• 제목/요약/키워드: new discovery

검색결과 903건 처리시간 0.03초

Cellular Mechanisms of a New Pyrazinone Compound that Induces Apoptosis in SKOV-3 Cells

  • Wang, Guan;Jiang, Meng-Ying;Meng, Ying;Song, Hong-Rui;Shi, Wei
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권2호
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    • pp.797-802
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    • 2014
  • We screened a small molecular library that was designed and independently synthesized in vitro and found a new drug (MY-03-01) that is active against ovarian cancer. We established that MY-03-01 effectively inhibited SKOV-3 cell survival in a dose-dependent manner, based on cell viability rates, and that it not only induced SKOV-3 apoptosis by itself, but also did so synergistically with paclitaxel. Secondly, when MY-03-01 was applied at $40{\mu}M$, its hemolytic activity was less than 10%, compared with the control, and there was almost no damage to nor mal cells at this concentration. In addition, we used DAPI staining and flow cytometry to show that MY-03-01 could significantly induce apoptosis of SKOV-3 cells. Finally, we found that MY-03-01 likely induced SKOV-3 apoptosis by activating caspase3 and caspase9 through the mitochondrial pathway.

콜럼부스의 대서양 항해 -항해의 경과와 역사적 의의를 중심으로- (A Case Study focused on Columbus's Sailing - A Study on the European Expansion in the later Middle Age -)

  • 김성준
    • 한국항해학회지
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    • 제21권1호
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    • pp.33-55
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    • 1997
  • The European expansion in the later middle age, as Adam Smith stated, influenced greatly on development of the world history. In the various events of the European expansion the discovery of the New World by Christopher Columbus is very important because the effect of the discovery of the New World have still continued to the present. I have interested to find out the reason why the western civilization has seized on the hegemony of the world over other civilizations. As many scholars pointed out, the most distinguished difference between the western civilization and other civilizations is that the western civilization was maritime-oriented, while other civilization were continental-oriented. So I set up the maritime histoy on the theme of my study in order to ruminate upon meaning of the se-power that is one of the motivating forces to drive histoy. Maritime history is not simply about that is maritime affairs, but a branch of history that inquires into inter-relations between maritime affairs and inland affairs. Maritime history constitutes of history of naval war, history of shipping and history of marine development. As above reasons, I have interested the European expansion in the later middle age that maritime activity was the most vigorous in the history. This is a case study to compose maritime history.

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가속질량분석기(Accelerator mass spectrometry, AMS)와 극미량 $^{14}C$-동위원소를 이용한 혁신적 임상시험개발동향 (Trends of Innovative Clinical Drug Development using AMS (Accelerator Mass Spectrometry) and $^{14}C$-micro Tracer)

  • 조경희;이희주;최형식;이경률;;신영근
    • 약학회지
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    • 제57권6호
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    • pp.412-419
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    • 2013
  • Drug discovery and development processes are time consuming and costly endeavors. It has been reported that on average it takes 10 to 15 years and costs more than $ 1billion to bring a molecule from discovery to market. Compounds fail for various reasons but one of the significant reasons that accounts for failures in clinical trials is poor prediction/understanding of pharmacokinetics and drug metabolism in human. In an effort to improve the number of compounds that exhibit optimal absorption, distribution, metabolism, elimination (ADME), and pharmacokinetic properties in human, drug metabolism, pharmacokinetic scientists have been continually developing new technologies and compound screening strategies. Over the last few years, accelerator mass spectrometry (AMS) and its applications to preclinical/clinical pharmacokinetics and ADME studies have significantly increased, particularly for new chemical/biological entities that are difficult to support with conventional radiolabel studies. In this review, the application of AMS for micro-dosing, micro-tracer absolute bioavailability, mass balance and metabolite profiling studies will be discussed.

Future Cancer Therapy with Molecularly Targeted Therapeutics: Challenges and Strategies

  • Kim, Mi-Sook
    • Biomolecules & Therapeutics
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    • 제19권4호
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    • pp.371-389
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    • 2011
  • A new strategy for cancer therapy has emerged during the past decade based on molecular targets that are less likely to be essential in all cells in the body, therefore confer a wider therapeutic window than traditional cytotoxic drugs which mechanism of action is to inhibit essential cellular functions. Exceptional heterogeneity and adaptability of cancer impose significant challenges in oncology drug discovery, and the concept of complex tumor biology has led the framework of developing many anticancer therapeutics. Protein kinases are the most pursued targets in oncology drug discovery. To date, 12 small molecule kinase inhibitors have been approved by US Food and Drug Administration, and many more are in clinical development. With demonstrated clinical efficacy of bortezomib, ubiquitin proteasome and ubiquitin-like protein conjugation systems are also emerging as new therapeutic targets in cancer therapy. In this review, strategies of targeted cancer therapies with inhibitors of kinases and proteasome systems are discussed. Combinational cancer therapy to overcome drug resistance and to achieve greater treatment benefit through the additive or synergistic effects of each individual agent is also discussed. Finally, the opportunities in the future cancer therapy with molecularly targeted anticancer therapeutics are addressed.

A Novel Approach to the Discovery of Non-systemic Anti-inflammatory Steroids; Antedrug

  • Lee, Henry-J.;Ko, Dong-Hoon
    • Archives of Pharmacal Research
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    • 제22권3호
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    • pp.279-287
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    • 1999
  • Therapeutic use of anti-inflammatory steroids is limited due primarily to their systemic suppressive effects on pituitary function and the immune system.. To overcome the clinical limitation, a new approach toward the discovery of non-systemic anti-inflammatory steroids is based upon the antedrug concept introduced by this laboratory. The new concept describes locally active agents which are designed to undergo a predictable biotransformation to inactive metabolites upon entry into systemic circulation from the applied site. Thus, true antedrugs are devoid of systemic adverse effects. In a continuing effort, 16$\alpha$-carboxylate and isoxazoline derivatives of prednisolone have been synthesized and screened. In the croton oil-induced ear edema bioassay, the following relative potencies were obtained setting hydrocortisone=1.0; 3a, 1.5; 3b, 3.1; 4a, 4.0; 4b, 12.2; 5b, 8.2; 6b, 11.2; 7a, 1.9; 7b, 4.1; 8a, 3.3; 8b 6.8; 9a, 0.7; 9b 8.6; 10a 2.6; 10b, 7.4. Results of the five-day bioassay indicated that, in contrast to the parent compound, the novel steroidal antedrugs did not significantly alter body weight gain, thymus weights, adrenal weights or plasma corticosterone levels. Taken together, the antedrug concept appears to be a fundamentally sound strategy for the separation of local anti-inflammatory activity form systemic adverse effects.

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Cell Surface Antigen Display for Neuronal Differentiation-Specific Tracking

  • Kim, Sang Chul;Lee, Eun-Hye;Yu, Ji Hea;Kim, Sang-Mi;Nam, Bae-Geun;Chung, Hee Yong;Kim, Yeon-Soo;Cho, Sung-Rae;Park, Chang-Hwan
    • Biomolecules & Therapeutics
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    • 제27권1호
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    • pp.78-84
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    • 2019
  • Cell therapeutic agents for treating degenerative brain diseases using neural stem cells are actively being developed. However, few systems have been developed to monitor in real time whether the transplanted neural stem cells are actually differentiated into neurons. Therefore, it is necessary to develop a technology capable of specifically monitoring neuronal differentiation in vivo. In this study, we established a system that expresses cell membrane-targeting red fluorescent protein under control of the Synapsin promoter in order to specifically monitor differentiation from neural stem cells into neurons. In order to overcome the weak expression level of the tissue-specific promoter system, the partial 5' UTR sequence of Creb was added for efficient expression of the cell surface-specific antigen. This system was able to track functional neuronal differentiation of neural stem cells transplanted in vivo, which will help improve stem cell therapies.

Elevated level of PLRG1 is critical for the proliferation and maintenance of genome stability of tumor cells

  • Hyunji Choi;Moonkyung Kang;Kee-Ho Lee;Yeon-Soo Kim
    • BMB Reports
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    • 제56권11호
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    • pp.612-617
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    • 2023
  • Pleiotropic regulator 1 (PLRG1), a highly conserved element in the spliceosome, can form a NineTeen Complex (NTC) with Prp19, SPF27, and CDC5L. This complex plays crucial roles in both pre-mRNA splicing and DNA repair processes. Here, we provide evidence that PLRG1 has a multifaceted impact on cancer cell proliferation. Comparing its expression levels in cancer and normal cells, we observed that PLRG1 was upregulated in various tumor tissues and cell lines. Knockdown of PLRG1 resulted in tumor-specific cell death. Depletion of PLRG1 had notable effects, including mitotic arrest, microtubule instability, endoplasmic reticulum (ER) stress, and accumulation of autophagy, ultimately culminating in apoptosis. Our results also demonstrated that PLRG1 downregulation contributed to DNA damage in cancer cells, which we confirmed through experimental validation as DNA repair impairment. Interestingly, when PLRG1 was decreased in normal cells, it induced G1 arrest as a self-protective mechanism, distinguishing it from effects observed in cancer cells. These results highlight multifaceted impacts of PLRG1 in cancer and underscore its potential as a novel anti-cancer strategy by selectively targeting cancer cells.

분산형 FP트리를 활용한 병렬 데이터 마이닝 (Parallel Data Mining with Distributed Frequent Pattern Trees)

  • 조두산;김동승
    • 대한전자공학회:학술대회논문집
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    • 대한전자공학회 2003년도 하계종합학술대회 논문집 V
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    • pp.2561-2564
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    • 2003
  • Data mining is an effective method of the discovery of useful information such as rules and previously unknown patterns existing in large databases. The discovery of association rules is an important data mining problem. We have developed a new parallel mining called Distributed Frequent Pattern Tree (abbreviated by DFPT) algorithm on a distributed shared nothing parallel system to detect association rules. DFPT algorithm is devised for parallel execution of the FP-growth algorithm. It needs only two full disk data scanning of the database by eliminating the need for generating the candidate items. We have achieved good workload balancing throughout the mining process by distributing the work equally to all processors. We implemented the algorithm on a PC cluster system, and observed that the algorithm outperformed the Improved Count Distribution scheme.

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A Novel Approach for Mining High-Utility Sequential Patterns in Sequence Databases

  • Ahmed, Chowdhury Farhan;Tanbeer, Syed Khairuzzaman;Jeong, Byeong-Soo
    • ETRI Journal
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    • 제32권5호
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    • pp.676-686
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    • 2010
  • Mining sequential patterns is an important research issue in data mining and knowledge discovery with broad applications. However, the existing sequential pattern mining approaches consider only binary frequency values of items in sequences and equal importance/significance values of distinct items. Therefore, they are not applicable to actually represent many real-world scenarios. In this paper, we propose a novel framework for mining high-utility sequential patterns for more real-life applicable information extraction from sequence databases with non-binary frequency values of items in sequences and different importance/significance values for distinct items. Moreover, for mining high-utility sequential patterns, we propose two new algorithms: UtilityLevel is a high-utility sequential pattern mining with a level-wise candidate generation approach, and UtilitySpan is a high-utility sequential pattern mining with a pattern growth approach. Extensive performance analyses show that our algorithms are very efficient and scalable for mining high-utility sequential patterns.