RESUMO
The dry root of Astragalus mongholicus has therapeutic effects such as tonifing the middle - jiao, replenishing qi, solidifing the surface, promoting diuresis, dispelling sepsis outwards and nourishing muscle. There are some slices having black spots after slicing the root of astragalus. The diversity of endophytic fungi between slices with black spots and normal slices was analysed in this paper. The endophytic fungal sequences obtained by high-throughput sequencing were 298,044 and 297,396, and the 116 OTU subsets obtained after clustering belonged to 3 phyla, 9 classes, 22 orders, 38 families and 46 genera. The dominant classes were Eurotiomycetes and Leotiomycetes. The dominant order is Eurotiales and Helotiales. The dominant families are Helotiales_fam_Incertae_sedis and Aspergillaceae. The dominant genera are Cadophora and Aspergillus. There are some peculiar fungal flora in both normal slices and spotted slices. The study on endophytic fungi diversity of astragalus slices will provide some help for drug development of this plant.
Assuntos
Astragalus propinquus , Plantas , Aspergillus , Fungos/genética , HumanosRESUMO
PURPOSE: BRCA2 defect exists in glioma and regulates drug resistance of glioma to chemotherapy. However, its role in medulloblastoma and the mechanism is not known. To investigate the effects of BRCA2 deficiency combined with Olaparib in medulloblastoma and the mechanism. METHODS: BRCA2 was knocked down by RNAi technology and cell proliferation was detected by CCK-8 assay. Cell apoptosis was determined by FACS analysis when the in vivo role of BRCA2 was explored with xenograft mice model. Western blotting technology was used to explore the mechanism of BRCA2. RESULTS: Knockdown of BRCA2 enhanced the inhibitory effect of Olaparib on proliferation of Daoy and LN229 cells. The inhibition rate of Olaparib on Daoy or LN229 cells was 61.1%, 66.03% in shBRCA2 group, while it was 42.9%, 41.1% in shNC group. Overexpression of RAD51 partially reversed the effect of shBRCA2. In Daoy cells, apoptotic rate was 26.9% in Olaparib group and 58.9% in Olaparib/shBRCA2 group. However, it was 33.4% after RAD51 was overexpressed. It was the same in LN229 cells. In xenograft mice model, tumor volume in Olaparib and Olaparib/shBRCA2 group was 376.12 and 84.95mm3 when tumor weight was 0.46 g and 0.12 g. In addition, the level of RAD51, RAD50, MRE11, and NBS was increased by Olaparib alone but decreased reversely after knockdown of BRCA2 in Daoy cells. CONCLUSIONS: Knockdown of BRCA2 increases the sensitivity of medulloblastoma cells to Olaparib and strengthens the efficacy of Olaparib in vitro and in vivo. Knockdown of BRCA2 causes DNA damage repair by regulating RAD51-mediated signaling pathway in Daoy cells.
Assuntos
Neoplasias Cerebelares , Glioma , Meduloblastoma , Animais , Proteína BRCA2/genética , Linhagem Celular Tumoral , Neoplasias Cerebelares/tratamento farmacológico , Neoplasias Cerebelares/genética , Dano ao DNA , Reparo do DNA , Humanos , Meduloblastoma/tratamento farmacológico , Meduloblastoma/genética , Camundongos , Ftalazinas , Piperazinas , Rad51 Recombinase/genética , Rad51 Recombinase/metabolismoRESUMO
PURPOSE: Breast cancer (BC) is one of the most common malignant tumors for women. The role and potential mechanisms of long non-coding RNA plasmacytoma variant translocation 1 (lncRNA PVT1) were explored in BC cell migration and invasion. METHODS: PVT1, miR-148a-3p and Rhoassociated, coiledcoil containing protein kinase 1 (ROCK1) mRNA expressions were detected using real-time fluorescent quantitative polymerase chain reaction (qRT-PCR). The ROCK1 protein expression was detected by Western blotting. The relationship of PVT1, miR-148a-3p and ROCK1 was analyzed by Dual Luciferase activity, RNA immunoprecipitation (RIP) and Spearman correlation analysis. Cell invasion and migration were detected by Transwell assay. RESULTS: Upregulation of PVT1 and ROCK1, and downregulation of miR-148a-3p were observed in BC tissues and cell lines. According to the analysis of Dual Luciferase activity, RIP and Spearman correlation analysis, miR-148a-3p directly binds to PVT1, and ROCK1 is a target of miR-148a-3p. In addition, PVT1 regulated the cells migration and invasion by regulating miR-148a-3p and ROCK1 expression. CONCLUSION: These data demonstrated that PVT1 was upregulated and facilitated to the cell migration and invasion of BC by the regulation of miR-148a-3p and ROCK1, indicating that PVT1 may be a potential biomarker of BC diagnosis and treatment.
Assuntos
Neoplasias da Mama , MicroRNAs , RNA Longo não Codificante/genética , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Luciferases/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Quinases Associadas a rho/genética , Quinases Associadas a rho/metabolismoRESUMO
The dry root of Astragalus mongholicus has therapeutic effects such as tonifing the middle - jiao, replenishing qi, solidifing the surface, promoting diuresis, dispelling sepsis outwards and nourishing muscle. There are some slices having black spots after slicing the root of astragalus. The diversity of endophytic fungi between slices with black spots and normal slices was analysed in this paper. The endophytic fungal sequences obtained by high-throughput sequencing were 298,044 and 297,396, and the 116 OTU subsets obtained after clustering belonged to 3 phyla, 9 classes, 22 orders, 38 families and 46 genera. The dominant classes were Eurotiomycetes and Leotiomycetes. The dominant order is Eurotiales and Helotiales. The dominant families are Helotiales_fam_Incertae_sedis and Aspergillaceae. The dominant genera are Cadophora and Aspergillus. There are some peculiar fungal flora in both normal slices and spotted slices. The study on endophytic fungi diversity of astragalus slices will provide some help for drug development of this plant.
A raiz seca de astrágalo tem a função de tonificar o zhongjiao, qi benéfico, superfície sólida, diurético, remoção externa de veneno e fortalecimento muscular. Depois de cortar o astrágalo em fatias finas, algumas fatias têm pontos pretos. Neste trabalho foi analisada a diversidade de fungos endofíticos em fatias de ponto negro versus fatias normais. O sequenciamento de alto rendimento resultou em 314.998 e 315.051 sequências de fungos endofíticos, respectivamente, que após agrupamento resultaram em 116 subgrupos de OTU, pertencentes a três filos, nove classes, 22 ordens, 38 famílias e 46 gêneros. As classes dominantes são Eurotiomycetes e Leotiomycetes. A ordem principal é euclides e hilllows. As famílias predominantes foram aspergilaceae e aspergilaceae. Os gêneros predominantes foram leucostilla e aspergillus. Tanto as seções normais como as secções manchadas apresentam uma flora fúngica distinta. O estudo da diversidade de fungos endofíticos em fatias de astrágalo pode contribuir para o desenvolvimento de fármacos para esta planta.
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Raízes de Plantas , FungosRESUMO
Chicken abdominal fat (AF) is an economically important trait, and many studies have been conducted on genetic selection for AF. However, previous studies have focused on detecting functional chromosome mutations or regions using gene chips. The present study used the specific-locus amplified fragment sequencing (SLAF-seq) technology to perform a genome-wide association study (GWAS) on purebred Wengshang Barred chicken. A total of 1,286,715 single-nucleotide polymorphisms (SNPs) were detected, and 175,211 SNPs were selected as candidate SNPs for genome-wide association analysis using TASSEL general linear models. Two SNPs markers reached genome-wide significance. Of these, rs7943847, rs127627362 were significantly associated with AF at 120 days. These SNPs are close to eight genes (SLC16A6, ARSG, WIPI1, PRKAR1A, FAM20A, ABCA8, ABCA9, CPQ,). These results would enrich the studies on AF and promote the use of Chinese chicken, especially the Wenshang Barred chicken.(AU)
Assuntos
Animais , Seleção Genética/fisiologia , Galinhas/genética , Polimorfismo Genético , Gordura Abdominal/fisiologiaRESUMO
Osteosarcoma, a common malignant tumor in orthopedics, often has a very poor prognosis after lung metastasis. Immunotherapy has not achieved much progress in the treatment because of the characteristics of solid tumors and immune environment of osteosarcoma. The tumor environment is rather essential for sarcoma treatment. Our previous study demonstrated that heat shock proteins could be used as antitumor vaccines by carrying tumor antigen peptides, and we hypothesize that an anti-osteosarcoma effect may be increased with an immune check point inhibitor (PD-L1 inhibitor) as a combination treatment strategy. The present study prepared a multisubtype mixed heat shock protein osteosarcoma vaccine (mHSP/peptide vaccine) and concluded that the mHSP/peptide vaccine was more effective than a single subtype heat shock protein, like Grp94. Therefore, we used the mHSP/peptide vaccine in combination with a PD-L1 inhibitor to treat osteosarcoma, and the deterioration of osteosarcoma was effectively hampered. The mechanism of combined therapy was investigated, and AKT expression participates with sarcoma lung metastasis. This study proposed an antisarcoma strategy via stimulation of the immune system as a further alternative approach for sarcoma treatment and elucidated the mechanism of combined therapy.
Assuntos
Neoplasias Ósseas/terapia , Vacinas Anticâncer/uso terapêutico , Proteínas de Choque Térmico/uso terapêutico , Inibidores de Checkpoint Imunológico/uso terapêutico , Osteossarcoma/terapia , Animais , Neoplasias Ósseas/imunologia , Neoplasias Ósseas/patologia , Neoplasias Ósseas/secundário , Linhagem Celular Tumoral , Terapia Combinada/métodos , Modelos Animais de Doenças , Feminino , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas de Choque Térmico HSP90/metabolismo , Humanos , Imunoterapia/métodos , Interferon gama/farmacologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/secundário , Glicoproteínas de Membrana/metabolismo , Camundongos Endogâmicos C57BL , Proteínas de Neoplasias/imunologia , Proteínas de Neoplasias/uso terapêutico , Osteossarcoma/genética , Osteossarcoma/imunologia , Osteossarcoma/secundário , Proteínas Proto-Oncogênicas c-akt/metabolismo , Evasão TumoralRESUMO
PURPOSE: To investigate the magnetic resonance imaging (MRI) images of brain glioma before postoperative radiotherapy, and to provide reference for the delineation of postoperative radiotherapy target area. METHODS: Retrospective analysis was performed on 106 cases of brain glioma confirmed by surgery and pathology in our hospital, including 70 cases of high-grade glioma (HGG) and 36 cases of low-grade glioma (LGG). The MRI images of the lesions within 1 month before and after surgery were analyzed, the apparent diffusion coefficient (ADC) values in the near and far tumor areas were measured, respectively, and the corresponding rADC values were calculated. RESULTS: The incidence of residual tumors of postoperative HGG and LGG was 0, 15.7% (0/36, 11/70), respectively. The incidence of postoperative reactive enhancement was 11.0% and 52.9% (4/36 and 37/70), respectively. About 30.6% and 81.4% (11/36 and 57/70) of patients with adjacent meningeal enhancement were found in the operative area. CONCLUSIONS: The MRI images of HGG and LGG before postoperative radiotherapy had certain characteristics, providing a favorable guidance for the delineation of the target area of radiotherapy and the formulation of treatment plan.
Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Glioma/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Adolescente , Adulto , Idoso , Edema Encefálico/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirurgia , Criança , Imagem de Tensor de Difusão , Feminino , Glioma/patologia , Glioma/radioterapia , Glioma/cirurgia , Humanos , Masculino , Meninges/diagnóstico por imagem , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/diagnóstico por imagem , Neoplasia Residual/diagnóstico por imagem , Cuidados Pós-Operatórios , Complicações Pós-Operatórias/diagnóstico por imagem , Estudos Retrospectivos , Adulto JovemRESUMO
The objective of this study was to determine the effects of cadmium (Cd) on histological changes, lipid metabolism, and oxidative and endoplasmic reticulum (ER) stress in the liver of layers. A total of 480 hens at 38 wk of age were randomly assigned in 5 groups that were fed a basal diet or basal diet supplemented with CdCl2 2.5H2O at 7.5, 15, 30, and 60 mg Cd/kg feed for 9 wk. The results showed that accumulation of Cd was the greatest in the kidney, followed by the liver, pancreas, and lung. Diet contaminated with 30 mg Cd/kg induced antioxidant defenses accompanied by the increase of the activities of antioxidant enzymes in the liver, while dietary supplementation with 60 mg Cd/kg decreased the antioxidant levels significantly (P < 0.05). Immunofluorescence assay showed Cd induced reactive oxygen species production and endoplasmic reticulum stress in hepatocytes. Exposure to 60 mg Cd/kg significantly upregulated the expression of cytochrome C, caspase 3, caspase 9, caspase 7, Grp78, and Chop (P < 0.05). Histopathology and quantitative real-time PCR results presented periportal fibrosis, bile duct hyperplasia, and periportal inflammatory cell infiltration in the liver accompanied by upregulating the expression of tumor necrosis factor-α, IL-6 and IL-10 in the 30- or 60-mg Cd/kg groups. Oil Red O staining and RT-qPCR results showed dietary supplementation with 7.5, 15, and 30 mg Cd/kg promoted the synthesis of lipid droplets and upregulated the expression of fatty acid synthase, while dietary supplementation with 60 mg Cd/kg attenuated the synthesis of lipid droplets and downregulated the expression of acyl-CoA oxidase 1, carnitine palmitoyltransferase-1, and perixisome proliferation-activated receptor α (P < 0.05). Besides, the expression of vitellogenin (VTG) II and microsomal triglyceride transfer protein were upregulated in the 7.5-mg Cd/kg group, and the expressions of apolipoprotein B, vitellogenin II, and apolipoprotein very-low-density lipoprotein-II were downregulated in the 30- and/or 60-mg Cd/kg groups (P < 0.05). Conclusively, although low-dose Cd exposure promoted the synthesis of lipids and lipoproteins in the liver, the increase of Cd exposure could trigger liver injury through inducing oxidative and endoplasmic reticulum stress and negatively affect lipid metabolism and yolk formation in laying hens.
Assuntos
Cádmio/efeitos adversos , Galinhas/fisiologia , Estresse do Retículo Endoplasmático , Poluentes Ambientais/efeitos adversos , Metabolismo dos Lipídeos , Fígado/metabolismo , Estresse Oxidativo , Animais , Galinhas/anatomia & histologia , Relação Dose-Resposta a Droga , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Feminino , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/anatomia & histologia , Fígado/fisiopatologia , Estresse Oxidativo/efeitos dos fármacosRESUMO
PURPOSE: Medulloblastoma (MB) is a malignant brain disease in young children. The overall survival of MB patients is disappointing due to absence of effective therapeutics and this could be attributed to the lack of molecular mechanism underlying MB. FHOD3 was an important gene during cardio-genesis and was reported to promote cell migration in cancer. However, its role in MB is not clear to date. METHODS: RT-qPCR and IHC analysis were used to determine expression of FHOD3. Survival curve was drawn by K-M analysis. FHOD3 was knocked down by RNAi technology. The effects of FHOD3 on medulloblastoma cells were determined by CCK-8 assay, colony formation assay, transwell assay and FACs analysis. RESULTS: FHOD3 expression increased by 1.5 fold in tumor tissues compared to the control and IHC analysis further confirmed strong expression of FHOD3 in medulloblastoma tissues. Then higher FHOD3 expression was associated with shorter survival time in MB patients (13.0 months versus 43.8 months). In medulloblastoma cells such as Daoy and D283med, FHOD3 also displayed abundant expression. When FHOD3 was knocked down, the ability of cell proliferation and colony formation was reduced over greatly. The capability of cell migration and invasion was also inhibited significantly. However, cell apoptotic rate increased significantly reversely. Mechanistically, the phosphorylation level of RhoA, ROCK1, and LIMK1 was decreased when FHOD3 was knocked down but increased reversely when FHOD3 was over-expressed in Daoy cells. CONCLUSIONS: FHOD3 was associated with overall survival time in medulloblastoma patients and was essential to cell proliferation, growth and survival in medulloblastoma and might regulates activation of RhoA/ROCK1/LIMK1 signaling pathway.
Assuntos
Neoplasias Cerebelares/metabolismo , Forminas/metabolismo , Quinases Lim/metabolismo , Meduloblastoma/metabolismo , Quinases Associadas a rho/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismo , Apoptose , Ciclo Celular , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Cerebelares/mortalidade , Pré-Escolar , Feminino , Forminas/genética , Técnicas de Silenciamento de Genes , Humanos , Estimativa de Kaplan-Meier , Masculino , Meduloblastoma/mortalidade , Meduloblastoma/patologia , Invasividade Neoplásica , Proteínas de Neoplasias/metabolismo , Fosforilação , Transdução de Sinais , Ensaio Tumoral de Célula-TroncoRESUMO
PURPOSE: To examine the possible prognostic factors in patients with type 1 and type 2 papillary renal cell carcinoma (pRCC) after surgical management and to identify the independent predictive factors of the prognosis. METHODS: From 2010 to 2017, 1405 patients underwent surgery for renal cell carcinoma, of whom 114 had type 1 or type 2 pRCC and follow-up data were available for 88 patients. Clinicopathological and prognostic parameters were compared between type 1 and type 2 pRCC. Possible prognostic factors were retrospectively analyzed by univariate and multivariate analyses with Cox regression. RESULTS: The study included 63 males and 25 females with a mean age of 54.27 ± 12.91. 53 patients were diagnosed by regular physical examination and others presented with hematuria or lumbago. 53 (60.2%) underwent radical nephrectomy and 35 (39.8%) underwent nephron sparing surgery. After a mean follow-up of 46.08 ± 22.65 months, 16 patients died of pRCC metastasis and the 5-year disease-specific survival was 79.3%. The comparison of the 39 (44.3%) type 1 and 49 (55.7%) type 2 pRCCs revealed that type 2 pRCC had significantly higher grade and worse prognosis. Univariate analysis showed that symptomatic diagnosis, type, grade, and tumor stage were prognostic factors. Multivariate analysis identified that type and tumor stage were independent factors of the prognosis. CONCLUSIONS: Pathological type and tumor stage could serve as independent factors for the prognosis of patients with pRCC.
Assuntos
Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Adulto , Idoso , Carcinoma de Células Renais/classificação , Carcinoma de Células Renais/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Renais/classificação , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Nefrectomia , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
PURPOSE: Dedifferentiated liposarcoma (DDLPS) is a soft tissue malignancy characterized by amplification of the mouse double minute 2 homolog (MDM2) gene. MDM2 is a negative regulator of tumor protein 53 (TP53). We tested the in vivo efficacy of BI-907828, a small molecule inhibitor of the MDM2-TP53 interaction, in two DDLPS patient-derived xenografts (PDX). METHODS: Partially immunodeficient mice were bilaterally engrafted with UZLX-STS3 (n = 24) and UZLX-STS5 (n = 24) human DDLPS tissue harboring MDM2 amplifications. Mice were grouped as follows: (a) vehicle (0.5% hydroxyethylcellullose) 10 ml/kg daily per os (p.o.); (b) doxorubicin 5 mg/kg weekly intraperitoneally (i.p.); (c) BI-907828 2.5 mg/kg daily p.o. and (d) BI-907828 10 mg/kg daily p.o. The treatment lasted for 15 days, all mice treated with BI-907828 were followed for 37 days post-treatment. Efficacy was assessed by tumor volume and histopathological evaluation. RESULTS: The 15-day treatment with 2.5 mg/kg and 10 mg/kg BI-907828 significantly inhibited tumor growth in UZLX-STS5 and -STS3 (p < 0.0001 compared to control for both models). All UZLX-STS5 and -STS3 tumors treated with BI-907828 decreased in size during treatment, and BI-907828-treated UZLX-STS5 tumors even disappeared completely. During the follow-up period, no tumor regrowth was observed in the UZLX-STS5 model and both doses of BI-907828 led to a pathological complete response, whereas a dose-dependent regrowth was seen in the UZLX-STS3 model. CONCLUSION: BI-907828 showed significant anti-tumor activity in DDLPS PDX harboring MDM2 amplifications, providing a strong rationale for early clinical testing of BI-907828 in a DDLPS patient population.
Assuntos
Antineoplásicos/uso terapêutico , Amplificação de Genes , Lipossarcoma/tratamento farmacológico , Compostos Orgânicos/uso terapêutico , Proteínas Proto-Oncogênicas c-mdm2/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteína Supressora de Tumor p53/antagonistas & inibidores , Animais , Antineoplásicos/farmacologia , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Dosagem de Genes , Humanos , Lipossarcoma/genética , Lipossarcoma/patologia , Camundongos , Compostos Orgânicos/farmacologia , Proteína Supressora de Tumor p53/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The effects of plant essential oil (PEO) on the production performance and immune function of laying hens were evaluated to provide theoretical basis for promoting the natural plant extracts. Eight thousand 1-day-old healthy laying hens were randomly divided into a control group or PEO group, with four replicates per treatment and 1000 hens per replicate. The PEO diet was supplemented with 3g/kg plant extract. Diets were fed for 56 days. The tibia length and keel length were detected on an empty stomach at the end of the trial. Blood samples were collected on the 28th and 56th days to detect the level of C3, C4, IL-1, IL-2, IL-17 and immunoglobulin in the serum. The results showed that, compared with the control, PEO supplementation significantly increased the weight gain rate (WGR) at the 2nd, 4th, 5th and 7th week (p 0.05), and decreased the WGR at the 3rd and 6th week. The tibial length was significantly increased at the 3rd, 5th, 6th and 7th week (p 0.01), and also the keel length at the 5th and 7th week in PEO group. The concentration of IgG and IgM also significantly influenced with PEO supplementation, but there was no significant difference in the complements, C3 and C4, and the IL levels between days 28 and 56. Moreover, no significant difference was observed in body weight and immune organ on day 56. Therefore, we conclude that the addition of PEO could improve the production performance and immune function in laying hens.
Assuntos
Animais , Galinhas/crescimento & desenvolvimento , Galinhas/imunologia , Óleos Voláteis/administração & dosagemRESUMO
The effects of plant essential oil (PEO) on the production performance and immune function of laying hens were evaluated to provide theoretical basis for promoting the natural plant extracts. Eight thousand 1-day-old healthy laying hens were randomly divided into a control group or PEO group, with four replicates per treatment and 1000 hens per replicate. The PEO diet was supplemented with 3g/kg plant extract. Diets were fed for 56 days. The tibia length and keel length were detected on an empty stomach at the end of the trial. Blood samples were collected on the 28th and 56th days to detect the level of C3, C4, IL-1, IL-2, IL-17 and immunoglobulin in the serum. The results showed that, compared with the control, PEO supplementation significantly increased the weight gain rate (WGR) at the 2nd, 4th, 5th and 7th week (p 0.05), and decreased the WGR at the 3rd and 6th week. The tibial length was significantly increased at the 3rd, 5th, 6th and 7th week (p 0.01), and also the keel length at the 5th and 7th week in PEO group. The concentration of IgG and IgM also significantly influenced with PEO supplementation, but there was no significant difference in the complements, C3 and C4, and the IL levels between days 28 and 56. Moreover, no significant difference was observed in body weight and immune organ on day 56. Therefore, we conclude that the addition of PEO could improve the production performance and immune function in laying hens.(AU)
Assuntos
Animais , Galinhas/crescimento & desenvolvimento , Galinhas/imunologia , Óleos Voláteis/administração & dosagemRESUMO
BACKGROUND: Synovial sarcoma (SS) is an aggressive soft-tissue sarcoma with a poor prognosis owing to its resistance to radiation and chemotherapy. Thus, novel therapeutic strategies for SS are urgently required. Anlotinib, a new oral tyrosine kinase inhibitor, is designed to primarily inhibit multi-targets in vasculogenesis and angiogenesis. This study was designed to characterize its antitumor efficacy and possible mechanism in patients with advanced refractory synovial sarcoma. METHODS: Anlotinib's antitumor effect was evaluated in vivo and vitro. Downstream targets of anlotinib in treating synovial sarcoma were analyzed through microarray assay. Cell proliferation and apoptosis analyses were performed to evaluate the impact of candidate downstream gene depletion in synovial sarcoma cells. Microarray assay were carried out to investigate potential signal network related with candidate downstream gene. RESULTS: Anlotinib significantly suppresses synovial sarcoma proliferation in PDTX model and cell lines. Additionally, GINS1 (also named as PSF1, Partner of SLD Five 1), rather than other conventional gene target, was demonstrated to be a vital target of anlotinib's antitumor effect in synovial sarcoma through microarray assay. Expression of GINS1 was remarkably higher in synovial sarcoma tumor samples and related with poor outcome. Knockdown of GINS1 expression could remarkably inhibit proliferation and promote apoptosis in vitro. Meanwhile, through microarray assay, CITED2, EGR1, SGK1 and SPP1 were identified and further validated by qPCR/WB as downstream targets of GINS1. CONCLUSION: Anlotinib might suppress proliferation of SS through a novel downstream GINS1-regulated network which plays a vital function in SS proliferation and also demonstrated that targeting the GINS1-regulated signal pathway could be a potential strategy for management of SS.
Assuntos
Neoplasias Ósseas/tratamento farmacológico , Proteínas de Ligação a DNA/efeitos dos fármacos , Indóis/uso terapêutico , Proteínas de Neoplasias/efeitos dos fármacos , Inibidores de Proteínas Quinases/uso terapêutico , Quinolinas/uso terapêutico , Sarcoma Sinovial/tratamento farmacológico , Apoptose/efeitos dos fármacos , Neoplasias Ósseas/genética , Proliferação de Células/efeitos dos fármacos , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Progressão da Doença , Proteína 1 de Resposta de Crescimento Precoce/efeitos dos fármacos , Proteína 1 de Resposta de Crescimento Precoce/genética , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Técnicas de Silenciamento de Genes , Humanos , Proteínas Imediatamente Precoces/efeitos dos fármacos , Proteínas Imediatamente Precoces/genética , Proteínas Imediatamente Precoces/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Osteopontina/efeitos dos fármacos , Osteopontina/genética , Osteopontina/metabolismo , Análise Serial de Proteínas , Proteínas Serina-Treonina Quinases/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , RNA Mensageiro/análise , Proteínas Repressoras/efeitos dos fármacos , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Sarcoma Sinovial/genética , Transativadores/efeitos dos fármacos , Transativadores/genética , Transativadores/metabolismoRESUMO
Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) represents a paradigm shift in the treatment of non-small cell lung cancer (NSCLC) patients and has been the first-line therapy in clinical practice. While erlotinib, gefitinib and afatinib have achieved superior efficacy in terms of progression-free survival and overall survival compared with conventional chemotherapy in NSCLC patients, most people inevitably develop acquired resistance to them, which presents another challenge in the treatment of NSCLC. The mechanisms of acquired resistance can be classified as three types: target gene mutation, bypass signaling pathway activation and histological transformation. And the most common mechanism is T790M which accounts for approximately 50% of all subtypes. Many strategies have been explored to overcome the acquired resistance to EGFR TKI. Continuation of EGFR TKI beyond progressive disease is confined to patients in asymptomatic stage when the EGFR addiction is still preserved in some subclones. While the combination of EGFR TKI and chemotherapy or other targeted agents has improved the survival benefit in EGFR TKI resistant patients, there are controversies within them. The next-generation EGFR TKI and immunotherapy represent two novel directions for overcoming acquired resistance and have achieved promising efficacy. Liquid biopsy provides surveillance of the EGFR mutation by disclosing the entire genetic landscape but tissue biopsy is still indispensable because of the considerable rate of false-negative plasma.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Acrilamidas/uso terapêutico , Afatinib/uso terapêutico , Compostos de Anilina/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Transformação Celular Neoplásica , Classe I de Fosfatidilinositol 3-Quinases/genética , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos/genética , Quimioterapia Combinada/métodos , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Cloridrato de Erlotinib/uso terapêutico , Gefitinibe/uso terapêutico , Humanos , Imunoterapia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas c-met/genética , Quinazolinonas/uso terapêutico , Receptores Proteína Tirosina Quinases/genética , Receptor IGF Tipo 1/genética , Transdução de Sinais , Receptor Tirosina Quinase AxlRESUMO
OBJECTIVE: To assess the effect of the intraoperative application of the Aquamantys® system to treat the hepatic resection margin on local and overall recurrence of HCC. METHODS: We retrospectively analyzed 101 patients admitted from November 2016 to June 2018 who underwent hepatectomy using the Aquamantys® as hemostatic device, who were matched with 101 patients (control group) using conventional hemostatic devices through PSM. Univariate and multivariate analyses of recurrence-free survival (RFS) and local recurrence-free survival (LRFS) were performed using the Cox proportional hazard model. RESULTS: There were no significant differences in baseline data and surgical procedures between the two groups. The Aquamantys® group showed less blood loss (P = 0.005) and a lower blood transfusion rate (P = 0.036), while the incidences of postoperative complications of the two groups showed no difference (P = 0.266). OS rates of the Aquamantys® group and the control group were 82.6% and 84.2%, respectively (P = 0. 446), and RFS rates were 65.5% and 58.2%, respectively (P = 0.153), with no significant differences. The Aquamantys® group and the control group had two cases and 11 cases of local recurrence, respectively, with LRFS rates of 98% and 87.9%, respectively, in the follow-up period, corresponding to a significant difference (P = 0.011). Multivariate analysis showed that microvascular invasion (MVI), tumor diameter > 5 cm, and the control group were independent risk factors for LRFS. CONCLUSION: Our results indicate that application of the Aquamantys® system in hepatectomy can reduce local recurrence, but it can neither reduce overall recurrence nor improve OS.
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Carcinoma Hepatocelular/cirurgia , Eletrocirurgia/instrumentação , Hemostasia Cirúrgica/instrumentação , Hepatectomia , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia , Perda Sanguínea Cirúrgica/prevenção & controle , Transfusão de Sangue/estatística & dados numéricos , Carcinoma Hepatocelular/prevenção & controle , Estudos de Casos e Controles , Intervalo Livre de Doença , Feminino , Hemostasia Cirúrgica/métodos , Humanos , Neoplasias Hepáticas/prevenção & controle , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Pontuação de Propensão , Modelos de Riscos Proporcionais , Análise de Regressão , Estudos RetrospectivosRESUMO
To investigate the hypothesis that APS can attenuate E. coli-induced microvascular dysfunction in chicken intestine, 60 0-day old male chickens were divided into three groups with 5 replications of 4 chicks. Chicken in the APS group were treated with 15 mg APS daily while the others were given 0 mg APS for 6 days. Then all 7-day old chicken were injected intraperitoneally by E. coli, except for the chicken in the control group. After 4 h, all chickens intestinal samples were collected to detect gene expressions involved in inflammatory factors and adhesion molecules. Results showed that APS attenuated the signs of edema and hemorrhage in 7-day old chicken intestinal mucosa which were induced by E. coli injection. Consistently, APS significantly reduced the increasing mRNA levels of inflammatory factors such as Tumor necrosis factor-a (TNF-a), interleukin (IL) -1 and inducible nitric oxide synthase (iNOS) (p 0.05), the same results were observed in vascular adhesion molecules such as E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Moreover, we observed that APS supplementation in water suppressed significantly (p 0.05) the decline of reparative factors such as epithelial growth factor (EGF) and basic fibroblast growth factor (bFGF) in E. coli injected group. Furthermore, supplementation with APS substantially blocked (p 0.05) the increase in Toll-like receptor-4 (TLR4) and Nuclear factor (NF)-B mRNA abundance (p=0.087) induced by E. coli infection. This study indicated that microvascular injured chicken intestine induced by E. coli would be attenuated with feeding APS, and the mechanism of repairing were probably mediated through TLR4-NF-B signal pathways.(AU)
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Animais , Galinhas/microbiologia , Polissacarídeos/administração & dosagem , Polissacarídeos/análise , Escherichia coli , Astrágalo , Microvasos/lesõesRESUMO
To investigate the hypothesis that APS can attenuate E. coli-induced microvascular dysfunction in chicken intestine, 60 0-day old male chickens were divided into three groups with 5 replications of 4 chicks. Chicken in the APS group were treated with 15 mg APS daily while the others were given 0 mg APS for 6 days. Then all 7-day old chicken were injected intraperitoneally by E. coli, except for the chicken in the control group. After 4 h, all chickens intestinal samples were collected to detect gene expressions involved in inflammatory factors and adhesion molecules. Results showed that APS attenuated the signs of edema and hemorrhage in 7-day old chicken intestinal mucosa which were induced by E. coli injection. Consistently, APS significantly reduced the increasing mRNA levels of inflammatory factors such as Tumor necrosis factor-a (TNF-a), interleukin (IL) -1 and inducible nitric oxide synthase (iNOS) (p 0.05), the same results were observed in vascular adhesion molecules such as E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Moreover, we observed that APS supplementation in water suppressed significantly (p 0.05) the decline of reparative factors such as epithelial growth factor (EGF) and basic fibroblast growth factor (bFGF) in E. coli injected group. Furthermore, supplementation with APS substantially blocked (p 0.05) the increase in Toll-like receptor-4 (TLR4) and Nuclear factor (NF)-B mRNA abundance (p=0.087) induced by E. coli infection. This study indicated that microvascular injured chicken intestine induced by E. coli would be attenuated with feeding APS, and the mechanism of repairing were probably mediated through TLR4-NF-B signal pathways.
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Animais , Escherichia coli , Galinhas/microbiologia , Polissacarídeos/administração & dosagem , Polissacarídeos/análise , Astrágalo , Microvasos/lesõesRESUMO
OBJECTIVES: This study was to evaluate the feasibility of simultaneous integrated boost on tumor hypoxia area by studying the dosimetric change of hypoxia imaging guidance on intensity-modulated radiation therapy for non-small cell lung cancer (NSCLC). METHODS: Five NSCLC patients with large hypoxic volume participated in this study. FDG PET/CT images were fused with CT localization images to delineate gross tumor volume. FMISO PET/CT images were fused with CT localization images to delineate hypoxic biological target volume (BTV) (tissue maximum ratio ≥ 1.3) by threshold. BTV was irradiated with 72, 78 and 84 Gy, respectively, 30 times. The dosimetry differences were compared in target volume and organ at risk between simultaneous integrated boost plans and conventional radiotherapy plans. RESULTS: Dosages on BTV of NSCLC hypoxic area were increased to 72, 78 and 84 Gy, respectively, by simultaneous integrated boost intensity-modulated radiation therapy. There was no obvious difference in dosage distributions on original target volume compared with those in conventional radiotherapy. Dosages on main organ at risk in chest met the dosimetric constraint, and there was no significant difference compared with those in conventional radiotherapy. CONCLUSION: It is feasible in dosiology that the dosages in NSCLC hypoxic area were added to 72, 78 and 84 Gy by simultaneous integrated boost with the guidance of 18F-FMISO PET/CT.
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Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Hipóxia/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Imagem Multimodal/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Idoso , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Humanos , Neoplasias Pulmonares/radioterapia , Masculino , Pessoa de Meia-Idade , Misonidazol/análogos & derivados , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Dosagem RadioterapêuticaRESUMO
PURPOSE: Trastuzumab plus chemotherapy is an effective therapy in HER2 positive advanced gastric cancer (AGC). However, the clinicopathologic factors that predict the outcome of routine trastuzumab therapy remain unclear. METHODS: The outcome and safety profile of trastuzumab therapy in untreated HER2 positive AGC was evaluated in this prospective observational study. Clinical and pathological data including demographics, treatment profiles, expression level of HER2 were analyzed to identify predictive factors of trastuzumab-based first-line therapy for their progression-free survival (PFS). RESULTS: Overall, 107 patients were eligible. The median number of treatment cycles was 9 (range 1-44), the median PFS and median overall survival (OS) were 7.7 months (95% CI 6.5-8.9) and 16.0 months (95% CI 13.2-18.8), respectively. The confirmed response rate was 58.9%, and the disease control rate was 82.2%. Patients with liver metastasis (HR 1.616) and poor performance status (PS, HR 2.518) were independently associated with a worse PFS, while the other clinicopathological factors including demographics, treatment profiles and some other clinical characteristics did not predict the survival. CONCLUSIONS: In routine clinical practice, the addition of trastuzumab to chemotherapy was effective and safe in real-world setting in Chinese patients with HER2 positive AGC, regardless of most of the clinicopathological factors. Further studies are needed to improve the prognosis of HER2 positive patients with liver metastasis or poor PS. Trial Registration clinicaltrials.gov Identifier: NCT03024450.