1.Effects of IFNα-2b on cell apoptosis and expression of hTERT and bcl-2 mRNA in keloid fibroblasts
Yong HUANG ; Qiang MENG ; Xin XING
Chinese Journal of Medical Aesthetics and Cosmetology 2008;14(4):261-264
Objective To observe the effects of IFNα-2b on keloid fibroblasts in cell prolifera-tion, apoptosis, expression of hTERT and bcl-2 mRNA and to explore its anti-keloid mechanism. Methods Primary cultures of dermal fibroblasts derived from 8 keloid and 8 normal skin samples were established, strains of fibroblasts at passages 3 to 4 were used in this study. Keloid and normal skin fibroblasts in culture medium in vitro were given IFNα-2b and were obsevered in different time. The proliferation of the fibroblasts was measured by MTT assay, the apoptosis was analysed by flow cytometry(FCM), and the expression of hTERT and bcl-2 mRNA were obsevered by semi-qnantitativere verse transcriptase-polymerase chain reaction (RT-PCR). The data were analyzed by statistical software (SPSS11. 5). Results IFNα-2b could inhibit the growth of keloid and nomal skin fibroblasts. The suppression of keloid and nomal skin fibroblasts was time-dependent. After the effect of 10 000 U/ml INFα-2b on cultured fibroblast of keloid and normal skin,the fibroblasts apoptosis was induced and the expression of hTERT and bcl-2 mRNA was lower than that of controlled group . The result was significantly different between control group and treatment group and was related with the treatment time of INFα-2b (P<0.01). Conclusions As a negative regulatory factor,interferon α-2b can suppress growth and proliferation of keloid fibroblasts and induce apoptosis. Decreasing the telomerase activity of keloid fibroblasts may be one of the most important mechamisms. That IFNa-2b inhibited telomerase activity in keloid fibroblasts is an important pathway that may play a key role in the anti- keloid therapy.
2.Research progress of endoplasmic reticulum targeting drug delivery system for anti-tumor immunotherapy
Li-qiang CHEN ; Xin-ran SHEN ; Yuan HUANG
Acta Pharmaceutica Sinica 2022;57(1):76-84
Endoplasmic reticulum (ER), a multifunctional organelle in eukaryotic cells, is responsible for protein synthesis and intracellular signal transduction, which dominates cell function, survival, and apoptosis. Disequilibrium of ER homeostasis may induce ER stress, which closely intertwines with tumor occurrence and progress. A few clinical-used drugs (such as anthraquinones and oxaliplatin) can mediate the immunogenic cell death of tumor cells through excessive ER stress, and sequentially stimulate anti-tumor immune responses as well as long-term immune memory. However, these drugs often exhibit poor targeting ability and extremely low ER accumulation in tumor cells, limiting their clinical efficacy. Therefore, the researches of ER-targeted delivery of these drugs will significantly benefit the efficient and precise anti-tumor immunotherapy. In this review, we introduce the relationship between ER and tumor immunity, and summarize the ER targeting strategies for anti-tumor immunotherapy in recent years. Furthermore, we discuss the problems of existing ER targeting strategies and look into its broad prospects of application.
3.Interventional therapy of biliary tract stricture by percutaneous transhepatic biliary tract drainage after orthotopic liver transplantation in 30 cases
Qiang LI ; Guokun AO ; Guosheng DU ; Bingyi SHI ; Xin HUANG ; Zhiyuan TAN ; Xiaoye WANG
Chinese Journal of Organ Transplantation 2010;31(12):745-748
Objective To discuss feasibility and therapeutic effect of the interventional management through biliary tract drainage with percutaneous transhepatic puncture technique for biliary tract stricture after orthotopic liver transplantation. Methods A retrospective review of the clinical and imaging materials of 292 postoperative orthotopic liver transplantation cases was made. Of these 292 cases, 30 patients suffered from biliary tract complications and treated with billiary balloon dilatation, bile drainage and biliary stenting techniques. Results After biliary balloon dilatation, 3 cases of biliary tract strictures and leaks, 3 cases of simple biliary anastomosis site strictures and 7 out of the 8 cases of multiple biliary tract strictures were cured. In one of the multiple biliary tract stricture patients, a hepatic hematoma after biliary balloon dilatation was found and a second liver transplantation was done. In the 14 cases of multiple biliary tract strictures accompanied with biliary sludge, balloon dilatation technique was repeatedly performed. In 12 of the 14 cases, the strictures were improved remarkably and jaundice was subsided; In one of 14 cases, biliary tract stenting procedure was performed, but liver re-transplatation was carried out because of stent obstruction by much sludge. In the remaining 1 of the 14 cases, because there was no improvement of the strictures and relief of jaundice was revealed after the repeated procedures, liver re-transplantation was finally done In 2 cases of strictures at the opening segment of the T tube, the procedure of percutaneous transhepatic puncture for bile drainage was managed. After the procedure, the strictures were alleviated and the jaundice relieved. Conclusion The interventional managements through percutaneous transhepatic puncture techniques were effective, convenient and minimally invasive for treating biliary tract strictures after orthotopic liver transplantation.
4.Intervetional therapy for portal vein occlusion after liver tansplantation
Jianfeng WANG ; Xin WANG ; Renyou ZHAI ; Kun GAO ; Baojie WEI ; Dingke DAI ; Qiang HUANG
Chinese Journal of Organ Transplantation 2014;35(4):206-210
Objective +o evaluate percutaneous intervetional therapy for portal vein anastomotic occlusion after liver transplantation.Method From July 2005 to July 2013,13 patients (9 male and 4 female; aged 25-65 years) with portal vein occlsion underwent interventional therapy.All patients accepted the imaging examation and 8 patients had typical clinical signs of portal hypertension.Percutaneous hepatic balloon venoplasty and stent placement was performed,trans-catherter urokinase infusion for thrombolysis and embolization for collateral pathways performed if necessary.+echnical success rate,complication rate and clinical symptoms were analyzed.Follow-ups including clinical course,stent patency and potal vein thrombosis which evaluated by imaging were performed.Result +echnical success was achieved in l1of 13 patients (84.6%) and 15 stents were deployed.Seven patients with localized portal vein occulsion accepted balloon dilation and stents deployment,4 patients with long segment cculsion also accept trans-catherter urokinase infusion for thrombolysis and embolization for collateral pathways.Portal vein flow recovered in all 11 patients.Procedure related complication occurred in 2 patient with hemothorax.During the follow-up period of 4-42 months,the clinical signs of portal hypertension were not observed in all patients.Stent stenosis was found in one patient with ultrasound in 23 months,but stent patency was proved by the percutaneous portal angiography.Conclusion Interventional therapy is effective for portal vein occulsion after liver transplantation,comprehensive interventional therapy should be performed in long segment portal vein cculsion.
5.Part II: Design, synthesis and antitumor action of C3/C3 bisfluoroquinolones linked-cross 2, 5-1, 3, 4oxadiazole.
Guo-qiang HU ; Yong YANG ; Lei YI ; Xin WANG ; Zhi-qiang ZHANG ; Song-qiang XIE ; Wen-long HUANG
Acta Pharmaceutica Sinica 2010;45(8):1012-1016
To develop a new small molecular probe for discovering an antitumor lead compound from the replacement of carboxylic group of two molecular antibacterial fluoroquinolones with a heterocyclic ring, a series of the C3/C3 bis-fluoroquinolones tethered with an 1, 3, 4-oxadiazole ring were synthesized as their respective HCl salts, and their structures were characterized by elemental analysis and spectral data. The in vitro antitumor activity against L1210, CHO and HL60 cell lines was also evaluated via the respective IC50 values by methylthiazole trazolium (MTT) assay.
Animals
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Antineoplastic Agents
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chemical synthesis
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chemistry
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pharmacology
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CHO Cells
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drug effects
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Cell Line, Tumor
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Cricetinae
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Cricetulus
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Drug Design
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Fluoroquinolones
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chemical synthesis
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chemistry
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pharmacology
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HL-60 Cells
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drug effects
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Humans
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Inhibitory Concentration 50
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Leukemia L1210
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pathology
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Molecular Structure
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Oxadiazoles
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chemical synthesis
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chemistry
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pharmacology
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Structure-Activity Relationship
6.The clinical significance of serum level of soluble intercellular adhesion molecule-1 detected before and after lung transplantation
Hua-long, XIAO ; Guo-qiang, XIE ; Guo-qian, CHEN ; Xiao-feng, ZHANG ; Xin-chen, QIANG ; Jing-feng, YU ; Lan, ZHU ; Bing-fang, ZHU ; Biao, HUANG
Chinese Journal of Nuclear Medicine 2010;30(5):343-345
Objective To evaluate serum soluble intercellular adhesion molecule-1 (sICAM-1) before and after lung transplantation for diagnosing acute rejection. Methods Biotin-streptavidin time resolved fluoroimmunoassay (BSA-TRFIA) was used to detect the concentration of serum sICAM-1 before and after lung transplantation in 26 patients. All patients were divided into stable lung transplantation group (n =16), acute rejection group (n =4) and infected group (n =6). The serum level of sICAM-1 in those groups was compared with that of the control group ( n = 30 ) by the non-parametric rank sum test ( KruskalWallis H test). Results No significant difference was found for serum sICAM-1 among the three groups and the control group before operation: (357.07 ± 220.01 ), ( 396. 18 ± 136.25 ), (468.95 ± 85.48 ) μg/L vs(348.63 ±69. 12) μg/L, H=6. 0436, P >0.05. However, when rejection and infection happened after operation, the serum sICAM-1 increased in the acute rejection group (455.53 ± 126.51 μg/L) and decreased in the infection group (146.43 ± 327.11 μg/L), and the level in the stable transplantation group was (274.23 ± 157.53 ) μg/L (H = 21. 8994, P < 0.01 ). Conclusion Serum sICAM-1 level might be a potential marker to differentiate acute rejection from infection after lung transplantation.
7.Simultaneous determination of repaglinide and pravastatin sodium in rat plasma by LC-ms/MS and its application on pharmacokinetic interactions study.
Yan-Rong MA ; Yan ZHOU ; Guo-Qiang ZHANG ; Zhi RAO ; Jing HUANG ; Yu-hui WEI ; Xin-An WU
Acta Pharmaceutica Sinica 2014;49(1):72-77
The study aims to establish a method for simultaneous determination of repaglinide and pravastatin sodium in rat plasma by LC-MS/MS and to study its pharmacokinetic interactions. Eighteen male SD rats were divided into repaglinide group, pravastatin sodium group and co-administration group. Blood samples were collected at different times after oral administration. Repaglinide and pravastatin sodium in rat plasma were separated by Agilent HC-C18 with the mobile phase consisting of methanol-0.1% formic acid (80 : 20). Detection and quantification were performed by using ESI-MS. The detector was operated in selected Reaction-monitoring mode at m/z 453.3-->230.1 for repaglinide, m/z 447.2-->327.4 for pravastatin sodium and m/z 285.1-->192.9 for diazepam as the internal standard. The calibration curve obtained was linear (R2>0.99) over the concentration range of 9.77-10,000 ng.mL-1 for repaglinide and 4.88-625 ng.mL-1 for pravastatin sodium. Compared with the single administration group, Cmax and AUC0-6h of repaglinide increased significantly (P<0.05) and tmax of pravastatin sodium prolonged (P<0.05) in co-administration group. The method is found to be simple, sensitive and accurate for determining the concentration of repaglinide and pravastatin sodium in rat plasma. There exists pharmacokinetic interactions in the co-administration of repaglinide and pravastatin sodium.
Administration, Oral
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Animals
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Carbamates
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administration & dosage
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blood
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pharmacokinetics
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Chromatography, High Pressure Liquid
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Drug Interactions
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Male
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Piperidines
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administration & dosage
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blood
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pharmacokinetics
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Pravastatin
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administration & dosage
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blood
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pharmacokinetics
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Random Allocation
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Rats
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Rats, Sprague-Dawley
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Reproducibility of Results
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Sensitivity and Specificity
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Spectrometry, Mass, Electrospray Ionization
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Tandem Mass Spectrometry
8.Effect of Neoadjuvant Chemotherapy Treatment on Prognosis of Patients with Advanced Gastric Cancer: a Retrospective Study.
Shu-bo TIAN ; Jian-chun YU ; Wei-ming KANG ; Zhi-qiang MA ; Xin YE ; Chao YAN ; Ya-kai HUANG
Chinese Medical Sciences Journal 2015;30(2):84-89
OBJECTIVETo evaluate the prognostic effects of neoadjuvant chemotherapy (NAC) in patients with local advanced gastric cancer.
METHODSWe retrospectively analyzed prognosis in 191 patients with advanced gastric cancer, of whom 71 were treated with NAC and 120 received surgery only between February 2007 and July 2013. Postoperative complication rate was recorded. Survival by clinicopathological features, pathological T and N stages, and histopathological tumor regression was retrospectively compared between the two groups.
RESULTSAccording to Response Evaluation Criteria in Solid Tumors, none of the 71 patients in the NAC followed by surgery group showed complete response, 36 showed partial response, 25 had stable disease, and 10 had progressive disease. The chemotherapy response rate was 50.7%; the disease control rate was 85.9%. Grade 3/4 adverse events were seen in less than 20% patients, with acceptable toxicities. No difference was found in the overall postoperative complication rates between the two groups (7 versus 22 cases, P=0.18). Median survival time was significantly different, at 54 months in the NAC combined with surgery group and 25 months in the surgery-only group (P=0.025).
CONCLUSIONIn patients with operable gastric adenocarcinomas, NAC can significantly improve overall survival without increasing surgical complications.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Neoadjuvant Therapy ; Prognosis ; Retrospective Studies ; Stomach Neoplasms ; drug therapy ; mortality ; pathology
9.An inquiry into blood loss in laparoscopic liver resections.
Rong LIU ; Yue-hua WANG ; Zhi-qiang HUANG ; Ning-xin ZHOU
Chinese Journal of Surgery 2003;41(8):591-593
OBJECTIVETo investigate the potential causes and preventive measures for blood loss in laparoscopic liver resection.
METHODSThe candidates for laparoscopic liver resections were 21 patients with liver lesions, including 13 patients with primary liver cancer, 2 patients with liver abscess, 3 patients with liver hemangioma, 1 patient with hepatic cellular adenoma, 1 patient with hepatic focal nodular hyperplasia, and 1 patient with infected liver cyst. They were classified as Child A in 16 and B in 5 patients.
RESULTSTwenty-one patients with liver lesions underwent 23 laparoscopic resections uneventfully. Operating procedures included partial liver resection in 12 patients, segment IV in 1 case and anatomical left liver resections in 8 patients. Operation duration was 80 - 320 (mean 193.8 +/- 78.3) minutes. The blood loss in operation was 100 - 1000 (mean 333.1 +/- 291.4) ml. The postoperative hospital stay averaged 6.3 +/- 1.5 days, which was markedly shortened in comparison to conventional laparotomy liver resections. In addition, there was no complication in this series.
CONCLUSIONSBased on these preliminary results, occlusion of hepatic vessels with clamp is very important for partial liver resection. The key technique is to control the blood loss in operation. We conclude that laparoscopic liver resection is a prospective minimally invasive technique. These experiences suggest that laparoscopic procedures could be employed both in the treatment of benign and malignant tumors in selected cases.
Adult ; Aged ; Blood Loss, Surgical ; prevention & control ; Female ; Hepatectomy ; adverse effects ; methods ; Humans ; Laparoscopy ; adverse effects ; methods ; Liver Diseases ; surgery ; Male ; Middle Aged
10.Essential Oil from Siegesbeckia pubescens Induces Apoptosis through the Mitochondrial Pathway in Human HepG2 Cells
LV DAN ; GUO KAI-WEN ; XU CHAN ; HUANG MI ; ZHENG SI-JIAN ; MA XIN-HUA ; PAN LI-HONG ; WANG QIANG ; YANG XIN-ZHOU
Journal of Huazhong University of Science and Technology (Medical Sciences) 2017;37(1):87-92
Siegesbeckia pubescens (SP) has been used as a traditional medicine for the treatment of and inflammatory diseases.However,the activities of SP against hepatocellular carcinoma and the related mechanisms remain unclear.The present study aimed to examine the effects of the essential oil of SP (SPEO) on the proliferation of hepatocellular carcinoma cells and the possible mechanisms.The growth inhibition of HepG2 cells was analyzed by MTT assay.Hoechst 33258 and fluorescence microscopy were utilized to observe the nuclear morphological changes of apoptotic cells.Flow cytometry was used to detect cell apoptosis and cell cycle.The expressions of the target proteins were detected by Western blotting.The results showed that SPEO obviously inhibited the proliferation of HepG2 cells in a dose-dependent manner.SPEO activated a series of apoptotic proteins in HepG2 cells,increasing expression levels of Bax,caspase-3 and caspase-9,and decreasing the bcl-2 expression level.SPEO displayed promising anti-hepatocellular carcinoma activities in vitro,partly by inducing apoptosis in HepG2 cells through activating the mitochondrial pathway.