• The Korean Journal of Nuclear Medicine
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• v.37 no.6
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• pp.382-392
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• 2003

Purpose: Uptakes of Tc-99m MIBI (MIBI) and Tc-99m tetrofosmin (tetrofosmin) in human non-small cell lung cancer A549, multidrug-resistance associated protein (MRP) expressing cell, were investigated in vitro and in vivo. Materials and Methods: Western blot analysis and immunohistochemistry were used for detection of MRP in A549 cells with anti-MRPr1 antibody. Cellular uptakes of two tracers were evaluated at $100{\mu}M$ of verapamil (Vrp), $50{\mu}M$ of cyclosporin A (CsA) and $25{\mu}M$ of butoxysulfoximide (BSO) after incubation with MIBI and tetrofosmin for 30 and 50 min at $37^{\circ}C$, using single cell suspensions at $1{\times}10^6cells/ml$. Radioactivities in supernatants and pellets were measured with gamma well counter. A549 cells were inoculated in each flanks of 24 nude mice. Group 1 (Gr1) and Gr3 mice were treated with only MIBI or tetrofosmin, and Gr2 and Gr4 mice were treated with 70mg/kg of CsA i.p. for 1 hour before injection of 370KBq of MIBI or tetrofosmin. Mice were sacrificed at 10, 60 and 240 min. Radioactivities of organs and tumors were expressed as percentage injected dose per gram of tissue (%ID/gm). Results: Western blot analysis of the A549 cells detected expression of MRPr1 (190 kDa) and immunohistochemical staining of tumor tissue for MRPr1 revealed brownish staining in cell membrane but not P-gp. Upon incubating A549 cells for 60 min with MIBI and tetrofosmin, cellular uptake of MIBI was higher than that of tetrofosmin. Coincubation with modulators resulted in an increase in cellular uptakes of MIBI and tetrofosmin. Percentage increase of MIBI was higher than that of tetrofosmin with Vrp by 623% and 427%, CsA by 753% and 629% and BSO by 219% and 140%, respectively. There was no significant difference in tumoral uptakes of MIBI and tetrofosmin between Gr1 and Gr3. Percentage increases in MIBI (114% at 10 min, 257% at 60 min, 396% at 240 min) and tetrofosmin uptake (110% at 10 min, 205% at 60 min, 410% at 240 min) were progressively higher by the time up to 240 min with CsA. Conclusion: These results indicate that MIBI and tetrofosmin are suitable tracers for imaging MRP-mediated drug resistance in A549 tumors. MIBI may be a better tracer than tetrofosmin for evaluating MRP reversal effect of modulators.

• The Journal of the Korean bone and joint tumor society
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• v.12 no.1
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• pp.37-46
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• 2006

Purpose: To evaluate the end results between the surgical treatment with neo-adjuvant chemotherapy in Korea and non-invasive high intensity focused ultrasound (HIFU) technique in China for osteogenic sarcomas. Materials and Methods: The surgical treatment with neoadjuvant chemotherapy for total 67 cases (4 IIA, 58 IIB, and 5 III) in Korea since 1993 and the HIFU therapy for total 71 cases (57 II and 14 III) in China since 1997 was performed. In Korea, neo-adjuvant chemotherapy in 66 cases out of total 67 patients, but the adjuvant chemotherapy in only one case was done. On the contrary, in China, full chemotherapy for more than 9 times for 37 patients with stage II out of total 71 cases, but for less than 8 times of partial chemotherapy for 23 patients (stage II) and 14 patients (stage III) was done. The surgical treatment in total 67 Korean patients was done with wide resection and reconstruction for 56 patients, but wide resection without reconstruction for 5 patients and amputation for 6 patients. In china, total 71 patients was treated with average 1.5 times (1~4 times) of HIFU, and if there are some evidences of residual tumor after HIFU with following MRI, the second HIFU therapy was given 2~4 weeks later. After then, the bony defect was in no touch, keep bracing for long time expecting regeneration. All of them were followed for average 46 Mo (12~150 Mo) in Korea, but followed for average 22 Mo (9 years~8 months) in China. Results: The 5 year survival rate (stage II), was average 92.7% (IIA 100%, IIB 85.5%) in Korea series, and average 78.7% (full chemotherapy 91.8%, part chemotherapy 56.6%) in China series. The 3 year survival rate (stage III) was 20% in Korea and 7.1% in China. So, the final overall survival rate was 65.2% in Korea and 51.8% in China. The overall functional outcome score by ISOLS was 24.3 (81%) in Korea and 19.8 (73%) in China. There are 25.4% (17/67 cases) of complications in Korea and 31% (27 complications in 22 patients out of total 71 cases) in China after each treatment. Conclusions: The end results of Korea series which was treated with neoadjuvant chemo- and surgical methods are better than that of non-invasive thermal ablation in china. But we also believe the HIFU, as one of, was also effective to decrease the local recurrence and symptomatic releaf for stage II or even in III of osteogenic sarcomas.

• The Journal of the Korean bone and joint tumor society
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• v.14 no.2
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• pp.95-105
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• 2008

Purpose: To identify which is the best procedure in recycling autograft according to the resection & reconstruction type and recycling methods, and so when the recycling autograft is used in limb salvage surgery. Materials and Methods: We have treated fifty-eight patients (34 male, 24 female; age range 5 to 74 years, mean age 36.5 years), who had the malignant musculoskeletal tumors, with recycling autograft (47 patients with extracoporeal irradiation, 11 patients with pasteurization) from December 1995 to February 2006. The resection and reconstruction type was 3 cases with fragmentary, 8 intercalary, 23 rAPC (recycling-Autograft-Prosthesis composite), 18 osteoarticular, 5 total joint and 1 soft tissue (achilles tendon). The result was evaluated by the radiologic union at junctional site, the functional score by musculoskeletal tumor society score and complications according to the resection & reconstruction type and recycling methods. Results: The junctional union was obtained at 15.0 months in extracoporeal irradiation and 12.6 months in pasteurization. Also the mean radiologic union was shown at 6.0 months in fragmentary, 12.8 months in intercalary, 10 months in rAPC, 23.3 months in osteoarticular and 15.6 months in total joint. The functional score was 65.5% in fragmentary, 60.8% in intercalary, 62.8% in APC (except pelvis), 66.0% in osteoarticular and 66.6% in total joint. We have experienced 1 infection, 1 prutrusio acetabuli in pasteurization (18.1%) and other 22 complications (3 deep infections, 8 nonunions, 2 fractures, 2 epiphyseal problems, 5 joint instabilities, 2 local recurrence) in extracoporeal irradiation (46.8%). Also we have experienced 3 complications (3 nonunions) in intercalary (37.5%), 9 complications (4 nonunions, 1 deep infection, 1 periprosthetic fracture, 1 epiphyseal problem, 1 local recurrence, 1 protrusio acetabuli) in rAPC (50.0%), 6 complications (2 deep infections, 2 nonunions, 1 epiphyseal problem, 1 pathologic fracture) in osteoarticular (33.3%), 5 complications (5 joint instabilities) in total joint (100%) and 1 complication(1 local recurrence) in soft tissue (100%). Conclusion: In our experience, according to the resection & reconstruction type fragmentary and intercalary may have several advantages such as good radiologic and functional result and low rate of complication. And it seems that rAPC was available in case which have no sufficient residual bone stock. Also the pasteurization may have more advantages than that of the extracorporeal irradiation.

• Korean Journal of Environmental Biology
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• v.22
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• pp.54-62
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• 2004

We examined the impacts of anthyopogenic pollutant (benzo〔a〕pyrene) on the growth and photosynthesis of five marine phytoplankton species (Skeletonema costatum, Heterosigma akashiwo, Prorocentrum dentatum, P. minimum, Aknshiwo sanguinea), which are dominant in Korean coastal water. After the 72 h exposure to benzo〔a〕pyrene, the dramatic decrease in cell numbers was observed in the range of 1 to 10 $\mu\textrm{g}$ L$^{-1}$ for S. costatum, P. minimum, P. dentatum, whereas for A. sanguinea and H. akashiwo at the low concentrations 0.1 to 1 $\mu\textrm{g}$ L$^{-1}$ . Among the 5 phytoplankton species, the highest growth inhibition concentration ($IC_{50}$/) was 6.20 $\mu\textrm{g}$ L$^{-1}$ for P. minimum, followed by 2.14 $\mu\textrm{g}$ L$^{-1}$ for P. dentatum, 1.68 $\mu\textrm{g}$ L$^{-1}$ for S. costatum, 0.74 $\mu\textrm{g}$ L$^{-1}$ for H. akashiwo, 0.10 $\mu\textrm{g}$ L$^{-1}$ for A. sanguinea. The five species exposed to the low concentration of 1 $\mu\textrm{g}$ L$^{-1}$ were recovered after transferring to new media, but the species exposed to the high concentrations of 10 and 100 $\mu\textrm{g}$ L$^{-1}$ were not recovered, with the exception of P. minimum. Those results indicate that the thecate dinoflagellate P. minimum is most tolerant to the chemical and the athecate dinoflagellate A. sanguinea is not. Geneyally, the cell-specific photosynthetic capacity of H. akashiwo exposed to the low concentrations of 0.1 and 1 $\mu\textrm{g}$ L$^{-1}$ was higher than that of the cells in the control, whereas the cells exposed to the high concentrations of 5 and 10 $\mu\textrm{g}$ L$^{-1}$ showed the negligible photosynthetic level by the first few days of the experiment. In the case of the cells exposed to the concentration of 5 $\mu\textrm{g}$ L$^{-1}$ , after 12 days of the experiment the photosynthetic capacity was increased toward the end of the experiment. This indicates that H. akashiwo may utilize the benzo〔a〕pyrene as a carton source for its growth when exposed to low concentrations. Results suggest that anthropogenic pollutants such as benzo〔a〕pyrene may have significant influence on the succession of phytoplankton species composition and the primary production in coastal marine environments.

• Investigative Magnetic Resonance Imaging
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• v.8 no.1
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• pp.32-41
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• 2004

Purpose : To measure the NMR relaxation properties of MnPC, to observe the characteristics of liver enhancement patterns on MR images in experimentally implanted rabbit VX2 tumor model, and to estimate the possibility of tissue specific contrast agent for MnPC in comparison with the hepatobiliary agent. Materials and Methods : Phthalocyanine (PC) was chelated with paramagnetic ions, manganese (Mn). 2.01 g (5.2 mmol) of phthalocyanine was mixed with 0.37 g (1.4 nlmol) of Mn chloride at $310^{\circ}C$ for 36 hours and then purified by chromatography ($CHCl_3:\;CH_3OH=98:2$, volume ratio) to obtain 1.04 g $(46\%)$ of MnPC (molecular weight = 2000 daltons). The T1/T2 relaxivity (R1/R2) for MnPC were determined at a 1.5 T (64 MHz) MR spectrometer. VX2 tumor model was experimentally implanted in the liver parenchyma of rabbits. All MR studies were performed on 1.5 T. The human extremity radio frequency coil of a bird cage type was employed. MR images were acquired at 17 to 24 days after VX2 carcinoma implantation.4 mmol/kg MnPC and 0.01 mmol/kg Mn-DPDP were injected via the ear vein of rabbits. T1-weighted images were obtained with spin-echo (TR/TE=516/14 msec) and fast multiplanar spoiled gradient recalled (TR/TE : 80/4 msec, $60^{\circ}$ flip angle) pulse sequence. Fast spin-echo (TR/TE=1200/85 msec) was used to obtain the T2-weighted images. Results : The value of T1/T2 relaxivity (R1/R2) of MnPC was $7.28\;mM^{-1}S^{-1}$ and $55.56\;mM^{-1}S^{-1}$ respectively at 1.5 T (64 MHz). Because the T2 relaxivity of MnPC that bonded strongly, covalently manganese with phthalocyanine was very high, the signal intensity of liver parenchyma was decreased on postcontrast T2-weighted images and we could easily distinguish the VX2 carcinoma within the liver parenchyma. When MnPC was administrated intravenously, the tumor margin delineation was more remarkable than Mn-DPDP-enhanced images. The enhancement of liver parenchyma with MnPC persisted at relatively high levels over at least one hour after injection of the contrast agents. Conclusion : The hepatic uptake and biliary excretion of MnPC, which are similar to Mn-DPDP, suggest that this agent is a new liver-specific agent. Also, MnPC seems to be used as a dual contrast agent (T1 and T2) with high T2 relaxivity. However, it is warranted that MnPC needs further investigation as a potential contrast agent for MR imaging of the liver. That is, further characterizations of MnPC are needed in vivo and in vitro before clinical trials. The diagnostic potential of MnPC will also have to be examined more in the animal models of additional types.

• The Korean Journal of Nuclear Medicine
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• v.33 no.3
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• pp.298-305
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• 1999

Purpose: N-(3-[$^{18}F$]Fluoropropyl)-$2{\beta}$-carbomethoxy-$3{\beta}$-(4-iodophenyl)nortropane [$^{18}F$]FP-CIT) has been shown to be very useful for imaging the dopamine transporter. However, synthesis of this radiotracer is somewhat troublesome. In this study, we used a new method for the preparation of [$^{18}F$]FP-CIT to increase radiochemical yield and effective specific activity. Materials and Methods: [$^{18}F$]FP-CIT was prepared by N-alkylation of nor-${\beta}$-CIT (2 mg) with 3-bromo-1-[$^{18}F$]fluoropropane in the presence of $Et_3N$ (5-6 drops of $DMF/CH_3CN$, $140^{\circ}C$, 20 min). 3-Bromo-1-[$^{18}F$]fluoropropane was synthesized from $5{\mu}L$ of 3-bromo-1-trifluoromethanesulfonyloxypropane (3-bromopropyl-1-triflate) and $nBu_4N^{18}F$ at $80^{\circ}C$. The final compound was purified by reverse phase HPLC and formulated in 13% ethanol in saline. Results: 3-Bromo-1-[$^{18}F$]fluoropropane was obtained from 3-bromopropyl-1-triflate and $nBu_4N^{18}F$ in 77-80% yield. N-Alkylation of nor-${\beta}$-CIT with 3-bromo-1-[$^{18}F$]fluoropropane was carried out at $140^{\circ}C$ using acetonitrile containing a small volume of DMF as the solvents. The overall yield of [$^{18}F$]FP-CIT was 5-10% (decay-corrected) with a radiochemical purity higher than 99% and effective specific activity higher than the one reported in the literature based on their HPLC data. The final [$^{18}F$]FP-CIT solution had the optimal pH (7.0) and it was pyrogen-free. Conclusion: In this study, 3-bromopropyl-1-triflate was used as the precursor for the [$^{18}F$]fluorination reaction and new conditions were developed for purification of [$^{18}F$]FP-CIT by HPLC. We established this new method for the preparation of [$^{18}F$]FP-CIT, which gave high effective specific activity and relatively good yield.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.1
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• pp.9-15
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• 2007

Purpose: Repetitive transcranial magnetic stimulation (rTMS) has recently been clinically applied in the treatment of drug resistant depressed patients. There are mixed findings about the efficacy of rTMS on depression. Furthermore, the influence of rTMS on the physiology of the brain is not clear. We prospectively evaluated changes of regional cerebral blood flow (rCBF) between pre- and post-rTMS treatment in patients with drug resistant depression. Materials and Methods: Twelve patients with drug-resistant depression (7 male, 5 female; age range: $19{\sim}52$ years; mean age: $29.3{\pm}9.3$ years) were given rTMS on right prefrontal lobe with low frequency (1 Hz) and on left prefrontal lobe with high frequency (20 Hz), with 20-minute-duration each day for 3 weeks. Tc-99m ECD brain perfusion SPECT was obtained before and after rTMS treatment. The changes of cerebral perfusion were analyzed using statistical parametric mapping (SPM; t=3.14, uncorrected p<0.01, voxel=100). Results: Following areas showed significant increase in rCBF after 3 weeks rTMS treatment: the cingulate gyrus, fusiform gyrus of right temporal lobe, precuneus, and left lateral globus pallidus. Significant decrement was noted in: the precental and middle frontal gyrus of right frontal lobe, and fusiform gyrus of left occipital lobe. Conclusion: Low-frequency rTMS on the right prefrontal cortex and high-frequency rTMS on the left prefrontal cortex for 3 weeks as an add-on regimen have increased and decreased rCBF in the specific brain regions in drug-resistant depressed patients. Further analyses correlating clinical characteristics and treatment paradigm with functional imaging data may be helpful in clarifying the pathophysiology of drug-resistant depressed patients.

• Journal of Chest Surgery
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• v.35 no.10
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• pp.712-723
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• 2002

Substantial alterations in cerebral blood flow(CBF) are known to occur during cardiopulmonary bypass(CPB). Many investigators have speculated that these changes may be responsible for both minor and major cerebral damages after CPB. More recently, these changes in CBF have been observed to be intimately related to the arterial carbon dioxide tension(Pa$CO_2$) maintained during CPB. The present study was prospectively designed to investigate the clinical effects of normocapnic and hypercapnic CPB on the cerebral oxygen metabolism in cardiac surgery Material and Method: Thirty-six adult patients scheduled for elective cardiac surgery were randomized to either normocapnic group (Pa$CO_2$35~40 mmHg, n＝18) or hypercapnic group(Pa$CO_2$, 45~55 mmHg, n＝18) with moderately hypothermic nonpulsatile CPB(nasopharyngeal temperature of 29~3$0^{\circ}C$). In each patient, middle cerebral artery blood flow velocity( $V_{MCA}$), cerebral arteriovenous oxygen content difference (C(a-v) $O_2$), cerebral oxygen extraction(COE), cerebral metabolic rate for oxygen(CMR $O_2$), cerebral oxygen transport( $T_{E}$ $O_2$), $T_{E}$ $O_2$/CMR $O_2$ ratio, cerebral desaturation(internal jugular bulb blood oxygen saturation $\leq$ 50%), and arterial and jugular bulb blood gas were evaluated throughout the operation. Postoperative neuropsychologic complications were assessed in all patients. All variables were compared between the two groups. Result: VMCA(169.13 $\pm$ 8.32 vs 153.11 $\pm$8.98%), TE $O_2$(1,911.17$\pm$250.14 vs 1,757.40$\pm$249.56), $T_{E}$ $O_2$,/CMR $O_2$ ratio(287.38$\pm$28.051 vs 246.77$\pm$25.84), $O_2$ tension in internal jugular bulb (41.66$\pm$9.19 vs 31.50$\pm$6.09 mmHg), and $O_2$saturation in internal jugular bulb(68.97$\pm$10.96 vs 58.12$\pm$12.11%) during CPB were significantly lower in normocapnic group(p＝0.03), whereas hypercapnic group had lower C(a-v) $O_2$(3.9$\pm$0.3 vs 4.9$\pm$0.3 mL/dL), COE(0.3$\pm$0.03 vs 0.4$\pm$0.03), CMR $O_2$(5.8 $\pm$0.5 vs 6.8$\pm$0.6), and arterial blood pH(7.36$\pm$0.09 vs 7.46$\pm$0.07, p＝0.04) during CPB. Hypercapnic group had lower incidence of cerebral desaturation than normocapnic group(3 vs 9 patients, p=0.03). Duration of the neuropsychologic complication(delirium) were shorter in hypercapnic group than in normocapnic group(36 vs 60 hrs, p＝0.009). Conclusion: These findings suggest that hypercapnic CPB may have salutary effects on the cerebral oxygen metabolism and postoperative neurologic outcomes in cardiac surgery.surgery.

• Reproductive and Developmental Biology
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• v.29 no.3
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• pp.163-168
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• 2005

The aim of this study was to investigate the changes in insulin-like growth factor-I (IGF-I) and growth hormone (GH) in serum, the quantitation of spermato-genesis and the comparable relationships among these measurements during pubertal period in New Zealand White male rabbits. To investigate the age-related testicular changes in DNA contents of spermatogenic cells, the fine-needle testicular biopsies from males aged 10 to 28 wks were evaluated by flow cytometry(FCM). Body weight increased significantly between the ages of 12 and 20 wks (P<0.05) and reached 3.4 kg at 28 wks of age. The highest serum IGF-I level (451.3ng/mL) was observed at 20wks of age (P<0.05) and thereafter remained stable at low levels. Serum GH level at 18 wks of age was 183.3 pg/mL which was significantly higher compared to the other ages (P<0.05), and the rising time in serum GH tend to be somewhat earlier than that of IGF-I. The relative percentage of It-cells in testicular cell compartments was $48.2\%$ at the age of 18 wks which significantly increased than those of 16-wk-old (P<0.05) and thereafter increased with the advance of age to $68\%$. The percentage of 2C-cells in testis was $26.8\%$ at 18 wks of age which was significantly lower than $54.3\%$ at 16 wks old (P<0.05). The percentage of 4C-cells was constantly maintained $2\~6\%$ except the $9.9\%$ at 18 wks of age. In conclusion, the results suggest that the puberty onset occurred at about the 18 wks of age and that the IGF-I and GH in serum during the pubertal period showed the age/growth-specific changes and these changes might be related to the spermatogenesis. The DNA FCM combined with fine-needle testicular biopsy could offer a very sensitive method to monitor the quantitative spermatogenic events related to the puberty onset.

• Journal of Intelligence and Information Systems
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• v.26 no.1
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• pp.1-21
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• 2020

With the rapid development of artificial intelligence technology, various techniques have been developed to extract meaningful information from unstructured text data which constitutes a large portion of big data. Over the past decades, text mining technologies have been utilized in various industries for practical applications. In the field of business intelligence, it has been employed to discover new market and/or technology opportunities and support rational decision making of business participants. The market information such as market size, market growth rate, and market share is essential for setting companies' business strategies. There has been a continuous demand in various fields for specific product level-market information. However, the information has been generally provided at industry level or broad categories based on classification standards, making it difficult to obtain specific and proper information. In this regard, we propose a new methodology that can estimate the market sizes of product groups at more detailed levels than that of previously offered. We applied Word2Vec algorithm, a neural network based semantic word embedding model, to enable automatic market size estimation from individual companies' product information in a bottom-up manner. The overall process is as follows: First, the data related to product information is collected, refined, and restructured into suitable form for applying Word2Vec model. Next, the preprocessed data is embedded into vector space by Word2Vec and then the product groups are derived by extracting similar products names based on cosine similarity calculation. Finally, the sales data on the extracted products is summated to estimate the market size of the product groups. As an experimental data, text data of product names from Statistics Korea's microdata (345,103 cases) were mapped in multidimensional vector space by Word2Vec training. We performed parameters optimization for training and then applied vector dimension of 300 and window size of 15 as optimized parameters for further experiments. We employed index words of Korean Standard Industry Classification (KSIC) as a product name dataset to more efficiently cluster product groups. The product names which are similar to KSIC indexes were extracted based on cosine similarity. The market size of extracted products as one product category was calculated from individual companies' sales data. The market sizes of 11,654 specific product lines were automatically estimated by the proposed model. For the performance verification, the results were compared with actual market size of some items. The Pearson's correlation coefficient was 0.513. Our approach has several advantages differing from the previous studies. First, text mining and machine learning techniques were applied for the first time on market size estimation, overcoming the limitations of traditional sampling based- or multiple assumption required-methods. In addition, the level of market category can be easily and efficiently adjusted according to the purpose of information use by changing cosine similarity threshold. Furthermore, it has a high potential of practical applications since it can resolve unmet needs for detailed market size information in public and private sectors. Specifically, it can be utilized in technology evaluation and technology commercialization support program conducted by governmental institutions, as well as business strategies consulting and market analysis report publishing by private firms. The limitation of our study is that the presented model needs to be improved in terms of accuracy and reliability. The semantic-based word embedding module can be advanced by giving a proper order in the preprocessed dataset or by combining another algorithm such as Jaccard similarity with Word2Vec. Also, the methods of product group clustering can be changed to other types of unsupervised machine learning algorithm. Our group is currently working on subsequent studies and we expect that it can further improve the performance of the conceptually proposed basic model in this study.