• BMB Reports
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• 제49권1호
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• pp.63-68
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• 2016

The serine/threonine kinase mTOR is essential for the phosphoinositide 3-kinases (PI3K) signaling pathway, and regulates the development and function of immune cells. Aberrant activation of mTOR signaling pathway is associated with many cancers including leukemia. Here, we report the contributions of mTOR signaling to growth of human leukemic cell lines and mouse T-cell acute leukemia (T-ALL) cells. Torin, an ATP-competitive mTOR inhibitor, was found to have both cytotoxic and cytostatic effects on U-937, THP-1, and RPMI-8226 cells, but not on Jurkat or K-562 cells. All cells were relatively resistant to rapamycin even with suppressed activity of mTOR complex 1. Growth of T-ALL cells induced by Notch1 was profoundly affected by torin partially due to increased expression of Bcl2l11 and Bbc3. Of note, activation of Akt or knockdown of FoxO1 mitigated the effect of mTOR inhibition on T-ALL cells. Our data provide insight on the effect of mTOR inhibitors on the survival and proliferation of leukemic cells, thus further improving our understanding on cell-context-dependent impacts of mTOR signaling. [BMB Reports 2016; 49(1): 63-68]

• 식품기술
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• 제23권3호
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• pp.400-406
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• 2010

TOR(target of rapamycin)은 모든 진행세포에서 성장과 대사를 조절하는 영양소 인식 단백질 인산화효소(nutrient-sensing protein kinase)로 곤충, 효모, 마우스를 이용한 실험 결과 TOR 신호 전달계는 노화를 조절하는 것으로 밝혀졌다. 또한 TOR은 식이제한 시 나타나는 다양한 보호 효과(생명 연장, 노화 관련 질환 발병 억제 등)의 강력한 중계자로 알려졌다. 본 리뷰에서는 TOR 신호 전달계가 어떻게 노화를 지연시키는가에 대해 다루고자 한다. 노화조절인자로서의 TOR 신호전달계 조절 기전 구명은 매우 중요한 연구 분야이며 노화 관련 질환을 타겟으로 한 제약 및 건강기능식품의 개발을 통해 인간 수명 연장의 꿈을 성취하는 것을 조금 더 앞당길 수 있을 것으로 사료된다.

• Elastomers and Composites
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• 제39권4호
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• pp.294-300
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• 2004

혼합폐플라스틱과 폐타이어분말을 혼합하여 복합체를 구성하고 그 기계적인 물성을 조사하였다. 수지-고무분말 사이의 계면접착력을 증대시키고자 두 요소와 친화성을 가질 것으로 예상되는 trans-octylene rubber(TOR)를 소량 첨가하였다. 고무분말의 투입량이 많아질수록 인장강도와 압축강도는 플라스틱자체보다 저하되었으며 파단신장률과 충격강도는 증가되었다. 상용화제 TOR이 첨가되면 인장강도와 충격강도 및 압축강도는 크게 향상되었으나 신장률은 변화가 없었다. 이러한 물성의 변화는 TOR의 화학적인 이중성에 기인한다고 여겨진다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권16호
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• pp.6463-6475
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• 2014

The mammalian target of rapamycin (mTOR) kinase plays an important role in regulating cell growth and cell cycle progression in response to cellular signals. It is a key regulator of cell proliferation and many upstream activators and downstream effectors of mTOR are known to be deregulated in various types of cancers. Since the mTOR signalling pathway is commonly activated in human cancers, many researchers are actively developing inhibitors that target key components in the pathway and some of these drugs are already on the market. Numerous preclinical investigations have also suggested that some herbs and natural phytochemicals, such as curcumin, resveratrol, timosaponin III, gallic acid, diosgenin, pomegranate, epigallocatechin gallate (EGCC), genistein and 3,3'-diindolylmethane inhibit the mTOR pathway either directly or indirectly. Some of these natural compounds are also in the clinical trial stage. In this review, the potential anti-cancer and chemopreventive activities and the current status of clinical trials of these phytochemicals are discussed.

• 대한수학회논문집
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• 제20권2호
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• pp.209-219
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• 2005

Tor-torsion theory was defined by Jan Trlifaj in 2000. In this paper we introduce the notion of Co envelopes, CoCovers and Tor-generators as dual of envelopes, covers and generators in cotorsion(Ext-torsion) theory and deduce that each R-module has a projective and a cotorsion coprecover.

• Asian Pacific Journal of Cancer Prevention
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• 제13권12호
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• pp.6139-6144
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• 2012

Aims: Mammalian target of rapamycin (mTOR) is master regulator of the PI3K/Akt/mTOR pathway and plays an important role in NSCLCs. Here we characterized mRNA and protein expression levels of mTOR and its functional associated molecules including PTEN, IGF-1R and 4EBP1 in surgically resected NSCLCs. Methods: Fifty-four patients with NSCLCs who underwent pulmonary resection were included in current study. mRNA levels of mTOR, PTEN, IGF-1R, and 4EBP1 were evaluated by RT-PCR and protein expression of mTOR, PTEN, and IGF-1R by immunohistochemistry (IHC). Association of expression of the relevant molecules with clinical characteristics, as well as correlations between mTOR and PTEN, 4EBP1 and IGF-1R were also assessed. Results: The results of RT-PCR showed that in NSCLCs, the expression level of mTOR increased, while PTEN, 4EBP1 and IGF-1R decreased. Statistical analysis indicated high IGF-1R expression was correlated with advanced clinical stage (stage III) and PTEN expression was reversely associated with tumor size (P=0.16). The results of IHC showed mTOR positive staining in 51.8% of cases, while IGF-1R positive staining was found in 83.3% and loss of PTEN in 46.3%. Protein expression of mTOR was correlated with its regulators, PTEN and IGF-1R, to some extent. Conclusions: Abnormal activation of mTOR signaling, high expression of IGF-1R, and loss of PTEN were observed in resected NSCLC specimens. The poor expression agreement of mTOR with its regulators, PTEN, and IGF-1R, implied that combination strategy of mTOR inhibitors with other targets hold significant potential for NSCLC treatment.

• Biomolecules & Therapeutics
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• 제29권6호
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• pp.667-677
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• 2021

The elevated expression of the hyaluronan-mediated motility receptor (HMMR) is known to be highly associated with tumor progression in prostate cancer, but the molecular mechanisms underlying the regulation of HMMR expression remain unclear. Here, we report that mammalian target of rapamycin (mTOR) is a key regulator of HMMR expression, for which its kinase activity is required. Pharmacological inhibitors of mTOR, such as rapamycin and Torin2, markedly suppressed the mRNA level as well as the protein level of HMMR in LNCaP and PC-3 cells. Our data demonstrate that such regulation occurs at the transcription level. HMMR promoter reporter assays revealed that the transcription factor SRF is responsible for the mTOR-mediated transcriptional regulation of HMMR gene. Consistently, the suppression of HMMR expression by Torin2 was noticeably reversed by the overexpression of SRF. Moreover, our findings suggest that the SRF binding sites responsible for the transcriptional regulation of HMMR through the mTOR-SRF axis are located in HMMR promoter sequences carrying the first intron, downstream of the translational start site. Furthermore, the upregulation of HMMR by DHT was abolished by stimulation with rapamycin, prior to DHT treatment, suggesting that mTOR activity is required for the induction of HMMR expression by androgen. Collectively, our study provides new mechanistic insights into the role of mTOR/SRF/AR signaling in HMMR regulation in prostate cancer cells.

• Elastomers and Composites
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• 제36권3호
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• pp.188-194
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• 2001

고무상으로 천연고무(NR)와 trans-octylene rubber(TOR)를 플라스틱상으로는 isotactic 폴리프로필렌(iPP)을 고무:플라스틱이 70:30(wt/wt)이 되도록 내부혼합기에서 용융혼합하고, 동적가황시킴으로써 열가소성탄성체를 제조하였으며, 고무상의 TOR 함량에 따른 기계적물성, 동적점탄성물성 및 열적특성의 변화에 관하여 UTM, DMA, TGA등을 이용하여 조사하였다. 고무상에 TOR이 첨가됨으로써 모듈러스, 인장강도 및 신율등의 인장물성의 증가, 영구압축줄음률의 감소, 경도의 증가를 가져왔으며, 또한, 동적특성 및 열적안정성도 함께 향상시킬 수 있음을 알았다. 이와같은 물성의 증가는 TOR이 천연고무에 첨가됨으로써 고무상의 가교밀도를 증가시키고, 고무상의 용융점도를 낮춤으로써 고무와 iPP와의 혼화성을 증대시키기 때문이라고 판단되었다.

• Annals of Coloproctology
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• 제34권6호
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• pp.317-321
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• 2018

Purpose: We evaluate the role of transanal tube drainage (TD) as a conservative treatment for patients with anastomotic leakage (AL). Methods: Patients treated for AL who had undergone a low or an ultralow anterior resection with colorectal or coloanal anastomosis for the treatment of rectal cancer between January 2013 and January 2017 were enrolled in this study. The data were collected prospectively and analyzed retrospectively. The primary outcomes were the diagnosis and the management of AL. Results: Two hundred thirteen consecutive patients, 122 males and 91 females, were included. The mean age was $66.91{\pm}11.15years$, and the median body mass index was $24kg/m^2$ (range, $20-35kg/m^2$). The median tumor distance from the anal verge was 8 cm (range, 4-12 cm). Ninety-three patients (44%) received neoadjuvant therapy for nodal disease and/or locally advanced rectal cancer. Only 13 patients (6%) developed AL. Six patients developed subclinical AL as they had a defunctioning ileostomy at the time of the initial procedure. They were treated conservatively with TD under endoscopic guidance in the endoscopy unit and received intravenous antibiotics. Six weeks after discharge, these 6 patients underwent follow-up flexible sigmoidoscopy which showed a completely healed anastomotic defect with no residual stenosis. Seven patients developed a clinically significant AL and required reoperation with pelvic abscess drainage and Hartmann colostomy formation. Conclusion: These results suggest that TD for management of patients with AL is safe, cheap, and effective. Salvaging the anastomosis will help decrease the need for Hartmann colostomy formation. Proper patient selection is important.

• 대한임상검사과학회지
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• 제49권4호
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• pp.470-476
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• 2017

mTOR 신호전달 단백질의 변화는 다양한 종류의 암에서 관찰 되었다. 따라서 이들 단백질은 최근에 암 치료제에 대한 새롭고 흥미로운 표적이 되고 있다. 우리는 대장암과 선종 환자의 mTOR 세포신호의 활성도를 조사하였다. 면역조직화학적 방법으로 대장암과 선종의 세포신호 단백질 성분인 mTOR, p70-S6K, S6, 4EBP1 발현을 분석하였다. 이번 연구는 모두 100개의 예를 악성(Colorectal Adenocarcinoma, CRAC) 40건, 고등급 선종(Adenoma with High grade intraepithelial neoplasms, HIN) 30건, 저등급 선종(Adenoma with Low-grade intraepithelial neoplasms, LIN) 30건으로 분류하여 진행하였다. p-mTOR의 발현률은 LIN 7%, HIN 30%, CRAC 75%였고 p-S6의 발현률 또한 LIN 10%, HIN 27%, CRAC 55%였다. p-mTOR, p-S6의 발현과 선종-선암 연속성은 중요한 상관관계 있다는 것이 발견되었다. 그리고 흥미롭게도 p-S6 발현률은 진행암보다 초기암에서 더 높았다.