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1.
Cancer Med ; 13(8): e7181, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38659376

RESUMO

BACKGROUND: Apatinib is an oral small-molecule tyrosine kinase inhibitor that blocks vascular endothelial growth factor receptor-2. Oral vinorelbine is a semisynthetic chemotherapeutic agent of vinorelbine alkaloids. Apatinib and oral vinorelbine have been proved to be effective in the treatment of metastatic breast cancer (mBC). At present, several small sample clinical trials have explored the efficacy of apatinib combined with oral vinorelbine in the treatment of mBC. METHODS: This retrospective study included 100 human epidermal growth factor receptor-2 (HER2)-negative mBC patients who received low-dose apatinib (250 mg orally per day) plus oral vinorelbine until disease progression or intolerance during February 2017 and March 2023. The progression-free survival (PFS), overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), disease control rate (DCR), and safety were analyzed by SPSS 26.0 software and GraphPad Prism 8 software. Cox proportional hazards regression model for univariate and multivariate was used to identify factors significantly related to PFS and OS. RESULTS: The median follow-up time for this study was 38.1 months. Among 100 patients with HER2-negative mBC, 66 were hormone receptor (HR)-positive/HER2-negative and 34 were triple-negative breast cancer (TNBC). The median PFS and OS were 6.0 months (95% CI, 5.2-6.8 months) and 23.0 months (95% CI, 19.9-26.1 months). There were no statistical differences in PFS (p = 0.239) and OS (p = 0.762) between the HR-positive /HER2-negative and TNBC subgroups. The ORR, CBR, and DCR were 21.0%, 58.0%, and 78.0%, respectively. Ninety-five patients (95.0%) experienced varying grades of adverse events (AEs) and 38.0% of patients for Grades 3-4. The most common Grades 3-4 AEs that we observed were neutropenia (30.0%) and leukopenia (25.0%). CONCLUSION: Low-dose apatinib combined with oral vinorelbine demonstrates potential efficacy and well tolerated for pretreated HER2-negative mBC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama , Piridinas , Receptor ErbB-2 , Vinorelbina , Humanos , Feminino , Piridinas/administração & dosagem , Piridinas/efeitos adversos , Piridinas/uso terapêutico , Vinorelbina/administração & dosagem , Vinorelbina/uso terapêutico , Pessoa de Meia-Idade , Receptor ErbB-2/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Adulto , Estudos Retrospectivos , Idoso , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Administração Oral , Intervalo Livre de Progressão
2.
Front Oncol ; 13: 1122294, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37124484

RESUMO

Background: Anlotinib is a novel oral small-molecule tyrosine kinase inhibitor (TKI), which can inhibit angiogenesis. The purpose of this study was to evaluate the efficacy and safety of anlotinib combined with chemotherapy in patients with metastatic triple-negative breast cancer (TNBC). Methods: This phase II clinical trial included 40 patients with metastatic TNBC who had previously received anthracycline and/or taxane treatment. All patients received anlotinib combined with chemotherapy. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), disease control rate (DCR) and safety. Results: During May 1, 2019 and April 30, 2022, there were 40 patients enrolled in this study. The median PFS and median OS were 8.8 months (95% confidence interval [CI] 6.5-11.1 months) and 19.0 months (95% CI, 12.1-25.9 months), respectively. The ORR, CBR and DCR were 40.0% (16/40), 85.0% (34/40) and 95.0% (38/40), respectively. Cox univariate and multivariate analyses demonstrated that having more than 3 metastatic sites (p = 0.001; p = 0.020) was an independent and meaningful unfavorable prognostic factor for PFS. 37.5% of patients had grade 3 to 4 treatment-related adverse events (TRAEs). The grade 3 to 4 TRAEs included neutropenia (22.5%), leukopenia (20.0%), secondary hypertension (10.0%), hand-foot syndrome (5.0%), vomiting (5.0%), proteinuria (5.0%) and thrombocytopenia (2.5%). None of the patients withdrew from the study or died due to TRAEs. Conclusion: In this single-arm study, the treatment of metastatic TNBC with anlotinib combined with chemotherapy showed certain efficacy, and its toxicity was acceptable.

3.
Breast Cancer Res Treat ; 197(1): 93-101, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36309908

RESUMO

PURPOSE: A substantial need for effective and safe treatment options is still unmet for patients with heavily pre-treated human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). Herein, we assessed the efficacy and safety of pyrotinib plus trastuzumab and chemotherapy in patients with heavily treated HER2-positive MBC. METHODS: In this single-arm exploratory phase II trial, patients with HER2-positive MBC previously treated with trastuzumab plus lapatinib or pertuzumab, received pyrotinib plus trastuzumab and chemotherapy. The primary end point was progression-free survival (PFS) in the total population (TP). Secondary end points included PFS in the subgroup with brain metastases (Sub-BrM), confirmed objective response rate (ORR), clinical benefit rate (CBR), disease control rate (DCR), exploration of predictive factors of PFS, and safety. RESULTS: Between November 1, 2018, and March 31, 2021, 40 patients were eligible for this study. The median PFS reached 7.5 months (95% confidence interval [CI] 4.7 to 9.9 months) and 9.4 months (95% CI 6.6 to 12.1 months) in the TP and Sub-BrM, respectively. ORR was 50.5% (20/40). CBR was 75.5% (30/40) and DCR reached 97.5% (39/40). Cox univariate and multivariate analyses demonstrated that liver or/and lung metastases was the significant adverse prognostic factor for PFS (p = 0.018; p = 0.026; respectively). The most frequent grade 3 or 4 treatment-related adverse events were diarrhea, neutropenia and leukopenia. No new safety signals were observed. CONCLUSION: Pyrotinib plus trastuzumab and chemotherapy offered a promising option with manageable safety profile for heavily pre-treated HER2-positive MBC, especially for those without liver or/and lung metastases.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Trastuzumab , Neoplasias da Mama/patologia , Receptor ErbB-2/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
4.
Cancer Lett ; 551: 215944, 2022 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-36209974

RESUMO

Poly ADP-ribose polymerase inhibitor (PARPi) treatment is effective in triple-negative breast cancer (TNBC) with BRCA mutation. However, its efficacy in BRCA-proficient TNBC remains unexplored. It is, therefore, an exciting proposition to broaden the indication of PARPi for BRCA-proficient TNBC patients. Chemokine receptor (CXCR4) is a transmembrane G protein-coupled receptor, which is involved in cell migration, proliferation, apoptosis, and damage repair, and it initiates many signalling pathways. Although administration of CXCR4 inhibitor alone is not ideal as a target drug, it can play a strong synergistic role in combination with other drugs. We explored the effect of CXCR4 and PARP1 on tumour cell proliferation, migration, metastasis, and apoptosis in vitro and in vivo and found that a CXCR4 inhibitor, AMD3100, enhanced the anti-tumour effect of PARP1 inhibitor, olaparib, on BRCA-proficient TNBC. When CXCR4 was inhibited and silenced, DNA damage repair and DNA replication fork activity were suppressed by up-regulating caspase-3-mediated increase in PARP1 cleavage; in combination with the inhibition of PARP1, AMD3100 resulted in the accumulation of fatal DNA damage and induction of apoptosis. This combination regimen can be effective against BRCA-proficient TNBC.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto , Ftalazinas/farmacologia , Ftalazinas/uso terapêutico , Dano ao DNA , Linhagem Celular Tumoral , Poli(ADP-Ribose) Polimerase-1/genética , Receptores CXCR4/genética
5.
J Int Med Res ; 50(7): 3000605221090097, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35899681

RESUMO

The efficacy and tolerability of eribulin mesylate, a synthetic halichondrin B analog, in patients with metastatic breast cancer (MBC) previously treated with anthracyclines and taxanes have been established. Acute-on-chronic liver failure (ACLF) is a clinical syndrome manifesting as acute and severe hepatic derangement resulting from varied insults in patients with established chronic liver disease or cirrhosis who did not previously receive eribulin. A middle-aged woman diagnosed with MBC and diffuse liver metastases who was pretreated with multi-line chemotherapy received eribulin as eighth-line chemotherapy and presented with hepatic encephalopathy, rapid bilirubin elevation, and significant coagulation dysfunction on day 4 in cycle 1. The patient was diagnosed with ACLF induced by eribulin. Therefore, ACLF may be a lethal and rare adverse event when patients with chronic liver metastases receive eribulin treatment, and clinicians' awareness should be increased for optimal prevention and prompt diagnosis and treatment.


Assuntos
Insuficiência Hepática Crônica Agudizada , Antineoplásicos , Neoplasias da Mama , Neoplasias Hepáticas , Antineoplásicos/efeitos adversos , Neoplasias da Mama/complicações , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Feminino , Furanos , Humanos , Cetonas , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Pessoa de Meia-Idade , Resultado do Tratamento
6.
Cancer Lett ; 545: 215827, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35842018

RESUMO

The endothelium is the critical barrier that controls transendothelial communications. Blood vessels in cancer tissue are poorly developed and highly permeable. However, it is poorly understood how circulating cancer cells released through these "leaky" vessels break the intact vasculature of remote organs to metastasize. We investigated the roles of cancer cell-derived extracellular vesicles (CEVs) in regulating cancer metastasis by analyzing samples from gastric cancer patients, performing in vitro experiments, and studying mouse models. We made several novel observations. First, the rate of metastasis was closely associated with plasma levels of CEVs in patients with gastric cancer. Second, cultured endothelial cells endocytosed CEVs, resulting in cytoskeletal rearrangement, low expression of the junction proteins cadherin and CD31, and forming large intercellular gaps to allow the transendothelial migration of cancer cells. The dynamin inhibitor Dynasore prevented these CEV-induced changes of endothelial cells by blocking CEVs endocytosis. Third, CEVs disrupted the endothelial barrier of cancer-bearing mice to promote cancer metastasis. Finally, lactadherin promoted the clearance of circulating CEVs to reduce metastasis. These results demonstrate the essential role of CEVs in promoting the metastasis of gastric cancer.


Assuntos
Vesículas Extracelulares , Neoplasias Gástricas , Animais , Caderinas/metabolismo , Células Endoteliais/metabolismo , Endotélio Vascular/metabolismo , Vesículas Extracelulares/metabolismo , Camundongos , Neoplasias Gástricas/patologia
7.
BMJ Open ; 11(8): e046515, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34344676

RESUMO

OBJECTIVES: The objective was to examine care willingness and demand of residents under 60 years of age after retirement. SETTING: The staged cluster sampling method was used between August and October 2018 in Dujiangyan, Sichuan Province, China. PARTICIPANTS: 2282 participants under 60 years of age were surveyed in 2018 by the staged cluster sampling method in China. PRIMARY AND SECONDARY OUTCOME MEASURES: The results of care willingness and demand were assessed by multiple comparisons of χ2 test and multivariable logistic regression. RESULTS: The respondents who preferred institution-based care, home-based care and community-based care accounted for 39.5%, 38.3% and 20.2% respectively, whereas only 2.1% preferred home-based self-care. The main reasons for the respondents to choose institution-based care included better medical care (31.9%), better daily care (27.0%), burden reduction for children (26.3%), better accommodation (22.8%), satisfied living environment (21.6%) and low consumption (12.3%). The factors that affected care willingness and demand included age, ethnicity, educational attainment, marital status, occupation and the current type of residence. CONCLUSIONS: The results revealed the care willingness and demand of residents under 60 years of age after retirement and relevant decision factors. This study provides a certain theoretical and practical significance for the development of the care willingness mode and promotes the cognition of policy-makers and researchers, and also provides the basis for decision-making.


Assuntos
Serviços de Assistência Domiciliar , Criança , China , Estudos Transversais , Humanos , Modelos Logísticos , Inquéritos e Questionários
8.
J Evid Based Complementary Altern Med ; 22(4): 883-891, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-29228810

RESUMO

Many studies have investigated the efficacy of Endostar combined with transcatheter arterial chemoembolization (TACE) versus TACE alone for hepatocellular carcinoma (HCC). A systematic review was conducted to evaluate the efficacy of Endostar. PubMed, Embase, and other databases were searched, and meta-analysis was performed using RevMan 5.3 software. Nine studies, all of which were clinical randomized controlled trials, involving 411 participants were included. The overall response rate, disease control rate and α-fetoprotein negative conversion ratio, and the 6- and 12-month survival rate of HCC patients treated with combined Endostar and TACE were higher than those treated with TACE alone ( P < .01). Furthermore, the incidence of tumor progression was low after Endostar treatment ( P = .005). The incidence of adverse effects (leukocytopenia, liver function damage, and vomiting) was similar in Endostar with TACE and in TACE alone ( P > .05). However, large studies and more randomized trials are necessary to determine the effects of Endostar on HCC.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Endostatinas/uso terapêutico , Neoplasias Hepáticas/terapia , Proteínas Recombinantes/uso terapêutico , Carcinoma Hepatocelular/mortalidade , Quimioembolização Terapêutica/efeitos adversos , Terapia Combinada , Endostatinas/efeitos adversos , Humanos , Neoplasias Hepáticas/mortalidade , Proteínas Recombinantes/efeitos adversos
9.
Sci Rep ; 7: 44543, 2017 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-28291253

RESUMO

The molecular mechanisms underlying colorectal cancer (CRC) development remain elusive. In this study, we examined the miRNA and mRNA expressions in the adenoma-carcinoma sequence (ACS), a critical neoplastic progression in CRC development. We found that miR-137 was down-regulated in all adenoma and carcinoma tissues. Low miR-137 levels were correlated negatively with tumor progression and metastasis. Then we identified the inhibition effect of the miR-137 in CRC development, both in CRC cell lines and mouse models. MiR-137 was shown to control CRC cell proliferation, colony formation, migration and invasion and to control tumor growth and metastasis. We further confirmed the negative association between miR-137 and c-Met expression and thus validated this important oncogene as the target of miR-137 in CRC. In addition, we found a DNA methyl-CpG-binding protein, Mecp2, was up-regulated in ACS tissues via mRNA sequencing. Further experiment showed that miR-137 expression in CRC was subjected to epigenetic regulation mediated by Mecp2. We also confirmed c-Met expression can be up-regulated by silencing of miR-137 and suppressed by coexpression of Mecp2 and miR-137. These findings highlight the critical role of miR-137-c-Met nexus in CRC development and reveal Mecp2-regulated epigenetic silence causes the downregulation of miR-137 in colorectal adenoma and carcinoma.


Assuntos
Neoplasias Colorretais/genética , Proteína 2 de Ligação a Metil-CpG/genética , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-met/genética , Adenoma/genética , Adenoma/patologia , Animais , Carcinoma/genética , Carcinoma/patologia , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Colorretais/patologia , Epigênese Genética , Regulação Neoplásica da Expressão Gênica/genética , Células HCT116 , Humanos , Camundongos , MicroRNAs/antagonistas & inibidores , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Metástase Neoplásica , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Chin J Cancer ; 36(1): 15, 2017 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-28103919

RESUMO

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a leading cause of cancer-related death, and new prognostic biomarkers are urgently needed. Apoptosis-stimulating P53-binding protein 1 (ASPP1) and 2 (ASPP2) have been reported to play important roles in the development, progression, metastasis, and prognosis of cancers, but their roles in ESCC have not been elucidated. In this study, we examined the expression of ASPP1 and ASPP2 in ESCC to evaluate their prognostic values. METHODS: The protein expression of ASPP1, ASPP2, and P53 in 175 specimens of ESCC was detected using immunohistochemical staining; their expression in cancerous and noncancerous tissues was scored according to the staining intensity and the percentage of stained cells. The associations of ASPP1, ASPP2, and P53 with clinicopathologic parameters, overall survival (OS), and disease-free survival (DFS) were analyzed. RESULTS: The protein expression levels of ASPP2 and P53 were significantly higher in cancerous tissues than in paired noncancerous tissues (P < 0.001), whereas the expression levels of ASPP1 in the two groups were similar. In ESCCs, ASPP1 expression was significantly associated with histological differentiation (P = 0.002) and invasive depth (P = 0.014); ASPP2 expression was associated with age (P = 0.029) and histological differentiation (P < 0.001); and P53 expression was associated with age (P = 0.021) and tumor size (P = 0.040). No correlations were found between ASPP1, ASPP2, and P53 expression. Survival analysis revealed that high ASPP2 expression was significantly associated with increased 5-year OS (P = 0.001) and DFS rates (P = 0.010) and that high P53 expression was significantly associated with a reduced 5-year DFS rate of ESCC patients (P = 0.015). Multivariate Cox analysis indicated that ASPP2 was an independent predictor of OS [hazard ratio (HR): 0.541, 95% confidence interval (CI) 0.363-0.804] and DFS (HR: 0.599, 95% CI 0.404-0.888) of ESCC patients and that P53 was an independent predictor of DFS (HR: 2.161, 95% CI 1.100-4.245). CONCLUSIONS: ASPP1 might be involved in the progression of ESCC, and ASPP2 was a potential prognostic biomarker of ESCC and should be evaluated in future studies.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Carcinoma de Células Escamosas/metabolismo , Neoplasias Esofágicas/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Intervalo Livre de Doença , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Masculino , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Carga Tumoral
11.
Aging (Albany NY) ; 8(9): 2204-2221, 2016 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-27689360

RESUMO

Tripartite motif-containing 24 (TRIM24), a member of the transcription intermediary factor 1 family, is defined as a co-regulator with several nuclear receptors, such as RARα. TRIM24 has been reported to be involved in many cancers. In this study, we aimed to investigate the expression pattern and prognostic significance of TRIM24 and its relationship with RARα in esophageal squamous cell cancer (ESCC). Both mRNA and protein expression levels of TRIM24 were found to be significantly decreased in ESCC, as judged by qRT-PCR and western blot. Immunohistochemistry staining shows that the reduced TRIM24 protein is associated with lymph node metastasis (P=0.024), advance pathological TNM (pTNM) stage (P=0.046) and recurrence/metastasis (P=0.001). Upregulated TRIM24 protein predicts longer overall survival and disease-free survival (both P<0.001) and is an independent predictor for good prognosis (HR, 0.519; 95%CI, 0.341-0.788; P=0.002). TRIM24 expression has been proven remarkably to improve prediction of survival of pTNM stage in ESCC patients, especially in stage I and II. However, no significant relationship was found between TRIM24 and RARα expression levels. In conclusion, reduced TRIM24 protein is associated with poor survival in ESCC patients, suggesting TRIM24 protein is a potential prognostic biomarker for ESCC.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Proteínas de Transporte/metabolismo , Neoplasias Esofágicas/metabolismo , Regulação Neoplásica da Expressão Gênica/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/genética , Proteínas de Transporte/genética , Neoplasias Esofágicas/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptor alfa de Ácido Retinoico/genética , Receptor alfa de Ácido Retinoico/metabolismo , Análise de Sobrevida
12.
Apoptosis ; 21(4): 473-88, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26767845

RESUMO

Epirubicin (EPI) is widely used for triple negative breast cancer (TNBC), but a substantial number of patients develop EPI resistance that is associated with poor outcome. The underlying mechanism for EPI resistance remains poorly understood. We have developed and characterized an EPI-resistant (EPI-R) cell line from parental MDA-MB-231 cells. These EPI-R cells reached stable growth in the medium containing 8 µg/ml of EPI. They overexpressed P-glycoprotein (P-gp) and contained numerous autophagic vacuoles. The suppression of P-gp overexpression and/or autophagy restored the sensitivity of these EPI-R cells to EPI. We further show that autophagy conferred resistance to EPI on MDA cells by blocking the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-mediated pro-apoptotic signals. Together, these results reveal a synergistic role of P-gp, autophagy, and NF-κB pathways in the development of EPI resistance in TNBC cells. They also suggest that blocking the P-gp overexpression and autophagy may be an effective means of reducing EPI resistance.


Assuntos
Autofagia/fisiologia , Resistencia a Medicamentos Antineoplásicos/fisiologia , Epirubicina/farmacologia , NF-kappa B/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Subfamília B de Transportador de Cassetes de Ligação de ATP/biossíntese , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Apoptose , Proteína Beclina-1/genética , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Feminino , Humanos , Interferência de RNA , RNA Interferente Pequeno/genética , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Células Tumorais Cultivadas
13.
Chin J Integr Med ; 22(3): 214-8, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26129902

RESUMO

OBJECTIVE: To study the influence of Yanyankang powder on Th1/Th2 in rats with experimental autoimmune uveitis (EAU). METHODS: The EAU models were induced in Lewis rats by immunization with interphotoreceptor retinoid binding protein (IRBP) 1177-1191 in complete Freund's adjuvant. The rats were randomly divided into 3 groups: a model control group, a Yanyankang group, and a prednisone group, 9 rats in each group. The model control group was intervened with saline solution by gavage. The Yanyankang group was intervened with Yanyankang powder 4 g/(kg day) by gavage. The prednisone group were intervened with prednisone acetate tablets 5 mg/(kg d) by gavage. All groups were intervened after immunization once every 2 days for 18 days and monitored by slit-lamp biomicroscopy daily until day 18. The levels of gamma interferon (INF-γ) and interleukin-10 (IL-10) in the supernatants of T cells were determined by enzyme-linked immunosorbent assay. Polymerase chain reaction (PCR) technology was used for measuring Th1 and Th2 related cytokine mRNA expressions. RESULTS: Slighter intraocular inflammation was found in the Yanyankang group and the prednisone group than the control group. The levels of the IFN-γ and IL-10 in the supernatants of the spleen lymph node cells were 382.33±6.30, 155.87±4.46 µg/L in the Yanyankang group and 270.93±7.76, 265.32±11.88 µg/L in the prednisone group. Both had significant differences compared with the control group (941.53±8.59, 20.67±4.65 µg/L; =0.01). The PCR results showed the same tendency. CONCLUSION: Yanyankang powder showed favorable effects in the rats with EAU by influencing the function of Th1 and Th2 cells.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Células Th1/imunologia , Células Th2/imunologia , Uveíte/tratamento farmacológico , Uveíte/imunologia , Animais , Medicamentos de Ervas Chinesas/farmacologia , Olho/patologia , Feminino , Imunização , Inflamação/patologia , Interferon gama/genética , Interferon gama/metabolismo , Interleucina-10/genética , Interleucina-10/metabolismo , Linfonodos/efeitos dos fármacos , Linfonodos/metabolismo , Pós , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Endogâmicos Lew , Baço/metabolismo , Células Th1/efeitos dos fármacos , Células Th2/efeitos dos fármacos , Uveíte/genética
14.
Pharmacol Biochem Behav ; 135: 53-9, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26013850

RESUMO

Chronic cerebral hypoperfusion (CCH) has been commonly associated with Alzheimer's disease and other types of dementia, but therapies that can improve cerebral blood flow displayed little effect on impaired cognition. Epigenetic intervention with histone deacetylase inhibitors, such as sodium butyrate (SB), on the other hand has been shown to improve cognition in several animal models of dementia. To investigate the effect of SB on cognitive impairment induced by CCH in rats, adult male SD rats were given intraperitoneal injections of SB at a daily dose of 840mg/kg for 4weeks, from the 29th day after permanent occlusion of bilateral common carotid arteries (2VO). Learning and memory were assessed by Morris water maze and novel object recognition. Following behavioral tests, western blotting of histone acetylation, of transcription factors, of neuronal/synaptic proteins, were performed using rat hippocampus and cortex. The data showed that SB treatment alleviated hippocampal dependent spatial learning disability in 2VO rats, and altered HDAC1/2 mRNA level, histone H4 acetylation and Nrf2 transcriptional activation in rat hippocampus. Accordingly, cognition-protective effect of SB appeared to be partially mediated by enhancing histone acetylation and hence by facilitating the transcription of Nrf2 downstream genes in the hippocampus. Thus, SB might be considered for putative treatment for CCH-related cognitive impairment.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/psicologia , Ácido Butírico/farmacologia , Ácido Butírico/uso terapêutico , Transtornos Cognitivos/tratamento farmacológico , Animais , Ácido Butírico/administração & dosagem , Estenose das Carótidas/psicologia , Histona Desacetilase 1/biossíntese , Histona Desacetilase 2/biossíntese , Histonas/metabolismo , Injeções Intraperitoneais , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Desempenho Psicomotor/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Reconhecimento Psicológico/efeitos dos fármacos
15.
J Surg Res ; 185(2): 638-44, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23941767

RESUMO

BACKGROUND: Many access devices have been developed for laparoendoscopic single-site surgery (LESS) during recent years. However, investigations are needed to determine which port is most suitable for this relatively new technique. The aim of this study was to evaluate commonly used ports using mechanical approaches in a training simulator. Any port that required less force and shorter surgery times had superior maneuverability. METHODS: The following three commercially available access devices were evaluated: Multi-ports, TriPort, and single-incision laparoscopic surgery (SILS) Port. A LESS mechanical evaluation platform was developed to investigate the forces that acted on the instruments in the ports while moving along horizontal and vertical axes. In addition, a strain-force measurement system was used to compare the average load on the ports when performing standard maneuvers. Additionally, the task completion time was recorded when the maneuvers in these ports were completed. RESULTS: During the horizontal displacement of the instrument, the traction forces of the Multi-ports were lower than those of the SILS Port, which were lower than those of the TriPort. The average traction forces were significantly different in pairwise multiple comparisons (P < 0.05). When the instrument was inserted into the ports, the vertical friction forces of the Multi-ports were the lowest and those of the TriPort were the highest. On extraction of the instrument, the friction forces of the Multi-ports remained the lowest, followed by those of the TriPort and SILS Port. There were statistically significant results among all the devices (P < 0.05). The average load required to perform the task was less for the SILS Port than that for the TriPort (P < 0.05). Similarly, the average load for the Multi-ports was significantly less than that for the TriPort (P < 0.001). The participants who used the Multi-ports had significantly faster task times than those who used the SILS Port or TriPort (P < 0.005). CONCLUSIONS: Compared with the TriPort and SILS Port, the Multi-ports was associated with the least average load and the shortest task performance times in a training simulator. This study demonstrates that the Multi-ports may offer superior maneuverability for LESS.


Assuntos
Endoscopia/instrumentação , Laparoscópios , Procedimentos Cirúrgicos Minimamente Invasivos/instrumentação , Abdome/cirurgia , Endoscopia/educação , Desenho de Equipamento , Fricção , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos/educação , Estresse Mecânico , Análise e Desempenho de Tarefas , Tração , Suporte de Carga
16.
Curr Neurovasc Res ; 9(3): 176-84, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22621232

RESUMO

Chronic cerebral hypoperfusion (CCH) has been gradually prevalent in the patients over middle age, especially the old over 60 years. It has been proved that CCH is highly related with cognitive impairment. CCH emerges not only in vascular dementia (VaD), but also in Alzheimer's disease (AD), which regarded as a critical causative for cognitive impairment in these diseases. Nevertheless, the mechanisms underlying cognitive deficit remain elusive. Moreover, there are no dramatically effective preventions. In the present study, by employing a recognized CCH rat model, we found that CCH induced spatial learning/memory deficits with simultaneously increasing tau hyperphosphorylation at multiple Alzheimer-related phosphorylation sites with activation of glycogen synthase kinase-3ß (GSK-3ß), Cyclin-dependent kinase (Cdk5), Calcium/calmodulin-dependent protein kinase II (CaMKII), and protein kinase B (Akt), and inhibition of protein phosphatase (PP) 2A (PP-2A). Interestingly, enriched environment (EE) treatment, an effect environment stimuli filled with various novel objects, could prevent rats from the EE-induced memory deficits and alterations of tau hyperphosphorylation. Our data suggested that EE might be potentially used for attenuating the detrimental cognition induced by CCH through regulating tau hyperphosphorylation.


Assuntos
Transtornos Cognitivos , Meio Ambiente , Hipóxia-Isquemia Encefálica/complicações , Hipóxia-Isquemia Encefálica/metabolismo , Proteínas tau/metabolismo , Animais , Encéfalo/patologia , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/metabolismo , Transtornos Cognitivos/prevenção & controle , Oclusão Coronária/complicações , Quinase 5 Dependente de Ciclina/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica/fisiologia , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Hipóxia-Isquemia Encefálica/etiologia , Sistema de Sinalização das MAP Quinases/fisiologia , Masculino , Aprendizagem em Labirinto/fisiologia , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Neurônios/fisiologia , Monoéster Fosfórico Hidrolases/metabolismo , Fosforilação/fisiologia , Ratos , Ratos Sprague-Dawley , Tempo de Reação
17.
Zhonghua Yi Xue Za Zhi ; 90(7): 447-50, 2010 Feb 23.
Artigo em Chinês | MEDLINE | ID: mdl-20368065

RESUMO

OBJECTIVE: To evaluate visual quality of patients implanted with the AcrySof IQ ReSTOR multifocal aspheric intraocular lens. METHOD: Retrospective study of patients who had implantation of an AcrySof IQ ReSTOR SN6AD3 IOL (Group test) or an AcrySof ReSTOR SN60D3 IOL (Group control). Group test comprised 30 patients (35 eyes) and Group control, 40 patients (56 eyes). Three months postoperatively, uncorrected and best corrected distance visual acuity, uncorrected and best corrected near visual acuity, best corrected intermediate visual acuity, the focus depth, higher order aberration, contrast sensitivity and glare sensitivity were measured in both IOL groups. Patients were orally administered a visual function questionnaire including questions about glare, halos, and other visual discomfort. RESULTS: The percentage of patients with uncorrected near, far and intermediate visual acuity > or = 0.5 in test group was 80% (20/35), 82.9% (29/35) and 45.7% (16/35) respectively, and that of the control group was 76.8% (43/56), 80.4% (45/56) and 39.3% (22/56) respectively. There was no statistical difference of uncorrected visual acuity between two groups (P > 0.05). When compare the best distance corrected near, far and intermediate visual acuity between two groups, we can get the same results (P > 0.05). The contrast sensitivity and glare sensitivity in all frequency sect of group test have been more obviously improved postoperatively than that of group control (P < 0.05). The Z(4, 0), Z(4, 2), S3 + S4 and total S of Zernike coefficients was statistically different (P < 0.05). The other Zernike coefficients and higher order aberration did not differ significantly between the two groups (P > 0.05). There were no statistical difference between two groups in focus depth (P > 0.05). Both groups had no serious glare. Though three eyes felt discomfort of halos in group control, only one eye felt the same phenomenon in group test. CONCLUSION: AcrySof IQ ReSTOR SN6AD3 intraocular lens has negative spherical aberration by an aspherical design in front surface, which makes it could counteract the positive spherical aberration of cornea. Consequently, IQ ReSTOR IOL gave good high-contrast visual acuity at distance, near and intermediate visual acuity.


Assuntos
Catarata/terapia , Lentes Intraoculares , Facoemulsificação , Visão Ocular , Idoso , Feminino , Humanos , Implante de Lente Intraocular , Masculino , Pessoa de Meia-Idade
18.
IEEE Trans Syst Man Cybern B Cybern ; 39(2): 489-502, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19095545

RESUMO

The multiagent optimization system (MAOS) is a nature-inspired method, which supports cooperative search by the self-organization of a group of compact agents situated in an environment with certain sharing public knowledge. Moreover, each agent in MAOS is an autonomous entity with personal declarative memory and behavioral components. In this paper, MAOS is refined for solving the traveling salesman problem (TSP), which is a classic hard computational problem. Based on a simplified MAOS version, in which each agent manipulates on extremely limited declarative knowledge, some simple and efficient components for solving TSP, including two improving heuristics based on a generalized edge assembly recombination, are implemented. Compared with metaheuristics in adaptive memory programming, MAOS is particularly suitable for supporting cooperative search. The experimental results on two TSP benchmark data sets show that MAOS is competitive as compared with some state-of-the-art algorithms, including the Lin-Kernighan-Helsgaun, IBGLK, PHGA, etc., although MAOS does not use any explicit local search during the runtime. The contributions of MAOS components are investigated. It indicates that certain clues can be positive for making suitable selections before time-consuming computation. More importantly, it shows that the cooperative search of agents can achieve an overall good performance with a macro rule in the switch mode, which deploys certain alternate search rules with the offline performance in negative correlations. Using simple alternate rules may prevent the high difficulty of seeking an omnipotent rule that is efficient for a large data set.

19.
Zhonghua Yan Ke Za Zhi ; 42(1): 37-41, 2006 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-16638279

RESUMO

OBJECTIVE: To evaluate the efficacy of 5-fluorouracil polyactic acid microsphere in prevention of proliferative vitreoretinopathy (PVR). METHODS: 5-fluorouracil polyactic acid microsphere or 5-fluorouracil were used to implant into rabbits vitreous cavity. 48 healthy rabbits were divided into 3 groups: rabbits in Group 1 received implantation of 5-fluorouracil polyactic acid microsphere; rabbits Group 2 served as polyactic acid microsphere control; rabbits in Group 3 received only 5-fluorouracil powder. Macrophages were injected into vitreous cavity of rabbit to induce PVR. 0.2 ml BSS containing 25 mg microsphere with 2.6 mg 5-fluorouracil was injected into vitreous cavity of two eyes in Group 1. 0.2 ml BSS containing 25 mg microsphere without medicine and 0.2 ml BSS containing 2.6 mg 5-fluorouracil were injected into rabbits vitreous cavity in Group 2 and 3 respectively, Drug content in aqueous humor was measured regularly. Release feature of 5-fluorouracil polyactic acid microsphere in vivo was observed. The efficacy of the inhibition of PVR was evaluated according to Ryan's grade of proliferative vitreoretinopathy. RESULTS: The releasing time of 5-fluorouracil polyactic acid microsphere was much longer than 5-fluorouracil powder. Its half life T(1/2) was 379.05 h with low clearance rate. The attack rate of retinal detachment in Group 2 was 62.5% and 71.9% on the 21st and 28th day respectively. The attack rate of retinal detachment in Group 3 was 64.3% and 78.6% whereas that of Group 1 was 13.3% and 13.3% on the 21st and 28th day. There was statistical difference in retinal detachment rate in Group 1 and 2 or 3 (P < 0.01). No differences was found in retinal detachment ration in Group 2 and 3 (P > 0.05). CONCLUSION: Implantation of 5-fluorouracil polyactic acid microsphere into vitreous cavity can effectively prevent proliferative vitreoretinopathy induced by macrophages in rabbit model.


Assuntos
Antimetabólitos/administração & dosagem , Fluoruracila/administração & dosagem , Lactatos/administração & dosagem , Vitreorretinopatia Proliferativa/tratamento farmacológico , Animais , Preparações de Ação Retardada , Microesferas , Coelhos , Corpo Vítreo
20.
Zhonghua Yan Ke Za Zhi ; 40(6): 385-8, 2004 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-15312603

RESUMO

OBJECTIVE: To study the results of using multifocal intraocular lens (MIOL) for the treatment of cataract. METHODS: After the small incision phacoemulsification, MIOL was inserted into the eye in 30 cases (36 eyes, test group); single-focal intraocular lens (SIOL) was inserted in 32 cases (40 eyes, control group). Visual acuity, focal depth, corneal astigmatism, contrast sensitivity, glare sensitivity, operative complications and untoward visual symptoms were observed. The follow-up period was 6.0 approximately 18.0 months. RESULTS: Percentage of patients with uncorrected near visual acuity 0.5 or better accounted was 80.6% (29/36) in the test group and 25.0% (10/40) in the control group, there was a significantly statistical difference between these two groups 6 months postoperatively (P < 0.05). There was no significantly statistical difference between the corrected near and far visual acuity and uncorrected far visual acuity of these two groups (P > 0.05). In patients with +1.00 - -1.00 D accommodation power, the percentage of patients with visual acuity 0.5 or better was 97.2% (35/36) in the test group and 97.5% (39/40) in the control group, there was no significantly difference between these two groups (P > 0.05). In patients with -1.50 D and -2.50 - -3.50 D accommodation power, the percentage of patients with visual acuity 0.5 or better was 97.2% (35/36) and 88.9% (32/36) in the test group, respectively; which was significantly greater than those in the control group [0.0% (0/40) and 0.0% (0/40), respectively] (P < 0.05). In patients with visual acuity 0.5 or better, the depth of focus was 4.50 D in 86.11% cases of the test group and was 2.00 D in 97.5% cases of the control group. There was no statistically significant difference between the preoperative corneal stigmatism and corneal astigmatism 1 week, 1 month, 3 months and 6 months after the operation in both groups (P > 0.05). Low frequency contrast sensitivity and glare sensitivity (28.49 +/- 6.45 and 16.97 +/- 4.40, respectively) in the test group were significantly lower than those of the control group (36.20 +/- 7.45 and 24.05 +/- 6.08, respectively) (P < 0.05). There was no significantly statistical difference in medium and high frequency contrast sensitivity and glare sensitivity between these two groups (P > 0.05). Two eyes needed Nd:YAG laser posterior capsulotomy in both groups. Two patients (5.6%) with unilateral MIOL complained glare at night. CONCLUSION: MIOL implantation is a safe and effective method for the treatment of cataract. MIOL has a distinct advantage in providing a full-distance visual acuity.


Assuntos
Lentes Intraoculares , Facoemulsificação , Feminino , Seguimentos , Humanos , Implante de Lente Intraocular , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Refração Ocular , Acuidade Visual
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