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Query: UMLS:C1864663 (HCC)
 2,985 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

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

A complementary way for the assessment of HCC prognosis is represented by the analysis of molecular markers. Thus, immunohistochemical assessment of proliferation can describe tumor aggressiveness, probability of local recurrence or metastasis potential, being very useful for the assessment of recurrence-free survival and survival until death. The aim of our study was to assess proliferating cell nuclear antigen activity in HCC and dysplastic nodules as compared with surrounding non-neoplasic areas. Immunohistochemical techniques were thus performed on the samples obtained by ultrasound-guided liver biopsies or intraoperative biopsies, in 32 patients with HCC, as well as in 3 patients with dysplastic nodules occurring in liver cirrhosis. Expression of PCNA within extranodular areas of the HCC patients in the absence or presence of cirrhosis, was increasing from 40% to 70%, respectively. PCNA expression further increased within intranodular areas of dysplastic nodules and HCC, to 100% and 96.88%, respectively. A progressive increase of the mean values of PCNA-LI was also observed from extranodular areas without or with cirrhosis, towards intranodular areas of dysplastic nodules and HCC (4.2%, 6.8%, 27.9%, 31.9%, respectively). Dysplastic nodules can thus be considered lesions with a high-proliferation rate, representing an early stage of hepatocarcinogenesis. This supported the current recommendations for borderline hepatocellular nodules identified by ultrasound, which indicate an aggressive treatment similar to malignant lesions. In summary, we demonstrated a progressively increasing rate of cellular proliferation, from extranodular non-neoplasic areas to intranodular areas (dysplastic nodules and HCC), as reflected by an increased expression of proliferating cell nuclear antigen labelling index.
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PMID:Immunohistochemical assessment of proliferating cell nuclear antigen in primary hepatocellular carcinoma and dysplastic nodules. 1475 12

The purpose of this study is to investigate if the EGFR-Stat3 signal pathway contributes to the carcinogenesis of hepatoma in rats. Hepatoma was induced in rats by 3'Me-DAB as a model. EGFR, TGFalpha, Stat3, p-Stat3 in different stages of carcinogenesis were detected by immunohistochemistry and Western blot. In situ hybridization was applied to investigate the expression of Stat3 mRNA. The expressions of signal molecules were assessed by KS400 Image Analysis system. The data were statistically evaluated. EGFR, TGFalpha, Stat3 were highly expressed in the stages of liver necrosis and repairment. All hepatocellular carcinoma cases revealed elevated expression of EGFR, TGFalpha. Elevation of Stat3 mRNA and protein levels were identified, increase of activation of Stat3 was also observed. In HCC, there was positive correlation between p-Stat3 level and the expression of TGFalpha and PCNA. Increased expression of Bcl-2 (P < 0.05) coincided with elevated level of p-Stat3. Therefore, the EGFR-Stat3 signal pathway was related to the development of hepatoma in rats. TGFalpha-EGFR autocrine ring formation may lead to the activation of Stat3 and in turn, promote proliferation and regulate the transcription of genes regulating cell apoptosis and cell cycle.
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PMID:Roles of EGFR-Stat3 signal pathway in carcinogenesis of experimental hepatoma in rats. 1703 71

To demonstrate in vivo tumor growth inhibition, the liver cancer cell lines HepG2, BEL7402, and SMMC7721 were independently inoculated into the livers of 45 6-week-old nude mice. After 24 h, mice were randomly divided into celecoxib (intragastric celecoxib suspension, 300 mg/kg), negative control (equal volume intragastric saline), and positive control (intraperitoneal injection of 6 mg/kg doxorubicin) and treated once per day for 3 days. Body weights, tumor diameters, and tumor expressions of proliferating cell nuclear antigen (PCNA) and c-Met were determined at 23 days posttreatments. Significant increases in body weight were observed in celecoxib- or doxorubicin-treated mice compared to saline-treated animals and tumor growth was significantly attenuated, accompanied by downregulation of tumor PCNA expression (p < 0.01). Weight gain, attenuated tumor growth, and reduced PCNA expression were similar following celecoxib or doxorubicin treatment. Celecoxib also significantly reduced c-Met expression in HepG2- and BEL7402-induced tumors, but not SMMC7721-induced tumors (p < 0.05). In conclusion, celecoxib effectively suppressed the in vivo growth of liver cancer in an orthotopic tumor model. Celecoxib also inhibited tumor cell PCNA expression independent of changes in c-Met expression, with some variability between different implanted cell lines. This preclinical demonstration of celecoxib efficacy and safety provides a foundation for future clinical investigations involving use of this agent alone or as a component of chemotherapeutic regimens for treatment of HCC.
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PMID:The cyclooxygenase-2 inhibitor celecoxib attenuates hepatocellular carcinoma growth and c-Met expression in an orthotopic mouse model. 2147 89

Some sulphated polysaccharides can bind bFGF but are unable to present bFGF to its high-affinity receptors. Fucoidan, a sulphated polysaccharide purified from brown algae, which has been used as an anticancer drug in traditional Chinese medicine for hundreds of years, exhibits a variety of anticancer effects, including the induction of the apoptosis and autophagy of cancer cells, the inhibition of the growth of cancer cells, the induction of angiogenesis, and the improvement of antitumour immunity. Our research shows that fucoidan dose not inhibit the expressions of VEGF, bFGF, IL-8, and heparanase in HCC cells and/or tumour tissues. Moreover, fucoidan exhibited low affinity for bFGF and could not block the binding of bFGF to heparan sulphated. Although fucoidan had no effect on angiogenesis and apoptosis in vivo, this drug significantly inhibited the tumour growth and the expression of PCNA. These results suggest that fucoidan exhibits an anticancer effect in vivo at least partly through inhibition of the proliferation of HCC cells, although it is unable to suppress the angiogenesis induced by HCC.
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PMID:Fucoidan inhibits the growth of hepatocellular carcinoma independent of angiogenesis. 2373 42


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