[A case of acute pancreatitis induced by interferon therapy for chronic hepatitis C].
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Acute Disease↗
Biomedical subjects
A Mitoro
Publications and source records attributed to A Mitoro.
Autoimmunity during alpha-interferon therapy for chronic hepatitis C.
One hundred twenty-five patients with chronic hepatitis C were treated with natural IFN alpha or recombinant IFN alpha-2a, daily doses of 3 MU or 9 MU, respectively. IFNs were given 6 times a week for the first 2 weeks followed by thrice weekly administration for 12 weeks or more. ANA, TMA, AMA and anti-DNA antibody newly developed in 8, 1, 2 and 1 patient, respectively. Furthermore, we encountered some cases in which underlying autoimmune disorders were thought to be exacerbated by IFNs. It is important to pay sufficient attention to the development of autoimmune diseases in IFN therapy for chronic hepatitis C.
Adult↗
Exacerbation of ulcerative colitis during alpha-interferon therapy for chronic hepatitis C.
We report a 34-year-old man with chronic hepatitis C who showed exacerbation of ulcerative colitis during alpha-interferon (IFN alpha) therapy. Discontinuance of the IFN alpha therapy improved his symptoms, suggesting that IFN alpha administration might worsen ulcerative colitis. The administration of sulfasalazine allowed the patient to receive IFN alpha again without flare-up of ulcerative colitis. This case suggests the possible efficacy of sulfasalazine therapy in patients with ulcerative colitis complicated by some other diseases requiring IFN alpha administration.
Adult↗
Sonographic estimation of liver tumor development induced by oral administration of thioacetamide in rat.
Animal models for various types of cancer are of great help in the study of tumors and antitumor effects. Subcutaneous models have been widely utilized because they can be produced easily by subcutaneously implanting tumor cells into animals. Although subcutaneous models are very convenient for examining tumor development, they are definitely different from clinical manifestations of original tumors. In orthotopic animal models for internal tumors, however, it is difficult to examine tumor development without sacrificing animals. We demonstrate here that the occurrence and growth of liver tumors induced by oral administration of thioacetamide into rats were clearly observable by ultrasonography, and that the sonographic estimation was accurate. It was observed sonographically that the number and volume of liver tumors increased proportionately with TAA treatment periods. These results indicate that sonography is a useful and non-invasive method to investigate liver tumor development in rats.
Administration, Oral↗
Inhibitory effects of human sera on adenovirus-mediated gene transfer into rat liver.
Recent advances in molecular biology have made gene therapy for cancer feasible in clinical trials. Although recombinant adenovirus is an attractive vehicle for transferring therapeutic genes in vivo, animal studies have indicated that the clinical usefulness of adenovirus vectors may be limited by their immunogenicity. It has been shown that neutralizing antibodies against adenoviruses reduce the efficiency of vector readministration. It is of great importance to examine the effects of human sera on adenovirus-mediated gene transfer, because the majority of prospective gene therapy patients are likely to have been exposed to wild-type adenoviruses. In the present study, it was shown that anti-adenovirus antibody-positive human sera with the lowest positive titer substantially inhibit the adenovirus-mediated gene transfer not only in vitro but also in vivo. These results may have important implications for efficacy considerations when adenovirus vectors are employed in the clinical setting.
3T3 Cells↗
Bystander effect caused by cytosine deaminase gene and 5-fluorocytosine in vitro is substantially mediated by generated 5-fluorouracil.
Because it appears impossible to transfer toxic genes to all the cells of a cancer, the bystander effect is critical to induce effective antitumor effects. In the present study, possible in vitro mechanisms of the bystander effect by the cytosine deaminase (CD) gene and 5-fluorocytosine (5-FC) were investigated. CD-transduced cancer cells exhibited much higher sensitivity to 5-FC compared to parental cells. CD-transduced cells caused killing of neighboring parental cells in the presence of 5-FC, irrespective of direct cell-to-cell contact. Media conditioned by CD-transduced cells and 5-FC contained considerable amounts of 5-fluorouracil (5-FU) and exhibited profound cytotoxicity on parental cells. Furthermore, this killing ability of conditioned media correlated well with 5-FU levels converted from 5-FC by CD-transduced cells. CD was shown not to be secreted into media from cells. These results indicate that diffusible 5-FU plays the substantially causative role in the in vitro bystander effect caused by the CD/5-FC system.
Animals↗
Analysis of intrahepatic invasion of hepatocellular carcinoma using fluorescent dye-labeled cells in mice.
Despite intensive efforts in the treatment of hepatocellular carcinoma (HCC), its prognosis remains poor, mainly because of intrahepatic metastasis. It is, therefore, important to investigate the invasive and metastatic behavior of HCC. To examine this, murine HCC cells were labeled with the fluorescent carbocyanine dye, DiI and implanted under the capsule of the liver of syngeneic mice. Optimal conditions are described for labeling HCC cells with DiI. Histological analysis using fluorescent and confocal microscopes revealed that HCC cells migrate to and invade the adjacent portal vein, but not the adjacent central vein. Conversely, DiI-labeled hepatocytes were shown not to migrate in the liver. These results suggest that intrahepatic metastasis of HCC occurs by invading the portal venous system. Furthermore, it is indicated that orthotopic implantation of fluorescent dye-labeled tumor cells may be a convenient and useful method to investigate the invasive and metastatic behavior of various types of cancer.
Animals↗