• Korean Journal of Veterinary Pathology
• /
• v.1 no.1
• /
• pp.33-39
• /
• 1997

We investigated metabolism and carcinogenesis in livers of Sprague-Dawley rats fed juices and pelleted diets containing Korean native plants petasites japonicus Maxim by evaluating cell localization and expression of cytochrome P450s and GST-P. Anti-cytochrome P450s application in liver sections revealed three to four times increased expression of cytochrome P450E1 immunoreactivity in degenerative hepatocytes when compared to histologically normal hepatocytes. Anti-GST-P in showed positive pren plastic foci as well as in individual hepatocytes randomly scattered throughout all liver sections examined. Additionally GST-P was evident in proliferative endothelial cells and biliary epithelial cells in exposed rat livers. These results suggested that the increased level of cytochrome P4502E1 in affected hepatocytes was a direct consequence of Petasites japonicus toxicity. Further immunoreactivity to anti-GST-P in hepatocytes endothelial cells and biliary epithelial cells indicated a possible preneoplastic effects of Petasites japonicus in Sprague-Dawley rat.

• Parasites, Hosts and Diseases
• /
• v.31 no.2
• /
• pp.83-90
• /
• 1993

We performed bromodeoxyuridine (BrdU) staining to observe the proliferation pattern of epithelial cells on the biliaJy mucosa in Clonorchis sinensis infection. Albino rats were infected with 100 metacercariae each and their livers were processed for histopathological observation after BrdU injection. Five to six sites in the liver of a rat were selected for paraffin section, and stained immunohistochemically to visualize BrdU incorporating cells. The flukes were mainly in the common bile duct and right or left hepatic bile ducts. The proportion of stained epithelial cells in the infected bile ducts where the worms were found on the section was 2.9-10.2% at 1 week after infection. 7.3-12.8% at 2 weeks, 7.3-13.4% at 5 weeks, and 8.4-14.8% at 15 weeks while in the non-infected ducts o to 2.7% cells were stained. The stained cells were mainly at the base of the mucosal layer. It is suggested that mucosal epithelial cells of the bile ducts infected with C. sinensis become hyperplastic mainly by direct and local stimulation of the worms.

• Parasites, Hosts and Diseases
• /
• v.31 no.1
• /
• pp.13-20
• /
• 1993

The histological change of the billary mucosa in clonorchiasis is characterized as adenomatous hyperplasia, and cross-sectioned mucosa looks like intestinal mucosa. In addition to the glandular hyperplasla, the metaplasia of mucin secreting cells is also known. The present study investigated the presence of intestinal secretion from the biliary mucosal cells of rabbits and rats with Clonorchis sinensis infection. The rabbit was infected with 300 and the rat was infected with 100 metacercariae of C. sinensif. A part of the animals were followed up after praziquantel treatment. The rabbit livers were prepared for histochemistry to observe any endocrine secretion and the bile duct mucosa of the mice was processed far the activity of brush border membrane (BBM)-bound enzymes of the small intestine. Immunohistochemistry with the polyclonal antibodies and biotin-streptavidin-peroxidase staining kit showed no positive cells for gastrin and secretin, but a few cells were positive for serotonin. The proliferated billiw mucosa of the mice revealed no activity of dissaccharidases and aminopeptidase. Only alkaline phosphatase activity was found both in the control and the infected. The hyperplastic billary mucosal cells showed no gastrointestinal secretory functions. The serotonin secreting cells may be one of the inflammatory cells.

• Parasites, Hosts and Diseases
• /
• v.25 no.2
• /
• pp.99-109
• /
• 1987

The present study was carried out to examine the effect of a calcinogen, aflatoxin B1 on the ultrastructural changes of ciliary epithelial cells in mice infected with Clonerchis sinensis. A total of 93 male albino mice(BALB/c strain) was divided into 3 groups; group I, treated with 1.0 ppm aflatoxin Bl for 12 weeks; group II, given 50 C. sinensis n;etacercariae, and group III, given 50 metacercariae and treated with 1.0 ppm aflatoxin Bl for 12 weeks. Three mice served for untreated-uninfected controls. From 4 weeks after the treatsment and/or in(ection, three mice from each group were sacrificed at 4 week intervals up to the 40th week, and their hepatobiliary tissues were prepared for transmission electron microscopy. The most prominent ultrastructural changes in group I were remarkable enlargement of nuclear size, separation of nucleolus, dispersed chromatin granules in nuclei and increased dense granules along the inner membrane of nuclei. In the cytoplasm there was slight proliferation of mitochondria and endoplasmic reticulum (ER) at earlier stage. At the 12th week separation of fibrillar and granular components of the nucleolus was a characteristic finding. As the time elapsed, epithelial cells showed fiattened-cuboidal form and a tendency of atrophy. Most of the nuclei were elongated and polygonal in shape. In group II the appearance of elaborate interwoven folds of lateral cytoplasm forming a labyrinth of interconnected intercellular space and variety in nuclear shape were the prominent fadings at earlier stage. The cytoplasm showed slight proliferation and dilatation of mitochondria and ER, and a small number of mucin droplets. In the basement membrane scanty fibrous cells were seen. With time, variety in nuclear shape, marked proliferation and dilatation of rough ER and some collagen fibrils were demonstrated. Other features of intracellular organelles and mucin droplets persisted. In group III cuboidal epithelial cells showed their remarkably enlarged and irregular nuclei, increased chromatin granules in the nuclei, separated nucleoli, proliferated and dilated rough ER. With time, sequestered mitochondria showed blob-like evaginations which lacked cristae and dense matrix, and were limited by a single membrane. Since the 20th week, microvilli were relatively scanty and poorly developed. Organelles and inclusions in the cytoplasm of metaplastic cells were poor. Nuclei were variable in shape. The nlost prominent changes at later stage were separation of nuclei from the cytoplasm, and appearance of numerous and irregularly angled electron dense granules in the nuclei.

• Toxicological Research
• /
• v.19 no.1
• /
• pp.67-72
• /
• 2003

Cholestatic liver injury results from the accumulation of toxic bile salts within the liver. The aim of the present study is to elucidate the changes in expression and cellular localization of apoptosis related proteins in the liver of bile duct-ligated (BDL) rat. Extrahepatic cholestasis was induced by double ligation of the common bile duct and cut between the ligatures. Animals were sacrificed at day 3 and at week 1, 2, 4, 6, and 8 after BDL. The number of TUNEL positive cells was increased significantly after 3 days of BDL, decreased over 2 weeks and remained constant thereafter. Fas expression was not changed and activation of caspase 8 did not occur. Fas immunoreactivity was exclusively observed in the cytoplasm of hepatocytes, indicating that Fas expressed in rat hepatocytes is a soluble form. Hepatocyte apoptosis was associated with Bax expression, which showed a peak at day 3 and decreased over time gradually. Immnunostaining of Bax was observed in hepatocytes and bile duct epithelial cells (BEC) of control and BDL rats. Bcl-2 was increased over time in BDL rats. These results suggest that apoptosis of hepatocytes in BDL rats is independent of Fas and controlled by Bax expression.

• Molecules and Cells
• /
• v.43 no.5
• /
• pp.491-499
• /
• 2020

Hippo signaling acts as a tumor suppressor pathway by inhibiting the proliferation of adult stem cells and progenitor cells in various organs. Liver-specific deletion of Hippo pathway components in mice induces liver cancer development through activation of the transcriptional coactivators, YAP and TAZ, which exhibit nuclear enrichment and are activated in numerous types of cancer. The upstream-most regulators of Warts, the Drosophila ortholog of mammalian LATS1/2, are Kibra, Expanded, and Merlin. However, the roles of the corresponding mammalian orthologs, WWC1, FRMD6 and NF2, in the regulation of LATS1/2 activity and liver tumorigenesis in vivo are not fully understood. Here, we show that deletion of both Wwc1 and Nf2 in the liver accelerates intrahepatic cholangiocarcinoma (iCCA) development through activation of YAP/TAZ. Additionally, biliary epithelial cell-specific deletion of both Lats1 and Lats2 using a Sox9-Cre^ERT2 system resulted in iCCA development through hyperactivation of YAP/TAZ. These findings suggest that WWC1 and NF2 cooperate to promote suppression of cholangiocarcinoma development by inhibiting the oncogenic activity of YAP/TAZ via LATS1/2.

• The Korean Journal of Pharmacology
• /
• v.17 no.1 s.28
• /
• pp.17-25
• /
• 1981

No evidence has accumulated that lead compound is an essential component for biological function in animals. Lead is absorbed primarily through the epithelial mucosal cells in duodenum and the absorption can be enhanced by the substances which bind lead and increase its solubility. Iron, zinc and calcium ions, however, decrease the absorption of lead without affecting its solubility, probably by competing for shared absorptive receptors in the intestinal mucosa. Therefore, the absorption of lead is increased in iron deficient animals. Lead shows a strong affinity for ligands such as phosphate, cysteinyl and histidyl side chains of proteins, pterins and porphyrins. Hence lead can act on various active sites of enzymes, inhibiting the enzymes which has functional sulfhydryl groups. lead inhibits the activity of ${\delta}$-aminolevulinic acid dehydratase for the biosynthesis of hemoproteins and cytochrome, which catalyzed the synthesis of monopyrrole prophobilinogen from ${\delta}$-aminolevulinic acid. Accordingly lead decrease hepatic cytochrome p-450 content, resulting an inhibition of the activity of demethylase and hydroxylase in liver. Little informations are available on the effect of lead on digestive system although the catastrophic effects of lead intoxication are well documented. The present study was, therefore, attempted to investigate the effect of lead on pancreaticobiliary secretion in rats. Albino rats of both sexes weighing $170{\sim}230g$ were used for this study. The animals were divided into one control and three treated groups, i.e., control (physiologic saline 1.5ml/kg i.p.), lead acetate $(l0{\mu}mole/kg/day\;i.p.)$, $Pb(Ac)_2$ and EDTA$(each\;10{\mu}mole/kg/day\;i.p.)$, $Pb(Ac)_2$ and $FeSO_4(each\;l0{\mu}mole/kg/day\;hp)$. The pancreatico-biliary juice was collected under urethane anesthesia, and activities of amylase and lipase were determined by employing Sumner's and Cherry and Crandall's methods. The summarized results are follows. 1) In the experiment for acute toxicity of lead acetate, 20% of mortality was observed in rat treated with lead acetate as well as inhibition of the activity of amylase in the juice at the 3 rd day of the treatment. 2) No increases in body weight were observed in rats treated with lead acetate, while in control group the significant increases were observed. However, the body weights of animals were increased in the group lead acetate plus EDTA or $FeSO_4$. 3) Lead acetate decreased significantly the volume of pancreatico-biliary juice whereas additional treatment of EDTA and $FeSO_4$ prevented it. 4) Total activity of amylase was markedly reduced due to lead acetate treatment, but no change was showed following additional treatment with EDTA and $FeSO_4$. 5) No changes in the cholate and lipase output were observed in rats treated with lead acetate as compared with that of control rats. 6) Increase in bilirubin output in rats treated with lead acetate was shown on the 2nd and 3rd weeks treatment. 7) In the case of in vitro experiment, lead acetate also markedly inhibited release of amylase from pancreatic fragment. 8) Histologic finding indicated that acini vacuolation was induced in the pancreatic tissue of rat treated with lead acete. From the above results, it might be concluded that lead acetate decreases the volume of pancreatico-biliary secretion and inhibits the amylase activity, by acting directly on pancreatic cells.

• The Korean Journal of Cytopathology
• /
• v.3 no.1
• /
• pp.1-11
• /
• 1992

From the one hundred forty eight patients with evidence of biliary tract obstruction, 275 bile samples were obtained from percutaneously placed biliary drainage catheters. Of the 148 patients, ova of Clonorchis sinensis were demonstrated in 17 patients (11.5%), with the epithelial cells. Among them, one case also demonstrated coexisting adenocarcinoma. In 105 patients, the medical records were available for review and the clinical diagnoses were malignancy in 99 patients and benign lesion in 6 patients. Of the 99 patients in which clinico-radiologic diagnosis were malignant, cytologic results were positive in 23.2%. Dividing the patients Into two groups, the ones with tumor of bile duct origin (group I) and the others with tumors producing extrinsic compression of bile duct, such as periampullary carcinoma, pancreas head carcinoma or metastatic carcinoma in lymph nodes from tumors of adjacent organs (group II), the cytologic results were positive in 37% and 11.6%, respectively. In patients with histologic confirmation, the positive correlation was found in 50% and 20% in group I and group II, respectively, with remarkable difference between two groups. There were no false positives in cytologic diangosis. The overall concordance rate of cytologic diagnosis with diagnosis of clinical investigation in both benign and malignant lesions was 27.6% and the diagnostic specificity was 100%.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.21
• /
• pp.9511-9515
• /
• 2014

Cholangiocarcinoma (CCA) is a cancer of the bile duct epithelial cells. The highest incidence rate of CCA with a poor prognosis and poor response to chemotherapy is found in Southeast Asian countries, especially in northeastern Thailand and Lao PDR. Cathepsin B is a lysosomal cysteine protease which is regulated by cysteine proteinase inhibitors such as cystatin C. Elevation of cathepsin B levels in biological fluid has been observed in patients with inflammatory diseases and many cancers. We aimed to investigate the serum cathepsin B and cystatin C levels of CCA patients to evaluate the feasibility of using cathepsin B and cystatin C as markers for the diagnosis of CCA. Fifty-six sera from CCA patients, 17 with benign biliary diseases (BBD) and 13 from controls were collected and the cathepsin B and cystatin C levels were determined. In addition, cathepsin B expression was investigated immunohistochemically for 9 matched-pairs of cancerous and adjacent tissues of CCA patients. Serum cathepsin B, but not cystatin C, was significantly higher in CCA and BBD patient groups compared to that in the control group. Consistently, all cancerous tissues strongly expressed cathepsin B while adjacent tissues were negative in 7 out of 9 cases. In contrast, serum cystatin C levels were comparable between CCA and control groups, although serum cystatin C levels in the BBD group was higher than that in the control or CCA groups. When the serum cathepsin B to cystatin C ratio was calculated, that of the CCA group was significantly higher than that of the control group, and, although statistically not significant, the ratio of CCA group showed a trend to be higher than that of the BBD group. Thus, the cathepsin B to cystatin C ratio might be used as an alternative marker for aiding diagnosis of CCA.