AIM To investigate the mechanisms of codon 249 mutation of p53 gene in the formation of hepatocellular carcinoma (HCC). METHODS Codon 249 mutation accompanied by loss of heterozygosity (LOH) and its effect on trans...AIM To investigate the mechanisms of codon 249 mutation of p53 gene in the formation of hepatocellular carcinoma (HCC). METHODS Codon 249 mutation accompanied by loss of heterozygosity (LOH) and its effect on translation and transcription were studied using SSCP, IHC and RT PCR/slot hybridization. RESULTS Codon 249 mutations were detected in 32 9%, LOH detected in 68 4% among the HCC patients. Mutations of condon 249 were accompanied by LOH in 90%. The positive rates of p53 protein and mRNA were 91 3% and 95 7%, in mutational group, both were significantly higher than those in the non mutational group (91 3% vs 19 1% and 95 7% vs 40 4%, respectively, both P <0 01). The translation of p53 gene was strongly related to its transcription by correlation analysis ( r =0 8208). CONCLUSIONS LOH might play an important role in hepatocarcinogenesis of codon 249 mutation, which could increase both transcription and translation of p53 gene. The increased expression of p53 protein mainly depend on the increased transcription of p53 gene.展开更多
AIM:To identify prognostic factors from pretreatment variables of the initial transarterial chemoembolization(TACE)procedure in unresectable hepatocellular carcinoma(HCC). METHODS:One thousand and five hundred and six...AIM:To identify prognostic factors from pretreatment variables of the initial transarterial chemoembolization(TACE)procedure in unresectable hepatocellular carcinoma(HCC). METHODS:One thousand and five hundred and sixtynine patients with unresectable HCC underwent TACE as initial treatment were retrospectively studied.Pretreatment variables of the initial TACE procedure with a P value less than 0.05 by univariate analysis were subjected to Cox proportional hazards model. RESULTS:The median overall survival time and 1-, 5-,10-year survival rates were 10.37 mo,47%,10%, and 7%,respectively.A Cox proportional hazard model showed that 8 pretreatment factors of regional lymphnodes metastasis,Child-Pugh class,macrovascular invasion,greatest dimension,α-fetoprotein(AFP), Hepatitis virus B,tumor capsule,and nodules were independent prognostic factors.Patients with multimodality therapy have better survival than those with TACE treatment only. CONCLUSION:Tumor status,hepatic function reserve,AFP,and hepatitis virus B status were independent prognostic factors for unresectable HCC.Distant metastasis might not be a contraindication to TACE. Multimodality therapy might improve survival.展开更多
AIM To improve the technique of intraportal embolization (PVE) therapy, a new embolic method, was devised and the safety, effectiveness and feasibility were evaluated. METHODS PVE with intraportal ethanol injection vi...AIM To improve the technique of intraportal embolization (PVE) therapy, a new embolic method, was devised and the safety, effectiveness and feasibility were evaluated. METHODS PVE with intraportal ethanol injection via a fine needle was performed in 28 normal dogs, 22 SD rats, and 24 cirrhotic SD rats. After PVE, portography, histological and functional alteration of the liver were evaluated in dogs and rats, and the changes in portal hemodynamics as well as hepatic anatomy were observed in rats. In the clinical study, PVE by ethanol injection was performed in 61 patients with hepatocellular carcinoma under the guidance of portoechography with intraportal injection of CO 2. The effect of PVE was evaluated by ultrasonography and laparotomy. RESULTS The effectiveness and toxicity were dependent on the dose of ethanol. In the dogs, 0 25*!mg/*!kg of ethanol caused incomplete embolization with least liver damage, while 1 0*!mg/*!kg induced complete embolization with a high mortality of 57 1% (4/*!7) due to respiratory arrest. The dose of 0 5*!mg/*!kg resulted in complete embolization with slight toxicity to the liver. In the rats, the survival rate was 100% in normal group but 40 9% in cirrhotic models after ethanol injection by dose of 0 05*!mg/*!100*!g . PVE for cirrhotic rats with 0 03*!mg/*!100*!g of ethanol induced satisfactory embolization with significant hypertrophy in nonembolized lobes, and only slight damage to the hepatic parenchyma, and transient alteration in liver function, portal pressure and portal flow. In the clinical study, 12 cases with reverse portal flow were excluded judged by portoechography. Satisfactory embolization was gained in 90 2% (55/*!61) of the remaining patients determined by ultrasonography and surgery. All cases ran an uneventful postembolization course with no aberrant embolization. CONCLUSION PVE with intraportal ethanol injection of appropriate dosage via a fine needle is safe and effective and has several advantages comparing with transcatheter method. Portoechography is a mandatory approach for the prevention of aberrant embolization.展开更多
INTRODUCTION When fulminant hepatitis progress to deep encephalopathy,with stage Ⅲ or Ⅳ coma,it is commonly irreversible with a high mortality rate(80%-100%).Liver transplantation may be
Multidrug resistance(MDR) in cancer cells can significantly attenuate the response to chemotherapy and increase the likelihood of mortality.The major mechanism involved in conferring MDR is the overexpression of ATP-b...Multidrug resistance(MDR) in cancer cells can significantly attenuate the response to chemotherapy and increase the likelihood of mortality.The major mechanism involved in conferring MDR is the overexpression of ATP-binding cassette(ABC) transporters,which can increase efflux of drugs from cancer cells,thereby decreasing intracellular drug concentration.Modulators of ABC transporters have the potential to augment the efficacy of anticancer drugs.This editorial highlights some major findings related to ABC transporters and current strategies to overcome MDR.展开更多
文摘AIM To investigate the mechanisms of codon 249 mutation of p53 gene in the formation of hepatocellular carcinoma (HCC). METHODS Codon 249 mutation accompanied by loss of heterozygosity (LOH) and its effect on translation and transcription were studied using SSCP, IHC and RT PCR/slot hybridization. RESULTS Codon 249 mutations were detected in 32 9%, LOH detected in 68 4% among the HCC patients. Mutations of condon 249 were accompanied by LOH in 90%. The positive rates of p53 protein and mRNA were 91 3% and 95 7%, in mutational group, both were significantly higher than those in the non mutational group (91 3% vs 19 1% and 95 7% vs 40 4%, respectively, both P <0 01). The translation of p53 gene was strongly related to its transcription by correlation analysis ( r =0 8208). CONCLUSIONS LOH might play an important role in hepatocarcinogenesis of codon 249 mutation, which could increase both transcription and translation of p53 gene. The increased expression of p53 protein mainly depend on the increased transcription of p53 gene.
基金Supported by The Eleventh Five-Year Key Plan of the China National Science and Technique Foundation,No.2006BAI02A04the 5010 Foundation of Sun Yat-sen University,No.2007043
文摘AIM:To identify prognostic factors from pretreatment variables of the initial transarterial chemoembolization(TACE)procedure in unresectable hepatocellular carcinoma(HCC). METHODS:One thousand and five hundred and sixtynine patients with unresectable HCC underwent TACE as initial treatment were retrospectively studied.Pretreatment variables of the initial TACE procedure with a P value less than 0.05 by univariate analysis were subjected to Cox proportional hazards model. RESULTS:The median overall survival time and 1-, 5-,10-year survival rates were 10.37 mo,47%,10%, and 7%,respectively.A Cox proportional hazard model showed that 8 pretreatment factors of regional lymphnodes metastasis,Child-Pugh class,macrovascular invasion,greatest dimension,α-fetoprotein(AFP), Hepatitis virus B,tumor capsule,and nodules were independent prognostic factors.Patients with multimodality therapy have better survival than those with TACE treatment only. CONCLUSION:Tumor status,hepatic function reserve,AFP,and hepatitis virus B status were independent prognostic factors for unresectable HCC.Distant metastasis might not be a contraindication to TACE. Multimodality therapy might improve survival.
基金Suppated by pats form the National Science Foundatian of China,No.393706697Science and Technology Gommission,Granglong Province,China,No.970066.
文摘AIM To improve the technique of intraportal embolization (PVE) therapy, a new embolic method, was devised and the safety, effectiveness and feasibility were evaluated. METHODS PVE with intraportal ethanol injection via a fine needle was performed in 28 normal dogs, 22 SD rats, and 24 cirrhotic SD rats. After PVE, portography, histological and functional alteration of the liver were evaluated in dogs and rats, and the changes in portal hemodynamics as well as hepatic anatomy were observed in rats. In the clinical study, PVE by ethanol injection was performed in 61 patients with hepatocellular carcinoma under the guidance of portoechography with intraportal injection of CO 2. The effect of PVE was evaluated by ultrasonography and laparotomy. RESULTS The effectiveness and toxicity were dependent on the dose of ethanol. In the dogs, 0 25*!mg/*!kg of ethanol caused incomplete embolization with least liver damage, while 1 0*!mg/*!kg induced complete embolization with a high mortality of 57 1% (4/*!7) due to respiratory arrest. The dose of 0 5*!mg/*!kg resulted in complete embolization with slight toxicity to the liver. In the rats, the survival rate was 100% in normal group but 40 9% in cirrhotic models after ethanol injection by dose of 0 05*!mg/*!100*!g . PVE for cirrhotic rats with 0 03*!mg/*!100*!g of ethanol induced satisfactory embolization with significant hypertrophy in nonembolized lobes, and only slight damage to the hepatic parenchyma, and transient alteration in liver function, portal pressure and portal flow. In the clinical study, 12 cases with reverse portal flow were excluded judged by portoechography. Satisfactory embolization was gained in 90 2% (55/*!61) of the remaining patients determined by ultrasonography and surgery. All cases ran an uneventful postembolization course with no aberrant embolization. CONCLUSION PVE with intraportal ethanol injection of appropriate dosage via a fine needle is safe and effective and has several advantages comparing with transcatheter method. Portoechography is a mandatory approach for the prevention of aberrant embolization.
基金the Key Clinical Project of Ministry of Health.No.97040230the Key Project of Scientific and Technological Committee of Guangdong Province No.963003
文摘INTRODUCTION When fulminant hepatitis progress to deep encephalopathy,with stage Ⅲ or Ⅳ coma,it is commonly irreversible with a high mortality rate(80%-100%).Liver transplantation may be
基金supported by funds from NIH R15 No. 1R15CA143701 (Z.S. Chen)St.John's University Seed Grant No. 579-1110 (Z.S. Chen)
文摘Multidrug resistance(MDR) in cancer cells can significantly attenuate the response to chemotherapy and increase the likelihood of mortality.The major mechanism involved in conferring MDR is the overexpression of ATP-binding cassette(ABC) transporters,which can increase efflux of drugs from cancer cells,thereby decreasing intracellular drug concentration.Modulators of ABC transporters have the potential to augment the efficacy of anticancer drugs.This editorial highlights some major findings related to ABC transporters and current strategies to overcome MDR.
