• Biomolecules & Therapeutics
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• 제31권3호
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• pp.330-339
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• 2023

Liver kinase B1 (LKB1) is a crucial tumor suppressor involved in various cellular processes, including embryonic development, tumor initiation and progression, cell adhesion, apoptosis, and metabolism. However, the precise mechanisms underlying its functions remain elusive. In this study, we demonstrate that LKB1 interacts directly with malic enzyme 3 (ME3) through the N-terminus of the enzyme and identified the binding regions necessary for this interaction. The binding activity was confirmed to promote the expression of ME3 in an LKB1-dependent manner and was also shown to induce apoptosis activity. Furthermore, LKB1 and ME3 overexpression upregulated the expression of tumour suppressor proteins (p53 and p21) and downregulated the expression of antiapoptotic proteins (nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and B-cell lymphoma 2 (Bcl-2)). Additionally, LKB1 and ME3 enhanced the transcription of p21 and p53 and inhibited the transcription of NF-κB. Moreover, LKB1 and ME3 suppressed the phosphorylation of various components of the phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B signaling pathway. Overall, these results suggest that LKB1 promotes pro-apoptotic activities by inducing ME3 expression.

• Clinical Endoscopy
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• 제56권2호
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• pp.143-154
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• 2023

Advanced malignant hilar biliary obstruction (MHBO) with inaccessible papilla poses a significant challenge to endoscopists, as drainage of multiple liver segments may be warranted. Transpapillary drainage may not be feasible in patients with surgically altered anatomy, duodenal stenosis, prior duodenal self-expanding metal stent, and after initial transpapillary drainage, but require re-intervention for draining separated liver segments. Endoscopic ultrasound-guided biliary drainage (EUS-BD) and percutaneous trans-hepatic biliary drainage are the feasible options in this scenario. The major advantages of EUS-BD over percutaneous trans-hepatic biliary drainage include a reduction in patient discomfort and internal drainage away from the tumor, thus reducing the possibility of tissue or tumor ingrowth. With innovations, EUS-BD is helpful not only for bilateral communicating MHBO but also for non-communicating systems with bridging hilar stents or isolated right intra-hepatic duct drainage by hepatico-duodenostomy. EUS-guided multi-stent drainage with specially designed cannulas and guidewires has become a reality. A combined approach with endoscopic retrograde cholangiopancreatography for re-intervention, interventional radiology, and intraductal tumor ablative therapies has been reported. Stent migration and bile leakage can be minimized with proper stent selection and technique, and stent blocks can be managed with EUS-guided interventions in a majority of cases. Future comparative studies are required to establish the role of EUS-guided interventions in MHBO as rescue or primary therapy.

• Asian Pacific Journal of Cancer Prevention
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• 제13권2호
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• pp.737-742
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• 2012

To evaluate efficacy of microwave ablation in a primary clinical study, sixty patients (44 men, 16 women; mean age 53 years) with 96, 1-8 cm (mean $3.20{\pm}0.17$ cm) liver cancers were treated with 2,450-MHz internally cooled-shaft antenna. Complete ablation (CA) and local tumor progression (LTP) rates as well as complications were determined. CA rates in small (< 3.0 cm), intermediate (3.1-5.0 cm) and large (5.1-8.0 cm) liver cancers were 96.4% (54/56), 92.3% (24/26) and 78.6% (11/14), respectively. During a mean follow-up period of $17.17{\pm}6.52$ months, LTP occurred in five (5.21%) treated cases. There was no significant difference in the CA and LTP rates between the HCC and liver metastasis patient subgroups (P<0.05). Microwave ablation provides a reliable, efficient, and safe technique to perform hepatic tumor ablation.

• 대한한방내과학회지
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• 제26권2호
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• pp.333-340
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• 2005

Background: Cancer reseach is done in earnest world-wide, because cancer is one of most threatening diseases to humans. Orostachyos Herba is a widely used herb that has long been in use in Korea as an anti-inflammatory and anti-cancer therapy. The purpose of this study is to verify any anti-cancer effects on stomach and liver cancer in vitro. Materials & Methods: AGS and KATO III stomach cancer cells and Hep3B and HepG2 liver cancer cells, all obtained from Korean Cell Line Bank, were used. The boiled extract of Orostachyos Herba(20 and 40 microliters) were injected into cultures and observed at 0 hours, and at 24-hour intervals up to 96 hours. The destruction of stomach and liver cancer cells was measured through Trypan blue exclusion testing. The suppression on viability of stomach and liver cancer cells was observed, and anti-cancer mechanisms was examined by analyzing the cell cycle. Results: In morphologic change, AGS, KATO III, HepG2 and Hep3B showed some of the withdrawn and floating appearance that is typical in cellular imparment. AGS, KATO III, HepG2 and Hep3B showed more destruction of stomach cancer cells in each test group than in the control group to a statistically significant degree. Analysis of the cell cycle after introduction of Orostachyos Herba showed very little inhibition of divisions of all cell lines. Conclusions: This experiment suggests that Orostachyos Herba has some anti-tumor effects on stomach and liver cancer cells. Progressive research on Orostachyos Herba and it's anti-tumor effects will be needed to determine its practicability as a cancer treatment.

• Asian Pacific Journal of Cancer Prevention
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• 제15권6호
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• pp.2655-2661
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• 2014

Background: Talin-1 is a cytoskeleton protein that participates in cell migration and plays a role in tumor formation, migration, and metastasis in different types of cancer. Chinese investigators have observed that the levels of Talin-1 protein and mRNA expression in HCC tissues are significantly lower than in the adjacent non-cancerous tissue. However, Japanese investigators have reported that Talin-1 is upregulated in HCC. Tln2 as homologous gene of Tln-1, which encodes a very similar protein, but the role of Talin-2 is very little known in primary liver cancer (PLC). We investigated whether the expression of Talin-1 in PLC may be associated with the histological subtype as well as the role of Talin-1 in tumor cell invasion and migration using human hepatocellular carcinoma cell lines. Materials and Methods: We measured the mRNA expression levels of Talin-1 and Talin-2 in five human liver cancer cell lines and normal human liver cell ($LO_2$ cell line) by real-time PCR and the protein expression levels of Talin-1 by Western blot. Migration and invasion of the cells were assessed using transwell assays and cell scratch experiments, respectively, and proliferation was assessed by soft AGAR colony formation. Results: Talin-1 and Talin-2 expression differed significantly between the five human liver cancer cell lines and $LO_2$ cell line (p<0.05). Compared with the $LO_2$ cell line, the invasion and migration capabilities of the five cancer cell lines differed significantly (p<0.05). Similarly, the colony-forming ability differed (p<0.05). Conclusions: High levels of Talin-1 expression are correlated with reduced invasion and migration as well as decreased malignancy in human liver cancer cell lines; the suppression of Talin-1 promotes invasion and migration. In addition, Talin-2 may be correlated with invasion and migration in human hepatocellular carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• 제13권8호
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• pp.4001-4005
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• 2012

Backgrouds: The hedgehog (Hh) signaling pathway is composed of patched (PTCH) and smoothened (SMO), two transmembrane proteins, and downstream glioma-associated oncogene homolog (Gli) transcription factors. Hh signaling plays a pathological role in the occurrence and development of various cancers. Methods: To investigate the expression of SMO protein in colon cancer and its association with clinicopathological parameters and postoperative liver metastasis, immunohistochemistry was performed with paraffin-embedded specimens of 96 cases. Relationships between SMO protein expression and clinicopathological parameters, postoperative liver metastasis were analyzed. Results: IHC examination showed that SMO protein expression was significantly increased in colon cancer tissues compared to normal colon tissues (P = 0.042), positively related to lymph node metastases (P = 0.018) and higher T stages (P = 0.026). Postoperative live metastasis-free survival was significantly longer in the low SMO expression group than in those with high SMO expression ($48.7{\pm}8.02$ months vs $28.0{\pm}6.86$ months, P=0.036). Multivariate analysis showed SMO expression level to be an independent prognostic factor for postoperative live metastasis-free survival (95% confidence interval [CI] =1.46-2.82, P = 0.008). Conclusions: Our results suggest that in patients with colon cancer, the SMO expression level is an independent biomarker for postoperative liver metastasis, and SMO might play an important role in colon cancer progression.

• Radiation Oncology Journal
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• 제30권3호
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• pp.146-151
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• 2012

Purpose: This treatment planning study was undertaken to evaluate the impact of beam angle configuration of intensity-modulated radiotherapy (IMRT) on the dose of the normal liver in hepatocellular carcinoma (HCC). Materials and Methods: The computed tomography datasets of 25 patients treated with IMRT for HCC were selected. Two IMRT plans using five beams were made in each patient; beams with equidistance of $72^{\circ}$ (Plan I), and beams with a $30^{\circ}$ angle of separation entering the body near the tumor (Plan II). Both plans were generated using the same constraints in each patient. Conformity index (CI), homogeneity index (HI), gamma index, mean dose of the normal liver (Dmean_NL), Dmean_NL difference between the two plans, and percentage normal liver volumes receiving at least 10, 20, and 30 Gy (V10, V20, and V30) were evaluated and compared. Results: Dmean_NL, V10, and V20 were significantly better for Plan II. The Dmean_NL was significantly lower for peripheral (p = 0.001) and central tumors (p = 0.034). Dmean_NL differences between the two plans increased in proportion to gross tumor volume to normal liver volume ratios (p = 0.002). CI, HI, and gamma indices were not significantly different for the two plans. Conclusion: The IMRT plan based on beams with narrow separations reduced the irradiated dose of the normal liver, which would allow radiation dose escalation for HCC.

• Asian Pacific Journal of Cancer Prevention
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• 제16권3호
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• pp.1191-1196
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• 2015

Background: Epidermal growth factor-like domain multiple 7 (EGFL7), recently identified as a secreted protein regulated by oxygen exposure, plays a critical role in promoting metastasis of hepatocellular carcinoma (HCC). Transcatheter arterial embolization (TAE) is widely used for treatment of HCC, resulting in hypoxia in tumors and surrounding liver tissues. Accordingly, we proposed the hypothesis that there could be a relationship between expression of EGFL7 and response to TAE. Materials and Methods: We established a rabbit VX2 liver tumor model using percutaneous puncture technique guided by computed tomography. TAE and sham embolization were performed and the results were confirmed by MRI 3 weeks after inoculation. We investigated the EGFL7 expression of the two groups at 6h and 3 days after intervention by means of immunohistochemistry and Western blotting. Results: Immunohistochemical staining demonstrated that the levels of EGFL7 protein significantly increased in the TAE-treated tumors compared with the control group at 6 hours (P=0.031) and 3 days (P=0.020) after intervention. Meanwhile, the relative EGFL7 protein detected in TAE group also up-regulated compared with the control group at 6 hours (P=0.020) and 3 days (P=0.024) after intervention. Conclusions: This study reveals an increase of EGFL7 expression in rabbit VX2 liver tumors after TAE. The role of EGFL7 in HCC, especially its biological behavior after TAE, needs further investigation.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제4권1호
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• pp.113-119
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• 2001

소아에서 간의 간엽 과오종은 주로 복부팽만을 주소로 내원하여 대부분 2세 이내에 발견되며, 비교적 크기가 큰 낭종의 소견을 보이는 것으로 알려져 있다. 저자들은 담도 폐쇄증으로 Kasai 수술받은 8개월 여아에서 복부 초음파 검사상 작은 기질성 종괴를 우연히 발견하여 병리학적으로 확진된 간엽과오종 1례를 보고하는 바이다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권1호
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• pp.369-374
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• 2014

Background: Colorectal cancer (CRC) is the fourth most common cause of cancer death in the world. Genetic variants in 8q24.21 including rs10505477 and rs6983267 have been hypothesized to be involved in susceptibility to CRC. This study aims to investigate the possible association between these loci and their haplotypes with CRC risk in Iranian population. Materials and Methods: Subjects were recruited from two hospitals in Tehran. The rs10505477 and rs6983267 polymorphisms were genotyped by TaqMan real time PCR using subject genomic DNA, extracted either from formalin-fixed, paraffin-embedded tissue of patients or from blood of the controls by standard methods. Results: A total of 715 subjects (380 CRC patients and 335 matched controls) were genotyped in this study. Allele and genotype analysis of the rs10505477 and rs6983267 polymorphisms by gender, age at diagnosis, tumor location, tumor grade, and tumor node metastasis (TNM) showed no significant association with CRC risk. There was a significant relationship between GG haplotype and susceptibility to age at diagnosis for both <60 and ${\geq}60$ (p=0.0005 and p=0.000004, respectively) and between GT and CRC in the age at diagnosis ${\geq}60$ (Table 3: p=0.031). The GG haplotype was less frequent in CRC patients with the age at diagnosis <60, but was more common in subjects with the age at diagnosis ${\geq}60$. Conclusions: Results of this study suggests that the rs6983267 and rs10505477 polymorphisms alone may not be relevant to CRC risk, but their GG haplotype plays a notable role in age at diagnosis of CRC in the Iranian population.