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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the relationship between the growth of HCC and nutrition, especially amino acids, and reconsidered the clinical application of amino acid imbalance. At first, rat chemical hepato-carcinogenesis was performed to investigate whether Aminoleban EN stimulates or restrains the occurrence of HCC. 2-Acetyl-amino-fluorene containing diet was administered intermittently according to Epstein's method. Rats were divided into two groups; group 1 was fed on Aminoleban EN containing diet and group 2 on a basal diet. There was no significant difference between the survival rate in the two groups. The average body weight of group 1 was significantly higher than that of group 2. The rats were sacrificed at the 25th week. All 11 rats of group 1 had no liver tumor, but 2 of 17 rats of group 2 had liver tumors, including a HCC and cholangiocellular carcinoma. The incidence of the liver tumor was significantly different between the two groups. Aminoleban EN could inhibit rat liver carcinogenesis, so it is considered to be a desirable nutritional product for LC patients from the stand point of cancer prevention. Secondly, the composition of amino acid was studied on HCC and surrounding tissue. There was no significant difference of Val, Leu, Leu, Phe, Tyr, Met and Fischer ratio between HCC and surrounding tissue.
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PMID:[Nutritional treatment of hepatocellular carcinoma]. 158 Jun 35

The importance of chronic hepatitis B virus (HBV) infection in the development of primary liver cancer has been established by epidemiological studies. However, the evidence for a direct role of the virus in liver carcinogenesis is still tentative. In addition, the findings of HBV DNA sequences in HBsAg-negative subjects with liver cancer has been reported, although it is controversial. Here we report the use of the polymerase chain reaction to detect HBV DNA in the serum and liver of HBsAg-negative patients. This technique allows both for the detection and cloning of HBV variants. In addition, the demonstration of HBV DNA and RNA molecules in HCC of HBsAg-negative individuals as determined by standard techniques reinforces the role of HBV in the pathogenesis of this tumor.
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PMID:The detection of hepatitis B virus (HBV) in HBsAG negative individuals with primary liver cancer. 165 Jun 88

In both cirrhotic and non cirrhotic livers, hepatic carcinogenesis appears as a multistep process commonly starting from hyperplastic nodules and reaching HCC via a continuous spectrum of lesions. Minute HCC without a background of hyperplastic lesions have also been identified in cirrhotic livers. These observations suggest that the morphological progression of carcinogenesis in the human liver can develop through two different main pathways.
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PMID:The morphogenesis of human hepatocellular carcinoma. 166 96

Intrahepatic distribution of Lipiodol and I-131 Lipiodol infused via the hepatic arteries was evaluated in six patients with HCC who had undergone hepatic lobectomy or segmentectomy. CT scan and gamma camera radiograph confirmed that the oily contrast material or I-131 radioactivity accumulated selectively in the tumor over a long period. One to two thirds of the tumor mass appeared necrotic, although the extent tended to be larger in the case of radioactive Lipiodol infusion. The tumor cells contained numerous lipid globules within the cytoplasm. Also, oil red 0 stain demonstrated that the individual tumor cells had non-globular lipid on their surface. In conclusion, Lipiodol leaks out of the vascular spaces to attach to the cancer cell membrane as a non-globular lipid as well as to enter the cancer cells as a globular lipid. This phenomenon specific to cancer cells suggests a biochemical membrane change which may have occurred during carcinogenesis, causing alteration of membrane transport and cell death.
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PMID:Distribution of Lipiodol in hepatocellular carcinoma. 216 78

Serum thyroxine was significantly higher in 59 patients with hepatocellular carcinoma than in normal subjects, patients with uncomplicated cirrhosis (48), or other primary tumours with or without hepatic metastases (50). Elevated thyroxine levels appeared attributable to high levels of thyroxine binding globulin which showed a positive linear correlation with serum thyroxine in all groups studied. Despite this hyperthyroxinaemia all patients appeared clinically euthyroid and, consistent with this, T3 was elevated in only one patient and the free thyroxine index was normal in all. Amongst a group of 25 cirrhotic patients who were followed-up for between 12 and 72 months, there was a striking dissociation between the TBG values of those destined to develop HCC and those who did not. In the former group TBG rose steadily with time whereas in the latter group levels remained stable, or, more often, fell. The rises in TBG occurred prior to any clinical signs of tumour development and may be one of the earliest serological changes to occur during carcinogenesis in the cirrhotic liver.
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PMID:Hyperthyroxinaemia in hepatocellular carcinoma: relation to thyroid binding globulin in the clinical and preclinical stages of the disease. 283 1

Forty patients with chronic liver disease and HCC were analyzed for infection with hepatitis C (HCV) and hepatitis B (HBV) viruses. All patients were negative for HBsAg, 16 were alcoholics, 6 had previous blood transfusions and 18 had sporadic chronic hepatitis. Antibodies to HCV were determined by EIA 2nd generation. HBV-DNA was detected by PCR using primers of the precore region. Analysis of HCV-RNA was done with nested PCR amplifying the 5' non-coding region of the HCV genome, using primers complementary to nucleotides 1-20 and 305-320 and nested primers complementary to nucleotides 21-31 and 271-286 of the HCV-J1. Anti-HCV were positive in 35/40 patients (87.5%). HCV-RNA was detected by PCR in 34 patients (85%) all of them positive for the anti-HCV. HCV-RNA was detected in 70.5% of the alcohol abusers, in 100% of patients with history of transfusion(s) and 94.1% of patients with cryptogenic chronic liver disease. HBV-DNA was detected in only 2 patients. In conclusion, there is a high rate of HCV and a low rate of HBV viremia detected by PCR in Spanish patients with HCC HBsAg negative. No patient without anti-HCV presents HCV-RNA. Our results suggest that persistent HCV replication may play a role in hepatic carcinogenesis, as HBV-DNA could be found in only 5% of our HCC patients.
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PMID:Demonstration of HCV-RNA and HBV-DNA in the serum of HBsAg negative patients with hepatocellular carcinoma. 781 97

Chronic liver diseases, in particular chronic HBV and HCV infections, frequently progress to liver cirrhosis and HCC. The molecular events underlying hepatocarcinogenesis are not yet well defined. It appears likely, however, that HCCs result from a stepwise carcinogenesis: due to chronic liver disease there is liver cell necrosis, inflammation and regeneration with a high mitotic rate of liver cells. In this setting, chromosomal DNA rearrangements occur which may result in the activation of cellular oncogenes or inactivation of tumor suppressor genes. Viral genes or gene products as well as cofactors, such as alcohol or aflatoxins, may make a specific contribution to these molecular events. Apart from the molecular aspects of hepatocarcinogenesis, for clinical practice the implementation of measures to prevent or treat chronic liver diseases should reduce the incidence of HCCs, one the most frequent malignancies in some areas of the world.
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PMID:[Hepatocellular carcinoma: molecular biology aspects]. 784 55

Preneoplastic and neoplastic hepatic lesions were induced in male Sprague-Dawley rats by oral exposure to N-nitrosomorpholine (12 mg/kg body wt/day) for 7 weeks (stop model). Twelve, 23 and 34 weeks after withdrawal of the carcinogen, cell proliferation and cell death (apoptosis) were studied in defined phenotypes of preneoplastic foci of altered hepatocytes (FAH), hepatocellular adenomas (HCA) and carcinomas (HCC) by autoradiographic determination of the labelling index (LI) resulting from continuous administration of [3H]thymidine for 48 h and by simultaneous counting of apoptotic bodies respectively. Compared with the liver parenchyma of untreated controls and the extrafocal parenchyma of treated animals, the mean LI was elevated in all types of FAH, HCA and HCC, but the extent of this increase differed markedly between the diverse phenotypes. The increase in the LI was significant for clear/acidophilic, intermediate and mixed/basophilic cell foci, but remained insignificant for the relatively rare tigroid and amphophilic cell foci. The previously established progression-linked phenotypic instability in the predominant cell lineage leading to HCC was associated with a gradual increase in the mean LI showing four significantly different proliferative stages: (i) clear/acidophilic and intermediate cell foci excessively storing glycogen, (ii) mixed/basophilic cell populations in FAH and glycogen-storing HCA, (iii) glycogen-poor HCA and glycogen-storing HCC and (iv) glycogen-poor HCC. The inverse correlation between glycogen accumulation and cell proliferation during progression from glycogenotic FAH to glycogen-poor HCC indicates that the fundamental metabolic shift associated with the gradual disappearance of the glycogenosis is essential for the evolution of the malignant phenotype. The mean ratio of necrotic cells (RN) was somewhat higher in all types of FAH compared to the normal and extrafocal liver parenchyma, but this was not statistically significant. Only when HCA and HCC appeared was there a significant increase in the mean RN, proceeding with the progression of neoplastic development. Our results do not support the concept that cell death (apoptosis) plays a major role in counterbalancing cell replication in FAH, but rather suggest that cell death occurs more frequently in the course of hepatocarcinogenesis the more neoplastic development advances.
Carcinogenesis 1994 Nov
PMID:Cell proliferation and cell death (apoptosis) in hepatic preneoplasia and neoplasia are closely related to phenotypic cellular diversity and instability. 795 93

The dose and time dependence of the cellular phenotype in preneoplastic and neoplastic liver lesions was evaluated quantitatively in groups of male Sprague-Dawley rats exposed for 7 weeks to 0, 12 and 24 mg/kg body wt of N-nitrosomorpholine (NNM) and studied at different time points up to 80 weeks after withdrawal of NNM (stop model). NNM-treated rats showed a dose- and time-dependent increase in the total number and volume of preneoplastic foci of altered hepatocytes (FAH) and in the incidence of hepatocellular adenomas (HCA) and carcinomas (HCC) at both dose levels, compared with the untreated controls. After stopping treatment with 12 mg/kg body wt, the well-known sequence of cellular changes leading from glycogenotic clear and clear/acidophilic cell foci to mixed and diffusely basophilic cell populations poor in glycogen was found. In contrast, at the higher NNM dose level (24 mg/kg) predominantly mixed and diffusely basophilic cell foci appeared immediately after cessation of treatment, but their number rapidly declined up to 13 weeks after withdrawal. At the same time, there was a reciprocal increase in the number of the less altered clear/acidophilic cell foci, indicating an early reversion-linked phenotypic instability of FAH. However, in spite of this reversion higher numbers of mixed and diffusely basophilic cell foci were retained after treatment with 24 compared to 12 mg/kg of NNM at all time points studied, and there was even a slow additional increase in the number of these types of FAH 20 weeks after withdrawal of NNM. At both dose levels, the volume fraction of the persistent mixed cell foci correlated positively with the incidence of HCA and HCC, suggesting that this phenotype of FAH represents a direct precursor of the neoplastic lesions. Tigroid cell foci, which appeared most frequently after treatment with the lower dose of NNM, were not integrated into the predominant sequence of cellular changes leading to HCC, but they may represent an intermediate stage in a side lineage of this sequence, endowed with the potential to progress at least to HCA. Our results show that reversion-linked phenotypic instability of FAH occurs mainly after high dose treatment, possibly resulting from rapid adaptive cellular responses to the primary carcinogenic lesion(s) which may be fixed by genetic or epigenetic mechanisms. In contrast, progression-linked phenotypic instability of FAH is a slow process developing in a dose- and time-dependent manner at all dose levels leading to hepatic neoplasia.
Carcinogenesis 1994 Jun
PMID:Dose and time dependence of the cellular phenotype in rat hepatic preneoplasia and neoplasia induced in stop experiments by oral exposure to N-nitrosomorpholine. 802 Jan 60

The dose and time dependence of the cellular phenotype in preneoplastic and neoplastic liver lesions was evaluated quantitatively in groups of male Sprague-Dawley rats continuously exposed to 0, 6, 12 and 24 mg/kg body wt of N-nitrosomorpholine (NNM) and studied at different time points up to 80, 50, 37 and 20 weeks respectively. Continuous oral administration of NNM resulted in a dose- and time-dependent increase in the total number and volume of preneoplastic foci of altered hepatocytes (FAH) and in the incidence of hepatocellular adenomas (HCA) and carcinomas (HCC) at all dose levels studied. In contrast to earlier stop experiments with 24 mg NNM/kg body wt, there was no reversion-linked phenotypic instability but a rapid progression of FAH of the mixed cell type to a high incidence of hepatocyte nodules and HCC after continuous treatment with NNM at this dose level. At the two lower dose levels of NNM (12 and 6 mg/kg) the well-known sequence of cellular changes leading from glycogenotic (clear, combined clear/acidophilic and acidophilic) to mixed and diffusely basophilic cell populations, in which HCC prevailed. A considerable part of the glycogenotic foci contained exclusively acidophilic cells, and HCA consisting of a mixture of acidophilic and basophilic cells were the most common benign tumour type in these groups. At the end of the observation period there was also a high incidence (> 50%) of HCC at both dose levels, indicating the potential of persistent nodules (HCA) containing acidophilic cells to progress to HCC. FAH and HCA exhibiting a tigroid cell pattern appeared only at the two lower dose levels, but for this type of HCA it remained open whether it may progress to HCC. From a comparison of the different dosing regimens of NNM studied in this and previous experiments we conclude that the rapid, potentially reversible shift from glycogenotic to mixed cell populations at the highest dose level of continuously applied NNM (24 mg/kg) and the high proportion of pure acidophilic glycogen storage foci observed after continuous administration of NNM at the two lower dose levels (6 and 12 mg/kg) represent different phenotypic expressions of promoting effects exerted by the ongoing influence of the carcinogen on FAH initiated by the same compound. The metabolic and molecular changes underlying these 'initiating' and 'promoting' effects of NNM seem to differ in terms of quantity rather than quality.
Carcinogenesis 1994 Jun
PMID:Dose and time dependence of the cellular phenotype in rat hepatic preneoplasia and neoplasia induced by continuous oral exposure to N-nitrosomorpholine. 802 Jan 61


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