RESUMEN

Background: Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer-related death. This study investigated the role of DPY30 in the development and progression of CRC cells, especially in the area of cellular glycolysis. Methods: HT29 control cells and DPY30 knockdown cells were collected for tandem mass tag (TMT) labeling quantitative proteomics analysis of cellular total proteins (n=3). To further assess the accuracy of the differential expression profile, representative genes were selected and confirmed by quantitative real-time polymerase chain reaction (qPCR) and western blot (WB). Glycolytic flux was studied by detecting the extracellular acidification rate (ECAR) using the Seahorse XFe96. In view of the vital role of DPY30 on the H3K4me3 level, chromatin immunoprecipitation (ChIP) assays were performed. Results: The results showed that the expression of HK1, a protein related to cellular glucose metabolism, was significantly down-regulated after DPY30 knockdown, while the expression of GSK3B was significantly increased. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated significant changes in several signaling pathways, with the PI3K-AKT signaling pathway being the most prominent. The data of Seahorse XFe96 revealed that DPY30 knockdown attenuated aerobic glycolysis. DPY30 knockdown repressed the establishment of H3K4me3 on promoters of HK1, PFKL, and ALDOA. Conclusions: DPY30 promoted the glycolysis of CRC cells through two channels: influencing signaling pathways and gene transcription, thereby promoting the progression of CRC.

RESUMEN

Loquat fruits are among the most popular Chinese fruits because of their unique taste and aroma. The quality profiles of these fruits during 18 days of shelf-life at 20 °C were elucidated by headspace gas chromatography-ion mobility spectrometry (HS-GC-IMS), E-nose, and E-tongue. During shelf-life period, the properties and variations of 43 (20 aldehydes, 7 esters, 6 ketones, 1 alcohol, and 1 furan) volatile flavored compounds were determined by GC-IMS, which showed that the contents of methyl 3-methyl butanoate, ethyl acetate, and dimethyl ketone gradually decrease with prolonged shelf-life time, while (E)-2-heptenal, heptanal, (E)-2-pentenal, 1-penten-3-one 3-pentanone and 2-pentylfuran increase. The PCA based on the signal intensity of GC-IMS and E-nose, revealed that loquat fruits are well distinguished at different shelf-life times. The taste profile alternates as the storage time increases, along with higher pH, and lower amounts of total soluble solids, vitamin C, and total phenolics. The visual plots of GC-IMS, E-nose, and E-tongue had good consistency, and they characterized the aroma characteristics of loquat fruits well during different shelf-life periods. The findings of this research provide a useful understanding of the flavors of loquat fruits during their prolonged shelf-life, and a potential research basis for advancements in the loquat industry.

RESUMEN

DPY30, a core subunit of the SET1/MLL histone H3K4 methyltransferase complexes, plays an important role in diverse biological functions through the epigenetic regulation of gene transcription, especially in cancer development. However, its involvement in human colorectal carcinoma (CRC) has not been elucidated yet. Here we demonstrated that DPY30 was overexpressed in CRC tissues, and significantly associated with pathological grading, tumor size, TNM stage, and tumor location. Furthermore, DPY30 knockdown remarkably suppressed the CRC cell proliferation through downregulation of PCNA and Ki67 in vitro and in vivo, simultaneously induced cell cycle arrest at S phase by downregulating Cyclin A2. In the mechanistic study, RNA-Seq analysis revealed that enriched gene ontology of cell proliferation and cell growth was significantly affected. And ChIP result indicated that DPY30 knockdown inhibited H3 lysine 4 trimethylation (H3K4me3) and attenuated interactions between H3K4me3 with PCNA, Ki67 and cyclin A2 respectively, which led to the decrease of H3K4me3 establishment on their promoter regions. Taken together, our results demonstrate overexpression of DPY30 promotes CRC cell proliferation and cell cycle progression by facilitating the transcription of PCNA, Ki67 and cyclin A2 via mediating H3K4me3. It suggests that DPY30 may serve as a potential therapeutic molecular target for CRC.

Asunto(s)

Neoplasias Colorrectales , Ciclina A2 , Humanos , Ciclina A2/genética , Factores de Transcripción , Epigénesis Genética , Antígeno Ki-67 , Antígeno Nuclear de Célula en Proliferación , Proliferación Celular/genética , Ciclo Celular/genética , Neoplasias Colorrectales/genética

RESUMEN

Currently available therapies for hepatocellular carcinoma (HCC), with a high morbidity and high mortality, are only marginally effective and with sharp adverse side effects, which makes it compulsory to explore novel and more effective anticancer molecules. Chinese medicinal herbs exhibited prominent anticancer effects and were applied to supplement clinical cancer treatment. Here, we reported a compound, trilobolide-6-O-isobutyrate (TBB), isolated from the flowers of Wedelia trilobata with a markedly cytotoxic effect on HCC cells. We found that TBB time- and dose-dependently inhibited HCC cells' growth and colony formation in vitro. Moreover, TBB induced cell cycle arrest at the G2/M phase, mitochondrial caspase-dependent apoptosis, and suppressed migration and invasion, as well as the glycolysis of HCC cells. Mechanistically, our data indicated that TBB inhibited the STAT3 pathway activation by directly interacting with the TYR 640/657 sites of the STAT3 protein and decreasing the level of p-STAT3. TBB also regulated the expression of PCNA, Ki67, Cyclin B1, Cyclin E, Bax, Bcl2, MMP2/9, and PGK1 through the inhibition of the IL-6/STAT3 signaling pathway. Lastly, we confirmed that TBB effectively eliminated tumor growth without causing overt toxicity to healthy tissues in the xenograft tumor model. The exploration of anticancer activity and the underlying mechanism of TBB suggested its usage as a promising chemotherapeutic agent for HCC.

Asunto(s)

Carcinoma Hepatocelular , Neoplasias Hepáticas , Apoptosis , Butiratos , Carcinogénesis , Carcinoma Hepatocelular/tratamiento farmacológico , Línea Celular Tumoral , Proliferación Celular , Furanos , Humanos , Interleucina-6/metabolismo , Isobutiratos , Neoplasias Hepáticas/tratamiento farmacológico , Factor de Transcripción STAT3/metabolismo , Transducción de Señal

RESUMEN

Colorectal cancer (CRC) is the most fatal gastrointestinal tumor and it is urge to explore powerful drugs for the treatment. Diosgenin (DSG) as a new steroidal had been reported exerts anti-tumor activity in multiple cancers, including CRC. However, the potential mechanism of DSG suppresses CRC remains further to be revealed. Here, we reported that DSG inhibited proliferation of CRC cells in dose- and time-dependent manner, induced apoptosis by modulating p53 and Bcl-2 family proteins expression to mediate mitochondrial apoptosis pathway, suppressed migration and invasion by reducing MMP-9 (matrix metalloproteinase) and decreased aerobic glycolysis by mediating glucose transporter (GLUT) like GLUT3 and GLUT4, and pyruvate carboxylase PC downregulation. Intriguingly, mechanistic study suggests those phenotypes involved DSG inhibited cAMP/PKA/CREB pathway in CRC cells, and result to inhibit the phosphorylation of CREB to regulate the transcription of genes above-mentioned. Finally, nude mice xenograft tumor model further indicated that DSG could be a great agent to suppress the growth of CRC cells in vivo and have no obvious side effects. Taken together, we revealed a unique mechanism that DSG suppresses CRC cells through cAMP/PKA/CREB pathway and DSG is a promising candidate drug for CRC treatment.

Asunto(s)

Diosgenina , Animales , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular , Ratones , Transducción de Señal

RESUMEN

BACKGROUND: Endometriosis is a benign gynecological disease with obviously feature of estrogen-dependence and inflammatory response. The applications of primary endometriotic stromal cells in research of endometriosis are restricted for short life span, dedifferentiation of hormone and cytokine responsiveness. The objective of this study was to establish and characterize immortalized human endometriotic stromal cells (ihESCs). METHODS: The endometriotic samples were from a patient with ovarian endometriosis and the primary endometriotic stromal cells were isolated from the endometriotic tissues. The primary cells were infected by lentivirus to establish telomerase reverse transcriptase (hTERT)-induced immortalized cells. Quantification of mRNA and proteins was examined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western Blot. CCK-8 assay and EdU labeling assay were assigned to assess the growth of ihESCs. Karyotype assay was performed to detect the chromosomes of ihESCs. Colony formation assay and nude mouse tumorigenicity assay were used to evaluate colony-formation and tumorigenesis abilities. RESULTS: ihESCs continuously overexpressed hTERT via infection of lentivirus and significant extended the life span reaching 31 passages. The morphology, proliferation and karyotype of ihESCs remained unchanged. The expression of epithelial-mesenchymal transition (EMT) markers, estrogen-metabolizing proteins and estrogen/progesterone receptors (ERs and PRs) were unaltered. Furthermore, the treatment of estrogen increased the proliferation and EMT of ihESCs. Lipopolysaccharides (LPS) and IL-1ß remarkably induced inflammatory response. The clonogenesis ability of ihESCs was consistent with primary cells, which were much lower than Ishikawa cells. In addition, nude mouse tumorigenicity assay demonstrated that ihESCs were unable to trigger tumor formation. CONCLUSION: This study established and characterized an immortalized endometriotic stromal cell line that exhibited longer life span and kept the cellular morphology and physiological function as the primary cells. The immortalized cells remained normal feedback to estrogen and inflammatory response. Moreover, the immortalized cells were not available with tumorigenic ability. Therefore, ihESCs would be serviceable as in vitro cell tool to investigate the pathogenesis of endometriosis.

Asunto(s)

Endometriosis/genética , Endometrio/metabolismo , Expresión Génica , Células del Estroma/metabolismo , Animales , Línea Celular Transformada , Línea Celular Tumoral , Proliferación Celular/genética , Supervivencia Celular/genética , Células Cultivadas , Endometriosis/metabolismo , Endometriosis/patología , Endometrio/patología , Transición Epitelial-Mesenquimal/genética , Femenino , Humanos , Ratones Endogámicos BALB C , Ratones Desnudos , Células del Estroma/citología , Trasplante Heterólogo/métodos , Carga Tumoral/genética

RESUMEN

Endometriosis is a benign gynaecological disease appearing with pelvic pain, rising dysmenorrhoea and infertility seriously impacting on 10% of reproductive-age females. This research attempts to demonstrate the function and molecular mechanism of RhoA/ROCK pathway on epithelial-mesenchymal transition (EMT) and proliferation in endometriosis. The expression of Rho family was abnormally changed in endometriotic lesions; in particular, RhoA and ROCK1/2 were significantly elevated. Overexpression of RhoA in human eutopic endometrial epithelial cells (eutopic EECs) enhanced the cell mobility, epithelial-mesenchymal transition (EMT) and proliferation, and RhoA knockdown exhibited the opposite function. Oestrogen up-regulated the RhoA activity and expression of RhoA and ROCK1/2. RhoA overexpression reinforced the effect of oestrogen on promoting EMT and proliferation, and RhoA knockdown impaired the effect of oestrogen. oestrogen receptor α (ERα) was involved with the regulation of oestrogen on EMT and proliferation and up-regulated RhoA activity and expression of RhoA and ROCK1/2. The function of ERα was modulated by the change in RhoA expression. Furthermore, phosphorylated ERK that was enhanced by oestrogen and ERα promoted the protein expression of RhoA/ROCK pathway. Endometriosis mouse model revealed that oestrogen enhanced the size and weight of endometriotic lesions. The expression of RhoA and phosphorylated ERK in mouse endometriotic lesions was significantly elevated by oestrogen. We conclude that abnormal activated RhoA/ROCK pathway in endometriosis is responsible for the function of oestrogen/ERα/ERK signalling, which promoted EMT and proliferation and resulted in the development of endometriosis.

Asunto(s)

Endometriosis/patología , Endometrio/patología , Transición Epitelial-Mesenquimal/fisiología , Estrógenos/fisiología , Transducción de Señal/fisiología , Quinasas Asociadas a rho/fisiología , Proteína de Unión al GTP rhoA/fisiología , Adulto , Animales , Células Cultivadas , Modelos Animales de Enfermedad , Endometriosis/cirugía , Endometrio/efectos de los fármacos , Endometrio/trasplante , Transición Epitelial-Mesenquimal/efectos de los fármacos , Estradiol/farmacología , Receptor alfa de Estrógeno/efectos de los fármacos , Receptor alfa de Estrógeno/genética , Receptor alfa de Estrógeno/fisiología , Femenino , Regulación de la Expresión Génica , Humanos , Ratones , Ratones Endogámicos BALB C , Quistes Ováricos/etiología , Quistes Ováricos/cirugía , Interferencia de ARN , ARN Mensajero/biosíntesis , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/farmacología , Proteínas Recombinantes/efectos de los fármacos , Proteínas Recombinantes/metabolismo , Transducción de Señal/efectos de los fármacos , Quinasas Asociadas a rho/biosíntesis , Quinasas Asociadas a rho/genética , Proteína de Unión al GTP rhoA/antagonistas & inhibidores , Proteína de Unión al GTP rhoA/biosíntesis , Proteína de Unión al GTP rhoA/genética

RESUMEN

PROBLEM: The application of primary eutopic endometrial cells from endometriosis patients in research is restricted for short life span, dedifferentiation of hormone responsiveness. METHOD OF STUDY: Human telomerase reverse transcriptase (hTERT)-induced immortalized cells (iheESCs) were infected by lentivirus. mRNA level was examined by qRT-PCR, and protein expression was quantified by Western blot. CCK-8 and EdU assay were assigned to assess the proliferation. The migration and invasion of cells were assessed by transwell assay. Clone formation assay and nude mouse tumorigenicity assay were used to evaluate colony-formation and tumorigenesis abilities. RESULTS: hTERT mRNA and protein were significantly expressed higher in iheESCs compared to primary cells. iheESCs grew without morphological change for 42 passages which is much longer than 18 passages of primary cells. There was no obvious difference between primary cells and iheESCs in growth, mobility, and chromosome karyotype. Furthermore, the expression of epithelial-mesenchymal transition (EMT) markers and estrogen/progesterone receptors remained unchanged. The decidualization of iheESCs could be induced by progesterone and cAMP. Estrogen increased the proliferation and mobility of iheESCs, and lipopolysaccharides (LPS) induced the IL-1ß and IL-6 promoting inflammatory response. The colony-forming ability of iheESCs, like primary cells, was lower than Ishikawa cells. In addition, tumorigenicity assay indicated that iheESCs were unable to trigger tumor formation in BALB/c nude mouse. CONCLUSIONS: This study established and characterized iheESCs that kept the cellular physiology of primary cells and were not available with tumorigenic ability. Thus, iheESCs would be useful as in vitro cell model to investigate pathogenesis of endometriosis.

Asunto(s)

Endometriosis/patología , Endometrio/citología , Células del Estroma/citología , Animales , Carcinogénesis , Línea Celular Transformada , Movimiento Celular , Proliferación Celular , Transición Epitelial-Mesenquimal , Femenino , Humanos , Ratones , Ratones Desnudos , Telomerasa/metabolismo , Ensayo de Tumor de Célula Madre

RESUMEN

PURPOSE: Diosgenin (DSG) is the precursor of steroid hormones and plays a crucial part in the proliferation of various carcinomas including human colorectal cancer and gastric carcinoma. Nevertheless, its specific features and mechanisms in human cholangiocarcinoma (CCA) remain unknown. METHODS: MTS assay, colony-forming assay, and EdU assay were performed to determine the role of DSG on the progression of human CCA cells. The distributions of cell cycle, the ratio of apoptosis, and the mitochondrial membrane potential (ΔΨm) were studied by flow cytometry (FCM). AO/EB and Hoechst 33258 staining were performed to observe the morphological features of cell apoptosis. TEM was performed to observe the ultrastructures of QBC939 and HuCCT1 cells. The mRNA and protein expression of mitochondrial apoptotic pathway and GSK3ß/ß-catenin pathway were further confirmed by qPCR and Western blotting. The xenograft tumor model of HuCCT1 cells was built. Immunohistochemistry of tumor tissues was performed. RESULTS: Our results indicated that DSG inhibited the progression of six CCA cell lines. In vivo tumor studies also indicated that DSG significantly inhibited tumor growth in xenografts in nude mice. The expression of mitosis-promoting factor cyclinB1 was decreased along with the elevating level of cell cycle inhibitor p21, resulting in arresting CCA cell cycles at G2/M phase. Furthermore, DSG induced apoptosis with the increased expressions of cytosol cytochrome C, cleaved-caspase-3, cleaved-PARP1 and the Bax/Bcl-2 ratio. Mechanistically, our study showed that GSK3ß/ß-catenin pathway was involved in the apoptosis of CCA cells. Thus, DSG might provide a new clue for the drug therapy of CCA. CONCLUSION: In our data, DSG was found to have efficient antitumor potential of human CCA cells in vitro and in vivo.

RESUMEN

Vasculogenic mimicry (VM) is a new pattern of blood supplement independent of endothelial vessels, which is related with tumor invasion, metastasis and prognosis. However, the role of VM in the prognosis of cancer patients is controversial. This study aimed to perform a meta-analysis of the published data to attempt to clarify the prognostic value of VM in the digestive cancer. Relevant studies were retrieved from the PubMed, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure and VIP databases published before March 29, 2018. Studies were included if they detected VM in the digestive cancer and analyzed the overall survival (OS) or disease-free survival (DFS) according to VM status. Two independent reviewers screened the studies, extracted data, and evaluated the quality of included studies with the Newcastle-Ottawa scale. Meta-analysis was performed using STATA 12.0 software. A total of 22 studies with 2411 patients were included in this meta-analysis. Meta-analysis showed that VM was related with the poor OS (HR = 2.30, 95% CI: 2.06-2.56, P < 0.001) and DFS (HR = 2.60, 95% CI: 2.07-3.27, P < 0.001) of patients with digestive cancer. Subgroup analysis showed VM was related with tumor differentiation, lymph node metastasis and TNM stage. Moreover, the present meta-analysis was reliable, and there was no obvious publication bias. This meta-analysis suggested that VM was a poor prognosis of digestive cancer patients. Further large and well-designed studies are required.

Asunto(s)

Neoplasias Gastrointestinales/patología , Neovascularización Patológica/patología , Diferenciación Celular/fisiología , Supervivencia sin Enfermedad , Humanos , Metástasis Linfática/patología , Pronóstico

RESUMEN

BACKGROUND: Aberrant expression of retinoic acid receptor α (RARα) was correlated with diverse carcinomas such as acute promyelocytic leukemia and colorectal carcinoma. Nevertheless, the function and mechanism of RARα in esophageal carcinoma (EC) remain unclear. AIM: To investigate the expression of RARα in EC and its effect in the tumorigenesis of EC. METHODS AND RESULTS: In immunohistochemistry study, RARα was overexpressed in human EC tissues, and its overexpression was closely related to the pathological differentiation, lymph node metastasis, and clinical stages in EC patients. Functionally, RARα knockdown suppressed the proliferation and metastasis of EC cells through downregulating the expression of PCNA, Ki67, MMP7, and MMP9, as well as enhanced drug susceptibility of EC cells to 5-fluorouracil and cisplatin. Mechanistically, RARα knockdown inhibited the activity of Wnt/ß-catenin pathway through reducing the phosphorylation level of GSK3ß at Ser-9 and inducing phosphorylation level at Tyr-216, which resulted in downregulation of its downstream targets such as MMP7, MMP9, and P-gP. CONCLUSIONS: Our results demonstrated that RARα knockdown suppressed the tumorigenicity of EC via Wnt/ß-catenin pathway. RARα might be a potential molecular target for EC clinical therapy.

Asunto(s)

Neoplasias Esofágicas , Regulación Neoplásica de la Expresión Génica , Receptor alfa de Ácido Retinoico/metabolismo , Vía de Señalización Wnt/fisiología , Carcinogénesis/metabolismo , Línea Celular Tumoral , Proliferación Celular , Supervivencia Celular , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patología , Femenino , Técnicas de Inactivación de Genes/métodos , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Ensayo de Tumor de Célula Madre/métodos

RESUMEN

The polysaccharides (AVP) was obtained from abalone (Haliotis discus hannai Ino) viscera, using the alkaline protease to enzymolysis, sevage method and repeated freezing and thawing method to remove protein and hydrogen peroxide method to depigment. The total sugar content was 46.27±1.5% and uronic acid, sulfate radical, hexosamine and protein contents were 17.44±0.22%, 16.98±0.15%, 0.65±0.02% and 1.64±0.13% in AVP respectively. The main monosaccharide compositions of AVP were d-galactose, d-xylose, d-mannose, d-glucose and d-glucuronic acid. MTT assay showed AVP had a significant anti-tumor activity to gastric carcinoma cells, especially to MGC 803, while it had no influence upon proliferation of normal stomach cells GES 1. The results of Morphological changes, cell migration ability and AO/EB staining indicated that MGC803 cells underwent apoptosis in a dose-dependent manner induced by AVP. Moreover, the western blotting results showed that the expressions of survivin, Bcl-2 and VEGF were decreased, while the expression of Bax and p53 were increased in a dose-dependent manner of AVP. The results suggested that AVP might be a potential anti-tumor agent securely and naturally.

Asunto(s)

Antineoplásicos/farmacología , Proliferación Celular/efectos de los fármacos , Células Epiteliales/efectos de los fármacos , Gastrópodos/química , Regulación Neoplásica de la Expresión Génica , Polisacáridos/farmacología , Animales , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Apoptosis/efectos de los fármacos , Línea Celular , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Células Epiteliales/metabolismo , Células Epiteliales/patología , Mucosa Gástrica/metabolismo , Hexosaminas/química , Hexosaminas/aislamiento & purificación , Humanos , Proteínas Inhibidoras de la Apoptosis/antagonistas & inhibidores , Proteínas Inhibidoras de la Apoptosis/genética , Proteínas Inhibidoras de la Apoptosis/metabolismo , Especificidad de Órganos , Polisacáridos/química , Polisacáridos/aislamiento & purificación , Proteínas/química , Proteínas/aislamiento & purificación , Proteínas Proto-Oncogénicas c-bcl-2/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Estómago/patología , Survivin , Proteína p53 Supresora de Tumor/agonistas , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Ácidos Urónicos/química , Ácidos Urónicos/aislamiento & purificación , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Vísceras/química , Proteína X Asociada a bcl-2/agonistas , Proteína X Asociada a bcl-2/genética , Proteína X Asociada a bcl-2/metabolismo

RESUMEN

Crocodile choline, an active compound isolated from Crocodylus siamensis, was found to exert potent anti-cancer activities against human gastric cancer cells in vitro and in vivo. Our study revealed that crocodile choline led to cell cycle arrest at the G2/M phase through attenuating the expressions of cyclins, Cyclin B1, and CDK-1. Furthermore, crocodile choline accelerated apoptosis through the mitochondrial apoptotic pathway with the decrease in mitochondrial membrane potential, the increase in reactive oxygen species production and Bax/Bcl-2 ratio, and the activation of caspase-3 along with the release of cytochrome c. In addition, this study, for the first time, shows that Notch pathway is remarkably deregulated by crocodile choline. The combination of crocodile choline and Notch1 short interfering RNA led to dramatically increased cytotoxicity than observed with either agent alone. Notch1 short interfering RNA sensitized and potentiated the capability of crocodile choline to suppress the cell progression and invasion of gastric cancer. Taken together, these data suggested that crocodile choline was a potent progression inhibitor of gastric cancer cells, which was correlated with mitochondrial apoptotic pathway and Notch pathway. Combining Notch1 inhibitors with crocodile choline might represent a novel approach for gastric cancer.

Asunto(s)

Apoptosis/efectos de los fármacos , Colina/administración & dosificación , Receptor Notch1/biosíntesis , Neoplasias Gástricas/tratamiento farmacológico , Caimanes y Cocodrilos/metabolismo , Animales , Protocolos de Quimioterapia Combinada Antineoplásica , Proteína Quinasa CDC2 , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Ciclina B1/biosíntesis , Quinasas Ciclina-Dependientes/biosíntesis , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Mitocondrias/efectos de los fármacos , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Receptor Notch1/genética , Transducción de Señal/efectos de los fármacos , Proteína X Asociada a bcl-2/biosíntesis

RESUMEN

Apoptosis, programmed cell death under physiological or pathological conditions, plays a critical role in the tissue homeostasis of eukaryotes. It is desirable to prevent the occurrence and metastasis of cancer through inducing apoptosis. Our previous study demonstrated that apoptosis could be induced by extract from crocodile in human cholangiocarcinoma. ESC-3, a novel cytotoxic compound isolated from the extract induced apoptosis in Mz-ChA-1 cells via the mitochondria-dependent pathway in a dose-dependent manner. In this study, ESC-3 significantly inhibited the proliferation of A2780 cells and arrested the cells at G2/M phase. After exposure to ESC-3, A2780 cells displayed typical morphological changes and the ability of colony-forming was remarkably inhibited. ESC-3 could significantly upregulate the expression of Bax proteins while Bcl-2 protein remained unchanged, resulting in the elevation of Bax/Bcl-2 ratio, which usually could induce apoptosis. The critical protein of Wnt signaling (ß-catenin) was significantly downregulated, whereas Hes1, the downstream protein of Notch signaling, was remarkably attenuated through upregulating the expression of P53. In addition, xenograft models demonstrated that ESC-3 effectively suppressed the growth of OvCa tumors (T/C=42%). Western blot analysis of PCNA and VEGF confirmed that ESC-3 could inhibit the growth and metastasis of OvCa tumors. In conclusion, apoptosis could be induced by ESC-3 through Wnt/ß-catenin and Notch signaling in vitro and in vivo, and might have therapeutic potential for the treatment of human OvCa.

Asunto(s)

Carcinoma/tratamiento farmacológico , Proteínas de Neoplasias/biosíntesis , Neoplasias Ováricas/tratamiento farmacológico , Extractos de Tejidos/administración & dosificación , Caimanes y Cocodrilos , Animales , Apoptosis/efectos de los fármacos , Carcinoma/genética , Carcinoma/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Mitocondrias/efectos de los fármacos , Mitocondrias/patología , Proteínas de Neoplasias/genética , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Receptores Notch/efectos de los fármacos , Extractos de Tejidos/química , Vía de Señalización Wnt/efectos de los fármacos

RESUMEN

OBJECTIVE: To study the method on comprehensive evaluation of the middle ear function in children with secretory otitis media (SOM) after tympanotomy tube insertion. METHOD: Ear canal volume (ECV), pure tone audiometry and distortion product otoacoustic emission(DPOAE) were carried out in 31 children(43 ears) with SOM before and 1 month after tube insertion,in the meantime Eustachian tube function was recorded. The tympanotomy tube was observed under microscope. RESULT: After one month of tube insertion, the hearing level was improved in 39 ears with an ECV > 2.0 ml. In addition,the detection rate and amplitude of DPOAE were significantly increased in these 39 ears. No case of the function of Eustachian tube was complete recovered. CONCLUSION: ECV, pure tone audiometry, DPOAE and inflation-deflation test are significantly clinical worth for comprehensive evaluation of the middle ear function in children with SOM after tympanotomy tube insertion.

Asunto(s)

Trompa Auditiva , Otitis Media con Derrame/fisiopatología , Pruebas de Impedancia Acústica , Audiometría de Tonos Puros , Niño , Preescolar , Oído Medio/fisiopatología , Oído Medio/cirugía , Femenino , Humanos , Masculino , Otitis Media con Derrame/cirugía , Resultado del Tratamiento

RESUMEN

OBJECTIVE: To summarize the symptoms, various diagnostic procedures, and therapy of extraluminal foreign body originated from pharynx and esophagus (EFBOPE). METHOD: Twenty-four patients with EFBOPE were retrospectively reviewed. RESULT: Twenty-two cases were removed surgically, 1 case was spontaneous expulsion, 1 case died. CONCLUSION: EFBOPE is seldom seen in the clinical, diagnosis of EFBOPE should be considered whenever haematemesis or haemorrhage, inflammation or abscess in parapharyngeal space outside of pharynx and esophagus are presented after ingesting foreign body. Radiography and computed tomography are main diagnostic tools. Surgical treatment is the only effective method for EFBOPE and must be performed in time.

Asunto(s)

Esófago , Cuerpos Extraños/diagnóstico por imagen , Cuerpos Extraños/cirugía , Faringe , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Radiografía , Estudios Retrospectivos

RESUMEN

OBJECTIVE: To investigate the objective methods for tinnitus exploration by analysing the cochlear activity in tinnitus patients with normal hearing. METHOD: The 50 cases (50 ears) of unilateral tinnitus with normal hearing (the plastic group 1), 24 cases (46 ears) of bilateral tinnitus with normal hearing(the plastic group 2) and the 34 persons (68 ears) of normal hearing without tinnitus (control group) were measured by evoked otoacoustic emissions (TEOAE and DPOAE). All the tinnitus patients were also tested by the subjective tinnitus frequency and analysed with appropriate characteristic in TEOAE and DPOAE audiogram. RESULT: (1) The passing rate of TEOAE was 64.0% in the tinnitus group 1, 91.3% in the group 2, and 100% in the control group (group 1 P < 0.01, group 2 P >0.05 ). (2) The passing rate of DPOAE was 100% in three groups. But comparing to the control group, the amplitudes of DPOAE at the limited frequency ranges (3.125 kHz and 8.837 kHz) of the tinnitus group 1 was significant decreased ( P <0.05). (3) The subjective tinnitus frequencies were 0.25 approximately 8.00 kHz. The decreases in amplitudes and absent within the tinnitus frequencies were observed in TEOAE and DPOAE audiogram. CONCLUSION: Some patients of normal hearing with tinnitus have had early harmness of outer hair cell in cochlear. Evoked otoacoustic emissions is one of worthy methods to evaluated objectively the tinnitus. TEOAE is more susceptible to harmness in cochlear than DPOAE. DPOAE is superior to the analysis of tinnitus frequencies.

Asunto(s)

Audiometría de Respuesta Evocada , Emisiones Otoacústicas Espontáneas , Acúfeno/diagnóstico , Adolescente , Adulto , Niño , Cóclea/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad

Asunto(s)

Analgesia/métodos , Fentanilo/administración & dosificación , Dolor Postoperatorio/prevención & control , Administración Cutánea , Adolescente , Adulto , Femenino , Humanos , Masculino , Tonsilectomía/métodos , Adulto Joven