• BMB Reports
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• 제50권6호
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• pp.329-334
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• 2017

Protein tyrosine phosphatases (PTPs) play crucial roles in signal transduction and their functional alteration has been detected in many diseases. PTP inhibitors have been developed as therapeutic drugs for diseases that are related to the activity of PTPs. In this study, PTP inhibitor XIX, an inhibitor of CD45 and PTEN, was investigated whether it inhibits other PTPs. Protein tyrosine phosphatase non-receptor type 2 (PTPN2) was selectively inhibited by the inhibitor in a competitive manner. Drug affinity responsive target stability (DARTS) analysis showed that the inhibitor induces conformational changes in PTPN2. Phosphorylation levels of signal transducer and activator of transcription 3 (STAT3) at Tyr-705, a crucial site for STAT3 activation and target site of PTPN2, decreased upon exposure to the inhibitor. Our results suggest that PTP inhibitor XIX might be considered as an effective regulator of PTPN2 for treating diseases related to PTPN2.

• 한국자원식물학회지
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• 제29권3호
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• pp.281-288
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• 2016

Apoptosis has been regarded as a therapeutic target because apoptosis is typically disturbed in human cancer. Silymarin found in the seeds of the milk thistle (Silybum marianum) has been reported to exert anti-cancer properties through apoptosis. This study was performed to investigate the molecular target for silymarin-mediated apoptosis in human colorectal cancer cells. Silymarin reduced the cell viability and induced an apoptosis in human colorectal cancer cells. ATF3 overexpression increased PARP cleavage by silymarin. Increased ATF3 expression in both protein and mRNA was observed in silymarin-treated cells. In addition, silymarin increased the luciferase activity of ATF3 promoter. Inhibition of JNK and IκK-α blocked silymarin-mediated ATF3 expression. The results suggest that silymarin induces apoptosis through JNK and IκKα-dependent ATF3 expression in human colorectal cancer cells.

• Radiation Oncology Journal
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• 제9권1호
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• pp.165-170
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• 1991

유방암의 근치적 또는 수술후 방사선 조사시 치료해야 할 부위는 유방과 주위임파 조직으로 매우 복잡한 3차인적 구조이다. 여러 방향의 조사에 의한 조사부위의 중복을 피하고 부작용을 최소화하기위한 여러 방법이 시도돼 왔으나 계산과정이나 치료방법이 매우 복잡하여 여러가지 문제점이 있었다. 이에 저자들은 Asymmetric jaw를 이용하고 gantry, collimator와 couch를 적절히 회전시켜 조사야가 만나는 부분에서 beam의 divergence를 없애줌으로써 가장 이상적으로 치료할 수 있는 방법을 소개하고자 한다. 5문 조사 방법은 다음과 같은 장점을 가진다. 1. 모든 조사야의 set up이 같은 위치에서 시행되므로 환자의 위치변동에 의한 target volume의 변화를 막을수 있다. 2. Half beam block을 사용하지 않아도 된다. 3. 조사야가 만나는 선(match line)에서 beam의 divergence가 없으므로 정확하다. 4. 계산이 쉽고 환자 set up이 용이하다. 5. 매일 치료를 같은 방법으로 정화하게 반복할 수 있다.

• The Korean Journal of Pain
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• 제27권3호
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• pp.219-228
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• 2014

Background: A lipo-prostaglandin E1 agonist is effective for the treatment of neurological symptoms of spinal stenosis when administered by an oral or intravenous route. we would like to reveal the therapeutic effect of an epidural injection of lipo-prostaglandin E1 on hyperalgesia in foraminal stenosis. Methods: A total of 40 male Sprague-Dawley rats were included. A small stainless steel rod was inserted into the L5/L6 intervertebral foramen to produce intervertebral foraminal stenosis and chronic compression of the dorsal root ganglia (DRG). The rats were divided into three groups: epidural PGE1 (EP) (n = 15), saline (n = 15), and control (n = 10). In the EP group, $0.15{\mu}g{\cdot}kg-1$ of a lipo-PGE1 agonist was injected daily via an epidural catheter for 10 days from postoperative day 3. In the saline group, saline was injected. Behavioral tests for mechanical hyperalgesia were performed for 3 weeks. Then, the target DRG was analyzed for the degree of chromatolysis, chronic inflammation, and fibrosis in light microscopic images. Results: From the fifth day after lipo-PGE1 agonist injection, the EP group showed significant recovery from mechanical hyperalgesia, which was maintained for 3 weeks (P < 0.05). Microscopic analysis showed much less chromatolysis in the EP group than in the saline or control groups. Conclusions: An epidurally administered lipo-PGE1 agonist relieved neuropathic pain, such as mechanical hyperalgesia, in a rat foraminal stenosis model, with decreasing chromatolysis in target DRG. We suggest that epidurally administered lipo-PGE1 may be a useful therapeutic candidate for patients with spinal stenosis.

• 방사선산업학회지
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• 제9권4호
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• pp.193-198
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• 2015

Most of targeted therapies block the action of certain enzymes, proteins, or other molecules involved in the growth and spread of cancer cells to produce its cytotoxic effect. Either small molecule drugs or monoclonal antibodies are mostly used in targeted therapies. Unfortunately, targeted therapy has a certain degree of unwanted side effect like other cytotoxicity inducing chemotherapies. To overcome and to reduce unwanted side effects during a cancer therapy, recently radiopeptide therapies has got the worlds' attraction for the tumor targeting modalities due to its beneficial effect on less side effect compared to cytotoxic chemotherapies. Among radiopeptide therapies, $^{177}Lu$-DOTATATE is a major modality as an effective one invented so far in treating neuroendocrine tumor (NET) and it has been in clinical trials at least one decade. Although it does have rather effective therapeutic effect on NET, it has less effective in rather large solid tumor. There are many ways to improve or increase therapeutic effect of radiopeptide are a finding the potent small molecules to target the tumor site selectively, or a labeling with radioisotope of emitting high energy, or an improving its biological half-life by introducing different moieties to increase lipophilicity. Present study was focus to increase a biological half-life of radio somatostatin which will target the somatostatin receptor by altering the bifunctional chelator (BFCA) by introducing lipophilic moiety to the somatostatin, which would make the labeled peptide stay longer in the tumor site and thus it can intensify the therapeutic effect on tumor cell itself and around tissues.

• IMMUNE NETWORK
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• 제21권1호
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• pp.8.1-8.17
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• 2021

The global crisis caused by the coronavirus disease 2019 (COVID-19) led to the most significant economic loss and human deaths after World War II. The pathogen causing this disease is a novel virus called the severe acute respiratory syndrome coronavirus 2 (SARSCoV-2). As of December 2020, there have been 80.2 million confirmed patients, and the mortality rate is known as 2.16% globally. A strategy to protect a host from SARS-CoV-2 is by suppressing intracellular viral replication or preventing viral entry. We focused on the spike glycoprotein that is responsible for the entry of SARS-CoV-2 into the host cell. Recently, the US Food and Drug Administration/EU Medicines Agency authorized a vaccine and antibody to treat COVID-19 patients by emergency use approval in the absence of long-term clinical trials. Both commercial and academic efforts to develop preventive and therapeutic agents continue all over the world. In this review, we present a perspective on current reports about the spike glycoprotein of SARS-CoV-2 as a therapeutic target.

• Molecules and Cells
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• 제46권11호
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• pp.675-687
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• 2023

Accumulation of pathogenic amyloid-β disrupts the tight junction of retinal pigment epithelium (RPE), one of its senescence-like structural alterations. In the clearance of amyloid-β, the autophagy-lysosome pathway plays the crucial role. In this context, mammalian target of rapamycin (mTOR) inhibits the process of autophagy and lysosomal degradation, acting as a potential therapeutic target for age-associated disorders. However, efficacy of targeting mTOR to treat age-related macular degeneration remains largely elusive. Here, we validated the therapeutic efficacy of the mTOR inhibitors, Torin and PP242, in clearing amyloid-β by inducing the autophagy-lysosome pathway in a mouse model with pathogenic amyloid-β with tight junction disruption of RPE, which is evident in dry age-related macular degeneration. High concentration of amyloid-β oligomers induced autophagy-lysosome pathway impairment accompanied by the accumulation of p62 and decreased lysosomal activity in RPE cells. However, Torin and PP242 treatment restored the lysosomal activity via activation of LAMP2 and facilitated the clearance of amyloid-β in vitro and in vivo. Furthermore, clearance of amyloid-β by Torin and PP242 ameliorated the tight junction disruption of RPE in vivo. Overall, our findings suggest mTOR inhibition as a new therapeutic strategy for the restoration of tight junctions in age-related macular degeneration.

• Genomics & Informatics
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• 제6권2호
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• pp.84-86
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• 2008

The Tetrahymena group I intron has been shown to employ a trans-splicing reaction and has been modified to specifically target and replace human telomerase reverse transcriptase (hTERT) RNA with a suicide gene transcript, resulting in the induction of selective cytotoxicity in cancer cells that express the target RNA, in animal models as well as in cell cultures. In this study, we evaluated the target RNA specificity of trans-splicing phenomena by the group I intron in mice that were intraperitoneally inoculated with hTERT-expressing human cancer cells to validate the anti-cancer therapeutic applicability of the group I intron. To this end, an adenoviral vector that encoded for the hTERT-targeting group I intron was constructed and systemically injected into the animal. 5'-end RACE-PCR and sequencing analyses of the trans-spliced cDNA clones revealed that all of the analyzed products in the tumor tissue of the virus-infected mice resulted from reactions that were generated only with the targeted hTERT RNA. This study implies the in vivo target specificity of the trans-splicing group I intron and hence suggests that RNA replacement via a trans-splicing reaction by the group I intron is a potent anti-cancer genetic approach.

• 한국정보과학회:학술대회논문집
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• 한국정보과학회 2007년도 가을 학술발표논문집 Vol.34 No.2 (B)
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• pp.17-21
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• 2007

Drug discovery is a long process with a low rate of successful new therapeutic discovery regardless of the advances in information technologies. Identification of candidate proteins is an essential step for the drug discovery and it usually requires considerable time and efforts in the drug discovery. The drug discovery is not a logical, but a fortuitous process. Nevertheless, considerable amount of information on drugs are accumulated in UniProt, NCBI, or DrugBank. As a result, it has become possible to try to devise new computational methods classifying drug target candidates extracting the common features of known drug target proteins. In this paper, we devise a method for drug target protein classification by using weighted feature summation and Support Vector Machine. According to our evaluation, the method is revealed to show moderate accuracy $85{\sim}90%$. This indicates that if the devised method is used appropriately, it can contribute in reducing the time and cost of the drug discovery process, particularly in identifying new drug target proteins.

• 한국임상약학회지
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• 제11권1호
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• pp.1-6
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• 2001

This research is conducted to evaluate the clinical and economic benefits from therapeutic drug monitoring(TDM) service on vancomycin in a tertiary general hospital. Total 99 pairs of steady state peak and trough concentrations of vancomycin were obtained from 73 patients. To see the clinical benefits, the appropriateness of vancomycin dosing before TDM was evaluated. In 72 pairs of vancomycin blood concentrations obtained prior to TDM consultation, $47.2\%$ of the cases had reached within therapeutic range. Serum vancomycin levels in patients with $40{\leq}CLcr<60$ (ml/min) were higher and than the levels in patients with 40>CLcr and $60{\leq}CLcr$ (ml/min). Dose reduction rate in patients with creatinine clearance $40{\leq}CLcr<60$ (ml/min) were also significantly higher than those of compared groups ($61.5\%$, p=0.0138). Serum vancomycin concentrations were re-obtained from 21 patients who received modified dose through TDM service. Ninety percent (19/21cases) of them were within the target therapeutic range. For the evaluation of economic benefits from TDM consultation, estimated cost savings were calculated in those patients. The total drug saving were 586 vials in 21 patients. The calculated mean cost saving from the drugs was 314,570 won (range: $11,273\sim473,466)$ per patient. The study revealed that TDM service for vancomycin is necessary because empirical dosing is not effective for obtaining therapeutic drug level, especially patients with mild renal insufficiencies. The cost saving from TDM is also beneficial for the patients.