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Article ; Online: Trifluoperazine and Its Analog Suppressed the Tumorigenicity of Non-Small Cell Lung Cancer Cell; Applicability of Antipsychotic Drugs to Lung Cancer Treatment

Joo Yeon Jeong / Haangik Park / Hong Yoo / Eun-Jin Kim / Borami Jeon / Jong Deog Lee / Dawon Kang / Changjoon Justin Lee / Sun Ha Paek / Eun Joo Roh / Gwan-Su Yi / Sang Soo Kang

Biomedicines, Vol 10, Iss 1046, p

2022 Volume 1046

Abstract: Despite significant advances in diagnostic and therapeutic technologies, lung cancer remains the leading cause of cancer-related mortality worldwide. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer cases. Recently, some ... ...

Abstract	Despite significant advances in diagnostic and therapeutic technologies, lung cancer remains the leading cause of cancer-related mortality worldwide. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer cases. Recently, some antipsychotics have been shown to possess anticancer activity. However, the effects of antipsychotics on NSCLC need to be further explored. We examined the effects of trifluoperazine (TFP), a commonly used antipsychotic drug, and its synthetic analogs on A549 human lung cancer cells. In addition, cell proliferation analysis, colony formation assay, flow cytometry, western blot analysis, and in vivo xenograft experiments were performed. Key genes and mechanisms possibly affected by TFP are significantly related to better survival outcomes in lung cancer patients. Treatment with TFP and a selected TFP analog 3dc significantly inhibited the proliferation, anchorage-dependent/independent colony formation, and migration of A549 cells. Treatment with 3dc affected the expression of genes related to the apoptosis and survival of A549 cells. Treatment with 3dc promoted apoptosis and DNA fragmentation. In all experiments, including in vivo studies of metastatic lung cancer development, 3dc had more substantial anticancer effects than TFP. According to our analysis of publicly available clinical data and in vitro and in vivo experiments, we suggest that some kinds of antipsychotics prevent the progression of NSCLC. Furthermore, this study indicates a synthetic TFP analog that could be a potential therapeutic for lung cancer.
Keywords	non-small cell lung cancer ; trifluoperazine ; antipsychotics ; apoptosis ; proliferation ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Clinical outcome prediction from analysis of microelectrode recordings using deep learning in subthalamic deep brain stimulation for Parkinson`s disease.

Kwang Hyon Park / Sukkyu Sun / Yong Hoon Lim / Hye Ran Park / Jae Meen Lee / Kawngwoo Park / Beomseok Jeon / Hee-Pyoung Park / Hee Chan Kim / Sun Ha Paek

PLoS ONE, Vol 16, Iss 1, p e

2021 Volume 0244133

Abstract: Background Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for improving the motor symptoms of advanced Parkinson's disease (PD). Accurate positioning of the stimulation electrodes is necessary for better clinical ... ...

Abstract	Background Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for improving the motor symptoms of advanced Parkinson's disease (PD). Accurate positioning of the stimulation electrodes is necessary for better clinical outcomes. Objective We applied deep learning techniques to microelectrode recording (MER) signals to better predict motor function improvement, represented by the UPDRS part III scores, after bilateral STN DBS in patients with advanced PD. If we find the optimal stimulation point with MER by deep learning, we can improve the clinical outcome of STN DBS even under restrictions such as general anesthesia or non-cooperation of the patients. Methods In total, 696 4-second left-side MER segments from 34 patients with advanced PD who underwent bilateral STN DBS surgery under general anesthesia were included. We transformed the original signal into three wavelets of 1-50 Hz, 50-500 Hz, and 500-5,000 Hz. The wavelet-transformed MER was used for input data of the deep learning. The patients were divided into two groups, good response and moderate response groups, according to DBS on to off ratio of UPDRS part III score for the off-medication state, 6 months postoperatively. The ratio were used for output data in deep learning. The Visual Geometry Group (VGG)-16 model with a multitask learning algorithm was used to estimate the bilateral effect of DBS. Different ratios of the loss function in the task-specific layer were applied considering that DBS affects both sides differently. Results When we divided the MER signals according to the frequency, the maximal accuracy was higher in the 50-500 Hz group than in the 1-50 Hz and 500-5,000 Hz groups. In addition, when the multitask learning method was applied, the stability of the model was improved in comparison with single task learning. The maximal accuracy (80.21%) occurred when the right-to-left loss ratio was 5:1 or 6:1. The area under the curve (AUC) was 0.88 in the receiver operating characteristic (ROC) curve. Conclusion Clinical improvements in PD patients who underwent bilateral STN DBS could be predicted based on a multitask deep learning-based MER analysis.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Long-term effects of bilateral subthalamic nucleus stimulation on sleep in patients with Parkinson's disease.

Ji-Hyun Choi / Han-Joon Kim / Jee-Young Lee / Dallah Yoo / Jin Hee Im / Sun Ha Paek / Beomseok Jeon

PLoS ONE, Vol 14, Iss 8, p e

2019 Volume 0221219

Abstract: Objectives Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been reported to have a positive effect on sleep-wake disturbance in Parkinson's disease (PD). We aimed to investigate the long-term effects of STN DBS on sleep in patients with ...

Abstract	Objectives Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been reported to have a positive effect on sleep-wake disturbance in Parkinson's disease (PD). We aimed to investigate the long-term effects of STN DBS on sleep in patients with PD. Methods Sixty-one patients with PD who had undergone bilateral STN DBS were followed for 3 years with assessments including the Parkinson's disease sleep scale (PDSS), Epworth sleepiness scale (ESS), total sleep hours per day, Unified PD Rating Scale part I-III, Hoehn & Yahr stage, levodopa equivalent dose, quality of life measure, and depression scale measured preoperatively and at 6 months after postoperatively, and annually thereafter. Results Among the 61 patients at baseline, 46 patients completed the last follow-up assessment. The total PDSS score significantly improved after STN DBS from baseline up to 3 years after STN DBS (79.0±30, 100.0±23.3, 98.8±23.0, 97.1±29.6, and 93.3±28.0 at baseline, 6, 12, 24, and 36 months, respectively, p = 0.006 for the change over time). Among the eight PDSS domains, the domains for overall quality of a night's sleep, sleep onset and maintenance insomnia, and nocturnal motor symptoms showed significant improvement after STN DBS (p = 0.036, 0.029, and < 0.001, respectively, for the change over time). The total sleep hours per day were increased, but the total ESS score did not show significant change after STN DBS (p = 0.001 and 0.055, respectively, for the change over time). Changes in the total PDSS were associated with changes in the depression and motivation items in the Unified PD Rating Scale part I, depression scale, and quality of life measure, but those variables at baseline were not predictive of changes in the total PDSS after STN DBS. Conclusion In the largest systematic long-term follow-up study, the improvement in subjective sleep quality after bilateral STN DBS was sustained in PD patients. Improved nocturnal sleep and nocturnal motor symptoms were correlated with an improved mood and quality of ...
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2019-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Refining diagnosis of Parkinson's disease with deep learning-based interpretation of dopamine transporter imaging

Hongyoon Choi / Seunggyun Ha / Hyung Jun Im / Sun Ha Paek / Dong Soo Lee

NeuroImage: Clinical, Vol 16, Iss , Pp 586-

2017 Volume 594

Abstract: Dopaminergic degeneration is a pathologic hallmark of Parkinson's disease (PD), which can be assessed by dopamine transporter imaging such as FP-CIT SPECT. Until now, imaging has been routinely interpreted by human though it can show interobserver ... ...

Abstract	Dopaminergic degeneration is a pathologic hallmark of Parkinson's disease (PD), which can be assessed by dopamine transporter imaging such as FP-CIT SPECT. Until now, imaging has been routinely interpreted by human though it can show interobserver variability and result in inconsistent diagnosis. In this study, we developed a deep learning-based FP-CIT SPECT interpretation system to refine the imaging diagnosis of Parkinson's disease. This system trained by SPECT images of PD patients and normal controls shows high classification accuracy comparable with the experts' evaluation referring quantification results. Its high accuracy was validated in an independent cohort composed of patients with PD and nonparkinsonian tremor. In addition, we showed that some patients clinically diagnosed as PD who have scans without evidence of dopaminergic deficit (SWEDD), an atypical subgroup of PD, could be reclassified by our automated system. Our results suggested that the deep learning-based model could accurately interpret FP-CIT SPECT and overcome variability of human evaluation. It could help imaging diagnosis of patients with uncertain Parkinsonism and provide objective patient group classification, particularly for SWEDD, in further clinical studies. Keywords: Parkinson's disease, FP-CIT, Deep learning, Deep neural network, SWEDD
Keywords	Computer applications to medicine. Medical informatics ; R858-859.7 ; Neurology. Diseases of the nervous system ; RC346-429
Subject code	006 ; 610
Language	English
Publishing date	2017-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Intrastriatal administration of coenzyme Q10 enhances neuroprotection in a Parkinson’s disease rat model

Hyung Woo Park / Chun Gwon Park / Min Park / Seung Ho Lee / Hye Ran Park / Jaesung Lim / Sun Ha Paek / Young Bin Choy

Scientific Reports, Vol 10, Iss 1, Pp 1-

2020 Volume 12

Abstract: Abstract Parkinson’s disease is a neurodegenerative disorder, and no treatment has been yet established to prevent disease progression. Coenzyme Q10, an antioxidant, has been considered a promising neuroprotective agent; however, conventional oral ... ...

Abstract	Abstract Parkinson’s disease is a neurodegenerative disorder, and no treatment has been yet established to prevent disease progression. Coenzyme Q10, an antioxidant, has been considered a promising neuroprotective agent; however, conventional oral administration provides limited efficacy due to its very low bioavailability. In this study, we hypothesised that continuous, intrastriatal administration of a low dose of Coenzyme Q10 could effectively prevent dopaminergic neuron degeneration. To this end, a Parkinson’s disease rat model induced by 6-hydroxydopamine was established, and the treatment was applied a week before the full establishment of this disease model. Behavioural tests showed a dramatically decreased number of asymmetric rotations in the intrastriatal Coenzyme Q10 group compared with the no treatment group. Rats with intrastriatal Coenzyme Q10 exposure also exhibited a larger number of dopaminergic neurons, higher expression of neurogenetic and angiogenetic factors, and less inflammation, and the effects were more prominent than those of orally administered Coenzyme Q10, although the dose of intrastriatal Coenzyme Q10 was 17,000-times lower than that of orally-administered Coenzyme Q10. Therefore, continuous, intrastriatal delivery of Coenzyme Q10, especially when combined with implantable devices for convection-enhanced delivery or deep brain stimulation, can be an effective strategy to prevent neurodegeneration in Parkinson’s disease.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2020-06-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Brain tumor diagnostic model and dietary effect based on extracellular vesicle microbiome data in serum

Jinho Yang / Hyo Eun Moon / Hyung Woo Park / Andrea McDowell / Tae-Seop Shin / Young-Koo Jee / Sungmin Kym / Sun Ha Paek / Yoon-Keun Kim

Experimental and Molecular Medicine, Vol 52, Iss 9, Pp 1602-

2020 Volume 1613

Abstract: ... and Sun Ha Paek at Seoul National University, both in Seoul, South Korea, and co-workers compared ...

Abstract	Brain cancer: Investigating the gut microbiome The gut microbiome affects brain health via tiny packets of microbial metabolites called extracellular vesicles (EVs) that are small enough to pass through the blood–brain barrier. The brain was thought to be sheltered from the microbiome’s effect on health by this barrier, which blocks microbes from entering the brain via the blood. Yoon-Keun Kim at MD Healthcare Inc. and Sun Ha Paek at Seoul National University, both in Seoul, South Korea, and co-workers compared the EVs in the blood of brain cancer patients and healthy individuals, and found the two groups harbored different types of microbes. Feeding mice brown rice oil, sorghum, and garlic markedly shifted their EV profiles towards those of the healthy microbiome. These results provide a foundation for investigating new methods for brain cancer risk assessment and dietary interventions to reduce that risk.
Keywords	Medicine ; R ; Biochemistry ; QD415-436
Subject code	610 ; 616
Language	English
Publishing date	2020-09-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Magnetic and near-infrared derived heating characteristics of dimercaptosuccinic acid coated uniform Fe@Fe3O4 core–shell nanoparticles

Changhyuk Koo / Hwichan Hong / Pyung Won Im / Hoonsub Kim / Chaedong Lee / Xuanzhen Jin / Bingyi Yan / Wooseung Lee / Hyung-Jun Im / Sun Ha Paek / Yuanzhe Piao

Nano Convergence, Vol 7, Iss 1, Pp 1-

2020 Volume 9

Abstract: Abstract Among the number of hyperthermia materials, magnetic nanoparticles have received much attention. In this work, we studied the heating characteristics of uniform Fe@Fe3O4 core–shell nanoparticle under near-infrared laser irradiation and external ... ...

Abstract	Abstract Among the number of hyperthermia materials, magnetic nanoparticles have received much attention. In this work, we studied the heating characteristics of uniform Fe@Fe3O4 core–shell nanoparticle under near-infrared laser irradiation and external AC magnetic field applying. The Fe@Fe3O4 core–shell nanoparticles were prepared by thermal decomposition of iron pentacarbonyl and followed by controlled oxidation. The prepared uniform particles were further coated with dimercaptosuccinic acid to make them well dispersed in water. Near-infrared derived photothermal study of solutions containing a different concentration of the core–shell nanoparticles was made by using 808 nm laser Source. Additionally, magnetic hyperthermia ability of the Fe@Fe3O4 nanoparticle at 150 kHz and various oersted (140–180 Oe) condition was systemically characterized. The Fe@Fe3O4 nanoparticles which exhibited effective photo and magnetic hyperthermia are expected to be used in biomedical application.
Keywords	Magnetic nanoparticles ; Core–shell nanoparticle ; Hyperthermia ; Photothermal material ; Technology ; T ; Chemical technology ; TP1-1185 ; Biotechnology ; TP248.13-248.65 ; Science ; Q ; Physics ; QC1-999
Subject code	620
Language	English
Publishing date	2020-06-01T00:00:00Z
Publisher	SpringerOpen
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: STAT3 Inhibitor ODZ10117 Suppresses Glioblastoma Malignancy and Prolongs Survival in a Glioblastoma Xenograft Model

Byung-Hak Kim / Haeri Lee / Cheol Gyu Park / Ae Jin Jeong / Song-Hee Lee / Kum Hee Noh / Jong Bae Park / Chung-Gi Lee / Sun Ha Paek / Hyunggee Kim / Sang-Kyu Ye

Cells, Vol 9, Iss 3, p

2020 Volume 722

Abstract: Constitutively activated STAT3 plays an essential role in the initiation, progression, maintenance, malignancy, and drug resistance of cancer, including glioblastoma, suggesting that STAT3 is a potential therapeutic target for cancer therapy. We recently ...

Abstract	Constitutively activated STAT3 plays an essential role in the initiation, progression, maintenance, malignancy, and drug resistance of cancer, including glioblastoma, suggesting that STAT3 is a potential therapeutic target for cancer therapy. We recently identified ODZ10117 as a small molecule inhibitor of STAT3 and suggested that it may have an effective therapeutic utility for the STAT3-targeted cancer therapy. Here, we demonstrated the therapeutic efficacy of ODZ10117 in glioblastoma by targeting STAT3. ODZ10117 inhibited migration and invasion and induced apoptotic cell death by targeting STAT3 in glioblastoma cells and patient-derived primary glioblastoma cells. In addition, ODZ10117 suppressed stem cell properties in glioma stem cells (GSCs). Finally, the administration of ODZ10117 showed significant therapeutic efficacy in mouse xenograft models of GSCs and glioblastoma cells. Collectively, ODZ10117 is a promising therapeutic candidate for glioblastoma by targeting STAT3.
Keywords	glioblastoma ; glioma stem cell (gsc) ; odz10117 ; stat3 ; targeted therapy ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2020-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Bilateral Subthalamic Nucleus Deep Brain Stimulation under General Anesthesia

Hye Ran Park / Yong Hoon Lim / Eun Jin Song / Jae Meen Lee / Kawngwoo Park / Kwang Hyon Park / Woong-Woo Lee / Han-Joon Kim / Beomseok Jeon / Sun Ha Paek

Journal of Clinical Medicine, Vol 9, Iss 3044, p

Literature Review and Single Center Experience

2020 Volume 3044

Abstract: Bilateral subthalamic nucleus (STN) Deep brain stimulation (DBS) is a well-established treatment in patients with Parkinson’s disease (PD). Traditionally, STN DBS for PD is performed by using microelectrode recording (MER) and/or intraoperative ... ...

Abstract	Bilateral subthalamic nucleus (STN) Deep brain stimulation (DBS) is a well-established treatment in patients with Parkinson’s disease (PD). Traditionally, STN DBS for PD is performed by using microelectrode recording (MER) and/or intraoperative macrostimulation under local anesthesia (LA). However, many patients cannot tolerate the long operation time under LA without medication. In addition, it cannot be even be performed on PD patients with poor physical and neurological condition. Recently, it has been reported that STN DBS under general anesthesia (GA) can be successfully performed due to the feasible MER under GA, as well as the technical advancement in direct targeting and intraoperative imaging. The authors reviewed the previously published literature on STN DBS under GA using intraoperative imaging and MER, focused on discussing the technique, clinical outcome, and the complication, as well as introducing our single-center experience. Based on the reports of previously published studies and ours, GA did not interfere with the MER signal from STN. STN DBS under GA without intraoperative stimulation shows similar or better clinical outcome without any additional complication compared to STN DBS under LA. Long-term follow-up with a large number of the patients would be necessary to validate the safety and efficacy of STN DBS under GA.
Keywords	general anesthesia ; intraoperative computed tomography ; intraoperative magnetic resonance imaging ; local anesthesia ; microelectrode recording ; Parkinson’s disease ; Medicine ; R
Subject code	610
Language	English
Publishing date	2020-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Electrophysiological and imaging evidence of sustained inhibition in limbic and frontal networks following deep brain stimulation for treatment refractory obsessive compulsive disorder.

Hye Ran Park / In Hyang Kim / Hyejin Kang / Kevin W McCairn / Dong Soo Lee / Bung-Nyun Kim / Dong Gyu Kim / Sun Ha Paek

PLoS ONE, Vol 14, Iss 7, p e

2019 Volume 0219578

Abstract: Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder that arises from a complex interaction of environmental and genetic factors. Despite numerous pharmacological and behavioral interventions, approximately 10% of patients remain refractory. ...

Abstract	Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder that arises from a complex interaction of environmental and genetic factors. Despite numerous pharmacological and behavioral interventions, approximately 10% of patients remain refractory. High-frequency deep brain stimulation (HF-DBS) has shown promising results for treatment-refractory OCD. We report the follow-up result of up to 6 years of 4 treatment-refractory OCD patients treated by HF-DBS. Targets of stimulation were the anterior limb of the internal capsule (ALIC) in two cases, and the nucleus accumbens (NAc) in the remaining cohort. The clinical profiles were quantified by the Yale-Brown obsessive-compulsive scale (Y-BOCS). Highly significant reductions in Y-BOCS scores were obtained from all patients during the follow-up period. A greater that 90% reduction in Y-BOCS, observed in the most successful case, was achieved with NAc HF-DBS. Y-BOCS scores in the other patients consistently achieved over 50% reductions in OCD symptoms. FDG-PET imaging indicated post-surgical reductions in metabolism, in not only targeted limbic networks, but also other frontal cortical and subcortical regions, suggesting that large-scale network modulation and inhibitions are associated with functional recovery in OCD. This study demonstrates that HF-DBS targeted to the ALIC and NAc is a safe and effective method for ameliorating intractable, treatment-refractory OCD symptoms. The NAc appeared to be the superior target for symptom reduction, and local inhibition of NAc activity and reduced frontal metabolism are key therapeutic indications.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2019-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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