It is suggested that lamivudine therapy is beneficial for patients after initial treatment for HBV-related HCC because it contributes to improving remnant liver function, thus decreasing the risk of liver failure and increasing the chances of receiving available treatment modalities for recurrent HCC.
Recently, it has been shown that approximately 80% of Merkel cell carcinomas harbor a novel polyomavirus named Merkel cell polyomavirus, thought to be a carcinogenic agent. However, it is not fully elucidated whether Merkel cell carcinomas differ with regard to the presence or absence of Merkel cell polyomavirus. To address this, we investigated morphologic differences between Merkel cell polyomavirus-positive and -negative Merkel cell carcinomas by morphometry. Using polymerase chain reaction and real-time quantitative polymerase chain reaction, Merkel cell polyomavirus was detected in 20 (77%) of 26 Merkel cell carcinoma cases, including 4 Merkel cell carcinomas combined with squamous cell carcinomas. Interestingly, Merkel cell polyomavirus was detected only in ordinary (pure) Merkel cell carcinomas; none of the 4 combined Merkel cell carcinomas + squamous cell carcinomas was positive for Merkel cell polyomavirus (P = .001). Morphometric analyses revealed that Merkel cell polyomavirus-negative Merkel cell carcinomas had more irregular nuclei (P < .001) and more abundant cytoplasm (P = .001) than Merkel cell polyomavirus-positive Merkel cell carcinomas, which had uniform round nuclei and scant cytoplasm. Reliability of the morphometry was confirmed using intraobserver and interobserver reliability tests. These results demonstrated statistically significant differences in tumor cell morphology between Merkel cell polyomavirus-positive and -negative Merkel cell carcinomas and reconfirmed the absence of Merkel cell polyomavirus in combined tumors. Furthermore, the results strongly suggest fundamental biological differences between Merkel cell polyomavirus-positive and -negative Merkel cell carcinomas, supporting that Merkel cell polyomavirus plays an important role in the pathogenesis of Merkel cell polyomavirus-positive Merkel cell carcinoma.
To investigate the lymphomagenesis of NK/T lymphoma, we comprehensively and systematically analyzed the expression pattern of the human NK/T cell line (NK-YS) genome by cDNA expression array and tissue microarray. We detected significant changes in the gene expression of NK-YS cell line: an increase in 18 and a decrease in 20 genes compared to normal NK cells or peripheral blood mononuclear cells. Among these genes, we found a strong decrease in hematopoietic cell specific protein-tyrosine-phosphatase SH-PTP1 (SHP1) mRNA by cDNA expression array and reverse transcriptase-polymerase chain reaction. Further analysis with standard immunohistochemistry and tissue microarray, which used 207 paraffin-embedded specimens of various kinds of malignant lymphomas, showed that 100% of NK/T lymphoma specimens and more than 95% of various types of malignant lymphoma were negative for SHP1 protein expression. On the other hand, SHP1 protein was strongly expressed in the mantle zone and interfollicular zone lymphocytes in reactive lymphoid hyperplasia specimens. In addition, various kinds of hematopoietic cell lines, particularly the highly aggressive lymphoma/leukemia lines, lacked SHP1 expression in vitro, suggesting that loss of SHP1 expression may be related to not only malignant transformation, but also tumor cell aggressiveness. SHP1 expression could not be induced in either of two NK/T cell lines by phorbol ester, suggesting that genetic impairment or modification with methylation of SHP1 DNA could be one of the critical events in the pathogenesis of NK/T lymphoma. This evidence strongly suggests that loss of SHP1 gene expression plays an important role in multistep tumorigenesis, possibly as an anti-oncogene in the wide range of lymphomas/leukemias as well as NK/T lymphomas.
Coding regions of the rbcL and matK genes of cpDNA were sequenced to analyze phylogenetic relationships of the family Liliaceae sensu stricto, including the major 16 genera of Medeoloideae and Lilioideae of the Liliaceae, in reference to several genera such as Scoliopus, Uvularia, Disporum, and Trillium used as outgoups. The results were congruent with the taxonomic concept of Liliaceae sensu stricto recently proposed by
Tamura (1998). The inter‐ and infrageneric relationships in the genus Lilium and allied taxa were then analyzed based upon the rbcL and matK gene sequencing data, using Medeola and Erythronium as outgroups. The rbcL gene has evolved more slowly than matK and its phylogenetic resolution has been poor as a result of the low base substitution rates; whereas the matK gene has shown a much higher base substitution: 104 variable sites (including 80 informative sites) out of 1641 base pairs were detected. In addition, a remarkably high number of indels, i.e. 19 insertion/deletion events, were detected in the matK gene, which provided us with new evidence for structural changes of this gene within the genus Lilium and allied taxa. Phylogenetic analyses based on the majority rule of the sequence data of matK gene revealed that the genus Lilium consists of three different major clades, including taxa that were placed into different sections by earlier taxonomic treatments, and thus the results of molecular systematic analysis was not congruent with sectional delimitations of the genus Lilium based on the morphological characters. Nomocharis pardanthina and Nomocharis saluenensis were ingroup taxa of Lilium. Notholirion, Cardiocrinum, and Fritillaria turned out to be sister groups to Lilium. An evaluation of the morphological and life‐history characteristics was also attempted in light of the molecular phylogeny.
Progressive fibrosis, assessed by sequential biopsies, was significantly correlated with development of hepatocellular carcinoma in patients who had achieved a sustained virological response for hepatitis C virus.
The SVR rate was lower in elderly patients than in younger patients. However, in elderly patients combination therapy was most beneficial for genotype 1 patients, male patients with HCV RNA concentrations < 2,000,000 IU/ml and patients with genotype 2.
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