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

To evaluate the objective proliferative activity in HCC nuclear DNA contents were measured by means of microspectrophotometry and at the same time the immunohistochemical technique using anti-PCNA antibody was employed. Surgically resected 26 HCCs were analyzed in terms of cell proliferative activity and regional heterogeneity. The analysis was performed by immunohistochemical demonstration of PCNA and pathologic histochemical study in formalin-fixed, paraffin-embedded specimens and cytophotometric measurements of nuclear DNA contents in fresh specimens. The results were as follows. 1) Nine HCCs showed regional ploidy heterogeneity. 2) PCNA labeling index and histological grade of the marginal area was much higher than that of the central area. From these results, we concluded that in the process of the HCC progression proliferative activity was decreased in the central area and was not decreased in the marginal area.
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PMID:[Analysis of nuclear DNA heterogeneity of the hepatocellular carcinoma (HCC)]. 751 14

A total of 128 surgically resected small hepatocellular carcinomas, measuring less than or equal to 3 cm in diameter, were studied by both macroscopic and histologic examinations. In 95 single nodular-type tumors of the 128 lesions, eight tumors were associated with the cancerous areas of well differentiated hepatocellular carcinoma around the nodule. These surrounding cancerous areas went undetected by both the preoperative radiological examinations and the gross findings of resected specimens. Based on the immunohistochemical findings, the labeling index, both of the proliferating cell nuclear antigen (PCNA) and of the Ki-67 in the surrounding cancerous areas, were lower than that of the main nodules but higher than in the nontumorous liver parenchyma in seven of eight cases. These results suggest that the main nodule was generated from the surrounding cancerous area, supporting the hypothesis of a stepwise progression of HCC. Even if the tumor seems to be a small and single nodular type, it is recommended that its surrounding areas should be closely examined and the surgical cutting margin should be made more than 1.0 cm away from the main nodule at hepatic resection.
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PMID:Small hepatocellular carcinoma of single nodular type: a specific reference to its surrounding cancerous area undetected radiologically and macroscopically. 756 84

Intense research using animal models has indicated that chemically-induced rat liver cancer proceeds through multiple, distinct stages that can be characterised morphologically and biochemically. Primary human liver cancer, with hepatitis B and other environmental factors such as poor nutrition and food contaminating mycotoxins as contributing etiological factors, is one of the major causes of cancer deaths in African, Asian and some Western countries. Recent advances in surgical and diagnostic techniques have also allowed the identification of potential morphological precursors of primary human liver cancer, and suggested a model consistent with the concepts of initiation--promotion--progression as in the rat. The expression of proliferating cell nuclear antigen (PCNA), silver-staining nucleolar organiser regions (AgNOR), oncogenes and the tumor suppressor gene p53 in preneoplastic and neoplastic lesions of rat and human livers is presently reviewed. This undertaking is an attempt to evaluate whether the current knowledge regarding molecular mechanisms of carcinogenesis is sufficient to permit the use of these molecular parameters as 'intermediate' markers in studies of risk assessment and cancer prevention, without having to resort to tumor appearance as an end-point.
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PMID:The potential for the use of cell proliferation and oncogene expression as intermediate markers during liver carcinogenesis. 760 May 46

To identify the preneoplastic lesions of hepatocellular carcinoma and the fine structure of preneoplastic hepatocytes, we studied proliferative conditions in cirrhosis of the liver. In all, 46 foci of cellular alteration (FCA), three regions of adenomatous hyperplasia (ADH), and 21 small hepatocellular carcinomas (sHCC) were studied by published criteria for sHCC and by the proliferative activity of the lesions as examined with monoclonal antibodies against DNA polymerase alpha and proliferating cell nuclear antigen. The four patients with FCA composed of basophilic hepatocytes were classified by the criteria as having sHCC; cells had features similar to those of sHCC. Two of these four patients with FCA were found to have HCC several years later. The number of hepatocytes stained for proliferating cell nuclear antigen was 72 and 81 per 1000 hepatocyte nuclei in the two patients who developed HCC. In one of the three patients with ADH, a sHCC was found 1 year later, and dysplastic hepatocytes from the region of ADH in this patient had features similar to those of HCC cells by light and electron microscopy. In this patient, the number of hepatocytes stained for DNA polymerase alpha was 452 per 1000 nuclei. Therefore, FCA and ADH might be preneoplastic lesions of sHCC in cirrhosis of the liver. Preneoplastic hepatocytes seem to be small cells with basophilic cytoplasm, with a large nucleus to cytoplasm ratio, finely indented nuclei with a smaller amount of condensed chromatin than normal, and poorly to moderately developed organelles.
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PMID:Detection of the preneoplastic lesions of small hepatocellular carcinoma in cirrhotic livers. 790 90

Using the Colloid silver staining technique to reveal AgNOR and immunostaining for anti-PCNA monoclonal antibody, 23 resected specimens with hepatocellular carcinoma (HCC, < or = 3.5cm in diameter) were examined. These cases were divided into two groups; Group A [9 cases without vascular invasion and a satellite nodule] and Group B [14 cases with satellite nodules]. Comparison of AgNOR score, the morphological features of AgNOR (the area and roundness factor of AgNOR) and PCNA labeling index between Group A and Group B was made by a image analyzer (SP-500). The AgNOR scores and PCNA labeling indices of HCCs in Group B were significantly higher than those of HCCs in Group A. And a close correlation was shown between AgNOR score and PCNA labeling index. Further more, the area, form, and distribution of AgNORs within the nucleus were also different in the two study groups. In Group A, many AgNORs were regular and medium-sized brown dots (AgNOR-roundness factor; > or = 80%, AgNOR-area; 1.5-4.5 microns 2). But in Group B, AgNORs showed marked variation in size and form. These results suggest that HCCs with multiple, smaller, irregular, and widely dispersed AgNOR in combination with high AgNOR scores have a more aggressive potential. The morphological features of AgNOR may be useful indicators for evaluating the proliferative activity of HCC.
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PMID:[Evaluation of the biological malignancy in hepatocellular carcinoma by argyrophilic nucleolar organizer region (AgNOR) staining--morphological study of AgNOR using image analyzer]. 790 44

Relationship between p53 protein overexpression and clinicopathological findings and the proliferative activity was studied in 50 cases of hepatocellular carcinoma (34 biopsy and 16 surgically resected cases) using immunohistochemistry. Overexpression of p53 was observed in 26.5% of biopsy cases and 31. 3% of surgically resected cases. Investigation of the relationship between the p53-positive rate and the clinical stage of HCC showed that it was significantly higher in Stage IV (the most advanced cancer; 54.5%) than in Stage I/II/III (13.0%) (p<0.05). Examination of the relationship between the p53-positive rate and tumor differentiation in the biopsy cases showed that p53 was positive in 9.1% of well differentiated carcinomas, 21.4% of moderately differentiated carcinomas, and 55.6% of poorly differentiated carcinomas, indicating that p53 positivity increased as tumors became less differentiated. The p53-positive rate of poorly differentiated carcinoma (55.6%) was significantly higher than that of well and moderately differentiated carcinoma (16.0%) (p<0.05). In the surgically resected cases, p53 overexpression tended to be more frequent in the less differentiated parts of each tumor nodule. In cases with nodule in nodule pattern of HCC, the p53-positive rate was different among nodules with the same level of differentiation. Examination of tumor cell proliferative activity using the proliferating cell nuclear antigen L.I. showed that this indicator was significantly higher in the p53-positive tumors than in the p53-negative tumors (52.7+/-32.4% vs. 32.4+/-15.3%: p<0.05). These results suggest that p53 overexpression may be involved in determining the dedifferentiation and the proliferative activity of HCC. Examination of the surgically resected cases confirmed that p53 overexpression became heterogeneous during the multistep carcinogenesis and growth process of HCC, which is considered to develop from a single cell. This finding suggests that p53 overexpression may be involved in tumor progression.
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PMID:Relationship between p53 overexpression and the proliferative activity in hepatocellular carcinoma. 1089 56

Mammalian cell cycle progression is regulated by the combined action of cyclins/cyclin-dependent kinases (CDKs) and CDK inhibitors. Abnormal expression as well as interaction of these proteins may result in malignant transformation of cells. To further address the role of these cell cycle proteins in hepatocellular carcinomas, we analyzed the expression of cyclin E and CDK2. A panel of livers with human hepatocellular carcinoma, liver cirrhosis, and chronic hepatitis were used as a human experimental system. The inbred LEC (Long-Evans with a cinnamon-like coat color) rats were used as an animal experimental HCC model. Immunohistochemical staining of serial paraffin sections was performed using antibodies to cyclin E and CDK2. The results showed that cyclin E and CDK2 were concurrently overexpressed in hepatocellular carcinomas both in human and rat livers. Western blot analysis and CDK2 kinase assay demonstrated expression levels of cyclin E and CDK2 and CDK2 kinase activity, respectively, and both were shown to increase along with the development of hepatocellular carcinomas. Analysis of the correlation between expression of cyclin E and CDK2 and clinicopathological parameters revealed a significant correlation between expression of cyclin E and tumor grade (P=0.013), and PCNA index (P=0.006) as well as CDK2 expression (P=0.015). Overexpression of CDK2 tended to be associated with poorly differentiated HCCs. The results suggest that overexpression of cyclin E and CDK2 plays an important role in the development of hepatocellular carcinoma.
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PMID:Overexpression of cyclin E and cyclin-dependent kinase 2 is correlated with development of hepatocellular carcinomas. 1147 Jun 26

To examine the potentially chemopreventive effects of alpha-tocopherol on hepatocarcinogenesis, we fed the transgenic mice line MT42, which overexpresses transforming growth factor-alpha (TGF-alpha) and which has been established as having a high incidence of liver tumor, with different concentrations of alpha-tocopherol and examined the hepatic tumorigenesis of these mice. At 3 weeks of age, MT42 male mice received a single intraperitoneal injection of diethylnitrosamine (DEN), 5 mg/kg body weight, to initiate the formation of liver tumors. The mice were divided into three groups: group A, control diet (20 mg/kg of alpha-tocopherylacetate); group B, deficient diet (less than 1 mg/kg); group C, supplemented diet (500 mg/kg). Neoplastic change was determined at 40 weeks of age. The incidence of adenomas (p < 0.05), the maximum tumor size (p < 0.01), the mean relative liver weight (p < 0.01), and the proliferating cell nuclear antigen (PCNA) labeling indices of the non-tumor sites (p < 0.01) of group B were significantly higher than those of group C. No toxic effects of alpha-tocopherol were found. Alpha-tocopherol-deficient diet accelerated the hepatocarcinogenesis of TGF-alpha transgenic mice treated with DEN. At best, these data demonstrate that alpha-tocopherol-deficiency is not beneficial for prevention of hepatocarcinogenesis in this model. Alpha-tocopherol may be useful for the chemoprevention for liver cancer.
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PMID:Effect of alpha-tocopherol on hepatocarcinogenesis in transforming growth factor-alpha (TGF-alpha) transgenic mice treated with diethylnitrosamine. 1172 90

It is now widely accepted that cancer development is a multistage process, starting from the original cell population and ending with a malignant tumor. However, the mechanisms involved in the progressive growth of cells from normalcy to preneoplasia, and from preneoplasia to malignancy are not clear. Because tyrosine phosphorylation and dephosphorylation reactions are known to play critical roles during normal and abnormal cellular growth, we have studied the tyrosine phosphorylation, tyrosine phosphorylated proteins, and protein phosphatases during the sequential development of liver cancer. The present investigation indicated that enhanced tyrosine phosphorylation and tyrosine phosphorylated proteins, with no change in the levels of tyrosine protein phosphatases may contribute to abnormal cellular proliferation during liver carcinogenesis. We have also seen an increase in the expression of proliferating cell nuclear antigen and G1/S cyclins during tumor development.
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PMID:Enhanced sequential expression of G1/S cyclins during experimental epatocarcinogenesis and tyrosine phosphorylation. 1179 28

We have reported that microwave cell death is a unique cell death preserving not only cell and nuclear shapes but also immunohistochemical antigenicity. However, their enzyme activity was lost, which indicated cell dysfunction and death. This peculiar observation implies that the microwave effect is likely an 'in situ' tissue fixation and that this type of cell death is morphologically different from cell death, by either oncosis or apoptosis, as previously known. To confirm whether this peculiar cell death was observed also in human tissue samples, we examined clinical samples from patients with metastatic liver cancer, which were treated with microwave irradiation. They were examined immunohistochemically for human Ki-67 antigen and proliferating cell nuclear antigen and enzyme histochemically for alkaline phosphatase, and the same morphological changes that were observed in microwave-treated rat liver were found. In conclusion, we believe that routine hematoxylin-eosin stain alone is not a suitable method to evaluate microwave treatment for cancer because microwave coagulation therapy-treated cells preserved their nuclei and cellular architectures, even after 3 months. For microwave-treated tumors, enzyme histochemistry is helpful to determine its effectiveness.
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PMID:Microwave cell death: Enzyme histochemical evaluation for metastatic carcinoma of the liver. 1462 49


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