• 제목/요약/키워드: Optimal drug therapy

검색결과 31건 처리시간 0.201초

항바이러스 효능을 가진 자연살해세포 치료제 플랫폼 개발 (Development of a Platform for Natural Killer Cell Therapy with Antiviral Efficacy)

  • 김동수;윤형석;이진희;연다영;유치호;구세훈;송영조;김정은;이승호;이용한;허경행;강정화
    • 한국군사과학기술학회지
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    • 제27권1호
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    • pp.107-115
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    • 2024
  • Various vaccines were rapidly developed during the COVID-19 pandemic to prevent and treat infections but global infections continue, and concerns about new mutations and infectious diseases persist. Thus, active research focuses on developing, producing, and supplying vaccines and treatments for various infectious diseases and potential pandemics. Natural killer(NK) cells, as innate immune cells, can recognize and eliminate abnormal cells like virus-infected and cancer cells. Hence, their development as anticancer and antiviral treatments is rapidly advancing. In this study, optimal short-term culture conditions were identified for allogeneic NK cells by simplifying the culture process through the isolation of NK cells(referred to as NKi cells) and eliminating CD3+ cells(referred to as CD3- cells). NK cells demonstrated reduced viral titer in injection of NK cells into SARS-CoV-2 infected ACE-tg mice increased survival. The study's findings could form the basis for an antiviral treatment platform that swiftly responds to new viral disease pandemics.

Molecular Target Therapy of AKT and NF-kB Signaling Pathways and Multidrug Resistance by Specific Cell Penetrating Inhibitor Peptides in HL-60 Cells

  • Davoudi, Zahra;Akbarzadeh, Abolfazl;Rahmatiyamchi, Mohammad;Movassaghpour, Ali Akbar;Alipour, Mohsen;Nejati-Koshki, Kazem;Sadeghi, Zohre;Dariushnejad, Hassan;Zarghami, Nosratollah
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권10호
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    • pp.4353-4358
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    • 2014
  • Background: PI3/AKT and NF-kB signaling pathways are constitutively active in acute myeloid leukemia and cross-talk between the two has been shown in various cancers. However, their role in acute myeloid leukemia has not been completely explored. We therefore used cell penetrating inhibitor peptides to define the contributions of AKT and NF-kB to survival and multi drug resistance (MDR) in HL-60 cells. Materials and Methods: Inhibition of AKT and NF-kB activity by AKT inhibitor peptide and NBD inhibitor peptide, respectively, resulted in decreased expression of mRNA for the MDR1 gene as assessed by real time PCR. In addition, treatment of HL-60 cells with AKT and NBD inhibitor peptides led to inhibition of cell viability and induction of apoptosis in a dose dependent manner as detected by flow cytometer. Results: Finally, co-treatment of HL-60 cells with sub-optimal doses of AKT and NBD inhibitor peptides led to synergistic apoptotic responses in AML cells. Conclusions: These data support a strong biological link between NF-kB and PI3-kinase/AKT pathways in the modulation of antiapoptotic and multi drug resistant effects in AML cells. Synergistic targeting of these pathways using NF-kB and PI3-kinase/AK inhibitor peptides may have a therapeutic potential for AML and possibly other malignancies with constitutive activation of these pathways.

HIT-T15 췌장세포의 인슐린분비 촉진을 유도하는 맥문동(Liriope platyphylla) 추출물의 효능 및 독성분석 (The Extracts from Liriope platyphylla Significantly Stimulated Insulin Secretion in the HIT-T15 Pancreatic β-Cell Line)

  • 김지하;김지은;이연경;남소희;허윤경;지승완;김선건;박다정;최영환;황대연
    • 생명과학회지
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    • 제20권7호
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    • pp.1027-1033
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    • 2010
  • 맥문동(Liriope platyphylla)은 한국과 중국에서 전통적으로 당뇨, 비만, 뇌신경질환, 천식 등의 치료를 위해 사용 해온 치료제이다. 최근에 이들 맥문동으로부터 새로운 치료제를 개발하려는 노력이 활발히 진행 중이지만 아직도 유력한 치료후보제는 확보되지 않았다. 따라서 본 연구에서는 맥문동의 새로운 추출물을 이용하여 당뇨치료 제로서의 가능성을 평가하기 위하여 새로운 방법으로 10가지 후보물질을 추출하고 이들의 독성과 효능을 평가하였다. 그 결과 10가지 추출물 중에서 LP9M80-H가 인슐린 분비를 가장 많이 촉진하였고 다음으로는 LP-H, LP-M, LP-E과 LP9M80-C 등의 순서로 촉진을 하였으나 나머지는 인슐린 분비를 촉지하지 못하였다. 그러나 이들 물질은 인슐린 분비를 촉진하는 농도에서 강한 세포 독성을 나타내었다. 따라서 이들 물질 중에서 가장 효능이 좋은 LP9M80-H의 치료용 최적농도를 설정하였으며, 대략 100-25 ug/ml가 최적농도로 결정되었다. 이러한 결과는 맥문동 추출물 중에서 LP9M80-H가 췌장 $\beta$-세포의 인슐린 분비능을 유도하는 새로운 당뇨치료 후보물질로서 향후에 사용될 가능성을 시사하고 있다.

Neuroprotective Effect of Epalrestat on Hydrogen Peroxide-Induced Neurodegeneration in SH-SY5Y Cellular Model

  • Lingappa, Sivakumar;Shivakumar, Muthugounder Subramanian;Manivasagam, Thamilarasan;Somasundaram, Somasundaram Thirugnanasambandan;Seedevi, Palaniappan
    • Journal of Microbiology and Biotechnology
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    • 제31권6호
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    • pp.867-874
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    • 2021
  • Epalrestat (EPS) is a brain penetrant aldose reductase inhibitor, an approved drug currently used for the treatment of diabetic neuropathy. At near-plasma concentration, EPS induces glutathione biosynthesis, which in turn reduces oxidative stress in the neuronal cells. In this study, we found that EPS reduces neurodegeneration by inhibiting reactive oxygen species (ROS)-induced oxidative injury, mitochondrial membrane damage, apoptosis and tauopathy. EPS treatment up to 50 µM did not show any toxic effect on SH-SY5Y cell line (neuroblastoma cells). However, we observed toxic effect at a concentration of 100 µM and above. At 50 µM concentration, EPS showed better antioxidant activity against H2O2 (100 µM)-induced cytotoxicity, ROS formation and mitochondrial membrane damage in retinoic acid-differentiated SH-SY5Y cell line. Furthermore, our study revealed that 50 µM of EPS concentration reduced the glycogen synthase kinase-3 β (GSK3-β) expression and total tau protein level in H2O2 (100 µM)-treated cells. Findings from this study confirms the therapeutic efficacy of EPS on regulating Alzheimer's disease (AD) by regulating GSK3-β and total tau proteins phosphorylation, which helped to restore the cellular viability. This process could also reduce toxic fibrillary tangle formation and disease progression of AD. Therefore, it is our view that an optimal concentration of EPS therapy could decrease AD pathology by reducing tau phosphorylation through regulating the expression level of GSK3-β.

Optimization of Dual Layer Phoswich Detector for Small Animal PET using Monte Carlo Simulation

  • Y.H. Chung;Park, Y.;G. Cho;Y.S. Choe;Lee, K.H.;Kim, S.E.;Kim, B.T.
    • 한국의학물리학회:학술대회논문집
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    • 한국의학물리학회 2003년도 제27회 추계학술대회
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    • pp.44-44
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    • 2003
  • As a basic measurement tool in the areas of animal models of human disease, gene expression and therapy, and drug discovery and development, small animal PET imaging is being used increasingly. An ideal small animal PET should have high sensitivity and high and uniform resolution across the field of view to achieve high image quality. However, the combination of long narrow pixellated crystal array and small ring diameter of small animal PET leads to the degradation of spatial resolution for the source located at off center. This degradation of resolution can be improved by determining the depth of interaction (DOI) in the crystal and by taking into account the information in sorting the coincident events. Among a number of 001 identification schemes, dual layer phsowich detector has been widely investigated by many research groups due to its practicability and effectiveness on extracting DOI information. However, the effects of each crystal length composing dual layer phoswich detector on DOI measurements and image qualities were not fully characterized. In order to minimize the DOI effect, the length of each layer of phoswich detector should be optimized. The aim of this study was to perform simulations using a simulation tool, GATE to design the optimum lengths of crystals composing a dual layer phoswich detector. The simulated small PET system employed LSO front layer LuYAP back layer phoswich detector modules and the module consisted of 8${\times}$8 arrays of dual layer crystals with 2 mm ${\times}$ 2 mm sensitive area coupled to a Hamamatsu R7600 00 M64 PSPMT. Sensitivities and variation of radial resolutions were simulated by varying the length of LSO front layer from 0 to 10 mm while the total length (LSO + LuYAP) was fixed to 20 mm for 10 cm diameter ring scanner. The radial resolution uniformity was markedly improved by using DOI information. There existed the optimal lengths of crystal layers to minimize the variation of radial resolutions. In 10 cm ring scanner configuration, the radial resolution was kept below 3.4 mm over 8 cm FOV while the sensitivity was higher than 7.4% for LSO 5 mm : LuYAP 15 mm phoswich detector. In this study, the optimal length of dual layer phoswich detector was derived to achieve high and uniform radial resolution.

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컬러광을 활용한 발반사요법이 인체 생리적 반응 변화에 미치는 영향에 관한 연구 (Study on Effect of Varience of Physiological Responses in Color Foot Reflexology Using Color Light)

  • 진혜련;유미;박경준;김남균;정성환;김동욱
    • 감성과학
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    • 제13권1호
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    • pp.187-196
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    • 2010
  • 최근 늘어나고 있는 스트레스로 인한 피로와 심리적 장애로 인해 현대인들은 고통 받고 있다. 다수의 사람들이 고통을 완화시키기 위해 약물치료에 의존하고 있는 추세이며 대체의학이나 대체요법으로 치료하는 사람들도 많이 있다. 그러나 약물치료는 약물 복용 후 더 많은 스트레스를 겪는 등 여러 가지 부작용을 가지고 있다. 이에 비해 대체요법의 테라피분야, 마사지, 발반사요법 등은 비 약물치료로써 인체에 부담이 덜하며 편안한 심신을 유지하며 치료받을 수 있는 부분이다. 이에 본 저자는 컬러테라피요법과 발반사요법의 장점을 종합하여 고통이 없이 간단한 방법으로 치료효과를 볼 수 있는 컬러 발반사요법(color foot reflexology)을 전 연구에서 공동개발한 바 있다. 이를 본 논문에서는 자극시 효과에 플라시보 효과를 대조군으로 비교하여 인체생리신호측정반응을 평가하여 발 컬러 반사요법이 인체생리반응에 어떠한 영향을 미치는지 정량적으로 연구하였다. 최적화된 실험환경과 객관화된 시스템에서 건강한 성인군을 대상으로 실험하였다. 그 결과 자극을 주었을 때는 HRV에서 부교감신경의 증가세가 나타났으며 혈압, 맥박, 체온 말초혈류량이 활발하게 작용하는 변화를 보였다. 그러나 플라시보에서는 거의 변화가 없거나 뷸규칙적인 결과가 나타났다. 이결과는 컬러 발반사요법이 자율신경계와 인체생리적반응에 긍정적인 영향에 관계됨을 알 수 있으며 이는 개발 기기의 유효성을 증명하는데 좋은 자료로써 충분한 근거이다. 그리고 이의 연구결과를 바탕으로 향 후 발과 관련하여 불규칙적인 생리현상에 의한 질병이나 질환에 관하여 특정군을 대상으로 실험 연구하여 객관적인 실험검증을 할 계획이다.

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RNAi and miRNA in Viral Infections and Cancers

  • Mollaie, Hamid Reza;Monavari, Seyed Hamid Reza;Arabzadeh, Seyed Ali Mohammad;Shamsi-Shahrabadi, Mahmoud;Fazlalipour, Mehdi;Afshar, Reza Malekpour
    • Asian Pacific Journal of Cancer Prevention
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    • 제14권12호
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    • pp.7045-7056
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    • 2013
  • Since the first report of RNA interference (RNAi) less than a decade ago, this type of molecular intervention has been introduced to repress gene expression in vitro and also for in vivo studies in mammals. Understanding the mechanisms of action of synthetic small interfering RNAs (siRNAs) underlies use as therapeutic agents in the areas of cancer and viral infection. Recent studies have also promoted different theories about cell-specific targeting of siRNAs. Design and delivery strategies for successful treatment of human diseases are becomingmore established and relationships between miRNA and RNAi pathways have been revealed as virus-host cell interactions. Although both are well conserved in plants, invertebrates and mammals, there is also variabilityand a more complete understanding of differences will be needed for optimal application. RNA interference (RNAi) is rapid, cheap and selective in complex biological systems and has created new insight sin fields of cancer research, genetic disorders, virology and drug design. Our knowledge about the role of miRNAs and siRNAs pathways in virus-host cell interactions in virus infected cells is incomplete. There are different viral diseases but few antiviral drugs are available. For example, acyclovir for herpes viruses, alpha-interferon for hepatitis C and B viruses and anti-retroviral for HIV are accessible. Also cancer is obviously an important target for siRNA-based therapies, but the main problem in cancer therapy is targeting metastatic cells which spread from the original tumor. There are also other possible reservations and problems that might delay or even hinder siRNA-based therapies for the treatment of certain conditions; however, this remains the most promising approach for a wide range of diseases. Clearly, more studies must be done to allow efficient delivery and better understanding of unwanted side effects of siRNA-based therapies. In this review miRNA and RNAi biology, experimental design, anti-viral and anti-cancer effects are discussed.

폐암 클리닉을 위한 공유 전자의무기록 (A Shared Electronic Medical Record for Lung Cancer Clinic)

  • 김규식;박은선;김승석;김형우;김영철;범희승;안성자;나국주;김윤현;김유일;임성철;문재동
    • Tuberculosis and Respiratory Diseases
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    • 제59권5호
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    • pp.480-486
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    • 2005
  • Since the year 2000, lung cancer has become the leading cause of cancer death in South Korea as in many other parts of the world. The current multidisciplinary approach for lung cancer includes a wide range of modalities, not only surgery, radiotherapy, medical drug therapy but also pain control, as well as social and psychological support. Therefore, thoracic surgeons, radiologists, nuclear medicine specialists, anesthetists, psychologist, nurses and social workers as well as medical doctors care for lung cancer patients. Sharing a common treatment protocol and optimal communication are vital aspects of shared care both from a medical and cost-effectiveness point of view. We developed a shared electronic medical record (SEMR) for treating patients with lung cancer in a university hospital to facilitate the sharing protocols and communications between doctors involved in a lung cancer clinic. A SEMR system was developed within a order communication system(OCS) for a lung cancer clinic. The records of radiological, laboratory and pathological studies as well as the records of surgery, chemotherapy, and radiotherapy were stored and presented to all doctors who treat the same patient. Every doctor was allowed to change his/her own records. They could review other doctor s records but could not alter them. With the SEMR, it was expected that the time to complete the medical records for one patient could be reduced because it was easy to review all the data from the other doctors who share the same patient. In addition, the confidence of the doctors who share a common treatment protocol would be higher. Therefore, a shared electronic medical record is expected to improve the quality of patient care.

Combination Therapy of the Active KRAS-Targeting Antibody inRas37 and a PI3K Inhibitor in Pancreatic Cancer

  • Lee, Ji Eun;Woo, Min Gyu;Jung, Kyung Hee;Kang, Yeo Wool;Shin, Seung-Min;Son, Mi Kwon;Fang, Zhenghuan;Yan, Hong Hua;Park, Jung Hee;Yoon, Young-Chan;Kim, Yong-Sung;Hong, Soon-Sun
    • Biomolecules & Therapeutics
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    • 제30권3호
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    • pp.274-283
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    • 2022
  • KRAS activating mutations, which are present in more than 90% of pancreatic cancers, drive tumor dependency on the RAS/mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/AKT signaling pathways. Therefore, combined targeting of RAS/MAPK and PI3K/AKT signaling pathways may be required for optimal therapeutic effect in pancreatic cancer. However, the therapeutic efficacy of combined MAPK and PI3K/AKT signaling target inhibitors is unsatisfactory in pancreatic cancer treatment, because it is often accompanied by MAPK pathway reactivation by PI3K/AKT inhibitor. Therefore, we developed an inRas37 antibody, which directly targets the intra-cellularly activated GTP-bound form of oncogenic RAS mutation and investigated its synergistic effect in the presence of the PI3K inhibitor BEZ-235 in pancreatic cancer. In this study, inRas37 remarkably increased the drug response of BEZ-235 to pancreatic cancer cells by inhibiting MAPK reactivation. Moreover, the co-treatment synergistically inhibited cell proliferation, migration, and invasion and exhibited synergistic anticancer activity by inhibiting the MAPK and PI3K pathways. The combined administration of inRas37and BEZ-235 significantly inhibited tumor growth in mouse models. Our results demonstrated that inRas37 synergistically increased the antitumor activity of BEZ-235 by inhibiting MAPK reactivation, suggesting that inRas37 and BEZ-235 co-treatment could be a potential treatment approach for pancreatic cancer patients with KRAS mutations.

Denosumab (Prolia®)의 투여 간격 및 칼슘·비타민 D 복합제제 처방 여부에 따른 임상적 결과 평가 (Evaluation of Clinical Outcomes by Therapeutic Dosing Interval of Denosumab (Prolia®) and Calcium-Vitamin D Prescriptions)

  • 김유경;김정현;도현정;정영미;이정화;이주연;김은경
    • 한국임상약학회지
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    • 제32권3호
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    • pp.185-190
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    • 2022
  • Background: Denosumab (Prolia®) is administered every 6 months for osteoporosis treatment. Co-administration of calcium and vitamin D is required to minimize hypocalcemia risk. We evaluated clinical outcomes based on the administration interval of denosumab and co-prescription with calcium-vitamin D combination products. Methods: A retrospective study was conducted using electronic medical records from 668 patients who started denosumab therapy between January 1 and December 31, 2018, at Seoul National University Bundang Hospital. Clinical outcomes, as measured by changes in T-score, were evaluated by the intervals and concurrent prescriptions with calcium-vitamin D combination products. Results: Of the 668 patients, 333 patients met the eligibility criteria. These patients were divided into two groups based on appropriateness of the administration interval: "Appropriate" (304 patients, 91.3%) and "Inappropriate" (29 patients, 8.3%). T-score changes were significantly higher in the "Appropriate" than in the "Inappropriate" group (0.30±0.44 vs. 0.13±0.37, p=0.048). At the beginning of the treatment, 221 patients (66.4%) were prescribed calcium-vitamin D combination products, but the changes in T-scores were not significantly different by the prescription status of the product (0.29±0.46 vs. 0.28±0.38, p=0.919). Conclusion: T-scores were significantly improved in patients with appropriate administration intervals. No significant changes in T-scores were observed by the prescription status with calcium-vitamin D combination products. For optimal treatment outcomes, prescribers should encourage adherence to the approved prescription information on dosage and administration, and pharmacists should provide medication counseling for patients.