• BMB Reports
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• 제55권8호
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• pp.401-406
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• 2022

Ahnak, a large protein first identified as an inhibitor of TGF-β signaling in human neuroblastoma, was recently shown to promote TGF-β in some cancers. The TGF-β signaling pathway regulates cell growth, various biological functions, and cancer growth and metastasis. In this study, we used Ahnak knockout (KO) mice that underwent a 70% partial hepatectomy (PH) to investigate the function of Ahnak in TGF-β signaling during liver regeneration. At the indicated time points after PH, we analyzed the mRNA and protein expression of the TGF -β/Smad signaling pathway and cell cycle-related factors, evaluated the cell cycle through proliferating cell nuclear antigen (PCNA) immunostaining, analyzed the mitotic index by hematoxylin and eosin staining. We also measured the ratio of liver tissue weight to body weight. Activation of TGF-β signaling was confirmed by analyzing the levels of phospho-Smad 2 and 3 in the liver at the indicated time points after PH and was lower in Ahnak KO mice than in WT mice. The expression levels of cyclin B1, D1, and E1; proteins in the Rb/E2F transcriptional pathway, which regulates the cell cycle; and the numbers of PCNA-positive cells were increased in Ahnak KO mice and showed tendencies opposite that of TGF-β expression. During postoperative regeneration, the liver weight to body weight ratio tended to increase faster in Ahnak KO mice. However, 7 days after PH, both groups of mice showed similar rates of regeneration, following which their active regeneration stopped. Analysis of hepatocytes undergoing mitosis showed that there were more mitotic cells in Ahnak KO mice, consistent with the weight ratio. Our findings suggest that Ahnak enhances TGF-β signaling during postoperative liver regeneration, resulting in cell cycle disruption; this highlights a novel role of Ahnak in liver regeneration. These results provide new insight into liver regeneration and potential treatment targets for liver diseases that require surgical treatment.

• BMB Reports
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• 제55권12호
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• pp.633-638
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• 2022

Liver regeneration is a well-known systemic homeostatic phenomenon. The N⁶-methyladenosine (m⁶A) modification pathway has been associated with liver regeneration and hepatocellular carcinoma. m⁶A methyltransferases, such as methyltransferase 3 (METTL3) and methyltransferase 14 (METTL14), are involved in the hepatocyte-specific-regenerative pathway. To illustrate the role of METTL14, secreted from non-parenchymal liver cells, in the initiation phase of liver regeneration, we performed 70% partial hepatectomy (PH) in Mettl14 heterozygous (HET) and wild-type (WT) mice. Next, we analyzed the ratio of liver weight to body weight and the expression of mitogenic stimulators derived from non-parenchymal liver cells. Furthermore, we evaluated the expression of cell cycle-related genes and the hepatocyte proliferation rate via MKI67-immunostaining. During regeneration after PH, the weight ratio was lower in Mettl14 HET mice compared to WT mice. The expressions of hepatocyte growth factor (HGF) and tumor necrosis factor (TNF)-α, mitogens derived from non-parenchymal liver cells that stimulate the cell cycle, as well as the expressions of cyclin B1 and D1, which regulate the cell cycle, and the number of MKI67-positive cells, which indicate proliferative hepatocyte in the late G1-M phase, were significantly reduced in Mettl14 HET mice 72 h after PH. Our findings demonstrate that global Mettl14 mutation may interrupt the homeostasis of liver regeneration after an acute injury like PH by restraining certain mitogens, such as HGF and TNF-α, derived from sinusoidal endothelial cells, stellate cells, and Kupffer cells. These results provide new insights into the role of METTL14 in the clinical treatment strategies of liver disease.

• 한국간담췌외과학회지
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• 제27권2호
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• pp.151-157
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• 2023

Backgrounds/Aims: Cholangiocarcinoma (CCA) can be classified as intrahepatic CCA or extrahepatic CCA (eCCA). We intended to analyze and reports the survival outcomes for eCCA. Methods: Surveillance, epidemiology, and end results (SEER) registry, site recode C24.0, was used to select cases of eCCA from 2000 to 2018. Patients with incomplete data or ages <18 years were excluded. Results: Male (52.69%) and White race (77.99%) predominated. Compared with 2000-2006, survival increased in 2013 (adjusted hazard ratio [HRadj]: 0.68, 95% confidence interval [CI] 0.58-0.70; p < 0.01). Surgery with chemoradiotherapy (HRadj: 0.69, 95% CI 0.60-0.7; p < 0.01) and surgery with chemotherapy (HRadj: 0.72, 95% CI 0.62-0.83; p < 0.01) improved survival over surgery alone. Compared with surgery without lymph node (LN) removal, surgery of four or more regional LN reduced the risk of death by 58% (HRadj: 0.42, 95% CI 0.36-0.51; p < 0.01). Compared with patients without surgery, patients who underwent bile duct excision (HRadj: 0.82, 95% CI 0.72-0.94; p < 0.01), simple or extended lobectomy (HRadj: 0.85, 95% CI 0.75-0.95; p = 0.009), and hepatectomy (HRadj: 0.80, 95% CI 0.72-0.88; p < 0.01) significantly improved survival. Patients with distal CCA had a 17% higher survival than perihilar CCA (HRadj: 0.83, 95% CI 0.74-0.92; p < 0.01) and LN dissection was equally beneficial for both subgroups (p < 0.01). Conclusions: Surgery with chemoradiotherapy has a proven increase in the 5-year survival of the eCCA. LN resection, bile duct excision, lobectomy, and hepatectomy have better outcomes.

• 한국간담췌외과학회지
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• 제26권4호
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• pp.313-317
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• 2022

Backgrounds/Aims: Despite its limited benefits, operative site drainage after elective hepatectomy is routinely used. This study aimed to investigate the safety and effectiveness of left lateral sectionectomy without operative site drainage. Methods: This study retrospectively collected data from 31 patients who underwent elective left lateral sectionectomy between January 2017 and June 2020. Based on whether operative site drainage was used, the patients were divided into two groups: drainage and non-drainage of the operative site and a comparative analysis was conducted. Results: A total of 31 patients underwent left lateral sectionectomy during the study period. Of these, 22 patients were diagnosed with hepatocellular carcinoma; three, with intrahepatic cholangiocarcinoma; three, with liver metastasis; and three, with benign liver disease. Ten patients underwent laparoscopy. No significant differences were observed between the open and laparoscopic surgery groups. In the univariate analysis, there were no significant differences in the pre-, intra-, and postoperative clinicopathological factors between the non-drainage and drainage groups. The hospitalization period in the non-drainage group was significantly shorter than in the drainage group (8.44 days vs. 5.87 days, p < 0.05). In the operative site drainage non-use group, there were no cases of intraperitoneal fluid collection requiring additional procedures. Conclusions: Routine use of surgical drainage for left lateral sectionectomy of the liver to prevent intraperitoneal fluid collection is unnecessary.

• Journal of Chest Surgery
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• 제9권2호
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• pp.117-124
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• 1976

Hemorrhage into the biliary system as a consequence of injury to the liver has been called "traumatic hemobilia," a term introduced by Sandblom in 1948. The source of gastrointestinal hemorrhage has been frequently misinterpreted, resulting in inadequate or inappropriate treatment, often with catastrophic results and needless fatalities. It is now being diagnosed with increasing frequency, due to more widespread knowledge of the syndrome and improved diagnostic means. we experienced 2 cases of hemobilia following blunt chest trauma, One patient had! multiple rib fractures on right chest by car traffic accident and 13 days later, suddenly massive melena was developed with nausea, vomiting, jaundice and severe pain on right upper quadrant. And so, he had operated on the ligation of Rt. hepatic artery and partial right hepatectomy for a traumatic hemobilia. The other one also revealed similar symptoms 20 days later following blunt chest injury by falling down accident. However, uneventful recovery was seen without any of surgical intervention in this case.

• Toxicological Research
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• 제7권1호
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• pp.93-112
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• 1991

This study was carried out to investigate the various factors on induction of experimental hepatocarcinogenesis in Sprauge-Dawley rats. The experimental animals were divided into three Experiment. Experiment I, II and III were began rats with initial age of 6, 16 and 55 weeks, respectively. All Experiment were injected intrapertioneal with diethylnitrosamine (DENA` 200 mg/kg) as an intiator and group 3, 4 of Experiment I, II and III were fed on diet containing 0.02% 2-acetylaminofluorene (2-AFF) as a promoter for 6 weeks. Three weeks after two-thirds partial hepatectomy was performed in group 2, 4 of Experiment I & II and group 3 of Experiment III.

• Toxicological Research
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• 제2권1호
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• pp.1-7
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• 1986

Procarcinogen induced DNA single-strand breaks and unschduled DNA synthesis were measured in primary rat hepatocytes culture. For DNA single-strand breaks assay, rat liver DNA was prelabeled by injection 3H-thymidine during the peak of DNA synthesis following partial hepatectomy. Hepatocytes were isolated from the rat 2 weeks after surgery by a collagenase perfusion techinique and maintained as monolayers in serum free medium on collagen-coated culture dishes. DNA sigle-strand breaks were measured by the alkaline elution techinique.

• Environmental Analysis Health and Toxicology
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• 제13권3_4호
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• pp.71-75
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• 1998

Carbendazim, which is widely used fungicide, was investigated for rat hepatocarcinogenesis using a medium-term carcinogenicity bioassay. All rats were initially given a single dose (200mg/kg) of diethylnitrosamine (DEN) i.p. and then, starting 2 weeks later, carbendazim treatment group and positive control group received carbendazim (7 mg/kg/ day) and 2-acetylaminofluorene (2-AAF, 1%), respectively, in the diet for 6 weeks. All rats were subjected to two-thirds partial hepatectomy (PH) at week 3 and sacrificed at week 8. Carcinogenic potential was scored by comparing the number and area per cm$^2$ of induced glutathione-S-transferase placental form (GST-P) positive foci in the liver. Carbendazim had no effect in the increase of body weight, hematological and biochemical values, and the number and area of GST-P positive loci. These results suggest that this bioassay using DEN-PH method can be useful for detection of hepatocarcinogenic potentials of pesticide.

• Toxicological Research
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• 제5권2호
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• pp.135-149
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• 1989

The effect of Ganoderma lucidum (Polyporaceae) extract on initiation and promotion of liver preneoplastic lesions in chemical carcinogenesis were examined in male rats. Male Fisher 344 rats, 8 weeks old, were injected i.p. with diethylnitro-samine(DENA` 200 mg/kg) as an initiator and were fed on diet containing 0.02%-acetaminofluorene (2-AAF) as a promoter for 2 weeks (group 1, 2` 2-4 week) and were fed on basal diet (group 3 and 4). The rats in test groups(group 1 and 3) were fed on diet containing 0.1% of Ganoderma lucidum extract for 6 weeks (2-8 week).

• 한국동물위생학회지
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• 제46권3호
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• pp.249-253
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• 2023

A 12-year-old neutered male Maltese was brought to our hospital with loss of appetite, generalized alopecia, anemia, and a palpable abdominal mass. Ultrasonography revealed multiple abdominal masses in the liver and spleen. Subsequently, splenectomy and liver biopsy were performed, and the masses were histologically diagnosed as metastatic fibrosarcomas of unknown primary origin. The owner refused further investigations such as computed tomography and hepatectomy, therefore, we decided to initiate chemotherapy in the form of metronomic therapy with toceranib phosphate, which has several advantages, such as better tolerability, low cost, and convenience. The size and number of hepatic fibrosarcomas continued to increase despite continued administration of toceranib (10 mg/dog, PO, q48h). The dog died approximately 43 days after initiation of the toceranib treatment. To the best of our knowledge, this is the first report on toceranib therapy for metastatic hepatic fibrosarcoma in a dog.