• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.747-752
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• 2013

Oncostatin M (OSM) is a multifunctional cellular regulator acting on a wide variety of cells, which has potential roles in the regulation of gene activation, cell survival, proliferation and differentiation. Previous studies have shown that OSM can induce morphological and/or functional differentiation and maturation of many tumor cells. However, the action of OSM on the induction of differentiation of human hepatocellular carcinoma (HCC) has not been reported. Here, we investigated the effects of different concentrations of OSM on human HCC cell line SMMC-7721 growth, proliferation, cell cycling, apoptosis and differentiation in vitro. Cell growth was determined via MTT assay, proliferation by cell cycle analysis, apoptosis by flow cytometry, morphology by transmission electronic microscopy, and cell function by detection of biochemical markers. Our results demonstrated that OSM strongly inhibited the growth of SMMC-7721 cells in a dose-dependent manner, associated with decreased clonogenicity. Cell cycle analysis revealed a decreased proportion of cells in S phase, with arrest at G0/G1. The apotosis rate was increased after OSM treatment compared to the control. These changes were associated with striking changes in cellular morphology, toward a more mature hepatic phenotype, accompanied by significant reduction of the expression of AFP and specific activity of ${\gamma}$-GT, with remarkable increase in secretion of albumin and ALP activity. Taken together, our findings indicate that OSM could induce the differentiation and reduce cell viability of SMMC-7721 cells, suggesting that differentiation therapy with OSM offers the opportunity for therapeutic intervention in HCC.

• Fisheries and Aquatic Sciences
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• v.21 no.6
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• pp.16.1-16.7
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• 2018

Background: Matrix metalloproteinases (MMPs) are linked with several complications such as metastasis of cancer progression, oxidative stress, and hepatic fibrosis. Brown seaweeds are being extensively studied for their bioactive molecule content against cancer progression. In this context, Sargassum horneri was reported to possess various bioactivities including antiviral, antimicrobial, and anti-inflammatory partly due to its phenolic compound content. Methods: In this study, potential of S. horneri was evaluated through anti-MMP effect in HT1080 fibrosarcoma cells. S. horneri crude extract was fractionated with organic solvents, namely, water ($H_2O$), n-buthanol (n-BuOH), 85% aqueous methanol (85% aq. MeOH), and n-hexane. The non-toxicity of fraction samples (Sargassum horneri solvent-partitioned extracts (SHEs)) was confirmed by cell-viability assay. SHEs were tested for their ability to inhibit MMP enzymatic activity through gelatin digestion evaluation and cell migration assay. Expressions of MMP-2 and MMP-9 and tissue inhibitors of MMP (TIMPs) were evaluated by reverse transcription and Western blotting. Results: All fractions inhibited the enzymatic activities of MMP-2 and MMP-9 according to gelatin zymography. Except $H_2O$ fraction, fractions hindered the cell migration significantly. All tested fractions suppressed both mRNA and protein levels of MMP-2, MMP-9, TIMP-1, and TIMP-2. Conclusion: Overall, current results suggested that S. horneri has potential to be a good source for anti-MMP agents, and further investigations are underway for better understanding of the action mechanism and isolation and elucidation of the bioactive molecules.

• Journal of Chest Surgery
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• v.25 no.12
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• pp.1530-1536
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• 1992

From January 1984 to December 1991, One hundred sixty five patients with carcinomoa of the esophagus were treated surgically at the department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital. Among them, hospital records were available in 121 patients and were included in this study. There were 115 men and 6 women, with ages ranging from 40 years to 79 years[mean age of 59.2 years]. The most frequent preoperative symptoms included dysphagia[72.7%], weight loss[60.3%], chest pain or discomfort[14.9%], general malaise[13.2%]. All were treated surgically: 100 patients were managed by curative or palliative resection with reconstruction, and 6 by palliative bypass surgery. In 15 patients, explorative thoracotomy or laparotomy was only done due to unresectability. [operability: 87.6%, resectability: 82.6%] All specimens[those from resectable 100 cases] were sent to pathology, and histopathologic examinations were done; squamous cell carcinomas were found in 95 cases, adenocarcinoma in l. Adenosquamous carcinomas were found in 3, and malignant melanoma in l. Postoperative complications occurred in 34 cases; anastomotic site leakage[10], which was followed by empyema in 9 of them, wound problem[7], hepatic failure[6], pneumonia [3], post-operative bleeding[3], chylothorax[2], post-operative stricture[2], sepsis[1], and tracheobronchial fistula[1]. Hospital deaths were in 6 cases[Hospital mortality: 5.0%]. During the follow up period, 26 patients were proven to be recurrence of cancer locally or distantly. The one, two, and five-year actuarial survival raf.es were 71.3$\pm$4.5%, 57.4$\pm$5.6%, 34.7$\pm$8.9%, respectively. The data from this study suggested that esophagectomy with reconstruction of gastrointestinal tract could be performed with a low operative mortality and a few serious postoperative complications and achieved reasonable long term palliation for carcinoma of the esophagus.

• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.2
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• pp.206-219
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• 2010

To establish the fundament for EBM of Traditional Korean Medicine, the papers on Sagunja-tang(Sijunzi-tang) frequently used in medical institutions of Traditional Korean Medicine were analyzed through researching domestic and international papers. The papers were classified by the registration of domestic or international journals, the year of publishment, experimental fields and the kinds of studies on biological activities. Of total 228 papers on Sagunja-tang(Sijunzi-tang), 121 volumes were selected according to creteria. 47 volumes were published in domestic journals, 71 in Chinese journal, 2 in Japanese journal, and 1 in Taiwan journal. The papers on instrumental analyses were preceeded by HPLC, MS, GC with standard compounds of herbal medicine in Sagunja-tang(Sijunzi-tang). The papers on biological activities of Sagunja-tang(Sijunzi-tang) showed improvement of gastrointestinal activity and blood circulation, immunoactivity, anti-cancer, anti-oxidant, anti-fatigue, anti-stress, pharmacokinetics, hepatic protection, radioprotection, muscular activity, hematopoiesis and nontoxical effect. Further studies including gastrointestinal disorder, immune related disease, cancer, oxidative injury and pharmacokinetic study need to be preceeded to establish the fundament for EBM of Sagunja-tang(Sijunzi-tang).

• The Journal of Korean Medicine
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• v.16 no.2 s.30
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• pp.414-432
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• 1995

In order to prove the antitumer effect of Bupleuri Radix(BR) and Artemisiae capillaris Herba(ACH) experimently, studies were done. The antitumer effect against hepatic cancer such as Hep G2, PLC & Hep 313, and also th synergastic action was evaulatcd in the combined treatment with anticancer drugs using chiefly for liver cancer, such as mitomycin(MMC), cisplatin(CPT) and 5-fluorouracil(5-FU). The results were obtained as follows: 1. IC50 against Hep G2, Hep 3B and PLC was 15.5ug/ml, 25.4ug/ml, 31.25ug/ml in Mitomycin (MMC), 92.5ug/ml, 50.2ug/ml, 62.5ug/ml in cisplatin(CPT) and 125ug/ml in 5-fluouracil(5- FU) respectively. 2. The antitumor effect was shown in the all concentrations of ACH, BR and below 55%-Cytotoxic effect against Hep G2 as compared with the date of control was shown in the concentration of $10^{-4}g/ml$ above of BR but not in ACH and also BR and ACHI revealed the synergistic effect with MMC. 3. The antitumor effect was shown in the concentration of $10^{-5}g/ml$ above of ACH, BR and below 55%-Cytotoxic effect against Hep 3B as compared with the data of control was shown in the concentration of $10^{-5}g/ml$ above of ACH but not in BH and also BR & ACH revealed the svnergistic effect with MMC. 4. The antitumor effect was shown in the all concentrations of ACH, BR and 55%-Cytotoxic effect against PLC as compared with the data of control was shown in the concentration of $10^{-5}g/ml$ above of ACH but not in BR and also ACH revealed the synergistic effect with MMC. From the above results it was concluded that Artemisiae capillaris had antitumor effect against PLC, Hep 3B, Bupleuri Radix against Hep G2 and also MMC showed the most synergistic effect in the anticancer drugs.

• Journal of Microbiology and Biotechnology
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• v.16 no.9
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• pp.1369-1376
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• 2006

Self-organized nanogels were prepared from pullulan/biotin conjugates (PU/Bio) for the development of an effective anticancer drug delivery system. The degree of biotin substitution was 11, 19, and 24 biotin groups per 100 anhydroglucose units of pullulan. The physicochemical properties of the nanogels (PU/Bio1, 2 and 3) in aqueous media were characterized by dynamic light scattering, transmission electron microscopy, and fluorescence spectroscopy. The mean diameter of all the samples was less than 300 nm with a unimodal size distribution. The critical aggregation concentrations (CACs) of the nanoparticles in distilled water were $2.8{\times}10^{-2},\;1.6{\times}10^{-2}$, and $0.7{\times}10^{-2}mg/ml$ for the PU/Bio1, 2, and 3, respectively. The aggregation behavior of the nanogels indicated that biotin can perform as a hydrophobic moiety. To observe the specific interaction with a hepatic carcinoma cell line (HepG2), the conjugates were labeled with rhodamine B isothiocyanate (RITC) and their intensities measured using a fluorescence microplate reader. The HepG2 cells treated with the fluorescence-labeled PU/Bio nanoparticles were strongly luminated compared with the control (pullulan). Confocal laser microscopy also confirmed internalization of the PU/Bio nanogels into the cancer cells. Such results demonstrated that the biotin in the conjugate acted as both a hydrophobic moiety for self-assembly and a tumor-targeting moiety for specific interaction with tumor cells. Consequently, PU/Bio nanogels would appear to be a useful drug carrier for the treatment of liver cancer.

• Biomolecules & Therapeutics
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• v.3 no.4
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• pp.279-287
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• 1995

This study examined the anti-cancer effects of diallyl sulfide(DAS) and/or diallyl disulfide(DDS), major components of garlic oil, with the DEN-PH model in rats, by the numbers and areas per cm$^2$ of induced glutathion S-transferase placental form(GST-P) positive foci and silver-stained nucleolar organizer regions(Ag-NORs) counts per nuclei in liver as indicator. Sprague-Dawley(SD) rats were given the diethylnitrosamine(DEN, 200 mg/kg, i.p.) as initiator and 2 weeks later, in experiment 1, rats were treated with DAS(200 mg/kg, i.g.) and/or DDS(50 mg/kg, i.g.) for 6 weeks, respectively and concomitantly and also were given the same dose of DAS and/or DDS prior to DEN treatment for 2 weeks, and in experiment II, rats were treated with potential cancer promoter, 2-acetylaminofluorene (2-AAF, 20 mg/kg, i.g.). The DAS and/or DDS were treated prior to 2-AAF for 8 weeks, respectively and concomitantly. Then the anti-promoting effects of DAS and/or DDS were assessed. All rats were subjected to the two-thirds partial hepatectomy(PH) at week 3 and sacrificed at week 8. In experiment I, DAS and/or DDS treatment only prior to DEN showed inhibition of the development of GST-P positive foci. In experiment II, DAS and/or DDS treatment prior to 2-AAF promotion showed obvious inhibition of the development of GST-P positive foci in numbers and areas and AgNORs counts. In conclusion, We found DAS and/or DDS had the preventive effects on the hepatocarcinogenesis in rats and the concomitant treatment had some additive effects compared with the each treatment and AgNORs counts correlated well with the preneoplastic hepatic lesion.

• Journal of Chest Surgery
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• v.55 no.5
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• pp.397-404
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• 2022

Background: Distant recurrence of esophageal cancer (EC), even after radical resection, is common, and the most frequent site of EC metastasis is the liver. However, a multidisciplinary treatment strategy for postoperative liver metastasis (LM) from EC has yet to be established; in particular, the role of liver-directed therapy (LDT) remains uncertain. We investigated the clinicopathological features and outcomes of patients undergoing post-esophagectomy LM with versus without LDT to explore its therapeutic implications. Methods: Among 624 consecutive patients undergoing R0/R1 esophagectomy for EC, 30 were identified in whom LM had developed as the initial recurrence. Their characteristics were retrospectively reviewed. Results: Six of the 30 subjects underwent LDT for metachronous LM. Five of those 6 also received systemic chemotherapy. A comparison between the 6 LDT and 24 non-LDT cases revealed no significant differences in major clinicopathological and operative factors, except for concurrent metastasis to extrahepatic organs (1/6 vs. 15/24, p=0.044). Twenty-nine of the 30 patients died during the study period, whereas 1 who had received multimodal treatment with LDT remained alive more than 200 months after multiple LM had been detected. Kaplan-Meier analysis for survival after LM demonstrated significantly prolonged survival in LDT cases compared to non-LDT cases treated with systemic chemotherapy alone (p=0.014). Even when the analysis was limited to patients without extrahepatic metastasis, this significant prognostic advantage of LDT was maintained (p=0.047). Conclusion: Multimodal treatment combined with LDT might be beneficial for patients with metachronous LM from EC and should therefore be considered a potential treatment option.

• Korean Journal of Radiology
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• v.22 no.6
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• pp.912-921
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• 2021

Objective: To compare the performance of the deep learning-based lesion detection algorithm (DLLD) in detecting liver metastasis with that of radiologists. Materials and Methods: This clinical retrospective study used 4386-slice computed tomography (CT) images and labels from a training cohort (502 patients with colorectal cancer [CRC] from November 2005 to December 2010) to train the DLLD for detecting liver metastasis, and used CT images of a validation cohort (40 patients with 99 liver metastatic lesions and 45 patients without liver metastasis from January 2011 to December 2011) for comparing the performance of the DLLD with that of readers (three abdominal radiologists and three radiology residents). For per-lesion binary classification, the sensitivity and false positives per patient were measured. Results: A total of 85 patients with CRC were included in the validation cohort. In the comparison based on per-lesion binary classification, the sensitivity of DLLD (81.82%, [81/99]) was comparable to that of abdominal radiologists (80.81%, p = 0.80) and radiology residents (79.46%, p = 0.57). However, the false positives per patient with DLLD (1.330) was higher than that of abdominal radiologists (0.357, p < 0.001) and radiology residents (0.667, p < 0.001). Conclusion: DLLD showed a sensitivity comparable to that of radiologists when detecting liver metastasis in patients initially diagnosed with CRC. However, the false positives of DLLD were higher than those of radiologists. Therefore, DLLD could serve as an assistant tool for detecting liver metastasis instead of a standalone diagnostic tool.

• Tuberculosis and Respiratory Diseases
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• v.47 no.1
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• pp.103-110
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• 1999

A thromboembolic event in patients later given a diagnosis of cancer is the result rather than the cause of the cancer. The risk of hidden cancer is significantly higher for patients with recurrent idiopathic thromboembolism compared to those with secondary deep vein thrombosis. Microemboli from hepatic or adrenal metastases and large-sized emboli from the great veins invaded by the tumor are the sources of tumor embolization The intraarterial tumor emboli less likely invade the arterial wall. Thrombus formation and organization may be capable of destroying tumor cells within pulmorlary blood vessels. Therefore, all tumor emboli are not true metastases. The treatment of deep vein thrombosis and pulmonary embolism in patients with cancer consists of anticoagulation with heparin and warfarin, venacaval filters, appropriate anti-neoplastic agents, and surgical methods(embolectomy, thromboendarterectomy). However, considerable literatures suggest that oral anticoagulant such as warfarin is ineffective in the treatment of those. We report a case of primary unknown squamous cell carcinoma incidentally found in the thrombus after pulmonary embolectomy.