AIM To characterize the survival of cirrhotic patients with Barcelona Clinic Liver Cancer(BCLC) stage C hepatocellular carcinoma(HCC) and to ascertain the factors predicting the achievement of disease control(DC).METH...AIM To characterize the survival of cirrhotic patients with Barcelona Clinic Liver Cancer(BCLC) stage C hepatocellular carcinoma(HCC) and to ascertain the factors predicting the achievement of disease control(DC).METHODS The cirrhotic patients with BCLC stage C HCC evaluated by the Hepatocatt multidisciplinary group were subjected to the investigation. Demographic, clinical and tumor features, along with the best tumor response and overall survival were recorded. RESULTS One hundred and ten BCLC stage C patients were included in the analysis; the median overall survival was 13.4 mo(95%CI: 10.6-17.0). Only alphafetoprotein(AFP) serum level > 200 ng/m L and DC could independently predict survival but in a time dependent manner, the former was significantly associated with increased risk of mortality within the first 6 mo of follow-up(HR = 5.073, 95%CI: 2.159-11.916, P = 0.0002), whereas the latter showed a protective effect against death after one year(HR = 0.110, 95%CI: 0.038-0.314, P < 0.0001). Only patients showing microvascular invasion and/or extrahepatic spread recorded lower chances of achieving DC(OR = 0.263, 95%CI: 0.111-0.622, P = 0.002).CONCLUSION The BCLC stage C HCC includes a wide heterogeneous group of cirrhotic patients suitable for potentially curative treatments. The reverse and time dependent effect of AFP serum level and DC on patients' survival confers them as useful predictive tools for treatment management and clinical decisions.展开更多
Chronic hepatitis B virus(HBV) infected patients have an almost 100-fold increased risk to develop hepatocellular carcinoma(HCC). HCC is the fifth most common and third most deadly cancer worldwide. Up to 50% of newly...Chronic hepatitis B virus(HBV) infected patients have an almost 100-fold increased risk to develop hepatocellular carcinoma(HCC). HCC is the fifth most common and third most deadly cancer worldwide. Up to 50% of newly diagnosed HCC cases are attributed to HBV infection. Early detection improves survival and can be achieved through regular screening. Six-monthly abdominal ultrasound, either alone or in combination with alphafetoprotein serum levels, has been widely endorsed for this purpose. Both techniques however yield limited diagnostic accuracy, which is not improved when they are combined. Alternative circulating or histological markers to predict or diagnose HCC are therefore urgently needed. Recent advances in systems biology technologies have enabled the identification of several new putative circulating biomarkers. Although results from studies assessing combinations of these biomarkers are promising, evidence for their clinical utility remains low. In addition, most of the studies conducted so far show limitations in design. Attention must be paid for instance to different ethnicities and different etiologies when studying biomarkers for hepatocellular carcinoma. This review provides an overview on the current understandings and recent progress in the field of diagnostic and predictive circulating biomarkers for hepatocellular carcinoma in chronically infected HBV patients and discusses the future prospects.展开更多
Morphological criteria have always been considered the benchmark for selecting hepatocellular carcinoma(HCC)patients for liver transplantation(LT).These criteria,which are often inappropriate to express the tumor’s b...Morphological criteria have always been considered the benchmark for selecting hepatocellular carcinoma(HCC)patients for liver transplantation(LT).These criteria,which are often inappropriate to express the tumor’s biological behavior and aggressiveness,offer only a static view of the disease burden and are frequently unable to correctly stratify the tumor recurrence risk after LT.Alpha-fetoprotein(AFP)and its progression as well as AFP-m RNA,AFP-L3%,des-γ-carboxyprothrombin,inflammatory markers and other serological tests appear to be correlated with post-transplant outcomes.Several other markers for patient selection including functional imaging studies such as18F-FDG-PET imaging,histological evaluation of tumor grade,tissue-specific biomarkers,and molecular signatures have been outlined in the literature.HCC growth rate and response to pre-transplant therapies can further contribute to the transplant evaluation process of HCC patients.While AFP,its progression,and HCC response to pretransplant therapy have already been used as a part of an integrated prognostic model for selecting patients,the utility of other markers in the transplant setting is still under investigation.This article intends to review the data in the literature concerning predictors that could be included in an integrated LT selection model and to evaluate the importance of biological aggressiveness in the evaluation process of these patients.展开更多
AIM To investigate the clinical utility of alpha-fetoprotein(AFP)-producing gastric cancer(AFPGC)-specific microRNA(mi RNA)for monitoring and prognostic prediction of patients.METHODS We performed a comprehensive miRN...AIM To investigate the clinical utility of alpha-fetoprotein(AFP)-producing gastric cancer(AFPGC)-specific microRNA(mi RNA)for monitoring and prognostic prediction of patients.METHODS We performed a comprehensive miRNA array-based approach to compare miRNA expression levels between AFP-positive and AFP-negative cells in three patients with primary AFPGC.We next examined the expression levels of the selected miRNAs in five AFPGC and ten non-AFPGC tissue samples by quantitative reverse transcription-polymerase chain reaction to validate their utility.We also investigated the expression levels of the selected miRNA not only in tissue but also in plasma samples.Moreover,we investigated the relationship between plasma AFP levels and plasma selected miRNA expression levels,and also investigated the correlation of the selected miRNA expression levels and malignant potential.RESULTS Among the five miRNAs selected from the miRNA array results,the expression levels of miR-122-5p were significantly higher in the AFPGC patients than in the non-AFPGC patients(P<0.05).In tissue samples,mi R-122-5p expression level tended to be lower in the non-AFPGC tissue than the normal gastric mucosa.Conversely,in the AFPGC tissue,miR-122-5p expression level was significantly higher in the AFPGC tissue than both the normal gastric mucosa and the nonAFPGC tissue samples(P<0.05).Plasma mi R-122-5p expression levels were also significantly higher in the AFPGC patients than the health volunteers and the nonAFPGC patients(P<0.05)and were strongly correlated with plasma AFP levels(r=0.7975,P<0.0001).Moreover,the correlation of miR-122-5p expression in tissue samples with malignant potential was stronger than that of plasma AFP level in the AFPGC patients.In contrast,no correlation was found between mi R-122-5p expression levels and liver metastasis in the non-AFPGC patients.CONCLUSION miR-122-5p might be a useful biomarker for early detection and disease monitoring in AFPGC.展开更多
Hepatocellular carcinoma(HCC) is a common neoplasia which represents the second leading cause of cancer related death. Most cases occur in developing countries, but its incidence is rising in Western countries due to ...Hepatocellular carcinoma(HCC) is a common neoplasia which represents the second leading cause of cancer related death. Most cases occur in developing countries, but its incidence is rising in Western countries due to hepatitis C. Although hepatitis therapies have evolved and the HCC screening has increased in several areas, 40% present with advanced disease which is only amenable for palliative systemic treatment. HCC continues posing a challenge, in part due to the inherent chemoresistance of this neoplasia, the pharmacologic challenges due to an ill liver, difficulty in assessing radiological responses accurately, etc. Traditional chemotherapy have shown some responses without clear survival benefit, however, sorafenib demonstrated advantages in survival in advanced HCC when liver function is kept and recently immunotherapy seems to be a promising approach for some patients. This article will briefly expose the most relevant systemic treatment modalities to offer a general view from the past to the future.展开更多
Fucose (6-deoxy-L-galactose) is a monosaccharide that is found on glycoproteins and glycolipids in verteb rates, invertebrates, plants, and bacteria. Fucosylation, which comprises the transfer of a fucose residue to o...Fucose (6-deoxy-L-galactose) is a monosaccharide that is found on glycoproteins and glycolipids in verteb rates, invertebrates, plants, and bacteria. Fucosylation, which comprises the transfer of a fucose residue to oligosaccharides and proteins, is regulated by many kinds of molecules, including fucosyltransferases, GDP-fucose synthetic enzymes, and GDP-fucose transporter(s). Dramatic changes in the expression of fucosylated oligosaccharides have been observed in cancer and inflammation. Thus, monoclonal antibodies and lectins recognizing cancer-associated fucosylated oligosaccharides have been clinically used as tumor markers for the last few de cades. Recent advanced glycomic approaches allow us to identify novel fucosylation-related tumor markers. Moreover, a growing body of evidence supports the functional significance of fucosylation at various pathophysiological steps of carcinogenesis and tumor progression. This review highlights the biological and medical signifi cance of fucosylation in gastrointestinal cancer.展开更多
文摘AIM To characterize the survival of cirrhotic patients with Barcelona Clinic Liver Cancer(BCLC) stage C hepatocellular carcinoma(HCC) and to ascertain the factors predicting the achievement of disease control(DC).METHODS The cirrhotic patients with BCLC stage C HCC evaluated by the Hepatocatt multidisciplinary group were subjected to the investigation. Demographic, clinical and tumor features, along with the best tumor response and overall survival were recorded. RESULTS One hundred and ten BCLC stage C patients were included in the analysis; the median overall survival was 13.4 mo(95%CI: 10.6-17.0). Only alphafetoprotein(AFP) serum level > 200 ng/m L and DC could independently predict survival but in a time dependent manner, the former was significantly associated with increased risk of mortality within the first 6 mo of follow-up(HR = 5.073, 95%CI: 2.159-11.916, P = 0.0002), whereas the latter showed a protective effect against death after one year(HR = 0.110, 95%CI: 0.038-0.314, P < 0.0001). Only patients showing microvascular invasion and/or extrahepatic spread recorded lower chances of achieving DC(OR = 0.263, 95%CI: 0.111-0.622, P = 0.002).CONCLUSION The BCLC stage C HCC includes a wide heterogeneous group of cirrhotic patients suitable for potentially curative treatments. The reverse and time dependent effect of AFP serum level and DC on patients' survival confers them as useful predictive tools for treatment management and clinical decisions.
基金Supported by Foundation Against Cancer Belgium,No.2014-087
文摘Chronic hepatitis B virus(HBV) infected patients have an almost 100-fold increased risk to develop hepatocellular carcinoma(HCC). HCC is the fifth most common and third most deadly cancer worldwide. Up to 50% of newly diagnosed HCC cases are attributed to HBV infection. Early detection improves survival and can be achieved through regular screening. Six-monthly abdominal ultrasound, either alone or in combination with alphafetoprotein serum levels, has been widely endorsed for this purpose. Both techniques however yield limited diagnostic accuracy, which is not improved when they are combined. Alternative circulating or histological markers to predict or diagnose HCC are therefore urgently needed. Recent advances in systems biology technologies have enabled the identification of several new putative circulating biomarkers. Although results from studies assessing combinations of these biomarkers are promising, evidence for their clinical utility remains low. In addition, most of the studies conducted so far show limitations in design. Attention must be paid for instance to different ethnicities and different etiologies when studying biomarkers for hepatocellular carcinoma. This review provides an overview on the current understandings and recent progress in the field of diagnostic and predictive circulating biomarkers for hepatocellular carcinoma in chronically infected HBV patients and discusses the future prospects.
文摘Morphological criteria have always been considered the benchmark for selecting hepatocellular carcinoma(HCC)patients for liver transplantation(LT).These criteria,which are often inappropriate to express the tumor’s biological behavior and aggressiveness,offer only a static view of the disease burden and are frequently unable to correctly stratify the tumor recurrence risk after LT.Alpha-fetoprotein(AFP)and its progression as well as AFP-m RNA,AFP-L3%,des-γ-carboxyprothrombin,inflammatory markers and other serological tests appear to be correlated with post-transplant outcomes.Several other markers for patient selection including functional imaging studies such as18F-FDG-PET imaging,histological evaluation of tumor grade,tissue-specific biomarkers,and molecular signatures have been outlined in the literature.HCC growth rate and response to pre-transplant therapies can further contribute to the transplant evaluation process of HCC patients.While AFP,its progression,and HCC response to pretransplant therapy have already been used as a part of an integrated prognostic model for selecting patients,the utility of other markers in the transplant setting is still under investigation.This article intends to review the data in the literature concerning predictors that could be included in an integrated LT selection model and to evaluate the importance of biological aggressiveness in the evaluation process of these patients.
文摘AIM To investigate the clinical utility of alpha-fetoprotein(AFP)-producing gastric cancer(AFPGC)-specific microRNA(mi RNA)for monitoring and prognostic prediction of patients.METHODS We performed a comprehensive miRNA array-based approach to compare miRNA expression levels between AFP-positive and AFP-negative cells in three patients with primary AFPGC.We next examined the expression levels of the selected miRNAs in five AFPGC and ten non-AFPGC tissue samples by quantitative reverse transcription-polymerase chain reaction to validate their utility.We also investigated the expression levels of the selected miRNA not only in tissue but also in plasma samples.Moreover,we investigated the relationship between plasma AFP levels and plasma selected miRNA expression levels,and also investigated the correlation of the selected miRNA expression levels and malignant potential.RESULTS Among the five miRNAs selected from the miRNA array results,the expression levels of miR-122-5p were significantly higher in the AFPGC patients than in the non-AFPGC patients(P<0.05).In tissue samples,mi R-122-5p expression level tended to be lower in the non-AFPGC tissue than the normal gastric mucosa.Conversely,in the AFPGC tissue,miR-122-5p expression level was significantly higher in the AFPGC tissue than both the normal gastric mucosa and the nonAFPGC tissue samples(P<0.05).Plasma mi R-122-5p expression levels were also significantly higher in the AFPGC patients than the health volunteers and the nonAFPGC patients(P<0.05)and were strongly correlated with plasma AFP levels(r=0.7975,P<0.0001).Moreover,the correlation of miR-122-5p expression in tissue samples with malignant potential was stronger than that of plasma AFP level in the AFPGC patients.In contrast,no correlation was found between mi R-122-5p expression levels and liver metastasis in the non-AFPGC patients.CONCLUSION miR-122-5p might be a useful biomarker for early detection and disease monitoring in AFPGC.
文摘Hepatocellular carcinoma(HCC) is a common neoplasia which represents the second leading cause of cancer related death. Most cases occur in developing countries, but its incidence is rising in Western countries due to hepatitis C. Although hepatitis therapies have evolved and the HCC screening has increased in several areas, 40% present with advanced disease which is only amenable for palliative systemic treatment. HCC continues posing a challenge, in part due to the inherent chemoresistance of this neoplasia, the pharmacologic challenges due to an ill liver, difficulty in assessing radiological responses accurately, etc. Traditional chemotherapy have shown some responses without clear survival benefit, however, sorafenib demonstrated advantages in survival in advanced HCC when liver function is kept and recently immunotherapy seems to be a promising approach for some patients. This article will briefly expose the most relevant systemic treatment modalities to offer a general view from the past to the future.
文摘Fucose (6-deoxy-L-galactose) is a monosaccharide that is found on glycoproteins and glycolipids in verteb rates, invertebrates, plants, and bacteria. Fucosylation, which comprises the transfer of a fucose residue to oligosaccharides and proteins, is regulated by many kinds of molecules, including fucosyltransferases, GDP-fucose synthetic enzymes, and GDP-fucose transporter(s). Dramatic changes in the expression of fucosylated oligosaccharides have been observed in cancer and inflammation. Thus, monoclonal antibodies and lectins recognizing cancer-associated fucosylated oligosaccharides have been clinically used as tumor markers for the last few de cades. Recent advanced glycomic approaches allow us to identify novel fucosylation-related tumor markers. Moreover, a growing body of evidence supports the functional significance of fucosylation at various pathophysiological steps of carcinogenesis and tumor progression. This review highlights the biological and medical signifi cance of fucosylation in gastrointestinal cancer.
