BEZ235 (PIK3/mTOR inhibitor) Overcomes Pazopanib Resistance in Patient-Derived Refractory Soft Tissue Sarcoma Cells

Kim, Hee Kyung,Kim, Sun Young,Lee, Su Jin,Kang, Mihyeon,Kim, Seung Tae,Jang, Jiryeon,Rath, Oliver,Schueler, Julia,Lee, Dong Woo,Park, Woong Yang,Kim, Sung Joo,Park, Se Hoon,Lee, Jeeyun Neoplasia Press 2016 Translational oncology Vol.9 No.3

<P><I>BACKGROUND:</I> Although pazopanib treatment has become the standard chemotherapy in salvage setting for metastatic sarcoma patients, most patients progress after pazopanib treatment in 4 to 6 months. After failure to pazopanib, patients have limited options for treatment. Therefore, subsequent therapy in patients who failed to pazopanib is urgently needed and the use of patient derived cells or patient derived tumors for accompanying testing with various pharmacological inhibitors could offer additional treatment options for these patients. <I>METHODS:</I> Patient derived tumor cells were collected from ascites at the time of progression to pazopanib and a 13-drug panel was tested for drug sensitivity. We confirmed the results using <I>in vitro</I> cell viability assay and immunoblot assay. We also performed the genomic profiling of PDX model. <I>RESULTS:</I> The growth of patient derived tumor cells was significantly reduced by exposure to 1.0 μM AZD2014 compared with control (control versus AZD2014, mean growth = 100.0% vs 16.04%, difference = 83.96%, 95% CI = 70.01% to 97.92%, <I>P</I> = .0435). Similarly, 1.0 μM BEZ235 profoundly inhibited tumor cell growth <I>in vitro</I> when compared to control (control versus BEZ235, mean growth = 100.0% vs 7.308%, difference = 92.69%, 95% CI = 78.87% to 106.5%, <I>P</I> < .0001). Despite the presence of CDK4 amplification in the patient-derived tumor cells, LEE011 did not considerably inhibit cell proliferation when compared with control (control vs LEE011, mean growth = 100.0% vs 80.23%, difference = 19.77%, 95% CI = 1.828% to 37.72%, <I>P</I> = .0377). The immunoblot analysis showed that BEZ235 treatment decreased pAKT, pmTOR and pERK whereas AZD2014 decreased only pmTOR. <I>CONCLUSION:</I> Taken together, upregulation of mTOR/AKT pathway in sarcoma patient derived cells was considerably inhibited by the treatment of AZD2014 and BEZ235 with downregulation of AKT pathway (greater extent for BEZ235). These molecules may be considered as treatment option in STS patient who have failed to pazopanib in the context of clinical trials.</P>

Analytical characterization of O₃ samples prepared for investigation of tropospheric heterogeneous reactions

Kim, Mihyeon,Park, Jong-Ho The Korean Society of Analytical Sciences 2022 분석과학 Vol.35 No.5

In this study, ozone (O₃) samples were prepared for investigating the heterogeneous reactions between O₃ and tropospheric aerosols and were characterized by spectroscopic methods. O₃ generated from an ozone generator was purified by selective adsorption on refrigerated silica gel, followed by transfer to a sample bulb. The amount of UV light (λ = 256 nm) absorbed by O₃ was measured as a function of time at two different temperatures (room temperature and 50 ℃) and under different irradiation conditions. A correlation plot of 1/[O₃] versus time showed that O₃ decomposition follows the 2^nd order reaction rate under a steady-state approximation. The initial concentration of O₃, observed rate constants (k_obs), and the half-life of O₃ in the sample stored at room temperature were determined to be 2.74 [±0.14] × 10¹⁶ molecules·cm^-3, 4.47 [±0.64] × 10^-23 molecules^-1·cm³·s^-1, and 9.5 [±1.4] days, respectively. The evaluation of O₃ stability under various conditions indicated that special care should be taken to prevent the exposure of the O₃ samples to hightemperature environment and/or UV radiation. This study established a protocol for the preparation of highly purified O₃ samples and confirmed that the O₃ samples can be stored for a day after preparation for further experiments.

식사대용식을 이용한 초저열량 식사요법이 20대 비만 여성들의 심리적 요인과 삶의 질에 미치는 효과

김지영(Kim Jiyoung),김상연(Kim Sangyeon),정경아(Jung Kyunga),장유경(Chang Yukyung),최형석(Choi Hyeongsuk),최승(Choi Sung),박미현(Park Mihyeon),홍성길(Hong Seonggil),황성주(Hwang Sungjo) 韓國營養學會 2007 Journal of Nutrition and Health Vol.40 No.7

This study was performed to investigate the effects of very low calorie diet (VLCD) using meal replacements that contain the wild grass extracts based on Samul-tang ingredients on psychological factors and quality of life in the obese women (BMI ≥ 25 ㎏/㎡) for four weeks. Seventy five women (20≤ age < 26) participated in this experiment. Subjects were randomly classified three groups: I) General diet group (GD group, n = 27) consumed 3 regular meals within 600 ㎉/day 2) Meal replacements group (MR group, n = 27) consumed 1 regular meal and 2 meal replacements within 600 ㎉/day 3) Herbal Meal replacements group (HMR group, n = 27) consumed 1 regular meal and 2 meal replacements within 600 kcal/day. Physical factors (weight, BMI, fat (%)) of the HMR group significantly decreased more than those of GD and MR groups. Moreover, binge eating habit and environmental factors (surrounding support, emotional reaction, expression of opinion) of the HMR group significantly decreased more than those of GD and MR groups. Psychological factor and quality of life were no significant differences among three groups during the experimental period, because both were significantly decreased in all groups after 4 weeks. Therefore, very low calorie diet using meal replacements that contain the wild grass extracts based on Samul-tang ingredients for 4 weeks was effective on improvement of psychological factor and quality of life as well as weight reduction in the obese preme-nopausal women.

장시간 진행된 뇌혈관수술에서 발생한 주술기 압박 손상

김미현 ( Mihyeon Kim ),최정현 ( Jeong-hyun Choi ) 경희대학교 경희의료원 2021 慶熙醫學 Vol.36 No.1

Incidence of intraoperative pressure injury is higher than incidence of pressure ulcer in patients who don’t have surgery. Efforts should be made to reduce the incidence of pressure injury as the number of prolonged operations increases and various surgical positions are applied. In this report, intraoperative pressure blister formation occurred to a 49-year old man who had 30 hours long neurovascular surgery. The causes of pressure induced blister in this case are expected to prolonged surgery time, low Hb concentration, park bench position, low albumin concentration below 3.0g/dL and hypertension. It is necessary to judge whether or not the patients are vulnerable to pressure injury and to perform early correction of risk factors before surgery. If the risk of pressure injury is high, more active prevention, for example, padding and protection tools such as gel pad or air mattress should be used.

식사대용식을 이용한 초저열량 식사요법이 성인 비만 여성들의 체중감량과 건강에 미치는 효과

김지영(Kim Jiyoung),김상연(Kim Sangyeon),정경아(Jung Kyung-Ah),장유경(Chang Yukyung),최형석(Choi Hyeongsuk),최승(Choi Sung),박미현(Park Mihyeon),홍성길(Hong Seonggil),황성주(Hwang Sungjoo) 韓國營養學會 2005 Journal of Nutrition and Health Vol.38 No.9

Effects of Temperature and Acetonitrile on Microwave-Assisted Weak Acid Protein Hydrolysis

Nam, Mihyeon,Lee, Dabin,Kim, Yeoseon,Kim, Jeongkwon Korean Society for Mass Spectrometry 2018 Mass spectrometry letters Vol.9 No.2

The effects of temperature and acetonitrile (ACN) concentration on microwave-assisted weak-acid hydrolysis of proteins were investigated. Myoglobin was hydrolyzed for 1 h using 2% formic acid and a microwave with different concentrations of ACN (0, 5, and 10%) at various temperatures (50, 60, 70, 80, 90, and $100^{\circ}C$). The numbers of peptides identified with each concentration of ACN were the same for each temperature. The greatest number of peptides (18 total) was obtained with hydrolysis at $100^{\circ}C$, and 6 of these were a result of additional removal of aspartic acid at the C-terminus. Hydrolysis at $80^{\circ}C$ resulted in 13 peptides, of which only 1 was generated by the additional removal of aspartic acid, and 12 were observed with hydrolysis at $100^{\circ}C$. Our results demonstrate that microwave-assisted weak-acid hydrolysis of proteins can be performed successfully at $80^{\circ}C$, which could be beneficial for limiting side reactions and generating larger peptide sequences.

ProbAttnGuard: Reinforcing Transformers with Robust Stochastic Attention

김서린(Seorin Kim),김미현(Mihyeon Kim),김영빈(Youngbin Kim) 대한전자공학회 2023 대한전자공학회 학술대회 Vol.2023 No.6

Recent advances in Transformer-based models have shown remarkable performance in text classification tasks. However, these models can be vulnerable to out-of-distribution (OOD) and adversarial attack scenarios. In this paper, we propose a robust Transformer model that leverages stochastic attention to improve its resilience against such challenges. By sampling attention weights from probability distributions during training, our model achieves better test accuracy on both in-distribution and OOD datasets, as well as adversarial attack datasets, compared to deterministic vanilla models. We conduct experiments using various text classification tasks, including sentiment analysis and news article classification. Our results demonstrate that the proposed model exhibits improved performance and reduced performance gap between in-distribution and OOD or adversarial attack datasets. In future work, we aim to investigate the effect of contextual priors and develop more advanced models for enhanced robustness.

한국 장애인 미충족 의료 현황

최경화 ( Choi Kyung-hwa ),김미현 ( Kim Mihyeon ),최용준 ( Choi Yong-jun ),조용민 ( Cho Yong Min ),김미소 ( Kim Mi So ),정은혜 ( Jeong Eunhye ),김정애 ( Kim Jung Ae ) 한국보건사회연구원 2021 保健社會硏究 Vol.41 No.3

본 연구의 목적은 장애인의 미충족 의료율을 파악하여 비장애인과 비교하고, 장애인이 필요로 할 때 의료서비스를 이용하지 못하는 이유가 비장애인과 어떻게 다른지 검토하는 것이다. 전국단위로 실시하고 있는 국민건강영양조사(1998, 2005, 2007~2018), 지역사회건강조사(2008~2019), 장애인실태조사(2000, 2005, 2008, 2011, 2014, 2017), 노인실태조사(2008, 2011, 2014, 2017), 한국의료패널(2008~2017) 자료를 활용하여 장애 또는 활동제한 여부, 장애인의 장애 유형 및 등급에 따라 연도별 미충족 의료율을 산출하였으며, 장애인과 비장애인의 미충족 의료 이유를 연도별로 산출하였다. 미충족 의료율은 감소하고 있으나, 장애인은 비장애인보다, 중증장애인은 경증장애인보다, 외부신체기능 장애인이 다른 장애인보다, 치과 이용에 대한 미충족 의료율은 병의원보다 높았다. 장애인과 비장애인의 미충족 의료율의 격차는 감소하지 않았으며, 치과 이용에서 병의원보다 그 격차가 더 컸다. 미충족 의료의 가장 큰 이유는 장애인은 경제적인 부담, 비장애인은 시간적 제약이었다. 향후 장애인과 비장애인의 미충족 의료율의 격차가 감소하지 않는 이유와 격차 해소를 위한 심층적 연구가 필요하다. This study aims to evaluate the proportion and factors of unmet health care needs (UHCNs) in the disabled and to compare UHCNs between disabled and non-disabled individuals. We conducted the annual proportion and cause of UHCNs by disabled or limited activity, type and grade of disabled using the Korea National Health and Nutrition Examination Survey (1998, 2005, 2007~2018), Community Health Survey (2008~2019), Disabled Health and Welfare Survey (2000, 2005, 2008, 2011, 2014, 2017), Korean Elderly Health and Welfare Survey (2008, 2011, 2014, 2017), Korea Health Panel Study (2008~2017). The proportion of UHCNs has been on the decrease overall, but it was higher in the disabled than in the non-disabled, higher in the severely disabled than in the moderately disabled, higher in those with external impairments than in people with other disability, and higher in dental care than in other health services. The difference in proportion of UHCNs did not decrease in between disabled and non-disabled individuals and was larger in dental care than in other health services. The main cause of UHCNs was “financial” for disabled persons and “not enough time” for non-disabled persons. Based on the results of this study, we suggest that further study is needed to find out the cause of the constant gap in the rate of unmet care needs between the disabled and non-disabled and to find ways to bridge the gap.

A Systematic Review of Current Advances in mRNA-loaded-LNP for Effective Vaccine Delivery

Mihyeon SEO,Minho LEE,Hyuncheol KIM 한국생물공학회 2023 한국생물공학회 학술대회 Vol.2023 No.4

Lipid Nanoparticles(LNPs) Beyond Vaccines: From COVID-19 to Gene Therapies

Mihyeon SEO,Minho LEE,Jaeho OH,Hyuncheol KIM 한국생물공학회 2023 한국생물공학회 학술대회 Vol.2023 No.10