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>

65세 이상의 노령층에서 고지혈증의 위험요인

김용배,장원기,황보영,김화성,안규동,이병국,이용진,김세훈,김승수,김승훈,김영록,김웅빈,이성수 순천향의학연구소 2006 Journal of Soonchunhyang Medical Science Vol.12 No.1

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냉동 건조 탈회 동종골 이식후 골막이 골 형성 과정에 미치는 영향에 관한 실험적 연구

이동근,엄인웅,민승기,권혁도 大韓顎顔面成形再建外科學會 1995 Maxillofacial Plastic Reconstructive Surgery Vol.17 No.4

Periosteum in general is described as a specialized fibrous membrane of mesenchymal origin consisting of two basis layers : outer fibrous layer consists of irregularly arranged dense connective-tissue with fibroblasts, and inner osteogenic or cambial layer is composed of more loosely arranged fibers, greater vascularity and flatted spindle-shaped pre-osteoblasts. This periosteum may serve in controlling bone growth, especially mandibular growth has been emphasized. But, the periosteum enwrapping the facial skeleton have been studied for many years leaving a controversy in opinion regarding the function of these structures. We evaluated the bone formation activity of te periosteum in allogeneic bone grafts which bones are made of freeze-dried preparation preoperatively. We made the calvarial bone defects, 5×7mm sized, amd grafted with allogeneic bone in rats, which a half of specimens has dissected the overlying periosteum and a rest intacted. After bone grafting, we evaluated the capacity ofbone formation of periosteum, 1, 2, 4, 6, 8 weeks postoperatively. There are subtle differences of bone formation during early healing period after demineralized allogeneic bone grafting between control groups with periosteum and experimental groups without periosteum.

생체분해성 고분자의 특성 및 의학적 응용

이진호,최선웅,강길선,노승무,민병무,김용백,김학용 충남대학교 의과대학 지역사회의학연구소 1998 충남의대잡지 Vol.25 No.1

"Biomaterials" are nonviable materials used in medical devices, intended to interact with biological systems. They should have "biocompativility", which is defined as the ability of materials to perform with an appropriate host response in a specific application. It includes many materials that are often classified as biomaterials. Metals, ceramics, polymers, glasses, carbons, and composite materials are some examples. Among them, biodegradable polymers are discussed in this revies article. Since a biodegradable polymeric implant does not have to be removed surgically once it is no longer needed, biodegradable polymers are of value in short-term applications that require only the temporary presence of a polymeric implant. Main short-term medical applications of biodegradable polymers include the temporary tissue scaffold, the temporary adhesion barrier, the drug delivery device, and the multifunctional implant. In this article, the properties, processing methods, and medical applications of the biodegradable polymers are reviewed.

석회화 치성 낭종 1례

이상학,염범우,이승훈,한승훈,김응식,김광일 한국의학사 1998 診斷과治療 Vol.18 No.10

Hinman 증후군(비신경인성 신경인성 방광) 1예

이경욱,채정호,이승주,김세웅,박원명,전태연,김광수 大韓神經精神醫學會 2003 신경정신의학 Vol.42 No.3

Objectives : The Hinman Syndrome is a condition representing urinary voiding dysfunction in a neurologically intact child. This syndrome probably is an acquired behavioral and psychosocial disorders. We present a case presenting voiding dysfuntion with no neurologic etiology. Case : The departmcnt of urology consulted the department of psychiatry for a psychiatric evaluation of a 14-year-o1d girl with a history of recurrent urinary tract infections, enuresis, and urinary dribbling since early childhood. She visited the emergency room bccausc of severe abdominal pain and hematuria. She was admitted to the department of urology. Neurological tests showed no abnormality, but a retrograde cystogram showed free vesicoureteral reflux to the level of the dilated intrarenal collecting systems. Marked blunting and dilatation of the caliccs suggested longstanding urinary flow obstruction. She had a history of scparation anxiety disorder and was very competetive, perfectionistic, and nervous. She also had very poor relationships with her friends and had difficults in managing them. Afer admission, she had stent operation and cystostomy. Antidepressant and anxiolytic medications with supportive psychotherapy were administered to treat anxiety, tension and depression. Gradually, her depressive symptoms and voiding difficulties improved. Conclusions : Psychological factors such as a perfectionistic and obsessive personality, a history of severe separation anxiety, stressors from poor interpersonal relationships and Ihe failure of an entrance examination seem to have contributes to the development and exacerbation of the urinary dysfunction. Pharmacotherapy and supportive psycho-therapy may be efective in treating associated psychiatric problems of these patients with hinman syndrome.

딜티아젬 함유 코아 펠렛으로부터 약물의 용출에 미치는 폴록사머 함량의 영향

이승우,감성훈,홍지웅,최기송,박은석,지상철 한국약제학회 2002 Journal of Pharmaceutical Investigation Vol.32 No.4

In order to evaluate the effect of poloxamer 407 content on the dissolution profiles of pellets, diltiazem HCl (DTL) core pellets were prepared with poloxamer 407 (50∼90% w/w, with lactose as filler) using an extruder and a spheronizer. Any possible interaction between the drug and excipients was evaluated using DSC, IR and TLC. Dissolution tests were performed using USP basket method. In addition, scanning electron micrograph was performed to examine the surface roughness and cross sections. The release of DTL from the core pellets was decreased with increasing poloxamer 407 content. Cracks appeared on the surface of the core pellets with increasing the poloxamer 407 content, which may play a role on the retardation of the release of DTL from core pellets. There was no any significant interaction between the drug and excipients employed to prepare the core pellets.

급성 단순하부요로감염의 경험적 치료로써 레보플록사신 3일요법의 효과

이지열,이승주,이상돈,정희창,오봉렬,김세웅,최한용,조용현,윤문수 대한화학요법학회 2001 대한화학요법학회지 Vol.19 No.4

목적 : 급성 단순요로감염의 원인균에 대한 내성증가에 따른 경험적 1차치료의 선택에 대한 어려움으로 인하여 최근 미국의 Infectious Disease Society of America(IDSA)에서는 이에 대한 가이드라인을 제시하였다. IDSA의 가이드라인에 따르면 그 지역의 TMP-SMX에 대한 내성균주의 비율이 10-20% 이상일 때는 급성 단순요로감염의 경험적 1차치료제로 플루오로퀴놀론제를 선택하도록 하였다. 이에 저자들은 급성 단순하부요로감염 환자에 있어서 레보플록사신에 대한 임상적, 미생물학적 유효성 및 안전성을 알아보고자 하였다. 방법 : 시험은 전향적, 비맹검, 공개, 비비교, 다기관 임상시험으로 시행되었고 전국 5개 대학병원을 방문한 56명의 급성 단순하부요로감염 환자에게 레보플록사신 100㎎을 1일 3회, 3일간 경구 투여하여 1-3일 후에 추적 관찰하였다. 결과 : 평가가 가능하였던 53명의 환자 중 50명의 환자에서 치료 후 5-7일 후에 증상이 소실되었거나 호전되어 94%의 임상적 유효성을 보였으며, 51명의 환자에서 치료 후 1-3일 후에 원인균이 제거되어 96%의 미생물학적 유효성을 보였다. 약물 관련 이상반응은 2%의 환자에서 나타났으나 이로 인한 치료 중단 사례는 없었으며 심각한 생화학적 또는 혈액학적 이상반응은 나타나지 않았다. 결론 : 레보플록사신 100㎎ 1일 3회 3일 요법은 임상적, 미생물학적 유효성이 뒤어나며 안전한 치료요법으로 급성 단순하부요로감염의 경험적 1차 치료에 적합할 것으로 생각된다. Background : The increasing frequency of clinical failure of uncomplicated urinary tract infections (UTIs) may be due to emerging resistance to commonly prescribed antimicrobials. Infectious Diseases Society of America guidelines state that uncomplicated UTIs should be treated empirically with a fluoroquinolone, if the proportion of trimethoprim/sulfamethoxazole-resistant isolates in the community is >10%-20%. The clinical efficacy and safety of levofloxacin were assessed in patients with acute, uncomplicated lower urinary tract infection. Methods : The study was a multicenter, prospective, open label, non-comparative, non-blinded trial. Fifty-six patients with acute, uncomplicated symptomatic lower urinary tract infections from five university hospitals were treated with levofloxacin 100㎎ tid for 3 days and were followed up for 1 to 5 days. Results : Fifty-three of the 56 patients were evaluable. Ninety-four per cent of patients were symptomatically cured or improved by the fifth to seventh day after therapy started. Bacteriological eradication of initial pathogen was achieved by 1 to 3 days in 96%. Drug related adverse experiences were seen in 2% of patients. None necessitated cessation of therapy. No significant biochemical or hematological abnormalities occurred. Conclusion : These results demonstrate the clinical efficacy and safety of empirical 3-day levofloxacin for acute, uncomplicated urinary tract infections.

출생전 흰쥐 콩팥에서 콩팥소체 벽상피 분화에 대한 아포프토시스의 역할

이승헌,김영희,김완영,차정호,김진,정진웅 대한해부학회 1997 Anatomy & Cell Biology Vol.30 No.6

지모(知母)의 항암활성성분에 관한 연구

이승호,유시용,최상운,노재성,김성기,이정옥,안종웅 영남대학교 약품개발연구소 1995 영남대학교 약품개발연구소 연구업적집 Vol.5 No.-

EtOAc soluble part of MeOH extract of Anemarrbena asphodeloides rhizome was evaluated for the cytotoxicity against the five kinds of human tumor cell lines (A-549, SK-OV-3, SK-MEL-2, XF498 and HCT15) in vitro. Bioassay-guided fractionation of EtOAc soluble part led to the isolation of active compound which was identified as timosaponin A-Ⅲ1 showed potent cytotoxic activity, but its genin, sarsasapogenin, did not show cell growth inhibition.