Research progress in the regulation mechanism of key signal pathways affecting the prognosis of glioma / 国际外科学杂志

Glioma has a high malignant degree, high recurrence rate and poor prognosis. We analyzed signal pathway of the Hippo/YAP, PI3K/AKT/mTOR, miRNA, WNT/β-catenin, Notch, Hedgehog, TGF-β and the mechanism of key enzymes in glioma. It is concluded that YAP1 inhibitor may become an effective target for the treatment of glioma in the future.Inhibiting PI3K/AKT/mTOR, Shh, Wnt/β-Catenin and HIF-1α can reduce the migration ability and drug resistance of tumor cells to improve the prognosis of glioma. The analysis shows that Notch1 and Sox2 have a positive feedback regulation mechanism, and Notch4 predicts the malignant degree of glioma. In this way, notch can not only be treated for glioma stem cells in clinic, but also be used as an evaluation index to evaluate the prognosis, and provide an exploratory attempt for the direction of glioma treatment. MiRNA plays an important role in diagnosis, and in the treatment of glioma, it can play a further role with the delivery of nanoparticles and TMZ. It is believed that these studies will help us to have a deeper understanding of glioma, so that we will find new and better treatment schemes to gradually conquer the problem of glioma.

Mechanism study of CeRNA regulatory network mediating malignant tumor phenotype / 国际肿瘤学杂志

Competing endogenous RNAs (CeRNAs) are crisscrossing regulatory networks. CeRNAs networks can mediate malignant tumor cell phenotypes, including proliferation and inhibition, autophagy, infinite growth, induction of angiogenesis and angiogenic mimicosis, immune escape, etc.. It is expected to provide new diagnostic markers and therapeutic targets for malignant tumors to master the regulation and function of CeRNAs mediated phenotype in malignant tumors.

TMPO-AS1 is an independent prognostic factor for patients with laryngeal squamous cell carcinoma

SUMMARY OBJECTIVE Long noncoding RNA (lncRNAs) are frequently abnormally expressed in tumors and involved in the occurrence and progression of human cancer. Recently, a disease-related lncRNA, TMPO antisense RNA 1 (TMPO-AS1), was identified to be dysregulated in several tumors. Hence, we aimed to demonstrate whether TMPO-AS1 could be a promising prognostic marker for patients with laryngeal squamous cell carcinoma (LSCC). METHODS RT-PCR was performed to test TMPO-AS1 expressions in 187 LSCC specimens compared with matched normal specimens. Chi-squared tests were used to determine the associations between TMPO-AS1 expressions and the clinicopathological characteristics of LSCC patients. Then, the clinical outcome of LSCC patients who had lower or higher TMPO-AS1 expression was analyzed using Kaplan-Meier assays. Finally, a Cox proportional hazards model was carried out to evaluate the prognostic values of TMPO-AS1 and other clinical features. RESULTS We found that TMPO-AS1 was distinctly upregulated in human LSCC tissues compared with corresponding normal specimens (p < 0.01). Higher expressions of TMPO-AS1 were observed to be positively associated with the clinical stage (p = 0.020) and lymph node metastasis (p = 0.027). A clinical study in 187 patients revealed that patients with TMPO-AS1 low expressions had poorer survival than those with TMPO-AS1 high expressions (p = 0.0012). In addition, the result of multivariate assays demonstrated TMPO-AS1 expression is an independent predictor for the overall survival of LSCC patients. CONCLUSIONS TMPO-AS1 might be considered a novel molecule involved in LSCC progression, which provides a possible prognostic biomarker.

RESUMO OBJETIVO RNAs longos não-codificantes (INcRNAs) são frequentemente expressos anormalmente em tumores e estão envolvidos na ocorrência e progressão do câncer humano. Recentemente, um INcRNA relacionado com a doença, o TMPO antisense RNA 1 (TMPO-AS1), foi identificado como desregulado em vários tumores. Por isso, procuramos demonstrar se o TMPO-AS1 poderia ser um marcador de prognóstico promissor para pacientes com carcinoma de células escamosas da laringe (LSCC). MÉTODOS RT-PCR foi realizado para medir as expressões do TMPO-AS1 em 187 espécimes de LSCC em comparação com espécimes normais correspondentes. Foram utilizados testes Qui-quadrado para determinar as associações entre as expressões do TMPO-AS1 e as características clínicas dos pacientes com LSCC. Em seguida, o desfecho clínico dos pacientes com LSCC que tinham uma expressão do TMPO-AS1 inferior ou superior foi analisado com ensaios Kaplan-Meier. Por último, o modelo de riscos proporcionais de Cox foi utilizado para avaliar o valor prognóstico do TMPO-AS1 e outras características clínicas. RESULTADOS Observamos que o TMPO-AS1 estava claramente super-regulado nos tecidos de LSCC humanos em comparação com os espécimes normais correspondentes (p<0,01). Expressões mais elevadas de TMPO-AS1 estavam positivamente associadas ao estágio clínico (p=0,020) e à metástase linfática (p=0,027). Um estudo clínico com 187 pacientes revelou que aqueles com expressões mais baixas de TMPO-AS1 tiveram uma sobrevida pior do que aqueles com expressões elevadas de TMPO-AS1 (p=0,0012). Além disso, o resultado de ensaios multivariados demonstrou que a expressão do TMPO-AS1 é um preditor independente para a sobrevida global de pacientes com LSCC. CONCLUSÕES TMPO-AS1 pode ser considerado uma molécula nova envolvida na progressão do LSCC, o que proporciona um possível biomarcador de prognóstico.

Expression and clinical value of glycogen synthase kinase-3β, Dickkopf-1 and β-catenin in proximal gastric cancer / 中国基层医药

Objective@#To study the expression and clinical value of glycogen synthase kinase-3β(GSK-3β), Dickkopf-1(DKK-1) and β-catenin in patients with proximal gastric cancer.@*Methods@#From April 2016 to April 2017, 47 patients with proximal gastric cancer in Chengfeng Hospital of Daqing Oilfield Group were enrolled in this study.Immunohistological tests were performed in all patients' lesions, adjacent tissues and healthy tissues.The effects of different factors on the expression of GSK-3β and DKK-1 were compared.@*Results@#The positive expression rate of GSK-3β in the normal tissues of patients with proximal gastric cancer was 70.21% (33/47), which was higher than those in the lesions and adjacent tissues[21.28% (10/47), 21.28%(10/47)](χ2=31.985, P<0.01). The positive expression rates of DKK-1 and β-catenin in the gastric cancer tissues were 38.30% (18/47), 82.98% (39/47), respectively, which were higher than those in the adjacent tissues and normal tissues[8.51% (4/47), 8.51% (4/47), and 6.38% (3/47), 2.13% (1/47)](χ2=20.517, 88.471, all P<0.01). The GSK-3β positive expression rate was higher in patients with tumor node metastasis (TNM) stage I-II, moderately well differentiated, infiltrated more than 50%, non-metastatic lymph nodes (P<0.05). The DKK-1 positive expression rate was higher in patients with TNM stage III-IV, moderately well differentiated and less than 50% infiltrated lymph nodes (P<0.05).@*Conclusion@#GSK-3β, DKK-1 and β-catenin are important indicators in the development and metastasis of gastric cancer.The above indicators have clinical value in the diagnosis and evaluation of curative effect.

The regulatory effect and mechanisms of LncRNA CRNDE in digestive system tumors / 中国医师杂志

Long non-coding RNA regulates gene expression at multiple levels (epigenetics,transcriptional level,post-transcriptional level) and plays an important role in the development and progression of individual development and tumors.With the deep research,it is found that LncRNA CRNDE is an important cancer-related long non-coding RNA,and it is necessary to understand the specific role of LncRNA CRNDE in regulating tumor cell life activities.In recent years,the role of LncRNA CRNDE in tumorigenesis and development has been increasing.It has been found that LncRNA CRNDE is up-regulated in various tumors and is closely related to tumor proliferation,invasion,metastasis and patients' prognosis,becoming a new hot spot in cancer research.The author combines the latest literatures at home and abroad to review the role and mechanism of LncRNA CRNDE in the development of digestive system tumors,hoping to prevent and treat tumors in the future.

Time-series analysis of expression profile of adrenocortical carcinoma in children for screening related targets / 天津医药

@#Objective To explore the potential pathogenic mechanism of adrenocortical carcinoma (ACT), and screen out genes that may be related to biological targets. Methods In this study, the gene expression datasets of ACT were obtained from the Gene Expression Omnibus (GEO) with the accession number of GSE75415. Through R programming software, the microarray preprocessing and differential expression analysis of 18 ACT tissue samples (experimental group) and 7 normal adrenocortical tissue samples (control group) were conducted to identify potential biomarkers for ACT in different stages. Besides, through functional enrichment and Kaplan-Meier analysis, several more reliable biomarkers for ACT were identified. At the same time, the two generation sequencing data of the TCGA database, including 79 ACT samples were analyzed, and the genes that can affect the survival of ACT patients were screened. Results There were 248, 334, 315 and 561 differentially expressed genes in stage1-4 respectively. There were 73 overlapping genes (OLDEGs) among the different grading samples. Central genes HSPA13, GARS, STXBP1, AKIRIN1 and TUBB3, were up-regulated in all of stages of ACT samples compared with those of normal samples, while, central genes ADH1B, DCN, RASSF2, PDGFRA, PLAT, C3 and FOS were down-regulated in ACT samples. They were found to be significantly associated with pathways of immune response, cell cycle, phosphorylation and cruor, which were all closely related with ACT progression. Besides, Kaplan-Meier analysis of 73 OLDEGs in 79 ACT samples from TCGA database identified several genes, including XPO1, RACGAP1, PDGFD, NR4A2, MXRA5, VPS51, TMED3, NDFIP1 and CDKN1C, which were significantly associated with ACT overall survival. Conclusion Differentially expressed genes and survival related genes in all of stages can serve as new targets for ACT therapy, and which should be helpful for the understanding of its pathogenesis and prognosis.

Research advances in the pathogenesis and surgical treatment of gallbladder carcinoma / 临床肝胆病杂志

Gallbladder carcinoma (GBC) is often obscured by some benign diseases in clinical practice and thus unsuspected GBC tends to occur.As for etiology,long-term stimulation by gallstones,gallbladder polyps larger than 1 cm,gallbladder adenoma,and adenomyomatosis of the gallbladder are closely associated with GBC.In the aspect of molecular biology,long non-coding RNA,microRNA,surface growth factor receptor,and some membrane proteins are involved in the development and progression of GBC,which may provide a reference for clinical practice.It is of great importance to perform intraoperative and postoperative surgical management of GBC,which is related to patients'survival.Patients with highly suspected or proven GBC should be converted to open surgery after disease assessment,in order to avoid reoperation.Reoperation should be performed for patients with unsuspected GBC found by postoperative pathological examination,in order to avoid tumor progression and metastasis.

The research progress of circular RNA in oncology / 中华检验医学杂志

[Abstact] Circular RNAs(circRNAs) were once mistakenly considered as the transcription splicing intermediates , affiliate by-products or splicing errors , and the understanding of circRNAs has been significantly revolutionized with the development of high-throughput sequencing technology of RNA and the improvement of the corresponding bioinformatics analysis .CircRNAs with their unique closed-loop structure and undenible important biological functions have become new favorites in both molecular biology studies and clinical trials.To our knowledge , circRNAs usually arise after transcription , stably express in a variety of biological cells and regulate or interfere genetic expression , thus affecting occurrence and progression of diseases.Recently, circRNAs′influences upon various cancers have begun to edge up and we elaborates them in detail here based on the latest researches .

Function and mechanism of PAR6 gene in the occurrence and development of tumor / 国际肿瘤学杂志

Cell polarity is a common feature of many different types of cells,and it is essential to the normal differentiation and function of cells. Partitioning defective 6( PAR6)gene encodes PAR6 protein, which is crucial to asymmetric cell division and polarized growth. PAR6 protein as a member of the PAR6 polarity complex,affects the synthetic of centrosome and protein recruitment to the centrosome. The abnormal number of centrosomal and the loss of cell polarity may eventually lead to the occurrence of tumor.

Analysis of differentially expressed genes and metabolic pathways in human uveal melanoma / 中华实验眼科杂志

Background Studies showed that there exsits differential gene expression in human uveal melanoma (UM).However, the researching results are somewhat inconsistently abroad, while relevant literature is still less in China.Few domestic researches have reported the abnormalities of gene transcription level or the pathways of these genes.Objective This study was to compare the gene expression profiles between human UM and normal uvea tissues and analyze the metabolic pathways involved in these differentially expressed genes.Methods Four human UM samples were collected in Beijing Tongren Eye Center,and 4 pieces of normal uveal tissues from 4 donors served as controls.The expression of genes was detected with Human Genome U133 Plus 2.0 chip,and the expression profiles were compared between two groups.The biological functions and active pathways of the genes were analyzed by Gene Ontology Enrichment Analysis Software Toolkit (GOEAST).Results Compared with the normal controls,4 165 differential genes were screened in human UM (12.50％) ,including 1 236 up-regulated genes (3.71％) and 2 929 down-regulated genes (8.79％) ,in which the genes of raised more than 5-, 10-,50-and 100-fold were 113,21,1 and 1, respectively, and the genes of reduced by 50％ ,90％ ,98％ and 99％ were 1 053,422,33 and 5,respectively.The functions of these differentially expressed genes were associated with cellular differentiation and growth,development, cell adhension, immun response, transcriptional contol, signal transduction and anti-apoptosis.The metabolic pathways of differentially expressed genes included angiogenesis pathway, cell-cycle related protein kinase pathway and immune regulatory pathway (involving B lymphocytes and T lymphocytes).ConclusionsGene expression profiles are evidently different between human UM and normal uveal tissue.The variation of the gene profiles in human UM leads to the changes of multiple biological functions including angiogenesis and kinase pathway even immun system.It is implied that the pathogenesis of human UM is a comprehensive effect of multiple genes and biological pathways.

Effect of DREAM on GLT-1 expression in spinal cord in rats with bone cancer pain and morphine tolerance / 中国医师杂志

Objective To investigate the effects of downstream regulatory element antagonist modulator (DREAM) on the expression of glutamate transporter-1 (GLT-1) in spinal cord in rats with bone cancer pain and morphine tolerance.Methods Sixty female healthy Sprague-Dawley (SD) rats weighing 200 ～230 g were randomly divided into tow groups,group Ⅰ cancer pain (CP,n =48) and group Ⅱ Sham (S,n =12).Cancer pain in each group was produced by inoculation of syngenetic Walker 256 rat mammary gland carcinoma cells (5 × 105) to left tibia.Pain threshold to mechanical stimulus was measured before (baseline) and after the surgical procedure.From 14 d to 18 d after the inoculation of carcinoma cells,36 rats from group CP received subcutaneous injection of morphine at 3 times per day with doses increasingly from 10 mg/kg initially to 20 mg/kg,30 mg/kg,40 mg/kg,and 60 mg/kg.Equal volume of normal saline was applied to the 12 rats left in group CP.On 19th day after the carcinoma cells inoculation once subcutaneous injection of morphine at 3mg/kg was performed in all rats in group CP.From the next day,the rats in group CP ever receiving injections of morphine for 5 days were randomized into thre subgroups,including subgroups morphine tolerance (MT,n =12),vehicle (V,n =12),and RNAi (R,n =12).They were injected intrathecally with 20 μl of normal saline (NS),10 μl vehicle plus 10 μ1 NS,and 10 μ1 of DREAM-shRNA plus l0 μ1 NS,respectively,once a day for 5 days.Focusing on the affected limb,mechanical pain threshold was measured one day before surgery (T0),and at day7 (T1),day 14 (T2),day 18 (T3),day 19 (T4),day21 d (T5),day 25 (T6),and day 28 (T7) after surgery.The animals were sacrificed at day 28 after the procedure.The lumbar 4 segments in rats were removed for detection of DREAM and GLT-1.Results The mechanical threshold was significantly decreased at T1 compared to the baseline in all groups,returned to the baseline at T2 ～ T7 in group S,at T4 in group CP,and at T2 in group MT,V,and R,but remained low at T5 ～T7 in group CP,and at T3 ～T7 in group MT,V,and R.Compared to that at T1,it was decreased at T2 ～T3 and T5 ～ T7 in group CP,at T4 ～ T7 in group MT and V,and at T4 ～ T5 in group R,going back to the baseline at T4 in group CP and at T2 in group MT,V and R,and increased at T6 ～ T7 in group R.Compared to that in group S,the mechanical threshold in group CP,MT,V and R was decreased,and lower at T2 in group CP and at T4 in group MT,V and R.Compared to that in group CP,the mechanical threshold was significantly higher at T2 ～ T3 but lower at T4 in group MT,V,and R,decreased at T5 in group R and at T5 ～ T7 in group MT and V.The mechanical threshold was increased at T6 ～ T7 in group R and higher than that in groups MT and V.The expression of DREAM,compared to that in group S,was down-regulated in other groups.Compared to group CP,increment was shown in groups MT and V,and decrease was exhibited in group R.It was cut down in group R compared to that in groups MT and V.Compared to group S,GLT-1 was decreased in other groups.It was down-regulated in groups MT,V and R compared to group CP.Conclusions DREAM is involved in the development of allodynia after morphine tolerance in rats with bone cancer pain.No evidence in this study supports a link between DREAM and GLT-l in spinal cord.

Molecular markess of mucosa harboring gastric adenoass

Context Gastric adenoma is a precursor lesion of the adenocarcinoma. Objective To characterize gastric adenomas according to the mucin immunoexpression and to evaluate the immunoexpression of p53, p16ink4a, BCL-2, cyclin D, Ki-67, in the adenoma and in the gastric mucosa harboring adenoma. Methods Forty gastric specimens from 20 patients were classified as intestinal (MUC2 - goblet cell mucin) or foveolar (MUC5AC - gastric-foveolar mucin) adenomas. Immunohistochemistry was performed using streptavidin-biotin-complex method. Results Twelve (60%) patients were men. The mean age was 67.9 ± 12.9 years-old. Intestinal adenomas were detected in 13 (65%) patients and gastric type in 7 (35%). Low-grade dysplasia was present in 13 (65%) of the adenomas, high-grade in 3 (15%), and adenocarcinoma within the polyp in 4 (20%). Six (30%) patients had synchronous adenocarcinoma. p53 immunoexpression was observed in 6/20 (30%) of adenomas, and in 2/6 (33.3%) of synchronous tumors. There was an association between p53 immunoexpression and intestinal type of adenoma/tumor, P = 0.04. There was no association between p16ink4a, Bcl-2, cyclin D and Ki-67 and adenoma clinicopathological characteristics. Conclusion Immunohistochemistry may be useful to classify the adenomas subtypes and may define the pathway of adenoma to carcinoma sequence. .

Contexto Adenoma gástrico é uma lesão precursora do adenocarcinoma. Objetivo Melhor caracterizar os adenomas de acordo com a imunoexpressão de mucinas e avaliar a imunoexpressão de p53, p16ink4a, BCL-2, cyclin D, Ki-67, nos adenomas e na mucosa gástrica adjacente. Métodos Quarenta espécimes gástricos provenientes de 20 pacientes portadores de adenomas foram classificados como do tipo intestinal (MUC2 – mucina presente nas células caliciformes) ou gástrico (MUC5AC – mucinas de padrão foveolar). Realizou-se imunoistoquímica para p53, p16ink4a, BCL-2, cyclin D e Ki-67 pelo método do complexo da estreptavidina-biotina. Resultados Doze (60%) pacientes eram homens e a média de idade foi de 67,9 ± 12,9 anos. Os adenomas foram classificados como do tipo intestinal em 13 (65%) pacientes e do tipo gástrico em 7 (35%). Displasia (neoplasia intraepitelial) de baixo grau estava presente em 13 (65%), displasia de alto grau em 3 (15%), e adenocarcinoma no pólipo adenomatoso em 4 (20%) pacientes. Observou-se immunoexpressão do p53 em 6/20 (30%) adenomas, e em 2/6 (33,3%) dos tumores sincrônicos. Houve associação entre imunoexpressão do p53 e adenoma/tumor tipo intestinal, P = 0.04. Não houve associação entre imunoexpressão do p16ink4a, Bcl-2, ciclina D e Ki-67 e as características clinicopatológicas dos adenomas. Conclusão Imunoistoquímica pode ser utilizada para caracterizar os subtipos de adenoma e talvez indicar o caminho de carcinogênese. .

Carcinogenesis of cell cycle-related kinase / 国际肿瘤学杂志

Cell cycle-related kinase (CCRK) as a novel CDK-activating kinase plays a significant role in cell cycle regulation.Related studies confirm that CCRK is overexpressed in various tumors,and is associated with poor prognosis of the patients,which indicates that CCRK takes part in the generation and development of the tumor.

Progress in mechanism of tumor metastatic colonization / 肿瘤

The concept of metastatic colonization was firstly proposed by Weinberg R A and his colleagues in 2011. It is defined as the process in which malignant cells disseminate from primary tumors, reach the potential metastatic sites and grow from minute clusters into macroscopic metastatic colonies after recovery of propagation ability. Metastatic colonization is considered as the speed-limiting step in metastasis, only a small fraction of metastatic cells can successfully achieve this goal. The process of metastatic colonization is regulated by a series of related genes and correlated with tissue structure. This review summarizes the recent progress in mechanism of metastatic colonization including the development, characteristics and influencing factors of metastatic colonization, and it also give a comprehensive view into antimetastic potential of therapeutic strategies targeting metastatic colonization in clinical practice. Copyright © 2013 by TUMOR.

TIMP-3 regulated by miR-181b as a target gene on invasion and migration of hepatocellular carcinoma cells / 中华肝胆外科杂志

Objective To explore the impact of TIMP 3 regulated by miR-181b as a target gene on invasion and migration of hepatocellular carcinoma (HCC) in vitro.Methods The expressions of miR-181b were detected using SYBR Green real-time fluorescence quantitative polymerase chain reaction on liver cancer specimens and on HCC cell lines.The protein expression of TIMP 3 in HCC was detected using westen blot,and SKHep-1 as a cell line expressing high miR-181b was chosen through reporter gene experiment.TIMP-3 as a target gene regulated by miR-181b and its effect on invasion and migration treated by anti-miR-181 b were studied using transwell and cell scarification test,respectively.Results The expression of miR-181b in HCC was higher than cancer-adjacent tissues and normal liver tissues.The differences among them were significant.There was a correlation between the high expression of miR-181b and invasiveness and metastasis in HCC.The protein expression of TIMP-3 in HCC was significantly lower than normal liver tissues and cancer-adjacent tissues.Expression of miR-181b mRNA was detected in various HCC cell lines such as Hep3B,HepG2,Huh 7,SKHep-1,SNU182,SNU449 and hepatocyte,with the expression of miR-181b in SKHep-1 being the highest (P＜0.01).TIMP3-3UTR was low when the expression of miR-181b was high (P＜0.05).The invasion and migration abilities of SKHep-1 were significantly inhibited by anti-miR-181b (P＜0.05).Conclusion The data suggested that miR-181b promoted invasion and migration of SKHep-1 by down-regulating TIMP-3 in HCC.

Androgen receptor and hepatocellular carcinoma / 国际肿瘤学杂志

Androgen receptors appear to play a significant role in the hepatocarcinogenesis.Androgen receptors are found to be expressed in liver tumor,and the overexpression of androgen receptor is associated with poor prognosis.Recent researches have indicated that androgen receptors regulate various cellular events in liver carcinogenesis through various ways,and androgen receptor could be a potential cancer therapeutic target in hepatocellular carcinoma.

Effect of siRNA Interference of HRG-1 on bladder cancer T24 cells in vitro / 中国医师杂志

Objective To observe the expression change of HRG-1 gene between urinary bladder carcinoma and normal tissues,and to investigate the effect of HRG-1-siRNA on the proliferation and apoptosis of human bladder carcinoma cells.Methods Immunohistochemisty was used to detect the expression of HRG-1 in 85 cases of bladder carcinomas and 20 normal bladder tissues.The siRNA of HRG-1 was designed,synthesized,and transfected into bladder cancer cell line T24.Results The HRG-1 gene expression had significant differences between bladder carcinoma and normal bladder tissues (P ＜ 0.05).The positive expression of HRG-1 gene had significant differences between the pathological grades and clinical stages of bladder carcinomas (P ＜0.05).After treated with siRNA,the expression levels of HRG-1 protein and mRNA in T24 cells decreased obviously (P ＜ 0.05).The apoptosis rate of T24 cells transfected with HRG-1-siRNA was significantly different from control-siRNA group and blank group (P ＜ 0.01).Conclusions The high expression of HRG-1 gene may play an important role in bladder carcinoma,and siRNA targeting HRG-1 can suppress HRG-1 protein expression markedly and enhance apoptosis of T24 cells.

Effect of XPG down-regulation gene expression towards the proliferation of epithelial ovarian cancer cells and its chemosensitivity to platinum / 中华妇产科杂志

ObjectiveTo investigate the effect of XPG down-regulation gene expression towards the proliferation of epithelial ovarian cancer cells and its chemosensitivity to platinum.Methods The small interference RNA ( siRNA ) -XPG fragments were designed and tranfected into SKOV3/DDP cell lines by lipofectamine transiently for choosing the best siRNA-XPG fragment to silence XPG gene expression.The pGPU6/GFP/Neo vector was used to construct the siRNA-XPG vectors,which was transfected into SKOV3/DDP cell line with expression of XPG gene.Real-time PCR and western blot were employed to confirm the silencing efficacy of siRNA-XPG.The growth curve of cells,cell cycle,the drug-resistance index of cells and intracellular drug concentration were measured by 4-methyl-thiazolyl-tetrazolium (MTT),flow cytometer (FCM) and high performance liguid chromatograph respectively.Results( 1 ) Real-time PCR results showed that XPG mRNA expression copy number in SKOV3/DDP tranfected with siRNA-XPG-733 fragment was 1.050 ± 0.023,which was significantly lower than that in SKOV3/DDP tranfected with other siRNA-XPG fragments(P ＜ 0.05,respectively),and was chosed to construct the siRNA-XPG vectors.The XPG mRNA expression was down-regulated in short hairpin RNA (shRNA)-XPG-733-SKOV3/DDP cell lines that confirmed by western blot.( 2 ) The growth curve showed that growth velocity of shRNA-XPG-733-SKOV3/DDP cell lines was lower than that of shRNA-GAPDH and shRNA-NC cell lines( P ＜ 0.05,respectively).The results of FCM also showed that 34.0％ of cells in shRNA-XPG-733-SKOV3/DDP cell lines were in S + G2/M phase,while only 58.7％ and 51.3％ in shRNA-GAPDH and shRNA-NC cell lines respectively ( P ＜ 0.05,respectively).( 3 ) The drug-resistance index of shRNA-XPG-733-SKOV3/DDP cell lines [ 50％ inhibiting concertration( IC50 ):( 13.79 ± 0.06) μg/ml ] was lower than that in shRNA-GAPDH and shRNANC cell lines [ IC50:( 27.84 ± 0.34 ) μg/ml and ( 28.32 ± 0.42 ) μg/ml,respectively ] statistically significant (P ＜ 0.05,respectively) ; but there was not statistically significant difference in intracellular drug concentration between shRNA-XPG-733-SKOV3/DDP cell lines [ (0.026 ± 0.005 ) μg/ml ] and shRNAGAPDH [ (0.024 ± 0.003 ) μg/ml ] and shRNA-NC cell lines [ ( 0.025 ± 0.007 ) μg/ml ] after treated by cisplatin in vitro ( P ＞ 0.05,respectively ).Conclusion The down-regulating of XPG gene resulted in slowing growth velocity and descending the drug-resistance index of shRNA-XPG-733-SKOV3/DDP cell lines,which may be related with descending in capability of DNA excision repair in cells.

Expression of p27, C-myc protein in lung squamous cell carcinoma and adenocarcinoma / 中国医师进修杂志

Objective To investigate the clinical pathology characteristics of the p27 and C-myc protein expression in lung squamous cell carcinoma and adenecarcinoma as well as the correlation between the expressions of them. Method The expressions of p27 and C-mye protein in tumor tissue of 35 cases excised during pulmonectomy for lung squamous cell carcinoma and adenocarcinoma patients were examined using immunochemical method,and compared with 10 cases of normal lung tissue. Results The total positive rate of p27 protein was 17.1%(6/35 ) in 35 eases of tumor tissue, but 90.0%(9/10) in normal lung tissue, and there was significant difference (P 0.05 ). The total positive rate of C-myc protein was 85.7% (30/35) in tumor tissue, but no expression existed in normal lung tissue (P 0.05). The expression of p27 and C-myc in lung squamous cell carcinoma and adenecareinoma showed negative correlation.Conclusions The expression of p27 protein is positive in normal lung tissue, but shows outstanding decrease in lung squamous cell carcinoma and adenocarcinoma tissue. Its expression correlates with the differentiated degree. The expression of C-myc is negative in normal lung tissue but shows significant increase in lung squamous cell carcinoma and adenocareinoma tissue and its expression correlates with lymph nodes metastasis. C-myc may be a valuable marker in evaluating prognosis.

Rebamipide-induced downregulation of phospholipase D inhibits inflammation and proliferation in gastric cancer cells

Rebamipide a gastroprotective drug, is clinically used for the treatment of gastric ulcers and gastritis, but its actions on gastric cancer are not clearly understood. Phospholipase D (PLD) is overexpressed in various types of cancer tissues and has been implicated as a critical factor in inflammation and carcinogenesis. However, whether rebamipide is involved in the regulation of PLD in gastric cancer cells is not known. In this study, we showed that rebamipide significantly suppressed the expression of both PLD1 and PLD2 at a transcriptional level in AGS and MKN-1 gastric cancer cells. Downregulation of PLD expression by rebamipide inhibited its enzymatic activity. In addition, rebamipide inhibited the transactivation of nuclear factor kappa B (NFkappaB), which increased PLD1 expression. Rebamipide or PLD knockdown significantly suppressed the expression of genes involved in inflammation and proliferation and inhibited the proliferation of gastric cancer cells. In conclusion, rebamipide-induced downregulation of PLD may contribute to the inhibition of inflammation and proliferation in gastric cancer.