1.Targets and developments in molecular targeted therapies for liver cancer with cirrhosis
Chinese Journal of Hepatobiliary Surgery 2011;17(12):963-968
Hepatocellular carcinoma (HCC) is a complex and heterogeneous tumor with various genomic alterations.In most patients,HCC is associated with cirrhosis which contributes to treatment morbidity and mortality.Cirrhosis adds difficulties to clinical management of HCC.Over the past decade,several molecular targets which are involved in the etiology of HCC have been identified.Among them,treatment with sorafenib,an antiangiogenic and Raf kinase inhibitor,has shown survival benefit.This represents a breakthrough in treatment of this complex disease,and proves that molecular therapies can be effective in HCC.It is becoming apparent that to overcome the complexity of genomic aberrations in HCC,combination therapies are essential.Several ongoing clinical trials show encouraging results.Future researches are necessary to identify new compounds to block important undruggable pathways,and to identify new oncogenes as targets for therapies through novel high throughout technologies.Ultimately,a molecular classification of HCC based on genome investigations and identification of patient subclasses using drug responsiveness will lead to a more personalized treatment.Although molecular therapy is a promising treatment for HCC with cirrhosis,surgery,if applicable,remains the first choice of treatment.
2.A study on the effects of PPARγ ligand rosiglitazone in the growth of MGC803 cells transplanted into subrenal-capsule of mice
Lihui ZHU ; Li ZHANG ; Dazhi ZHONG
Cancer Research and Clinic 2008;20(3):155-157
Objective To investigate the inhibitory effects of PPARγ ligand rosiglitazone in vivo of mice which were transplanted the human gastric carcinoma cells line MGC803 into subrenal-capsule.Methods To establish kunming mouse tumor modles of MGC803 cells transplanted into subrenal-capsule and assay the inhibiting growth effects of 50 mg/kg rosiglitazone which were continuously poured into mice gastric for five days by the dissect microscope and HE stain.Results Rosiglitazone could inhibit the growth of MGC803 cells transplanted into subrenal-capsule of mice in vivo by inhibiting proliferation and inducting apoptosis,the tumor inhibitory rate was 62.9%.Conclusion PPARγ ligand rosiglitazone can inhibit the growth of MGC803 cells transplanted into subrenal-capsule of mice in vivo.
3.Epigenetic changes and reprogramming of hepatocellular carcinoma
Lixin LI ; Qiang HE ; Dazhi CHEN
International Journal of Surgery 2010;37(2):115-117
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. In ad-dition to genetic alterations, epigenetic inactivation of (tumor suppressor) genes has been recognized as an important and alternative mechanism in tumorigenesis. In recent years, increasing evidence has shown that ep-igenetic silencing of those genes is essential to carcinogenesis and metastasis. Epigenetics include two main forms: histone acetylation and DNA methylation, histone acetylation and DNA hypomethylation can promote gene expression,otherwise, they will inhibit gene expression. It is important to the methylation especially the hypermethylation of the tumor suppressor gene during the hepatocarcinogencsis. The study of epigenetics will be proved valuable for early diagnosis and disease monitoring at hepatocell.
4.Acute hypotensive episodes prediction based on non-linear chaotic analysis.
Dazhi JIANG ; Liyu LI ; Chenfeng PENG
Journal of Biomedical Engineering 2015;32(1):209-213
In intensive care units (ICU) , the occurrence of acute hypotensive episodes (AHE) is the key problem for the clinical research and it is meaningful for clinical care if we can use appropriate computational technologies to predict the AHE. In this study, based on the records of patients in ICU from the MIMIC II clinical data, the chaos signal analysis method was applied to the time series of mean artery pressure, and then the patient's Lyapunov exponent curve was drawn ultimately. The research showed that a curve mutation appeared before AHE symptoms took place. This is powerful and clear basis for AHE determination. It is also expected that this study may offer a reference to research of AHE theory and clinical application.
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diagnosis
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Nonlinear Dynamics
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5.Hyponatremia after liver transplantation
Xiaowen WANG ; Ning LI ; Dazhi CHEN
Chinese Journal of Organ Transplantation 2003;0(01):-
Objective To explore the causes and treatment measures of hyponatremia after liver transplantation. Methods The clinical data of 27 patients with hyponatremia after liver transplantation were analyzed retrospectively. Results Among the 27 patients, postoperative hyponatremia occurred in 25 cases in about one week, and preoperative hyponatremia occurred in 2 cases and severe ~hyponatre -mia occurred immediate after operation. Acute hyponatremia occurred in one case. Blood natrium was 130 to 135 mmol/L in 10 cases, 120 to 130 mmol/L in 12 cases and less than 120 mmol/L in 5 cases. The levels of blood potassium, phosphor and calcium were all normal. Urinary natrium, potassium and chlorine levels were all normal. The ascites natrium level was higher than blood natrium at the same time. Hyponatremia was treated by supply of hypertonic saline via gastrointestine an/or veins. Conclusion Various causes could result in hyponatremia after liver transplantation. The hyponatremia was treated by supply of hypertonic saline constantly and slowly.
6.Application of Laparoscopic Ultrasonography in Hepatobiliary Surgeries
Dehong XIE ; Dazhi CHEN ; Peng LI
Chinese Journal of Minimally Invasive Surgery 2001;0(01):-
Objective To analyze the clinical value of laparoscopic ultrasonography (LUS) in laparoscopic hepatobiliary surgeries. Methods A total of 156 cases of laparoscopic hepatectomy, hepatic abscess fenestration, and complicated cholecystectomy were analyzed. LUS was used during all the 156 operations; the anatomy and stage of the tumors were investigated. Results In 19 cases of hepatectomy and 39 cases of hepatic abscess fenestration, the direction of critical intrahepatic and extrahepatic ducts were indicated by using LUS, and the operations were performed under the guidance of LUS. Moreover, in 15 cases of complicated cholecystectomy, the tumor was precisely located and further distinguished by LUS. Conclusions Laparoscopic ultrasonography can precisely locate the tumor, guide the treatment, and resolve the problem of reduced feedback in touching for surgeons during laparoscopic hepatobiliary surgeries. It is of value to improve the operative outcomes.
7.Effects and mechanisms of ghrelin on plaque neovascularization in rabbits with atherosclerosis
Li WANG ; Guiqiong LI ; Qingwei CHEN ; Dazhi KE
Chinese Journal of Endocrinology and Metabolism 2015;(8):717-724
Objective The aim of our study was to investigate the effects and mechanisms of ghrelin on neovascularization in atherosclerosis plaque. Methods 30 male New Zealand rabbits were randomly divided into normal control group ( CON group) , atherosclerosis model group ( AS group) , and ghrelin treatment group ( ghrelin group) , and each group of 10 rabbits. The AS group and ghrelin group underwent balloon-induced arterial wall injury and then fed with high fat diet, the CON group was fed only on a regular diet. They were all fed for 3 months. Then the ghrelin group was given ghrelin 25μg·kg-1 ·d-1 , the other two groups received the same amount of sterile normal saline only. Four weeks later, body weight and blood lipids were detected. The thickness ratio of the intima to media was measured by HE staining. Degree of intra-plaque angiogenesis was evaluated by CD31+ cells immunohisto-chemistry. The vascular endothelial growth factor ( VEGF ) and vascular endothelial growth factor receptor 2 ( VEGFR2) were detected by quantitative realtime PCR and Western blot. The expressions of matrix metalloproteinase ( MMP)-2 and MMP-9 were detected by immunohistochemistry and Western blot. Results ( 1 ) No significant differences in body weight and blood lipids were found between the AS group and the ghrelin group(P>0. 05), but both items were significantly higher than those of the CON group(P<0. 05). (2)The thickness ratio of the intima to media in the ghrelin treated group was distinctly less than that in the AS group(P<0. 05). (3)Compared with the AS group, the ghrelin group showed significantly decreased microvascular density and the expressions of VEGF and VEGFR2 (P<0. 05). (4)Compared with the AS group, ghrelin dramatically inhibited the plaque contents of MMP-2 and MMP-9 ( P<0. 05 ). Conclusions Ghrelin is able to inhibit the growth of neovascularizationin in the atherosclerotic plaque and the development of plaque. And these beneficial effects derive from downregulation of VEGF, VEGFR2, MMP-2, and MMP-9 at the advanced stage of atherosclerosis in rabbits.
8.Relationship Between Prevalence of Atrial Fibrillation, Ischemia Stoke and CHA2DS2-VASc Score in Elderly Patients
Li WANG ; Qingwei CHEN ; Qin FENG ; Dazhi KE ; Guiqiong LI
Chinese Circulation Journal 2017;32(5):452-456
Objective: To explore the relationship between prevalence of atrial fibrillation (AF), iskhemia stoke and CHA2DS2-VASc score in patients≥65 years in order to provide prevention and treatment basis in clinical practice. Methods: A total of 5016 patients admitted in our hospital from 2013-10 to 2015-10 were enrolled. The patients were divided into 2 groups: AF group, n=437 and Non-AF patients, n=4579; according to age, the patients were further assigned into 4 subgroups as <65 years subgroup, (65-74) years subgroup, (75-84) years subgroup and ≥85 years subgroup. The risk factors for AF occurrence were retrospectively studied. Results: Compared with the Non-AF group, the patients in AF group had the elder age and more male gender, both P<0.001; more patients combining with hypertension, coronary artery disease (CAD), diabetes, sick sinus syndrome and rheumatic heart disease, all P<0.001. Age, male gender, CAD, sick sinus syndrome and rheumatic heart disease were the independent risk factors for AF occurrence. Compared with Non-AF group, AF group showed the higher prevalence rate of ischemic stroke and the elder onset age, both P<0.01. For non-valvular AF, the ratio of patients with CHA2DS2-VASc score≥2 was higher than those with CHA2DS2-VASc score<2 and the rate of anticoagulant therapy was decreasing by age increasing, all P<0.001. Conclusion: Age, male gender, CAD, sick sinus syndrome and rheumatic heart disease were independently related to AF occurrence. Non-valvular AF patients had the higher risk for ischemic stroke than non-AF patients, anticoagulation therapy should be conducted at the early stage.
9.Signal transduction in erythropoiesis induced by total saponins of Panax ginseng
Chunli LI ; Jianwei WANG ; Rong JIANG ; Yaping WANG ; Dazhi KE
Chinese Journal of Tissue Engineering Research 2009;13(23):4568-4572
BACKGROUND: Most of hematopoietic growth factor regulates proliferation and differentiation of blood cells through JAKs-STATs signal transduction pathway. Total saponins of Panax ginseng (TSPG) can promote in vitro differentiation of CD34+ hematopoietic progenitor cells into erythroid cells, with similar effectiveness of hematopoietic growth factor.Erythropoietin receptor (EpoR) expression on the cell membrane of progenitor cells is critical during the erythroid differentiation process.OBJECTIVE: To investigate the molecular mechanism of TSPG to induce erythroid cells through erythropoiesis and its receptor-mediated JAK2/STAT5 signal transduction.DESIGN, TIME AND SETTING: An in vitro cytological observation. The study was performed at the Department of Histology and Embryology, Institute of Basic Medicine, Chongqing Medical University from May 2006 to October 2008.MATERIALS: Umbilical cord blood of normal full-term pregnancy was provided by the First Hospital of Chongqing Medical University. TSPG, purity>95%, provided by Chongqing Institute of Traditional Chinese Medicine, was diluted in RPMI-1640 for work concentration of 1 g/L and degermed by positive pressure filtration.in RPMI-1640 culture solution containing horse serum, with various dilutions of TSPG (0 as blank control, 10, 25, 50, 75,100 mg/L). The MNCs were cultured on 96-well culture plate, with 0.2 mL in each well. Early erythroid cells were counted on were harvested and cultured separately in RPMI-1640 culture solution containing 10% horse serum as control group and in TSPG (25 mg/L)- conditioned culture system as experimental group. 5 U/mL Epo was added for 0, 2, 5 and 30 minutes.Immunoprecipitation of JAK2/STAT5 was used for the effect of TSPG on Epo/EpoR-induced tyrosine phosphorylation of JAK2/STAT5.MAIN OUTCOME MEASURES: Effect of TSPG on proliferation of erythroid progenitor cells from human umbilical cord blood;Effect of Epo on the proliferation of hematopoietic cells; Effect of TSPG on EpoR expression of the umbilical blood cells; tyrosine phosphorylations of JAK2 and STAT5.RERULTS: TSPG (10-75 mg/L) promoted the colony formation of BEU-E, CFU-E, and the preferential differentiation into erythroid lineage cells was most induced from 25 mg/L of TSPG. Using the colorimetric MTT assay, MNCs exhibited proliferative responses to Epo (2-50 U/mL) reaching maximum at 5 U/mL Epo. The addition of TSPG did not increase the expression of EpoR after MNCs were incubated in the presence of with or without TSPG for 24 hours. The pretreatment with TSPG for 24 hours enhanced Epo-induced tyrosine phosphorylation of JAK2 and STAT5 (STAT5a and STAT5b).
10.The development and breakthrough of clinical organ transplant tolerance induction
Jianke DING ; Fei PAN ; Xianliang LI ; Dazhi CHEN
Chinese Journal of Hepatobiliary Surgery 2013;(4):243-251
The long-term use of immunosuppressive agents after organ transplantation is associated with many undesirable side effects which may limit the survival of patients and transplanted organs.To patients and transplant surgeons,organ transplantation tolerance is the ultimate goal to improve patient's quality of life.The clinical state of allograft acceptance termed operational tolerance has remained infrequent in clinical transplantation because of the lack of validated assays or biomarkers predictive of tolerance and the concerns about the safety and ethics of complete withdrawal of immunosuppression.Despite these barriers,a number of investigators have continued to conduct well-designed studies with the long-term goal of inducing clinical transplantation tolerance.This review provides an overviewof the currently successful approaches to achieve clinical operational tolerance,including using immunosuppression slow withdrawal in organ transplantation,transplantation tolerance through mixed chimerism and clinical application of T regulatory cells in tolerance.