This is the first epidemiological study of Hepatocellular Carcinoma (HCC) in the province of Bergamo, an area well-known to have a high incidence of HBsAg (9.1%) and chronic alcoholic liver disease. 72 cases of HCC (60 male, 12 female) al from the province of Bergamo and encountered in 1980-84 were subjected to an epidemiological case-control study. Analysis of the results confirmed the role of certain known Risk Factors (RF) with a prevalence of male sex (83.3%), age (mean age 63), association with live cirrhosis (79.2%) and HBsAg+ (31.9%). Such findings are in line with the Italian average found in previous studies. No difference between the sexes was found in these RF except for alcoholic abuse which was significantly higher in the males (53.3%, p less than 0.05). The case-control correlation analysis revealed no difference in the prevalence of alcohol addiction and previous HBV infection (HBV-Ab+) between the HCC (with or without cirrhosis) and the various control groups (Group A: patients with no liver pathology. Group B: patients with cirrhosis of the liver). HBsAg+ was significantly higher among HCC patients without cirrhosis (46.6%, p less than 0.001), but there was no significant difference between HCC + cirrhosis and cirrhosis alone (88%). The difference between "expected" and "observed" HCC-HBsAg+ was highly significant (p less than 0.001). The overall Relative Risk (RR) of HCC for the RF-HBsAg+ was 4.6. When divided into subgroups this gave: RR = 1 for patients with cirrhosis of the liver. RR = 11.5 for patients with no liver pathology. These data confirm the importance of current HBV infection (HBsAg+), in the province, though the presence or absence of cirrhosis probably influences its significance. The approximate incidence of HCC is 9.7%/100,000/year. Considering the limitations of data on a small monocentric study in a limited area (USSL no. 30) the figure is probably underestimated and the real incidence probably higher.

Aged↗

PubMed1986

Isolation and characterization of complementary DNA clones for genes overexpressed in chemically induced rat hepatomas.

In order to characterize the genes overexpressed in an hepatoma cell line, the HTC cells, and in diethylnitrosamine induced solid hepatomas, we constructed a complementary DNA library from HTC cells and performed differential screening with probes from HTC cells, from malignant nodules obtained 70 weeks after the carcinogen treatment, and from hepatocytes from normal rat liver. Eight clones corresponding to messenger RNAs (mRNAs) much more expressed in hepatomas than in hepatocytes from normal liver were isolated. Three, clones pHT 71, pHT 13, and pHT 26, were further analyzed by the study of their corresponding transcripts in hepatocytes from regenerating liver and in the hepatocytes from the nontumorous parts of the liver. Clone pHT 71 corresponds to a single 2.3-kilobase mRNA which is present in high levels in carcinoma nodules in hepatoma cell lines, in the nontumorous parts of the liver, and in hepatocytes isolated from regenerating liver 30 h after partial hepatectomy. Clone pHT 13 hybridizes with three distinct transcripts 3.8, 2.6, and 1.6 kilobases long. High levels of the 3.8- and 1.6-kilobase mRNAs are present in carcinoma nodules, in hepatoma cell lines, and in the nontumorous parts of the liver. However, the levels of these RNAs are similar in hepatocytes from regenerating liver and in hepatocytes obtained from normal rat liver. Clone pHT 26 corresponds to a 0.6-kilobase mRNA which exists at a high level only in cancer nodules and in hepatoma cell lines. We were unable to observe any cross-hybridization between these clones and the oncogenes which have been found to be expressed in hepatomas (c-fos, c-Ha-ras, c-Ki-ras, N-ras, and c-myc). The mRNAs corresponding to the three clones have not been detected in various tissues from normal adult rats. Our study shows that a high level of these mRNAs might be associated with rat liver carcinogenesis.

Animals↗

PubMed1985

Expression of c-fos oncogene during hepatocarcinogenesis, liver regeneration and in synchronized HTC cells.

We have studied the expression of c-fos gene in rat hepatoma induced by DENA. An increase of c-fos mRNA concentration was observed after 8 days, but the maximal 5- to 6-fold increase was observed after 70 weeks. This increase was found in perinodular hepatocytes as well as in cancer nodules. c-fos expression was also enhanced during liver regeneration at a period corresponding to cell proliferation. In HTC cells the arrest of the cell cycle at early G1 phase by addition of sodium butyrate was accompanied by a strong increase of c-fos gene expression. However the c-fos mRNA rapidly decreased after removal of sodium butyrate during the progression of the cells in the cell cycle and increased transiently when the cells entered again in G1 phase.

Animals↗

PubMed1984

Correlated increase of the expression of the c-ras genes in chemically induced hepatocarcinomas.

The expression of the c-Ha-ras, the c-Ki-ras and the N-ras genes was measured by the dot blot technique in rat liver tumors induced by a short diethylnitrosamine (DENA) treatment and in the surrounding liver cells. A 2 to 25 times higher level of transcript was found as well in the surrounding cells, as in the tumor cells, as compared to the level in hepatocytes. In addition the increase of expression was parallel for the three ras genes. We conclude that this enhanced expression can be attributed to an epigenetic mechanism and it can, in certain cases, be dissociated from cell proliferation.

Animals↗

PubMed1983

Effects of the cold pressor test on the left ventricular function of patients with coronary artery disease.

We used the cold pressor test as provocative of myocardial ischemia in 23 subjects evaluated for chest pain on effort. Seven of them (group N) had normal coronary arteries, and 16 (group CAD) had critical stenoses along the main branches of the left coronary artery. In both groups exposure to cold induced increase in arterial pressure and double product. Left ventricular end-diastolic pressure increased +60% from baseline (P less than 0.001). Angiocardiographic parameters, unchanged in group N, showed an impairment of left ventricular function in group CAD. End-diastolic volume increased +11% (P less than 0.01), ejection fraction decreased -8% (P less than 0.0025), with a significant reduction in segmental wall motion in the area of the diseased artery (P less than 0.001). The mean Vcf was slightly and not significantly reduced, while early-systolic and end-diastolic stress and the constant of stiffness consistently increased in both groups. The appearance or extension of ventricular wall contraction abnormalities in group CAD, in the absence of demonstrable coronary spasm and in the presence of a remarkable increase in left ventricular end-diastolic pressure and stress, was interpreted as due to ischemia secondary to increased extravascular resistances to coronary flow. The cold pressor test is proposed as a useful tool for the diagnosis and evaluation of patients with ischemic heart disease.

Adult↗

PubMed1982