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Development and Validation of the Determination of Sorafenib in Human Plasma using Tandem Mass Spectrometry Coupled with Liquid Chromatography (고속액체크로마토그래피 텐덤질량분석기법을 이용한 사람 혈장 내 소라페닙 농도분석법의 개발 및 검정)

  • Park, Daejin;Lee, Sunggon;Kim, Woomi
    • Journal of Life Science
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    • v.22 no.11
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    • pp.1456-1462
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    • 2012
  • Sorafenib is a multikinase inhibitor and an oral anticancer drug approved for the treatment of patients with advanced renal cell carcinoma and those with unresectable hepatocellular carcinoma. The purpose of this study was to develop an efficient method of the determination of sorafenib in human plasma using tandem mass spectrometry coupled with liquid chromatography (LC/MS/MS) and validate the method by the guidelines of the Korean Food and Drug Administration (KFDA). Plasma samples ($100{\mu}l$) were added with chlorantraniliprole as an internal standard and then mixed with the 0.1% formic acid-containing extraction solution composed of isopropyl alcohol and ethyl acetate (1:4, v/v). After centrifugation, the supernatant was concentrated at $45^{\circ}C$ under negative pressure and centrifugal force. The residue was reconstituted with a mobile phase and injected into the HPLC instrument using a reverse phase Waters XTerra$^{TM}$ C18 column (particle size $3.5{\mu}m$). Liquid chromatography was carried out within the run time of 5 min using a mobile phase composed of buffer (0.1% formic acid and 10 mM ammonium formate), methanol, and acetonitrile (1:6:3, v/v/v). The analytes were monitored by tandem mass spectrometry in the multiple reaction monitoring method programmed to detect sorafenib at 'm/z 465.2 ${\rightarrow}$ 252.5' and chlorantraniliprole at 'm/z 484.4 ${\rightarrow}$ 286.2' with positive electrospray ionization mode ($ES^+$). The result showed the proper linearity ($r^2$ > 0.99) over the range of 2,000-5,000 ng/ml with good accuracy (90.7-103.9%) and precision (less than 10%). The newly developed method using LC/MS/MS was validated by the guideline of KFDA and identified as more sensitive compared to the previous methods.

Effect of Ni on Pt/$Ce_{(1-x)}Zr_{(x)}O_2$ catalysts for water gas shift reaction (WGS 반응용 Pt/$Ce_{(1-x)}Zr_{(x)}O_2$ 촉매에 Ni 첨가에 따른 영향)

  • Jeong, Dae-Woon;Kim, Ki-Sun;Eum, Ic-Hwan;Lee, Sung-Hun;Koo, Kee-Young;Yoon, Wang-Lai;Roh, Hyun-Seog
    • 한국신재생에너지학회:학술대회논문집
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    • 2009.11a
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    • pp.232-232
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    • 2009
  • 최근 WGS반응용 Pt 촉매의 성능 향상을 위한 다양한 담체 및 조촉매(Promotor) 개발에 대한 연구가 활발하게 진행되고 있다. 선행 연구결과, 입방(Cubic)구조를 가지는 $Ce_{0.8}Zr_{0.2}O_2$ 담체는 정방 입계(Tetragonal)구조를 가지는 $Ce_{0.2}Zr_{0.8}O_2$ 담체 또는 혼합산화물(Mixed oxide)구조를 가지는 $Ce_{0.5}Zr_{0.5}O_2$ 담체 보다 높은 활성과 안전성을 가진다. 이것은 촉매의 성능 향상이 Ce-$ZrO_2$의 결정구조에 의존한다는 것을 나타낸다. 따라서 WGS 반응에서 Ce/Zr 비에 따라 변화된 담체 특성이 Pt 촉매의 활성에 영향이 있을 것으로 예상되며 실험결과 1% Pt/$CeO_2$ 촉매가 가장 높은 활성을 나타내었다. 따라서 Pt/Ce-$ZrO_2$ 촉매의 성능 향상을 위해 Ce-$ZrO_2$ 담체에 조촉매인 Ni을 첨가하여 촉매적 활성을 비교하여 보았다. 촉매는 2%의 Pt과 15%의 Ni로 고정하였고 Ce/Zr 비를 제조변수로 하였다. 제조된 모든 담체는 공침법(Co-precipitation)을 사용하여 제조하였으며 $500^{\circ}C$에서 6시간 소성하였다. Pt 촉매는 함침법 (Incipient wetness impregnation)으로 담지 시켰다. 2% Pt/Ce-$ZrO_2$ 촉매와 2% Pt/15% Ni-Ce-$ZrO_2$ 촉매는 저온영역($200^{\circ}{\sim}320^{\circ}C$)에서 비슷한 CO 전환율을 나타내었으나 고온영역($360^{\circ}C{\sim}400^{\circ}C$)에서는 2% Pt/15% Ni-Ce-$ZrO_2$ 촉매가 더 높은 CO의 전환율을 나타내었다. 이것은 Ni의 영향으로 고온에서 부반응인 메탄화 반응(Methanation reaction)이 생긴 것으로 판단되어 메탄($CH_4$)의 선택도를 살펴본 결과 2% Pt/15% Ni-Ce-$ZrO_2$ 촉매가 고온영역($360^{\circ}{\sim}400^{\circ}C$)에서 급격하게 증가하는 것으로 나타나 메탄화 반응이 일어난 사실을 증명한다.

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MD Simulation of PLA-PEG Composites for Additive Manufacturing (적층 가공에서 적용 가능한 PLA-PEG 복합재료의 MD Simulation)

  • Songhee Ham;Youngjoon Jeon
    • Applied Chemistry for Engineering
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    • v.34 no.3
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    • pp.285-290
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    • 2023
  • Poly-lactic acid (PLA) is the most promising polymer in additive manufacturing as an alternative to acrylonitrile butadiene styrene (ABS). Since it is produced from renewable resources such as corn starch and sugar beets, it is also biocompatible and biodegradable. However, PLA has a couple of issues that limit its use. First, it has a comparatively low glass transition temperature of around 60 ℃, such that it exhibits low thermal resistance. Second, PLA has low impact strength because it is brittle. Due to these problems, scientists have found methods to improve the crystallinity and ductility of PLA. Polyethylene glycol (PEG) is one of the most studied plasticizers for PLA to give it chain mobility. However, the blend of PLA and PEG becomes unstable, and phase separation occurs even at room temperature as PEG is self-crystallized. Thus, it is necessary to investigate the optimal mixing ratio of PLA-PEG at the molecular scale. In this study, molecular dynamics will be conducted with various ratios of L-type PLA (PLLA) or DL-type PLA-PEG (PDLA-PEG) systems by using BIOVIA Materials Studio.

Optical Absorption and Polarogram of Macrocyclic Nickel (II) Complexes in Polar Solvents (극성용매에서 거대고리 Ni (II) 착물의 광흡수와 폴라로그램)

  • Park Yuj-Chul;Jong-Chul Byun
    • Journal of the Korean Chemical Society
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    • v.31 no.2
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    • pp.168-177
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    • 1987
  • The equilibria of chemical reaction between $\alpha$-Ni(rac-[14]-decane)$^{2+}$ and polar solvents(L; ANT, MFA, DMSO, DMF, and DMA) have been investigated by the spectrophotometric method at $25^{\circ}C$. (The equilibrium constants($K_1$) of) the first step in ANT, MFA, DMSO, DMF, and DMA were 31.0, 27.5, 21.3 15.9, and 6.4, respectively. The smallness of equilibrium constants ($K_2$) of the second step compared with $K_1$, was observed. $\alpha$-Ni(rac-[14]-dacane)$^{2+}$ + L $\leftrightharpoons$ [$\alpha$-Ni(rac-[14]-decane){\cdot}L]$^{2+}$ : $K_1$.[$\alpha$-Ni(rac-[14]-decane){\cdot}L)$^{2+}$+ L $\leftrightharpoons$ [$\alpha$-Ni(rac-[14]-decane){\cdot}$L_2$)$^{2+}$ :$K_2$. The relationship between d-d absorption energy and half-wave potential of complex ions at ACT was considered. Macrocyclic ligands increasing d-d transition energy caused half-wave potentials of Ni(II)-macrocycle to be shifted more positively. The half-wave potentials for Ni(rac-1[14]7-diene)$^{2+}$, Ni(meso-1[14]7-diene)$^{2+}$, Ni(1[14]4-diene)$^{2+}$, $\alpha$-Ni(rac-[14]-decane)$^{2+}$, ${\beta}-Ni(rac-[14]-decane)$^{2+}$, and Ni(meso-[14]-decane)$^{2+}$ reductions were -1.419, -1.431, -1.450, -1.473, and -1.480 (V vs. SCE), respectively. The d-d transition energies ($\nu_{max},\;cm^{-1}$) of the Ni(meso-[14]-decane)$^{2+}$ isomer were discussed with the dielectric constant (${\varepsilon}/{\varepsilon}_0$) of the various solvents, $\nu_{max}(cm^{-1})$ increased with increasing ${\varepsilon}/{\varepsilon}_0$.

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Gastrointestinal Stromal Tumor (GIST) of the Stomach: Clinicopathologic Analysis and Outcome (위에 발생한 위장관 간질성 종양의 임상병리학적 특성과 치료성적)

  • Ryu Je-Seock;Lee Sung-Ryul;Choi Sae-Byeol;Park Sung-Soo;Lee Ju-Han;Kim Seung-Joo;Kim Chong-Suk;Chae Yang-Seok;Mok Young-Jae
    • Journal of Gastric Cancer
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    • v.5 no.1
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    • pp.40-46
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    • 2005
  • Purpose: Gastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms of the gastrointestinal tract. GISTs are positive for the expression of c-Kit protein at immunohistochemistry, and their clinical presentations vary. This retrospective study was performed to evaluate the clincopathologic characteristics of GISTs and to define the prognostic factors. Materials and Methods: 40 patients who underwent a complete resection of a GIST during the period $1996\~2003$ at the Department of Surgery, Korea University College of Medicine, were studied. We divided them into low- and high-risk. groups by using tumor size and mitotic count: 23 cases were low risk, and 17 were high risk. Clinicopathologic features, immunohistochemical findings, and prognoses were compared between the low- and the high-risk groups. Results: The mean age of the 40 patients was $61.3\pm11.1$years, and the male-to-female ratio was 1:1.1. There was no significant difference in age and sex between the groups. A comparative analysis revealed tumor size, mitotic count, clinical symptoms, preoperative pathologic diagnosis, ulceration, and necrosis to be variables that had statistically significant differences between the high- and the low-risk groups. In the univariate analysis, tumor size, mitotic count, ulceration, necrosis, and abnormal endoscopic ultrasound findings were associated with disease-free survival, but in the multivariate analysis, mitotic activity was the only independent factor associated with disease-free survival. 8 patients had recurrences during the follow-up period, and four of them were treated with STI-571 (imatinib mesylate, $Gleevec^{(R)}$). The treated patients have survived until now; however, two of non-treated patients died from disease progression. Conclusion: Based on this study, tumor size, ulceration, and necrosis are significant factors affecting survival, and mitotic activity may be a useful prognostic marker. STI-571 may be used in an adjuvant setting because the drug has shown anticancer activity in patients with recurrence or metastasis.

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Role of Ghrelin in the Control of Reproductive Endocrine Function (포유류 생식 내분비 기능 조절에서 Ghrelin의 역할)

  • Lee, Sung-Ho
    • Development and Reproduction
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    • v.13 no.4
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    • pp.207-215
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    • 2009
  • Numerous factors can affect the activities of hypothalamus-pituitary-gonad (HPG) hormonal axis, resulting in alteration of reproductive capacity or status such as onset of puberty and menopause. Soon after the finding of leptin, a multifunctional hormone secreted from adipocytes, a close relationship between reproduction and body energy balance have been manifested. Ghrelin, another multifunctional hormone from gastrointestinal tract, is an endogenous ligand of growth hormone secretagogue receptor (GHSR), and is thought to be a counterpart of leptin in the regulation of energy homeostasis. As expected, ghrelin can also modulate the reproductive capacity through the modulation of activities of HPG axis. This paper summarizes the current knowledge on the discovery, gene structures, tissue distribution and roles of ghrelin and GHSRs in mammalian reproduction in particular modulation of reproductive hormone secretion in HPG axis. Like POMC gene expression in pituitary gland, preproghrelin gene can generate a complex repertoire of transcripts which further undergo alternative splicing and posttranslational modifications. Concerning the roles of preproghrelin gene products in the control of body physiology except energy homeostasis, limited knowledge is available so far. Several lines of evidence, however, show the interplay of ghrelin between metabolism and reproduction. In rat and human, the distribution of ghrelin receptor GHSRs (GHSR1a and GHSR1b) has been confirmed not only in the hypothalamus and pituitary which were originally postulated as target of ghrelin but also in the testis and ovary. Expression of the preproghrelin gene in the brain and gonads was also verified, suggesting the local role (s) of ghrelin in HPG axis. Ghrelin might play a negative modulator in the secretions of hypothalamic GnRH, pituitary gonadotropins and gonadal steroids though the action on pituitary is still questionable. Recent studies suggest the involvement of ghrelin in regulation of puberty onset and possibly of menopause entry. It is now evident that ghrelin is a crucial hormomal component in 'brain-gut' axis, and is a strong candidate links between metabolism and reproduction. Opposite to that for leptin, ghrelin signaling is likely representing the 'hunger' state of body energy balance and is necessary to avoid the energy investment into reproduction which has not a top priority in maintaining homeostasis. Further researches are needed to gain a deep insight into the more precise action mechanism and role of ghrelin in reproduction, and to guarantee the successful biomedical applications.

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THE CERVICAL ISLAND FLAP FOR INTRAORAL RECONSTRUCTION FOLLOWING EXCISION OF ORAL CANCER -REPORT OF 3 CASES- (구강암 적출후 경부 도상 피판을 이용한 구강내 결손부의 재건 -3 치험례-)

  • LEE, Seong-Geun;LIM, Jong-Soo;KIM, Kyung-Hyun;JEON, So-Yeun;CHO, Young-Sung;SHIN, Sang-Hun;CHO, Young-Cheol;SUNG, Iel-Yong;KIM, Uk-Kyu;KIM, Jong-Ryoul;CHUNG, In-Kyo;YANG, Dong-Kyu
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.20 no.3
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    • pp.263-268
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    • 1998
  • Many myocutaneous flaps have been used for the reconstruction of intraoral defects caused by the excision of oral cancer. Among these myocutaneous flaps, cervical island flap has been introduced by Farr et al. Although different in detail, this flap was designed as the platysma myocutaneous flap by Futrell et al in the supraclavicular site. Since many authors applied this flap to cover intraoral defect, they discussed deeply the blood supply of this flap. To improve further flap survival, it was modified by Tashiro et al. This flap makes its vascularity highly reliable. The amount of tissue needed for reconstruction can be accurately planned. The surgical and reconstruction procedure can be performed simply, rapidly, and effectively. Oral functions including deglutition, speech, and denture fitting are not compromised. With it's minimal deformity, new donor fields is not necessory. Of course, we keep in mind that this flap has limitations in patients where much bulk of tissue defects is needed and more than 3000 rad radiation due to the metastasis of neck lymph node is exposed. In three patients with intraoral squamous cell carcinoma($T_{1-3}N_0M_0$), we performed induction chemotherapy with FP regimen including pepleomycin. Thereafter, we ablated oral cancer and peformed reconstruction of intraoral defects with cervical island flap designed by Tashiro et al. Due to these significant benefits and minimal limitations, we have found that this flap is adequate for reconstruction of most intraoral defects following cancer ablation.

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Study of 188Re(V)-DMSA for Treatment of Cancer: Radiolabeling and Biodistribution (암 치료를 위한 188Re(V)-DMSA에 관한 연구: 방사성동위원소 표지와 생체내 분포)

  • Kim, Young Ju;Jeong, Jae Min;Chang, Young Soo;Lee, Dong Soo;Chung, June-Key;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.81-88
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    • 1998
  • The purpose of this study was to examine the radiolabeling and biodistribution of $^{188}Re(V)$-DMSA as a therapeutic cancer radiopharmaceutical. We made a DMSA kit($NaHCO_3$ 1.5 mg, meso-2,3-dimercaptosuccinic acid 1.0 mg, L(+)-ascorbic acid 0.7 mg, $SnCl_2{\cdot}2H_2O$ 0.34 mg, pH 2.9) for labeling with $^{188}Re$. In this kit, $^{188}ReO_4{^-}$ 5 mCi/2 ml added and boiled at $100^{\circ}C$ for 3 hr in water bath. The final pH adjusted to 7.5 with 7% $NaHCO_3$ solution. We checked the labelling efficacy with TLC-SG(n-butanol : acetic acid : $H_2O$ = 3 : 2 : 3) and examined the stability both in room temperature and in serum at $37^{\circ}C$. Biodistribution(1, 3, 13, 24, 48 hr) of $^{188}Re(V)$-DMSA compound was evaluated in Sarcoma 180 tumor-bearing mice. Each labeling efficiency and stability at room temperature for 48 hours was over 98% and 95%, respectively. The stability in serum were 82%(6 hr) and 85%(48 hr). Tumor uptake of $^{188}Re(V)$-DMSA in Sarcoma 180-bearing mice were $0.66{\pm}0.15%$(1 hr), $0.51{\pm}0.10%$(3 hr), $0.19{\pm}0.05%$(24 hr) and $0.13{\pm}0.02%$(48 hr). These result are consistent with those of $^{99m}Tc(V)$-DMSA which were reported previously. In conclusion, $^{188}Re(V)$-DMSA may be a useful therapeutic radiopharmaceutical for treating some cancers and metastatic bone lesion.

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Development of cordycepin fortified milk production in Holstein cows I. Effects of various levels of Cordyceps militaris mycelia from grains supplement on cordycepin content in milk in dairy cows (Cordycepin 강화 우유 생산에 관한 연구 I. 동충하초 균사체의 적정사용량 결정을 위한 사양연구)

  • Yeo, J.M.;Lee, S.H.;Kim, D.H.;Hwang, J.H.;Kim, W.Y.
    • Journal of Practical Agriculture & Fisheries Research
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    • v.11 no.1
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    • pp.103-111
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    • 2009
  • This study was carried out to determine effects of long-term supply of Cordyceps militaris mycelia on cordycepin content in milk in dairy cows. Ten Holstein cows in the early stages of lactation were divided into two groups. Control group received no supplement whereas treatment group received 6% of C. militaris mycelia of their dry matter intake for 6 months. Feed intake, milk urea nitrogen and somatic cell counts were not affected by long-term supply of C. militaris mycelia for the whole period. In addition, milk yield and milk composition were not affected by long-term supply of C. militaris mycelia at any time of the periods with the exception of milk protein content and yield. The average of milk protein content and yield from the whole period was higher for C. militaris mycelia supplement group than for the control group. As expected, cordycepin in whole blood and milk was not detected in the control group. The range of cordycepin content in the treatment was 0.31~0.38µ/ml and 0.18~0.26(µ/ml for whole blood and milk, respectively. Individual variation was found to be very high and, furthermore cordycepin was undetected in some milk samples. Thus, no clear pattern could be seen in cordycepin content in milk throughout the whole period. Overall, the results of the present study suggest that the transfer efficiency of cordycepin to milk by supplementing C. militaris mycelia in dairy cows was unpredictable and low.

Experimental Studies on the Antitumor Effects of Jinryungtang Gagambang Extract (진령탕가감방의 항종양효과(抗腫瘍效果)에 관(關)한 실험적(實驗的) 연구(硏究))

  • Jeong, Jun-Tak;Moon, Goo;Moon, Suk-Jae
    • THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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    • v.4 no.1
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    • pp.37-53
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    • 1998
  • The sprig of Jinryungtang Gagambang has been used for curing as a traditional medicine without any experimental evidence to support the rational basis for their clinical use. This experiment was carried out to evaluate the possible therapeutic or antitumoral effects of Jinryungtang Gagambang extract against cancer, and to study some mechanisms responsible for its effect. The cytotoxic and antitumor effects were evaluated on human cell liens (A549, hep3B, Caki-1, Sarcoma 180) after exposure to Jinryungtang Gagambang extract using in ILS, colony forming efficency and SRB assay which were regarded as a valuable method for cytotoxic and antitumor effects of unknown compound on tumor cell lines. The results obtained in this studies were as follows. 1. As a result of exposure to Jinryungtang Gagambang extract, the proliferation of A549, hep3B, Caki-1, good correlations were shown from the results of SRB assay and those of clogenetic assay. 2. The oral administration of Jinryungtang Gagambang extract showed significant effects of increase of MST(mean survival time) and ILS(increased life span) depending on the increasing concentration. 3. Against squamous cell carcinoma induced by MCA, Jinryungtang Gagambang decreased not only the frequency of tumor production but also the number and weight of tumors per tumor bearing mice(TBM). Jinryungtang Gagambang also significantly suppressed the development of 3LL cell-implanted tumors by frequency and their size, and some developed tumors were regressed by the continuous treatment of Jinryungtang Gagambang extract into TBM. 4. Jinryungtang Gagambang extract also increased NK cell activities. According to the above results, it could be suggested that Jinryungtang Gagambang extract has prominent antiutmor effect.

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