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윤신교,양한나,류현민,이은진,조유진,서세영,김덕훈,이창훈,김완림,정경해,박숙련,최은경,김상위,박강서,이대호 대한암학회 2022 Cancer Research and Treatment Vol.54 No.3
PurposeHeat shock protein-90 (HSP90) remains an important cancer target because of its involvement in multiple oncogenic protein pathways and biologic processes. Although many HSP90 inhibitors have been tested in the treatment of KRAS-mutant non–small cell lung cancer (NSCLC), most, including AUY922, have failed due to toxic effects and resistance generation, even though a modest efficacy has been observed for these drugs in clinical trials. In our present study, we investigated the novel mechanism of resistance to AUY922 to explore possible avenues of overcoming and want to provide some insights that may assist with the future development of successful next-generation HSP90 inhibitors.Materials and MethodsWe established two AUY922-resistant KRAS-mutated NSCLC cells and conducted RNA sequencing to identify novel resistance biomarker.ResultsWe identified novel two resistance biomarkers. We observed that both integrin Av (ITGAv) and β3 (ITGB3) induce AUY922-resistance via focal adhesion kinase (FAK) activation, as well as an epithelial-mesenchymal transition, in both <i>in vitro</i> and <i>in vivo</i> xenograft model. mRNAs of both ITGAv and ITGB3 were also found to be elevated in a patient who had shown acquired resistance in a clinical trial of AUY922. ITGAv was induced by miR-142 downregulation, and ITGB3 was increased by miR-150 downregulation during the development of AUY922-resistance. Therefore, miR-150 and miR-142 overexpression effectively inhibited ITGAvB3-dependent FAK activation, restoring sensitivity to AUY922.ConclusionThe synergistic co-targeting of FAK and HSP90 attenuated the growth of ITGAvB3-induced AUY922-resistant KRAS-mutated NSCLC cells <i>in vitro</i> and <i>in vivo</i>, suggesting that this combination may overcome acquired AUY922-resistance in KRAS-mutant NSCLC.
윤신교,류민희,유창훈,백모율,류백렬,강윤구 대한의학회 2013 Journal of Korean medical science Vol.28 No.8
Imatinib, the first-line treatment in patients with advanced gastrointestinal stromal tumors (GIST), is generally well tolerated, although some patients have difficulty tolerating the standard dose of 400 mg/day. Adjusting imatinib dosage by plasma level monitoring may facilitate management of patients who experience intolerable toxicities due to overexposure to the drug. We present two cases of advanced GIST patients in whom we managed imatinib-related toxicities through dose modifications guided by imatinib plasma level monitoring. Imatinib blood level testing may be a promising approach for fine-tuning imatinib dosage for better tolerability and optimal clinical outcomes in patients with advanced GIST.
윤신교,김미소,홍용상,김한상,김승태,김지훈,윤홍석,유창훈,안희경,김효송,이인희,김인호,박인근,정재호,천재경,김진원,윤지나,임선민,차용준,장세진,장대영,김태원,강진형,김지현 대한암학회 2022 Cancer Research and Treatment Vol.54 No.1
Next-generation sequencing (NGS) is becoming essential in the fields of precision oncology. With implementation of NGS in daily clinic, the needs for continued education, facilitated interpretation of NGS results and optimal treatment delivery based on NGS results have been addressed. Molecular tumor board (MTB) is multidisciplinary approach to keep pace with the growing knowledge of complex molecular alterations in patients with advanced solid cancer. Although guidelines for NGS use and MTB have been developed in western countries, there is limitation for reflection of Korea’s public health environment and daily clinical practice. These recommendations provide a critical guidance from NGS panel testing to final treatment decision based on MTB discussion.
균혈증이 동반된 중증 지역사회 획득 Acinetobacter baumannii 폐렴 1예
이유미,윤신교,이호수,강보형,안지현,김유재,홍상범,최상호 대한감염학회 2012 Infection and Chemotherapy Vol.44 No.2
Acinetobacter baumannii is a significant pathogen in nosocomial infections, especially in intensive care units. However, community-acquired A. baumannii (CAAB) pneumonia is an uncommon disease. Most of the CAAB pneumonia in the literature is characterized by an abrupt onset and rapid progression to respiratory failure and hemodynamic instability. In our case, a 51-year-old man without underlying diseases developed severe pneumonia. Respiratory distress rapidly worsened and mechanical ventilation was applied. Extra-corporeal membrane oxygenation was applied due to refractory septic shock. Fully sensitive A. baumannii pneumonia was confirmed by the sputum culture and blood culture. The patient was effectively treated by the meropenem. However, the patient died of uncontrolled ventilatorassociated pneumonia, developed on the 10th hospital day, and refractory septic shock. We report the case of severe CAAB pneumonia with bacteremia in a patient without underlying diseases in Korea.
강지훈,윤신교,서철원 대한혈액학회 2017 Blood Research Vol.52 No.4
Background: The International Prognostic Index (IPI) has been a useful tool for predicting the prognosis of aggressive non-Hodgkin lymphoma in the last 20 years. Herein, we aimed to develop a new prognostic model for diffuse large B-cell lymphoma (DLBCL) in the rituximab era. Methods: Between March 2004 and June 2012, patients with DLBCL treated with rituximab, cyclo-phosphamide, doxorubicin, vincristine, and prednisolone chemotherapy regimen were identified in the database of the Asan Medical Center (AMC) Lymphoma Registry. The primary and secondary endpoints were a new prognostic index for DLBCL and validation of the National Comprehensive Cancer Network-International Prognostic Index in our cohort, respectively. Results: The AMC cohort comprised 621 patients. The median follow-up duration was 43.3 months (range, 6.2‒122.5 mo). Univariate analysis revealed that age (≤60 vs. >60 yr), lactate dehydrogenase (LDH; within normal vs. increased), Eastern Cooperative Oncology Group performance status (ECOG PS; 0 or 1 vs. ≥2), advanced stage (Ann Arbor stage I/II vs. III/IV), extra-nodal involvement (≤1 vs. >1), B symptoms (no vs. yes), and beta-2 microglobulin (β2MG, ≤2.5 vs. >2.5) can be used to predict overall survival (OS). In multivariate analysis, only age, LDH, ECOG performance status, and β2MG were significantly associated with OS, and we developed a new prognostic model with these 4 factors. The new prognostic model showed better discriminative power compared with the classic IPI. Conclusion: Our new prognostic index model for DLBCL in the rituximab era has good discriminative power and is convenient to use.
강지훈,윤신교,서철원 대한혈액학회 2017 Blood Research Vol.51 No.4
Background: The International Prognostic Index (IPI) has been a useful tool for predicting the prognosis of aggressive non-Hodgkin lymphoma in the last 20 years. Herein, we aimed to develop a new prognostic model for diffuse large B-cell lymphoma (DLBCL) in the rituximab era. Methods: Between March 2004 and June 2012, patients with DLBCL treated with rituximab, cyclo-phosphamide, doxorubicin, vincristine, and prednisolone chemotherapy regimen were identified in the database of the Asan Medical Center (AMC) Lymphoma Registry. The primary and secondary endpoints were a new prognostic index for DLBCL and validation of the National Comprehensive Cancer Network-International Prognostic Index in our cohort, respectively. Results: The AMC cohort comprised 621 patients. The median follow-up duration was 43.3 months (range, 6.2‒122.5 mo). Univariate analysis revealed that age (≤60 vs. >60 yr), lactate dehydrogenase (LDH; within normal vs. increased), Eastern Cooperative Oncology Group performance status (ECOG PS; 0 or 1 vs. ≥2), advanced stage (Ann Arbor stage I/II vs. III/IV), extra-nodal involvement (≤1 vs. >1), B symptoms (no vs. yes), and beta-2 microglobulin (β2MG, ≤2.5 vs. >2.5) can be used to predict overall survival (OS). In multivariate analysis, only age, LDH, ECOG performance status, and β2MG were significantly associated with OS, and we developed a new prognostic model with these 4 factors. The new prognostic model showed better discriminative power compared with the classic IPI. Conclusion: Our new prognostic index model for DLBCL in the rituximab era has good discriminative power and is convenient to use.