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1.
World J Clin Cases ; 10(1): 254-259, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-35071525

RESUMO

BACKGROUND: There has been no report to use camrelizumab with chemotherapy for advanced bladder cancer patients with positive programmed death-ligand 1 (PD-L1) expression and high tumor mutational burden (TMB). More effective predictors of bladder cancer immunotherapy have yet to be explored, and the combination of multiple factors may be more predictive than a single factor. CASE SUMMARY: We report the case of a 74-year-old male patient with recurrent metastatic bladder cancer, which demonstrated positive PD-L1 expression and high TMB. The immune checkpoint inhibitor camrelizumab was administered to the patient in combination with gemcitabine and cisplatin. The patient achieved a partial response with a progression-free survival of 11 mo. CONCLUSION: This is the first report to use camrelizumab with chemotherapy for advanced bladder cancer patients with positive PD-L1 expression and high TMB.

2.
J Asian Nat Prod Res ; : 1-17, 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34698619

RESUMO

The safety evaluation of timosaponin BII (TBII) in beagle dogs with toxicokinetic study was performed. For the acute oral toxicity study, the minimum lethal dose (MLD) of TBII was more than 2000 mg/kg and suggested the characteristics of absorption saturation. For the 28-day repeated dose oral toxicity and toxicokinetic studies, there was no significant effect on all test parameters except for prolonged APTT in the 60 and 180 mg/kg groups, which recovered after withdrawal. The increase of drug exposure of 180 mg/kg group was not proportional to the increase of administration dose, showing the characteristics of absorption saturation.

3.
Cell Death Discov ; 7(1): 224, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34455417

RESUMO

Hepatocellular carcinoma (HCC) is a heterogeneous tumor with an increased incidence worldwide accompanied by high mortality and dismal prognosis. Emerging evidence indicates that mesenchymal stem cells (MSCs)-derived exosomes possess protective effects against various human diseases by transporting microRNAs (miRNAs or miRs). We aimed to explore the role of exosomal miR-15a derived from MSCs and its related mechanisms in HCC. Exosomes were isolated from transduced MSCs and co-incubated with Hep3B and Huh7 cells. miR-15a expression was examined by RT-qPCR in HCC cells, MSCs, and secreted exosomes. CCK-8, transwell, and flow cytometry were used to detect the effects of miR-15a or spalt-like transcription factor 4 (SALL4) on cell proliferative, migrating, invasive, and apoptotic properties. A dual-luciferase reporter gene assay was performed to validate the predicted targeting relationship of miR-15a with SALL4. Finally, in vivo experiments in nude mice were implemented to assess the impact of exosome-delivered miR-15a on HCC. The exosomes from MSCs restrained HCC cell proliferative, migrating, and invasive potentials, and accelerated their apoptosis. miR-15a was expressed at low levels in HCC cells and could bind to SALL4, thus curtailing the proliferative, migrating, and invasive abilities of HCC cells. Exosomes successfully delivered miR-15a to HCC cells. Exosomal miR-15a depressed tumorigenicity and metastasis of HCC tumors in vivo. Overall, exosomal miR-15a from MSCs can downregulate SALL4 expression and thereby retard HCC development.

4.
J Integr Neurosci ; 18(1): 43-49, 2019 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-31091847

RESUMO

Hippocampal neurogenesis plays an important role in the onset and treatment of depressive disorders. Previous studies suggest that paeoniflorin could be used as an antidepressant for treating rats subjected to chronic unpredictable stress. In this study, the effects of paeoniflorin on neurogenesis in the hippocampus dentate gyrus and potential mechanism of action are further investigated in chronic unpredictable stress-induced rat. Results suggest that paeoniflorin markedly increased both sucrose consumption and the number of 5-bromo-2-deoxyuridine-positive cells in the dentate gyrus of chronic unpredictable stress-induced rats, and the ratio of co-expressed 5-bromo-2-deoxyuridine and glial fibrillary acidic protein-positive cells, but exerted no significant effect on the ratio of co-expressed 5-bromo-2-deoxyuridine and neuronal nuclei-positive cells. Compared with the vehicle group, a significant increase was detected in the number of brain-derived neurotrophic factor-positive cells and the expression of brain-derived neurotrophic factor mRNA in the hippocampus of the paeoniflorin-treated group. According to the results, paeoniflorin promoted neural stem cell proliferation, their differentiation into astrocytes, and neurogenesis in the hippocampal dentate gyrus of chronic unpredictable stress-induced rats. Apart from enhancing the protein expression and gene transcription of brain-derived neurotrophic factor, it also activated the expression of tropomyosin receptor kinase B (a high-affinity receptor of brain-derived neurotrophic factor). This suggests that paeoniflorin might promote neurogenesis in the hippocampus dentate gyrus of chronic unpredictable stress-induced rats and act as an antidepressant by regulating the brain-derived neurotrophic factor-tropomyosin receptor kinase B signaling pathway.


Assuntos
Antidepressivos/farmacologia , Giro Denteado/efeitos dos fármacos , Transtorno Depressivo/tratamento farmacológico , Glucosídeos/farmacologia , Monoterpenos/farmacologia , Neurogênese/efeitos dos fármacos , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Doença Crônica , Giro Denteado/fisiopatologia , Transtorno Depressivo/fisiopatologia , Modelos Animais de Doenças , Imipramina/farmacologia , Masculino , Neurogênese/fisiologia , RNA Mensageiro/metabolismo , Distribuição Aleatória , Ratos Sprague-Dawley , Receptor trkB/metabolismo , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/fisiopatologia , Incerteza
5.
Mol Cancer ; 18(1): 72, 2019 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-30940192

RESUMO

Following publication of the original article [1], the authors reported an error in affiliation 5.

6.
J Exp Clin Cancer Res ; 37(1): 252, 2018 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-30326936

RESUMO

BACKGROUND: There is increasing evidence that liver cancer stem cells (LCSCs) contribute to hepatocellular carcinoma (HCC) initiation and progression. MicroRNA (miRNA) plays a significant functional role by directly regulating respective targets in LCSCs-triggered HCC, however, little is known about the function of the miRNA-302 family in LCSCs. METHODS: MiRNAs microarray was used to detect the miRNAs involved in LCSCs maintenance and differentiation. Biological roles and the molecular mechanism of miRNA-302a/d and its target gene E2F7 were detected in HCC in vitro. The expression and correlation of miRNA-302a/d and E2F7 in HCC patients was evaluated by quantitative PCR and Kaplan-Meier survival analysis. RESULTS: We found that the miRNA-302 family was downregulated during the spheroid formation of HCC cells and patients with lower miRNA-302a/d expression had shorter overall survival (OS) and progression-free survival (PFS). Moreover, E2F7 was confirmed to be directly targeted and inhibited by miRNA-302a/d. Furthermore, concomitant low expression of miRNA-302a/d and high expression of E2F7 correlated with a shorter median OS and PFS in HCC patients. Cellular functional analysis demonstrated that miRNA-302a/d negatively regulates self-renewal capability and cell cycle entry of liver cancer stem cells via suppression of its target gene E2F7 and its downstream AKT/ß-catenin/CCND1 signaling pathway. CONCLUSIONS: Our data provide the first evidence that E2F7 is a direct target of miRNA-302a/d and miRNA-302a/d inhibits the stemness of LCSCs and proliferation of HCC cells by targeting the E2F7/AKT/ß-catenin/CCND1 signaling pathway.


Assuntos
Carcinoma Hepatocelular/patologia , Fator de Transcrição E2F7/metabolismo , Neoplasias Hepáticas/patologia , MicroRNAs/metabolismo , Células-Tronco Neoplásicas/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Ciclo Celular/fisiologia , Linhagem Celular Tumoral , Ciclina D1/metabolismo , Fator de Transcrição E2F7/biossíntese , Fator de Transcrição E2F7/genética , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Células-Tronco Neoplásicas/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Esferoides Celulares
7.
Mol Ther ; 26(12): 2751-2765, 2018 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-30301667

RESUMO

Increasing evidence indicates that tumor-initiating cells (TICs) are responsible for the occurrence, development, recurrence, and development of the drug resistance of cancer. MicroRNA (miRNA) plays a significant functional role by directly regulating targets of TIC-triggered non-small-cell lung cancer (NSCLC), but little is known about the function of the miR-30 family in TICs. In this study, we found the miR-30 family to be downregulated during the spheroid formation of NSCLC cells, and patients with lower miR-30a/c expression had shorter overall survival (OS) and progression-free survival (PFS). Moreover, transmembrane 4 super family member 1 (TM4SF1) was confirmed to be a direct target of miR-30a/c. Concomitant low expression of miR-30a/c and high expression of TM4SF1 correlated with a shorter median OS and PFS in NSCLC patients. miR-30a/c significantly inhibited stem-like characteristics in vitro and in vivo via suppression of its target gene TM4SF1, and then it inhibited the activity of the mTOR/AKT-signaling pathway. Thus, our data provide the first evidence that TM4SF1 is a direct target of miR-30a/c and miR-30a/c inhibits the stemness and proliferation of NSCLC cells by targeting TM4SF1, suggesting that miR-30a/c and TM4SF1 may be useful as tumor biomarkers for the diagnosis and treatment of NSCLC patients.


Assuntos
Antígenos de Superfície/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Transformação Celular Neoplásica/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , MicroRNAs/genética , Proteínas de Neoplasias/genética , Células-Tronco Neoplásicas/metabolismo , Regiões 3' não Traduzidas , Animais , Apoptose/genética , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Diferenciação Celular/genética , Linhagem Celular Tumoral , Modelos Animais de Doenças , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Camundongos , Família Multigênica , Oncogenes , Prognóstico , Interferência de RNA , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Mol Cancer ; 17(1): 139, 2018 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-30241526

RESUMO

BACKGROUND: Proteogenomic characterization and integrative and comparative genomic analysis provide a functional context to annotate genomic abnormalities with prognostic value. METHODS: Here, we analyzed the proteomes and performed whole exome and transcriptome sequencing and single nucleotide polymorphism array profiling for 2 sets of triplet samples comprised of normal colorectal tissue, primary CRC tissue, and synchronous matched liver metastatic tissue. RESULTS: We identified 112 CNV-mRNA-protein correlated molecules, including up-regulated COL1A2 and BGN associated with prognosis, and four strongest hot spots (chromosomes X, 7, 16 and 1) driving global mRNA abundance variation in CRC liver metastasis. Two sites (DMRTB1R202H and PARP4V458I) were revealed to frequent mutate only in the liver metastatic cohort and displayed dysregulated protein abundance. Moreover, we confirmed that the mutated peptide number has potential prognosis value and somatic variants displayed increased protein abundance, including high MYH9 and CCT6A expression, with clinical significance. CONCLUSIONS: Our proteogenomic characterization and integrative and comparative genomic analysis provides a new paradigm for understanding human colon and rectal cancer liver metastasis. TRIAL REGISTRATION: ClinicalTrials, NCT02917707. Registered 28 September 2016, https://clinicaltrials.gov/ct2/show/NCT02917707 .

9.
Oncol Lett ; 15(4): 4571-4577, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29541227

RESUMO

In order to examine the prognostic significance of miR-33a in patients with hepatocellular carcinoma (HCC), total RNA was extracted from 149 HCC biopsies, 36 of which were paired with para-carcinoma tissues, and miR-33a expression was measured by reverse transcription-quantitative polymerase chain reaction. The results demonstrated that miR-33a expression was decreased in HCC biopsies compared with normal liver tissue samples. It was also demonstrated that miR-33a expression was significantly associated with tumor foci number. Furthermore, overall and progression-free survival time was decreased in patients expressing low miR-33a with multiple tumor foci. Taken together, the low expression of miR-33a may be a potential risk factor for HCC.

10.
Oncotarget ; 8(57): 97304-97312, 2017 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-29228611

RESUMO

Glioblastoma multiforme (GBM), the most aggressive and lethal primary brain tumor, is characterized by very low life expectancy. Understanding the genomic and proteogenomic characteristics of GBM is essential for devising better therapeutic approaches.Here, we performed proteomic profiling of 8 GBM and paired normal brain tissues. In parallel, comprehensive integrative genomic analysis of GBM was performed in silico using mRNA microarray and sequencing data. Two whole transcript expression profiling cohorts were used - a set of 3 normal brain tissues and 22 glioma tissue samples and a cohort of 5 normal brain tissues and 49 glioma tissue samples. A validation cohort included 529 GBM patients from The Cancer Genome Atlas datasets. We identified 36 molecules commonly changed at the level of the gene and protein, including up-regulated TGFBI and NES and down-regulated SNCA and HSPA12A. Single amino acid variant analysis identified 200 proteins with high mutation rates in GBM samples. We further identified 14 differentially expressed genes with high-level protein modification, among which NES and TNC showed differential expression at the protein level. Moreover, higher expression of NES and TNC mRNAs correlated with shorter overall survival, suggesting that these genes constitute potential biomarkers for GBM.

11.
Mol Med Rep ; 16(1): 238-246, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28534972

RESUMO

Previous studies have suggested that dysregulation of microRNA (miR) -124a is associated with various types of human cancer. However, there are few studies reporting the level of miR­124a expression in non­small cell lung cancer (NSCLC). The present study investigated the association between miR­124a and NSCLC by analyzing the differential expression of miR­124a in NSCLC using the GEO database, as well as subsequently performing reverse transcription­quantitative polymerase chain reaction analysis on 160 NSCLC biopsies, 32 of which were paired with adjacent normal tissues. The results indicated that mir­124a expression levels were decreased in NSCLC tumor biopsies compared with adjacent normal tissues. The overall survival (OS) in patients with a high expression of miR­124a was prolonged relative to patients with low expression of miR­124a. The expression levels of miR­124a were associated with clinical characteristics, including lymph­node metastasis, tumor differentiation, tumor node metastasis (TNM) stage and diameter. Frequently, lymph­node metastasis, TNM stage, diameter and lack of chemotherapy have been associated with a worse prognosis in patients. In addition, the present study identified that high expression of miR­124awith chemotherapy may increase OS. In conclusion, the current study demonstrated that miR­124a was downregulated in NSCLC, and miR­124a was a potential prognostic tumor biomarker response to chemotherapy.


Assuntos
Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , MicroRNAs/genética , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/terapia , Linhagem Celular Tumoral , Biologia Computacional/métodos , Bases de Dados de Ácidos Nucleicos , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais
12.
Jpn J Clin Oncol ; 47(7): 590-596, 2017 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-28531325

RESUMO

Background: An increasing understanding of the genes and molecular pathways of glioblastoma multiforme (GBM) can provide us a useful insight for the development of more effective targeted therapeutic. Methods: To investigate the expression and clinical significance of miR-299 and its target genes in GBM, the expression levels of miR-299 and its target gene in human normal brain tissues and GBM were analyzed in silico using genes microarray and hierarchical clustering analysis followed by validation with quantitative RT-PCR. Results: Our results show that miR-299 is up-regulated in GBM patients. Moreover, patients with low miR-299 expression had longer overall survival (OS) compared with those with high miR-299 expression. RNA polymerase II elongation factor, ELL2, was identified as a miR-299 direct target. High expression of ELL2 together with miR-299 down-regulation correlated with a shorter median OS. Conclusions: Our results provide the first evidence that ELL2 is a direct target of miR-299 and increased ELL2 expression and down-regulation of miR-299 are associated with GBM progression and poor prognosis in patients, suggesting that ELL2 and miR-299 might have potential prognostic value and be used as tumor biomarkers for the diagnosis of patients with GBM.


Assuntos
Neoplasias Encefálicas/genética , Glioblastoma/genética , MicroRNAs/genética , Fatores de Elongação da Transcrição/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , MicroRNAs/biossíntese , MicroRNAs/metabolismo , Análise em Microsséries , Prognóstico , Fatores de Elongação da Transcrição/metabolismo , Transfecção , Regulação para Cima
13.
J Ethnopharmacol ; 192: 390-397, 2016 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-27616028

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: In-vitro cultured calculus bovis (ICCB) is a quality substitute for natural bezoar which is used for the therapeutic purpose of treating encephalopathy. ICCB has been authorized to use on clinic. The aim of the study is to evaluate the effects and the potential mechanisms of in-vitro cultured calculus bovis (ICCB) on learning and memory impairments of hyperlipemia vascular dementia (HVD) rats. MATERIALS AND METHODS: The HVD model was established by permanent occlusion of bilateral common carotid arteries based on hyperlipemia rats. Learning and memory abilities were evaluated by morris water maze test and shuttle box test. Ultraviolet-visible spectrophotometry (UV-vis) was employed to determine the SOD, MDA and NO in cerebral tissue, as well as the TG in serum. HE staining and toluidine blue staining were employed to evaluate cone cells damage in hippocampus CA1. An immunohistochemistry was used to measure the Bax and Bcl-2 expressions in cerebral tissue. RESULTS: Compared with control group, the abilities of spatial learning and memory and conditional memory were decreased significantly in HVD group (P<0.01, P<0.05). MDA content in cerebral tissue was remarkably increased while the SOD activity and NO content were both decreased (P<0.01). TG content in serum was increased remarkably (P<0.01). And the cone cells in hippocampus CA1 were damaged obviously. Compared with HVD group, ICCB treatment improved the abilities of learning and memory, elevated the SOD activity (P<0.01, P<0.05), reduced the MDA content (P<0.01) as well as the TG content in serum (P<0.01), increased the NO content (P<0.01), improved the damaged cone cells in hippocampus CA1, increased the number of cones cells (P<0.01), decreased the Bax expression, and increased the Bcl-2 expression (P<0.01). CONCLUSION: ICCB could improve the abilities of learning and memory in HVD rats. It might be related to anti-oxidative, regulation of Bax and Bcl-2 expressions, and the alleviation of cone cells damage.


Assuntos
Comportamento Animal/efeitos dos fármacos , Bezoares , Região CA1 Hipocampal/efeitos dos fármacos , Demência Vascular/tratamento farmacológico , Cálculos Biliares/química , Hiperlipidemias/complicações , Transtornos da Memória/tratamento farmacológico , Memória/efeitos dos fármacos , Nootrópicos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Aprendizagem da Esquiva/efeitos dos fármacos , Região CA1 Hipocampal/metabolismo , Região CA1 Hipocampal/patologia , Região CA1 Hipocampal/fisiopatologia , Estenose das Carótidas/complicações , Bovinos , Demência Vascular/sangue , Demência Vascular/etiologia , Demência Vascular/psicologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Hiperlipidemias/sangue , Masculino , Malondialdeído/metabolismo , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/sangue , Transtornos da Memória/etiologia , Transtornos da Memória/psicologia , Óxido Nítrico/metabolismo , Nootrópicos/isolamento & purificação , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo , Triglicerídeos/sangue , Proteína X Associada a bcl-2/metabolismo
14.
Int J Oncol ; 49(1): 217-24, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27176932

RESUMO

To investigate the expression and clinical significance of miR-181a and its target genes in glioblastoma multiforme (GBM), the expression levels of miR-181a and three target genes in human normal brain tissues and GBM were analyzed in silico using gene microarray, gene ontology, KEGG pathway and hierarchical clustering analysis followed by validation with quantitative RT-PCR. Our results show that miR-181a is down-regulated in GBM patients. The three target genes, ANGPT2, ARHGAP18 and LAMC1, are negatively correlated with the expression of miR-181a. Moreover, high expression of ANGPT2 or LAMC1 together with large size of GBM is correlated with a shorter median overall survival. In conclusion, our results showed that miR-181a and it targets ANGPT2 and LAMC1 might be predictors of prognosis in GBM patients.


Assuntos
Angiopoietina-2/biossíntese , Proteínas Ativadoras de GTPase/biossíntese , Glioblastoma/genética , Laminina/biossíntese , MicroRNAs/biossíntese , Adulto , Idoso , Angiopoietina-2/genética , Linhagem Celular Tumoral , Intervalo Livre de Doença , Feminino , Proteínas Ativadoras de GTPase/genética , Regulação Neoplásica da Expressão Gênica , Glioblastoma/patologia , Humanos , Estimativa de Kaplan-Meier , Laminina/genética , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Prognóstico
16.
Tumour Biol ; 36(1): 453-8, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25270739

RESUMO

Altered expression of prostate tumor overexpressed-1 (PTOV1) is observed in various types of human cancers. However, the role of PTOV1 in epithelial ovarian cancer (EOC) remains unclear. PTOV1 messenger (m)RNA expression in EOC patients was evaluated by quantitative real-time PCR (qRT-PCR). PTOV1 protein expression was also analyzed in archived paraffin-embedded EOC tissues using immunohistochemistry (IHC), and its association with overall survival of patients was analyzed by statistical analysis. Results from qRT-PCR analysis show that the expression level of PTOV1 mRNA was significantly higher in tumor tissues of EOC, compared to that in adjacent noncancerous tissues (P < 0.001). IHC staining showed that high expression of PTOV1 was detected in 57.2 % (87/152) of EOC cases. High expression of PTOV1 was significantly associated with pathological grade (P = 0.029) and clinical stage (P = 0.001). Moreover, the results of Kaplan-Meier analysis indicated that a high expression level of PTOV1 resulted in a significantly poor prognosis of EOC patients. Multivariate analysis showed that high expression of PTOV1 was an independent prognostic factor for overall survival (P < 0.001). In conclusion, PTOV1 protein abnormal expression might contribute to the malignant progression of EOC. High expression of PTOV1 predicts poor prognosis in patients with EOC.


Assuntos
Biomarcadores Tumorais/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias Epiteliais e Glandulares/metabolismo , Neoplasias Ovarianas/metabolismo , Biomarcadores Tumorais/genética , Carcinoma Epitelial do Ovário , Progressão da Doença , Feminino , Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Análise Multivariada , Proteínas de Neoplasias/genética , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/mortalidade , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Prognóstico , Modelos de Riscos Proporcionais
17.
Neurochem Int ; 74: 36-41, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24816193

RESUMO

A mouse model of depression has been recently developed by exogenous corticosterone administration. The present study aimed to examine the antidepressant-like effect and the possible mechanisms of piperine, a major alkaloid of black pepper (Piper nigrum Linn.) and long pepper (Piper longum Linn.), in corticosterone-induced depression in mice. The results showed that 3-weeks corticosterone injections caused depression-like behavior in mice, as indicated by the significant decrease in sucrose consumption and increase in immobility time in the forced swim test and tail suspension test. Moreover, it was found that brain-derived neurotrophic factor protein and mRNA levels in the hippocampus were significantly decreased in corticosterone-treated mice. Treating the animals with piperine significantly suppressed behavioral and biochemical changes induced by corticosterone. The results suggest that piperine produces an antidepressant-like effect in corticosterone-treated mice, which is possibly mediated by increasing brain-derived neurotrophic factor expression in the hippocampus.


Assuntos
Alcaloides/farmacologia , Comportamento Animal/efeitos dos fármacos , Benzodioxóis/farmacologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Corticosterona/farmacologia , Hipocampo/efeitos dos fármacos , Piperidinas/farmacologia , Alcamidas Poli-Insaturadas/farmacologia , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Corticosterona/antagonistas & inibidores , Hipocampo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , RNA Mensageiro/genética
18.
J Asian Nat Prod Res ; 16(4): 422-5, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24597721

RESUMO

A new ursane-type triterpene, cymosic acid (1) together with two known compounds, 3ß,19α-dihydroxy-2-oxo-12-ursen-28-oic acid (2) and 2α,19α-dihydroxy-3-oxo-12-ursen-28-oic acid (3), were isolated from Rosa cymosa Tratt. The structure of compound 1 was elucidated by analyzing its ¹H and ¹³C NMR, ¹H-¹H COSY, HSQC, HMBC, NOESY, and HR-ESI-MS values. The three compounds were found to display moderate inhibitory activities against nitric oxide production in lipopolysaccharide-activated macrophage cell lines, RAW 264.7 cells.


Assuntos
Medicamentos de Ervas Chinesas/isolamento & purificação , Rosa/química , Triterpenos/isolamento & purificação , Animais , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Camundongos , Estrutura Molecular , Óxido Nítrico/biossíntese , Ressonância Magnética Nuclear Biomolecular , Triterpenos/química , Triterpenos/farmacologia
19.
Cell Mol Neurobiol ; 34(3): 403-8, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24401942

RESUMO

Previous studies in our laboratory have demonstrated that piperine produced antidepressant-like action in various mouse models of behavioral despair, which was related to the serotonergic system. The present study aimed to examine the behavioral and biochemical effects of piperine in rats exposed to chronic unpredictable mild stress (CUMS). The results showed that CUMS caused depression-like behavior in rats, as indicated by the significant decrease in sucrose consumption and increase in immobility time in the forced swim test. In addition, it was found that serotonin (5-HT) and brain-derived neurotrophic factor (BDNF) contents in the hippocampus and frontal cortex were significantly decreased in CUMS-treated rats. Treating the animals with piperine significantly suppressed behavioral and biochemical changes induced by CUMS. The results suggest that piperine produces an antidepressant-like effect in CUMS-treated rats, which is possibly mediated by increasing 5-HT and BDNF contents in selective brain tissues.


Assuntos
Alcaloides/uso terapêutico , Antidepressivos/uso terapêutico , Benzodioxóis/uso terapêutico , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Piperidinas/uso terapêutico , Alcamidas Poli-Insaturadas/uso terapêutico , Serotonina/metabolismo , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/metabolismo , Animais , Doença Crônica , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Estresse Psicológico/psicologia
20.
Croat Med J ; 55(6): 638-46, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25559835

RESUMO

AIM: To explore the association of NFKB1 c.-798_-795delATTG (rs28362491), NFKBIA c.-949C>T (rs2233406), IL-8 c.-352A>T (rs4073), IL-10 c.-854T>C (rs1800871), TNF c.-418G>A (rs361525), and TNF c.-488G>A (rs1800629) polymorphisms with breast cancer risk in an East Chinese population. METHODS: We conducted a case-control study including 975 study participants (474 breast cancer patients and 501 female controls without cancer) and genotyped the polymorphisms employing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Logistic regression was used to assess the association of the polymorphisms with breast cancer risk. RESULTS: We found that the ins/del and del/del genotypes of NFKB1 polymorphism and TT genotype of IL-10 polymorphism significantly increased breast cancer risk (NFKB1 ins/del odds ratio [OR] 1.69, 95% [CI] 1.23-2.33, P=0.001; NFKB1 del/del OR 2.42, 95% CI 1.72-3.42, P<0.001; IL-10 TT OR 2.36, 95% CI 1.58-3.52, P<0.001). On the other hand, the TT genotype of IL-8 polymorphism, GA and AA genotypes of TNF c.-418G>A polymorphism, and GA genotype of TNF c.-488G>A polymorphism significantly reduced breast cancer risk (IL-8 TT OR 0.48, 95% CI 0.33-0.72, P<0.001; TNF c.-418 GA OR 0.58, 95% CI 0.41-0.80, P=0.001; TNF c.-418 AA OR 0.38, 95% CI 0.14-0.98, P=0.044; TNF c.-488 GA OR 0.68, 95% CI 0.48-0.96, P=0.029). When stratified by menopausal status, the CT genotype of NFKBIA polymorphism significantly reduced the risk among pre-menopausal women (OR 0.63, 95% CI 0.40-0.99, P=,043), but not among post-menopausal women. CONCLUSIONS: NFKB1, NFKBIA, IL-8, IL-10, and TNF polymorphisms could serve as useful predictive biomarkers for breast cancer risk among women in East China.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Predisposição Genética para Doença , Proteínas de Neoplasias/genética , Polimorfismo Genético , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Proteínas I-kappa B/genética , Interleucina-10/genética , Interleucina-8/genética , Pessoa de Meia-Idade , Inibidor de NF-kappaB alfa , Subunidade p50 de NF-kappa B/genética , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Fator de Necrose Tumoral alfa
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