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The Effect of $I{\kappa}B{\alpha}$-SR Gene Transfer on the Sensitivity of Human Lung Cancer Cell Lines to Cisplatin and Paclitaxel ($I{\kappa}B{\alpha}$-SR 유전자이입이 Cisplatin, Paclitaxel에 대한 폐암세포주의 감수성에 미치는 영향)

  • Lee, Seok-Young;Seol, Ja-Young;Park, Kyung-Ho;Park, Gun-Min;Hwang, Yong-Il;Kim, Cheol-Hyeon;Jang, Seung-Hun;Kwon, Sung-Youn;Yoo, Chul-Gyu;Kim, Young-Whan;Han, Sung-Koo;Shim, Young-Soo;Lee, Choon-Taek
    • Tuberculosis and Respiratory Diseases
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    • v.51 no.2
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    • pp.122-134
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    • 2001
  • Background : Some chemotherapeutic drugs induce NF-${\kappa}B$ activation by degrading the $I{\kappa}B{\alpha}$ protein in cancer cells which contributes to anticancer drug resistance. We hypothesized that inhibiting $I{\kappa}B{\alpha}$ degradation would block NF-${\kappa}B$ activation and result in increased tumor cell mortality in response to chemotherapy. Methods : The "superrepressor" form of the NF-${\kappa}B$ inhibitor was transferred by an adenoviral vector (Ad-$I{\kappa}B{\alpha}$-SR) to the human lung cancer cell lines (NCI H157 and NCI H460). With a MIT assay, the level of sensitization to cisplatin and paclitaxel were measured. To confirm the mechanism, an EMSA and Annexin V assay were performed. Results : EMSA showed that $I{\kappa}B{\alpha}$-SR effectively blocked the NF-${\kappa}B$ activation induced by cisplatin. Transduction with Ad-$I{\kappa}B{\alpha}$-SR resulted in an increased sensitivity of the lung cancer cell lines to cisplatin and paclitaxel by a factor of 2~3 in terms of $IC_{50}$. Annexin-V analysis suggests that this increment in chemosensitivity to cisplatin probably occurs through the induction of apoptosis. Conclusion : The blockade of chemotherapeutics induced NF-${\kappa}B$ activation by inducing Ad-$I{\kappa}B{\alpha}$-SR, increased apoptosis and increasing the chemosensitivity of the lung cancer cell lines tested, subsequently. Gene transfer of $I{\kappa}B{\alpha}$-SR appears to be a new therapeutic strategy of chemosensitization in lung cancer.

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Development of Manual Multi-Leaf Collimator for Proton Therapy in National Cancer Center (국립암센터의 양성자 치료를 위한 수동형 다엽 콜리메이터 개발)

  • Lee, Nuri;Kim, Tae Yoon;Kang, Dong Yun;Choi, Jae Hyock;Jeong, Jong Hwi;Shin, Dongho;Lim, Young Kyung;Park, Jeonghoon;Kim, Tae Hyun;Lee, Se Byeong
    • Progress in Medical Physics
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    • v.26 no.4
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    • pp.250-257
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    • 2015
  • Multi-leaf collimator (MLC) systems are frequently used to deliver photon-based radiation, and allow conformal shaping of treatment beams. Many proton beam centers currently make use of aperture and snout systems, which involve use of a snout to shape and focus the proton beam, a brass aperture to modify field shape, and an acrylic compensator to modulate depth. However, it needs a lot of time and cost of preparing treatment, therefore, we developed the manual MLC for solving this problem. This study was carried out with the intent of designing an MLC system as an alternative to an aperture block system. Radio-activation and dose due to primary proton beam leakage and the presence of secondary neutrons were taken into account during these iterations. Analytical calculations were used to study the effects of leaf material on activation. We have fabricated tray model for adoption with a wobbling snout ($30{\times}40cm^2$) system which used uniform scanning beam. We designed the manual MLC and tray and can reduce the cost and time for treatment. After leakage test of new tray, we upgrade the tray with brass and made the safety tool. First, we have tested the radio-activation with usually brass and new brass for new manual MLC. It shows similar behavior and decay trend. In addition, we have measured the leakage test of a gantry with new tray and MLC tray, while we exposed the high energy with full modulation process on film dosimetry. The radiation leakage is less than 1%. From these results, we have developed the design of the tray and upgrade for safety. Through the radio-activation behavior, we figure out the proton beam leakage level of safety, where there detects the secondary particle, including neutron. After developing new design of the tray, it will be able to reduce the time and cost of proton treatment. Finally, we have applied in clinic test with original brass aperture and manual MLC and calculated the gamma index, 99.74% between them.

The physiological characteristics of Pleurotus ferulae Lanzi (아위버섯균의 생리적 특성)

  • Kim, Dae-Sik;Chai, Jung-Ki;Wi, Kye-Moon;Yoon, Dai-Ryoung;Oh, Deuk-Sil;Chang, Kyoung Soo;Son, Han-Gil
    • Journal of Mushroom
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    • v.2 no.2
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    • pp.88-96
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    • 2004
  • This study was executed to decide the physiological characteristics of Ferule mushroom. Four strains of Ferule mushroom were tested to select a superior strain in its mycelial growth. The pertinent substrates, temperature and pH ranges for the growth of selected strain were determined. And then, the wood rotting ability and type of the Ferule mushroom were determined. The superior strain F-2 among four strains was selected, on the basis of its vegetative mycelial growth and density on agar media. Mycelial growth of F-2 was the best on MYPA among other tested synthetic or semi-synthetic media. The temperature range for pertinent mycelial growth was about $25{\sim}34^{\circ}C$ and best at $30^{\circ}C$. The optimum pH range on MYPA was 5.0~6.0. The mycelial growth was mostly stimulated by soluble starch at cont. 1% (w/w) and secondly, maltose among several carabon sources and by mixed solution of YE(0.25%) and ME(0.25%) but not by ME alone. Cell thining and erosion of Pinus rigida wood by the mycelia of Ferule mushroom were found only on a few cell but largely at wood block test, indicating that the softwood rotting ability of Ferule mushroom mycelia was not so good. The result of polarized light microscopy appeared that cellulose of some tracheides showing the S3 layer lost brifringence was degraded by Ferule mushroom. But only part of cellulose of P. rigida wood was degraded by Ferule mushroom, because most of wood cells continued to showing briefingence. A largely degraded ray parenchyma and longitudinal parenchyma cell and partly thinning and erosion of hardwood(Quercus serrata) cell was found and it indicates that the rotting ability of Ferule mushroom mycelia on hardwood was higher than on softwood. It could be concluded that the difference in the wood rot by Ferule mushroom between the hardwood and softwood was made by the difference of chemical constitutions between them, especially in the contents and the types of lignin. Ferule mushroom was considered as white rotter as a result of bavendam test, although more research should be required.

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Role of the Nuclear Transcription Factor NF-κB Caused by Acute Hypoxia in the Heart (급성 저산소증 상태에서 심장 내 전사인자 NF-κB의 기능)

  • Joo, Chan Uhng;Juhng, Woo Suk;Kim, Jae Cheol;Yi, Ho Keun
    • Clinical and Experimental Pediatrics
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    • v.45 no.9
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    • pp.1106-1113
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    • 2002
  • Purpose : Nuclear ($factor-{\kappa}BNF-{\kappa}B$) is now recognized as playing a potential role in programmed cell death and the adaptive response to various stress. Cellular hypoxia is a primary manifestation of many cardiovascular diseases. It seems that vascular endothelial growth factor (VEGF) and insulin like growth factor-I(IGF-I) have a function as a protective molecule in the heart against several stress including hypoxia. In this study, the role of $NF-{\kappa}B$ to the cellular response and regulation of protective molecules against the acute hypoxia in the heart was studied. Methods : To cause acute hypoxic stress to the heart, Sprague Dawley rats were exposed to hypoxic chamer($N_2$ 92% and $O_2$ 8%). After the hypoxic exposure, nuclear proteins, total proteins and mRNA were isolated from heart. Translocation of the transcription factors $NF-{\kappa}B$, NF-ATc, AP-1 and NKX-2.5 were evaluated by electrophoretic mobility shift assay(EMSA). The expression of IGF-I and VEGF were studied before and after the hypoxic stress by competitive-PCR, Northern hybridization and Western hybridization. To confirm the role of the $NF-{\kappa}B$ in the heart, the rats also were pretreated with diethyl-dithiocarbamic acid(DDTC) into peritoneal cavity to block $NF-{\kappa}B$ translocation into nucleus. Results : The expression of $NF-{\kappa}B$, AP-1 and NF-ATc were increased by the hypoxic stress. Increased expression of the VEGF and IGF-I were also observed by the hypoxic stress. However, the blocking of the $NF-{\kappa}B$ translocation reduced those expressions of VEGF and IGF-I. Conclusion : These results suggest that $NF-{\kappa}B$ has a protective role against the acute hypoxia through several gene expression, especially VEGF and IGF-I in heart muscle.

Interpretation of depositional setting and sedimentary facies of the late Cenozoic sediments in the southern Ulleung Basin margin, East Sea(Sea of Japan), by an expert system, PLAYMAKER2 (PLAYMAKER2, 전문가 시스템을 이용한 동해 울릉분지 남부 신생대 후기 퇴적층의 퇴적환경 해석)

  • Cheong Daekyo
    • The Korean Journal of Petroleum Geology
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    • v.6 no.1_2 s.7
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    • pp.20-24
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    • 1998
  • Expert system is one type of artificial intelligence softwares that incorporate problem-solving knowledges and experiences of human experts by use of symbolic reasoning and rules about a specific topic. In this study, an expert system, PLAYMAKER2, is used to interpret sedimentary facies and depositional settings of the sedimentary sequence. The original version of the expert system, PLAYMAKER, was developed in University of South Carolina in 1990, and modified into the present PLAYMAKER2 with some changes in the knowledge-base of the previous system. The late Cenozoic sedimentary sequence with maximum 10,000 m in thickness, which is located in the Korean Oil Exploration Block VI-1 at the southwestern margin of the Ulleung Basin, is analysed by the expert system, PLAYMAKER2. The Cenozoic sedimentary sequence is divided into two units-lower Miocene and upper Pliocene-Pleistocene sediments. The depositional settings and sedimentary facies of the Miocene sediments interpreted by PLAYMAKER2 in terms of belief values are: for depositional settings, slope; $57.4\%$, shelf; $21.4\%$, basin; $10.1\%$, and for sedimentary facies, submarine fan; $35.7\%$, continental slope; $26.3\%$, delta; $16.1\%$, deep basinplain; $6.1\%$ continental shelf; $3.2\%$, shelf margin; $1.4\%$. The depositional settings and sedimentary facies of the Pliocene-Pleistocene sediments in terms of belief values we: for depositional settings, slope; $59.0\%$, shelf; $22.8\%$, basin; $7.0\%$, and for sedimentary facies, delta; $24.1\%$, continental slope; $22.2\%$, submarine fan; $17.3\%$, continental shelf; $7.0\%$, deep basinplain; $4.8\%$, shelf margin; $2.6\%$. The comparison of the depositional settings and sedimentary facies consulted by PLAYMAKER2 with those of the classical interpretation from previous studies shows resonable similarity for the both sedimentary units-the lower Miocene sediments and the upper Pliocene-Pleistocene sediments. It demonstrates that PLAYMAKER2 is an efficient tool to interpret the depositional setting and sedimentary facies for sediments. However, to be a more reliable system, many sedimentologists should work to refine and add geological rules in the knowledge-base of the expert system, PLAYMAKER2.

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Effect of Feeding Aflatoxin $B_1$ and Vitamin $D_3$ on Metatarsus Bone Minerals of Broiler Chicks (Aflatoxin $B_1$과 Vitamin $D_3$ 결여가 Broiler병아리의 중족골 무기물함량에 미치는 영향)

  • 장윤환;여영수
    • Korean Journal of Poultry Science
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    • v.17 no.4
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    • pp.296-302
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    • 1990
  • This study was conducted to investigate the interaction of aflatoxin B$_1$($AFB_1$) and vitamin D$_3$($VD_3$) in broiler chicks. The 336 broiler chicks(Hubbard line) of equally mixed sex were allocated to triplicate 8(2$\times$4 factorial) treatment groups. The 0 or 1ppm of AFB$_1$and 0, 500, 1,000 or 1,500IU/kg of VD$_3$ were supplemented to the basal diet Fourteen broilers of equally mixed sex were allocated to each replica and 24 groups were arranged in a randomized block design After 3 weeks of feeding the metatarsus were collected from the right and left legs of 4 chicks (2 for each sex) per group. The bone ash and minerals were measured. 1. In respect to the fresh weight of metatarsus bone no significant difference was found between 0 and 1ppm $AFB_1$ treatments, however, decreasing trend was recognized when fed increasing level of $VD_3$(P<.01). 2. The ash content in non-fat dry metatarsus bone decreased when fed 1ppm $AFB_1$(P<.01). However, that increased according to the increasing amount of $VD_3$(P<.01). Although there was no interaction between $AFB_1$ and $VD_3$ it was shown that the 1500IU/kg of $VD_3$ was neccessary to cover the decrease in ash content of metatarsus. when fed 1ppm of $AFB_1$. 3. The Ca contents in metatarsus were not influenced by feeding $AFB_1$ but an increasing trend was verified by feeding increasing levels of $VD_3$(P<.05). 4. The P content decreased as $AFB_1$ was fed(P<.01), while no response was found when fed'different levels of $VD_3$ 5. The Cu content decreased when fed $AFB_1$(P<.05). 6. The Na, Mg, K, Zn, Fe and Mn contents were not affected by feeding $AFB_1$ and /or $VD_3$.

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Development of a Small Animal Positron Emission Tomography Using Dual-layer Phoswich Detector and Position Sensitive Photomultiplier Tube: Preliminary Results (두층 섬광결정과 위치민감형광전자증배관을 이용한 소동물 양전자방출단층촬영기 개발: 기초실험 결과)

  • Jeong, Myung-Hwan;Choi, Yong;Chung, Yong-Hyun;Song, Tae-Yong;Jung, Jin-Ho;Hong, Key-Jo;Min, Byung-Jun;Choe, Yearn-Seong;Lee, Kyung-Han;Kim, Byung-Tae
    • The Korean Journal of Nuclear Medicine
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    • v.38 no.5
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    • pp.338-343
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    • 2004
  • Purpose: The purpose of this study was to develop a small animal PET using dual layer phoswich detector to minimize parallax error that degrades spatial resolution at the outer part of field-of-view (FOV). Materials and Methods: A simulation tool GATE (Geant4 Application for Tomographic Emission) was used to derive optimal parameters of small PET, and PET was developed employing the parameters. Lutetium Oxyorthosilicate (LSO) and Lutetium-Yttrium Aluminate-Perovskite(LuYAP) was used to construct dual layer phoswitch crystal. $8{\times}8$ arrays of LSO and LuYAP pixels, $2mm{\times}2mm{\times}8mm$ in size, were coupled to a 64-channel position sensitive photomultiplier tube. The system consisted of 16 detector modules arranged to one ring configuration (ring inner diameter 10 cm, FOV of 8 cm). The data from phoswich detector modules were fed into an ADC board in the data acquisition and preprocessing PC via sockets, decoder block, FPGA board, and bus board. These were linked to the master PC that stored the events data on hard disk. Results: In a preliminary test of the system, reconstructed images were obtained by using a pair of detectors and sensitivity and spatial resolution were measured. Spatial resolution was 2.3 mm FWHM and sensitivity was 10.9 $cps/{\mu}Ci$ at the center of FOV. Conclusion: The radioactivity distribution patterns were accurately represented in sinograms and images obtained by PET with a pair of detectors. These preliminary results indicate that it is promising to develop a high performance small animal PET.

The Heterogeneity of Flow Distribution and Partition Coefficient in [15O-H2O] Myocardium Positron Emission Tomography ([15O-H2O] 심근 양전자 단층 촬영에서 혈류 분포의 비균일성과 분배계수)

  • Ahn, Ji Young;Lee, Dong Soo;Kim, Kyung Min;Jeong, Jae Min;Chung, June-Key;Shin, Seung-Ae;Lee, Myung Chul;Koh, Chang-Soon
    • The Korean Journal of Nuclear Medicine
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    • v.32 no.1
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    • pp.32-49
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    • 1998
  • For estimation of regional myocardial blood flow with O-15 water PET, a few modifications considering partial volume effect based on single compartment model have been proposed. In this study, we attempted to quantify the degree of heterogeneity and to show the effect of tissue flow heterogeneity on partition coefficient(${\lambda}$) and to find the relation between perfusable tissue index(PTI) and ${\lambda}$ by computer simulation using two modified models. We simulated tissue curves for the regions with homogeneous and heterogeneous blood flow over a various flow range(0.2-4.0ml/g/min). Simulated heterogeneous tissue composed of 4 subregions of the same or different size of block which have different homogeneous flow and different degree of slope of distribution of blood flow. We measured the index representing heterogeneity of distribution of blood flow for each heterogeneous tissue by the constitution heterogeneity(CH). For model I, we assumed that tissue recovery coefficient ($F_{MME}$) was the product of partial volume effect($F_{MMF}$) and PTI. Using model I, PTI, flow, and $F_{MM}$ were estimated. For model II, we assumed that partition coefficient was another variable which could represent tissue characteristics of heterogeneity of flow distribution. Using model II, PTI, flow and ${\lambda}$ were estimated. For the simulated tissue with homogeneous flow, both models gave exactly the same estimates, of three parameters. For the simulated tissue with heterogeneous flow distribution, in model I, flow and $F_{MM}$ were correctly estimated as CH was increased moderately. In model II, flow and ${\lambda}$ were decreased curvi-linearly as CH was increased. The degree of underestimation of ${\lambda}$ obtained using model II, was correlated with CH. The degree of underestimation of flow was dependent on the degree of underestimation of ${\lambda}$. PTI was somewhat overestimated and did not change according to CH. We conclude that estimated ${\lambda}$ reflect the degree of tissue heterogeneity of flow distribution. We could use the degree of underestimation of ${\lambda}$ to find the characteristic heterogeneity of tissue flow and use ${\lambda}$ to recover the underestimated flow.

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Effects of Dietary Probiotics on Feed Intakes, Nutrient Digestibility and Nitrogen Retention in Korean Black Goats Fed Two Diets Differing in Forage to Concentrate Ratios (사료 내 조농비율에 따른 생균제의 첨가가 흑염소의 사료섭취량, 영양소 소화율 및 질소축적에 미치는 영향)

  • HwangBo, Soon;Jo, Ik-Hwan;Song, Ki-Jun;Lee, Sung-Hoon
    • Korean Journal of Organic Agriculture
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    • v.15 no.2
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    • pp.195-205
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    • 2007
  • This study was conducted to determine effects of probiotics on performance, nutrient digestibility and nitrogen retention in Korean black goats fed two diets differing in forage to concentrate (F:C) ratio (30:70 and 70:30), for the establishment of their more efficient feeding management system. The probiotics employed in this trial were mixtures of different microbial species, which consisted of Lactobacillus casei, Bacillus subtilis, Saccharomyces cerevisiae, Aspergillus oryzae and Streptomyces griseus. Additional levels of probiotics to each F:C ratio (70:30 or 30:70) were 0 and 0.2%, respectively. Thus, twelve Korean black male goats were allotted to treatments in four groups of three goats per treatment and then they were housed in individual metabolism cages with a randomized complete block design for 21 days. Dry matter (DM) intakes were not affected by dietary F:C ratio and probiotics. Digestible DM amounts were significantly (p<0.05) decreased with increasing levels of dietary forage, but they were not affected by probiotics addition. Dry matter intakes per metabolic body weight and their ratio per body weight had a similar trend to DM intakes with no significant difference by F:C ratio and probiotics addition. The nutrient digestibility was significantly (p<0.05) increased with decreasing levels of forage in the diet, but it was not affected by probiotics addition. Urinary nitrogen loss was significantly (p<0.05) decreased with decreasing levels of dietary forage, but there was no significant difference between probiotics-supplemented and unsupplemented groups within the same F:C ratio. On the contrary, nitrogen retention was decreased with increasing levels of dietary forage, and probiotics supplementation to two diets differing in F:C ratio showed slightly increasing trends in the nitrogen retention. From the above results, probiotics supplementation to two diets differing in F:C ratio did not have the significant influence on feed intakes, nutrient digestibility and nitrogen retention. Consequently, these parameters of Korean black goats were dominated rather by F:C ratio than by dietary probiotics.

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Growth Effect of Oncorhychus masou by Recombinant Myostatin Prodomain Proteins Derived from Fish (어류 유래 마이오스타틴 프로도메인 단백질에 의한 시마연어(Oncorhychus masou) 성장효과)

  • Kim, Jeong-Hwan;Lee, Sang-Beum;Cho, Mi-Jin;Ahn, Ji-Young;Lee, Suk-Keun;Hong, Sung-Youl;Seong, Ki-Baik;Jin, Hyung-Joo
    • Journal of Life Science
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    • v.21 no.8
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    • pp.1149-1155
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    • 2011
  • Myostatin (MSTN) belongs to the transforming growth factor-${\beta}$ superfamily or growth and differentiation factor 8 (GDF-8), and functions as a negative regulator of skeletal muscle development and growth. Previous studies in mammals have suggested that myostatin knock-out increased muscle mass and decreased fat content compared to those of the wide type. Recently, several studies on myostatin have beenconducted on the block myostatin signal pathway with myostatin antagonists and the MSTN regulation with RNAi to control myostatin function. This study was performed to analyze growth and muscle alteration of Oncorhychus masou by treatment with recombinant myostatin prodomains derived from fish. We designed myostatin prodomains derived from P. olivaceus (pMALc2x-poMSTNpro) and S. schlegeli (pMALc2x-sMSTNpro) in a pMALc2x expression vector, and then purified the recombinant proteins using affinity chromatography. The purified recombinant proteins were treated in O. masou through an immersion method. Recombinant protein treated groups did not show a significant difference in weight, protein, or lipid composition compared to the control. However, there was a difference in the average number and area for histological analyses in the muscle fiber. At twelve and twenty-two weeks from the initial treatment, there were differences in averagefiber number and area between the 0.05 mg/l treated-group and the control, but the numbers were similar to those of the control during the same time period. At twelve weeks, however, 0.2 mg/l treated-group had an increase in average fiber number and decrease in average fiber area compared to the control. At twenty-two weeks, the pMALc2x-sMSTNpro 0.2 mg/l treated-group was induced and showed a decrease in average fiber number and increase in average fiber area. The results between twelve and twenty-two weeks showed that the fiber numbers had decreased, whereas average fiberarea had increased due to sMSTNpro. It is understood that the sMSTNpro induced only hyperplasia at twelve weeks, after which it induced hypertrophy. Recombinant myostatin prodomains derived from fish may induce hyperplasia and hypertrophy in O. masou depending upon the time that has elapsed.