AIM: To explore the possibility of marrow mesenchymal stem cells (MSC) in vitro differentiating into functional isletlike cells and to test the diabetes therapeutic potency of Islet-like cells. METHODS: Rat MSCs were ...AIM: To explore the possibility of marrow mesenchymal stem cells (MSC) in vitro differentiating into functional isletlike cells and to test the diabetes therapeutic potency of Islet-like cells. METHODS: Rat MSCs were isolated from Wistar rats and cultured. Passaged MSCs were induced to differentiate into islet-like cells under following conditions: pre-induction with L-DMEM including 10 mmol/L nicotinamide+l mmol/L β-mercaptoethanol+200 mL/L fetal calf serum (FSC) for 24 h, followed by induction with serum free H-DMEM solution including 10 mmol/L nicotinamide+1 mmol/L,β-mercaptoethanol for 10 h. Differentiated cells were observed under inverse microscopy, insulin and nestin expressed in differentiated cells were detected with immunocytochemistry. Insulin excreted from differentiated cells was tested with radioimmunoassay. Rat diabetic models were made to test in vivo function of differentiated MSCs. RESULTS: Typical islet-like clustered cells were observed. Insulin mRNA and protein expressions were positive in differentiated cells, and nestin could be detected in predifferentiated cells. Insulin excreted from differentiated MSCs (446.93±102.28 IU/L) was much higher than that from pre-differentiated MSCs (2.45+0.81 IU/L (P<0.01). Injected differentiated MSCs cells could down-regulate glucose level in diabetic rats. CONCLUSION: Islet-like functional cells can be differentiated from marrow mesenchymal stem cells, which may be a new procedure for clinical diabetes stem -cell therapy, these cells can control blood glucose level in diabetic rats. MSCs may play an important role in diabetes therapy by islet differentiation and transplantation.展开更多
AIM: To investigate the clinical features, diagnosis,treatment and prognosis of multiple primary colorectal carcinomas (MPCC). METHODS: A retrospective analysis of 37 patients with MPCC from 1974 to 1998 was carried o...AIM: To investigate the clinical features, diagnosis,treatment and prognosis of multiple primary colorectal carcinomas (MPCC). METHODS: A retrospective analysis of 37 patients with MPCC from 1974 to 1998 was carried out.RESULTS: The incidence of MPCC was 2.74%(37/1 348) in patients with primary colorectal carcinomas, 15 cases of them were patients with synchronous carcinomas (SC) and 22 cases were diagnosed as metachronous carcinomas (MC). Most tumors were located in the right colon and rectum. Fifty-five percent (12/22) of MC were diagnosed within 3 years after tumor resection and 41%(9/22) of MC occurred after 8 years. Radical resections were performed in all patients except for 1 case. The 5-year survival rate of SC was 72.7%(8/11) and that of MC after the first cancer and second cancer was 71.4%(15/21) and 38.9%(7/18), respectively. CONCLUSION: The results indicate the importance of complete preoperative examination, careful intraoperative exploration and periodic postoperative surveillance. Early diagnosis and radical resection can increase survival rate of MPCC.展开更多
AIM: Signal transducers and activators of transcription (STATs) are a family of transcription factors activated in response to cytokines and growth factors. Constitutive activation of Stat3 has been observed in a grow...AIM: Signal transducers and activators of transcription (STATs) are a family of transcription factors activated in response to cytokines and growth factors. Constitutive activation of Stat3 has been observed in a growing number of tumor-derived cell lines, as well as tumor specimens from human cancers. The purpose of this study was to investigate the expression of p-Stat3, activated form of Stat3, and its downstream mediators including cyclin D1 and Bcl-XL in colorectal carcinoma (CRC), and to explore the possible mechanism of Stat3 signaling pathway in the tumorigenesis of colorectal carcinoma. METHODS: Tissue samples from 45 patients of primary colorectal carcinoma were selected for studying Stat3 signaling pathway protein expression. Western blot analysis was used to measure the expression of p-Stat3, cyclin D1, and Bcl-xu proteins in colorectal carcinomas. Furthermore, the expression patterns of these proteins were analyzed for their distribution at the cellular level by immunohistochemical staining of the tissues. RESULTS: Protein levels of p-Stat3, cyclin D1, and Bcl-XL were increased in colorectal carcinomas compared with adjacent normal mucosae (P<0.05). Elevated levels of pStat3 were correlated with the nodal metastasis and the stage (P<0.05). Overexpression of cyclin D1 was associated with the nodal metastasis (P<0.05). There was also a significant correlation between the expressions of p-Stat3 and cyclin D1 (r=0.382, P<0.05). CONCLUSION: Constitutive activation of Stat3 may play an important role in the tumorigenesis of colorectal carcinoma, and the detailed mechanism of Stat3 signaling pathway in CRC deserves further investigation.展开更多
AIM: To investigate the expression of cysteine-rich61 (Cyr61),connective tissue growth factor (CTGF) and nephroblastomaoverexpressecl gene (Nov) in hepatocellular carcinoma (HCC),and to evaluate the relationship betwe...AIM: To investigate the expression of cysteine-rich61 (Cyr61),connective tissue growth factor (CTGF) and nephroblastomaoverexpressecl gene (Nov) in hepatocellular carcinoma (HCC),and to evaluate the relationship between Cyr61, CTGF and Nov genes expression with invasion and metastasis of HCC.METHODS: Thirty-one HCC specimens were divided into small hepatocellular carcinoma (SHCC), nodular hepatocellular carcinoma (NHCC), solitary large hepatocellular carcinoma (SLHCC) according to their diameter and number of nodes. Reverse transcription polymerse chain reaction (RT-PCR) was used to detect the mRNA expression levels of Cyr61, CTGF and Nov genes in 31 resected specimens of hepatocellular carcinoma and para-cancerous normal liver tissues semi-quantitatively and the relation between their expression levels and clinical pathological parameters were compared.RESULTS: The expressions of Cyr61 and CTGF mRNA in carcinoma tissues were significantly higher than those in para-cancerous normal liver tissues (P<0.01). The expressions of Cyr61 and CTGF mRNA in HCC with venous invasion were higher than those in HCC without venous invasion. CTGF expression in HCC Edmondson's grade Ⅲ-IV was significantly higher than that in HCC Edmondson's grade I-II (P = 0.022). There was no obvious correlation between Nov mRNA and clinical-pathological features.Compared to NHCC, SLHCC had better cell differentiation,easier capsule formation, less microscopic venous invasion,milder liver cirrhosis. The expressions of Cyr61 and CTGF mRNA in NHCC were significantly higher than those in SLHCC and SHCC.CONCLUSION: Cyr61 and CTGF genes may play an important role in hepatocellular carcinogenesis and correlate with recurrence and metastasis of hepatocellular carcinoma.SLHCC has better biological behaviors than NHCC.展开更多
AIM: To investigate the effect of norcantharidin on proliferation and invasion of human gallbladder carcinoma GBC-SD cells in vitro and its anticancer mechanism. METHODS: Human gallbladder carcinoma GBC-SD cells were ...AIM: To investigate the effect of norcantharidin on proliferation and invasion of human gallbladder carcinoma GBC-SD cells in vitro and its anticancer mechanism. METHODS: Human gallbladder carcinoma GBC-SD cells were cultured by cell culture technique. The growth and the invasiveness of GBC-SD cells in vitro were evaluated by the tetrazolium-based colorimetric assay and by the Matrigel experiment and the crossing-river test. Expression of PCNA, Ki-67, MMP2 and TIMP2 proteins of GBC-SD cells was determined by streptavidin-biotin complex method. RESULTS: In vitro norcantharidin inhibited the growth and proliferation of GBC-SD cells in a dose- and time-dependent manner, with the IC50 value of 56.18 μ/mL at 48 h. Norcantharidin began to inhibit the invasion of GBC-SD cells at the concentration of 5 μg/mL, and the invasive action of GBC-SD cells was inhibited completely and their crossing-river time was prolonged significantly at 40 μg/mL. After treatment with norcantharidin, the expression of PCNA, Ki-67, and MMP2 was significantly decreased. With the increase in TIMP2 expression, the MMP2 to TIMP2 ratio was decreased significantly (P<0.05). CONCLUSION: Norcantharidin inhibits the proliferation and growth of human gallbladder carcinoma cells in vitro at relatively low concentrations by inhibiting PCNA and Ki-67 expression. Its anti-invasive activity may be the result of decrease in MMP2 to TIMP2 ratio and reduced cell motility.展开更多
AIM: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominantly- inherited cancer-susceptibility syndrome that confers an increased risk for colorectal cancer and a variety of other tumors at a young...AIM: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominantly- inherited cancer-susceptibility syndrome that confers an increased risk for colorectal cancer and a variety of other tumors at a young age. It has been associated with germline mutations in five mismatch repair (MMR) genes (hMSH2, hMLH1, hPMS1, hPMS2, and hMSH6/GTBP). The great majority of germline mutations were found in hMSH2 and hMLH1. The purpose of this study was to analyze the clinical features of Chinese HNPCC patients and to screen hMSH2 and hMLH1 gene mutations.METHODS: Twenty-eight independent Chinese families were collected, of which 15 met Amsterdam criteria I and 13 met the Japanese clinical diagnosis criteria. The data were recorded including sex, site of colorectal cancer (CRC),age of diagnosis, history of synchronous and/or metachronous CRC, instance of extracolonic cancers, and histopathology of tumors. Peripheral blood samples were collected from all pedigrees after formal written consents were signed. PCR and denaturing high-performance liquid chromatography (DHPLC) were used to screen the coding regions of hMSH2 and hMLH1 genes. The samples showing abnormal DHPLC profiles were sequenced by a 377 DNA sequencer.RESULTS: One hundred and seventy malignant neoplasms were found in one hundred and twenty-six patients (multiple cancer in twenty-three), including one hundred and twentyseven CRCs, fifteen gastric, seven endometrial, and five esophageal cancers. Seventy-seven point eight percent of the patients had CRCs, sharing the features of early occurrence (average age of onset, 45.9 years) and of the right-sided predominance reported in the literature. In Chinese HNPCC patients, gastric cancer occurred more frequently, accounting for 11.9% of all cancers patients and ranking second in the spectrum of HNPCC predisposing cancers. Synchronous CRCs occurred less frequently, only accounting for 3.1% of the total CRCs. Twenty percent of the colorectal patients had metachronous CRCs within 10 years after operation. Eight hMSH2 or hMLH1 gene sequence variations were found in twelve families, including the first Mongolian kindred with a hMSH2 gene mutation.CONCLUSION: HNPCC is characterized by an early-age onset, proximal predominance of CRC, multiple metachronous CRCs, and an excess of extra-colonic cancers. Frequent gastric cancer occurrence and less synchronous CRCs are the remarkable features in Chinese HNPCC patients. DHPLC is a powerful tool in hMSH2 and hMLH1 gene mutation screening, hMLH1 gene mutations, especially of the first nine exons, have been found more common than hMSH2 gene mutations in Chinese patients. Three of seven mutations have been found to be novel, and the germline G204X nonsense mutation in the third exon of hMSH2 has become the first MMR gene mutation found in Chinese Mongolian people.展开更多
AIM: To study the interactive relationship of gallbladder motor function, plasma cholecystokinin (CCK) and cholecystokinin A receptor (CCK-R) of gallbladder in patients with cholesterol stone disease.METHODS: Gallblad...AIM: To study the interactive relationship of gallbladder motor function, plasma cholecystokinin (CCK) and cholecystokinin A receptor (CCK-R) of gallbladder in patients with cholesterol stone disease.METHODS: Gallbladder motility was studied by ultrasonography in 33 patients with gallbladder stone and 10 health subjects as controls. Plasma CCK concentration was measured by radioimmunoassay in fasting status (CCK-f) and in 30 min after lipid test meal (CCK-30).Radioligand method was employed to analyze the amount and activity of CCK-R from 33 gallstone patients having cholecystectomy and 8 persons without gallstone died of severe trauma as controls.RESULTS: The percentage of cholesterol in the gallstone composition was more than 70%. The cholesterol stone type was indicated for the patients with gallbladder stone in this study. Based on the criterion of gallbladder residual fraction of the control group, 33 gallstone patients were divided into two subgroups, contractor group (14 cases)and non-contractor group (19 cases), The concentration of CCK-30 was significantly higher in non-contractor group than that in both contractor group and control group (55.86±3.86 pmol/l vs 37.85±0.88 pmol/l and 37.95±0.74 pmol/L, P<0.01), but there was no difference between contractor group and control group. Meanwhile no significant difference of the concentration of CCK-f could be observed among three groups. The amount of CCK-R was lower in non-contractor group than those in both control group and contractor group (10.27±0.94 fmol/mg vs24.59±2.39 fmol/mg and 22.66±0.55 fmol/mg, P<0.01).The activity of CCK-R shown as KD in non-contractor group decreased compared to that in control group and contractor group. Only was the activity of CCK-R lower in contractor group than that in control group. The ejection fraction correlated closely with the amount of CCK-R (r = 0.9683,P<0.01), and the concentration of CCK-30 correlated negatively with the amount of CCK-R closely (r = -0.9627,P<0.01).CONCLUSION: The distinctive interactive relationship of gallbladder emptying, plasma CCK and CCK-R in gallbladder from this study suggested that the defect of CCK-R may be a key point leading to the impairment of gallbladder motor function and the pathogenesis of cholesterol gallstoneformation may differ in two subgroups of gallstone patient,gallbladder non-contractor group or contractor group.展开更多
AIM:To study clinical characteristics and management of patients with early severe acute pancreatitis (ESAP).METHODS: Data of 297 patients with severe acute pancreatitis (SAP) admitted to our hospital within 72h after...AIM:To study clinical characteristics and management of patients with early severe acute pancreatitis (ESAP).METHODS: Data of 297 patients with severe acute pancreatitis (SAP) admitted to our hospital within 72h after onset of symptoms from January 1991 to June 2003 were reviewed for the occurrence and development of early severe acute pancreatitis (ESAP).ESAP was defined as presence of organ dysfunction within 72 h after onset of symptoms.Sixtynine patients had ESAP, 228 patients without organ dysfunction within 72 h after onset of symptoms had SAR The clinical characteristics,incidence of organ dysfunction during hospitalization and prognosis between ESAP and SAP were compared.RESULTS.Impairment degree of pancreas (Balthazar CT class) in ESAP was more serious than that in SAP (5.31±0.68vs 3.68±0.29, P<0.01). ESAP had a higher mortality than SAP (43.4% vs 2.6%, P<0.01), and a higher incidence ofhypoxemia (85.5% vs 25%, P<0.01), pancreas infection (15.9% vs 7.5%, P<0.05),abdominal compartment syndrome (ACS) (78.3% vs 23.2%,P<0.01) and multiple organ dysfunction syndrome (MODS)(78.3% vs 10.1%,P<0.01).In multiple logistic regression analysis,the main predisposing factors to ESAP were higher APACHE II score, Balthazar CT class,MODS and hypoxemia.CONCLUSION:ESAP is characterised by MODS, severe pathological changes of pancreas,early hypoxemia and abdominal compartment syndrome. Given the poor prognosis of ESAP,these patients should be treated in specialized intensive care units with special measures such as close supervision, fluid resuscitation, improvement of hypoxemia,reduction of pancreatic secretion, elimination of inflammatory mediators,prevention and treatment of pancreatic infections.展开更多
AIM: To study the correlation between expression of MMP-2, TIMP-2 protein and the ratio of MMP-2/TIMP-2 and clinicalpathological parameters of patients with gallbladder carcinoma.METHODS: Carcinomas (n=45) and polypoi...AIM: To study the correlation between expression of MMP-2, TIMP-2 protein and the ratio of MMP-2/TIMP-2 and clinicalpathological parameters of patients with gallbladder carcinoma.METHODS: Carcinomas (n=45) and polypoid lesions (n=15) of the gallbladder were studied for the expression of MMP-2 and TIMP-2 protein by immunohistochemical avidin-biotin-complex method and image analysis. Clinicalpathological data of patients with gallbladder carcinoma such as histological type, grade of differentiation, level of infiltration, liver invasion and lymph node involvement, etc, were recorded.RESULTS: There was significant difference between the average level (1.123±0.108 VS 1.030±0.054, P=0.002) of MMP-2, the ratio (1.050±0.013 VS0.937±0.078, P=0.003) of MMP-2/TIMP-2 in gallbladder carcinomas and in polypoid lesions of the gallbladder. Significant difference was found between the expression of MMP-2 in early stage and advanced tumors, but there was no correlation between MMP-2 protein expression and histological type, differentiation degree, infiltration level, lymph node involvement or liver invasion. Although no difference was observed between TIMP-2 expression and histological type or differentiation degree, signific ant difference was found between TIMP-2 expression and different Nevin stage, infiltration level, local lymph node involvement or liver invasion (1.168±0.067 VS1.048±0.075, 1.170±0.062 vs 1.039±0.06g, 1.039±0.076 VS1.147±0.083, 1.048±0.074 vs 1.103±0.095, P<0.05). MMP-2/TIMP-2 ratio did not correlate with histological type, grade of differentiation and liver invasion, but significant differences were found between MMP-2/TIMP-2 ratio and different Nevin stage, infiltration level and lymph node involvement in patients with carcinoma of gallbladder.CONCLUSION: TIMP-2 and MMP-2/TIMP-2 ratio could reflect more accurately biological characteristic of gallbladder carcinoma and MMP-2/TIMP-2 ratio might be a new significant marker in early diagnosis, in the judgment of invasion or metastasis and the estimate of prognosis in patients with gallbladder carcinomas.展开更多
AIM: Heat shock protein (HSP)70 is over-expressed in human gastric cancer and plays an important role in the progression of this cancer. We investigated the effects of antisense HSP70 oligomer on human gastric cancer ...AIM: Heat shock protein (HSP)70 is over-expressed in human gastric cancer and plays an important role in the progression of this cancer. We investigated the effects of antisense HSP70 oligomer on human gastric cancer cell line SGC-7901, and its potential role in gene therapy for this cancer.METHODS: Human gastric cancer cell line SGC-7901 was treated in vitro with various concentrations of antisense HSP70 oligonucleotides at different intervals. Growth inhibition was determined as percentage by trypan blue dye exclusion test. Extracted DNA was electrophoresed on agarose gel, and distribution of cell cycle and kinetics of apoptosis induction were analyzed by propidium iodide DNA incorporation using flow cytometry, which was also used to detect the effects of antisense oligomer pretreatment on the subsequent apoptosis induced by heat shock in SGC-7901 cells. Proteins were extracted for simultaneous measurement of HSP70 expression level by SDS-PAGE Western blotting.RESULTS: The number of viable cells decreased in a doseand time-dependent manner, and ladder-like patterns of DNA fragments were observed in SGC-7901 cells treated with antisense HSP70 oligomers at a concentration of 10 μmol/L for 48 h or 8 μmol/L for 72 h, which were consistent with inter-nucleosomal DNA fragmentation. Flow cytometric analysis showed a dose- and time-dependent increase in apoptotic rate by HSP70 antisense oligomers. This response was accompanied with a decrease in the percentage of cells in the G1 and S phases of the cell cycle, suggesting inhibition of cell proliferation. In addition, flow cytometry also showed that pretreatment of SGC-7901 cells with HSP70 antisense oligomers enhanced the subsequent apoptosis induced by heat shock treatment. Western blotting demonstrated that HSP70 antisense oligomers inhibited HSP70 expression, which preceded apoptosis, and HSP70 was undetectable at the concentration of 10 μmol/L for 48 h or 8 μmol/L for 72 h.CONCLUSION: Antisense HSP70 oligomers can abrogate HSP70 expression in SGC-7901 cells, which may in turn induce apoptosis and inhibit cell proliferation, conversely suggesting that HSP70 is required for the proliferation and survival of human gastric cancer cells under normal conditions.展开更多
AIM:To study different approaches to caudate Iobectomy with'curettage and aspiration'technique using Peng's multifunctional operative dissector(PMOD).The surgical procedure of isolated complete caudate Iob...AIM:To study different approaches to caudate Iobectomy with'curettage and aspiration'technique using Peng's multifunctional operative dissector(PMOD).The surgical procedure of isolated complete caudate Iobectomy was specially discussed. METHODS:In 76 cases of various types of caudate Iobectomy,three approaches were used including left side approach,right side approach,and anterior approach. Among the 76 cases,isolated complete caudate Iobectomy was carried out in 6 cases with transhepatic anterior approach.The surgical procedure consisted of mobilization of the total liver,ligation and separation of the short hepatic veins,splitting the liver parenchyma through the Cantlie's plane,ligation and division of the caudate portal triads from the hilum,dissection of the root of major hepatic veins, detachment of the caudate lobe from liver parenchyma. RESULTS:The mean operative time was 285±51 min, the mean blood loss was 1 600 ml.No severe complications were observed.Among the 6 cases receiving isolated complete caudate lobectomy with transhepatic anterior approach,one case died 17 months after operation due to disease recurrence and liver failure,the other 5 cases have been alive without recurrence,with one longest survival of 49 months. CONCLUSION:The choice of approach is essential to the success of caudate Iobectomy.As PMOD and'curettage and aspiration'technique can delineate intrahepatic or extrahepatic vessels clearly,caudate lobe resection has become safer,easier and faster.展开更多
AIM: To investigate the clinical characteristics and prognostic factors of a consecutive series of patients with severe acute pancreatitis (SAP). METHODS: Clinical data of SAP patients admitted to our hospital from Ja...AIM: To investigate the clinical characteristics and prognostic factors of a consecutive series of patients with severe acute pancreatitis (SAP). METHODS: Clinical data of SAP patients admitted to our hospital from January 2003 to January 2004 were retrospectively reviewed. Collected data included the age, gender, etiology, length of hospitalization, APACHE Ⅱ score at admission, local and organ/systemic complications of the patients. RESULTS: Of the 268 acute pancreatitis patients, 94 developed SAP. The mean age of SAP patients was 52 years, the commonest etiology was cholelithiasis (45.7%), the mean length of hospitalization was 70 d, the mean score of APACHE Ⅱ was 7.7. Fifty-four percent of the patients developed necrosis, 25% abscess, 58% organ/systemic failure. A total of 23.4% (22/94) of the SAP patients died. Respiratory failure was the most common organ dysfunction (90.9%) in deceased SAP patients, followed by cardiovascular failure (86.4%), renal failure (50.0%). In the SAP patients, 90.9% (20/22) developed multiple organ/systemic failures. There were significant differences in age, length of hospitalization, APACHE Ⅱ score and incidences of respiratory failure, renal failure, cardiovascular failure and hematological failure between deceased SAP patients and survived SAP patients. By multivariate logistic regression analysis, independent prognostic factors for mortality were respiratory failure, cardiovascular failure and renal failure. CONCLUSION: SAP patients are characterized by advanced age, high APACHE Ⅱ score, organ failure and their death is mainly due to multiple organ/systemic failures. In patients with SAP, respiratory, cardiovascular and renal failures can predict the fatal outcome and more attention should be paid to their clinical evaluation.展开更多
AIM:To compare the therapeutic effect of transcatheter arterial chemoembolization (TACE), laparoscopic radiofrequency ablation (LRFA), and conservative treatment for the therapy of decompensated liver cirrhosis patie...AIM:To compare the therapeutic effect of transcatheter arterial chemoembolization (TACE), laparoscopic radiofrequency ablation (LRFA), and conservative treatment for the therapy of decompensated liver cirrhosis patients with hepatocellular carcinomas (HCC).METHODS:Between October 2000 and July 2003, one hundred patients with histologically proven primary HCC and clinical decompensated liver cirrhosis (Child classification B or C) were included in this study. Forty patients received LRFA (LRFA group), twenty received TACE (TACE group),and forty received conservative treatment (control group).We compared the survival, recurrence, and complication rates in these three groups, making adjustment using the tumor metastastic node staging system.RESULTS:The major complication rate in the TACE group (9/20) was significantly higher than that in the LRFA group (7/40). For patients with TMN stage Ⅱ HCC, the survival rate of the LRFA group was better than that of the TACE and control groups (P=0.003) but the recurrence rates befween the LRFA and TACE groups did not differ.CONCLUSION: The LRFA group of patients had betterclinical outcomes in terms of survival and complication rates in comparison with the TACE group or conservative treatment in patients with decompensated liver cirrhosis, especially in TMN patients with stage Ⅱ HCC. LRFA is thus an appropriate alternative treatment for poor liver function among patientswith HCC.展开更多
AIM: Cancer gene therapy has received more and moreattentions in the recent decade. Various systems of genetherapy for cancer have been developed. One of the mostpromising choices is the suicide gene. The product ofth...AIM: Cancer gene therapy has received more and moreattentions in the recent decade. Various systems of genetherapy for cancer have been developed. One of the mostpromising choices is the suicide gene. The product ofthymidine kinase (TK) gene can convert ganciclovir (GCV)to phosphorylated GCV, which inhibits the synthesis of cellDNA, and then induces the cells to death. Cytolines play animportant role in anti-tumor immunity. This experiment wasdesigned to combine theTK gene and mIL-2/mGM-CSFgenes to treat gastric cancer, and was expected to producea marked anti-tumor effect.METHODS: TK gene was constructed into the retroviralvector pLxSN, and the mIL-2 and mGM-CSF genes wereinserted into the eukaryotic expressing vector pIRES. Thegastric cancer cells were transfected by retroviral serum thatwas harvested from the package cells. In vitro study, thetransfected gastric cancer cells were maintained in the GCV-contained medium, to assay the cell killing effect andbystander effect. In vivo experiment, retroviral serum andcytokines plasmid were transfected into tumor-bearing mice,to observe the changes of tumor volumes and survival ofthe mice.RESULTS: In vitro experiment, 20 % TK gene transducedcells could cause 70-80 % of total cells to death. In vivoresults showed that there was no treatment effect in controlgroup and TK/GCV could inhibit the tumor growth. Thestrongest anti-tumor effect was shown in TK+mIL-2+mGM-CSF group. The pathologic examination showed necrosis ofthe cancer in the treated groups.CONCLUSION: TK/GCV can kill tumor cells and inhibit thetumor growth in vivo IL-2 and GM-CSF strongly enhancethe anti-tumor effect. Through the retrovirus and liposomemethods, the suicide gene and cytokine genes are allexpressed in the tissues.展开更多
AIM: To investigate the relationship between gallbladder stone disease (GSD) and single nucleotide polymorphisms of cholesterol 7α-hydroxylase (CYP7A) gene promoter,apolipoprotein (APO) B gene exon 26, APOEgene exon ...AIM: To investigate the relationship between gallbladder stone disease (GSD) and single nucleotide polymorphisms of cholesterol 7α-hydroxylase (CYP7A) gene promoter,apolipoprotein (APO) B gene exon 26, APOEgene exon 4 or microsatellite polymorphism of low density lipoprotein receptor (LDLR) gene exon 18.METHODS: Genotypes of CYP7A, APOB, APOE and LDLR genes were determined in 105 patients with GSD diagnosed by B-mode ultrasonography and 274 control subjects.Serum lipids were analyzed with HITACHI 7060 automaic biochemical analyzer.RESULTS: Body mass index (BMI) was significantly higher in patients with GSD (24.47±3.09) than in controls (23.50±2.16).Plasma total cholesterol was lower in patients with GSD (4.66±0.92 mmol/L) than in controls (4.91±0.96 mmol/L),P<0.01 after adjusted for age, sex and BMI. The significantly higher frequency of A allele of CYP7A gene polymorphism and X+ allele of APOBgene polymorphism was seen in GSD patients. Percentages of A allele in patients and controls were 62.86% and 54.38% (P <0.05) and those of X+ allele 8.57% and 4.01% (P<0.01). Subjects with A allele had significantly lower plasma total cholesterol and LDL cholesterol than subjects with CC homozygote. In a multiple variable logistic regression model, the BMI (OR=1.13, 95% CI: 1.05-1.22), A allele (OR=1.48, 95% CI: 1.05-2.09) and X+ allele (OR=2.28, 95% CI: 1.14-4.59) were positively associated with GSD (P <0.05). Plasma total cholesterol (OR=0.69, 95% CI: 0.64-0.74) was negatively related to GSD (P<0.05).CONCLUSION: With an association analysis, it was determined that A allele of CYP7A gene and X+ allele of APOB gene might be considered as risk genes for GSD. These alleles are related with differences of serum lipids among subjects.Multiple-variable logistic regression model analysis showed that besides BMI, GSD was affected by polygenetic factors.But the mechanism for these two alleles responsible for GSD requires further investigations.展开更多
基金Supported by the National Natural Science Foundation of China,No.30170911
文摘AIM: To explore the possibility of marrow mesenchymal stem cells (MSC) in vitro differentiating into functional isletlike cells and to test the diabetes therapeutic potency of Islet-like cells. METHODS: Rat MSCs were isolated from Wistar rats and cultured. Passaged MSCs were induced to differentiate into islet-like cells under following conditions: pre-induction with L-DMEM including 10 mmol/L nicotinamide+l mmol/L β-mercaptoethanol+200 mL/L fetal calf serum (FSC) for 24 h, followed by induction with serum free H-DMEM solution including 10 mmol/L nicotinamide+1 mmol/L,β-mercaptoethanol for 10 h. Differentiated cells were observed under inverse microscopy, insulin and nestin expressed in differentiated cells were detected with immunocytochemistry. Insulin excreted from differentiated cells was tested with radioimmunoassay. Rat diabetic models were made to test in vivo function of differentiated MSCs. RESULTS: Typical islet-like clustered cells were observed. Insulin mRNA and protein expressions were positive in differentiated cells, and nestin could be detected in predifferentiated cells. Insulin excreted from differentiated MSCs (446.93±102.28 IU/L) was much higher than that from pre-differentiated MSCs (2.45+0.81 IU/L (P<0.01). Injected differentiated MSCs cells could down-regulate glucose level in diabetic rats. CONCLUSION: Islet-like functional cells can be differentiated from marrow mesenchymal stem cells, which may be a new procedure for clinical diabetes stem -cell therapy, these cells can control blood glucose level in diabetic rats. MSCs may play an important role in diabetes therapy by islet differentiation and transplantation.
文摘AIM: To investigate the clinical features, diagnosis,treatment and prognosis of multiple primary colorectal carcinomas (MPCC). METHODS: A retrospective analysis of 37 patients with MPCC from 1974 to 1998 was carried out.RESULTS: The incidence of MPCC was 2.74%(37/1 348) in patients with primary colorectal carcinomas, 15 cases of them were patients with synchronous carcinomas (SC) and 22 cases were diagnosed as metachronous carcinomas (MC). Most tumors were located in the right colon and rectum. Fifty-five percent (12/22) of MC were diagnosed within 3 years after tumor resection and 41%(9/22) of MC occurred after 8 years. Radical resections were performed in all patients except for 1 case. The 5-year survival rate of SC was 72.7%(8/11) and that of MC after the first cancer and second cancer was 71.4%(15/21) and 38.9%(7/18), respectively. CONCLUSION: The results indicate the importance of complete preoperative examination, careful intraoperative exploration and periodic postoperative surveillance. Early diagnosis and radical resection can increase survival rate of MPCC.
基金Supported by the National Natural Science Foundation of China,No.30271269
文摘AIM: Signal transducers and activators of transcription (STATs) are a family of transcription factors activated in response to cytokines and growth factors. Constitutive activation of Stat3 has been observed in a growing number of tumor-derived cell lines, as well as tumor specimens from human cancers. The purpose of this study was to investigate the expression of p-Stat3, activated form of Stat3, and its downstream mediators including cyclin D1 and Bcl-XL in colorectal carcinoma (CRC), and to explore the possible mechanism of Stat3 signaling pathway in the tumorigenesis of colorectal carcinoma. METHODS: Tissue samples from 45 patients of primary colorectal carcinoma were selected for studying Stat3 signaling pathway protein expression. Western blot analysis was used to measure the expression of p-Stat3, cyclin D1, and Bcl-xu proteins in colorectal carcinomas. Furthermore, the expression patterns of these proteins were analyzed for their distribution at the cellular level by immunohistochemical staining of the tissues. RESULTS: Protein levels of p-Stat3, cyclin D1, and Bcl-XL were increased in colorectal carcinomas compared with adjacent normal mucosae (P<0.05). Elevated levels of pStat3 were correlated with the nodal metastasis and the stage (P<0.05). Overexpression of cyclin D1 was associated with the nodal metastasis (P<0.05). There was also a significant correlation between the expressions of p-Stat3 and cyclin D1 (r=0.382, P<0.05). CONCLUSION: Constitutive activation of Stat3 may play an important role in the tumorigenesis of colorectal carcinoma, and the detailed mechanism of Stat3 signaling pathway in CRC deserves further investigation.
基金Supported by the National Key Technologies R and D Program,No.2001BA703BO4 and the National Natural Science Foundation of China,No.30371595
文摘AIM: To investigate the expression of cysteine-rich61 (Cyr61),connective tissue growth factor (CTGF) and nephroblastomaoverexpressecl gene (Nov) in hepatocellular carcinoma (HCC),and to evaluate the relationship between Cyr61, CTGF and Nov genes expression with invasion and metastasis of HCC.METHODS: Thirty-one HCC specimens were divided into small hepatocellular carcinoma (SHCC), nodular hepatocellular carcinoma (NHCC), solitary large hepatocellular carcinoma (SLHCC) according to their diameter and number of nodes. Reverse transcription polymerse chain reaction (RT-PCR) was used to detect the mRNA expression levels of Cyr61, CTGF and Nov genes in 31 resected specimens of hepatocellular carcinoma and para-cancerous normal liver tissues semi-quantitatively and the relation between their expression levels and clinical pathological parameters were compared.RESULTS: The expressions of Cyr61 and CTGF mRNA in carcinoma tissues were significantly higher than those in para-cancerous normal liver tissues (P<0.01). The expressions of Cyr61 and CTGF mRNA in HCC with venous invasion were higher than those in HCC without venous invasion. CTGF expression in HCC Edmondson's grade Ⅲ-IV was significantly higher than that in HCC Edmondson's grade I-II (P = 0.022). There was no obvious correlation between Nov mRNA and clinical-pathological features.Compared to NHCC, SLHCC had better cell differentiation,easier capsule formation, less microscopic venous invasion,milder liver cirrhosis. The expressions of Cyr61 and CTGF mRNA in NHCC were significantly higher than those in SLHCC and SHCC.CONCLUSION: Cyr61 and CTGF genes may play an important role in hepatocellular carcinogenesis and correlate with recurrence and metastasis of hepatocellular carcinoma.SLHCC has better biological behaviors than NHCC.
基金Supported by the Scientific Foundation of Tongji University, China, No. KPB027
文摘AIM: To investigate the effect of norcantharidin on proliferation and invasion of human gallbladder carcinoma GBC-SD cells in vitro and its anticancer mechanism. METHODS: Human gallbladder carcinoma GBC-SD cells were cultured by cell culture technique. The growth and the invasiveness of GBC-SD cells in vitro were evaluated by the tetrazolium-based colorimetric assay and by the Matrigel experiment and the crossing-river test. Expression of PCNA, Ki-67, MMP2 and TIMP2 proteins of GBC-SD cells was determined by streptavidin-biotin complex method. RESULTS: In vitro norcantharidin inhibited the growth and proliferation of GBC-SD cells in a dose- and time-dependent manner, with the IC50 value of 56.18 μ/mL at 48 h. Norcantharidin began to inhibit the invasion of GBC-SD cells at the concentration of 5 μg/mL, and the invasive action of GBC-SD cells was inhibited completely and their crossing-river time was prolonged significantly at 40 μg/mL. After treatment with norcantharidin, the expression of PCNA, Ki-67, and MMP2 was significantly decreased. With the increase in TIMP2 expression, the MMP2 to TIMP2 ratio was decreased significantly (P<0.05). CONCLUSION: Norcantharidin inhibits the proliferation and growth of human gallbladder carcinoma cells in vitro at relatively low concentrations by inhibiting PCNA and Ki-67 expression. Its anti-invasive activity may be the result of decrease in MMP2 to TIMP2 ratio and reduced cell motility.
基金Supported by National Natural Science Foundation of China,No.39970817,and Fund From Ministry of Education of China(the FormerNational Education Committee)
文摘AIM: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominantly- inherited cancer-susceptibility syndrome that confers an increased risk for colorectal cancer and a variety of other tumors at a young age. It has been associated with germline mutations in five mismatch repair (MMR) genes (hMSH2, hMLH1, hPMS1, hPMS2, and hMSH6/GTBP). The great majority of germline mutations were found in hMSH2 and hMLH1. The purpose of this study was to analyze the clinical features of Chinese HNPCC patients and to screen hMSH2 and hMLH1 gene mutations.METHODS: Twenty-eight independent Chinese families were collected, of which 15 met Amsterdam criteria I and 13 met the Japanese clinical diagnosis criteria. The data were recorded including sex, site of colorectal cancer (CRC),age of diagnosis, history of synchronous and/or metachronous CRC, instance of extracolonic cancers, and histopathology of tumors. Peripheral blood samples were collected from all pedigrees after formal written consents were signed. PCR and denaturing high-performance liquid chromatography (DHPLC) were used to screen the coding regions of hMSH2 and hMLH1 genes. The samples showing abnormal DHPLC profiles were sequenced by a 377 DNA sequencer.RESULTS: One hundred and seventy malignant neoplasms were found in one hundred and twenty-six patients (multiple cancer in twenty-three), including one hundred and twentyseven CRCs, fifteen gastric, seven endometrial, and five esophageal cancers. Seventy-seven point eight percent of the patients had CRCs, sharing the features of early occurrence (average age of onset, 45.9 years) and of the right-sided predominance reported in the literature. In Chinese HNPCC patients, gastric cancer occurred more frequently, accounting for 11.9% of all cancers patients and ranking second in the spectrum of HNPCC predisposing cancers. Synchronous CRCs occurred less frequently, only accounting for 3.1% of the total CRCs. Twenty percent of the colorectal patients had metachronous CRCs within 10 years after operation. Eight hMSH2 or hMLH1 gene sequence variations were found in twelve families, including the first Mongolian kindred with a hMSH2 gene mutation.CONCLUSION: HNPCC is characterized by an early-age onset, proximal predominance of CRC, multiple metachronous CRCs, and an excess of extra-colonic cancers. Frequent gastric cancer occurrence and less synchronous CRCs are the remarkable features in Chinese HNPCC patients. DHPLC is a powerful tool in hMSH2 and hMLH1 gene mutation screening, hMLH1 gene mutations, especially of the first nine exons, have been found more common than hMSH2 gene mutations in Chinese patients. Three of seven mutations have been found to be novel, and the germline G204X nonsense mutation in the third exon of hMSH2 has become the first MMR gene mutation found in Chinese Mongolian people.
基金Supported by the Science Development Foundation of Shanghai,No. 95411902
文摘AIM: To study the interactive relationship of gallbladder motor function, plasma cholecystokinin (CCK) and cholecystokinin A receptor (CCK-R) of gallbladder in patients with cholesterol stone disease.METHODS: Gallbladder motility was studied by ultrasonography in 33 patients with gallbladder stone and 10 health subjects as controls. Plasma CCK concentration was measured by radioimmunoassay in fasting status (CCK-f) and in 30 min after lipid test meal (CCK-30).Radioligand method was employed to analyze the amount and activity of CCK-R from 33 gallstone patients having cholecystectomy and 8 persons without gallstone died of severe trauma as controls.RESULTS: The percentage of cholesterol in the gallstone composition was more than 70%. The cholesterol stone type was indicated for the patients with gallbladder stone in this study. Based on the criterion of gallbladder residual fraction of the control group, 33 gallstone patients were divided into two subgroups, contractor group (14 cases)and non-contractor group (19 cases), The concentration of CCK-30 was significantly higher in non-contractor group than that in both contractor group and control group (55.86±3.86 pmol/l vs 37.85±0.88 pmol/l and 37.95±0.74 pmol/L, P<0.01), but there was no difference between contractor group and control group. Meanwhile no significant difference of the concentration of CCK-f could be observed among three groups. The amount of CCK-R was lower in non-contractor group than those in both control group and contractor group (10.27±0.94 fmol/mg vs24.59±2.39 fmol/mg and 22.66±0.55 fmol/mg, P<0.01).The activity of CCK-R shown as KD in non-contractor group decreased compared to that in control group and contractor group. Only was the activity of CCK-R lower in contractor group than that in control group. The ejection fraction correlated closely with the amount of CCK-R (r = 0.9683,P<0.01), and the concentration of CCK-30 correlated negatively with the amount of CCK-R closely (r = -0.9627,P<0.01).CONCLUSION: The distinctive interactive relationship of gallbladder emptying, plasma CCK and CCK-R in gallbladder from this study suggested that the defect of CCK-R may be a key point leading to the impairment of gallbladder motor function and the pathogenesis of cholesterol gallstoneformation may differ in two subgroups of gallstone patient,gallbladder non-contractor group or contractor group.
文摘AIM:To study clinical characteristics and management of patients with early severe acute pancreatitis (ESAP).METHODS: Data of 297 patients with severe acute pancreatitis (SAP) admitted to our hospital within 72h after onset of symptoms from January 1991 to June 2003 were reviewed for the occurrence and development of early severe acute pancreatitis (ESAP).ESAP was defined as presence of organ dysfunction within 72 h after onset of symptoms.Sixtynine patients had ESAP, 228 patients without organ dysfunction within 72 h after onset of symptoms had SAR The clinical characteristics,incidence of organ dysfunction during hospitalization and prognosis between ESAP and SAP were compared.RESULTS.Impairment degree of pancreas (Balthazar CT class) in ESAP was more serious than that in SAP (5.31±0.68vs 3.68±0.29, P<0.01). ESAP had a higher mortality than SAP (43.4% vs 2.6%, P<0.01), and a higher incidence ofhypoxemia (85.5% vs 25%, P<0.01), pancreas infection (15.9% vs 7.5%, P<0.05),abdominal compartment syndrome (ACS) (78.3% vs 23.2%,P<0.01) and multiple organ dysfunction syndrome (MODS)(78.3% vs 10.1%,P<0.01).In multiple logistic regression analysis,the main predisposing factors to ESAP were higher APACHE II score, Balthazar CT class,MODS and hypoxemia.CONCLUSION:ESAP is characterised by MODS, severe pathological changes of pancreas,early hypoxemia and abdominal compartment syndrome. Given the poor prognosis of ESAP,these patients should be treated in specialized intensive care units with special measures such as close supervision, fluid resuscitation, improvement of hypoxemia,reduction of pancreatic secretion, elimination of inflammatory mediators,prevention and treatment of pancreatic infections.
基金Scientific Research Foundation of the Railway Ministry,China,No.TDB99-69
文摘AIM: To study the correlation between expression of MMP-2, TIMP-2 protein and the ratio of MMP-2/TIMP-2 and clinicalpathological parameters of patients with gallbladder carcinoma.METHODS: Carcinomas (n=45) and polypoid lesions (n=15) of the gallbladder were studied for the expression of MMP-2 and TIMP-2 protein by immunohistochemical avidin-biotin-complex method and image analysis. Clinicalpathological data of patients with gallbladder carcinoma such as histological type, grade of differentiation, level of infiltration, liver invasion and lymph node involvement, etc, were recorded.RESULTS: There was significant difference between the average level (1.123±0.108 VS 1.030±0.054, P=0.002) of MMP-2, the ratio (1.050±0.013 VS0.937±0.078, P=0.003) of MMP-2/TIMP-2 in gallbladder carcinomas and in polypoid lesions of the gallbladder. Significant difference was found between the expression of MMP-2 in early stage and advanced tumors, but there was no correlation between MMP-2 protein expression and histological type, differentiation degree, infiltration level, lymph node involvement or liver invasion. Although no difference was observed between TIMP-2 expression and histological type or differentiation degree, signific ant difference was found between TIMP-2 expression and different Nevin stage, infiltration level, local lymph node involvement or liver invasion (1.168±0.067 VS1.048±0.075, 1.170±0.062 vs 1.039±0.06g, 1.039±0.076 VS1.147±0.083, 1.048±0.074 vs 1.103±0.095, P<0.05). MMP-2/TIMP-2 ratio did not correlate with histological type, grade of differentiation and liver invasion, but significant differences were found between MMP-2/TIMP-2 ratio and different Nevin stage, infiltration level and lymph node involvement in patients with carcinoma of gallbladder.CONCLUSION: TIMP-2 and MMP-2/TIMP-2 ratio could reflect more accurately biological characteristic of gallbladder carcinoma and MMP-2/TIMP-2 ratio might be a new significant marker in early diagnosis, in the judgment of invasion or metastasis and the estimate of prognosis in patients with gallbladder carcinomas.
文摘AIM: Heat shock protein (HSP)70 is over-expressed in human gastric cancer and plays an important role in the progression of this cancer. We investigated the effects of antisense HSP70 oligomer on human gastric cancer cell line SGC-7901, and its potential role in gene therapy for this cancer.METHODS: Human gastric cancer cell line SGC-7901 was treated in vitro with various concentrations of antisense HSP70 oligonucleotides at different intervals. Growth inhibition was determined as percentage by trypan blue dye exclusion test. Extracted DNA was electrophoresed on agarose gel, and distribution of cell cycle and kinetics of apoptosis induction were analyzed by propidium iodide DNA incorporation using flow cytometry, which was also used to detect the effects of antisense oligomer pretreatment on the subsequent apoptosis induced by heat shock in SGC-7901 cells. Proteins were extracted for simultaneous measurement of HSP70 expression level by SDS-PAGE Western blotting.RESULTS: The number of viable cells decreased in a doseand time-dependent manner, and ladder-like patterns of DNA fragments were observed in SGC-7901 cells treated with antisense HSP70 oligomers at a concentration of 10 μmol/L for 48 h or 8 μmol/L for 72 h, which were consistent with inter-nucleosomal DNA fragmentation. Flow cytometric analysis showed a dose- and time-dependent increase in apoptotic rate by HSP70 antisense oligomers. This response was accompanied with a decrease in the percentage of cells in the G1 and S phases of the cell cycle, suggesting inhibition of cell proliferation. In addition, flow cytometry also showed that pretreatment of SGC-7901 cells with HSP70 antisense oligomers enhanced the subsequent apoptosis induced by heat shock treatment. Western blotting demonstrated that HSP70 antisense oligomers inhibited HSP70 expression, which preceded apoptosis, and HSP70 was undetectable at the concentration of 10 μmol/L for 48 h or 8 μmol/L for 72 h.CONCLUSION: Antisense HSP70 oligomers can abrogate HSP70 expression in SGC-7901 cells, which may in turn induce apoptosis and inhibit cell proliferation, conversely suggesting that HSP70 is required for the proliferation and survival of human gastric cancer cells under normal conditions.
文摘AIM:To study different approaches to caudate Iobectomy with'curettage and aspiration'technique using Peng's multifunctional operative dissector(PMOD).The surgical procedure of isolated complete caudate Iobectomy was specially discussed. METHODS:In 76 cases of various types of caudate Iobectomy,three approaches were used including left side approach,right side approach,and anterior approach. Among the 76 cases,isolated complete caudate Iobectomy was carried out in 6 cases with transhepatic anterior approach.The surgical procedure consisted of mobilization of the total liver,ligation and separation of the short hepatic veins,splitting the liver parenchyma through the Cantlie's plane,ligation and division of the caudate portal triads from the hilum,dissection of the root of major hepatic veins, detachment of the caudate lobe from liver parenchyma. RESULTS:The mean operative time was 285±51 min, the mean blood loss was 1 600 ml.No severe complications were observed.Among the 6 cases receiving isolated complete caudate lobectomy with transhepatic anterior approach,one case died 17 months after operation due to disease recurrence and liver failure,the other 5 cases have been alive without recurrence,with one longest survival of 49 months. CONCLUSION:The choice of approach is essential to the success of caudate Iobectomy.As PMOD and'curettage and aspiration'technique can delineate intrahepatic or extrahepatic vessels clearly,caudate lobe resection has become safer,easier and faster.
文摘AIM: To investigate the clinical characteristics and prognostic factors of a consecutive series of patients with severe acute pancreatitis (SAP). METHODS: Clinical data of SAP patients admitted to our hospital from January 2003 to January 2004 were retrospectively reviewed. Collected data included the age, gender, etiology, length of hospitalization, APACHE Ⅱ score at admission, local and organ/systemic complications of the patients. RESULTS: Of the 268 acute pancreatitis patients, 94 developed SAP. The mean age of SAP patients was 52 years, the commonest etiology was cholelithiasis (45.7%), the mean length of hospitalization was 70 d, the mean score of APACHE Ⅱ was 7.7. Fifty-four percent of the patients developed necrosis, 25% abscess, 58% organ/systemic failure. A total of 23.4% (22/94) of the SAP patients died. Respiratory failure was the most common organ dysfunction (90.9%) in deceased SAP patients, followed by cardiovascular failure (86.4%), renal failure (50.0%). In the SAP patients, 90.9% (20/22) developed multiple organ/systemic failures. There were significant differences in age, length of hospitalization, APACHE Ⅱ score and incidences of respiratory failure, renal failure, cardiovascular failure and hematological failure between deceased SAP patients and survived SAP patients. By multivariate logistic regression analysis, independent prognostic factors for mortality were respiratory failure, cardiovascular failure and renal failure. CONCLUSION: SAP patients are characterized by advanced age, high APACHE Ⅱ score, organ failure and their death is mainly due to multiple organ/systemic failures. In patients with SAP, respiratory, cardiovascular and renal failures can predict the fatal outcome and more attention should be paid to their clinical evaluation.
文摘AIM:To compare the therapeutic effect of transcatheter arterial chemoembolization (TACE), laparoscopic radiofrequency ablation (LRFA), and conservative treatment for the therapy of decompensated liver cirrhosis patients with hepatocellular carcinomas (HCC).METHODS:Between October 2000 and July 2003, one hundred patients with histologically proven primary HCC and clinical decompensated liver cirrhosis (Child classification B or C) were included in this study. Forty patients received LRFA (LRFA group), twenty received TACE (TACE group),and forty received conservative treatment (control group).We compared the survival, recurrence, and complication rates in these three groups, making adjustment using the tumor metastastic node staging system.RESULTS:The major complication rate in the TACE group (9/20) was significantly higher than that in the LRFA group (7/40). For patients with TMN stage Ⅱ HCC, the survival rate of the LRFA group was better than that of the TACE and control groups (P=0.003) but the recurrence rates befween the LRFA and TACE groups did not differ.CONCLUSION: The LRFA group of patients had betterclinical outcomes in terms of survival and complication rates in comparison with the TACE group or conservative treatment in patients with decompensated liver cirrhosis, especially in TMN patients with stage Ⅱ HCC. LRFA is thus an appropriate alternative treatment for poor liver function among patientswith HCC.
基金Health Ministry Scientific and Research Foundation of China,No.98-1-312
文摘AIM: Cancer gene therapy has received more and moreattentions in the recent decade. Various systems of genetherapy for cancer have been developed. One of the mostpromising choices is the suicide gene. The product ofthymidine kinase (TK) gene can convert ganciclovir (GCV)to phosphorylated GCV, which inhibits the synthesis of cellDNA, and then induces the cells to death. Cytolines play animportant role in anti-tumor immunity. This experiment wasdesigned to combine theTK gene and mIL-2/mGM-CSFgenes to treat gastric cancer, and was expected to producea marked anti-tumor effect.METHODS: TK gene was constructed into the retroviralvector pLxSN, and the mIL-2 and mGM-CSF genes wereinserted into the eukaryotic expressing vector pIRES. Thegastric cancer cells were transfected by retroviral serum thatwas harvested from the package cells. In vitro study, thetransfected gastric cancer cells were maintained in the GCV-contained medium, to assay the cell killing effect andbystander effect. In vivo experiment, retroviral serum andcytokines plasmid were transfected into tumor-bearing mice,to observe the changes of tumor volumes and survival ofthe mice.RESULTS: In vitro experiment, 20 % TK gene transducedcells could cause 70-80 % of total cells to death. In vivoresults showed that there was no treatment effect in controlgroup and TK/GCV could inhibit the tumor growth. Thestrongest anti-tumor effect was shown in TK+mIL-2+mGM-CSF group. The pathologic examination showed necrosis ofthe cancer in the treated groups.CONCLUSION: TK/GCV can kill tumor cells and inhibit thetumor growth in vivo IL-2 and GM-CSF strongly enhancethe anti-tumor effect. Through the retrovirus and liposomemethods, the suicide gene and cytokine genes are allexpressed in the tissues.
基金Supported by a grant from Shanghai Science and Technology Committee in China,No.954119027
文摘AIM: To investigate the relationship between gallbladder stone disease (GSD) and single nucleotide polymorphisms of cholesterol 7α-hydroxylase (CYP7A) gene promoter,apolipoprotein (APO) B gene exon 26, APOEgene exon 4 or microsatellite polymorphism of low density lipoprotein receptor (LDLR) gene exon 18.METHODS: Genotypes of CYP7A, APOB, APOE and LDLR genes were determined in 105 patients with GSD diagnosed by B-mode ultrasonography and 274 control subjects.Serum lipids were analyzed with HITACHI 7060 automaic biochemical analyzer.RESULTS: Body mass index (BMI) was significantly higher in patients with GSD (24.47±3.09) than in controls (23.50±2.16).Plasma total cholesterol was lower in patients with GSD (4.66±0.92 mmol/L) than in controls (4.91±0.96 mmol/L),P<0.01 after adjusted for age, sex and BMI. The significantly higher frequency of A allele of CYP7A gene polymorphism and X+ allele of APOBgene polymorphism was seen in GSD patients. Percentages of A allele in patients and controls were 62.86% and 54.38% (P <0.05) and those of X+ allele 8.57% and 4.01% (P<0.01). Subjects with A allele had significantly lower plasma total cholesterol and LDL cholesterol than subjects with CC homozygote. In a multiple variable logistic regression model, the BMI (OR=1.13, 95% CI: 1.05-1.22), A allele (OR=1.48, 95% CI: 1.05-2.09) and X+ allele (OR=2.28, 95% CI: 1.14-4.59) were positively associated with GSD (P <0.05). Plasma total cholesterol (OR=0.69, 95% CI: 0.64-0.74) was negatively related to GSD (P<0.05).CONCLUSION: With an association analysis, it was determined that A allele of CYP7A gene and X+ allele of APOB gene might be considered as risk genes for GSD. These alleles are related with differences of serum lipids among subjects.Multiple-variable logistic regression model analysis showed that besides BMI, GSD was affected by polygenetic factors.But the mechanism for these two alleles responsible for GSD requires further investigations.