Ki-67 labeling index as a prognostic marker in advanced stomach cancer

Sang Hyuk Seo,Kwang Hee Kim,Sang Hoon Oh,Yunseon Choi,Ki Jung Ahn,Ji Young Lee,Sang Min Lee,박지선,Woo Gyeong Kim 대한외과학회 2019 Annals of Surgical Treatment and Research(ASRT) Vol.96 No.1

Purpose: Proliferation marker Ki-67 is widely used in cancer prognosis prediction. We tried to investigate the role of Ki-67 as a prognostic factor in stomach cancer after surgery in this study. Methods: We retrospectively evaluated 251 patients who underwent curative resection for gastric cancer from 2010 to 2015. In pathologic examination, Ki-67 labeling index was defined as the percentage of Ki-67 antigen positive cells. Prognostic significance of Ki-67 for gastric cancer was evaluated. Disease-free survival (DFS) was assessed as a primary end-point. Results: The median follow-up period was 28.0 months. Thirty-one patients (12.4%) showed Ki-67 labeling index (LI) lower than 25%. Sixty-eight patients (26.6%) showed recurrence during follow-up period. Recurrence was associated with Ki- 67 LI level (≤25%, P = 0.016), and lymph node metastasis status (P = 0.002). High Ki-67 LI level (>25%) was also related to p53 positivity (P < 0.001) and poorly cohesive type (P = 0.002). The 3-year DFS was 69.4%. Low Ki-67 LI level (≤25%) was related with low DFS (47.6% vs. 72.6%, P = 0.016). T stage (P < 0.001), N stage (P = 0.006), lymphovascular invasion (P = 0.010), and neuronal invasion (P = 0.001) also affected the DFS. In addition, T stage (P = 0.03) and Ki-67 LI (P = 0.035) were independent prognostic factors for DFS. In patients treated with adjuvant chemotherapy (n = 239, 93.4%), low Ki-67 (≤25%) was a poor prognostic factor for DFS (P = 0.013). Conclusion: Low Ki-67 LI predicts high rate of progression and low DFS of stomach cancer. Ki-67 LI can be a predictive marker in resected stomach cancer treated with surgery and adjuvant chemotherapy.

간내 담석과 동반된 간내 담도암에서의 p53과 Ki-ras의 발현

김명환,이성구,서동완,이승규,남승우,박능화,민영일,김연석,심기남,공경엽 대한소화기학회 1997 대한소화기학회지 Vol.30 No.5

Background/Aims: Hepatolithiasis or primary intrahepatic stones may be accompanied later by intrahepatic cholangiocarcinoma. This cancerous lesion is frequently associated with atypical hyperplastic epithelium that was suspected of being precancerous. To investigate the Ki-ras or p53 mutation may play a role in carcinogenesis, and to determine whether atypical hyperplastic epithelium may be precancerous, this study was performed in intrahepatic cholangiocarcinomas associated with hepatolithiasis. Methods: We examined 12 patients with intrahepatic cholangiocarcinomas associated with hepatolithiasis. Ki-ras point mutations were assessed by direct DNA sequencing. Expressions of p53 protein were immunohistochemically assessed. The overexpression of p53 and point mutation of Ki-ras were examined in normal, hyperplastic, atypical hyperplastic, and can- cerous tissues separately. Results: The expressions of p53 protein were detected in 4 (33%) of 12 cholangiocarcinomas and Ki-ras point mutations at codon 12 were found in 2 (17%) of 12 cholangiocarcinomas. In those two carcinoma cases which contained the mutant sequence of Ki-ras, the same point mutation from wild type GGT (glycine) to GAT (aspartic acid) was. found in the associated atypical hyperplastic epithelium. However, none of the normal and hyperplastic epithelium harbored Ki-ras or p53 mutations. Conclusions: The overexpression of p53 may play a part in the carcinogenesis of some intrahepatic cholangiocarcinomas associated with hepatolithiasis, whereas the role of Ki-ras mutations in those cases is dubious. However, Ki-ras point mutation at codon 12 may be responsible for either cancer or atypical hyperplastic epithelium associated with hepatolithiasis in certain cases, suggesting atypical hyperplastic epithelium may give rise to carcinoma.

촉매를 이용한 이산화탄소 고정화 및 고리형 카보네이트 합성반응에 대한 계산화학적 해석

안혜영(Hye Young An),김민경(Min-Kyung Kim),정희철(Hui Cheol Jeong),엄기헌(Ki Heon Eom),원용선(Yong Sun Won) 한국청정기술학회 2016 청정기술 Vol.22 No.1

본 연구에서는 이론화학 또는 분자모델링이라 불리는 계산화학을 기존에 연구된 촉매반응 실험결과를 해석하는 데 접목시켜 보았다. 온실효과의 주범인 이산화탄소를 에폭사이드와 반응을 통해 고정화하고 카보네이트를 생성하는 반응을 선택하였는데 이 반응은 활성화 에너지(55~59 kcal/mol)가 높아 촉매의 사용이 불가피하다. 많은 기존 연구들 중에 ZIF-90/ionic liquid immobilized ZIF-90 (IL-ZIF-90), polystyrene-supported quaternized ammonium salt, KI/KI-glycine, dimethylethanolamine (DMEA)를 촉매로 사용한 경우에 대해 반응의 각 단계를 계산하여 반응의 경로를 예측하고 단계별로 구한 에너지를 바탕으로 에너지도를 구성함으로써 실험결과를 열역학적으로 해석하였다. ZIF-90/IL-ZIF-90과 KI/KI-glycine의 경우는 실험적으로 후자들이 상대적으로 높은 수율을 얻었는데 계산 결과 활성화에너지가 낮아진 이유가 아니라 전자들의 경우 반응 중간체가 높은 에너지를 가져 반응물로 되돌아가는 역반응에 의해 정반응의 진행이 방해를 받은 것으로 밝혀졌다. DMEA를 촉매로 사용하였을 경우는 활성화 에너지를 ~42 kcal/mol로 낮춰줌으로써 금속이나 할로겐염 없이도 촉매의 활성이 잘 일어남을 증명하였다. 폴리스티렌(polystyrene)으로 지지된 quaternized 암모늄염 촉매의 경우 클러스터 가정을 사용하여 계산을 진행하였으며 암모늄염의 -NH기와 에폭사이드의 O 원자 사이의 상호작용의 가능성을 확인할 수 있는 반응경로를 제시하였다. In this study, a computational chemistry methodology called as molecular modeling was been applied to explain several experiment results mechanistically. The reaction chosen for this study was to remove carbon dioxide, known as a primary greenhouse gas, by an epoxide via the carbon dioxide fixation to produce carbonates. This reaction inherently needs the use of catalysts because it has a significantly high activation barrier (55~59 kcal/mol). Among various types of catalysts, we studied in zeolitic imidazolate framework 90 (ZIF-90)/ionic liquid immobilized ZIF-90 (IL-ZIF-90), polystyrene-supported quaternized ammonium salt, KI/KI-glycine, and dimethylethanolamine (DMEA). First, probable reaction pathways were proposed based on calculated energetics by computational chemistry. The energetics was then used for the thermodynamic interpretation on the activity of catalysts. In the case of ZIF-90/IL-ZIF-90 and KI/KI-glycine, IL-ZIF-90 and KI-glycine showed better yields compared to their counterparts. The calculation proposed interesting results that it is not from the lowering of activation energy but from the unstable intermediates of ZIF-90 and KI-glycine. For DMEA, the calculated activation energy was ~42 kcal/mol, much lower than that of the non-catalytic reaction. A possible reaction pathway was located to confirm the interaction between -NH group from ammonium and oxygen from epoxide for polystyrene-supported quaternized ammonium salt.

Uncoupling Protein 3의 골격근 세포내 과발현이 OLETF 백서 및 배양된 골격근 세포에서 포도당대사에 미치는 영향

한정희,박혜선,고정민,김하영,강호경,이인규,박중열,홍성관,이재담,이기업 대한당뇨병학회 2002 Diabetes and Metabolism Journal Vol.25 No.6

연구배경:Uncoupling protein(UCP)는 미토콘드리아의 내막에 위치하는 단백질로 세포내의 과다한 에너지를 열로 발산시키는 기능을 가진다. 최근 동물의 갈색지방조직에만 존재하는 UCP와 유사성을 가진 아형들(UCP2,3)이 사람에게도 존재함이 알려져 큰 관심을 끌도 있는데 이중 UCP3는 그 발현이 골격근세포와 갈색지방조직에만 국한된다. 본 연구에서는 UCP3가 체내 인슐린 감수성을 결정하는데 가장 중요한 조직인 골격근에 국한되어 발현되는 점에 착안하여 UCP3를 골격근세포에 과발현시켰을 때 포도당 대사에 어떠한 영향이 나타나는 지를 조사하였다. 방법:25주령의 8마리의 OLETF 백서를 대상으로 하여 4마리는 골격근에 adenovirus 2mL(1×10¹²pfu/mL)를 주사하여 대조군으로 하였고 4마리는 골격근에 재조합법으로 제작된 adenovirus­UCP3 2mL(1×10¹²pfu/mL)를 주사하였다(UCP3 과발현군). UCP3를 투여한 백서에서 먹이섭취가 증가하는 경향이 있어 그 전날 대조군이 먹은 야의 먹이만큼 투여하였다. 골격근에 adenovirus를 주사한 10일 후에 euglycemic hyperinsulinemic clamp를 시행하였다. Adenovirus­UCP를 C2C12 골격근 세포에 transfection시켜 UCP3를 C2C12 골격근 세포에 transfection시켜 UPS3­C2C12를 만들고 C2C12 골격근 세포와 UPS3­C2C12 골격근 세포에서 포도당 수송 및 당원합성을 측정하였다. 결과:UCP3 과발현 OLETF에서 체중이 감소하는 경향을 보였고 인슐린 감수성이 증가하였다. C2C12세포에서 기저상태 포도당 수송은 1.28±0.17μmol/L/min였고 100nM 인슐린으로 2시간 처리한 후 2.67±0.20 μmol/L/min로 증가하였다. UCP3­C2C12 세포에서는 기저상태 포도당 수송이 3.98±0.13μmol/L/min로 증가되었고 인슐린 처리 후 5.74±0.44μmol/L/min로 증가하였다. 인슐린을 처리한 UCP3­C2C12 세포에 P13K 억제제인 wortmannin을 첨가하였을 때 포도당 수송활성이 3.81±0.20μmol/L/min로 감소하였다. 기저상태 당원합성은 C2C12 세포에서 0.25±0.01μmol/L/min였고 인슐린 처리 후 0.45±0.01μmol/L/min로 증가하였다. UCP3­C2C12 세포에서는 기저상태 당원합성이 0.62±0.01μmol/L/min였고 인슐린 처리 후 1.26±454μmol/L/min로 증가하였다. UCP3­C2C12세포에 wortmannin을 첨가하였을 때 당원합성율이 0.80±0.04μmol/L/min로 감소하였다. 결론:UCP3 과발현이 OLETF 백서에서 인슐린 감수성을 증가시켰고 골격근세포에서 포도당 수송 및 당원합성을 증가시켰다. wortmannin을 첨가하였을 때 포도당 수송 및 당원합성이 감소함으로 보아 이 과정이 인슐린 신호전달체계인 P13K에 일부 의존함을 알 수 있었다. Background : UC P3 is a mitochondrial membrane protein expressed selectively in the skeletal muscle and brown adipose tissue. Since the skeletal muscle is the main organ determining insulin sensitivity in the body, it was hypothesized that UCP3 overexpression in skeletal muscle cells would improve glucose metabolism. Methods : An adenovirus-UCP3 was produced by a recombinant DNA method. OLETF rats were divided into 2 groups. Four rats were injected with the adenovirus-UCP3 (UCP3 group) and others were injected with the adenovirus(control group) in the skeletal muscle. The UCP3 group was provided with the same quantity of food as that consumed by the control group on the previous day. Insulin sensitivity was evaluated by the euglycemic hyperinsulinemic clamp method. In a separate experiment, glucose transport and glycogen synthesis we evaluated in C2C212 cells transfected with ether an adenovirus or the adenovirus-UCP3. Results : The insulin sensitivity improved significantly and the body weight decreased in the UCP3 group. The glucose transport and glycogen synthesis were higher in the UCP3-C2C12 skeletal muscle cells at the basal state. After insulin treatment, glucose transport and glycogen synthesis were also higher in the UCP3-C2C12 cells but the increments were reduced after treatment with wortmannin, a PI3K inhibitor. Conclusion : Insulin sensitivity was higher in the UCP3-overexpressed OLETF rats in the in vivo study. UCP3 transfection also increased glucose transport and glycogen synthesis in the cultured skeletal muscle cells by a PI3K dependent mechanism(J Kor Diabetes Asso 25 :460~468, 2001).

Evaluating the Degree of Macrodispersion of Carbon Nanotubes using UV-VIS-NIR Absorption Spectroscopy

Ki-Kang Kim,Soo-Min Kim,Yan Cui,Mun-Seok Jeong,Jong-Hun Han,Young-Chul Choi,Kay-Hyeok An,Kyung-Hui Oh,Young-Hee Lee 한국탄소학회 2009 Carbon Letters Vol.10 No.1

We measured the degree of macrodispersion of the various single-walled carbon nanotubes (SWCNTs) and multi-walled carbon nanotubes (MWCNTs) using UV-VIS-NIR absorption spectroscopy. CNTs were dispersed with SDS of 2 wt % in deionized water using the homogenizer and then were further centrifugated at 6000 g for 10 min. The degree of macrodispersion, expressed by Dm(λ)=Aa(λ)/Ab(λ)*100 (%), where λ is the wavelength and Aa(λ) and Ab(λ) are the absorbance of the sample after and before centrifugation, respectively. In the case of MWCNTs, we evaluated the degree of macrodispersion by the average degree of macrodispersion (Dm(λ)) between 1000 and 1200 nm. The degree of macrodispersion of SWCNTs was evaluated at the wavelength in which van Hove singularity-related transition regions were excluded, i.e., the range was chosen between E11S and E22S peaks. We have estimated six samples with the same method. The standard deviation of each sample was lower than 5. Therefore, we presented a reliable evaluation method for the macrodispersion of CNTs for standardization.

요관압 상승시 신혈류량 조절에 prostaglandin이 미치는 효과

민영기,양훈모,김종규,이석호 순천향의학연구소 2001 Journal of Soonchunhyang Medical Science Vol.7 No.1

Higher ureteral pressure than in normal condition causes increase in renal blood flow (RBF) and partial impairment of the autoregulation of RBF. Higher ureteral pressure increased renal prostaglandin production, it is not clear whether or not it is also responsible for partial impairment of the autoregulation of RBF. Therefore, we investigated the role which prostaglandin play in the autoregulation of RBF, studying the interaction between ureteral pressure and RBF autoregulation may reveal the role of prostaglandin in tubuloglomerular feedback. For the purpose of this experiment, six anesthetized mongrel dogs were prepared for the measurements of RBF, mean systemic and renal arterial pressure (RAP) and the manipulation of ureteral pressure to 0 cmH20, 20 cmH20 and 40 cmH20. The autoregulation curves were determined during both control and elevation of the ureteral pressure, before and after the pretreatment with indomethacin, a cyclooxygenase inhibitor. The desired ureteral pressure was achieved by vertically elevating the water-filled reservoir connected to the ureteral catheter to 20 cm and 40 cm above the kidney level. In response to the elevation of the ureteral pressure, RBF increased from 167±11 ml/min to 185±8 ml/min, 204±11 ml/min respectively and the renal arterial pressure and the systemic arterial pressure didn't change significantly. During 0 mmHg of ureteral presure threshold pressure of RBF autoregulation was 59±3 mmHg. On the other hand, during 20 cmH20, 40 cmH20 of ureteral pressure, the autoregulation curves shifted upward and rightward from control, threshold pressure is elevated by 74±3 mmHg. The pretreatment of the dogs with indomethacin failed to affect the lower limit of RBF autoregulation during both control (63±5 mmHg) and the elevated ureteral pressure (77±5 mmHg). Since RBF failed to increase in response to the elevated ureteral pressure, RBF autoregulation curves obtained during the elevated ureteral pressure shifted only rightward from indomethacin control. The results indicate that the increased intrarenal level of prostaglandin by increased ureteral pressure or prostaglandin-induced vasodilation does not appear to bear any relation to the reduction in the autoregulatore capacity during elevated ureteral pressure. It seems that the partial impairment of the autoregulation during acute ureteral obstruction is due to the consumption of tubuloglomerular feedback mechanism at 0 mmHg of ureteral pressure and that prostaglandin is neither mediator nor effector of tubuloglomerular feedback mechanism.

Characterizations of Modified Silica Nanoparticles(I)

Min, Seong-Kee,Park, Chan-Young,Lee, Won-Ki,Seul, Soo-Duk Materials Research Society of Korea 2012 한국재료학회지 Vol.22 No.6

(3-mercaptopropyl)trimethoxysilane (MPTMS) was used as a silylation agent, and modified silica nanoparticles were prepared by solution polymerization. 2.0 g of silica nanoparticles, 150 ml of toluene, and 20 ml of MPTMS were put into a 300 ml flask, and these mixtures were dispersed with ultrasonic vibration for 60 min. 0.2 g of hydroquinone as an inhibitor and 1 to 2 drops of 2,6-dimethylpyridine as a catalyst were added into the mixture. The mixture was then stirred with a magnetic stirrer for 8 hrs. at room temperature. After the reaction, the mixture was centrifuged for 1 hr. at 6000rpm. After precipitation, 150 ml of ethanol was added, and ultrasonic vibration was applied for 30 min. After the ultrasonic vibration, centrifugation was carried out again for 1 hr. at 6000rpm. Organo-modification of silica nanoparticles with a ${\gamma}$-methacryloxypropyl functional group was successfully achieved by solution polymerization in the ethanol solution. The characteristics of the ${\gamma}$-mercaptopropyl modified silica nanoparticles (MPSN) were examined using X-ray photoelectron spectroscopy (XPS, THERMO VG SCIENTIFIC, MultiLab 2000), a laser scattering system (LSS, TOPCON Co., GLS-1000), Fourier transform infrared spectroscopy (FTIR, JASCO INTERNATIONL CO., FT/IR-4200), scanning electron microscopy (SEM, HITACHI, S-2400), an elemental analysis (EA, Elementar, Vario macro/micro) and a thermogravimetric analysis (TGA, Perkin Elmer, TGA 7, Pyris 1). From the analysis results, the content of the methacryloxypropyl group was 0.98 mmol/g and the conversion rate of acrylamide monomer was 93%. SEM analysis results showed that the organo-modification of ultra-fine particles effectively prevented their agglomeration and improved their dispensability.

교감신경 자극시 신관류압 변화가 신혈관 저항에 미치는 영향

민영기 순천향의학연구소 1999 Journal of Soonchunhyang Medical Science Vol.5 No.2

Our purpose of this study was to evaluated whether the change of the renal resistance to sympathetic stimuli depends on renal perfusion pressure. In anesthetized momgrel dogs, the silastic occluder was placed around the aorta cephalad to the bification of renal artery. The occluder was connected with servocontrol unit, which enabled us to maintain perfusion pressure at freely intentional level, with electromagnetic flow probes around the renal artery, renal blood flow (RBF), renal arterial pressure (RAP), and mean arterial pressure (MAP) were measured during control condition in which RAP was allowed to change during norepinephrine (NE) infusion as sympathetic stimulation, when RAP was maintained constant at NE-preinfusion and stepwisely reduced by 10 mmHg when RAP was maintained at levels where autoregulation of RBF no longer occurs. During control condition, NE-L (0.3 ㎍/kg/min) and NE-H (0.8 ㎍/kg/min) increased MAP from 119±4 to 123±4 mmHg and 129±4 mmHg and renal resistance (RR) from 0.57±0.05 to 0.593±0.058 mmHg·min/ml and 0.63±4 mmHg·min/ml. There was no significant change in RBF by means of RR being increased as much as RAP. The maintenance of RAP at preinfusion level prevented RR from increasing during NE infusion. However, when renal perfusion pressure was reduced to and maintained at RAP below which autoregulation no longer occurs (70±2 ml), NE infusion decreased RBF and increased RR. Also when RPP is reduced stepwisely to below threshold pressure by 10 mmHg, decrease of RBF and increase of RR is proportion to ratio of below reduced RPP and volume of NE infusion. These data indicate that the at renal perfusion pressure above threshold pressure by normal or NE infusion autoregulation of the kidney effects vascular resistance, and that at RAP below the autoregulatory limit the enhanced sensitivity of renal vasculature to NE is likely to be due to the lack of tubuloglomerular feedback-mediated afferent arteriolar vasodilation at the low pressure levels.

Hair growth promoting effects of different alternating- current parameter settings are mediated by the activation of Wnt/β-catenin and MAPK pathway

( Ki Min Sohn ),( Kwan Ho Jeong ),( Jung Eun Kim ),( Young Min Park ),( Hoon Kang ) 대한피부과학회 2015 대한피부과학회 학술발표대회집 Vol.67 No.2

Background: There are clinical studies demonstrating the positive effect of electrical stimuli on hair regrowth. However, the underlying mechanism and optimal parameter settings are not clarified. Objectives: To investigate the effects of different parameter settings of electrical stimuli on hair growth by examining changes in human dermal papilla cells (hDPCs) in vitro and by observing molecular changes in animal tissue. Methods: In vitro, cultured hDPCs were electrically stimulated with different parameter settings. Cell proliferation was measured by MTT assay. The Ki67 expression was measured by immunofluorescence. Hair growth-related gene expressions were measured by RT-PCR. In animal model, different parameter settings were applied to the shaved dorsal skin of rabbit for 8 weeks. Expression of hair-related genes in the skin of rabbit was examined by RT-PCR.Results: At low voltage power (3.5V) and low frequency (1MHz or 2MHz) alterating current, in vitro proliferation of hDPCs was successfully induced. A significant increase in Wnt/モ-catenin, Ki67, p-ERK and p-AKT expression was observed. In animal model, hair regrowth was observed in the entire stimulated areas and expression of hair-related genes in the skin significantly increased. Conclusion: There are optimal conditions for electric stimulated hair growth and they might be different in the cells, animal, and human tissue. Electric stimuli induces mechanisms such as activation of Wnt/モ-catenin and MAPK pathway in hair follicles.

진공열간가압성형 (VHP) 법 및 압출로 제조한 SiCp/Al 및 SiCp/2024Al 복합재료의 동적탄성계수와 감쇄능 (내부마찰) : 금속기 복합재료의 동적탄성계수 및 감쇄능 측정

김영만,조기현,이경민,홍성길 대한금속재료학회(대한금속학회) 1999 대한금속·재료학회지 Vol.37 No.9

To shorten the processes of MMC fabrication, a number of techniques are being studied. In this study, a new process for MMC's fabrication was developed utilizing vacuum hot pressing and subsequent extrusion. MMC's with pure Al and 2024Al matrices reinforced with various volume fractions of SiC particulates were produced at 400℃ by vacuum hot pressing(VHP), followed by direct extrusion with extrusion ratios of 10:1 at 480℃ at constant ram speed of 2㎜/sec. The effects of extrusion pressure and relative density according to the volume fractions of the reinforcement were compared with the resultant metallurgical microstructures. Young's moduli of the manufactured composites were measured by the sonic resonance method, damping capacity by free decay method. Measured Young's moduli of the composites at room temperature were compared with the predictions based on Rule of Mixtures, Halpin-Tsai and Mean-field models. Measured Young's moduli of the composites are in good agreement with the predictions based on Mean-field model. The composites reinforced with finer particles showed higher damping capacity under the same amount of SiC reinforcement.