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Query: UMLS:C0345904 (liver cancer)
 15,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present paper, the authors applied Sanjie pellet in the anti-cancer study on the animals. The results indicated that in the extracorporeal experiment, stomach perfusion with Sanjie pellet 12.5g/kg daily for 10 successive days, the inhibitory rate for the substantive liver cancer was 84%. For ascites liver carcinoma, it could raise the average rate of prolonging life span to 76%. Lethal dose (LD50) was 25 g/kg. The pathological observations indicated that Sanjie pellet acted directly on the cell membrane and organelle of the liver cancer cells and causing lysis of the cell membrane, dilation of rough surface endoplasmic reticulum, the swelling of mitochondria and disintegration of the liver cancer cells body. The authors concluded that these were the main pharmacological efficacies of Sanjie pellet.
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PMID:[Anti-cancer effects of sanjie pellets]. 220 26

Firstly, using HCC cell lines, the effects of r-h TNF were investigated. The authors had already confirmed that these cell lines were derived from human HCC. Each cell line showed a different growth curve on addition of TNF to the culture medium. JHH-4 exhibited enhancement of growth under the optimum concentration of TNF. On the other hand, growth of JHH-5 and JHH-7 was inhibited by TNF. JHH-7 were more sensitive to TNF than JHH-5, however, the direct effect of TNF on JHH-7 was not potent, as 10(4) u/ml TNF could not prevent proliferation of JHH-7. Morphological examinations were also performed. Phase-contrast microscopy showed that the JHH-4 cells were enlarged and tended to pile up after the addition of TNF to the culture medium. JHH-7 cells became detached from the culture dish due to cell death. Electron microscopy showed irregular proliferation of the rough endoplasmic reticulum of JHH-4 cells and increased number of lysosomes in JHH-7 cells. Furthermore, hyperthermia exhibited an interesting reciprocal action. Proliferation of JHH-4 was inhibited by low concentrations of TNF together with 41.4 degrees C hyperthermia in contrast to the effects of TNF alone. JHH-7 became more sensitive to TNF under hyperthermia at 41.4 degrees C. On the other hand, normal human fibroblast 'HAIN-55' were not affected by TNF at 37.0 degrees C, 41.4 degrees C or 42.5 degrees C. In this paper, the authors tried to study the effects of TNF and hyperthermia on human HCC cell lines.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effects of TNF on human hepatocellular carcinoma cell lines and their modification by hyperthermia]. 285

Surgical specimens of 175 cases of primary hepatocellular carcinoma were prepared by routine paraffin section and HE stain. The clear cell cancer specimens were stained with PAS. All the specimens were observed by light microscope. Ultrathin sections were made for 50 samples and studied by electron microscope. Under the light microscope, 79 (45.1%) showed varying amounts of clear cells. According to the proportion and distribution of these cells, clear cell carcinoma of the liver was divided into three types: scattered type (16 cases, 20.3%), localized (43, 54.4%) and diffuse types (20, 25.3%). The clear cancer cells could be found in hepatoma with various degrees of differentiation. Of these 79 cases, 4 (5.1%) were grade I, 53 (67%) and 22 (27.9%) were grades II and III. Positive PAS stain gives an evidence of glycogen in the clear cell cytoplasm. 7 diffuse type clear cell hepatomas were observed with electron microscope. The cytoplasm had only fewer organelles, leading to a void appearance. The amount of the rough endoplasmic reticulum, free ribosome and polyribosome was markedly decreased. So was mitochondria, usually showing swelling and abnormality. The residual rough endoplasmic reticulum and mitochondria were out of normal arrangement. They often aggregated on one side of the nucleus or near the cell membrane. Glycogen particles were increased in some cell cytoplasms. Some particles were even and fine, some were aggregated into masses or scattered. Nuclei showed abnormalities mild to moderate. The nature of the clear cells in liver cancer is the variance of glycogen or lipid in the cytoplasm.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Ultrastructure of primary clear cell carcinoma of the liver]. 358 12

Using hexachlorocyclohexane (BHC) as a model histopathological, histoenzymological, biochemical, and electrophoretic studies were undertaken to find out certain parameters for early diagnosis of liver cancer. In addition, cytogenetic studies were carried out to evaluate the effect of BHC feeding on mitotic and meiotic divisions. The results of these investigations suggest that there is a significant change in liver weight in experimental group. Histologically, liver cells follow a definite sequential cellular alteration ultimately leading to liver tumor. Histochemically, well defined pattern of glycogen accumulation and iron distribution in hepatocytes was observed. The electron-microscopic observation demonstrated prominently the proliferation of agranular endoplasmic reticulum in early stages. The distribution of certain enzymes linked with plasma membrane, lysosomes, and mitochondria showed the functional alteration of these organelles both in neoplastic nodules and tumours induced by BHC. The biochemical changes observed in gluconeogenic enzymes (G6Pase and F1,6dipase) and dehydrogenases (LDH, ICDH, and MDH) at different duration of exposure to BHC indicated decrease in enzyme activity of both gluconeogenic pathway and tricarboxylic acid cycle, linked with energy metabolism. These changes tend to recover with discontinuation of BHC but 8 months continuous feeding produces irreversible changes in G6Pase activity. Using polyacrylamide gel electrophoresis technique a change in serum proteins and LDH isoenzymes was observed. However, extrapolation of these findings to human situation needs more extensive studies, taking into account all possible variables, such as the DDT and BHC load in our environment and the body burden resulting there from.
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PMID:Experimental studies on insecticides commonly used in India. 616 13

These studies have provided evidence that DEHP and DEHA do not bind covalently to DNA and do not therefore possess the characteristics of a genotoxic agent (Lutz, 1982). This suggests that the tumours induced in the rodent liver may result from some non-genotoxic mechanism and supports the view that the weakly positive dominant lethal test seen on administration of DEHP by the ip (but not the oral) route (Singh et al. 1974) is unlikely to have resulted from a direct effect on the genome of the sperm cells. Although the mechanism responsible for the induction of tumours by high doses of DEHP in rodents is not clear, it would appear both from these studies and from work on hypolipidaemic agents, that peroxisomal proliferation and the induction of enzymes associated with this organelle are in some way implicated (Cohen & Grasso, 1981). Other studies have shown that changes of this type are produced by doses of hypolipidaemic agents that induce liver cancer in rodents (Cohen & Grasso, 1981) and our investigations have indicated that they were also prominent at dose levels of DEHP similar to those that induced liver cancer in the NCI study (National Toxicology Program, 1982). No cancer induction would be expected to occur in the absence of these changes. In our dose-response study in rats it was shown that at the lowest dose (50 mg/kg body weight/day, approximately equivalent to a dietary level of 1000 ppm) several effects seen with higher doses were not apparent and others differed only slightly from normal control values. This is particularly relevant to assessments of the risk posed by DEHP and DEHA present as contaminants in foods, since human exposure via the food chain has been estimated by Shiota, Chou & Nishimura (1980) as 30 micrograms/kg body weight/day, several orders of magnitude less than the lowest exposure level used in these experiments. In addition, our studies indicate that none of the changes found in the rat were observed in the marmoset, suggesting that rodents and primates differ fundamentally in their hepatic and testicular response to DEHP. Previous studies by other authors (reviewed by Cohen & Grasso, 1981) indicated that morphological changes in the endoplasmic reticulum and the proliferation of peroxisomes are not features of the response of monkeys and man to high doses of hypolipidaemic agents.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Genotoxicity studies on di-(2-ethylhexyl) phthalate and adipate and toxicity studies on di-(2-ethylhexyl) phthalate in the rat and marmoset. 642 84

A positive association between the incidence of hepatocellular carcinoma and the consumption of alcoholic beverages has been reported from some countries. The possible mechanistic nature of the association remains unclear, however. The effects of alcohol, as ethanol and as ethanol in various complex mixtures in the many different alcoholic beverages, were compared with the effects of well-known genotoxic and nongenotoxic or epigenetic carcinogens in carcinogenesis. There is no convincing evidence that alcohol can initiate the long multistep process of development of hepatocellular carcinoma. Thus, it appears that alcohol cannot be considered as a complete carcinogen. The effects of alcohol were also compared with known promoting agents for liver cancer. Although the available data are less clear, nevertheless it appears that alcohol cannot be considered as a bona fide promoting agent for liver cancer development. The most likely roles of alcohol in the genesis of liver cancer are: (1) to induce a well-known precancerous liver lesion, cirrhosis, and (2) to modulate, in an as yet ill-defined manner, the process of cancer development with known human carcinogenic influences such as hepatitis due to hepatitis B and hepatitis C viruses. Alcohol is well known to induce several enzymes in the liver and, thus, could theoretically modulate one or more steps in the carcinogenic process. Because alcohol has been found to alter cell membranes in well-defined ways and cell membrane changes, especially in the liver endoplastic reticulum, appear to be common in the later steps in liver cancer development, it is suggested that one site of alcohol action might be in the modulation of the biophysical composition of the liver endoplasmic reticulum and plasma membrane, favoring the cellular evolution to neoplasia.
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PMID:Alcohol and other chemicals in the development of hepatocellular carcinoma. 879 78

Tigroid cell foci (TCF) are a well-defined entity induced in rat liver by chemical carcinogens, their significance for hepatocarcinogenesis being controversial. Using cytomorphological, cytochemical and morphometric approaches, we studied the evolution and fate of TCF sequentially from 7 to 110 weeks in groups of 50 male Sprague-Dawley rats, which remained untreated or received N-nitrosomorpholine (NNM) orally at concentrations of 3 and 1 mg/kg body wt/day for 7 and up to 75 weeks, respectively. An increased incidence of hepatocellular neoplasms developed in exposed animals compared with controls, which was significant for adenomas at both dose levels, and for carcinomas (HCC) after the longer exposure to the lower dose level (P < 0.0001). TCF appeared frequently in addition to other types of proliferative foci of altered hepatocytes (FAH) including clear/acidophilic and mixed cell foci (MCF) in NNM-treated and rarely in untreated rats. Striking similarities in the cellular phenotypes of TCF and many hepatocellular neoplasms indicated the potential of TCF for progression to both adenomas and carcinomas. TCF emerged from xenomorphic cell foci (XCF), which consisted of hypertrophied hepatocytes typically presenting an enlarged nucleus, abundant glycogen, smooth and rough endoplasmic reticulum, altered activities of several enzymes of carbohydrate metabolism and an increased cell proliferation (P < 0.001) compared with the extrafocal parenchyma. TCF shared many features with XCF, but their basophilia and proliferative activity was higher. The number of FAH appearing at the two dose levels of NNM was similar but the average size of TCF and MCF was frequently higher at late time points in the group developing a significantly higher incidence of HCC, which suggests a pronounced acceleration of neoplastic conversion in established preneoplastic cell populations rather than the induction of additional FAH by sustained effects of low doses of carcinogens.
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PMID:Xenomorphic hepatocellular precursors and neoplastic progression of tigroid cell foci induced in rats with low doses of N-nitrosomorpholine. 988 59

Hepatitis B virus is a major cause of human liver disease. In the case of chronic infection the virus can lead to liver cancer and cirrhosis. The virion consists of an outer envelope containing lipids of the endoplasmic reticulum and virally-encoded surface proteins. This lipoprotein shell encloses the nucleocapsid or core antigen (HBcAg), which contains the viral genome. The capsid consists of dimers of a 183-residue protein, which can be divided into an assembly (residues 1-149) and a protamin-like domain (residues 150-183), responsible for polymerization into particles and RNA packaging, respectively. Upon expression of the core gene in bacteria the products are assembled into capsids resembling those of wild type particles. A purification protocol was developed for unpolymerised (dimeric) and polymerized HBcAg by fusion of six histidine residues to a C-terminal deletion mutant of the core protein allowing the isolation of the respective antigens after denaturing Ni2+-chelate affinity chromatography and renaturing dialysis. The possible incorporation of E. coli proteins during the assembly process and the inclusion of nucleic acids can be avoided. The method might be an attractive alternative to common purification protocols of hybrid virus-like particles (VLPs) for vaccine use.
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PMID:Purification of E. coli-expressed HIS-tagged hepatitis B core antigen by Ni2+ -chelate affinity chromatography. 1009 42

The use of many halogenated alkanes such as carbon tetrachloride (CCl4), chloroform (CHCl3) or iodoform (CHI3), has been banned or severely restricted because of their distinct toxicity. Yet CCl4 continues to provide an important service today as a model substance to elucidate the mechanisms of action of hepatotoxic effects such as fatty degeneration, fibrosis, hepatocellular death, and carcinogenicity. In a matter of dose,exposure time, presence of potentiating agents, or age of the affected organism, regeneration can take place and lead to full recovery from liver damage. CCl4 is activated by cytochrome (CYP)2E1, CYP2B1 or CYP2B2, and possibly CYP3A, to form the trichloromethyl radical, CCl3*. This radical can bind to cellular molecules (nucleic acid, protein, lipid), impairing crucial cellular processes such as lipid metabolism, with the potential outcome of fatty degeneration (steatosis). Adduct formation between CCl3* and DNA is thought to function as initiator of hepatic cancer. This radical can also react with oxygen to form the trichloromethylperoxy radical CCl3OO*, a highly reactive species. CCl3OO* initiates the chain reaction of lipid peroxidation, which attacks and destroys polyunsaturated fatty acids, in particular those associated with phospholipids. This affects the permeabilities of mitochondrial, endoplasmic reticulum, and plasma membranes, resulting in the loss of cellular calcium sequestration and homeostasis, which can contribute heavily to subsequent cell damage. Among the degradation products of fatty acids are reactive aldehydes, especially 4-hydroxynonenal, which bind easily to functional groups of proteins and inhibit important enzyme activities. CCl4 intoxication also leads to hypomethylation of cellular components; in the case of RNA the outcome is thought to be inhibition of protein synthesis, in the case of phospholipids it plays a role in the inhibition of lipoprotein secretion. None of these processes per se is considered the ultimate cause of CCl4-induced cell death; it is by cooperation that they achieve a fatal outcome, provided the toxicant acts in a high single dose, or over longer periods of time at low doses. At the molecular level CCl4 activates tumor necrosis factor (TNF)alpha, nitric oxide (NO), and transforming growth factors (TGF)-alpha and -beta in the cell, processes that appear to direct the cell primarily toward (self-)destruction or fibrosis. TNFalpha pushes toward apoptosis, whereas the TGFs appear to direct toward fibrosis. Interleukin (IL)-6, although induced by TNFalpha, has a clearly antiapoptotic effect, and IL-10 also counteracts TNFalpha action. Thus, both interleukins have the potential to initiate recovery of the CCl4-damaged hepatocyte. Several of the above-mentioned toxication processes can be specifically interrupted with the use of antioxidants and mitogens, respectively, by restoring cellular methylation, or by preserving calcium sequestration. Chemicals that induce cytochromes that metabolize CCl4, or delay tissue regeneration when co-administered with CCl4 will potentiate its toxicity thoroughly, while appropriate CYP450 inhibitors will alleviate much of the toxicity. Oxygen partial pressure can also direct the course of CCl4 hepatotoxicity. Pressures between 5 and 35 mmHg favor lipid peroxidation, whereas absence of oxygen, as well as a partial pressure above 100 mmHg, both prevent lipid peroxidation entirely. Consequently, the location of CCl4-induced damage mirrors the oxygen gradient across the liver lobule. Mixed halogenated methanes and ethanes, found as so-called disinfection byproducts at low concentration in drinking water, elicit symptoms of toxicity very similar to carbon tetrachloride, including carcinogenicity.
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PMID:Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model. 1270 12

P-Glycoprotein (P-gp) encoded by the MDR gene is one of the main factors in multidrug resistance. Its expression in cancer cells, which compromises cancer outcome, can be enhanced by some stress signals. Energy depletion, frequently observed in malignant cells, was shown to induce chemoresistance and could be one of these signals. To test this hypothesis, we studied the effect of glucose deprivation on P-gp expression in a rat hepatoma cell line (Fao). Incubation of Fao cells with a glucose-free medium enhanced P-gp mRNA and protein expression in a time-dependent manner, up to 400% at 40 h. This effect was associated with a stimulation of [(3)H]vinblastine efflux by P-gp despite impaired glycosylation. It was reproduced by inducers of endoplasmic reticulum stress response, such as 2-deoxyglucose (DG), tunicamycin, and thapsigargin. P-gp mRNA induction by DG was preceded by an increase in activator protein binding activity, c-Jun expression, and phosphorylation. In contrast, nuclear factor-kappaB binding activity was unaffected by DG. The antioxidant N-acetylcysteine partially reversed the increase in P-gp mRNA and protein levels induced by DG, as well as the enhancement of c-Jun phosphorylation and activator protein binding activity. Finally, transient transfection of the cells with a deleted mutant of c-Jun, Tam 67, abolished the DG-induced P-gp mRNA expression and mdr1b promoter activation. In conclusion, glucose deprivation enhances P-gp expression and transport function in liver cancer cells. This effect is mediated by endoplasmic reticulum stress response and involves MDR transcriptional induction through c-Jun activation. These results emphasize the importance of glucose metabolism in chemoresistance.
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PMID:Glucose depletion enhances P-glycoprotein expression in hepatoma cells: role of endoplasmic reticulum stress response. 1461 25


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