• Journal of Veterinary Clinics
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• v.35 no.3
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• pp.100-102
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• 2018

A nine-year-old spayed female Turkish angora cat presented for evaluation of anorexia, lethargy, vomiting, ptyalism and jaundice. Based on clinical examinations including laboratory examinations, concurrent inflammatory condition of the biliary system, pancreas and intestines (triaditis) was suspected. The cat was under antibiotic and immune-suppressive therapy, but there was no response. Further examination revealed the possibility of malignant hepatobiliary tumor with pulmonary metastasis. The condition of the cat continued to deteriorate and the cat died 3 weeks after the diagnosis. This case demonstrates the clinical findings of triaditis combined with suspected malignant hepatobiliary tumor.

• BMB Reports
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• v.45 no.11
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• pp.629-634
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• 2012

The human glycoprotein, stanniocalcin 2 (STC2) plays multiple roles in several tumor types, however, its function and clinical significance in hepatocellular carcinoma (HCC) remain unclear. In this study, we detected STC2 expression by quantitative real-time PCR and found STC2 was upregulated in HCC tissues, correlated with tumor size and multiplicity of HCC. Ectopic expression of STC2 markedly promoted HCC cell proliferation and colony formation, while silencing of endogenous STC2 resulted in a reduced cell growth by cell cycle delay in G0/G1 phase. Western blot analysis demonstrated that STC2 could regulate the expression of cyclin D1 and activate extracellular signal-regulated kinase 1/2 (ERK1/2) in a dominant-positive manner. Transwell chamber assay also indicated altered patterns of STC2 expression had an important effect on cell migration. Our findings suggest that STC2 functions as a potential oncoprotein in the development and progression of HCC as well as a promising molecular target for HCC therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6393-6398
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• 2013

In this research, we used $GdCl_3$ (gadolinium chloride) to restrain the function of Kupffer cells and assessed effects on hepatocarcinogenesis and metastasis in the Kunming mouse. A 0.25% $GdCl_3$ solution (10 mg/kg b.w.) was infused via the vena caudalis of each mouse 1 week before inoculation of H22 cells and was continued once per three days. Then we observed the follow indexes 3 weeks after injection of H22 cells: tumor weight, histologic characteristics of tumor tissue by light microscopy, ultramicrostructure of Kupffer cells under the electron microscope, distribution and number of Kupffer cells by histochemical staining, and TNF-${\alpha}$ and IFN-${\gamma}$ levels in blood-serum and liver tissue by ELISA and RT-PCR. MMP-2 protein expression was tested by immunohistochemistry. The $GdCl_3$ pretreatment had no effect on the quantity of Kupffer cells, but clearly restrained their functions, with decrease of TNF-${\alpha}$ and IFN-${\gamma}$ levels and elevation of MMP2. Tumor immunity functions were markedly suppressed and tumor growth was accelerated with appearance of metastasis. Furthermore, survival time of trial mice was shortened.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.1
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• pp.23-29
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• 2015

Background: Current cancer therapy mainly focuses on identifying novel targets crucial for tumorigenesis. The FoxM1 is of preference as an anticancer target, due to its significance in execution of mitosis, cell cycle progression, as well as other signal pathways leading to tumorigenesis. FoxM1 is partially regulated by oncoproteins or tumor suppressors, which are often mutated, lost, or overexpressed in human cancer. Since sustaining proliferating signaling is an important hallmark of cancer, FoxM1 is overexpressed in a series of human malignancies. Alarge-scale gene expression analysis also identified FoxM1 as a differentially-expressed gene in most solid tumors. Furthermore, overexpressed FoxM1 is correlated with the prognosis of cancer patients, as verified in a series of malignancies by Cox regression analysis. Thus, extensive studies have been conducted to explore the roles of FoxM1 in tumorigenesis, making it an attractive target for anticancer therapy. Several antitumor drugs have been reported to target or inhibit FoxM1 expression in different cancers, and down-regulation of FoxM1 also abrogates drug resistance in some cancer cell lines, highlighting a promising future for FoxM1 application in the clinic.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.8
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• pp.4759-4763
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• 2013

Background: Prognostic factors of postoperative early and late recurrence in patients with hepatocellular carcinoma (HCC) undergoing curative resection remain to be clarified. The aim of this study was to identify risk factors for postoperative early (${\leq}$ 2 year) and late (> 2 year) intrahepatic recurrences in patients with single HCCs without macrovascular invasion. Methods: A total of 280 patients from December 2004 to December 2007 were retrospectively included in this study. Intrahepatic recurrence was classified into early (${\leq}$ 2 year) and late (> 2 year) and the Chi-Square test or Fisher's exact test and multivariate logistic regression analysis were performed to determine significant risk factors. Results: During the follow-up, 124 patients had intrahepatic recurrence, early and late in 82 and 42 patients, respectively. Multivariate logistic regression analysis showed that microvascular invasion (p=0.006, HR: 2.397, 95% CI: 1.290-4.451) was the only independent risk factor for early recurrence, while being female (p = 0.031, HR: 0.326, 95% CI: 0.118-0.901), and having a high degree of cirrhosis (P=0.001, HR: 2.483, 95% CI: 1.417-4.349) were independent risk factors for late recurrence. Conclusions: Early and late recurrence of HCC is linked to different risk factors in patients with single HCC without macrovascular invasion. This results suggested different emphases of strategies for prevent of recurrence after curative resection, more active intervention including adjuvant therapy, anti-cirrhosis drugs and careful follow-up being necessary for patients with relevant risk factors.

• BMB Reports
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• v.51 no.12
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• pp.630-635
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• 2018

C-X-C motif chemokine ligand 2 (CXCL2) is a small secreted protein that exhibits a structure similar to the proangiogenic subgroup of the CXC chemokine family. Recently, accumulating evidence suggests that chemokines play a pivotal role in cancer progression and carcinogenesis. We examined the expression levels of 7 types of $ELR^+$ CXCLs messenger RNA (mRNA) in 264 clinical samples. We found that CXCL2 expression was stably down-regulated in 94% of hepatocellular carcinoma (HCC) specimens compared with paired adjacent normal liver tissues and some HCC cell lines. Moreover, CXCL2 overexpression profoundly attenuated HCC cell proliferation and growth and induced apoptosis in vitro. In animal studies, we found that overexpressing CXCL2 by lentivirus also apparently inhibited the size and weight of subcutaneous tumours in nude mice. Furthermore, we demonstrated that CXCL2 induced HCC cell apoptosis via both nuclear and mitochondrial apoptosis pathways. Our results indicate that CXCL2 negatively regulates the cell cycle in HCC cells via the ERK1/2 signalling pathway. These results provide new insights into HCC and may ultimately lead to the discovery of innovative therapeutic approaches of HCC.

• Molecules and Cells
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• v.45 no.5
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• pp.329-342
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• 2022

The liver is the predominant metastatic site for pancreatic cancer. However, the factors that determine the liver metastasis and the specific molecular mechanisms are still unclear. In this study, we used human pancreatic cancer cell line Hs766T to establish Hs766T-L3, a subline of Hs766T with stable liver metastatic ability. We performed RNA sequencing of Hs766T-L3 and its parental cell line Hs766T, and revealed huge differences in gene expression patterns and pathway activation between these two cell lines. We correlated the difference in pathway activation with the expression of the four core transcriptional factors including STAT1, NR2F2, GATA2, and SMAD4. Using the TCGA database, we examined the relative expression of these transcription factors (TFs) in pan-cancer and their relationship with the prognosis of the pancreatic cancer. Among these TFs, we considered GATA2 is closely involved in tumor metastasis and may serve as a potential metastatic driver. Further in vitro and in vivo experiments confirmed that GATA2-mediated transcriptional activation of Notch3 promotes the liver metastasis of Hs766T-L3, and knockdown of either GATA2 or Notch3 reduces the metastatic ability of Hs766T-L3. Therefore, we claim that GATA2 may serve as a metastatic driver of pancreatic cancer and a potential therapeutic target to treat liver metastasis of pancreatic cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10209-10215
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• 2015

To assess the contribution of tumor necrosis factor $(TNF){\beta}$ +252 polymorphisms to risk and prognosis of hepatocellular carcinoma (HCC), we enrolled 150 pairs of sex- and age-matched patients with HCC, patients with cirrhosis alone, and unrelated healthy controls. $TNF{\beta}$ +252 genotypes were determined by polymerase chain reaction with restriction fragment length polymorphism. Multivariate analysis indicated that $TNF{\beta}$ G/G genotype [odds ratio (OR), 3.64; 95%CI, 1.49-8.91], hepatitis B surface antigen (OR, 16.38; 95%CI, 8.30-32.33), and antibodies to hepatitis C virus (HCV) (OR, 39.11; 95%CI, 14.83-103.14) were independent risk factors for HCC. There was an additive interaction between $TNF{\beta}$ G/G genotype and chronic hepatitis B virus (HBV)/HCV infection (synergy index=1.15). Multivariate analysis indicated that factors associated with $TNF{\beta}$ G/G genotype included cirrhosis with Child-Pugh C (OR, 4.06; 95%CI, 1.34-12.29), thrombocytopenia (OR, 6.55; 95%CI, 1.46-29.43), and higher serum ${\alpha}$-fetoprotein concentration (OR, 2.53; 95%CI, 1.14-5.62). Patients with $TNF{\beta}$ G/G genotype had poor cumulative survival (p=0.005). Cox proportional hazard model indicated that $TNF{\beta}$ G/G genotype was a biomarker for poor HCC survival (hazard ratio, 1.70; 95%CI, 1.07-2.69). In conclusion, there are independent and additive effects between $TNF{\beta}$ G/G genotype and chronic HBV/HCV infection on risk for HCC. It is a biomarker for poor HCC survival. Carriage of this genotype correlates with disease severity and advanced hepatic fibrosis, which may contribute to a higher risk and poor survival of HCC. Chronic HBV/HCV infected subjects with this genotype should receive more intensive surveillance for early detection of HCC.

• The Korean Journal of Nuclear Medicine
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• v.19 no.2
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• pp.25-41
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• 1985

간흡충증은 한국 및 동남아세아에 널리 분포되어 있는 중요한 풍토병의 하나로서 진단은 전통적으로 분변검사에 의존하여 오고 있다. 최근 들어 담관내 간흡충 및 이의 합병증의 진단을 위해 ERCP 및 contrast cholangiogram등이 시도되었으나 실제에 이용하기에는 많은 제약이 있다 하겠다. 저자는 간흡충증에 있어서 최근 소개된 $^{99m}Tc-DISIDA$ hepatobiliary scintigraphy의 진단적 의의를 규명하고자 1982년부터 1983년까지 고신의대 부속 복음병원에서 검진한 간흡충증 환자 90명을 대상으로 하여 $^{99m}Tc-DISIDA$ hepatobiliary scintigraphy와 formalin-ether 원침법에 의한 분변검사를 시행하였다. $^{99m}Tc-DISIDA$ scintigram소견은 간내 담관 bile flow 및 총수담관 bile flow defect, 그리고 간세포기능의 정도에 따라 자료를 분석하였고 그외 합병증의 진단은 병록 기록, 수술 소견, ERCP 등에 의존하여 결론을 얻었다. $^{99m}Tc-DISIDA$ scintigraphy는 특이한 양상의 bile flow dynamics를 나타내었으며 간내 주담관의 intermittent irregular focal bile flow defect 및 tile flow stasis를 나타내고 말초담관의 bile flow defect는 경미하고 60분 내에 담관 bile flow activity의 완전한 배설을 나타내는 경우를 mild pattern, 간내 담관의 심한 irregular bile flow dynamics 및 간내담관의 심한 irregularity (담관내벽의 심한 불규칙성), 총수담관, 간내 주담관 및 말초 담관까지 심하게 irregular bile flow stasis를 나타내며 bile flow activity의 완전 베설이 $60\sim90$분사이 혹은 90분이상까지 인지된 경우를 moderate-severe pattern으로 분류하였다. 1) 분변검사상 간흡충증은 95검사중 70검사(환자 86명중 67명)에서 양성을 보여 분변 충난검사의 양성율은 73.7%였고 음성율은 26.3%였다. 2) $^{99m}Tc-DISIDA$ hepatobiliary scintigraphy는 90명중 70명에서 특이한 Cs-bile flow양성을 보였으며 양성율은 77.8%였으며 음성율은 22.2%였다. 3) $^{99m}Tc-DISIDA$ hepatobiliary scintigram양성율을 나타낸 환자 70명중 11명은 mild pattern, 59명은 moderate-severe pattern을 나타냈으며 그중 21명은 여러가지 간세포 기능 및 담관에 영향을 미치는 질환과 합병했지만 특이한 Cs-bile flow pattern을 dominent하게 나타내었으며 합병된 여러 질환들도 bile flow pattern상 인지 할 수 있었다. 4) $^{99m}Tc-DISIDA$ hepatobiliary scintigram 음성율을 나타낸 환자 20명중 8명은 만성간염, 5명은 간경변증, 3명은 재발성 농양성담관염(recurrent pyogenic cholangitis)과 간내담도의 stricture 및 담관담석증이 합병되었으며 scintigram상 합병증의 pattern을 나타냈고 4명에서는 low CBD obstruction을 나타내었으며 후에 CBD stone, CBD carcinoma, gall bladder Ca.의 porta hepatis 전이 및 clonorchis worms의 cluster에 의한 obstruction이 operation 및 ERCP로서 진단 되었다. 5) $^{99m}Tc-DISIDA$ hepatobiliary scintigraphy pattern은 현재의 자각증상과 관계된 dominent disease를 나타내었으며, 공간 점유병소도 multiple project images를 시행하므로서 쉽게 발견할 수 있었다. 이와 같이 간흡충증에 있어서 $^{99m}Tc-DISIDA$ hepatobiliary scintigram은 환자의 자각증상과 관계된 질환을 규명하는 데 필요한 정보를 얻었을 수 있었으며 간내담관의 damage정도를 규명하는데 필요한 procedure임이 판명되었다.

• The Korean Journal of Nuclear Medicine
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• v.31 no.1
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• pp.102-107
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• 1997

Laparoscopic cholecystectorny can be performed safely in most patients with symptomatic cholelithiasis. Preoperative evaluation should assess the potential problems that affect the performance of laparoscopic cholecystectomy. Hepatobiliary scintigraphy or oral cholecystography can assess the gallbladder function and nonvisualization of gallbladder usually indicates acute or severe chronic cholecystitis. The purpose of this study was to evaluate the role of preoperative hepatobiliary scintigraphy or oral cholecystography in predicting the performance of laparoscopic cholecystectorny. The study group consists of 176 patients who underwent both hepatobiliary scintigraphy with Tc-99m DISIDA and oral cholecystography within one month before laparoscopic cholecystectomy. Nonvisualization of gallbladder was defined as persistent nonvisualization of gallbladder until 4 hours on hepatobiliary scintigraphy or 12 hours on oral cholecystography. Among 176 patients, gallbladder was not visualized in 38 patients on hepatobiliary scintigraphy and 41 patients on oral cholecystography. Concordance rate between hepatobiliary scintigraphy and oral cholecystography was 89.2%. The conversion rate to open cholocystectomy was significantly higher in patients with nonvisualization of gallbladder than in patients with gallbladder visualization(15.8% vs 2.9% on hepatobiliary scintigraphy, 12.2% vs 3.7% on oral cholecystography p<0.01 and p<0.05 respectively). The operative complication rate was also significantly higher in patients with nonvisualization of gallbladder (13.2% vs 2.9% on hepatobiliary scintigraphy, 14.6% vs 2.2% on oral cholecystography p<0.01 and p<0.001, respectively). Similarly, operation time was significantly prolonged in patients with nonvisualization of gallbladder ($88.8{\pm}41.9min$ vs $62.5{\pm}23.6min$ on hepatobiliary scintigraphy : p<0.001, $89.4{\pm}41.3$ min vs $61.8{\pm}22.8$ min on oral cholecystography : p<0.001). It is concluded that nonvisualization of gallbladder on hepatobiliary scintigraphy or oral cholecystography is a valuable preoperative clinical risk factor in predicting increased conversion rate to open cholecystectomy, increased operative complication and prolonged operation time.