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1.
Chinese Journal of Microbiology and Immunology ; (12): 243-247, 2023.
Article in Chinese | WPRIM | ID: wpr-995281

ABSTRACT

Intestinal fungal dysbiosis is closely associated with the development and progression of many diseases including tumors. The disruption of fungal communities is involved in tumorigenesis and progression through inducing aberrant host immune responses and the production of certain metabolites as well as promoting the establishment of interactions with bacteria. Fungal dysbiosis is a potential marker for early detection of digestive tumors and a factor influencing the efficacy of tumor therapy. Studying the association between gut fungi and digestive tumors may facilitate the prevention, diagnosis and treatment of digestive tumors.

2.
Chinese Journal of Medical Education Research ; (12): 555-557, 2020.
Article in Chinese | WPRIM | ID: wpr-865837

ABSTRACT

Integrated medical curriculums are becoming more and more popular in medical colleges at home and abroad. In this article, the methods and teaching of integrated digestive system course at Shanghai Jiao Tong University School of Medicine was thoroughly introduced from the theoretical course, PBL course, trainee course, assessment method and effect evaluation. The successful experience of practice of the integrated digestive system curriculum was summarized as follow: strong guarantee from systems, adequate reserves of teaching faculty and good mechanism of feedback. Also, the problems in the practice of the curriculum were presented, which include the shortage of corresponding textbook and of deep running-in between teachers.

3.
Chinese Journal of Gastroenterology ; (12): 70-74, 2018.
Article in Chinese | WPRIM | ID: wpr-698145

ABSTRACT

Background:Deoxyhypusine synthase(DHPS)is a key factor in post-translational modification of the precursor of eukaryotic initiation factor 5A(eIF-5A),and eIF-5A is closely related to the regulation of proliferation and invasion of tumor cells. Aims:To investigate the expression of DHPS in gastric cancer and its clinical significance,and to explore the possible mechanism of its effect on metastasis of gastric cancer. Methods:Tissue microarray containing 92 gastric cancer tissues and paired adjacent cancerous tissues was employed to detect the DHPS expression by using immunohistochemical staining,and the correlation of DHPS expression with the clinicopathological characteristics of gastric cancer was analyzed. DHPS-siRNA and GC7,an inhibitor of DHPS were used,respectively to intervene human gastric cancer cell line MGC803. The invasive ability of MGC803 cells was assessed by cell invasion assay,and the expressions of metastasis-related proteins including vascular endothelial growth factor(VEGF),matrix metalloproteinase 2(MMP2)and MMP9 were detected by ELISA. Results:In 62(67.4%)cases of gastric cancer,DHPS was highly expressed,and its expression was closely related to tumor diameter,TNM stage and depth of invasion(P <0.05),but not related to gender,age,lymph node metastasis and distant metastasis(P >0. 05). Both DHPS-siRNA and GC7 could down-regulate the invasiveness of MGC803 cells,while the former could also reduce the expressions of VEGF,MMP2 and MMP9 proteins(P <0.05). Conclusions:DHPS is highly expressed in gastric cancer and associated with tumor invasion and progression. DHPS is expected to be a new target for diagnosis and treatment of gastric cancer because of its regulatory effect on invasion and metastasis of tumor cells.

4.
Chinese Journal of Gastroenterology ; (12): 341-345, 2017.
Article in Chinese | WPRIM | ID: wpr-619817

ABSTRACT

TRIM55 is a member of TRIM family.Most TRIM proteins, which can be defined as E3 ubiquitin ligase because of the RING-finger domain, are closely related with the initiation and progression of cancer.Aims: To study the expression and clinical significance of TRIM55 in colorectal cancer, and explore the potential mechanism of TRIM55 in colorectal cancer.Methods: Seventy colorectal cancer tissues and corresponding paracancerous tissues taken from colorectal cancer patients from October 2014 to December 2015 at Shanghai Ren Ji Hospital were enrolled.Real-time PCR was performed to examine the expression of TRIM55.Human colorectal cancer cell line HCT116 was transfected with TRIM55 small interfering RNA (siRNA), cell proliferation was measured by CCK-8 assay, Western blotting was implemented to determine the protein expressions of TRIM55 and SOCS1.Results: The expression of TRIM55 was significantly increased in 49 colorectal cancer tissues than in corresponding paracancerous tissues.Increased expression of TRIM55 was closely correlated with tumor differentiation (P=0.032), AJCC staging (P=0.001) and lymph node metastasis (P=0.001), but not related to gender, age, tumor size, invasion depth, distant metastasis and vascular invasion (P>0.05).After transfection with TRIM55 siRNA, mRNA and protein expressions of TRIM55 were significantly decreased (P<0.01), proliferation of HCT116 cells was significantly decreased (P<0.01), and protein expression of SOCS1 was significantly increased (P<0.01).Conclusions: E3 ubiquitin ligase TRIM55 may promote the proliferation of colorectal cancer cells via influencing the expression of SOCS1, thus promoting the progression of colorectal cancer.This indicates that detection of TRIM55 expression may provide a new approach for diagnosis and therapy of colorectal cancer.

5.
Chinese Journal of Gastroenterology ; (12): 1-3, 2017.
Article in Chinese | WPRIM | ID: wpr-508390

ABSTRACT

Most colorectal cancers develop from adenomas. Environmental factors play an important role in the development and progression of adenoma. Recently,epidemiologic investigations on lifestyle change including diet and exercise and drug intervention studies have proved the relationship between environmental factors and colorectal cancer. Screening,polypectomy and surveillance via colonoscopy are the main measures of colorectal cancer prevention. However, the efficacy is unsatisfactory. Therefore,attention should be paid to studies on colorectal cancer prophylaxis via intervention on environmental factors. Emphasis should be put on various aspects of environmental intervention in clinical practice,and prophylaxis strategies should be generated individually in accordance with the local condition and situation.

6.
China Oncology ; (12): 182-187, 2016.
Article in Chinese | WPRIM | ID: wpr-490089

ABSTRACT

Colorectal cancer remains a major threat to people’s health around the world. Researchers have paid more and more attention to colorectal cancer epigenetics. From two main aspects of colorectal cancer epigenetics: DNA methylation and histone modiifcation, this article analyzes the similarities and differences between patients with colorectal cancer in Eastern and Western countries. This review brielfy introduces epigenetic modiifcation of genes that were used to be biomarkers and therapeutic targets. Although there are some common features of colorectal cancer in the world, analysis has showed that some obvious epigenetic differences do exist in different races. For example, it had been conifrmed in the studies that there are differences in speciifc gene methylation, histone modiifcation sites and the degree of methylation and acetylation among countries, which provide the basis for speciifc diagnosis, treatment and prognosis of colorectal cancer in different ethnic groups. With improved research methods and increased sample size, more and more special molecular targets of colorectal cancer tissues will be found, and then personalized therapy for colorectal cancer can be achieved.

7.
Chinese Journal of Digestion ; (12): 169-173, 2015.
Article in Chinese | WPRIM | ID: wpr-469260

ABSTRACT

Objective To investigate the relationship between genetic variants in the Toll-like receptor (TLR) pathway genes and susceptibility of gastric cancer (GC) and esophageal squamous cell carcinoma (ESCC).Methods The data of whole genome association studies of the high-risk population of GC and ESCC in China were analyzed by adaptive rank-truncated product (ARTP) method in pathway and gene level.The associations between single nucleotide polymorphism (SNP) and susceptibility of GC and ESCC were analyzed with additive model of unconditional Logistic regressions.PLINK 1.07 and SPSS 19.0 software were performed for statistical analyses,and ARTP package in R3.0.2 was used for pathway and gene level analysis.Results In gene-level analyses,eight genes were found to be associated with susceptibility of GC (P <0.05) and six genes were associated with susceptibility of ESCC (P < 0.05).In single SNP-level analyses,21 SNPs were statistically correlated with susceptibility of GC (P < 0.01),and 11 SNPs were statistically correlated with susceptibility of ESCC (P <0.01).Conclusions Some genetic variants in TLR pathway are associated with risk of GC and ESCC.The potential molecular mechanisms need further investigation.

8.
Chinese Journal of Digestion ; (12): 753-757, 2015.
Article in Chinese | WPRIM | ID: wpr-485044

ABSTRACT

Objective To explore the efficacy and safety of compound azintamide enteric‐coated tablets in the treatment of patients with dyspepsia after gastrointestinal surgery .Methods Multicenter , randomized ,double blind ,placebo‐controlled ,parallel controlled method w as applied .From January 2011 to January 2013 , of 240 patients with dyspepsia after gastrointestinal surgery from 12 hospitals in Shanghai were enrolled and divided into medicine treatment group (n= 120) and placebo control group (n= 120 ) ,received compound azintamide enteric‐coated tablets or placebo , respectively . Compound azintamide enteric‐coated tablet (100 mg) or placebo was oral taken each time ,three times per day for four weeks .Total and respective score of dyspeptic symptoms (abdominal distension ,loss of appetite ,early satiety ,belching ,nausea ,abdominal pain or abdominal discomfort) were evaluated prior to study and on the 1st , 2nd , 3rd and 4th week after treatment . On the 4th week after treatment ,the efficacy of the improvement of dyspeptic symptoms was compared between the two groups ,and the safety was also evaluated .The score of the quality‐of‐life was compared between the two groups prior to study and on the 4thweek after treatment .The t‐test was performed for comparison between measurement data ,Chi‐square test was used for count data ,and rank sum test was used for rank data .Results At one week after treatment ,the scores of abdominal distension (4 .61 ± 0 .98 ) ,early satiety (2 .87 ± 0 .64 ) ,belching (3 .03 ± 0 .58) ,abdominal pain or abdominal discomfort (3 .13 ± 0 .79) and total score (18 .32 ± 3 .44) of patients in medicine treatment group were significantly lower than those of placebo control group (8 .83 ± 1 .28、4 .28 ± 0 .61、4 .87 ± 1 .07、5 .46 ± 0 .87、29 .63 ± 5 .50) ,and the differences were statistically significant (t=28 .524、17 .400、16 .453、21 .619 and 18 .983 ,all P 0 .05) .At 2nd ,3rd and 4th week after treatment ,respective score of dyspeptic symptoms and total score of medicine treatment group (2nd week:2.57±1.28,1.87±1.17,1.55±1.27,1.55±1.08,1.09±0.82,1.98±1.02,10.53±4.54,3rdweek:1 .42 ± 0 .60 ,1 .11 ± 0 .45 ,0 .94 ± 0 .37 ,0 .94 ± 0 .41 ,0 .79 ± 0 .31 ,1 .42 ± 0 .55 ,6 .52 ± 2 .41 ,4th w eek:1.13±0.51,0.46±0.12,0.58±0.13,0.38±0.16,0.30±0.07,0.81±0.33,3.65±1.06)wereall significantly lower than those of placebo control group (2nd week:8 .50 ± 2 .61 ,3 .78 ± 2 .01 ,4 .08 ± 2 .14 , 4.73±2.64,2.27±2.13,4.91±2.24,28.25±8.86,3rdweek:7.92±2.51,3.68±1.76,4.08±1.86, 4.71±1.77,2.14±0.83,5.01±1.31,27.54±8.09,4th week:7.63±2.37,3.67±1.63,3.92±2.08, 4 .66 ± 2 .95 ,2 .14 ± 1 .65 ,4 .67 ± 2 .34 ,and 26 .68 ± 7 .45) ,and the differences were statistically significant (all t=0 .000 ,all P<0 .01) .At 4th week after treatment ,the total efficacy of total score improvement of dyspepsia symptoms in medicine treatment group was 86 .21% (100/116) ,which was significantly better than that of placebo control group (39 .16% (47/120)) ,and the difference was statistically significant (Z=9 .464 ,P<0 .01) .The total score of quality of life in medicine treatment group was significantly lower than that of placebo control group (12 .24 ± 4 .30 and 22 .13 ± 6 .18) ,and the difference was statistically significant (t=14 .225 , P< 0 .01 ) .No adverse events was observed in both groups during treatment period . Conclusion Compound azintamide enteric‐coated tablets may effectively improve dyspeptic symptoms and quality of life in patients with dyspepsia after gastrointestinal surgery ,and with good safety .

9.
Chongqing Medicine ; (36): 3855-3857, 2014.
Article in Chinese | WPRIM | ID: wpr-459565

ABSTRACT

Objective To investigate whether EZH2 participates in the process of authphagy and its regulatory mechanism in CRC (colorectal cancer) .Methods ZEB1 ,EZH2 and PTEN expression were measured by Western blot and immunohistochemistry respectively .ZEB1 ,EZH2 and PTEN mRNA level were measured by real-time PCR .Electron microscopy was introduced to validate the existence of autophagy .Results Knockdown of EZH2 induced the formation of autophagosome in colorectal cancer cell lines , which was evident on electron microscopy .Furthermore ,Western Blot and real-time PCR data showed that ZEB1 and EZH2 may regulate the expression of PTEN ,which played a vital role in autophagy .Moreover ,downregulation of ZEB1 significantly reduced the expression of EZH2 .An inverse correlation between the expression of EZH2 and ZEB1 ,and the expression of PTEN was also revealed in CRC tissues ,when compared with normal tissue in patients .Conclusion The impact of EZH2 on autophagy via PTEN during CRC carcinogenesis is revealed .At the same time ,EZH2 expression may be regulated by ZEB1 in colorectal cancer .

10.
Chinese Journal of Digestion ; (12): 178-182, 2014.
Article in Chinese | WPRIM | ID: wpr-447154

ABSTRACT

Objective To evaluate the efficacy and safety of compound azintamide enteric-coated tablet in the treatment of patients with post-cholecystectomy dyspepsia.Methods A multicentre,randomized,double-blinded,placebo-controlled trail was conducted.A total of 120 patients with post-cholecystectomy dyspepsia were divided into azintamide group (n=60) and placebo group (n=60),taking compound azintamide enteric-coated tablet or placebo 100 mg each time,three times per day for 28 days.The score of each dyspeptic symptom (abdominal distension,loss of appetite,early satiety,belching,nausea,abdominal pain or abdominal discomfort) and total score of dyspepsia were evaluated prior to study and on the 7th,14th,21st and 28th day after treatment.The efficacy of the improvement of dyspeptic symptoms was compared between the two groups on the 28th day after treatment and the safety was evaluated.The score of the quality-of-life was compared between the two groups prior to study and on the 28th day after treatment.The t-test or chi-square test was performed for statistical analysis.Results The scores of abdominal distension,belching,nausea,abdominal pain or abdominal discomfort and the total score of azintamide group on the 7th day after treatment (5.7±3.1,3.5±2.1,0.3±0.1,3.3±1.7 and 17.9±9.6) were significantly lower than those prior to study (8.9±5.3,5.3±2.5,0.9±0.4,4.5±3.7,24.3±14.5;t=3.758,3.976,10.494,2.125 and 2.654,allP<0.05).On the14th,21st and28thday after treatment in azintamide group,the score of each dyspeptic symptom and the total score were lower than those prior to study.The symptom of abdominal distension significantly improved on the 7th,14th,21st and 28th day after treatment in placebo group,and the score of early satiety and total score of dyspepsia were significantly lower on the 28th day after treatment compared with those before treatment.In azintamide group,the total efficacy rate was 66.7% (40/60),which was higher than that of placebo group (38.3%,23/60) and the difference was statistically significant (x2 =9.653,P < 0.01).On the 28th day after treatment,SF-NDI of azintamide group was 4.4±3.4,which was significantly lower than that of placebo group (9.6±6.0) and the difference was statistically significant (t=5.450,P<0.01).In azintamide group there was one patient with rash on the 7th day after treatment,and in placebo group there was one patient with headache on the 14th day after treatment.The symptoms disappeared seven days after medicine withdrawal.Conclusion Compound azintamide enteric-coated tablet effectively improves dyspeptic symptoms and quality of life in patients with post-cholecysteetomy dyspepsia and has good safety.

11.
Chinese Journal of Digestion ; (12): 166-170, 2013.
Article in Chinese | WPRIM | ID: wpr-431412

ABSTRACT

Objective To investigate the activation and clinical significance of the mammalian target of rapamycin (mTOR) pathway related protein and eukaryotic translation factor 4E-binding protein 1 (4E-BP1) in gastric cancer.Methods The activation of mTOR and 4E-BP1 in gastric cancer tissues of 38 surgical patients were detected by immunohistochemical method.The differences of phosphorylated mTOR and 4E-BP1 expression among cancerous tissues,para-cancerous tissues and normal gastric mucosa tissues and dinicopathological variables were analyzed by Chi square test and Kruskal-Wallis test.Results The positive expression rate of phosphorylated mTOR in the gastric cancerous tissues was significantly higher than that of para-cancerous tissues and normal tissues [71.1% (27/38),50.0 % (19/38) and 44.7 % (17/38),x2 =11.031,P =0.026].The positive expression rate of downstream protein 4E-BP1 in the gastric cancer tissues was also significantly higher than that of paracancerous tissues and normal tissues [68.4%(26/38),57.9%(22/38) and 28.9% (11/38),x2 =13.943,P=0.007].There was no correlation between phosphorylated mTOR and 4E-BP1 expression and tumor Lauren's sub-type,infiltration,differentiation degree,lymph node metastasis and patient's age.There was statistical significant difference between activated 4E-BP1 expression and tumor size in gastric cancer (H=3.86,P<0.05).Conclsions mTOR pathway was over activated in gastric cancer.There was difference between phosphorylation degree of its downstream protein 4E-BP1 and the tumor size.

12.
Chinese Journal of Medical Education Research ; (12): 359-361, 2013.
Article in Chinese | WPRIM | ID: wpr-435979

ABSTRACT

Problem-based learning has gradually become an important pedagogical tool in the medical curriculum.Behaviors of PBL tutor play an unique role in teaching.A good PBL tutor must consider the following issues:ample preparing before class,awareness of learning outside the tutorial room,social congruence,dealing with the difficult student and dysfunctional group,sharing the PBL experience and seeking support or advice from peers.

13.
Chinese Journal of Digestion ; (12): 217-221, 2012.
Article in Chinese | WPRIM | ID: wpr-428633

ABSTRACT

ObjectiveTo investigate the related factors which influencing endoscopists in the accuracy of diagnosis of chronic atrophic gastritis (CAG). Methods With retrospective analysis method,from January to December in 2009,10 765 chronic gastritis cases underwent endoscopy examination in Renji Hospital,school of medicine,Shanghai Jiaotong University were collected.The influence of congestion and exudation,gastric ulcer,bile reflux,gastric polyps and H.pylori infection under endoscopy on CAG endoscopic and pathological diagnosis was analyzed.ResultsThe percentage of histopathological diagnosed CAG was 69.41%,endoscopic diagnosed CAG was 54.27%. The coincidence rate was 62.30%.2575 cases were H.pylori positive (23.92%),the coincidence rate between endoscopic and histopathological diagnosis in H.pylori positivc cascs was 90%.of that of H.pylori negative cases (β=-0.1067,P<0.05).The coincidence was positively related to age.For each 1 year increase in age,the coincidence rate increased by 0.01 time [OR=exp(0.00855)=1.01]; For each 10-year increase in age,the coincidence rate increased by 0.09 time [OR=exp(0.0855) =1.09].The coincidence rate was negatively related to congestion and exudation.The coincidence rate of CAG between endoscopic and histopathological diagnosis in cases with congestion and exudation was 40% of that without congestion and exudation (β=-0.1067,P<0.01).ConclusionCAG diagnosed under endoscopy was somewhat subjective and should be combined with histopathological analysis.The patients' age,H.pylori infection,congestion and exudation may have influence on the coincidence rate between endoscopic and histopathological diagnosis of CAG.

14.
Chinese Journal of Internal Medicine ; (12): 385-389, 2012.
Article in Chinese | WPRIM | ID: wpr-425572

ABSTRACT

ObjectiveTo study the pathogcncsis of gastrointestinal vascular malformation (GIVM) and the potential mechanism of thalidomide in the treatment of gastrointestinal bleeding due to GIVM.Methods We collected the surgical intestinal specimens from 10 patients who suffered from massive hemorrhage of gastrointestinal tract owning to GIVM and the normal intestinal mucosa around the lesions,as well as normal intestinal mucosa from healthy subjects.Immunohistochemical(IHC) staining was carried out to investigate the differences of angiopoietin 2 ( Ang2 ),Notch1 and delta like ligand 4 (Dll4) in the above three intestinal mucosa to find the relationship with the pathogenesis of GIVM. Human umbilical vein endothelial cells(HUVECs) were cultured with 0,25,50,100 and 200 mg/L thalidomide for 24 or 48 hours to observe their mRNA and protein expressions of Ang2,Notch1,Dll4 by real-time PCR and Western blot.ResultsBy IHC staining,more expressions of Ang2,Notch1 and Dll4 in the lesions were detected than those in the normal intestinal mucosa around the lesions and the normal intestinal mucosa in healthy people.The expressions of Ang2,Notch1 and Dll4 were significantly correlated (P =0.016,r =0.732),and the expressions of Notch1 and Dll4 were absolutely correlated ( P =0.000,r =1.000).Real-time PCR and Western blot showed that thalidomide could down-regulate the expressions of them,which were in a concentration-dependent manner.ConclusionAng2,Notch1 and Dll4 may correlate with the pathogenesis of GIVM,while thalidomide can concentration-dependently down-regulate the expression of Ang2,Notch1 and Dll4,which may be one of the mechanism that thalidomide play a therapeutic role in GIVM.

15.
Chinese Journal of Digestion ; (12): 312-317, 2011.
Article in Chinese | WPRIM | ID: wpr-415769

ABSTRACT

Objective To investigate the effect of folic acid on the DNA methylation of tumorrelated genes promoters in healthy human peripheral blood mononuclear cells(PBMC). Methods Ten healthy volunteers were divided into two groups, and were randomized to receive either 5 mg folic acid (n=5)or placebo(n = 5) , one time per day for 3 months. The serum folic acid concentration was detected with chemiluminescence enzyme immunoassay kit before and after the intervention. The methylation statuses of five tumor-related genes promoter, including oncogenes c-myc, c-Ha-ras,tumor suppressor genes p16INK4A, E-cadherin and mismatch repair gene hMLH1 in PBMC were detected by bisufite sequencing. Results After folic acid intervention, the level of serum folic acid increased significantly in intervention group (t= -4. 739,P<0. 05) , however no significant difference in control group. After three-month folic acid intervention, the level of methylation of oncogene c-myc promoter increased from 4%, 3. 3%, 4. 1% before intervention, one week after intervention, one month after intervention respectively to 8%(t= -4. 079,P<0. 05), while no significant change in placebo taken group. Before and after the folic acid intervention, there was no significant difference of DNA methylation of other tumor-related genes promoter, including c-Ha-ras、E-cadherin、p16INK4Aand hMLH1. Conclusion Folic acid intervention can up-regulate DNA methylation of oncogene c-myc promoter, but can not affect the promoter methylation status of tumor suppressor genes E-cadherin,p16INK4Aand hMLH1.

16.
Chinese Journal of Digestion ; (12): 160-163, 2011.
Article in Chinese | WPRIM | ID: wpr-412444

ABSTRACT

Objective To study the expressions of hypoxia inducible factor (HIF)-1 and angiopoietin (Ang)-2 in repeated gastrointestinal bleeding due to vascular malformation, and the efficacy of treatment with thalidomide. Methods Twenty-five patients with repeated gastrointestinal bleeding due to vascular malformation confirmed by capsule endoscopy or enteroscopy were collected and 18 subjects without severe diseases were served as controls. Ten patients with gastrointestinal vascular malformation, who received 25 mg of thalidomide 4 times daily for 4 months and were followed up for at least one year, were also enrolled. The serum samples from all participauts were detected for expressions of HIF-1 and Ang-2 using enzyme-linked immunosorbent assay (ELISA).The expressions of HIF-1 and Ang-2 were compared between angiodysplasia group and control group.The expressions of HIF-1 and Ang-2 were comparatively evaluated before and after treatment with thalidomide in treatment group. Results The expressions of HIF-1 and Ang-2 in vascular malformation group [( 113. 84 ± 26. 66 ) ng/ml and ( 652. 11 ± 140. 39) ng/ml, respectively] were significantly higher than that of control group [(43.28±17.30) ng/ml and (265.60±53.88) ng/ml,respectively, P=0. 000]. The expression of HIF-1 was positively associated with that of Ang-2. (r=0. 700, P= 0. 000). There was no difference in expressions of HIF-1 and Ang-2 before and after treatment with thalidomide (P=0. 498 and =0. 136, respectively). However, significant reduction of Ang-2 [(113. 80±73. 60) ng/ml(P=0. 003)] was found in 8 effectively treated patients after thalidomide treatment. Conclusions HIF-1 and Ang-2 might play an important role in the formation of vascular malformation. The extent of Ang-2 reduction after thalidomide treatment may be helpful in evaluating its efficacy or prognosis.

17.
Chinese Journal of Digestion ; (12): 317-321, 2010.
Article in Chinese | WPRIM | ID: wpr-379745

ABSTRACT

Objective To study the effects of extracellular-signal regulated kinase mitogenactivated protein kinase (ERK-MAPK) signaling pathway inhibition on histone phosphorylation and the related gene expression in human colorectal cancer cells.Methods Two human colorectal cancer cell lines (SW1116 and HCT116) were cultured and treated with gradient(0,20,40/μmol/L) doses of ERK-MAPK signaling pathway inhibitor U0126.Cell viability was determined by cell counting kit 8 (CCK-8) assay.Cell cycle distribution was assessed by flow cytometry.The expression levels of histone H3 kinases including ribosomal S6 serine-threonine kinase (RSK-2) and mitogen-and stressactivated protein kinase 1 and 2 (MSK1 and MSK2),and the levels of histone H3 (Ser10) phosphorylation and c-Fos protein were detected using Western blotting.Results Treatment of these two human colorectal cancer cell lines with ERK-MAPK inhibitor resulted in a time and dose-dependent inhibition of cell proliferation significantly. Proliferation rate of HCT116 was reduced to 47% at 72 hours after 40/μmol/L U0126 treatment. Cell cycle analysis showed that the percentage of phase G0/G1 cells significantly increased (P<0. 01) and the percentage of phase S cells decreased (P<0.01) after treatment with ERK-MAPK inhibitor. The expression of MSK1 and RSK2 reduced obviously in both of human colorectal cancer cell lines treated with U0126, which resulted in a 28% and 40% reduction of levels of MSK1 and RSK2 as compared with control HCT116 cells respectively,while no detectable change in the expression of MSK2 was found. Consistent with this, the expression level of histone H3 (ser10) phosphorylation was markedly down-regulated by ERK-MAPK inhibitor, and the related protein c-Fos expression decreased accordantly. Conclusions Decreased ERK-MAPK signaling pathway may reduce histone H3 (Ser10) phosphorylation via suppression of the activity of histone H3 kinase including MSK1 and RSK2, but not MSK2, consequently decrease the expression of c-Fos protein, which results in the inhibition of colorectal cancer cells proliferation.

18.
Chinese Journal of Digestion ; (12): 619-622, 2010.
Article in Chinese | WPRIM | ID: wpr-383264

ABSTRACT

Objective To evaluate the clinical efficacy and safety of hydrotalcite chewable tablets in treatment of patients with functional dyspepsia epigastric pain syndrome(EPS), and to investigate the onset time of hydrotalcite after the first dosage and whether use of hydrotalcite in EPS is a costeffective strategy. Methods A multicenter, randomized, open, positive controlled clinical trial was carried out in 240 patients with EPS. The subjects randomly received eigher hydrotalcite or omeprazole for 2 weeks. The improvemcnt and the disappear time of symptoms were evaluated before and after treatment and cost-effective was analyzed between two groups. Results It was demonstrated that both hydrotalcite and omeprazole could relief symptoms after treatment. After treatment for 2 weeks, the total effective rate was 85. 71% in hydrotalcite group and 90. 43% in omeprazole group with no significant difference (P>0.05). The median onset time of hydrotalcite after first dosage was 0.417 h. The overall direct cost per patient was RMB ¥122. 29 for hydrotalcite treatment and RMB ¥242.95 for omeprazole treatment. The main adverse events included diarrhea, thirst, bloating,headache and belching. No severe adverse event was found in two groups. Conclusions Hydrotalcite has fast effect on relief of EPS symptoms. Use of hydrotalcite is a cost-effective strategy in the management of EPS. It is a safe and effective medicine in treatment of EPS.

19.
Chinese Journal of Digestive Endoscopy ; (12): 69-72, 2009.
Article in Chinese | WPRIM | ID: wpr-381383

ABSTRACT

Objective To evaluate the diagnosis and management of ectopic pancreas.Methods The clinical data of 62 cases of ectopic pancreas,which were diagnosed by endoscopic uhrasonography (EUS)or pathologic findings between July 2006 and December 2007 were retrospectively analyzed.The cases were divided into 4 groups according to different ways of management.Group A included 37 patients,who were diagnosed as having ectopic pancreas(<19mm)by EUS only and were followed up via phone call every 3 months.Eight patients in group B were diagnosed by EUS as having submucosal lesions suspected as ectopic pancreas,and underwent operation because of large size or difficulty in diagnosis.Eight patients in group C received operation for other diseases and the eetopic pancreases were found in operation.Group D included 9 patients who underwent surgery due to malignant tumors.ResultsEctopic pancreas were most commonly found as a single lesion in gastric antrum(35/62,56.5%)with mean size of 9.2±5.4 mm.All patients in group A were asymptomatic,of which 10 received followed-up endoscopy and no changes in size of the lesion were found.All patients in group B,C and D were diagnosed as ectopic pancreas pathologically.Conclusion Ectopic pancrea is relatively common and asymptomatic,only part of them could be diagnosed clinically.Carcinoma arising from the ectopic pancreas is rare and lesion of small size diagnosed by EUS could be followed up endoseopieally.

20.
Chinese Journal of Digestion ; (12): 109-113, 2009.
Article in Chinese | WPRIM | ID: wpr-381193

ABSTRACT

Objective To investigate the combined inhibition effect and the potential mechanism of rapamycin (mammalian target of rapamycin inhibitor) and PD98059 (mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK) inhibitor) on mouse colorectal cancer (CRC). Methods S-ICR mice were subcutaneously injected with 20 mg/kg of 1,2-dimethylhydrazine dihydrochloride in the nape for 20 weeks to induce CRC. From the 16th week, the mice were treated with alone or combined injection with 0.25 mg/kg rapamycin and 2.5 mg/kg PD98059. The drugs were administered for 8 weeks. Subsequently, the animals were sacrificed and dissected, the tumor sizes were measured, and the tumors were harvested for pathological assay. Furthermore, the phosphorylation of mTOR, p70S6K, and 4E-BPl proteins was detected by using immunohistoehemistry. Results The mice treated with rapamycin (44. 44 %) or PD 98059 (either alone (38.89%) or combination treatment (6.67%) were significantly less likely to develop cancer compared with mice receiving none of them (77.78%, P<0. 05). The average size of tumors was (6.15±2. 192), (8.85±3. 983), (2.917±0. 191), (16.36±6.855) mm3 respectively (P<0.05).The anti-cancer effect of the combination treatment was substantially significant. The proteins of phospho-mTOR, phospho-p70s6K and phospho-4E-BPl were significantly down-regulated after treatments (all P values < ,0.05). Conclusions Combined treatment was more effective than single-drug treatments of rapamycin or PD98059 alone for the prevention and treatment of mouse CRC. The mTOR signal pathway might be involved in the inhibitory mechanism.

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