• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.33 no.1
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• pp.11-19
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• 2007

This study was to evaluate the expression of vascular endothelial growth factor receptors (VEGFRs) in tumor and stromal cells of tougue squamous cell carcinoma (SCC). We also wanted to characterize the differences, from the angiogenic aspect, between cancer-associated stromal cells and non-malignant stromal cells. Paraffin-embedded tumor specimens from eleven patients with tongue SCCs were studied. Immunohistochemical staining for VEGFR-1,-2, and -3 was performed on the tumor cells, stromal fibroblasts and tumor-associated macrophages of the specimens. The expression of all 3 receptors was detected in the tumor cells themselves of the biopsy specimens. All 3 receptors were also expressed on stromal cells, except that VEGFR-2 was not expressed in stromal fibroblasts. In radical excision specimens, the staining intensity for VEGFR-1, -2 in the tumor cells and VEGFR-1,-3 in the tumor-associated macrophages was significantly lower than that in the biopsy specimens (P < 0.05). By using the general marker of fibroblast and macrophage, 5B5 and CD68, respectively, we performed double immunofluorescence staining for 5B5 and each VEGFR in the stromal fibroblasts and for CD68 and each VEGFR in the tumor-associated macrophages of the radical excision specimens. We used 4 cases of fibroma and 4 cases of chronic inflammation tissue as the controls. It was found that only each marker was expressed in the control group, however, 5B5/VEGFR-1 and 5B5/VEGFR-3 in the stromal fibroblasts, and CD68/VEGFR-1 and CD68/VEGFR-3 in the tumor-associated macrophages were double stained in the radical excision specimens. Although our study used small number of specimens, the results of our study showed that in tongue SCC, in association with the angiogenesis, the stromal cells showed the activated phenotype and this was different from the nonmalignant stromal cells.

• Journal of Life Science
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• v.21 no.12
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• pp.1778-1783
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• 2011

Hematopoietic cytokines regulate production of blood cells by stimulating proliferation and differentiation of bone marrow cells. Among these hematopoietic cytokines, called hematopoitic growth factors, glranulocyte-colony stimulating Factor (G-CSF), which regulates growth of neutrophils, is one of important therapeutic factors because cancer patients suffer with neutropenia which is severe reduction of neutrophils after chemotherapy. Two groups of recombinant G-CSF have approved and used for therapeutic purposes and many researches are still on-going to produce recombinant G-CSF by different techniques. We engineered human G-CSF with Bombyx specific endoplasmic reticulum (ER) signal sequence, therefore, secretion of human G-CSF protein was improved in Bombyx mori-origined cell line, Bm5. The Bombyx ER signal sequence and human G-CSF matured protein region chimera was further remodeled at the N-terminus of matured G-CSF protein to understand roles of N-terminus on outer cellular secretion and/or production. Three different mutants were generated deleting three amino acids in non alpha-helical region in N-terminus in order to scan important amino acids for G-CSF secretion. One of 3 different N-terminal deletion mutants showed dramatically reduction of secreted amount of G-CSF indicating its important role on secretion. The data suggest that remodeling in non alpha-helical region of N-terminus is also important for recombinant G-CSF production.

• Journal of Yeungnam Medical Science
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• v.6 no.1
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• pp.69-80
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• 1989

From December 1987 to September 1988, clinical evaluation were performed at the Yeungnam University Hospital on 138 patients with exudative pleural effusion comparing with biochemical, bacteriologic, cytologic and pathologic studies. The results were as follows 1. Among thease 138 cases, Incidence of tuberculosis was 57.3%, neoplasm 26.8%. High tendency in malignant pleural effusion occured in elder age. 2. In tuberculosis pleural effusion, the rate of positive smear and culture for acid-fast bacilli in the pleural fluid was 3.7% and positive biopsy for granuloma 75%. 3. In malignant pleural effusion, the rate of positive cytology for cancer cell in the fluid was 42% and positive biopsy 60%. 4. Analysis in tuberculosis and malignancy showed the tendency of high pH, WBC, protein and of low glucose, but there were clinically not significant in differentiating malignant pleural effusion from tuberculous pleural effusion. 5. Among 23 cases in which the pleural tissue findings were chronic nonspecific reaction pathologically, tuberculosis(52.2%), malignancy(26%) and idiopathic(21.8%) eventually in follow up studies.

• Korean Journal of Radiology
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• v.19 no.6
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• pp.1066-1076
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• 2018

Objective: The reliability of size measurements of liver metastases from neuroendocrine tumors (NETs) on contrast-enhanced computed tomography (CT) phases made by different readers may be hampered due to transient, variable rim enhancement in arterial phase (AP) or portal venous phase (PVP) images. We aimed to assess the reliability of tumor size measurements in pre- and post-contrast scans. Materials and Methods: The study coordinator selected target lesions according to Response Evaluation Criteria in Solid Tumors 1.1 guidelines in 44 consecutive patients with pathologically confirmed NET liver metastases. Two blinded readers measured the longest diameters of target lesions on pre-contrast, AP, and PVP images twice with a 4-week interval. Inter- and intra-observer agreements were evaluated using Bland-Altman plots and 95% limit of agreement (LOA) calculations. Results: Of the 79 target lesions (approximate mean size of 3 cm), 45 showed rim enhancement. Inter-observer agreement assessed based on LOA was highest in pre-contrast CT images (-6.1-5.7 mm), followed by PVP (-7.9-7.1 mm) and AP (-8.5-7.4 mm) images. Intra-observer agreement showed the same trend: -2.8-2.9 mm and -2.9-2.9 mm for readers 1 and 2, respectively, on pre-contrast CT, -2.8-2.9 mm and -3.0-3.2 mm, respectively, on PVP, and -3.2-4.2 mm and -3.4-3.2 mm, respectively, on AP images. Mean tumor diameters differed significantly among the phases in the following increasing order: pre-contrast CT, PVP, and AP images. Conclusion: There was better inter- and intra-observer agreement in size measurements of NET liver metastases on pre-contrast scans than on AP and PVP scans. Pre-contrast CT may be the optimal for measuring NET liver metastases if its accuracy is proven.

• Journal of Life Science
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• v.29 no.9
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• pp.964-971
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• 2019

Hepatic lipid accumulation and insulin resistance increases in patients with non-alcoholic fatty liver disease. Piperine is a major compound found in black pepper (Piper nigrum) and long pepper (P. longum). Piperine has been used in fine chemical for its anti-cancer, anti-obesity, anti-diabetic, anti-inflammatory and anti-oxidant properties. However, the signaling-based mechanism of piperine and its role as an inhibitor of lipogenesis and insulin resistance in human hepatocyte cells remains ill-defined. In the present study, we explored the effects of piperine on lipid accumulation and insulin resistance, and explored the potential underlying molecular mechanisms in palmitate-treated HepG2 cells. Piperine treatment resulted in a significant reduction of triglyceride content. Furthermore, piperine treatment decreased palmitate-treated intracellular lipid deposition by inhibiting the lipogenic target genes, sterol-regulatory-element-binding protein 1c (SREBP-1c) and fatty acid synthase (FAS); whereas the expression of carnitine palmitoyl transferase (CPT-1) and phosphorylation of acetyl coenzyme A carboxylase (ACC) gene involved in fatty acid oxidation was increased. Moreover, piperine also inhibited the phosphorylation of insulin receptor substrate (IRS)-1 (Ser307). Piperine treatment modulated palmitate-treated lipid accumulation and insulin resistance in HepG2 cells with concomitant reduction of lipogenic target genes, such as SREBP-1 and FAS, and induction of CPT-1-ACC and phosphorylation of IRS-1 (Tyr632)-Akt pathways. Therefore, piperine represents a promising treatment for the prevention of lipid accumulation and insulin resistance.

• Journal of Ginseng Research
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• v.46 no.3
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• pp.418-425
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• 2022

Background: Sorafenib is effective in treating hepatoma, but most patients develop resistance to it. STAT3 signaling has been implicated in sorafenib resistance. Artesunate (ART) and 20(R)-ginsenoside Rg3 (Rg3) have anti-hepatoma effects and can inhibit STAT3 signaling in cancer cells. This study aimed to evaluate the effects of Rg3 in combination with ART (Rg3-plus-ART) in overcoming sorafenib resistance, and to examine the involvement of STAT3 signaling in these effects. Methods: Sorafenib-resistant HepG2 cells (HepG2-SR) were used to evaluate the in vitro anti-hepatoma effects of Rg3-plus-ART. A HepG2-SR hepatoma-bearing BALB/c-nu/nu mouse model was used to assess the in vivo anti-hepatoma effects of Rg3-plus-ART. CCK-8 assays and Annexin V-FITC/PI double staining were used to examine cell proliferation and apoptosis, respectively. Immunoblotting was employed to examine protein levels. ROS generation was examined by measuring DCF-DA fluorescence. Results: Rg3-plus-ART synergistically reduced viability of, and evoked apoptosis in HepG2-SR cells, and suppressed HepG2-SR tumor growth in mice. Mechanistic studies revealed that Rg3-plus-ART inhibited activation/phosphorylation of Src and STAT3 in HepG2-SR cultures and tumors. The combination also decreased the STAT3 nuclear level and induced ROS production in HepG2-SR cultures. Furthermore, overactivation of STAT3 or removal of ROS diminished the anti-proliferative effects of Rg3-plus-ART, and removal of ROS diminished Rg3-plus-ART's inhibitory effects on STAT3 activation in HepG2-SR cells. Conclusions: Rg3-plus-ART overcomes sorafenib resistance in experimental models, and inhibition of Src/STAT3 signaling and modulation of ROS/STAT3 signaling contribute to the underlying mechanisms. This study provides a pharmacological basis for developing Rg3-plus-ART into a novel modality for treating sorafenib-resistant hepatoma.

• Molecules and Cells
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• v.46 no.6
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• pp.360-373
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• 2023

Papillary thyroid carcinoma (PTC) is the most common subtype of thyroid carcinoma. Despite a good prognosis, approximately a quarter of PTC patients are likely to relapse. Previous reports suggest an association between S-phase kinase-associated protein 2 (SKP2) and the prognosis of thyroid cancer. SKP1 is related to apoptosis of PTC cells; however, its role in PTC remains largely elusive. This study aimed to understand the expression and molecular mechanism of SKP2 in PTC. SKP2 expression was upregulated in PTC tissues and closely associated with clinical diagnosis. In vitro and in vivo knockdown of SKP2 expression in PTC cells suppressed cell growth and proliferation and induced apoptosis. SKP2 depletion promoted cell autophagy under glucose deprivation. SKP2 interacted with PH domain leucine-rich repeat protein phosphatase-1 (PHLPP1), triggering its degradation by ubiquitination. Furthermore, SKP2 activates the AKT-related pathways via PHLPP1, which leads to the cytoplasmic translocation of SKP2, indicating a reciprocal regulation between SKP2 and AKT. In conclusion, the upregulation of SKP2 leads to PTC proliferation and survival, and the regulatory network among SKP2, PHLPP1, and AKT provides novel insight into the molecular basis of SKP2 in tumor progression.

• Tuberculosis and Respiratory Diseases
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• v.43 no.4
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• pp.500-518
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• 1996

Background : The solitary pulmonary nodule(SPN) presents a diagnostic dilemma to the physician and the patient. Many clinical characteristics(i.e. age, smoking history, prior history of malignancy) and radiological characteristics( i.e. size, calcification, growth rate, several findings of computed tomography) have been proposed to help to determine whether the SPN was benign or malignant. However, most of these diagnostic guidelines are based on the data collected before computed tomography(CT) has been introduced and lung cancer was not as common as these days. Moreover, it is not well established whether these guidelines from western populations could be applicable to Korean patients. Methods : We had a retrospective analysis of the case records and radiographic findings in 114 patients presenting with SPN from Jan. 1994 to Feb. 1995 in Seoul National University Hospital, a tertiary referral hospital. Results : We observed the following results ; (1) Out of 113 SPNs, the etiology was documented in 94 SP IS. There were 34 benign SP s and 60 malignant SPNs. Among which, 49 SPNs were primary lung cancers and the most common hi stologic type was adenocarcinoma. (2) The average age of patients with benign and malignant SPNs was $49.7{\pm}12.0$ and $58.1{\pm}10.0$ years, respectively( p=0.0004), and the malignant SPNs had a striking linear propensity to increase with age. (3) No significant difference in the hi story of smoking was noted between the patients with benign SPNs($13.0{\pm}17.6$ pack- year) and those with malignant SPNs($18.6{\pm}25.1$ pack-year) (p=0.2108). (4) 9 out of 10 patients with prior history of malignancy had malignant SPNs. 5 were new primary lung cancers with no relation to prior malignancy. (5) The average size of benign SPNs($3.01{\pm}1.20cm$) and malignant SPNs($2.98{\pm}0.97cm$) was not significantly different(p=0.8937). (6) The volume doubling time could be calculated in 22 SPNs. 9 SPNs had the volume doubling time longer than 400 days. Out of these, 6 were malignant SPNs. (7) The CT findings suggesting malignancy included the lobulated or spiculated border, air- bronchogram, pleural tail, and lymphadenopathy. In contrast, calcification, central low attenuation, cavity with even thickness, well-marginated border, and peri nodular micronodules were more suggestive for benign nodule. (8) The diagnostic yield of percutaneous needle aspiration and biopsy was 57.6%(19/33) of benign SPNs and 81.0%(47/58) of malignant SPNs. The diagnostic value of sputum analysis and bronchoscopic evaluations were relatively very low. (9) 42.3%(11/26) of SPNs of undetermined etiology preoperatively turned out to be malignant after surgical resection. Overall, 75.4%(46/61) of surgically resected SPNs were malignant. Conclusions : We conclude that the likelihood of malignant SPN correlates the age of patient, prior history of malignancy, some CT findings including lobulated or spiculated border, air-bronchogram, pleural tail and lymphadenopathy. However, the history of smoking, the size of the nodule, and the volume doubling time are not helpful to determent whether the SPN is benign or malignant, which have been regarded as valuable clinical parameters previously. We suggest that aggressive diagnostic approach including surgical resection is necessary in patient with SPNs.

• The Journal of Korean Society for Radiation Therapy
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• v.25 no.1
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• pp.77-85
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• 2013

Purpose: The accurate movement of gantry rotation, collimator and correct application of dose rate are very important to approach the successful performance of Volumetric Modulated Arc Therapy (VMAT), because it is tightly interlocked with a complex treatment plan. The interruption and restart of dose delivery, however, are able to occur on treatment by various factors of a treatment machine and treatment plan. If unexpected problems of a treat machine or a patient interrupt the VMAT, the movement of treatment machine for delivering the remaining dose will be restarted at the start point. In this investigation, We would like to know the effect of interruptions and restart regarding dose delivery at VMAT. Materials and Methods: Treatment plans of 10 patients who had been treated at our center were used to measure and compare the dose distribution of each VMAT after converting to a form of digital image and communications in Medicine (DICOM) with treatment planning system (Eclipse V 10.0, Varian, USA). We selected the 6 MV photon energy of Trilogy (Varian, USA) and used OmniPro I'mRT system (V 1.7b, IBA dosimetry, Germany) to analyze the data that were acquired through this measurement with two types of interruptions four times for each case. The door interlock and the beam-off were used to stop and then to restart the dose delivery of VMAT. The gamma index in OmniPro I'mRT system and T-test in Microsoft Excel 2007 were used to evaluate the result of this investigation. Results: The deviations of average gamma index in cases with door interlock, beam-off and without interruption on VMAT are 0.141, 0.128 and 0.1. The standard deviations of acquired gamma values are 0.099, 0.091, 0.071 and The maximum gamma value in each case is 0.413, 0.379, 0.286, respectively. This analysis has a 95-percent confidence level and the P-value of T-test is under 0.05. Gamma pass rate (3%, 3 mm) is acceptable in all of measurements. Conclusion: As a result, We could make sure that the interruption of this investgation are not enough to seriously affect dose delivery of VMAT by analyzing the measured data. But this investigation did not reflect all cases about interruptions and errors regarding the movement of a gantry rotation, collimator and patient So, We should continuously maintain a treatment machine and program to deliver the accurate dose when we perform the VMAT for the many kinds of cancer patients.

• Radiation Oncology Journal
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• v.16 no.2
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• pp.167-175
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• 1998

Purpose : It is not a simple task to achieve the ideal isodose curve with a standard vaginal applicator or sing1e plane needle impant in the paravaginal tissue when primary or recurrent gynecological neoplasms(cervical cancers, vaginal cancers and vulvar cancers) are treated as a boost following external beam radiotherapy. The authors introduce the development and construction of a simple, inexpensive, customized applicator for volume implant to maximize the radiation dose to the tumor while minimizing the dose to the rectum and the bladder. Materials and Methods : Nine patients underwent Ir-192 transperineal interstitial implantation for either recurrent(5 cases) or primary(3 cases) cervical cancers or primary vaginal cancer(1 case) between August 1994 and February 1998 at Ajou university hospital. First 3 cases were performed with a sing1e plane implant guided by digital palpation. Because of inadequate isodose coverage in the tumor volume in first 3 cases, we designed and constructed interstitial vaginal applicator for volume implant to improve tumor dose distribution and homogeneity while sparing the surrounding normal tissue. Our applicators consist of vaginal obturator and perineal template that made of the clear acrylamide and dental mold material$(Provil^{(R)})$. The applicators were customized individually according to the tumor size and its location Both HDR and LDR irradiation were given with these applicators accomodating 6 Fr needles(Microselectron Nucletron). The pretreatment planning prior to actual implant was performed whenever possible. Results : Needles can be inserted easily and evenly into the tumor volume through the holes of templates, requiring less efforts and time for the implant procedure. Our applicators made of materials available from commercial vendors. These have an advantage that require easy procedure, and spend relatively short time to construct. Also it was possible to fabricate applicators to individualize according to the tumor size and its location and to achieve the ideal isodose coverage. We found an accurate needle arrangement and ideal dose distribution through the CT scan that was obtained in 3 cases after needle implant. Three patients with primary cervical and vaginal cancers were controlled locally at final follow up. But all recurrent cases failed to do so. Conclusion : The authors introduce inexpensive, simple interstitial vaginal templates which were self-designed and constructed using materials available from commercial vendors such as acrylanide and dental mold material $(Provil^{(R)})$.