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Biomedical subjects

Luigi Bolondi

Publications and source records attributed to Luigi Bolondi.

At least 19 recordsLinked to original sources
PubMed2007

Characterization of liver lesions by real-time contrast-enhanced ultrasonography.

OBJECTIVE: The aim of this study was to identify the most common patterns of various common liver lesions at real-time contrast-enhanced ultrasonography with second-generation contrast agents and their role in the differentiation of malignant from benign lesions. PATIENTS AND METHODS: The enhancement pattern in the arterial phase and its modifications in subsequent portal and sinusoidal phases were separately evaluated in (i) 171 liver lesions detected at conventional ultrasonography in 125 noncirrhotic patients (87 metastases, six cholangiocellular carcinoma, 38 focal nodular hyperplasia, 30 hemangiomas, seven focal fatty sparing/changes, two hepatocellular adenomas and one hepatocellular carcinoma) and (ii) 75 lesions detected in 67 cirrhotic patients (66 hepatocellular carcinoma and nine dysplastic nodules). The final diagnosis was made by contrast-enhanced helical computed tomography and/or magnetic resonance imaging or by ultrasonography-guided biopsy when the diagnosis was equivocal at conventional imaging techniques (45 lesions). RESULTS: In noncirrhotic patients, the hypoechoic pattern in portal and sinusoidal phase (rapid washout) or the markedly hypoechoic or anechoic pattern in sinusoidal phase (marked late washout) showed a sensitivity, specificity and accuracy of 96.8, 100 and 98.2% for the diagnosis of malignancy. In cirrhotic patients, early arterial enhancement showed a sensitivity of 93.9% for the diagnosis of malignancy, with a specificity as low as 55.5% given the presence of arterial enhancement in 5/9 nodules resulted dysplastic at histological analysis. CONCLUSION: Real-time contrast-enhanced ultrasonography provides sensitive and specific criteria for the differential diagnosis between benign and malignant liver lesions, and in most cases it may replace more expensive and invasive imaging techniques.

Adenoma, Liver Cell↗
PubMed2006

Effect of potassium canrenoate, an anti-aldosterone agent, on incidence of ascites and variceal progression in cirrhosis.

BACKGROUND & AIMS: Because aldosterone-dependent sodium and water retention contribute to portal hypertension, the safety and effect of an antialdosteronic drug (Kcanrenoate) have been evaluated on the occurrence of de novo appearance of ascites and the development of esophageal varices or the progression of small varices. METHODS: Inclusion criteria were as follows: Child-Pugh A viral pre-ascitic cirrhosis, with either F1 esophageal varices or no varices, but endoscopic and/or ultrasound evidence of portal hypertension. Thirteen Italian Liver Units prospectively enrolled 120 patients randomized to receive double-blind either Kcanrenoate (100 mg/day; 66 patients) or placebo (54 patients). Endoscopy and sonography were performed at entry and at 52 weeks unless the patient developed ascites earlier, whereas laboratory examinations were performed at entry and every 3 months thereafter. An intention-to-treat analysis was performed, with each end point assessed by the Fisher exact test; the cumulative risk for the appearance of any end point was analyzed by the adjusted log-rank test (Tarone-Ware), with censoring for drop-outs. RESULTS: The progression of variceal status or appearance of ascites, analyzed independently, was not significantly more frequent on placebo (24.1% and 9.2%, respectively) than on Kcanrenoate (12.1% and 1.5%, respectively), whereas the cumulative occurrence of end points was decreased on Kcanrenoate (17.6% vs 38.3% with placebo; P < .05, Tarone-Ware test). The incidence of adverse events was negligible and did not differ between groups. CONCLUSIONS: This preliminary study shows that 100 mg/day of Kcanrenoate is well tolerated and does not reduce the individual incidence of ascites and/or the appearance or progression of esophageal varices in preascitc cirrhosis, but may decrease their 1-year cumulative occurrence.

Aged↗
PubMed2006

Outcomes from a program of home care attendance in very frail elderly subjects.

This study evaluated various outcomes of home care in a group of 121 chronically ill and frail elderly subjects followed for 24 months, starting from September 2001. The scheduled times of follow up were baseline, 6, 12, and 24 months. Subjects of both sexes were assigned to one of two groups. Control group (CG) (60 subjects: mean age 85.4 years, home care provided by the Social Health Service of the Emilia Romagna Region) and Intervention group (IG) (61 subjects, mean age 82.0 years), for whom the institutional home care was empowered providing a home care attendant. The home care attendant was a person trained in the care of the frail elderly. He/she served from 4 to 24 h daily, according to a program established by a Geriatric Evaluation Unit, considering the needs of the subject and of his/her family members. The cost of the additional home care attendance (HCA) was sponsored (totally or in part), by the "Fondazione del Monte di Bologna e di Ravenna", a non profit foundation. This report takes into consideration the data coming from the first 24 months of follow-up. The two groups were homogenous at baseline. Genetic/molecular pattern including interleukine-1-beta (IL-1b), alfa1-antichimotrypsine (a1ACT), apolipoprotein E4 (APOE4), interleukine-6 (IL-6), tumor necrosis factor-alfa (TNFa), and progression of frailty and disability were considered and discussed. Mortality was lower in the IG than in the CG at 6, 12, and 24 months. Depressive symptoms and disability increased more in IG than in CG; a decrease of the stress of the family members was observed in the IG. The number of drugs used was higher in the CG than in the IG. These outcomes can be related to the additional program of home attendance. The correlation between pro-inflammatory cytokine levels and degree of frailty are observed in both groups without statistically significant difference.

Aged, 80 and over↗
PubMed2006

The safety of Sonovue in abdominal applications: retrospective analysis of 23188 investigations.

The aim of the present retrospective study was to assess the incidence of adverse events (AE) of a second-generation ultrasound contrast agent in real clinical practice. A total of 28 Italian Centres provided data on the postmarketing use of SonoVue (Bracco Spa, Milan, Italy) in abdominal examination performed between December 2001 and December 2004. A total of 23 188 investigations were reported. No fatal event occurred. AEs were reported in 29 cases, of which only two were graded as serious; the rest, 27, were nonserious (23 mild, three moderate and one severe). The overall reporting rate of serious AE was 0.0086%. Overall, only four AEs required treatment (two serious, two nonserious including one moderate and one severe AEs). In conclusion, the present large-scale retrospective analysis showed that SonoVue has a good safety profile in abdominal applications, with an AE reporting rate lower than or similar to that reported for radiologic and magnetic resonance contrast agents.

Abdomen↗
PubMed2006

Prediction of significant fibrosis in hepatitis C virus infected liver transplant recipients by artificial neural network analysis of clinical factors.

OBJECTIVES: Interest in developing noninvasive markers of liver fibrosis continues to increase, especially in recurrent hepatitis C virus infection after liver transplantation. Recently, a model for predicting significant fibrosis (bridging fibrosis and cirrhosis) on the basis of logistic regression and routine laboratory data has been proposed (logit model). The aim of the present study was to evaluate the accuracy of an artificial neural network, a technique reported to work better than logit models in complex biological situations, built on those same clinical variables and data set of patients, in predicting significant fibrosis. METHODS: The neural network was constructed on the training set of 414 protocol biopsies, from liver transplant recipients, and then tested on the remaining 96 biopsies, as validation set. Model performances of neural network and logit model were evaluated and compared by means of areas under receiver operating characteristic curves. RESULTS: With a cutoff value of >0.4 to predict significant fibrosis, the neural network provided sensitivity, specificity, positive and negative predictive values, respectively, of 100, 79.5, 60.5 and 100%, in the validation set. The performance of the neural network was significantly better than that of the logit model (in the validation set area under the curve = 0.93 vs. 0.84; P = 0.045). CONCLUSIONS: Artificial neural network provides accurate prediction of the presence or absence of significant fibrosis from clinical variables, allowing theoretically protocol liver biopsy to be avoided in several instances, a result of particular interest, given the lack of other types of reliable noninvasive indexes of fibrosis in the setting of transplantation.

Adult↗
PubMed2006

A conjugate of doxorubicin with lactosaminated albumin enhances the drug concentrations in all the forms of rat hepatocellular carcinomas independently of their differentiation grade.

BACKGROUND/AIMS: Doxorubicin (DOXO) was coupled to lactosaminated human serum albumin (L-HSA) in order to enhance the drug concentration in the well differentiated hepatocellular carcinomas (HCCs), which can accumulate L-HSA through the asialoglycoprotein receptor. In the present experiments we compared the DOXO concentrations produced by this conjugate (L-HSA-DOXO) and by the uncoupled drug in the well, moderately, and poorly differentiated rat HCCs. METHODS: The same dose (1 microg/g) of free or L-HSA coupled-DOXO was injected in rats with HCCs induced by diethylnitrosamine. At different times, the animals were killed and the neoplastic nodules of liver were isolated. Their differentiation grade was determined histologically and their DOXO content was measured. RESULTS: Unexpectedly, we found that also in the poorly differentiated forms of HCCs, which display no or only a poor capacity of accumulating L-HSA, the conjugate raised DOXO levels that were approximately twofold higher than those produced by the free drug. CONCLUSIONS: The conjugate L-HSA-DOXO could improve the potential of DOXO in the treatment of all HCCs, including the poorly differentiated tumors that are the common forms in the advanced disease for which an effective chemotherapy is particularly needed.

Animals↗
PubMed2006

A modeling study of bilirubin kinetics during Molecular Adsorbent Recirculating System sessions.

This work presents a quantitative description, by means of a mathematical model, of bilirubin removal during Molecular Adsorbent Recirculating System sessions. The model includes four compartments: two for the patient, and two for the albumin circuit. Equations in each compartment express mass preservation, mass exchange between compartments, and bilirubin-albumin binding kinetics. Model development and validation are based on in vivo data of bilirubin concentration acquired in eight sessions at different times during the session. The accuracy of the model in reproducing real data is high (error in blood = -0.3 +/- 0.93 mg/dL), if three parameters, representing the depurative efficacy of the system (the dialysance of the blood filter and the initial and final clearance of the depurative elements in the albumin circuit), are estimated on each single session. However, model accuracy is only slightly deteriorated (error in blood = -0.4 +/- 0.99 mg/dL) if a single set of parameters (fixing the three parameters at their mean values) is adopted. These results suggest that the model may be used a priori (i.e., using a single set of parameters) to achieve a satisfactory prediction of the overall bilirubin removal, as well as a posteriori for the estimation of device parameters. The latter use may allow the investigation of the dependence of these parameters on the operative and clinical conditions, in the effort to arrive at a rationalization and optimization of the treatment.

Algorithms↗
PubMed2006

Metabolic Syndrome: prevalence and prediction of mortality in elderly individuals.

OBJECTIVE: Little is known about the prevalence of the metabolic syndrome among elderly people in Italy, its association with all-cause mortality, and whether measurement of serum C-reactive protein (CRP) and interleukin (IL)-6 affects this association. RESEARCH DESIGN AND METHODS: The baseline prevalence of metabolic syndrome, diagnosed according to the National Cholesterol Education Program (NCEP) criteria, and all-cause mortality at 4 years were recorded in an Italian population-based cohort (981 subjects, 55% women, aged 65-97 years). A Cox model adjusted for sociodemographic, lifestyle, and medical variables was used to investigate 1) whether metabolic syndrome was a predictor of mortality and 2) how the association was affected by baseline high CRP (>3 mg/l) and IL-6 (>1.33 pg/ml). RESULTS: Overall, metabolic syndrome prevalence was 27.2% [95% CI 24.0-30.5] and higher in women (33.3% [28.7-38.0]) than in men (19.6% [15.5-24.2]). During follow-up, 137 deaths occurred. Using the no metabolic syndrome/no high IL-6 group as the reference, mortality was not associated with the metabolic syndrome alone (multivariable-adjusted hazard ratio 1.24 [0.60-2.59]), only weakly associated with high IL-6 alone (1.66 [1.04-2.63]), but strongly associated with the concurrent presence of metabolic syndrome and high IL-6 (3.26 [2.00-5.33]). High CRP was not a mortality predictor (0.83 [0.58-1.20]) nor did it affect the association of the other variables with mortality. CONCLUSIONS: Metabolic syndrome by NCEP criteria is highly prevalent in the Italian elderly population. It is not itself associated with mortality but may improve the usefulness of IL-6 as a mortality predictor in older age.

Age Distribution↗
PubMed2005

Interleukin-1beta and interleukin-6 gene polymorphisms as risk factors for AD: a prospective study.

Risk of incident dementia from any cause and Alzheimer's disease (AD) in relation to the IL-1beta-511 (C-->T) and IL-6-174 (G-->C) polymorphisms was investigated in an Italian elderly cohort (n=791) with 4 years of follow-up. Analyses were adjusted for socio-demographic confounders (age, gender, education), presence of the Apolipoprotein E-epsilon4 allele, and plasma total homocysteine (tHcy), a newly proposed AD risk factor. No significant association was found for the IL-1beta-511 and IL-6-174 polymorphisms with either dementia or AD. However, in the baseline dementia-free cohort considered as a whole, independently of other confounders, IL-1beta-511 T/T homozygotes had lower plasma tHcy than both heterozygotes (P=0.036) and wild-types (P=0.004). These data do not support the hypothesis that the IL-1-beta-511 and IL-6-174 polymorphisms affect dementia or AD risk. The relationship between the AD risk factor plasma tHcy and the IL-1beta-511 polymorphism was never reported before and might explain previous cross-sectional reports of an association between this polymorphism and AD.

Aged↗
PubMed2005

GADD45-alpha expression in cirrhosis and hepatocellular carcinoma: relationship with DNA repair and proliferation.

Growth arrest and DNA damage 45-alpha (GADD45-alpha) is a nuclear protein involved in maintenance of genomic stability, DNA repair, and suppression of cell growth through interaction with nuclear elements, including cyclin-dependent kinase inhibitor 1A (CDKN1A) and PCNA. In this study, GADD45-alpha expression was assessed in 28 cases of hepatocellular carcinoma (HCC) and matched cirrhosis tissues, and correlated with the presence of DNA-bound PCNA and CDKN1A as markers of DNA repair, as well as with clinicopathologic variables including histopathologic grade, tumor size, nodularity, viral status, alpha-fetoprotein serum levels, and p53 and Ki67 immunostaining. GADD45-alpha and CDKN1A messenger RNA (mRNA) were analyzed by reverse transcriptase-polymerase chain reaction. GADD45-alpha protein expression was evaluated by Western blot (WB) and enzyme-linked immunosorbent assays (ELISAs). PCNA and CDKN1A DNA-bound fractions were determined by WB. GADD45-alpha mRNA was down-regulated in 20 of 26 HCCs with respect to matched cirrhosis, but no correlation was found with the corresponding protein levels assessed by both WB and ELISA. GADD45-alpha and CDKN1A protein levels were related to each other both in cirrhotic and in neoplastic tissues, and a concordant up- or down-regulation was observed in HCCs with respect to cirrhosis. DNA-bound PCNA and CDKN1A were present in 5 HCCs and were associated with higher GADD45-alpha protein levels assessed by ELISA. No significant association was found in HCCs between GADD45-alpha protein expression and histopathologic grading, nodule size, focality, and proliferation, whereas a positive correlation was found with alpha-fetoprotein serum levels. In conclusion, GADD45-alpha mRNA was down-regulated with respect to matched cirrhosis in most HCCs; however, no correlation was found between mRNA and protein levels. GADD45-alpha protein levels were higher in HCCs with DNA-bound CDKN1A and PCNA, suggesting a possible role in DNA repair.

Aged↗
PubMed2005

Characterization of small nodules in cirrhosis by assessment of vascularity: the problem of hypovascular hepatocellular carcinoma.

In a prospective study, we examined the impact of arterial hypervascularity, as established by the European Association for the Study of the Liver (EASL) recommendations, as a criterion for characterizing small (1-3 cm) nodules in cirrhosis. A total of 72 nodules (1-2 cm, n = 41; 2.1-3 cm, n = 31) detected by ultrasonography in 59 patients with cirrhosis were included in the study. When coincidental arterial hypervascularity was detected at contrast perfusional ultrasonography and helical computed tomography, the lesion was considered to be hepatocellular carcinoma (HCC) according to EASL criteria. When one or both techniques showed negative results, ultrasound-guided biopsy was performed. In cases with negative results for malignancy or high-grade dysplasia, biopsy was repeated when an increase in size was detected at the 3-month follow-up examination. Coincidental hypervascularity was found in 44 of 72 nodules (61%; 44% of 1-2-cm nodules and 84% of 2-3-cm nodules). Fourteen nodules (19.4%) had negative results with both techniques (hypovascular nodules). Biopsy showed HCC in 5 hypovascular nodules and in 11 of 14 nodules with hypervascularity using only one technique. All nodules larger than 2 cm finally resulted to be HCC. Not satisfying the EASL imaging criteria for diagnosis were 38% of HCCs 1 to 2 cm (17% hypovascular) and 16% of those 2 to 3 cm (none hypovascular). In conclusion, the noninvasive EASL criteria for diagnosis of HCC are satisfied in only 61% of small nodules in cirrhosis; thus, biopsy frequently is required in this setting. Relying on imaging techniques in nodules of 1 to 2 cm would miss the diagnosis of HCC in up to 38% of cases. Any nodule larger than 2 cm should be regarded as highly suspicious for HCC.

Aged↗
PubMed2005

Analysis of risk factors for tumor recurrence after liver transplantation for hepatocellular carcinoma: key role of immunosuppression.

To confirm recent observations about the relationship between immunosuppression and the recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT), we retrospectively analyzed 70 consecutive HCC patients who underwent LT and received cyclosporine (CsA)-based immunosuppression. CsA trough blood levels, measured with the same technique (fluorescence polarization immunoassay), were analyzed at different time points after transplantation. The exposure to the drug was calculated with the trapezoidal rule in each patient. CsA was associated with steroids in 26 patients and steroids and azathioprine in 44 patients. HCC recurred in 7 patients (10.0%). Different immunosuppressive schedules (CsA and steroids vs. CsA, steroids, and azathioprine) or the cumulative dosage of steroids and azathioprine did not influence HCC recurrence that was associated instead with CsA exposure (278.3 +/- 86.4 ng/mL in recurrent vs. 169.9 +/- 33.3 in tumor-free patients; P < 0.001); CsA exposure above 189.6 ng/mL was related to HCC recurrence at the receiver operating characteristic analysis (ROC). The relationship between CsA exposure; various clinical (sex, age, viral- vs. non-viral-related cirrhosis, preoperative vs. incidental diagnosis of HCC, alpha-fetoprotein [AFP] blood level), pathologic (pathologic tumor staging [pT] stage, presence of Milan criteria), and histologic (grading, presence of microvascular tumor invasion) parameters; and tumor recurrence were assessed. AFP (P = 0.032), microvascular tumor invasion (P = 0.044), and CsA exposure (P < 0.001) influenced recurrence-free survival at the univariate analysis; CsA exposure was the only independent prognostic determinant at multivariate analysis (P < 0.001). High CsA exposure favors tumor recurrence; CsA blood levels should be kept to the effective minimum in HCC patients. In the presence of pathologic and histologic risk factors, specific immunosuppressive protocols should be considered.

Adult↗
PubMed2005

Associations of the -174 G/C interleukin-6 gene promoter polymorphism with serum interleukin 6 and mortality in the elderly.

Serum interleukin-6 (sIL6) is an acknowledged predictor of all-cause mortality in older age. A common G/C polymorphism has been identified at position -174 of the IL6 gene promoter (IL6-174G>C), but its associations with sIL6 and mortality are still unclear. Data from a population-based elderly cohort (n=824) were used to study the associations of baseline sIL6 with the IL6-174 C-allele (C+) carrier status and all-cause mortality at 4 years, in the presence and absence of preexisting major diseases (PMD). Analyses were adjusted for socio-demographic factors and body-mass-index. Three-hundred-eighty-eight participants (47.1%) had PMD. Compared to the bottom sIL6 quartile, mortality increased both in presence [Hazard Ratio (HR)=3.04; 95% confidence interval (CI): 1.48-6.25] and absence of PMD [HR=3.91; 95%CI: 1.42-10.72] for the third higher sIL6 quartile, but only in presence of PMD for the top sIL6 quartile [HR=2.30; 95%CI: 1.09-4.83]. In absence of PMD, C+ carrier status did not affect both sIL6 and mortality. In presence of PMD, C+ carrier status was associated with increased baseline sIL6 [odds ratio 2.01; 95%CI: 1.25-3.22, for all sIL6 quartiles above the bottom] but not with increased mortality risk. A survival advantage was even found for C+ carriers with PMD and sIL6 in the top quartile [HR=0.31, 95%CI: 0.13-0.76]. In conclusion, although associated with increased sIL6 levels in presence of major diseases, the IL6-174 C-allele does not seem to have direct detrimental effects on survival in older age.

Aged↗
PubMed2005

Doxorubicin coupled to lactosaminated albumin inhibits the growth of hepatocellular carcinomas induced in rats by diethylnitrosamine.

BACKGROUND/AIMS: The hepatocyte receptor for asialoglycoproteins internalizes galactosyl terminating macromolecules which can be used as hepatotropic drug carriers. Since this receptor is also expressed on the cells of well differentiated human hepatocellular carcinomas (HCCs), we studied whether conjugation of doxorubicin (DOXO) with lactosaminated human albumin (L-HSA) increases the drug efficacy on HCCs induced in rats by diethylnitrosamine (DENA). METHODS: DENA was given in the drinking water for 8 weeks. One week after the last day of DENA administration, animals were randomly assigned to three groups. Each group was administered with either saline, free or coupled DOXO (1 microg/g). Rats received 4 weekly intravenous injections. One week after the last administration, rats were killed and HCC development was evaluated by counting the tumor nodules on the surface of hepatic lobes. RESULTS: In rats treated with L-HSA coupled DOXO the number of neoplastic nodules was significantly lower (P < 0.05) than that counted in animals injected with saline or with free DOXO. Coupled DOXO did not decrease body rat weight, which was markedly reduced by the free drug. CONCLUSIONS: Conjugation with L-HSA increased the antineoplastic efficacy and decreased the systemic toxicity of DOXO administered to rats with HCCs produced by DENA.

Animals↗
PubMed2005

Tumor doubling time predicts recurrence after surgery and describes the histological pattern of hepatocellular carcinoma on cirrhosis.

BACKGROUND/AIMS: Recurrence of hepatocellular carcinoma (HCC) following surgical resection is influenced by parameters detectable on the resection specimen or through a biopsy. The prognostic significance of HCC doubling time (DT) after surgery has never been investigated. METHODS: We evaluated 62 patients who underwent curative resection of a single HCC on cirrhosis; tumors were assessed before surgery on two subsequent occasions with the same imaging technique allowing the calculation of DT. The influence of tumor DT, clinical and pathological parameters on recurrence-rate and patients survival was assessed with uni- and multivariate analysis. Relationship between DT and pathological features was also analyzed. RESULTS: Three-year recurrence rate was 32.3% (20 patients): this was significantly higher in the presence of DT shorter than 100 days (58 versus 18% when equal to or longer; P=0.008), microvascular invasion (59 versus 17% when absent; P=0.008) or tumor undifferentiation (54 versus 25% when well/moderately differentiated; P=0.015). DT was the only independent predictor of recurrence (P=0.005). Patients survival was affected by Child-Pugh class only. DT was significantly shorter in tumors with microvascular invasion (P=0.007), undifferentiation (P=0.003) and high alpha-fetoprotein levels (P=0.011). CONCLUSIONS: DT is easy to estimate and indicates the prognosis of single HCCs prior to liver resection.

Aged↗
PubMed2005

Caution in the use of boldo in herbal laxatives: a case of hepatotoxicity.

A case is reported in which a several-fold increase in transaminases and gamma-GT was detected in an elderly male patient with fatty liver. The patient was regularly taking a mixture of herbal products, used as a laxative, for a number of years, with no alteration of blood chemistry until 6 months before the present observation. However, the composition of the mixture had been modified by the manufacturer in the past 5 months, with addition of boldo leaf extracts. Transaminases promptly returned to normal after withdrawal of the laxative. It is concluded that boldo leaf extracts might be hepatotoxic, at least in elderly patients with fatty liver.

Aged↗
PubMed2005

Enhanced uptake of lactosaminated human albumin by rat hepatocarcinomas: implications for an improved chemotherapy of primary liver tumors.

BACKGROUND/AIMS: The hepatocyte receptor for asialoglycoproteins (ASGP-R) internalizes macromolecules exposing galactosyl residues (MEGRs) which can be used as liver-addressed drug carriers. This receptor was also found on the cells of the large majority of well differentiated hepatocarcinomas (HCCs). The aim of the present experiments was to ascertain whether ASGP-R of HCCs is functionally active and these tumors can internalize higher quantities of MEGRs than extra-hepatic tissues. METHODS: We injected radioactive lactosaminated human albumin (L-HSA) in rats with HCCs produced by nitroso-diethylamine and measured the radioactivity of tumors, surrounding liver, heart, intestine and kidney. L-HSA is a MEGR successfully used in humans as a hepatotropic drug carrier. RESULTS: The levels of radioactivity of HCCs were two to three times lower than those of surrounding liver, but several times higher than those of extra-hepatic tissues. L-HSA accumulation in the tumors mainly occurred via the ASGP-R, as indicated by the 20 times lower penetration of non-lactosaminated HSA. L-HSA uptake by the well-differentiated tumors were four times higher compared with that by the poorly differentiated forms. CONCLUSIONS: The present results suggest that in the chemotherapy of HCCs expressing the ASGP-R the extra-hepatic toxicity of anticancer agents can be reduced by conjugation to L-HSA.

Animals↗