• Biomolecules & Therapeutics
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• 제25권5호
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• pp.504-510
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• 2017

Inhibitor of nuclear factor kappa-B kinase beta ($IKK{\beta}$) plays a critical role in cell proliferation and inflammation in various cells by activating $NF-{\kappa}B$ signaling. However, the interrelationship between peroxisome proliferator-activated receptor ${\alpha}$ ($PPAR{\alpha}$) and $IKK{\beta}$ in cell proliferation is not clear. In this study, we investigated the possible role of $PPAR{\alpha}$ in the hepatic cell death in the absence of $IKK{\beta}$ gene using liver-specific Ikkb-null ($Ikkb^{F/F-AlbCre}$) mice. To examine the function of $PPAR{\alpha}$ activation in hepatic cell death, wild-type ($Ikkb^{F/F}$) and $Ikkb^{F/F-AlbCre}$ mice were treated with $PPAR{\alpha}$ agonist Wy-14,643 (0.1% w/w chow diet) for two weeks. As a result of Wy-14,643 treatment, apoptotic markers including caspase-3 cleavage, poly (ADP-ribose) polymerase (PARP) cleavage and TUNEL-positive staining were significantly decreased in the $Ikkb^{F/F-AlbCre}$ mice. Surprisingly, Wy-14,643 increased the phosphorylation of p65 and STAT3 in both Ikkb and $Ikkb^{F/F-AlbCre}$ mice. Furthermore, BrdU-positive cells were significantly increased in both groups after treatment with Wy-14,643. Our results suggested that $IKK{\beta}-derived$ hepatic apoptosis could be altered by $PPAR{\alpha}$ activation in conjunction with activation of $NF-{\kappa}B$ and STAT3 signaling.

• 대한세포병리학회지
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• 제3권2호
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• pp.100-103
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• 1992

We experienced a case of primary hepatic actinomycosis which was initially diagnosed by means of fine needle aspiration. The patient was a 31-year-old emaciated man with a 2-month history of 10 kg weight loss, right upper quadrant pain and flank pain. The liver was palpable and tender on physical examination. Computerized tomography scan of the liver showed two ill-defined hypodense masses in gallbladder fossa and inferior pole of right lobe. Hepatocellular carcinoma was clinically suspected. A CT-guided fine needle aspiration was peformed. Microscopically, smears showed numerous radiating clusters of filamentous bacteria with many neutrophils and monocytes in necrotic background. The symptoms were improved by incision and drainage and massive administration of penicillin.

• Asian Pacific Journal of Cancer Prevention
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• 제16권17호
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• pp.7871-7874
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• 2015

Background: There is no consensus regarding the selection of treatment options for hepatocellular carcinoma (HCC) after initial transarterial chemoembolization (TACE). This meta-analysis aimed to explore the survival benefit of hepatic resection after initial TACE for the treatment of HCC. Materials and Methods: We searched three major databases to identify all relevant papers comparing the outcomes of hepatic resection after initial TACE versus TACE alone for the treatment of HCC. Hazard ratios (HRs) with 95% confidence intervals (95%CIs) were calculated to evaluate the survival benefit of hepatic resection after initial TACE over TACE alone. Results: Three of 2037 initially identified papers were included. All of them were cohort studies from Asia. There was a significantly better overall survival (OS) in patients undergoing hepatic resection after initial TACE than in those undergoing TACE alone (HR=0.63, 95%CI=0.52-0.76, P<0.00001). The heterogeneity among studies was not statistically significant (P=0.96; I2=0%). Conclusions: Hepatic resection could improve the OS of HCC patients treated with initial TACE. Further randomized controlled trials should be necessary to identify the target population for the sequential use of hepatic resection after initial TACE and to compare the outcomes between patients undergoing hepatic resection after initial TACE session versus those undergoing TACE alone.

• The Korean Journal of Physiology and Pharmacology
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• 제20권5호
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• pp.487-498
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• 2016

Leptin, an adipokine predominantly produced from adipose tissue, is well known to induce tumor growth. However, underlying molecular mechanisms are not established yet. While p53 has long been well recognized as a potent tumor suppressor gene, accumulating evidence has also indicated its potential role in growth and survival of cancer cells depending on experimental environments. In the present study, we examined if p53 signaling is implicated in leptin-induced growth of cancer cells. Herein, we demonstrated that leptin treatment significantly increased p53 protein expression in both hepatic (HepG2) and breast (MCF-7) cancer cells without significant effect on mRNA expression. Enhanced p53 expression by leptin was mediated via modulation of ubiquitination, in particular ubiquitin specific protease 2 (USP2)-dependent manner. Furthermore, gene silencing of p53 by small interfering RNA (siRNA) suppressed leptin-induced growth of hepatic and breast cancer cells, indicating the role of p53 signaling in tumor growth by leptin. In addition, we also showed that knockdown of p53 restored suppression of caspase-3 activity by leptin through modulating Bax expression and prevented leptin-induced cell cycle progression, implying the involvement of p53 signaling in the regulation of both apoptosis and cell cycle progression in cancer cells treated with leptin. Taken together, the results in the present study demonstrated the potential role of p53 signaling in leptin-induced tumor growth.

• Asian Pacific Journal of Cancer Prevention
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• 제16권17호
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• pp.7517-7522
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• 2015

Onion (Allium cepa) consumption has been remarked in folk medicine which has not been noted to be administered so far as an adjunct to conventional doxorubicin-based chemotherapy in breast cancer patients. To our knowledge, this is the first study aimed to investigate the effects of consuming fresh yellow onions on hepatic enzymes and cancer specific antigens compared with a low-onion containing diet among breast cancer (BC) participants treated with doxorubicin. This parallel design randomized controlled clinical trial was conducted on 56 BC patients whose malignancy was confirmed with histopathological examination. Subjects were assigned in a stratified-random allocation into either group received body mass index dependent 100-160 g/d of onion as high onion group (HO; n=28) or 30-40 g/d small onion in low onion group (LO; n=28) for eight weeks intervention. Participants, care givers and laboratory assessor were blinded to the assignments (IRCT registry no: IRCT2012103111335N1). The compliance of participants in the analysis was appropriate (87.9%). Comparing changes throughout pre- and post-dose treatments indicated significant controls on carcinoembryonic antigen, cancer antigen-125 and alkaline phosphatase levels in the HO group (P<0.05). Our findings for the first time showed that regular onion administration could be effective for hepatic enzyme conveying adjuvant chemotherapy relevant toxicity and reducing the tumor markers in BC during doxorubicin-based chemotherapy.

• Molecules and Cells
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• 제38권3호
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• pp.202-209
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• 2015

Hepatocellular carcinoma (HCC), a highly malignant disease and the third leading cause of all cancer mortalities worldwide, often responses poorly to current treatments and results in dismal outcomes due to frequent chemoresistance and tumor relapse. The heterogeneity of HCC is an important attribute of the disease. It is the outcome of many factors, including the cross-talk between tumor cells within the tumor microenvironment and the acquisition and accumulation of genetic and epigenetic alterations in tumor cells. In addition, there is accumulating evidence in recent years to show that the malignancy of HCC can be attributed partly to the presence of cancer stem cell (CSC). CSCs are capable to self-renew, differentiate and initiate tumor formation. The regulation of the stem cell-like properties by several important signaling pathways have been found to endow the tumor cells with an increased level of tumorigenicity, chemoresistance, and metastatic ability. In this review, we will discuss the recent findings on hepatic CSCs, with special emphasis on their putative origins, relationship with hepatitis viruses, regulatory signaling networks, tumor microenvironment, and how these factors control the stemness of hepatic CSCs. We will also discuss some novel therapeutic strategies targeted at hepatic CSCs for combating HCC and perspectives of future investigation.

• Asian Pacific Journal of Cancer Prevention
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• 제13권3호
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• pp.1015-1018
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• 2012

Objective: To improve the diagnosis of primary gallbladder carcinoma (GBC) with/without hepatic metastases by analyzing our experience of different GBC treatment in our patients. Methods: A retrospective study was carried out to analyze the clinical data of the 139 patients with GBC who underwent hepatic resection in our unit from January 2003 to December 2007. Patients were divided into two groups according to whether they demonstrated hepatic invasion. Tumor presentation, surgical modes, and prognosis of each patient were retrospectively reviewed. Kaplan-Meier curves and log-rank tests were employed to compare the survival rates of those patients undergoing different surgical procedures. Results: Of the 139 patients, 46 were men and 93 were women with the male to female ratio of 1:2.0. Their ages were ranged from 35 to 86 years with a mean age of $62.8{\pm}10.4$ years. There were 73 patients complicated with hepatic invasion (group A), and no hepatic invasion occurred in the other 66 patients (group B). Compared with the group B, the patients with hepatic invasion suffered lower differentiation of tumor (p=0.000), more advanced Nevin staging (p=0.008) and poorer prognosis (p=0.013). Radical resection were more frequently performed in group B (75.76%) than in group A (45.20%) with better outcomes (p=0.000). Conclusion: GBC patients complicated with hepatic invasion had poorer prognosis than those without invasion in long-term follow-ups. Radical resection might result in a satisfied prognosis in patients without hepatic invasion, but appears less favorable than palliative resection in those who were complicated with hepatic invasion.

• Asian Pacific Journal of Cancer Prevention
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• 제14권10호
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• pp.6151-6158
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• 2013

Radio frequency ablation (RFA) is an effective means of achieving local control of liver cancer. It is a particularly suitable mode of therapy for small and favorably located tumors. However, local progression rates are substantially higher for large tumors (>3.0 cm). In the current study, we report on a mathematical model based on geometric optimization to treat large liver tumors. A database of mathematical models relevant to the configuration of liver cancer was also established. The specific placement of electrodes and the frequency of ablation were also optimized. In addition, three types of liver cancer lesion were simulated by computer guidance incorporating mathematical models. This approach can be expected to provide a more effective and rationale mechanism for employing RFA in the therapy of hepatic carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• 제16권8호
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• pp.3131-3135
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• 2015

Objective: To investigate whether the expression of serum soluble neural cell adhesion molecule (sNCAM) is associated with hepatic encephalopathy (HE) in hepatocelular carcinoma (HCC) patients. Materials and Methods: The Oncomine Cancer Microarray database was used to determine the clinical relevance of NCAM expression in different kinds of human cancers. Sera from 75 HCC cases enrolled in this study were assessed for expression of sNCAM by enzyme linked immunosorbent assay (ELISA). Results: Dependent on the Oncomine Cancer Microarray database analysis, NCAM was down regulated in 10 different kinds of cancer, like bladder cancer, brain and central nervous system cancer, while up-regulated in lung cancer, uterine corpus leiomyoma and sarcoma, compared to normal groups. Puzzlingly, NCAM expression demonstrated no significant difference between normal and HCC groups. However, we found by quantitative ELISA that the level of sNCAM in sera from HCC patients with HE ($347.4{\pm}151.9ng/ml$) was significantly more up-regulated than that in HCC patients without HE ($260.3{\pm}104.2ng/ml$), the p-value being 0.008. sNCAM may be an important risk factor of HE in HCC patients, the correlation coefficients was 0.278 (P<0.05) on rank correlation analysis. Conclusions: This study highlights that up-regulated level of serum sNCAM is associated with HE in HCC patients and suggests that the high expression can be used as an indicator.

• 대한두경부종양학회지
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• 제16권2호
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• pp.206-211
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• 2000

Objectives: Any uptake of I-131 after total thyroidectomy means the remant thyroid tissue or distant metastasis of the thyroid cancer. However diffuse hepatic uptake of I-131 without abnormal uptake was showen in many cases on I-131 whole body scan. The aim of this study was to classify the liver uptake after I-131 scan and to evaluate the analysis of this finding. Materials and Methods: Between 1982 and 1998, 104 patients(l4 males, 90 females) with normal liver function underwent I-131 scan after total thyroidectomy. Prospectively we reviewed the films of the whole body scan and analysed the correlations between results of radioiodine uptake, pathologic diagnosis, prognostic factors, lymphatic metastasis, and thyroid function test. Result: Diffuse hepatic uptake was found in 44 of 104(42%) patients. 10 of 39(26%) patients on I-131 100mCi, and 34 of 63(54%) on I-131 150mCi showed hepatic uptake. 52 of 104(50%) patients was locally invasive thyroid cancer. The rate of the hepatic uptake was no significant differences with the thyroid hormone levels(T3, Free T4) and thyroglobulin between uptake group and non-uptake group. Conclusion: The rate of I-131 uptake was high in high-dose radioiodine treatment group. However, we can not find any correlation among the thyroid functions, the extent of metastasis or the extent of local invasion. We need further study to find out the causes of the hepatic uptake of I-131 after total thyroidectomy, besides liver metabolism of I-131 attached thyroid hormones.