous report revealed that immature dendritic cells (imDCs) with adenovirus-mediated CCR7 overexpression acquired an enhanced migratory ability but also exhibited the lower immune tolerance observed in more mature cells. In the present study, we aimed to investigate whether BTLA overexpression was sufficient to preserve immune tolerance in imDCs with exogenous CCR7 overexpression. Scanning electron microscopy and surface antigens analysis revealed that BTLA overexpression suppressed DC maturation, an effect further potentiated in CCR7 and BTLA cooverexpressing cells. Correspondingly, in vitro chemotaxis assays and mixed lymphocyte reactions demonstrated increased migratory potential and immune tolerance in CCR7 and BTLA coexpressing cells. Furthermore, CCR7 and BTLA cooverexpressed imDCs suppressed IFN-γ and IL-17 expression and promoted IL-4 and TGF-beta expression of lymphocyte, indicating an increase of T helper 2 (Th2) regulatory T cell (Treg). Thus, these data indicate that CCR7 and BTLA cooverexpression imparts an intermediate immune phenotype in imDCs when compared to that in CCR7- or BTLA-expressing counterparts that show a more immunocompetent or immunotolerant phenotype, respectively. All these results indicated that adenovirus-mediated CCR7 and BTLA overexpression could enhance immune tolerance and migration of imDCs. Our study provides a basis for further studies on imDCs in immune tolerance, with the goal of developing effective cellular immunotherapies for transplant recipients.


Assuntos
Células Dendríticas/imunologia , Tolerância Imunológica , Receptores CCR7/biossíntese , Receptores Imunológicos/biossíntese , Adenoviridae/genética , Animais , Movimento Celular/imunologia , Células Dendríticas/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Receptores CCR7/genética , Receptores Imunológicos/genética , Linfócitos T Reguladores/imunologia
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