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AKT inhibitor suppresses hyperthermia-induced Ndrg2 phosphorylation in gastric cancer cells BJMBR
Tao,Yurong; Guo,Yan; Liu,Wenchao; Zhang,Jian; Li,Xia; Shen,Lan; Ru,Yi; Xue,Yan; Zheng,Jin; Liu,Xinping; Zhang,Jing; Yao,Libo.
Hyperthermia is one of the most effective adjuvant treatments for various cancers with few side effects. However, the underlying molecular mechanisms still are not known. N-myc downstream-regulated gene 2 (NDRG2), a tumor suppressor, has been shown to be involved in diverse cellular stresses including hypoxia, lipotoxicity, etc. In addition, Ndrg2 has been reported to be related to progression of gastric cancer. In the current study, our data showed that the apoptosis rate of MKN28 cells increased relatively rapidly to 13.4% by 24 h after treatment with hyperthermia (42°C for 1 h) compared to 5.1% in control cells (P < 0.05). Nevertheless, there was no obvious change in the expression level of total Ndrg2 during this process. Further investigation...
Tipo: Info:eu-repo/semantics/article Palavras-chave: Hyperthermia; Gastric cancer; Ndrg2; Apoptosis; AKT inhibitor.
Ano: 2013 URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2013000400394
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Chemotherapy versus support cancer treatment in advanced gastric cancer: a meta-analysis BJMBR
Casaretto,L.; Sousa,P.L.R.; Mari,J.J..
The aim of the present study was to compare the efficacy of chemotherapy and support treatment in patients with advanced non-resectable gastric cancer in a systematic review and meta-analysis of randomized clinical trials that included a comparison of chemotherapy and support care treatment in patients diagnosed with gastric adenocarcinoma, regardless of their age, gender or place of treatment. The search strategy was based on the criteria of the Cochrane Base, using the following key words: 1) randomized clinical trials and antineoplastic combined therapy or gastrointestinal neoplasm, 2) stomach neoplasm and drug therapy, 3) clinical trial and multi-modality therapy, 4) stomach neoplasm and drug therapy or quality of life, 5) double-blind method or...
Tipo: Info:eu-repo/semantics/article Palavras-chave: Gastric cancer; Systematic review; Combined antineoplastic therapy; Cancer support treatment; Meta-analysis; Chemotherapy.
Ano: 2006 URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2006000400002
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Correlation of cadherin-17 protein expression with clinicopathological features and prognosis of patients with sporadic gastric cancer BJMBR
Meng,W.; Gu,T.; Gao,L. M.; Zong,Z. G.; Meng,L.; Fu,Z. Z.; Guo,L..
This study aimed to explore the correlations between cadherin-17 (CDH17) protein expression and the clinicopathological features and prognosis of patients with sporadic gastric cancer (GC). Nine relevant studies of 1,960 patients were identified using electronic database searches supplemented with a manual search in strict accordance with inclusion and exclusion criteria. Statistical analyses were conducted using STATA 12.0 statistical software. Relative risks and 95% confidence intervals were determined, and Z test was used to measure the significance of the overall effect size. A total of nine eligible cohort studies were included in this meta-analysis. The expression of CDH17 in patients with diffuse GC was significantly higher than in those with...
Tipo: Info:eu-repo/semantics/article Palavras-chave: Cadherin-17; Gastric cancer; Clinicopathological features; Prognosis; Meta-analysis; Cohort study.
Ano: 2015 URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2015001201077
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COX-2 gene expression and methylation profile in Sapajus apella as an experimental model for gastric adenocarcinoma Genet. Mol. Biol.
Rosário Pinheiro,Danilo do; Harada,Maria Lucia; Rodriguez Burbano,Rommel Mario; Nascimento Borges,Barbara do.
Abstract Gastric cancer (GC) remains one of the main causes of cancer-related death worldwide. There are two distinct histological types of GC: diffuse and intestinal. The latter is characterized by the presence of pre-neoplastic lesions. One of the most frequently altered enzymes in intestinal GC is COX-2, an important lesion marker. This work aimed to study COX-2 methylation and expression in N-methyl-N-Nitrosurea (MNU)-induced intestinal GC in six Sapajus apella animals. The partial promoter sequence of S. apella COX-2 gene was obtained and used to identify transcription factors and cis-regulatory element binding sites. The COX-2 methylation pattern was assessed using Methylation-Specific PCR (MSP), and expression was analyzed by immunohistochemistry...
Tipo: Info:eu-repo/semantics/article Palavras-chave: PTGS2; Gene regulation; Animal model; Gastric cancer.
Ano: 2018 URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572018000300496
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Cytogenetic characterization and evaluation of c-MYC gene amplification in PG100, a new Brazilian gastric cancer cell line BJMBR
Ribeiro,H.F.; Alcântara,D.F.A.; Matos,L.A.; Sousa,J.M.C.; Leal,M.F.; Smith,M.A.C.; Burbano,R.R.; Bahia,M.O..
Gastric cancer is the fourth most frequent type of cancer and the second cause of cancer mortality worldwide. The genetic alterations described so far for gastric carcinomas include amplifications and mutations of the c-ERBB2, KRAS, MET, TP53, and c-MYC genes. Chromosomal instability described for gastric cancer includes gains and losses of whole chromosomes or parts of them and these events might lead to oncogene overexpression, showing the need for a better understanding of the cytogenetic aspects of this neoplasia. Very few gastric carcinoma cell lines have been isolated. The establishment and characterization of the biological properties of gastric cancer cell lines is a powerful tool to gather information about the evolution of this malignancy, and...
Tipo: Info:eu-repo/semantics/other Palavras-chave: Carcinogenesis; Chromosomal abnormalities; Gastric cancer; Oncogenes.
Ano: 2010 URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2010000800004
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DNA methylation regulates expression of VEGF-C, and S-adenosylmethionine is effective for VEGF-C methylation and for inhibiting cancer growth BJMBR
Da,M.X.; Zhang,Y.B.; Yao,J.B.; Duan,Y.X..
DNA hypomethylation may activate oncogene transcription, thus promoting carcinogenesis and tumor development. S-adenosylmethionine (SAM) is a methyl donor in numerous methylation reactions and acts as an inhibitor of intracellular demethylase activity, which results in hypermethylation of DNA. The main objectives of this study were to determine whether DNA hypomethylation correlated with vascular endothelial growth factor-C (VEGF-C) expression, and the effect of SAM on VEGF-C methylation and gastric cancer growth inhibition. VEGF-C expression was assayed by Western blotting and RT-qPCR in gastric cancer cells, and by immunohistochemistry in tumor xenografts. VEGF-C methylation was assayed by bisulfite DNA sequencing. The effect of SAM on cell apoptosis was...
Tipo: Info:eu-repo/semantics/article Palavras-chave: VEGF-C; Methylation; S-adenosylmethionine; Gastric cancer.
Ano: 2014 URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2014001201021
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DNA mismatch repair gene methylation in gastric cancer in individuals from northern Brazil Biocell
Moura Lima,Eleonidas; Ferreira Leal,Mariana; de Arruda Cardoso Smith,Marília; Rodríguez Burbano,Rommel; Pimentel de Assumpção,Paulo; Bello,Maria Jose; Rey,Juan Antonio; Ferreira de Lima,Francinaldo; Casartelli,Cacilda.
Gastric cancer is one of the most common malignancies. DNA methylation is implicated in DNA mismatch repair genes deficiency. In the present study, we evaluated the methylation status of MLH1, MSH2, MSH6 and PMS2 in 20 diffuse- and 26 intestinal-type gastric cancer samples and 20 normal gastric mucosal of gastric cancer patients from Northern Brazil. We found that none of the nonneoplastic samples showed methylation of any gene promoter and 50% of gastric cancer samples showed at least one methylated gene promoter. Methylation frequencies of MLH1, MSH2, MSH6 and PMS2 promoter were 21.74%, 17.39%, 0% and 28.26% respectively in gastric cancer samples. MLH1 and PMS2 methylation were associated with neoplastic samples compared to nonneoplastic ones. PMS2...
Tipo: Info:eu-repo/semantics/article Palavras-chave: Gastric cancer; MLH1; MSH2; MSH6; PMS2.
Ano: 2008 URL: http://www.scielo.org.ar/scielo.php?script=sci_arttext&pid=S0327-95452008000300004
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Effect of surgical treatment on the cellular immune response of gastric cancer patients BJMBR
Barbieri,C.; Fujisawa,M.M.; Yasuda,C.L.; Metze,I.L.; Oliveira,E.C.; Santos,L.M.B.; Lopes,L.R.; Andreollo,N.A..
Patients with gastric cancer have a variety of immunological abnormalities. In the present study the lymphocytes and their subsets were determined in the peripheral blood of patients with gastric cancer (N = 41) both before and after surgical treatment. The percent of helper/inducer CD4 T cells (43.6 ± 8.9) was not different after tumor resection (43.6 ± 8.2). The percent of the cytotoxic CD8+ T cell population decreased significantly, whether patients were treated surgically (27.2 ± 5.8%, N = 20) or not (27.3 ± 7.3%, N = 20) compared to individuals with inflammatory disease (30.9 ± 7.5%) or to healthy individuals (33.2 ± 7.6%). The CD4/CD8 ratio consequently increased in the group of cancer patients. The peripheral blood lymphocytes of gastric cancer...
Tipo: Info:eu-repo/semantics/article Palavras-chave: Gastric cancer; Cellular immune response; Transforming growth factor beta; Immunosuppression.
Ano: 2003 URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2003000300008
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Elementary screening of lymph node metastatic-related genes in gastric cancer based on the co-expression network of messenger RNA, microRNA and long non-coding RNA BJMBR
Song,Zhonghua; Zhao,Wenhua; Cao,Danfeng; Zhang,Jinqing; Chen,Shouhua.
Gastric cancer (GC) is the fifth most common cancer and the third leading cause of cancer-related deaths worldwide. The high mortality might be attributed to delay in detection and is closely related to lymph node metastasis. Therefore, it is of great importance to explore the mechanism of lymph node metastasis and find strategies to block GC metastasis. Messenger RNA (mRNA), microRNA (miRNA) and long non-coding RNA (lncRNA) expression data and clinical data were downloaded from The Cancer Genome Atlas (TCGA) database. A total of 908 differentially expressed factors with variance >0.5 including 542 genes, 42 miRNA, and 324 lncRNA were screened using significant analysis microarray algorithm, and interaction networks were constructed using these...
Tipo: Info:eu-repo/semantics/article Palavras-chave: Gastric cancer; Lymph node metastasis; Co-expression network; Modular analysis.
Ano: 2018 URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2018000400602
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Expression of TERT in precancerous gastric lesions compared to gastric cancer BJMBR
Duarte,M.C.; Babeto,E.; Leite,K.R.M.; Miyazaki,K.; Borim,A.A.; Rahal,P.; Silva,A.E..
The objective of this study was to determine the levels of TERT mRNA and TERT protein expression in stomach precancerous lesions such as intestinal metaplasia (IM) and gastric ulcer (GU) and compare them to gastric cancer (GC). Real-time PCR was performed to detect TERT mRNA expression levels in 35 biopsies of IM, 30 of GU, and 22 of GC and their respective normal mucosas. TERT protein was detected by immunohistochemistry in 68 samples, 34 of IM, 23 of GU, and 11 of GC. Increased TERT mRNA expression levels were observed in a significant number of cases, i.e., 46% of IM, 50% of GU, and 79% of GC. The relative mean level of TERT mRNA after normalization with the β-actin reference gene and comparison with the respective adjacent normal mucosa was slightly...
Tipo: Info:eu-repo/semantics/other Palavras-chave: Gastric ulcer; Intestinal metaplasia; Gastric cancer; TERT; Gene expression; Protein expression.
Ano: 2011 URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2011000200003
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FGFR1 is an independent prognostic factor and can be regulated by miR-497 in gastric cancer progression BJMBR
Xie,Gang; Ke,Qi; Ji,Yu Zu; Wang,An-qun; Jing,Meng; Zou,li-li.
Fibroblast growth factor receptor 1 (FGFR1) has been reported in gastric cancer to be a prognostic factor. However, miR-497-targeted FGFR1 has not been explored in the carcinogenesis of gastric cancer. The present study intended to revalidate the prognostic significance of FGFR1 in patients with gastric cancer, and the mechanism of miR-497-regulated FGFR1 was investigated in gastric cancer cell proliferation and apoptosis. The messenger RNA (mRNA) and protein levels were assayed by RT-qPCR and western blotting, respectively. The targeted genes were predicted by a bioinformatics algorithm and confirmed by a dual luciferase reporter assay. Cell proliferation was analyzed by CCK-8 assay. Annexin V-FITC/PI staining was used to evaluate the apoptosis in AGS and...
Tipo: Info:eu-repo/semantics/article Palavras-chave: FGFR1; MiR-497; Apoptosis; Post-transcriptional; Gastric cancer.
Ano: 2019 URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2019000100602
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Growth inhibitory effect and Chk1-dependent signaling involved in G2/M arrest on human gastric cancer cells induced by diallyl disulfide BJMBR
Ling,H.; Wen,L.; Ji,X.X.; Tang,Y.L.; He,J.; Tan,H.; Xia,H.; Zhou,J.G.; Su,Q..
Diallyl disulfide (DADS) inhibits growth and induces cell cycle G2/M arrest in human gastric cancer MGC803 cells. In this study, 15 mg/L DADS exerted similar effects on growth and cell cycle arrest in human gastric cancer BGC823 cells. Due to the importance of cell cycle redistribution in DADS-mediated anti-carcinogenic effects, we investigated the role of checkpoint kinases (Chk1 and Chk2) during DADS-induced cell cycle arrest. We hypothesized that DADS could mediate G2/M phase arrest through either Chk1 or Chk2 signal transduction pathways. We demonstrated that DADS induced the accumulation of phosphorylated Chk1, but not of Chk2, and that DADS down-regulated Cdc25C and cyclin B1. The expression of mRNA and total protein for Chkl and Chk2 was unchanged....
Tipo: Info:eu-repo/semantics/article Palavras-chave: Diallyl disulfide; Cell cycle G2/M arrest; Checkpoint kinase-1; Gastric cancer.
Ano: 2010 URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2010000300008
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Kaempferol suppresses human gastric cancer SNU-216 cell proliferation, promotes cell autophagy, but has no influence on cell apoptosis BJMBR
Zhang,Fan; Ma,Cuimei.
Gastric cancer remains a serious threat to human health worldwide. Kaempferol is a plant-derived flavonoid compound with a wide range of pharmacological activities. This study aimed to investigate the effects of kaempferol on gastric cancer SNU-216 cell proliferation, apoptosis, and autophagy, as well as underlying potential mechanisms. Viability, proliferation, and apoptosis of SNU-216 cells after kaempferol treatment were evaluated using cell counting kit-8 assay, 5-btomo-2′-deoxyuridine incorporation assay, and annexin V-FITC/PI staining, respectively. Quantitative reverse transcription PCR was performed to measure the mRNA expressions of cyclin D1 and microRNA-181a (miR-181a) in SNU-216 cells. Cell transfection was used to down-regulate the expression...
Tipo: Info:eu-repo/semantics/article Palavras-chave: Gastric cancer; Kaempferol; MicroRNA-181a; Cell proliferation; Cell autophagy.
Ano: 2019 URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2019000200610
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Knockdown of long non-coding RNA ANRIL inhibits tumorigenesis in human gastric cancer cells via microRNA-99a-mediated down-regulation of BMI1 BJMBR
Liu,Pei; Zhang,Mingming; Niu,Qinghui; Zhang,Fengjuan; Yang,Yuling; Jiang,Xiangjun.
Long non-coding RNA antisense non-coding RNA in the INK4 locus (ANRIL) has been reported to promote tumorigenesis via regulating microRNA (miR)-99a in gastric cancer cells. However, the role of each component involved in it is still not well understood. This study aimed to verify the role of ANRIL in gastric cancer as well as the underlying mechanisms. ANRIL levels in clinical gastric cancer tissues and cell lines were tested by qPCR. Effects of ANRIL silence on cell viability, migration and invasion, apoptosis, and miR-99a expression in MKN-45 and SGC-7901 cells were measured using CCK-8, Transwell assay, flow cytometry, and qPCR assays, respectively. Then, effects of miR-99a inhibition on ANRIL-silenced cells were evaluated. B-lymphoma Mo-MLV insertion...
Tipo: Info:eu-repo/semantics/article Palavras-chave: Gastric cancer; LncRNA ANRIL; MiR-99a; BMI1; Apoptotic pathway; Notch/mTOR pathway.
Ano: 2018 URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2018001000609
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lnterleukin-8 gene polymorphism and susceptibility to gastric cancer in a brazilian population Biol. Res.
Felipe,Aledson V; Silva,Tiago D; Pimenta,Célia A; Kassab,Paulo; Forones,Nora M.
BACKGROUND: Studies have demonstrated that some polymorphisms in different interleukin genes may increase the risk of cancer. The aim of this study was to investigate the association between the IL-8 (rs4073) -251A/T gene polymorphism and the risk of gastric cancer (GC). PATIENTS AND METHODS: A case-control study was conducted on patients with noncardia gastric cancer. DNA was extracted from leukocytes and the IL-8 (rs4073) -251A/T polymorphism was analyzed by PCR-RFLP. Infection with Helicobacter pylori was investigated in the serum by ELISA. RESULTS: The sample consisted of 104 patients with GC and 196 controls. Cigarette smoking (P=0.007) and high fat intake (P=0.01) were more frequent in patients with GC. The proportion of patients infected with H....
Tipo: Journal article Palavras-chave: IL-8; Polymorphism; Gastric cancer.
Ano: 2012 URL: http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602012000400007
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Methylation status of ANAPC1, CDKN2A and TP53 promoter genes in individuals with gastric cancer BJMBR
Lima,E.M.; Leal,M.F.; Burbano,R.R.; Khayat,A.S.; Assumpção,P.P.; Bello,M.J.; Rey,J.A.; Smith,M.A.C.; Casartelli,C..
Gastric cancer is the forth most frequent malignancy and the second most common cause of cancer death worldwide. DNA methylation is the most studied epigenetic alteration, occurring through a methyl radical addition to the cytosine base adjacent to guanine. Many tumor genes are inactivated by DNA methylation in gastric cancer. We evaluated the DNA methylation status of ANAPC1, CDKN2A and TP53 by methylation-specific PCR in 20 diffuse- and 26 intestinal-type gastric cancer samples and 20 normal gastric mucosa in individuals from Northern Brazil. All gastric cancer samples were advanced stage adenocarcinomas. Gastric samples were surgically obtained at the João de Barros Barreto University Hospital, State of Pará, and were stored at -80°C before DNA...
Tipo: Info:eu-repo/semantics/article Palavras-chave: DNA methylation; Gastric cancer; ANAPC1; CDKN2A; TP53.
Ano: 2008 URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2008000600017
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microRNA-3129 promotes cell proliferation in gastric cancer cell line SGC7901 via positive regulation of pRb BJMBR
Yang,Shaofeng; Sheng,Nan; Pan,Lili; Cao,Jing; Liu,Jiao; Ma,Ran.
Several microRNAs (miRNAs) have been reported as oncogenes or tumor suppressors in many cancers, including gastric cancer (GC). However, the role and molecular mechanism of miR-3129 in GC is largely unknown. We aimed to explore the function and the underlying molecular mechanism of miR-3129 in GC. Cancer tissues and corresponding adjacent tissues were collected from 50 patients with GC, and the expression of miR-3129 was detected by RT-qPCR. The expression of miR-3129 and pRb in human GC cell line SCG7091 was altered by transient transfection. Thereafter, MTT and flow cytometry assays were used to analyze cell viability and cell cycle. The expression of cyclin E, CDK2, CDK2 inhibitors (p16 and 21), and pRb were detected by RT-qPCR and western blot. A...
Tipo: Info:eu-repo/semantics/article Palavras-chave: MicroRNA-3129; Gastric cancer; PRb; Proliferation; Cell cycle.
Ano: 2018 URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2018000600612
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MicroRNA-383-5p inhibits the progression of gastric carcinoma via targeting HDAC9 expression BJMBR
Xu,Gang; Li,Na; Zhang,Yan; Zhang,Jinbiao; Xu,Rui; Wu,Yanling.
MicroRNAs (miRNAs), as post-transcriptional regulators, have been reported to be involved in the initiation and progression of various types of cancer, including gastric cancer (GC). The present study aimed to investigate the role of miR-383-5p in gastric carcinogenesis. Cell viability was analyzed using CCK-8 kit. Annexin V-fluorescein isothiocyanate/propidium iodide double staining was used to evaluate cell apoptosis. The expression levels of miR-383-5p and histone deacetylase 9 (HDAC9) mRNA in GC tissues and cell lines were analyzed using RT-qPCR. The protein expression of HDAC9 was detected by western blotting. We found that HDAC9 was up-regulated and miR-383-5p was down-regulated in GC tissues and cell lines. High HDAC9 expression or low miR-383-5p...
Tipo: Info:eu-repo/semantics/article Palavras-chave: MicroRNA-383-5p; Gastric cancer; HDAC9; Post-transcriptional regulation.
Ano: 2019 URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2019000800602
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MicroRNA-4290 suppresses PDK1-mediated glycolysis to enhance the sensitivity of gastric cancer cell to cisplatin BJMBR
Qian,Yan; Wu,Xu; Wang,Haixiao; Hou,Guowei; Han,Xiao; Song,Wei.
The development of chemotherapy resistance significantly impairs the efficiency of chemotherapy, but the underlying mechanisms of chemotherapy resistance in gastric cancer (GC) are complicated and still need to be further explored. Here, we aimed to reveal the effects of miR-4290/PDK1 (pyruvate dehydrogenase kinase 1) axis on chemotherapy resistance of GC in vitro. The expression patterns of miR-4290 in GC tissues and cell lines were determined by real-time quantitative PCR. Kaplan-Meier was used to assess the relationship between miR-4290 expression levels and patients' overall survival. CCK-8 and flow cytometry technologies were applied to detect cell proliferation and apoptosis. The luciferase gene reporter assay was used to evaluate the interaction...
Tipo: Info:eu-repo/semantics/article Palavras-chave: MiR-4290; PDK1; Cisplatin; Chemoresistance; Gastric cancer.
Ano: 2020 URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2020000500604
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Oridonin induces growth inhibition and apoptosis in human gastric carcinoma cells by enhancement of p53 expression and function BJMBR
Bi,Enxu; Liu,Dengqiang; Li,Youxi; Mao,Xuying; Wang,Aihua; Wang,Jingtao.
The tumor suppressive role of oridonin, an active compound extracted from Rabdosia rubescens, has been proven in several gastric cancer (GC) cell lines. The present study aimed to evaluate the effect of oridonin on another GC cell line, SNU-216, and explore the potential mechanisms. The viable cell numbers, cell migration, survival fraction, and cell viability were, respectively, evaluated by trypan blue exclusion assay, wound healing assay, clonogenic assay, and CCK-8 assay. Cell apoptosis was determined by flow cytometry assay and western blot. The expression of p53 was inhibited by transient transfection, and the efficiency was verified by western blot. qRT-PCR was performed to measure the mRNA expression of p53. Western blot was used to evaluate the...
Tipo: Info:eu-repo/semantics/article Palavras-chave: Oridonin; P53; Gastric cancer; Cell apoptosis; Mdm2.
Ano: 2018 URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2018001200608
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