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1.
Article in Chinese | WPRIM | ID: wpr-921710

ABSTRACT

This study aims to explore the mechanism of fresh Phragmitis Rhizoma against chronic bronchitis airway inflammation. The SD rats of SPF grade were divided into control group, model group, Guilongkechuanning group(GLKCN, 1.125 g·kg~(-1)), high-dose fresh Phragmitis Rhizoma group(LG-HD, 15 g·kg~(-1)), and low-dose fresh Phragmitis Rhizoma group(LG-LD, 7.5 g·kg~(-1)). The chronic bronchitis models of rats in other groups except the control group were induced by the modified smoking method. From the 15 th day of modeling, the rats were given corresponding agents by gavage for 20 consecutive days. After the last administration, the rats were sacrificed for sample collection. Enzyme-linked immunosorbent assay(ELISA) was employed to detect serum transforming growth factor-β(TGF-β) and interleukin-6(IL-6) levels. The protein expression of TGF-β, IL-1β and IL-6 in lung tissue was detected by immunohistochemical method. Masson staining was performed to detect collagen fibers and muscle fibers in lung tissue, and HE staining to detect the pathological changes of lung tissue. Human bronchial epithelial(16 HBE) cells were cultured in vitro, and CCK-8(cell counting kit-8) method was used to detect the cytotoxicity of cigarette smoke extract(CSE) and fresh Phragmitis Rhizoma. After the exposure of 16 HBE cells to 3.5% CSE and appropriate concentration(800, 400 μg·mL~(-1)) of fresh Phragmitis Rhizoma for 24 h, quantitative real-time PCR was conducted to determine the mRNA levels of TGF-β and IL-1β, and Western blot was employed to determine the protein levels of TGF-β and IL-6 in the cells. The rat model of chronic bronchitis induced by smoking was successfully established. Fresh Phragmitis Rhizoma reduced serum TGF-β and IL-6 levels, down-regulated the protein levels of TGF-β, IL-1β, and IL-6 in lung tissue, and alleviated pathological changes and fibrotic lesions in lung tissue. Moreover, it down-regulated the CSE-induced protein expression of TGF-β and IL-6 as well as the mRNA level of TGF-β in 16 HBE cells. These results indicated that fresh Phragmitis Rhizoma could prevent airway inflammation from chronic bronchitis and promote cell repair by inhibiting the TGF-β signaling pathway.


Subject(s)
Animals , Bronchitis, Chronic/genetics , Drugs, Chinese Herbal/pharmacology , Inflammation , Lung , Poaceae/chemistry , Rats , Rats, Sprague-Dawley , Rhizome , Signal Transduction , Transforming Growth Factor beta/genetics
2.
Article in Chinese | WPRIM | ID: wpr-773909

ABSTRACT

OBJECTIVE@#To explore the clinical effect of acupoint puncture combined with Ilizarov technique in the treatment of knee osteoarthritis in the elderly.@*METHODS@#From March 2015 to February 2016, 76 patients with primary knee osteoarthritis were treated with tibial osteotomy acupoint puncture grouop and Ilizarov technique anatomical puncture group, including 24 males and 52 females, aged 56 to 75 years old with an average of 61.4 years old, and a course of 3 to 17 years with an average of 5.2 years. Among them, 38 cases were treated with external fixation of acupoint puncture needle and 38 cases were treated with external fixation of anatomical puncture needle. Preoperative full-length X-ray of both lower limbs showed tibial varus deformity, narrowing of medial knee joint space and enlargement of lateral knee joint space. The force line of the affected knee and lower limb was moved inward by body surface measurement, and the KSS knee function score was decreased. Symptoms included medial knee pain, flexion and extension, and conservative treatment for more than 2 years.@*RESULTS@#The lower limb force lines of both groups were corrected and the osteotomy ends healed well. No nonunion of osteotomy, inadequate correction of lower limbs or recurrence of deformity were found. Seventy-five patients were followed up for 3, 6, 12 and 24 months after operation. There was no significant difference in knee joint mobility between the two groups before operation and on 6, 12, 24 months after operation(=1.346, >0.05). There were significant difference in KSS pain and total score between the two groups at 3 months after operation, acupoint puncture group was better than anatomical puncture group(0.05).@*CONCLUSIONS@#The acupoint puncture group formed a potential acupuncture effect in the acupoint area by continuously tightening the steel needle on Ilizarov ring external fixator during the post-operative adjustment. Within three months after wearing external fixator, the knee pain symptoms of knee osteoarthritis were relieved rapidly, continuously and effectively, which was significantly better than that of the anatomical puncture group.


Subject(s)
Acupuncture Points , Aged , Female , Humans , Ilizarov Technique , Knee Joint , Male , Middle Aged , Osteoarthritis, Knee , Therapeutics , Punctures , Tibia , Treatment Outcome
3.
Article in Chinese | WPRIM | ID: wpr-667742

ABSTRACT

Adverse drug reactions (ADRs) induced by drug-drug interactions have posed a serious threat to patients′health and caused immense economic losses. With the increase in the number of combined drugs, the occurrence rate of side effects has surged. Since traditional methods for discovering drug interactions are infficient and costly, the biomedical informatics based methods are able to acquire valuable information about ADR by analyzing and mining from biomedical big data at a low cost and with high throughput. Methods of discovering potential drug interactions through literature mining, data mining and physiologically based pharmacokinetic models are systematically reviewed in this paper. Also, the prospect of potential research fields of drug conbination is outlined.

4.
Article in Chinese | WPRIM | ID: wpr-304855

ABSTRACT

In the present study, the effects of six Coptidis alkaloids (berberine, epiberberine, coptisine, jatrorrhizine, palmatine and magnoflorine) on liver microsomes UGTs and UGT1A1 activities in rats and mice were investigated in vitro and in vivo to study the mechanism of metabolic drug-drug interactions of Coptidis Rhizoma with other drugs. In vitro rat and mice liver microsomal incubation systems combined with UDPGA were applied, as well as mice liver microsomes after administration of six Coptidis alkaloids. 4-Nitrophenol and β-estradiol were selected as substrates to determine activities of UGTs and UGT1A1 by UV and HPLC, respectively. According to the in vitro rat study, berberine, epiberberine, coptisine and jatrorrhizine significantly inhibited rat liver microsome UGTs activity, particularly epiberberine showed the strongest inhibition. UGT1A1 activity was lowly inhibited by jatrorrhizine, with IC₅₀ at about 227 μmol•L⁻¹, whereas coptisine and magnoflorine significantly activated UGT1A1. According to the in vitro mice study, berberine, coptisine, jatrorrhizine and palmatine significantly inhibited mice liver microsome UGTs activity, and the six alkaloids all significantly activated UGT1A1. According to the in vivo mice study, UGTs activity was significantly activated only in berberine group, while UGT1A1 activity was significantly activated only in jatrorrhizine group. In conclusion, the effects of Coptidis alkaloids on UGT activity showed significant differences in species and between in vitro and in vivo. Meanwhile, the changes in structures of Coptidis alkaloids also have a big impact on UGT activity, which may be one of the causes for the drug-drug interactions between Coptidis Rhizoma and other drugs.

5.
Article in Chinese | WPRIM | ID: wpr-320877

ABSTRACT

The dried flower buds or initial flowers of Lonicerae Japonicae Flos and Lonicerae Flos, which belong to different species of Lonicera or Caprifoliaceae, are usually taken to clear away heat and toxic material and treat the exopathogenic wind-heat. They are two different herbs, and due to various reasons, there are far more controversies. This paper reviews the research on the chemical constituents and their differences between Lonicerae Japonicae Flos and Lonicerae Flos. Both of them contain the similar chemical constituents, such as organic acids, flavonoids, triterpenoidal saponins, iridoids, volatile oils and trace elements. But there are also differences between them. The main differences:Lonicerae Japonicae Flos contains a wealth of iridoids and flavonoids, while Lonicerae Flos contains more kinds of triterpenoidal saponins; the content of chlorogenic acid in Lonicerae Flos is significantly higher than that of Lonicerae Japonicae Flos; the content of rutin, luteoloside,luteolin-7-O-β-D-galactoside and lonicerin in Lonicerae Japonicae Flos is much higher than that of Lonicerae Flos; the content of Fe and Ni in Lonicerae Japonicae Flos is higher, while the content of Mn is higher in Lonicerae Flos. Finally, main problems and suggestions on chemical composition between Lonicerae Japonicae Flos and Lonicerae Flos were also discussed.

6.
Article in Chinese | WPRIM | ID: wpr-236011

ABSTRACT

It's a common phenomenon that two kinds or more than two kinds of herbs belong to different parts of the same plant. Lonicera Japonica Flos, Lonicera Japonica Caulis and Lonicera Japonica Folium are the typical representative of this phenomenon. They belong to different parts of the Lonicera japonica Thunb. This paper reviewed the research progress on pharmacological effects and their differences among them. It was found that the research mainly concentrated on Lonicera Japonica Flos, and the others were ignored. However, some pharmacological effects in leaves are stronger than that of flowers and stems, such as antibacterial, anti-bird flu and antioxidant activity.Lonicera Japonica Flos is mainly used for the treatment of respiratory tract virus infection while Lonicera Japonica Caulis is mainly used for the treatment of hepatitis virus infection, respectively. Finally, main problems and suggestions on pharmacological effects among them were also discussed.

7.
Article in Chinese | WPRIM | ID: wpr-230129

ABSTRACT

To predit the mechanism of metabolic drug-drug interactions of hydroxygenkwanin with other drugs, we investigated the inhibition inhibitory effect of hydroxygenkwanin on UGTs and UGT1A1 activities of different liver microsomes. In the present study, 4-nitrophenol (4-NP) and β-estradiol were elected as substrates to determine activities of UGTs and UGT1A1 by UV and HPLC, respectively. The results showed that, hydroxygenkwanin significantly inhibited UGTs activity in rat, mouse and human liver microsomes. UGT1A1 activity was inhibited by hydroxygenkwanin to varying degrees, with IC₅₀ about 190, 10.93, 20.07, 76.31 μmol•L⁻¹ in mouse liver microsome(MLM), rat liver microsome (RLM) and recombinant UGT1A1, and human liver microsome (HLM), respectively. The inhibition types were competitive inhibition (RLM, HLM) and linear mixed-typed linear inhibition (recombinant UGT1A1). The order for the inhibitory intensity was RLM>rUGT1A1>HLM>MLM. In conclusion, hydroxygenkwanin has an inhibitory effect on UGTs and UGT1A1 activities of different liver microsomes, with differences in species, indicating its potential drug interactions based on UGT1A1 enzyme. This study aims to provide a reliable experimental basis for its further research and development of hydroxygenkwanin, and provide theoretical reference for the clinic drug combination research.

8.
Chinese Journal of Cancer ; (12): 177-183, 2015.
Article in English | WPRIM | ID: wpr-349606

ABSTRACT

<p><b>INTRODUCTION</b>An increasing number of targeted drugs have been tested for the treatment of nasopharyngeal carcinoma (NPC). However, targeted therapy-related oncogenic mutations have not been fully evaluated. This study aimed to detect targeted therapy-related oncogenic mutations in NPC and to determine which targeted therapy might be potentially effective in treating NPC.</p><p><b>METHODS</b>By using the SNaPshot assay, a rapid detection method, 19 mutation hotspots in 6 targeted therapy-related oncogenes were examined in 70 NPC patients. The associations between oncogenic mutations and clinicopathologic factors were analyzed.</p><p><b>RESULTS</b>Among 70 patients, 12 (17.1%) had mutations in 5 oncogenes: 7 (10.0%) had v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) mutation, 2 (2.8%) had epidermal growth factor receptor (EGFR) mutation, 1 (1.4%) had phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutation, 1 (1.4%) had Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation, and 1 (1.4%) had simultaneous EGFR and v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutations. No significant differences were observed between oncogenic mutations and clinicopathologic characteristics. Additionally, these oncogenic mutations were not associated with tumor recurrence and metastasis.</p><p><b>CONCLUSIONS</b>Oncogenic mutations are present in NPC patients. The efficacy of targeted drugs on patients with the related oncogenic mutations requires further validation.</p>


Subject(s)
Carcinoma , Class I Phosphatidylinositol 3-Kinases , Humans , Mutation , Nasopharyngeal Neoplasms , Neoplasm Recurrence, Local , Oncogenes , Pharmacogenetics , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins B-raf , ErbB Receptors
9.
Article in Chinese | WPRIM | ID: wpr-310975

ABSTRACT

Epiberberine, one of the most important isoquinoline alkaloid in Coptidis Rhizoma, possesses extensive pharmacological activities. In this paper, the liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to study phase I and phase II metabolites. A Thermo HPLC system (including Surveyor AS, Surveyor LC Pump, Surveyor PDA. USA) was used. The cocktail probe drugs method was imposed to determine the content change of metoprolol, dapsone, phenacetin, chlorzoxazone and tolbutamide simultaneously for evaluating the activity of CYP2D6, CYP3A4, CYP1A2, CYP2E1 and CYP2C9 under different concentrations of epiberberine in rat liver microsomes. The result showed that epiberberine may have phase I and phase II metabolism in the rat liver and two metabolites in phase I and three metabolites in phase II are identified in the temperature incubation system of in vitro liver microsomes. Epiberberine showed significant inhibition on CYP2D6 with IC50 value of 35.22 μmol L(-1), but had no obvious inhibiting effect on the activities of CYP3A4, CYP1A2, CYP2E1 and CYP2C9. The results indicated that epiberberine may be caused drug interactions based on CYP2D6 enzyme. This study aims to provide a reliable experimental basis for its further research and development of epiberberine.


Subject(s)
Animals , Berberine , Chemistry , Metabolism , Chromatography, High Pressure Liquid , Cytochrome P-450 CYP2D6 , Metabolism , Cytochrome P-450 CYP2D6 Inhibitors , Chemistry , Metabolism , Drugs, Chinese Herbal , Chemistry , Metabolism , Male , Microsomes, Liver , Metabolism , Molecular Structure , Rats , Rats, Sprague-Dawley , Tandem Mass Spectrometry
10.
Article in Chinese | WPRIM | ID: wpr-341873

ABSTRACT

To figure out the stability and intestinal bacteria metabolites of rats in vitro of astragaloside IV ( AST), this research was done to explore the stability of AST in the artificial gastric juice. artificial intestinal juice and rat liver homogenate and the metabolism in rat intestinal in vitro. HPLC was used to calculate the remaining rate of AST in biological samples by measuring the content of AST, while metabolites were determined by combining the methods of TLC, HPLC and LC-MS/MS. It turned out that AST was difficult to metabolize in the artificial gastric juice, artificial intestinal juice and rat liver. Also, the metabolic pathway of AST was stepped by deglycosylation. Firstly, AST was converted to its secondary etabolites (6-O-β-D-glucopyranosyl- cycloastragenol, CMG) by removal of xylose moiety at C-3, then transformed into cycloastragenol (CAG) after hydrolytic removal of the glucose moiety at C-6. All the results suggested that the metabolism of AST in vivo occurs mainly in the intestinal by hydrolysis of glycosyl. In conclusion, hydrolysis of intestinal flora is the main reason that AST metabolizes.


Subject(s)
Animals , Bacteria , Metabolism , Chromatography, High Pressure Liquid , Drug Stability , Intestines , Microbiology , Liver , Metabolism , Rats , Rats, Sprague-Dawley , Saponins , Chemistry , Metabolism , Tandem Mass Spectrometry , Triterpenes , Chemistry , Metabolism
11.
Chinese Journal of Cancer ; (12): 105-114, 2014.
Article in English | WPRIM | ID: wpr-320573

ABSTRACT

Both platinum-based doublet chemotherapy (PBC) and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) prolong the survival of patients with advanced non-small cell lung cancer (NSCLC). In early studies, most patients underwent PBC as first-line treatment, but not all patients could afford EGFR-TKIs as second-line treatment. To understand the impact of PBC and EGFR-TKIs on NSCLC prognosis, we evaluated the association between the receipt of both regimens and overall survival (OS). Using MEDLINE and EMBASE, we identified prospective, randomized, controlled phase III clinical trials in advanced NSCLC that met the inclusion criteria: in general population with advanced NSCLC, the percentage of patients treated with both PBC and EGFR-TKIs was available in the trial and OS was reported. After collecting data from the selected trials, we correlated the percentage of patients treated with both PBC and EGFR-TKIs with the reported OS, using a weighted analysis. Fifteen phase III clinical trials--involving 11,456 adult patients in 32 arms--were included in the analysis, including 6 trials in Asian populations and 9 in non-Asian (predominantly Caucasian) populations. The OS was positively correlated with the percentage of patients treated with both PBC and EGFR-TKIs (r = 0.797, P < 0.001). The correlation was obvious in the trials in Asian populations (r = 0.936, P < 0.001) but was not statistically significant in the trials in predominantly Caucasian populations (r = 0.116, P = 0.588). These results suggest that treatment with PBC and EGFR-TKIs may provide a survival benefit to patients with advanced NSCLC, highlighting the importance of having both modalities available for therapy.


Subject(s)
Aged , Antineoplastic Combined Chemotherapy Protocols , Therapeutic Uses , Carcinoma, Non-Small-Cell Lung , Drug Therapy , Genetics , Pathology , Clinical Trials, Phase III as Topic , Disease-Free Survival , Female , Humans , Lung Neoplasms , Drug Therapy , Genetics , Pathology , Male , Middle Aged , Neoplasm Staging , Platinum , Protein Kinase Inhibitors , Therapeutic Uses , Randomized Controlled Trials as Topic , ErbB Receptors , Genetics , Survival Rate
12.
Chinese Journal of Cancer ; (12): 323-329, 2014.
Article in English | WPRIM | ID: wpr-320515

ABSTRACT

To improve cancer pain management, the Medical Oncology Department of Sun Yat-sen University Cancer Center (SYSUCC) launched the Good Pain Management (GPM) Ward Program, which has been recognized by the Chinese Ministry of Health and promoted throughout the nation. This retrospective case-control study was designed to evaluate the effectiveness of the program. Patients diagnosed with malignant solid tumors with bone metastasis were eligible. Patients who were admitted 6 months before the initiation of the GPM program were used as the control group, and patients admitted 6 months after the initiation of the program were used as the GPM group. The pain-reporting rate and pain management index (PMI) were calculated. The pain levels before and after pain management were compared. A total of 475 patients (244 in the control group and 231 in the GPM group) were analyzed. The pain-reporting rate of the GPM group was significantly higher than that of the control group (62.8% vs. 37.7%, P < 0.001). The PMI of the GPM group was significantly higher than that of the control group (0.083 vs. -0.261, P < 0.001). Therefore, the GPM Ward Program improved the pain management of cancer patients and provided experience for improving cancer pain management in the future.


Subject(s)
Aged , Bone Neoplasms , Case-Control Studies , China , Humans , Medical Oncology , Neoplasms , Pain , Pain Management , Methods , Pain Measurement , Retrospective Studies
13.
Journal of Preventive Medicine ; (12): 565-568, 2014.
Article in Chinese | WPRIM | ID: wpr-792308

ABSTRACT

Objective To evaluate the effect of community health self-management which was carried out by health club. Methods A total of 163 health club members attended 6 lessons of standardized health self-management course during 3 months. The awareness rate of related healthy knowledge,self-management behavior forming rate,BMI,blood pressure, FBG and other indexes were measured before and after 3 months. Results The average awareness rate increased significantly after the project(P<0. 05). In terms of self-management behavior forming condition,the achievement rates significantly increased in aspects of"Daily exercise time longer than 30 minutes"and"Daily intake of vegetables more than 250g"(both P<0. 05). While the average diastolic pressure among 121 hypertensive participants and fasting blood -glucose value of 47 diabetic participants both decreased significantly after the project(both P<0. 05). Conclusion The effect of education on community health self-management for chronic disease prevention which carried out by health club is positive apparently. It has certain functions on blood pressure and FBG control while short-term influence on BMI has not been found.

14.
Chinese Journal of Cancer ; (12): 476-483, 2012.
Article in English | WPRIM | ID: wpr-295870

ABSTRACT

Gemcitabine has high activity against nasopharyngeal carcinoma (NPC). The level of ribonucleotide reductase subunit M1 (RRM1) expression is closely related to the efficacy of gemcitabine on non-small cell lung cancer and pancreatic cancer. However, the expression of RRM1 and its association with sensitivity to gemcitabine-based chemotherapy in advanced NPC is not known. In this study, we retrospectively collected 48 formalin-fixed, paraffin-embedded NPC tissues to evaluate the expression of RRM1 using immunohistochemistry. All patients were diagnosed and treated with gemcitabine-based chemotherapy at Sun Yat-sen University Cancer Center. RRM1 expression was positive in 17(35%) patients. RRM1 expression was not associated with sex, age, performance status, WHO histological type, number of distant metastases, previous treatment, or cycles of gemcitabine-based chemotherapy(P> 0.05). The progression-free survival of the RRM1-positive group was shorter than that of the RRM1-negative group (5 months vs. 7 months, P = 0.036), and the response rate of the RRM1-positive group was somewhat lower than that of the RRM1-negative group (51.6% vs. 35.3%, P = 0.278). There was no significant difference in median survival between the RRM1-positive and RRM1-negative groups (22 months vs. 19 months, P = 0.540). Our results show that RRM1-negative expression is related with longer progression-free survival in advanced NPC patients treated with gemcitabine-based regimens.


Subject(s)
Adult , Aged , Antimetabolites, Antineoplastic , Therapeutic Uses , Deoxycytidine , Therapeutic Uses , Disease-Free Survival , Drug Resistance, Neoplasm , Female , Humans , Immunohistochemistry , Male , Middle Aged , Nasopharyngeal Neoplasms , Drug Therapy , Metabolism , Pathology , Neoplasm Staging , Remission Induction , Retrospective Studies , Survival Rate , Tumor Suppressor Proteins , Metabolism
15.
Chinese Journal of Cancer ; (12): 541-548, 2012.
Article in English | WPRIM | ID: wpr-295837

ABSTRACT

Secreted protein, acidic and rich in cysteine (SPARC) is expressed in numerous types of tumors and is suggested to have prognostic value. Moreover, because of its strong affinity for albumin, and hence albumin-bound drugs, SPARC has increasingly become a focus for research. In this study, we aimed to determine SPARC expression in patients with non-small cell lung cancer (NSCLC) and investigate the association of SPARC with disease prognosis. Tissue microarrays were constructed with specimens from 105 patients with NSCLC treated at Sun Yat-sen University Cancer Center, and immunohistochemical analysis was performed on these tissue microarrays to assess SPARC expression. Our results showed that SPARC expression status did not significantly relate with age, gender, and tumor stage. However, SPARC was expressed more frequently in squamous cell carcinoma than in adenocarcinoma (75% vs. 43.5%, P = 0.004). Patients with smoking history had higher SPARC expression than non-smokers (68.2% vs. 33.3%, P = 0.002). In both univariate and multivariate analyses, SPARC was a prognostic factor of overall survival (HR = 0.32; 95% CI: 0.16-0.65) but not disease-free survival. Our study indicates that SPARC expression is higher in squamous cell carcinoma than in adenocarcinoma in NSCLC. Most notably, SPARC can be used as a prognostic factor for NSCLC.


Subject(s)
Adenocarcinoma , Metabolism , Pathology , Adult , Aged , Carcinoma, Non-Small-Cell Lung , Metabolism , Pathology , Carcinoma, Squamous Cell , Metabolism , Pathology , Disease-Free Survival , Female , Humans , Immunohistochemistry , Lung Neoplasms , Metabolism , Pathology , Male , Middle Aged , Neoplasm Staging , Osteonectin , Metabolism , Proportional Hazards Models , Smoking , Survival Rate
16.
Article in Chinese | WPRIM | ID: wpr-266106

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the influence of genetic polymorphism in NF-E2-related factor-2 (nrf2) gene promoter locus at 336 in alcoholic liver disease (ALD) with Vibrio vulnificus (VV) sepsis.</p><p><b>METHODS</b>Through the simple random sampling method, C57B6 male mice were divided into normal feeding group (group A, 10 mice), alcoholic liver disease group (group B, 10 mice), normal feeding group infected with VV through intraperitoneal injection (group C, 8 mice), alcoholic liver disease group infected with VV (group D, 110 mice). Through gene sequencing method, nrf2 gene promoter 336 polymorphism in D group was analyzed and grouped into: non-mutation group (336T) (group D1, 7 mice) and mutation group (336C) (group D2, 10 mice). Through RT-PCR, Western-blotting and ELISA method, expressions of nrf2, tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), high mobility group protein 1 (HMGB(1)) gene and protein of liver were measured. The pathological changes in liver were recorded with light microscope.</p><p><b>RESULTS</b>After infected with VV for 48 hours for A, B, C, D1, D2 group, the expression medians of nrf2 mRNA in liver were 0.115, 0.173, 0.211, 0.764, 0.352, respectively (χ(2) = 40.64, P < 0.05), the expression medians of IL-10 mRNA in liver were 0.338, 0.637, 1.002, 1.825, 1.403, respectively (χ(2) = 41.05, P < 0.05), the expression medians of TNF-α mRNA in liver were 0.140, 0.254, 0.372, 0.399, 0.699, respectively (χ(2) = 38.16, P < 0.05), the expression medians of HMGB(1) mRNA in liver were 0.230, 0.410, 0.668, 0.508, 1.021, respectively (χ(2) = 31.45, P < 0.05). After infected with VV 48 hours for mice in A, B, C, D1, D2 group, the expression medians of nrf2 protein in liver were 0.908, 1.461, 2.061, 3.982, 2.243, respectively (χ(2) = 33.72, P < 0.05), the expression medians of IL-10 protein in liver were 13.97, 22.54, 30.14, 57.98, 41.53, respectively (χ(2) = 37.31, P < 0.05), the expression medians of TNF-α protein in liver were 114.07, 142.94, 175.44, 174.60, 266.11, respectively (χ(2) = 32.29, P < 0.05), the expression medians of HMGB(1) protein in liver were 2.01, 6.05, 9.62, 6.24, 12.89, respectively (χ(2) = 36.94, P < 0.05). Compared with group A, there were large amount of fat drops, fatty changes in group B, inflammatory cell infiltration, disorder of hepatic cell in group C, and extension of hepatic duct and vein, edema of liver cells and disorder of hepatic cells in group D.</p><p><b>CONCLUSION</b>The nrf2 gene promoter of T336C mutation in C57B6 mouse of ALD can significantly decrease the expression of nrf2, and intensify organ inflammation and damage when they were infected by VV.</p>


Subject(s)
Animals , Liver Diseases, Alcoholic , Genetics , Metabolism , Microbiology , Male , Mice , Mice, Inbred C57BL , NF-E2-Related Factor 2 , Genetics , Metabolism , Polymorphism, Single Nucleotide , Promoter Regions, Genetic , Sepsis , Genetics , Microbiology , Vibrio Infections , Genetics , Vibrio vulnificus
17.
Chinese Medical Journal ; (24): 19-25, 2011.
Article in English | WPRIM | ID: wpr-241537

ABSTRACT

<p><b>BACKGROUND</b>Molecular targeted drugs is now widely used in non-small cell lung cancer (NSCLC) clinical treatment. Icotinib hydrochloride is a new type of oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs). In this study, we examined the role of EGFR, K-RAS, B-RAF somatic mutations and EGFR mRNA expression in tumor specimens from advanced NSCLC patients as predicators of the efficacy of icotinib hydrochloride.</p><p><b>METHODS</b>We analyzed tumor paraffin-embedded specimens, which were obtained from 14 of 40 patients with advanced NSCLC who enrolled in the stage I clinical trial of icotinib hydrochloride. Somatic mutations were evaluated by mutant-enriched liquidchip (MEL) technology, and EGFR mRNA expression was measured by branched DNA liquidchip (MBL) technology.</p><p><b>RESULTS</b>In the 14 specimens, seven patients showed EGFR mutations, exon 19 deletion (3/7) and exon 21 point mutation (4/7); and two patients showed K-RAS mutation. No mutations in EGFR exon 20 or B-RAF were detected. In patients with EGFR mutation, one patient developed progress disease (PD), three patients had stable disease (SD), two patients had partial responses (PR) and one patient had a complete response (CR). In patients with wild-type EGFR, four patients had PD, three patients acquired SD, and none had PR/CR (P = 0.0407). EGFR mutations were associated with better progress-free survival (PFS) (141 days vs. 61 days) but without a statistically significant difference (P = 0.8597), and median overall survival (OS) (≥ 449 days vs. 140 days). EGFR mRNA expression levels were evaluated (three high, eight moderate, one low, and two that can not be measured due to insufficient tumor tissue) and no statistically significant relationships was observed with response, PFS or OS.</p><p><b>CONCLUSIONS</b>The EGFR mutation rate was consistent with that reported in the Asian population, so the MEL technology is reliable for measuring EGFR mutation with high throughput and rapidity. EGFR exon 19 deletions and exon 21 point mutation are predictive biomarkers for response to icotinib hydrochloride as second line treatment or above.</p>


Subject(s)
Adult , Aged , Antineoplastic Agents , Therapeutic Uses , Carcinoma, Non-Small-Cell Lung , Drug Therapy , Genetics , Crown Ethers , Therapeutic Uses , Exons , Genetics , Female , Humans , Male , Middle Aged , Mutation , Proto-Oncogene Proteins B-raf , Genetics , Proto-Oncogene Proteins p21(ras) , Genetics , Quinazolines , Therapeutic Uses , RNA, Messenger , Genetics , ErbB Receptors , Genetics
18.
Article in Chinese | WPRIM | ID: wpr-298803

ABSTRACT

<p><b>OBJECTIVE</b>To investigate effects of two kinds of anti-cancer bioactive peptide (ACBP) on proliferation and cell cycle in human nasopharyngeal carcinoma strain CNE.</p><p><b>METHODS</b>Cell culture was used in vitro, CNE cells were exposed to different concentration ACBP, in all groups, contrast groups were set up. And 24, 48, 72 hours later, growth characteristics of CNE cells were studied by morphological observation and MTT assay . Cell cycle and apoptosis were analyzed by flow cytometry (FCM).</p><p><b>RESULTS</b>In normal contrast group, CNE cells grew intensively and contacted with each other. However, cells which were treated with ACBP were inhibitory greatly in higher dose ACBP group, necrosis could be found. MTT assay showed that ACBP inhibited growth of CNE cell. FCM showed that ACBP (20.0 microg/ml) could raise cell ratio of S phase and induce apoptosis of CNE cells. CNE cells were treated by two kind of ACBP (5.0 microg/ml) for 24 h, FCM showed that early apoptosis rate were (11.8 +/- 0.3)% and (8.1 +/- 0.2)% respectively, which showed statistical significance in comparison with control group (t = 42.535, 47.300 respectively, P = 0.000). Under light microscope, some sings of cell apoptosis including coagulation of chromatin, fragmentation of nuclei and apoptotic body could be found.</p><p><b>CONCLUSIONS</b>Two kinds of ACBP inhibited human nasopharyngeal carcinoma strain CNE proliferation and arrested the cells to S phase, also induced the cells to apoptosis. Nasopharyngeal neoplasms;</p>


Subject(s)
Apoptosis , Cell Cycle , Cell Line, Tumor , Cell Proliferation , Humans , Nasopharyngeal Neoplasms , Pathology , Peptides , Pharmacology
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