• Title/Summary/Keyword: Treat-to-target

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Prediction of Drug Side Effects Based on Drug-Related Information (약물 관련 정보를 이용한 약물 부작용 예측)

  • Seo, Sukyung;Lee, Taekeon;Yoon, Youngmi
    • The Journal of Korean Institute of Information Technology
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    • v.17 no.12
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    • pp.21-28
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    • 2019
  • Side effects of drugs mean harmful and unintended effects resulting from drugs used to prevent, diagnose, or treat diseases. These side effects can lead to patients' death and are the main causes of drug developmental failures. Thus, various methods have been tried to identify side effects. These can be divided into biological and systems biology approaches. In this study, we use systems biology approach and focus on using various phenotypic information in addition to the chemical structure and target proteins. First, we collect datasets that are used in this study, and calculate similarities individually. Second, we generate a set of features using the similarities for each drug-side effect pair. Finally, we confirm the results by AUC(Area Under the ROC Curve), and showed the significance of this study through a comparison experiment.

Systemic and molecular analysis dissect the red ginseng induction of apoptosis and autophagy in HCC as mediated with AMPK

  • Young Woo Kim;Seon Been Bak;Won-Yung Lee;Su Jin Bae;Eun Hye Lee;Ju-Hye Yang;Kwang Youn Kim;Chang Hyun Song;Sang Chan Kim;Un-Jung Yun;Kwang Il Park
    • Journal of Ginseng Research
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    • v.47 no.3
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    • pp.479-491
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    • 2023
  • Background: Hepatocellular carcinoma (HCC) has a high incidence and is one of the highest mortality cancers when advanced stage is proceeded. However, Anti-cancer drugs available for treatment are limited and new anti-cancer drugs and new ways to treat them are minimal. We examined that the effects and possibility of Red Ginseng (RG, Panax ginseng Meyer) as new anti-cancer drug on HCC by combining network pharmacology and molecular biology. Materials and Methods: Network pharmacological analysis was employed to investigate the systems-level mechanism of RG focusing on HCC. Cytotoxicity of RG was determined by MTT analysis, which were also stained by annexin V/PI staining for apoptosis and acridine orange for autophagy. For the analyze mechanism of RG, we extracted protein and subjected to immunoblotting for apoptosis or autophagy related proteins. Results: We constructed compound-target network of RG and identified potential pathways related to HCC. RG inhibited growth of HCC through acceleration of cytotoxicity and reduction of wound healing ability of HCC. RG also increased apoptosis and autophagy through AMPK induction. In addition, its ingredients, 20S-PPD (protopanaxadiol) and 20S-PPT (protopanaxatriol), also induced AMPK mediated apoptosis and autophagy. Conclusion: RG effectively inhibited growth of HCC cells inducing apoptosis and autophagy via ATG/AMPK in HCC cells. Overall, our study suggests possibility as new anti-cancer drug on HCC by proof for the mechanism of the anti-cancer action of RG.

Assessment of the Single Oral dose Toxicity of Glycyrrhiza New Variety Extract in Sprague-Dawley Rats (Sprague-Dawley rats에서 감초 신품종 추출물의 단회투여 독성 평가)

  • Dong-Gu Kim;Jeonghoon Lee;Wonnam Kim;yo-Jin An;Jong-Hyun Lee;Jaeki Chang;Sa-Haeng Kang;Young-Jae Song;Yong-Deok Jeon;Jong-Sik Jin
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2021.04a
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    • pp.65-66
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    • 2021
  • Glycyrrhiza species (Licorice) are one of the most commonly used medicinal plants in Asian countries such as China, India and Korea. It has been traditionally used to treat many disease including cough, cold, asthma, fatigue, gastritis and respiratory tract infections. Glycyrrhiza new variety, Wongam (WG), have been developed by Korea Rural Development Administration and revealed several pharmacological effects. However, limited data are available on the potential adverse effects of the WG. Here, we evaluated the general toxicity of the WG extract through single oral dose toxicity study in Sprague-Dawley rats. After single oral dose administration, there was no mortality up to 5000 mg/kg during experiment period. In addition, there was no clinical signs including body weight change, gross findings and necropsy findings up to 5000 mg/kg during experiment period. To conclude, the no-observed-adverse-effect level (NOAEL) of WG was higher than 5000 mg/kg and no target organs were identified in male and female Sprague-Dawley rats.

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Thyroid Radiology Practice: Diagnosis and Interventional Treatment of Patients with Thyroid Nodules (갑상선 영상의학 진료: 갑상선 결절 환자의 진단과 중재적 치료)

  • Jung Hwan Baek;Dong Gyu Na
    • Journal of the Korean Society of Radiology
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    • v.81 no.3
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    • pp.530-548
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    • 2020
  • Thyroid radiology practice is a medical practice in which thyroid diseases are diagnosed using imaging modality and treated by imaging-based interventional techniques, and the primary care target is thyroid nodular disease. Diagnosis of thyroid nodules is primarily done by ultrasound imaging and biopsy; thyroid nodules can be treated by non-surgical interventional treatment and thyroidectomy. Ethanol ablation is the first-line treatment for cystic benign nodules, and radiofrequency ablation is used for the treatment of benign solid nodules and recurrent thyroid cancers. Thyroid radiology practice has an essential clinical role in diagnosis and nonsurgical treatment of thyroid nodular diseases, and treatment should be performed based on standard care guidelines for proper patient care. In order to provide the best care to patients with thyroid nodular disease, it is desirable to treat patients in the radiology outpatient clinic. Thyroid radiology practice centered on outpatient clinic practice needs to be expanded.

Survival benefit of neoadjuvant FOLFIRINOX for patients with borderline resectable pancreatic cancer

  • Evelyn Waugh;Juan Glinka;Daniel Breadner;Rachel Liu;Ephraim Tang;Laura Allen;Stephen Welch;Ken Leslie;Anton Skaro
    • Annals of Hepato-Biliary-Pancreatic Surgery
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    • v.28 no.2
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    • pp.229-237
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    • 2024
  • Backgrounds/Aims: While patients with borderline resectable pancreatic cancer (BRPC) are a target population for neoadjuvant chemotherapy (NAC), formal guidelines for neoadjuvant therapy are lacking. We assessed the perioperative and oncological outcomes in patients with BRPC undergoing NAC with FOLFIRINOX for patients undergoing upfront surgery (US). Methods: The AHPBA criteria for borderline resectability and/or a CA19-9 level > 100 µ/mL defined borderline resectable tumors retrieved from a prospectively populated institutional registry from 2007 to 2020. The primary outcome was overall survival (OS) at 1 and 3 years. A Cox Proportional Hazard model based on intention to treat was used. A receiver-operator characteristics (ROC) curve was constructed to assess the discriminatory capability of the use of CA19-9 > 100 µ/mL to predict resectability and mortality. Results: Forty BRPC patients underwent NAC, while 46 underwent US. The median OS with NAC was 19.8 months (interquartile range [IQR], 10.3-44.24) vs. 10.6 months (IQR, 6.37-17.6) with US. At 1 year, 70% of the NAC group and 41.3% of the US group survived (p = 0.008). At 3 years, 42.5 % of the NAC group and 10.9% of the US group survived (p = 0.001). NAC significantly reduced the hazard of death (adjusted hazard ratio, 0.20; 95% confidence interval, 0.07-0.54; p = 0.001). CA19-9 > 100 µ/mL showed poor discrimination in predicting mortality, but was a moderate predictor of resectability. Conclusions: We found a survival benefit of NAC with FOLFIRINOX for BRPC. Greater pre-treatment of CA19-9 and multivessel involvement on initial imaging were associated with progression of the disease following NAC.

A Novel Anti-PD-L1 Antibody Exhibits Antitumor Effects on Multiple Myeloma in Murine Models via Antibody-Dependent Cellular Cytotoxicity

  • Ahn, Jae-Hee;Lee, Byung-Hyun;Kim, Seong-Eun;Kwon, Bo-Eun;Jeong, Hyunjin;Choi, Jong Rip;Kim, Min Jung;Park, Yong;Kim, Byung Soo;Kim, Dae Hee;Ko, Hyun-Jeong
    • Biomolecules & Therapeutics
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    • v.29 no.2
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    • pp.166-174
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    • 2021
  • Multiple myeloma is a malignant cancer of plasma cells. Despite recent progress with immunomodulatory drugs and proteasome inhibitors, it remains an incurable disease that requires other strategies to overcome its recurrence and non-response. Based on the high expression levels of programmed death-ligand 1 (PD-L1) in human multiple myeloma isolated from bone marrow and the murine myeloma cell lines, NS-1 and MOPC-315, we propose PD-L1 molecule as a target of anti-multiple myeloma therapy. We developed a novel anti-PD-L1 antibody containing a murine immunoglobulin G subclass 2a (IgG2a) fragment crystallizable (Fc) domain that can induce antibody-dependent cellular cytotoxicity. The newly developed anti-PD-L1 antibody showed significant antitumor effects against multiple myeloma in mice subcutaneously, intraperitoneally, or intravenously inoculated with NS-1 and MOPC-315 cells. The anti-PD-L1 effects on multiple myeloma may be related to a decrease in the immunosuppressive myeloid-derived suppressor cells (MDSCs), but there were no changes in the splenic MDSCs after combined treatment with lenalidomide and the anti-PD-L1 antibody. Interestingly, the newly developed anti-PD-L1 antibody can induce antibody-dependent cellular cytotoxicity in the myeloma cells, which differs from the existing anti-PD-L1 antibodies. Collectively, we have developed a new anti-PD-L1 antibody that binds to mouse and human PD-L1 and demonstrated the antitumor effects of the antibody in several syngeneic murine myeloma models. Thus, PD-L1 is a promising target to treat multiple myeloma, and the novel anti-PD-L1 antibody may be an effective anti-myeloma drug via antibody-dependent cellular cytotoxicity effects.

Hair Diameter Variation in Different Vertical Regions of the Occipital Safe Donor Area

  • Yun, Seon Sik;Park, Jae Hyun;Na, Young Cheon
    • Archives of Plastic Surgery
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    • v.44 no.4
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    • pp.332-336
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    • 2017
  • Background Little is known concerning hair diameter variation within the safe donor area for hair transplantation surgery. Thicker or thinner hair may be needed, depending on the recipient area, hairline design, and the purpose of surgery. Methods Twenty-seven patients (7 men and 20 women; mean age, 28 years; range, 20-47 years) were included in this study. The midoccipital point was used as the reference point on the horizontal plane at the upper border of the helical rim. The target area width was 15 cm (7.5 cm to the right and left of the reference point) and the height was 8 cm (2 cm above and 6 cm below the reference point). The study area was divided horizontally into 3 5-cm sections (A, B, C) and vertically into 4 2-cm sections (1-4), creating a total of 12 zones. Ten anagen hairs were randomly obtained from each zone and their diameters were measured. Results Hair diameter in the 4 vertical sections varied significantly, gradually decreasing from sections 1 (superior) to 4 (inferior) in all 3 horizontal sections (A, B, and C). Conclusions Our results suggest that sections 1 and 2 of the occipital safe donor area would be useful for obtaining thicker hair, such as in procedures to treat male- and female-pattern hair loss, whereas hair from zones 3 and 4 could be useful for transplantation surgery requiring thinner hair, such as eyebrows, eyelashes, and female hairline correction. Our results may be clinically valuable for planning hair transplant surgery and choosing the optimal donor region.

Anemia Screening, Prevalence, and Treatment in Pediatric Inflammatory Bowel Disease in the United States, 2010-2014

  • Miller, Steven D.;Cuffari, Carmelo;Akhuemonkhan, Eboselume;Guerrerio, Anthony L.;Lehmann, Harold;Hutfless, Susan
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.22 no.2
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    • pp.152-161
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    • 2019
  • Purpose: We examined the prevalence of anemia, annual screening for anemia, and treatment of anemia with iron among children with inflammatory bowel disease (IBD). Methods: A retrospective study of U.S. pediatric patients with IBD was performed in the MarketScan commercial claims database from 2010-2014. Children (ages 1-21) with at least two inpatient or outpatient encounters for IBD who had available lab and pharmacy data were included in the cohort. Anemia was defined using World Health Organization criteria. We used logistic regression to determine differences in screening, incident anemia, and treatment based on age at first IBD encounter and sex. Results: The cohort (n=2,446) included 1,560 Crohn's disease (CD) and 886 ulcerative colitis (UC). Approximately, 85% of CD and 81% of UC were screened for anemia. Among those screened, 51% with CD and 43% with UC had anemia. Only 24% of anemia patients with CD and 20% with UC were tested for iron deficiency; 85% were iron deficient. Intravenous (IV) iron was used to treat 4% of CD and 4% UC patients overall and 8% of those with anemia. Conclusion: At least 80% of children with IBD were screened for anemia, although most did not receive follow-up tests for iron deficiency. The 43%-50% prevalence of anemia was consistent with prior studies. Under-treatment with IV iron points to a potential target for quality improvement.

Brown preadipocyte transplantation locally ameliorates obesity

  • Takaya, Kento;Matsuda, Naruhito;Asou, Toru;Kishi, Kazuo
    • Archives of Plastic Surgery
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    • v.48 no.4
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    • pp.440-447
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    • 2021
  • Background Brown adipose tissue (BAT) is a potential target for anti-obesity treatments. Previous studies have shown that BAT activation causes an acute metabolic boost and reduces adiposity. Furthermore, BAT and BAT-derived cell transplantation reportedly help treat obesity by regulating glucose and fatty acid metabolism. However, since BAT transplantation leads to whole-body weight loss, we speculated that earlier approaches cause a generalized and unnecessary fat tissue loss, including in breast and hip tissues. Methods We transplanted white adipose tissue-derived or BAT-derived preadipocytes prepared from C57BL/6 mice into one side of the inguinal fat pads of an obese mouse model (db/db mice) to examine whether it would cause fat loss at the peri-transplant site (n=5 each). The same volume of phosphate-buffered saline was injected as a control on the other side. Six weeks after transplantation, the inguinal fat pad was excised and weighed. We also measured the concentrations of glucose, triglycerides, fatty acids, and total cholesterol in the peripheral blood. Results BAT-derived preadipocytes showed abundant mitochondria and high levels of mitochondrial membrane uncoupling protein 1 expression, both in vivo and in vitro, with a remarkable reduction in weight of the inguinal fat pad after transplantation (0.17±0.12 g, P=0.043). Only free fatty acid levels tended to decrease in the BAT-transplanted group, but the difference was not significant (P=0.11). Conclusions Our results suggest that brown adipocytes drive fat degradation around the transplantation site. Thus, local transplantation of BAT-derived preadipocytes may be useful for treating obesity, as well as in cosmetic treatments.

Review of Experimental Researches on Gastrointestinal Activity of Agastache rugosa (Fisch. & C. A. Mey.) Kuntze and Pogostemon cablin (Blanco) Benth. (곽향(藿香) 및 광곽향(廣藿香)의 위장관 효능에 대한 실험연구 고찰)

  • Jerng, Ui Min;Oh, Yong Taek;Kim, Jung Hoon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.31 no.2
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    • pp.138-144
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    • 2017
  • The pharmacological rationale of Agastache rugosa (AR) or Pogostemon cablin (PC), which have been used in traditional Korean medicine to treat dampness pattern or syndrome in gastrointestinal tract, was investigated on the gastrointestinal disorders. In-vivo model studies that examined the effect on the gastrointestinal disorders of AR or PC were collected. They were classified into disease-induced in-vivo models or non-disease in vivo models. The target disease, animal species, induction method, administration, and outcomes (changes in morphological and histological parameter, or blood and fluid) of each study were analyzed. The therapeutic mechanism of AR or PC extract was evaluated by the induced diseases and the changes in outcomes. There were contradictory reports on gastrointestinal motility of AR or PC in disease non-disease in-vivo model. AR or PC inhibited gastrointestinal motility in disease model of increased gastrointestinal motility, while promoted motility in disease model of decreased gastrointestinal motility. AR or PC also inhibited inflammatory changes in gastrointestinal inflammation model. These results suggest that the bidirectional regulation of gastrointestinal motility and the improvement of gastrointestinal inflammatory disorders might underpin traditional therapeutic effect of AR or PC, that is effect to resolve dampness of gastrointestinal tract.