Lory Croce | Università degli Studi di Trieste (original) (raw)
Papers by Lory Croce
Annals of Hepatology, 2020
Introduction: Spleen stiffness (SS) has been found to mirror dynamic changes in portal pressure a... more Introduction: Spleen stiffness (SS) has been found to mirror dynamic changes in portal pressure after transjugular intrahepatic portosystemic shunt (TIPS) placement. However, there is no data available regarding SS in patients with spontaneous portosystemic shunting (SPSS), especially in regards to prediction of hepatic decompensation. Methods: We retrospectively selected patients with confirmed SPSS and esophageal varices (EVs) at endoscopic examination, and recorded any decompensating event (i.e., variceal hemorrhage, overt hepatic encephalopathy, refractory ascites, spontaneous bacterial peritonitis, hepatorenal syndrome) in the first twelve months following liver and spleen elastography. Results: The patients who presented decompensating events showed lower platelet count (94.5 vs. 121.5 g/L, p < 0.001), higher SS (44 vs. 30 kPa, p < 0.001), higher probability of EVs according to SS (77 vs. 2 %, p < 0.001), and higher spleen diameter (14 vs. 12 cm, p = 0.043). They also showed a higher prevalence of splenorenal shunts (66.7 vs. 31.2%), and a significantly wider SPSS major diameter (14.5 vs. 8 mm, p < 0.001). Conclusion: SS could predict SPSS efficacy in relieving portal pressure, and could predict decompensating events in patients with SPSS.
Journal of Medical Virology, 1994
The presence of the "Japanese type" NS4 region was investigated in two series of patients (53 fro... more The presence of the "Japanese type" NS4 region was investigated in two series of patients (53 from Italy and 58 from Japan) with hepatitis C virus (HCV)-related chronic liver disease. The two populations were homogeneous as regard to age, male/female ratio, histological diagnosis, and serum aminotransferase activities. Genomic amplification was carried out by "nested" polymerase chain reaction (PCR) with a pair of primers synthesized according to the sequence of JK-1 isolated in Japan. The presence of viral replication was confirmed further by PCR amplification of the 5°C region. The NS4 region of the Japanese strain was detected in 24 sera (45%) from Italy and in 44 (71%) from Japan. NS4-positive patients were significantly older and showed an ALT serum level significantly lower (P < 0.01) than NS4 negative cases in each group. Cirrhosis was significantly (P < 0.0007) more common in NS4-positive than in NSCnegative patients. The HCV genotype was subsequently obtained according to Okamoto. All the NS4-positive patients were infected by Type ll, whereas in NS4negative patients all four genotypes were present though Type II still constituted the majority. Cirrhosis was associated exclusively with Type II both in NS4-positive and-negative subjects. These data indicate that, although the positivity for NS4 "Japanese" region seems to be associated with a more aggressive liver disease, the most prevalent Type II predicts more specifically those who are likely to develop cirrhosis. Since the same findings were obtained in two population from different areas of the world, the genotype of HCV appears to be one of the major determinants of the progression of chronic active hepatitis to cirrhosis.
Journal of Hepatology, 2001
Hepatology, 2007
Nonalcoholic fatty liver disease (NAFLD) is systematically associated with insulin resistance and... more Nonalcoholic fatty liver disease (NAFLD) is systematically associated with insulin resistance and the metabolic syndrome, where behavior therapy remains the primary treatment, simultaneously addressing all the clinical and biochemical defects. However, very few studies have tested the effectiveness of intensive behavior therapy in NAFLD, aimed at lifestyle modifications to produce stable weight loss by reduced calorie intake and increased physical activity. Searching the literature for studies testing weight loss and lifestyle modifications for the treatment of NAFLD, only 14 reports were traced where the entry assessment satisfied well-defined criteria. The final effectiveness was based on hard histological outcomes in 5 cases. All but 1 were pilot, uncontrolled studies or limited case series, and in general the details of treatment were scanty. In only 3 cases treatment was carried out along the guidelines of behavior treatment to reduce excess nutrition and increase exercise; in these cases, a remarkable effect on weight loss and an improvement in liver histology were reported. The principles of behavior therapy are presented in detail, to help physicians change their prescriptive attitude into a more empowerment-based approach. A brief section is also included on the practical aspects and public policies to be implemented at societal level to obtain the maximum effects in lifestyle changes. There is a need for multidisciplinary teams including dietitians, psychologists, and physical activity supervisors caring for patients with NAFLD. Alternatively, general practitioners and physicians working in gastrointestinal units should limit their intervention to engage patients with NAFLD before referral to specialized teams set up for the treatment of diabetes and obesity. (HEPATOLOGY 2008;47: 746-754.) N onalcoholic fatty liver disease (NAFLD) is a relevant challenge for gastroenterology and liver units. The disease is highly prevalent in the Western countries (approximately 25%-30% of the adult population), 1 and 1 patient in 3 is expected to have non-alcoholic steatohepatitis (NASH), which has the potential to progress to cryptogenic cirrhosis and advanced liver failure. NAFLD is associated with metabolic syndrome and its individual components, 2,3 and both being overweight or obese 4 and having prediabetes/type 2 diabetes 5 have been identified as risk factors for disease progression. Accordingly, NAFLD treatment and the prevention of disease progression are largely based on weight loss and insulin-sensitizing drugs, even if only a few controlled studies are available. In most cases, both the control and the experimental group were given nutritional counseling, with some extra drugs (insulin-sensitizers, antioxidants, lipid-lowering, and the like) in the experimental arm. The problem in all these studies lies in the definition of the lifestyle-modifying control treatment. We have already brought to the attention of the scientific community a superficial attitude in the definition of programs aimed at lifestyle modifications. 6 In general, the programs referred to as "nutritional counseling" are not structured according to the principles of behavioral treatment, and the intervention is limited to diet prescription.
BioMed research international, 2018
Chronic inflammatory response is one of major contributors in the development of hepatocellular c... more Chronic inflammatory response is one of major contributors in the development of hepatocellular carcinoma (HCC). Inflammatory molecules, such as cytokines and growth factors in the circulation, can be useful in the diagnosis and prognosis of the patients. The stem cell growth factor beta (SCGF), a newly found protein, is a secreted sulfated glycoprotein and it functions as a growth factor for primitive hematopoietic progenitor cells. The level of SCGF had been reported to be elevated in several cancer types. However, there is very few or even no information on this protein in the study of HCC, even more in clinical studies. A multiplex immunoassay panel of 48 cytokines and growth factors were utilized to screen 68 sera from 29 HCC patients at pretreatment (T0), 1 month (T1), and 6 months (T6) after treatment by either radiofrequency ablation (RF) or transarterial chemoembolization (TACE). Treatment response was evaluated according to mRECIST criteria. Immunoassay screening showed th...
Liver international : official journal of the International Association for the Study of the Liver, Jan 26, 2017
Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disorder, tightly associated with ob... more Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disorder, tightly associated with obesity. The histological spectrum of the disease ranges from simple steatosis to steatohepatitis, with different stages of fibrosis, and fibrosis stage is the most significant predictor of mortality in NAFLD. Liver biopsy continues to be the gold standard for its diagnosis and reliable non-invasive diagnostic tools are unavailable. We investigated the accuracy of candidate proteins, identified by an in silico approach, as biomarkers for diagnosis of fibrosis. 71 morbidly obese (MO) subjects with biopsy-proven NAFLD were enrolled, and the cohort was subdivided according to minimal (F0/F1) or moderate (F2/F3) fibrosis. The plasmatic level of CD44 antigen (CD44), secreted protein acidic and rich in cysteine (SPARC), epidermal growth factor receptor (EGFR) and insulin-like growth factor 2 (IGF2) were determined by ELISA. Significant associations between plasmatic levels and histological fibro...
Cutis, 2016
Strontium ranelate, which is used for postmenopausal osteoporosis, has been associated with drug ... more Strontium ranelate, which is used for postmenopausal osteoporosis, has been associated with drug rash with eosinophilia and systemic symptoms (DRESS) syndrome, a severe, acute, potentially fatal, multisystem adverse drug reaction characterized by skin rash, fever, hematological abnormalities, and lymphadenopathy with involvement of several internal organs. We report the case of a woman who developed DRESS syndrome with a generalized maculopapular rash, eosinophilia, dyspnea, bilateral cervical lymphadenopathy, and reactivation of Epstein-Barr virus (EBV) with liver damage 3 weeks after administration of strontium ranelate for postmenopausal osteoporosis. Approximately 6 months after total remission of cutaneous symptoms, the patient developed autoimmune hepatitis. This case confirms that strontium ranelate should be considered as a possible factor in the etiopathology of DRESS syndrome as well as in the subsequent development of autoimmune hepatitis. The possibility of developing au...
Annals of hepatology
Introduction and aim. Liver disease is associated with cognitive dysfunction also at early stage... more Introduction and aim. Liver disease is associated with cognitive dysfunction also at early stages, and minimal hepatic encephalopathy, affecting 20-70% of patients, is frequently under-recognized. The main purpose of this work was to demonstrate that a substantial number of patients, enrolled due to an acute confusional state in absence of a diagnosis of liver disease, suffers of hepatic encephalopathy. Before a diagnosis of a well-compensated liver diseases was performed, 410 patients with an acute confusional state were enrolled in this study. Even in the presence of minimal alterations of hepatic function, the psychometric tests applied demonstrated early signs of cerebral frontal alteration. The alteration was associated with the severity of liver disease, paralleling the progression of the patient to minimal hepatic failure or chronic liver disease. These psychometric tests are essential to detect early and subclinical frontal failure. Frontal dysfunction may be a useful tool ...
World journal of hepatology, Jan 27, 2010
Hepatocellular carcinoma (HCC) is one of most common malignancies in the world. Systemic treatmen... more Hepatocellular carcinoma (HCC) is one of most common malignancies in the world. Systemic treatments for HCC, particularly for advanced stages, are limited by the drug resistance phenomenon which ultimately leads to therapy failure. Recent studies have indicated an association between drug resistance and the existence of the cancer stem cells (CSCs) as tumor initiating cells. The CSCs are resistant to conventional chemotherapies and might be related to the mechanisms of the ATP Binding Cassette (ABC) transporters and alterations in the CSCs signaling pathways. Therefore, to contribute to the development of new HCC treatments, further information on the characterization of CSCs, the modulation of the ABC transporters expression and function and the signaling pathway involved in the self renewal, initiation and maintenance of the cancer are required. The combination of transporters modulators/inhibitors with molecular targeted therapies may be a potent strategy to block the tumoral pro...
Journal of Clinical Pathology, 2006
To report a retrospective analysis on the presence of hepatitis B virus (HBV), hepatitis C virus ... more To report a retrospective analysis on the presence of hepatitis B virus (HBV), hepatitis C virus (HCV), and transfusion transmitted virus (TTV) sequences in formalin fixed, paraffin embedded liver biopsies from eight patients with hepatocellular carcinoma, in comparison with blood markers. A direct in situ polymerase chain reaction (PCR) technique was developed for the detection and localisation of genomic signals in the liver tissue. Conventional serological and molecular methods were used for blood evaluation. In situ PCR showed the presence of one of the three viruses (four HCV, two HBV, and one TTV) in seven of the eight patients. In addition, a co-infection with HBV and HCV was detected in one patient. HCV and HBV sequences were located in the cytoplasm and the nucleus, respectively. When compared with blood markers, these findings were compatible with one occult HBV and two occult HCV infections. These findings provide further evidence for occult HBV and HCV infections in cancerous tissues from patients with hepatocellular carcinomas. In situ PCR could be an additional tool for evaluating the viral aetiology of hepatocellular carcinoma alongside conventional diagnostic procedures.
Annals of …, 2006
Background: Despite the availability of effective vaccines, hepatitis B virus (HBV) infection is ... more Background: Despite the availability of effective vaccines, hepatitis B virus (HBV) infection is still frequent world-wide, and accounts for significant morbidity and mortal-ity. However, data of acute HBeAg negative hepatitis still remain limited. Aims and Methods: To understand ...
BMC Gastroenterology, 2012
Background: The Breast Cancer Resistance Protein (BCRP/ABCG2) is one member of ABC transporters p... more Background: The Breast Cancer Resistance Protein (BCRP/ABCG2) is one member of ABC transporters proteins super family responsible of drug resistance. Since data on ABCG2 expression in liver malignances are scanty, here we report the expression of ABCG2 in adult human hepatocellular carcinoma (HCC) in both in vivo and in vitro models with different degree of malignancy.
Biochemical and Biophysical Research Communications, 1993
PloS one, 2015
Human Hepatocellular Carcinoma (HCC) is the fifth most frequent neoplasm worldwide and the most s... more Human Hepatocellular Carcinoma (HCC) is the fifth most frequent neoplasm worldwide and the most serious complication of long-standing chronic liver diseases (CLD). Its development is associated with chronic inflammation and sustained oxidative stress. Deregulation of apurinic apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1), a master regulator of cellular response to oxidative stress, has been associated with poor prognosis in several cancers including HCC. In the present study we investigated the APE1/Ref-1 mRNA levels in cirrhotic and HCC tissues obtained during HCC resection. The possible protective role of APE1/Ref-1 against oxidative stress and apoptosis was evaluated in vitro in immortalized human hepatocytes (IHH) over-expressing APE1/Ref-1. APE1/Ref-1 was up-regulated in HCC, regulation occurring at the transcriptional level. APE1/Ref-1 mRNA content increased with the progression of liver disease with the transcriptional up-regulation present in cirrhosis sig...
Molecular medicine (Cambridge, Mass.)
APE1/Ref-1, normally localized in the nucleus, is a regulator of the cellular response to oxidati... more APE1/Ref-1, normally localized in the nucleus, is a regulator of the cellular response to oxidative stress. Cytoplasmic localization has been observed in several tumors and correlates with a poor prognosis. Because no data are available on liver tumors, we investigated APE1/Ref-1 subcellular localization and its correlation with survival in 47 consecutive patients undergoing hepatocellular carcinoma (HCC) resection. APE1/Ref-1 expression was determined by immunohistochemistry in HCC and surrounding liver cirrhosis (SLC) and compared with normal liver tissue. Survival probability was evaluated using Kaplan-Meier curves (log-rank test) and Cox regression. Cytoplasmic expression of APE1/Ref-1 was significantly higher in HCC than in SLC (P = 0.00001); normal liver showed only nuclear reactivity. Patients with poorly differentiated HCC showed a cytoplasmic expression three times higher than those with well-differentiated HCC (P = 0.03). Cytoplasmic localization was associated with a medi...
Annals of Hepatology, 2020
Introduction: Spleen stiffness (SS) has been found to mirror dynamic changes in portal pressure a... more Introduction: Spleen stiffness (SS) has been found to mirror dynamic changes in portal pressure after transjugular intrahepatic portosystemic shunt (TIPS) placement. However, there is no data available regarding SS in patients with spontaneous portosystemic shunting (SPSS), especially in regards to prediction of hepatic decompensation. Methods: We retrospectively selected patients with confirmed SPSS and esophageal varices (EVs) at endoscopic examination, and recorded any decompensating event (i.e., variceal hemorrhage, overt hepatic encephalopathy, refractory ascites, spontaneous bacterial peritonitis, hepatorenal syndrome) in the first twelve months following liver and spleen elastography. Results: The patients who presented decompensating events showed lower platelet count (94.5 vs. 121.5 g/L, p < 0.001), higher SS (44 vs. 30 kPa, p < 0.001), higher probability of EVs according to SS (77 vs. 2 %, p < 0.001), and higher spleen diameter (14 vs. 12 cm, p = 0.043). They also showed a higher prevalence of splenorenal shunts (66.7 vs. 31.2%), and a significantly wider SPSS major diameter (14.5 vs. 8 mm, p < 0.001). Conclusion: SS could predict SPSS efficacy in relieving portal pressure, and could predict decompensating events in patients with SPSS.
Journal of Medical Virology, 1994
The presence of the "Japanese type" NS4 region was investigated in two series of patients (53 fro... more The presence of the "Japanese type" NS4 region was investigated in two series of patients (53 from Italy and 58 from Japan) with hepatitis C virus (HCV)-related chronic liver disease. The two populations were homogeneous as regard to age, male/female ratio, histological diagnosis, and serum aminotransferase activities. Genomic amplification was carried out by "nested" polymerase chain reaction (PCR) with a pair of primers synthesized according to the sequence of JK-1 isolated in Japan. The presence of viral replication was confirmed further by PCR amplification of the 5°C region. The NS4 region of the Japanese strain was detected in 24 sera (45%) from Italy and in 44 (71%) from Japan. NS4-positive patients were significantly older and showed an ALT serum level significantly lower (P < 0.01) than NS4 negative cases in each group. Cirrhosis was significantly (P < 0.0007) more common in NS4-positive than in NSCnegative patients. The HCV genotype was subsequently obtained according to Okamoto. All the NS4-positive patients were infected by Type ll, whereas in NS4negative patients all four genotypes were present though Type II still constituted the majority. Cirrhosis was associated exclusively with Type II both in NS4-positive and-negative subjects. These data indicate that, although the positivity for NS4 "Japanese" region seems to be associated with a more aggressive liver disease, the most prevalent Type II predicts more specifically those who are likely to develop cirrhosis. Since the same findings were obtained in two population from different areas of the world, the genotype of HCV appears to be one of the major determinants of the progression of chronic active hepatitis to cirrhosis.
Journal of Hepatology, 2001
Hepatology, 2007
Nonalcoholic fatty liver disease (NAFLD) is systematically associated with insulin resistance and... more Nonalcoholic fatty liver disease (NAFLD) is systematically associated with insulin resistance and the metabolic syndrome, where behavior therapy remains the primary treatment, simultaneously addressing all the clinical and biochemical defects. However, very few studies have tested the effectiveness of intensive behavior therapy in NAFLD, aimed at lifestyle modifications to produce stable weight loss by reduced calorie intake and increased physical activity. Searching the literature for studies testing weight loss and lifestyle modifications for the treatment of NAFLD, only 14 reports were traced where the entry assessment satisfied well-defined criteria. The final effectiveness was based on hard histological outcomes in 5 cases. All but 1 were pilot, uncontrolled studies or limited case series, and in general the details of treatment were scanty. In only 3 cases treatment was carried out along the guidelines of behavior treatment to reduce excess nutrition and increase exercise; in these cases, a remarkable effect on weight loss and an improvement in liver histology were reported. The principles of behavior therapy are presented in detail, to help physicians change their prescriptive attitude into a more empowerment-based approach. A brief section is also included on the practical aspects and public policies to be implemented at societal level to obtain the maximum effects in lifestyle changes. There is a need for multidisciplinary teams including dietitians, psychologists, and physical activity supervisors caring for patients with NAFLD. Alternatively, general practitioners and physicians working in gastrointestinal units should limit their intervention to engage patients with NAFLD before referral to specialized teams set up for the treatment of diabetes and obesity. (HEPATOLOGY 2008;47: 746-754.) N onalcoholic fatty liver disease (NAFLD) is a relevant challenge for gastroenterology and liver units. The disease is highly prevalent in the Western countries (approximately 25%-30% of the adult population), 1 and 1 patient in 3 is expected to have non-alcoholic steatohepatitis (NASH), which has the potential to progress to cryptogenic cirrhosis and advanced liver failure. NAFLD is associated with metabolic syndrome and its individual components, 2,3 and both being overweight or obese 4 and having prediabetes/type 2 diabetes 5 have been identified as risk factors for disease progression. Accordingly, NAFLD treatment and the prevention of disease progression are largely based on weight loss and insulin-sensitizing drugs, even if only a few controlled studies are available. In most cases, both the control and the experimental group were given nutritional counseling, with some extra drugs (insulin-sensitizers, antioxidants, lipid-lowering, and the like) in the experimental arm. The problem in all these studies lies in the definition of the lifestyle-modifying control treatment. We have already brought to the attention of the scientific community a superficial attitude in the definition of programs aimed at lifestyle modifications. 6 In general, the programs referred to as "nutritional counseling" are not structured according to the principles of behavioral treatment, and the intervention is limited to diet prescription.
BioMed research international, 2018
Chronic inflammatory response is one of major contributors in the development of hepatocellular c... more Chronic inflammatory response is one of major contributors in the development of hepatocellular carcinoma (HCC). Inflammatory molecules, such as cytokines and growth factors in the circulation, can be useful in the diagnosis and prognosis of the patients. The stem cell growth factor beta (SCGF), a newly found protein, is a secreted sulfated glycoprotein and it functions as a growth factor for primitive hematopoietic progenitor cells. The level of SCGF had been reported to be elevated in several cancer types. However, there is very few or even no information on this protein in the study of HCC, even more in clinical studies. A multiplex immunoassay panel of 48 cytokines and growth factors were utilized to screen 68 sera from 29 HCC patients at pretreatment (T0), 1 month (T1), and 6 months (T6) after treatment by either radiofrequency ablation (RF) or transarterial chemoembolization (TACE). Treatment response was evaluated according to mRECIST criteria. Immunoassay screening showed th...
Liver international : official journal of the International Association for the Study of the Liver, Jan 26, 2017
Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disorder, tightly associated with ob... more Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disorder, tightly associated with obesity. The histological spectrum of the disease ranges from simple steatosis to steatohepatitis, with different stages of fibrosis, and fibrosis stage is the most significant predictor of mortality in NAFLD. Liver biopsy continues to be the gold standard for its diagnosis and reliable non-invasive diagnostic tools are unavailable. We investigated the accuracy of candidate proteins, identified by an in silico approach, as biomarkers for diagnosis of fibrosis. 71 morbidly obese (MO) subjects with biopsy-proven NAFLD were enrolled, and the cohort was subdivided according to minimal (F0/F1) or moderate (F2/F3) fibrosis. The plasmatic level of CD44 antigen (CD44), secreted protein acidic and rich in cysteine (SPARC), epidermal growth factor receptor (EGFR) and insulin-like growth factor 2 (IGF2) were determined by ELISA. Significant associations between plasmatic levels and histological fibro...
Cutis, 2016
Strontium ranelate, which is used for postmenopausal osteoporosis, has been associated with drug ... more Strontium ranelate, which is used for postmenopausal osteoporosis, has been associated with drug rash with eosinophilia and systemic symptoms (DRESS) syndrome, a severe, acute, potentially fatal, multisystem adverse drug reaction characterized by skin rash, fever, hematological abnormalities, and lymphadenopathy with involvement of several internal organs. We report the case of a woman who developed DRESS syndrome with a generalized maculopapular rash, eosinophilia, dyspnea, bilateral cervical lymphadenopathy, and reactivation of Epstein-Barr virus (EBV) with liver damage 3 weeks after administration of strontium ranelate for postmenopausal osteoporosis. Approximately 6 months after total remission of cutaneous symptoms, the patient developed autoimmune hepatitis. This case confirms that strontium ranelate should be considered as a possible factor in the etiopathology of DRESS syndrome as well as in the subsequent development of autoimmune hepatitis. The possibility of developing au...
Annals of hepatology
Introduction and aim. Liver disease is associated with cognitive dysfunction also at early stage... more Introduction and aim. Liver disease is associated with cognitive dysfunction also at early stages, and minimal hepatic encephalopathy, affecting 20-70% of patients, is frequently under-recognized. The main purpose of this work was to demonstrate that a substantial number of patients, enrolled due to an acute confusional state in absence of a diagnosis of liver disease, suffers of hepatic encephalopathy. Before a diagnosis of a well-compensated liver diseases was performed, 410 patients with an acute confusional state were enrolled in this study. Even in the presence of minimal alterations of hepatic function, the psychometric tests applied demonstrated early signs of cerebral frontal alteration. The alteration was associated with the severity of liver disease, paralleling the progression of the patient to minimal hepatic failure or chronic liver disease. These psychometric tests are essential to detect early and subclinical frontal failure. Frontal dysfunction may be a useful tool ...
World journal of hepatology, Jan 27, 2010
Hepatocellular carcinoma (HCC) is one of most common malignancies in the world. Systemic treatmen... more Hepatocellular carcinoma (HCC) is one of most common malignancies in the world. Systemic treatments for HCC, particularly for advanced stages, are limited by the drug resistance phenomenon which ultimately leads to therapy failure. Recent studies have indicated an association between drug resistance and the existence of the cancer stem cells (CSCs) as tumor initiating cells. The CSCs are resistant to conventional chemotherapies and might be related to the mechanisms of the ATP Binding Cassette (ABC) transporters and alterations in the CSCs signaling pathways. Therefore, to contribute to the development of new HCC treatments, further information on the characterization of CSCs, the modulation of the ABC transporters expression and function and the signaling pathway involved in the self renewal, initiation and maintenance of the cancer are required. The combination of transporters modulators/inhibitors with molecular targeted therapies may be a potent strategy to block the tumoral pro...
Journal of Clinical Pathology, 2006
To report a retrospective analysis on the presence of hepatitis B virus (HBV), hepatitis C virus ... more To report a retrospective analysis on the presence of hepatitis B virus (HBV), hepatitis C virus (HCV), and transfusion transmitted virus (TTV) sequences in formalin fixed, paraffin embedded liver biopsies from eight patients with hepatocellular carcinoma, in comparison with blood markers. A direct in situ polymerase chain reaction (PCR) technique was developed for the detection and localisation of genomic signals in the liver tissue. Conventional serological and molecular methods were used for blood evaluation. In situ PCR showed the presence of one of the three viruses (four HCV, two HBV, and one TTV) in seven of the eight patients. In addition, a co-infection with HBV and HCV was detected in one patient. HCV and HBV sequences were located in the cytoplasm and the nucleus, respectively. When compared with blood markers, these findings were compatible with one occult HBV and two occult HCV infections. These findings provide further evidence for occult HBV and HCV infections in cancerous tissues from patients with hepatocellular carcinomas. In situ PCR could be an additional tool for evaluating the viral aetiology of hepatocellular carcinoma alongside conventional diagnostic procedures.
Annals of …, 2006
Background: Despite the availability of effective vaccines, hepatitis B virus (HBV) infection is ... more Background: Despite the availability of effective vaccines, hepatitis B virus (HBV) infection is still frequent world-wide, and accounts for significant morbidity and mortal-ity. However, data of acute HBeAg negative hepatitis still remain limited. Aims and Methods: To understand ...
BMC Gastroenterology, 2012
Background: The Breast Cancer Resistance Protein (BCRP/ABCG2) is one member of ABC transporters p... more Background: The Breast Cancer Resistance Protein (BCRP/ABCG2) is one member of ABC transporters proteins super family responsible of drug resistance. Since data on ABCG2 expression in liver malignances are scanty, here we report the expression of ABCG2 in adult human hepatocellular carcinoma (HCC) in both in vivo and in vitro models with different degree of malignancy.
Biochemical and Biophysical Research Communications, 1993
PloS one, 2015
Human Hepatocellular Carcinoma (HCC) is the fifth most frequent neoplasm worldwide and the most s... more Human Hepatocellular Carcinoma (HCC) is the fifth most frequent neoplasm worldwide and the most serious complication of long-standing chronic liver diseases (CLD). Its development is associated with chronic inflammation and sustained oxidative stress. Deregulation of apurinic apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1), a master regulator of cellular response to oxidative stress, has been associated with poor prognosis in several cancers including HCC. In the present study we investigated the APE1/Ref-1 mRNA levels in cirrhotic and HCC tissues obtained during HCC resection. The possible protective role of APE1/Ref-1 against oxidative stress and apoptosis was evaluated in vitro in immortalized human hepatocytes (IHH) over-expressing APE1/Ref-1. APE1/Ref-1 was up-regulated in HCC, regulation occurring at the transcriptional level. APE1/Ref-1 mRNA content increased with the progression of liver disease with the transcriptional up-regulation present in cirrhosis sig...
Molecular medicine (Cambridge, Mass.)
APE1/Ref-1, normally localized in the nucleus, is a regulator of the cellular response to oxidati... more APE1/Ref-1, normally localized in the nucleus, is a regulator of the cellular response to oxidative stress. Cytoplasmic localization has been observed in several tumors and correlates with a poor prognosis. Because no data are available on liver tumors, we investigated APE1/Ref-1 subcellular localization and its correlation with survival in 47 consecutive patients undergoing hepatocellular carcinoma (HCC) resection. APE1/Ref-1 expression was determined by immunohistochemistry in HCC and surrounding liver cirrhosis (SLC) and compared with normal liver tissue. Survival probability was evaluated using Kaplan-Meier curves (log-rank test) and Cox regression. Cytoplasmic expression of APE1/Ref-1 was significantly higher in HCC than in SLC (P = 0.00001); normal liver showed only nuclear reactivity. Patients with poorly differentiated HCC showed a cytoplasmic expression three times higher than those with well-differentiated HCC (P = 0.03). Cytoplasmic localization was associated with a medi...