Publications by authors named "Eun Kyung Choi"

299 Publications

The Role of Dexmedetomidine in Hepatic Ischemia-Reperfusion Injury Via a Nitric Oxide-Dependent Mechanism in Rats.

Transplant Proc 2021 Jul 6. Epub 2021 Jul 6.

Department of Anesthesiology and Pain Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, South Korea. Electronic address:

Background: Dexmedetomidine is known to protect against ischemia-reperfusion (IR) in various organs; however, the mechanisms of dexmedetomidine in the liver remain unclear. We investigated whether dexmedetomidine preconditioning leads to hepatic protection and whether nitric oxide was associated with this protective mechanism by employing N-nitro-l-arginine methyl ester (l-NAME), a nitrous oxide synthase inhibitor.

Methods: Experiment 1 included 24 rats in 4 groups: sham, IR, 30 μg/kg of dexmedetomidine, and 50 μg/kg of dexmedetomidine. Experiment 2 included 36 rats in 6 groups: IR, 50 μg/kg of dexmedetomidine, 10 mg/kg of l-NAME, 10 mg/kg of l-NAME + 50 μg/kg of dexmedetomidine, 30 of mg/kg l-NAME, and 30 mg/kg of l-NAME + 50 μg/kg of dexmedetomidine. All drugs were administered intraperitoneally. The levels of serum transaminases, malondialdehyde, superoxide dismutase, tumor necrosis factor-α, nuclear factor-κB, and c-Jun N-terminal kinase were measured 6 hours after hepatic surgery.

Results: Dexmedetomidine demonstrated a dose-dependent decrease in serum transaminase levels. The 50-μg/kg dexmedetomidine group showed a significant decrease in malondialdehyde levels (P = .002), increase in superoxide dismutase levels (P = .002), and a significantly lower level of phosphorylated tumor necrosis factor-α, nuclear factor-κB, and c-Jun N-terminal kinase (P = .002, respectively) compared with the IR injury group. These protective effects of dexmedetomidine were partially reversed by pretreatment with l-NAME (P < .01 for 20 and 30 mg/kg of l-NAME).

Conclusion: In hepatic IR injury, dexmedetomidine might protect the liver via antioxidative and anti-inflammatory responses, and nitric oxide production could play a role in these protective mechanisms.
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http://dx.doi.org/10.1016/j.transproceed.2021.05.008DOI Listing
July 2021

Discovery of a novel CDK7 inhibitor YPN-005 in small cell lung cancer.

Eur J Pharmacol 2021 Jul 3;907:174298. Epub 2021 Jul 3.

Department of Convergence Medicine, Asan Medical Center, University of Ulsan, College of Medicine, Seoul 05505, South Korea. Electronic address:

In contrast to non-small cell lung cancer, there has been no significant progress in the development of therapies for the small cell lung cancer (SCLC) in recent decades. Although various targeted agents, including immunotherapies, have recently been developed for testing in clinical trials, novel therapeutic agents are still needed for SCLC. We developed a potent inhibitor of cyclin-dependent kinase 7 (CDK7), designated YPN-005, and sought to determine whether it showed any anticancer effects in SCLC cells, cisplatin or etoposide-resistant cells, or organoids derived from SCLC patients. In a panel of kinases assay, YPN-005 was highly selective for CDK7 and showed antiproliferative effects in SCLC and cells with acquired resistance to conventional anticancer drugs. Similar to other CDK7 inhibitors, YPN-005 treatment significantly decreased the phosphorylation of the carboxyl-terminal domain of RNA polymerase II. Consistent with the in vitro results, YPN-005 treatment showed a significant inhibition of tumor growth through the suppression of RNA polymerase II phosphorylation. Finally, YPN-005 showed potent anticancer effects in organoids derived from SCLC patients compared to another CDK7 inhibitor, THZ1. Therapeutic targeting of CDK7 in SCLC might be suitable for clinical investigation, and YPN-005 may be a promising therapeutic option for primary SCLC and SCLC with acquired resistance to conventional therapy.
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http://dx.doi.org/10.1016/j.ejphar.2021.174298DOI Listing
July 2021

Undervaluation of Radiotherapy for Gross Desmoid Tumors: The Need for Absolute Volume Assessment.

In Vivo 2021 May-Jun;35(3):1777-1784

Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Background/aim: To compare absolute volume (AV) assessment according to Response Evaluation Criteria in Solid Tumors (RECIST) for the response evaluation of desmoid tumors (DTs) treated with radiotherapy.

Patients And Methods: Eighteen patients with DTs ≥3 cm in size were included.

Results: The median follow-up duration was 78.0 months. Five patients achieved a complete response according to RECIST, seven reached a partial response (PR), and one eventually exhibited progression. The overall response rate was 61%, the median time to PR was 8.0 months. Six patients achieved stable disease, although three developed progressions. Of the six patients with a PR, the median change in maximum diameter was -46%, and the median change in maximum volume was -84%. Three patients could have been diagnosed with progression at least 6 months earlier if the AV increment was considered.

Conclusion: An AV assessment is essential for an accurate response assessment of DTs and radiotherapy seems feasible as a first-line treatment for DTs.
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http://dx.doi.org/10.21873/invivo.12437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193310PMC
June 2021

Prognostic value of the 21-gene recurrence score for regional recurrence in patients with estrogen receptor-positive breast cancer.

Breast Cancer Res Treat 2021 Aug 23;188(3):583-592. Epub 2021 Apr 23.

Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Purpose: To evaluate the prognostic value of the 21-gene recurrence score (RS) for regional recurrence (RR) in patients with estrogen receptor-positive breast cancer.

Methods: We reviewed the medical records of 446 patients who underwent 21-gene RS assay after breast-conserving surgery or mastectomy. The high-RS group was defined as patients who were (1) older than 50 years with an RS of 26 or higher, or (2) 50 years or younger with an RS of 16 or higher.

Results: The 5-year rates of local recurrence (LR), RR, and distant metastasis (DM) were 2.2%, 2.7%, and 4.7%, respectively. The 5-year overall survival (OS) rate was 99.1%. Of the patients, 269 (60.3%) had low-RS, while 177 (39.7%) had high-RS. The 5-year OS rate of the high-RS group was significantly lower than that of the low-RS. The 5-year rates of RR and DM in the high-RS group were significantly higher than those in the low-RS group, while the LR rates did not differ significantly. In multivariable analysis, the high-RS group had a significant relationship with increased RR rate (p = 0.037). Patients who had both high-RS and clinical high-risk features had a significantly higher 5-year RR rate (7.9%) compared with other groups.

Conclusions: High-RS was an independent risk factor for RR. The significantly higher RR rate of patients with both high-RS and clinical high-risk features compared with other groups suggests that this patient group can be a potential candidate for regional nodal irradiation.
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http://dx.doi.org/10.1007/s10549-021-06228-1DOI Listing
August 2021

Transcriptome Analysis of the Cerebellum of Mice Fed a Manganese-Deficient Diet.

Front Genet 2020 3;11:558725. Epub 2020 Dec 3.

Department of Human Genetics, Michigan Medicine, University of Michigan, Ann Arbor, MI, United States.

Manganese (Mn), primarily acquired through diet, is required for brain function and development. Epidemiological studies have found an association between both low and high levels of Mn and impaired neurodevelopment in children. Recent genetic studies have revealed that patients with congenital Mn deficiency display severe psychomotor disability and cerebral and cerebellar atrophy. Although the impact of Mn on gene expression is beginning to be appreciated, Mn-dependent gene expression remains to be explored in vertebrate animals. The goal of this study was to use a mouse model to define the impact of a low-Mn diet on brain metal levels and gene expression. We interrogated gene expression changes in the Mn-deficient mouse brain at the genome-wide scale by RNA-seq analysis of the cerebellum of mice fed low or normal Mn diets. A total of 137 genes were differentially expressed in Mn-deficient cerebellums compared with Mn-adequate cerebellums (adj < 0.05). Mn-deficient mice displayed downregulation of key pathways involved with "focal adhesion," "neuroactive ligand-receptor interaction," and "cytokine-cytokine receptor interaction" and upregulation of "herpes simplex virus 1 infection," "spliceosome," and "FoxO signaling pathway." Reactome pathway analysis identified upregulation of the splicing-related pathways and transcription-related pathways, as well as downregulation of "metabolism of carbohydrate," and "extracellular matrix organization," and "fatty acid metabolism" reactomes. The recurrent identifications of splicing-related pathways suggest that Mn deficiency leads to upregulation of splicing machineries and downregulation of diverse biological pathways.
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http://dx.doi.org/10.3389/fgene.2020.558725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780674PMC
December 2020

Feasibility of automated planning for whole-brain radiation therapy using deep learning.

J Appl Clin Med Phys 2021 Jan 19;22(1):184-190. Epub 2020 Dec 19.

Department of Radiation Oncology, Asan Medical Center, Seoul, Republic of Korea.

Purpose: The purpose of this study was to develop automated planning for whole-brain radiation therapy (WBRT) using a U-net-based deep-learning model for predicting the multileaf collimator (MLC) shape bypassing the contouring processes.

Methods: A dataset of 55 cases, including 40 training sets, five validation sets, and 10 test sets, was used to predict the static MLC shape. The digitally reconstructed radiograph (DRR) reconstructed from planning CT images as an input layer and the MLC shape as an output layer are connected one-to-one via the U-net modeling. The Dice similarity coefficient (DSC) was used as the loss function in the training and ninefold cross-validation. Dose-volume-histogram (DVH) curves were constructed for assessing the automatic MLC shaping performance. Deep-learning (DL) and manually optimized (MO) approaches were compared based on the DVH curves and dose distributions.

Results: The ninefold cross-validation ensemble test results were consistent with DSC values of 94.6 ± 0.4 and 94.7 ± 0.9 in training and validation learnings, respectively. The dose coverages of 95% target volume were (98.0 ± 0.7)% and (98.3 ± 0.8)%, and the maximum doses for the lens as critical organ-at-risk were 2.9 Gy and 3.9 Gy for DL and MO, respectively. The DL technique shows the consistent results in terms of the DVH parameter except for MLC shaping prediction for dose saving of small organs such as lens.

Conclusions: Comparable with the MO plan result, the WBRT plan quality obtained using the DL approach is clinically acceptable. Moreover, the DL approach enables WBRT auto-planning without the time-consuming manual MLC shaping and target contouring.
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http://dx.doi.org/10.1002/acm2.13130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856520PMC
January 2021

The role of postoperative radiotherapy after primary tumor resection in patients with de novo stage IV breast cancer.

Asia Pac J Clin Oncol 2020 Nov 11. Epub 2020 Nov 11.

Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

Aim: This study was undertaken to investigate the role of postoperative radiotherapy (PORT) including post-breast conserving radiotherapy (PBCRT) and post-mastectomy radiotherapy (PMRT) in stage IV breast cancer patients who underwent planned primary tumor resection (PTR).

Methods: This study enrolled 112 patients diagnosed with de novo stage IV breast cancer who were treated with potentially curative PTR with or without PORT. The primary outcome was overall survival (OS), and the secondary outcomes were locoregional recurrence-free survival (LRRFS) and distant progression-free survival (DPFS).

Results: At a median follow-up of 48.9 months (range, 3.5-183.4 months), the median OS was 54.9 months (range, 5.3-185.9 months) with a 5 year OS rate of 59.6%. Lower clinical T stage, Luminal A or B type tumors and PBCRT were significantly predictive of longer OS. The 5 year LRRFS and DMFS rates were 79.0% and 34.3%, respectively. In multivariate analysis for LRRFS, the PBCRT arm demonstrated significant superiority compared to the No PORT arm. A comparison of patients who did and did not receive PORT showed that patients with disseminated metastasis more likely did not receive PORT and were excluded from the analysis. PBCRT arm demonstrated significantly superior LRRFS of 100% while PMRT and No PORT arm demonstrated 81.5% and 84.0%, respectively CONCLUSIONS: De novo stage IV breast cancer patients who received planned PTR showed favorable survival outcomes compared with historical cohorts. PTR may be predictive of a good prognosis, especially in patients with luminal A or B type tumors. PORT, especially PBCRT was predictive of LRRFS, suggesting that patients may benefit from this treatment.
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http://dx.doi.org/10.1111/ajco.13506DOI Listing
November 2020

A randomized, double-blind, placebo-controlled pilot study to assess the effects of protopanaxadiol saponin-enriched ginseng extract and pectinase-processed ginseng extract on the prevention of acute respiratory illness in healthy people.

J Ginseng Res 2020 Sep 11;44(5):697-703. Epub 2019 Feb 11.

Clinical Trial Center for Functional Foods, Jeonbuk National University Hospital, Jeonju, Jeonbuk, Republic of Korea.

Background: GS-3K8 and GINST, both of which are modified ginseng extracts, have never been examined in terms of their effectiveness for the prevention of acute respiratory illness (ARI) in humans. We conducted a pilot study to assess the feasibility of performing a large-scale, randomized, controlled trial.

Methods: This study was a randomized, double-blind, placebo-controlled, pilot study at a single center from October 2014 to March 2015. The 45 healthy applicants were randomly divided into the GS-3K8 (n = 15), GINST (n = 15), and placebo groups (n = 15). The study drug was administered as a capsule (500 mg/cap and 3000 mg/day). GS-3K8 contained 6.31 mg/g of Rg1, 15.05 mg/g of Re, 30.84 mg/g of Rb1, 15.02 mg/g of Rc, 12.44 mg/g of Rb2, 6.97 mg/g of Rd, 1.59 mg/g of Rg3, 3.25 mg/g of Rk1, and 4.84 mg/g of Rg5. GINST contained 7.54 mg/g of Rg1, 1.87 mg/g of Re, 5.42 mg/g of Rb1, 0.29 mg/g of Rc, 0.36 mg/g of Rb2, 0.70 mg/g of Rd, and 6.3 mg/g of compound K. The feasibility criteria were the rates of recruitment, drug compliance, and successful follow-up. The primary clinical outcome measure was the incidence of ARI. The secondary clinical outcome measures were the duration of symptoms.

Results: The rate of recruitment was 11.3 participants per week. The overall rate of completed follow-up was 97.8%. The mean compliance rate was 91.64 ± 9.80%, 95.28 ± 5.75%, and 89.70 ± 8.99% in the GS-3K8, GINST, and placebo groups, respectively. The incidence of ARI was 64.3% (9/14; 95% confidence interval [CI], 31.4-91.1%), 26.7% (4/15; 95% CI, 4.3-49.0%), and 80.0% (12/15; 95% CI, 54.8-93.0%) in the GS-3K8, GINST, and placebo groups, respectively. The average days of symptoms were 3.89 ± 4.65, 9.25 ± 7.63, and 12.25 ± 12.69 in the GS-3K8, GINST, and placebo groups, respectively.

Conclusion: The results support the feasibility of a full-scale trial. GS-3K8 and GINST appear to have a positive tendency toward preventing the development of ARI and reducing the symptom duration. A randomized controlled trial is needed to confirm these findings.
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http://dx.doi.org/10.1016/j.jgr.2019.01.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471208PMC
September 2020

Characterization of sphere cells derived from a patient-derived xenograft model of lung adenocarcinoma treated with ionizing radiation.

Int J Radiat Biol 2020 11 28;96(11):1413-1422. Epub 2020 Aug 28.

Center for Advancing Cancer Therapeutics, Seoul, Korea.

Purpose: Cancer stem cells (CSCs) are relatively resistant to radiation compared to their non-tumorigenic progeny. Ionizing radiation (IR) can expand the pool of CSCs that leads to more aggressive cancers, but the reason underlying CSC-induced cancer aggressiveness after radiation therapy remains unclear. To understand this, we investigated the phenotypic and molecular characteristics of sphere cells formed from IR-treated patient-derived xenograft (PDX) lung adenocarcinoma tumors.

Materials And Methods: After treatment with various modes of IR, we collected tumors from PDX mice and successfully obtained sphere cells. To compare tumorigenicity, we performed migration, invasion, and mouse transplantation assays with sphere cells from each group. To investigate the molecular features, we used a cDNA microarray and compared gene expression among groups.

Results And Conclusions: Tumorigenicity assays revealed that sphere cells from 2- or 5-Gy IR-treated tumors more aggressive than sphere cells from non-IR treated tumors. Microarray results showed that and were upregulated in sphere cells from IR-treated tumors compared to that in sphere cells from non-IR treated tumors. Interestingly, these genes are related to immune reactions in cancer. Taken together, our results suggest that the aggressiveness of sphere cells obtained after IR treatment is related to resistance, and provide new opportunities for exploring targeted therapies to overcome common radioresistance.
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http://dx.doi.org/10.1080/09553002.2020.1793019DOI Listing
November 2020

Role of Remote Ischemic Preconditioning in Hepatic Ischemic Reperfusion Injury.

Dose Response 2020 Jul-Sep;18(3):1559325820946923. Epub 2020 Aug 13.

Department of Anesthesiology and Pain Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.

The effect of remote ischemic preconditioning (RIPC) has been proposed that mediates the protective response in ischemia reperfusion injury (IRI) of various organs. In this study, we investigated the effect of RIPC in hepatic IRI, by assessing biomarker of oxidative stress and inflammatory cytokines. Moreover, we intended to demonstrate any such protective effect through nitric oxide (NO). Twenty-five rats were divided into the 5 groups: (1) Sham; (2) RIPC; (3) hepatic IRI; (4) RIPC + hepatic IRI; (5) C-PTIO, 2-(4-carboxyphenyl)-4,5dihydro-4,4,5,5-tetramethyl-1H-imidazolyl-1-oxy-3oxide, + RIPC + hepatic IRI. RIPC downregulated the level of aspartate aminotransferase (AST), alanine aminotransferase (ALT), histologic damage, and activity of Malondialdehyde (MDA). However, there was no significant reduction in the level of tumor necrosis factor-alpha (TNF-α) and nuclear factor kappa B (NF-κB). AST and ALT levels, and hepatic tissue morphology in the C-PTIO group showed a significant improvement compared to those of the RIPC + hepatic IRI group. The application of RIPC before hepatic ischemia downregulated the oxidative stress, not the inflammatory cytokines. Moreover, these protective effect of RIPC would be mediated through the activation of NO as well as anti-oxidant effect.
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http://dx.doi.org/10.1177/1559325820946923DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7427033PMC
August 2020

A Randomized Controlled Trial Comparing Analgesic Efficacies of an Ultrasound-Guided Approach with and without a Combined Pressure Measurement Technique for Thoracic Paravertebral Blocks After Open Thoracotomy.

Ther Clin Risk Manag 2020 6;16:727-734. Epub 2020 Aug 6.

Department of Anesthesiology and Pain Medicine, Yeungnam University College of Medicine, Daegu, Republic of Korea.

Purpose: Ultrasound-guided thoracic paravertebral block (TPVB) is an established means for providing postoperative analgesia in thoracic surgery. However, there are conflicting results regarding the efficacy of post-thoracotomy pain management of ultrasound-guided TPVB when compared with that using traditional landmark approach. We therefore conducted a comparative study to evaluate the analgesic efficacy of TPVB when pressure measurement during needle advancement is combined with an ultrasound-guided approach.

Patients And Methods: The patients scheduled for lobectomy through thoracotomy were randomly allocated to receive either the ultrasound-guided approach only group (U group) or the ultrasound-guided approach combined with pressure measurement group (UP group) (n = 36 per group). Before thoracic muscle closure, 0.375% ropivacaine (20 mL) was administered as a bolus, followed by a continuous infusion of 0.2% ropivacaine (0.1 mL/kg/hr) in both groups. Postoperative pain was assessed using the visual analogue scale (VAS) pain score while resting and coughing. Local anesthetics and pethidine usage and sensory block area were also evaluated.

Results: The UP group showed significantly lower VAS scores, local anesthetics and pethidine usage, and a wider sensory block area than the U group.

Conclusion: A combined technique with ultrasound guidance and pressure measurement provided a superior analgesic effect over that of an ultrasound-guided approach alone for the management of post-thoracotomy pain.
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http://dx.doi.org/10.2147/TCRM.S263353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418159PMC
August 2020

The effect of dexmedetomidine and remifentanil on the postoperative sore throat after thyroidectomy.

Medicine (Baltimore) 2020 Jul;99(29):e21060

Department of Anesthesiology and Pain Medicine, Yeungnam University College of Medicine, Daegu, Republic of Korea.

Background: Postoperative sore throat (POST) is an important concern in surgical patients undergoing endotracheal intubation. Its prevalence after thyroidectomy is up to 80%. The current study aimed to assess the effect of dexmedetomidine and remifentanil on postoperative sore throat.

Methods: Seventy-four patients who underwent thyroidectomy were randomized to receive either dexmedetomidine (group D) or remifentanil (group R). At anesthesia induction, group D received dexmedetomidine 1 μg/kg over 10 minutes, followed by continuous dexmedetomidine infusion at 0.3 to 0.6 μg/kg/hour during surgery. Group R received remifentanil of 3 to 4 ng/ml during induction, followed by 1.5 to 2.5 ng/ml remifentanil infusion during surgery. POST at rest and swallowing was assessed during the first 24 hours in serial time periods (0-1, 1-6, and 6-24 hours). Hoarseness and postoperative pain score were also assessed.

Results: POST incidence at rest (0-1, 1-6, and 6-24 hours) and swallowing (1-6 and 6-24 hours) was lower in group D than in group R. POST severity was significantly lower in group D than in group R during each time period. The incidence of postoperative hoarseness was also lower in group D than in group R at 1 to 6 and 6 to 24 hours. The postoperative pain score was lower in group D than in group R during each time period.

Conclusion: Intraoperative dexmedetomidine infusion reduced the incidence and severity of POST for 24 hours after thyroidectomy.
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http://dx.doi.org/10.1097/MD.0000000000021060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373553PMC
July 2020

A randomized, double-blind, placebo-controlled crossover clinical trial to evaluate the anti-diabetic effects of Allium hookeri extract in the subjects with prediabetes.

BMC Complement Med Ther 2020 Jul 6;20(1):211. Epub 2020 Jul 6.

Clinical Trial Center for Functional Foods, Chonbuk National University Hospital, Jeonju, Republic of Korea.

Background: Allium hookeri is widely consumed as a vegetable and herbal medicine in Asia. A. hookeri has been reported anti-inflammatory, anti-obesity, osteoblastic, anti-oxidant, and anti-diabetic effects in animal studies. We investigated the anti-diabetic effects of A. hookeri aqueous extract (AHE) in the Korean subjects.

Methods: Prediabetic subjects (100 ≤ fasting plasma glucose (FPG) < 126 mg/dL) who met the inclusion criteria were recruited for this study. The enrolled subjects (n = 30) were randomly divided into either an AHE (n = 15, 486 mg/day) or placebo (n = 15) group. Outcomes were measurements of FPG, glycemic response to an oral glucose tolerance test (OGTT), insulin, C-peptide, hemoglobin A1c (HbA1c), total cholesterol, triglyceride, HDL-cholesterol, and LDL-cholesterol. The t-test was used to assess differences between the groups. A p-value < 0.05 was considered statistically significant.

Results: Eight weeks after AHE supplementation, HbA1c level was significantly decreased in the AHE group compared with the placebo group. No clinically significant changes in any safety parameter were observed.

Conclusion: The findings suggest that AHE can be effective in reducing HbA1c, indicating it as an adjunctive tool for improving glycemic control.

Trial Registration: The study protocol was retrospectively registered at www.clinicaltrials.gov ( NCT03330366 , October 30, 2017).
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http://dx.doi.org/10.1186/s12906-020-03005-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339438PMC
July 2020

A novel nanoparticle-based theranostic agent targeting LRP-1 enhances the efficacy of neoadjuvant radiotherapy in colorectal cancer.

Biomaterials 2020 10 27;255:120151. Epub 2020 May 27.

Center for Advancing Cancer Therapeutics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, South Korea; Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, South Korea. Electronic address:

Neoadjuvant radiotherapy has become an important therapeutic option for colorectal cancer (CRC) patients, whereas complete tumor response is observed only in 20-30% patients. Therefore, the development of diagnostic probe for radio-resistance is important to decide an optimal treatment timing and strategy for radiotherapy-resistant CRC patients. In this study, using the patient-derived xenograft (PDX) mouse model established with a radio-resistant CRC tumor tissue, we found low-density lipoprotein receptor-related protein-1 (LRP-1) as a radio-resistant marker protein induced by initial-dose radiation in radio-resistant CRC tumors. Simultaneously, we discovered a LRP-1 targeting peptide in a radio-resistant CRC PDX through in vivo peptide screening. We next engineered the theranostic agent made of human serum albumin nanoparticles (HSA NPs) containing 5-FU for chemo-radiotherapy and decorating LRP-1-targeting peptide for tumor localization, Cy7 fluorophore for diagnostic imaging. The nanoparticle-based theranostic agent accurately targeted the tumor designated by LRP-1 responding radiation and showed dramatically improved therapeutic efficacy in the radio-resistant PDX model. In conclusion, we have identified LRP-1 as a signature protein of radio-resistant CRC and successfully developed LRP-1-targeting HSA-NP containing 5-FU that is a novel theranostic tool for both diagnostic imaging and neoadjuvant therapy of CRC patients. This approach is clinically applicable to improve the effectiveness of neo-adjuvant radiotherapy and increase the ratio of complete tumor response in radio-resistant CRC.
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http://dx.doi.org/10.1016/j.biomaterials.2020.120151DOI Listing
October 2020

A 12-week, randomized, double-blind study to evaluate the efficacy and safety of liver function after using fermented ginseng powder (GBCK25).

Food Nutr Res 2020 6;64. Epub 2020 Apr 6.

Clinical Trial Center for Functional Foods, Chonbuk National University Hospital, Jeonju, Republic of Korea.

Background: Recently, clinical research has suggested that red ginseng components play a role in liver protection and combating fatigue. However, fermented ginseng has not been analyzed for liver-protective or anti-fatigue effects.

Objective: This study evaluates the positive effects of fermented ginseng powder (GBCK25) on liver function.

Methods: Ninety participants with elevated alanine aminotransferase levels (35 ≤ ALT ≤1 05 IU/L) were randomized to one of three groups. The participants were treated with GBCK25 tablets at a dose of 500 mg/day (high dose), 125 mg/day (low dose), or placebo group daily for 12 weeks. The primary outcomes included changes in ALT and gamma-glutamyl transferase (GGT) levels. The secondary outcomes included changes in aspartate amino-transferase (AST), high-sensitivity C-reactive protein (hs-CRP), multidimensional fatigue scale, lipid profile, and antioxidant markers.

Results: In male subjects, after 12 weeks of low-dose GBCK25 (125 mg) supplementation, the GGT ( = 0.036) and hs-CRP ( = 0.021) levels decreased significantly more than those in the placebo group. High-dose GBCK25 (500 mg) supplementation significantly decreased the fatigue score compared with the placebo group. There were no clinically significant differences between the groups when studying any safety parameter.

Conclusion: Our results suggest that GBCK25 supplementation has beneficial effects on liver function.

Trial Registration: This study was registered at Clinical Trials.gov (NCT03260543).
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http://dx.doi.org/10.29219/fnr.v64.3517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217291PMC
April 2020

Surgical impact on anxiety of patients with breast cancer: 12-month follow-up prospective longitudinal study.

Ann Surg Treat Res 2020 May 28;98(5):215-223. Epub 2020 Apr 28.

Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Purpose: Breast cancer diagnosis and treatment often produce stress in patients. Anxiety is one of the most prevalent psychological symptoms perceived by breast cancer patients. This study aims to evaluate the temporal patterns of anxiety and find factors associated with persistent anxiety during breast cancer treatment.

Methods: This is prospective cohort study. Between July 2010 and July 2011, we recruited patients with nonmetastatic breast cancer who were expected to receive adjuvant chemotherapy (n = 411) from 2 cancer hospitals in Seoul, Korea. Anxiety was measured using the Hospital Anxiety and Depression Scale.

Results: The mean age of the participants was 46.4 ± 7.9 years. Preoperatively, 44.5% (183 of 411) of the patients showed abnormal anxiety. The proportion of the abnormal anxiety group significantly decreased after surgery (P < 0.01) and this phenomenon continued until the 12-month follow-up point. Patients experienced renewed anxiety at 12 months when the main adjuvant therapies were finished. Socioeconomic factors were not associated with persistent anxiety. Pain, breast, and arm symptoms were significantly higher in the persistently abnormal group, especially at postoperative months 6 and 12.

Conclusion: Surgery was a major relieving factor of anxiety, and patients who finished their main adjuvant treatment experienced renewed anxiety. Surgeons should be the main detectors and care-givers with respect to psychological distress in breast cancer patients. To reduce persistent anxiety, caring for the patient's physical symptoms is important.
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http://dx.doi.org/10.4174/astr.2020.98.5.215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7200606PMC
May 2020

Serum Follicle-Stimulating Hormone Levels Are Associated with Cardiometabolic Risk Factors in Post-Menopausal Korean Women.

J Clin Med 2020 Apr 18;9(4). Epub 2020 Apr 18.

Clinical Trial Center for Functional Foods, Chonbuk National University Hospital, Jeonju, Jeonbuk 54907, Korea.

Menopause compounds many cardiometabolic risk factors through endogenous estrogen withdrawal. This study aimed to find the association between serum follicle-stimulating hormone (FSH) levels and cardiometabolic risk factors in post-menopausal Korean women. A total of 608 post-menopausal women from eight randomized double-blind, placebo-controlled clinical trials on menopause during the year 2012-2019 were analyzed. Cardiometabolic risk factors such as body mass index, waist circumference, systolic blood pressure, fasting glucose, triglycerides (TG), high density lipoprotein-cholesterol (HDL-C), and TG/HDL-C ratio were significantly improved as the FSH quartiles increased. Metabolic syndrome (MetS) and the number of components of MetS decreased as FSH quartiles increased. In regression analysis, FSH level was negatively associated with cardiometabolic risk factors including body mass index, body weight, waist circumference, fasting glucose and TG, while it was positively associated with HDL-C. The odds ratio of MetS in the first quartile of FSH was 2.682 compared with that in the fourth quartile of FSH in a logistic regression model. Serum FSH levels had a negative correlation with cardiometabolic risk factors in post-menopausal Korean women, suggesting that a low FSH can be a predictor for cardiovascular disease in post-menopausal women.
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http://dx.doi.org/10.3390/jcm9041161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230188PMC
April 2020

CD226CD8 T Cells Are a Prerequisite for Anti-TIGIT Immunotherapy.

Cancer Immunol Res 2020 07 7;8(7):912-925. Epub 2020 Apr 7.

Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul, South Korea.

Clinical trials are evaluating the efficacy of anti-TIGIT for use as single-agent therapy or in combination with programmed death 1 (PD-1)/programmed death-ligand 1 blockade. How and whether a TIGIT blockade will synergize with immunotherapies is not clear. Here, we show that CD226CD8 T cells accumulate at the tumor site and have an exhausted phenotype with impaired functionality. In contrast, CD226CD8 tumor-infiltrating T cells possess greater self-renewal capacity and responsiveness. Anti-TIGIT treatment selectively affects CD226CD8 T cells by promoting CD226 phosphorylation at tyrosine 322. CD226 agonist antibody-mediated activation of CD226 augments the effect of TIGIT blockade on CD8 T-cell responses. Finally, mFOLFIRINOX treatment, which increases CD226CD8 T cells in patients with pancreatic ductal adenocarcinoma, potentiates the effects of TIGIT or PD-1 blockade. Our results implicate CD226 as a predictive biomarker for cancer immunotherapy and suggest that increasing numbers of CD226CD8 T cells may improve responses to anti-TIGIT therapy.
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http://dx.doi.org/10.1158/2326-6066.CIR-19-0877DOI Listing
July 2020

The emerging role of myeloid-derived suppressor cells in radiotherapy.

Radiat Oncol J 2020 Mar 25;38(1):1-10. Epub 2020 Mar 25.

Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Radiotherapy (RT) has been used for decades as one of the main treatment modalities for cancer patients. The therapeutic effect of RT has been primarily ascribed to DNA damage leading to tumor cell death. Besides direct tumoricidal effect, RT affects antitumor responses through immune-mediated mechanism, which provides a rationale for combining RT and immunotherapy for cancer treatment. Thus far, for the combined treatment with RT, numerous studies have focused on the immune checkpoint inhibitors and have shown promising results. However, treatment resistance is still common, and one of the main resistance mechanisms is thought to be due to the immunosuppressive tumor microenvironment where myeloid-derived suppressor cells (MDSCs) play a crucial role. MDSCs are immature myeloid cells with a strong immunosuppressive activity. MDSC frequency is correlated with tumor progression, recurrence, negative clinical outcome, and reduced efficacy of immunotherapy. Therefore, increasing efforts to target MDSCs have been made to overcome the resistance in cancer treatments. In this review, we focus on the role of MDSCs in RT and highlight growing evidence for targeting MDSCs in combination with RT to improve cancer treatment.
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http://dx.doi.org/10.3857/roj.2019.00640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113146PMC
March 2020

Cutting Edge: Activation-Induced Iron Flux Controls CD4 T Cell Proliferation by Promoting Proper IL-2R Signaling and Mitochondrial Function.

J Immunol 2020 04 2;204(7):1708-1713. Epub 2020 Mar 2.

Immunology Graduate Program, University of Michigan Medical School, Ann Arbor, MI 48109;

Iron has long been established as a critical mediator of T cell development and proliferation. However, the mechanisms by which iron controls CD4 T cell activation and expansion remain poorly understood. In this study, we show that stimulation of CD4 T cells from C57BL/6 mice not only decreases total and labile iron levels but also leads to changes in the expression of iron homeostatic machinery. Additionally, restraining iron availability in vitro severely inhibited CD4 T cell proliferation and cell cycle progression. Although modulating cellular iron levels increased IL-2 production by activated T lymphocytes, CD25 expression and pSTAT5 levels were decreased, indicating that iron is necessary for IL-2R-mediated signaling. We also found that iron deprivation during T cell stimulation negatively impacts mitochondrial function, which can be reversed by iron supplementation. In all, we show that iron contributes to activation-induced T cell expansion by positively regulating IL-2R signaling and mitochondrial function.
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http://dx.doi.org/10.4049/jimmunol.1901399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329364PMC
April 2020

An RNA-binding-protein, NONO governs energy metabolism by regulating NAMPT in lung cancer.

Biochem Biophys Res Commun 2020 07 19;528(2):376-382. Epub 2020 Feb 19.

Department of Convergence Medicine, University of Ulsan College of Medicine, Seoul, South Korea; Asan Institute for Life Sciences, Asan Medical Center, Seoul, South Korea. Electronic address:

The RNA binding proteins (RBPs) have multiple roles in human cancer. However, their molecular target and function have not been clearly identified. Our genomic analysis derived from patients reveals that NONO is a potential oncogenic gene in lung cancer. NONO is highly expressed in lung cancer tissues compared with normal tissues, and its expression has been correlated with the prognosis of lung cancer patients. We found that NONO significantly influences cancer cell proliferation in lung cancer. Gene expression profiles with NONO-depleted cells revealed that the sirtuin signaling pathway is highly correlated with NONO. Thus, NONO-silenced cells caused reduction of the TCA cycle and glycolysis metabolism. We identified that NONO regulated NAMPT, which is a well-known gene involved in sirtuin signaling, and NONO has a significant correlation with NAMPT in lung cancer patients. We propose that NONO modulates energy metabolism by direct interaction with NAMPT and suggest that a functional relationship between NONO and NAMPT contributes to lung cancer cell survival. Targeting the axis can be a promising approach for patient treatment in lung cancer.
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http://dx.doi.org/10.1016/j.bbrc.2020.01.011DOI Listing
July 2020

The effects of steamed ginger ethanolic extract on weight and body fat loss: a randomized, double-blind, placebo-controlled clinical trial.

Food Sci Biotechnol 2020 Feb 11;29(2):265-273. Epub 2019 Oct 11.

1Clinical Trial Center for Functional Foods, Chonbuk National University Hospital, Jeonju-si, Republic of Korea.

Steamed ginger ethanolic extract (SGE) is a product with a high 6-shogaol contents and is thought to be more potent than other ginger products. We conducted a 12-week, randomized, double-blind, placebo-controlled clinical trial to determine the effects of SGE on weight and body fat loss. Eighty healthy obese participants were recruited and randomly divided into the SGE and placebo groups. The outcome measures comprised indicators of efficacy (body weight, body mass index, body composition, and blood markers) and safety. Following the supplementation period, mean body weight, body mass index, and body fat level were significantly lower in the SGE group than in the placebo group. No clinically significant changes were observed for any safety parameter. These results suggest that SGE is a potent anti-obesity agent that does not cause significant side effects. Therefore, SGE supplementation combined with lifestyle modification could be effective in the management of body weight and fat mass.
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http://dx.doi.org/10.1007/s10068-019-00649-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6992804PMC
February 2020

Impact of dietary manganese on experimental colitis in mice.

FASEB J 2020 02 29;34(2):2929-2943. Epub 2019 Dec 29.

Department of Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA.

Diet plays a significant role in the pathogenesis of inflammatory bowel disease (IBD). A recent epidemiological study has shown an inverse relationship between nutritional manganese (Mn) status and IBD patients. Mn is an essential micronutrient required for normal cell function and physiological processes. To date, the roles of Mn in intestinal homeostasis remain unknown and the contribution of Mn to IBD has yet to be explored. Here, we provide evidence that Mn is critical for the maintenance of the intestinal barrier and that Mn deficiency exacerbates dextran sulfate sodium (DSS)-induced colitis in mice. Specifically, when treated with DSS, Mn-deficient mice showed increased morbidity, weight loss, and colon injury, with a concomitant increase in inflammatory cytokine levels and oxidative and DNA damage. Even without DSS treatment, dietary Mn deficiency alone increased intestinal permeability by impairing intestinal tight junctions. In contrast, mice fed a Mn-supplemented diet showed slightly increased tolerance to DSS-induced experimental colitis, as judged by the colon length. Despite the well-appreciated roles of intestinal microbiota in driving inflammation in IBD, the gut microbiome composition was not altered by changes in dietary Mn. We conclude that Mn is necessary for proper maintenance of the intestinal barrier and provides protection against DSS-induced colon injury.
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http://dx.doi.org/10.1096/fj.201902396RDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103308PMC
February 2020

Postoperative emergence agitation and intraoperative sevoflurane sedation under caudal block in children: a randomized comparison of two sevoflurane doses.

Anesth Pain Med (Seoul) 2019 Oct;14(4):434-440

Department of Anesthesiology and Pain Medicine, School of Medicine, Kyungpook National University, Daegu, Korea.

Background: Sub-umbilical surgery under caudal block in conjunction with sevoflurane sedation may be safe in terms of maintaining spontaneous breathing and avoiding complications associated with general anesthesia. However, sevoflurane-induced emergence agitation (EA) continues to be a clinically important phenomenon in children. To compare the incidence of EA in children undergoing sub-umbilical surgery under caudal block with two different doses of sevoflurane.

Methods: Forty children (aged 1-5 years) scheduled to undergo inguinal hernia repair under caudal block with sevoflurane sedation via a face mask were randomized into either the low-dose (1.0%) end-tidal sevoflurane concentration group (Group LS) or the high-dose (2.5%) end-tidal sevoflurane concentration group (Group HS). We monitored EA episodes at 5 and 30 min in the post-anesthetic care unit (PACU) by using the fourpoint agitation scale and the Pediatric Anesthesia Emergence Delirium (PAED) scale.

Results: The four-point agitation scale scores and PAED scores were not different between the groups at 5 min. However, the agitation score was higher in Group HS than in Group LS at 30 min after arriving in the PACU. The time required to recover from sedation was longer in Group HS than in Group LS.

Conclusions: Face-mask sedation with 1.0% sevoflurane in conjunction with caudal block may be more effective than that with 2.5% sevoflurane in preventing EA.
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http://dx.doi.org/10.17085/apm.2019.14.4.434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713797PMC
October 2019

Successful difficult airway management using GlideScope video laryngoscope in a child with Cornelia de Lange Syndrome.

Yeungnam Univ J Med 2018 12 31;35(2):219-221. Epub 2018 Dec 31.

Department of Anesthesiology and Pain Medicine, Yeungnam University College of Medicine, Daegu, Korea.

Management of airway in a child with Cornelia de Lange Syndrome (CdLS) should be given due consideration because most of them have the problems related to difficult airway. The GlideScope video laryngoscope can be attempted during routine intubation, however it is mostly used in case of difficulty. With adequate preoperative airway assessment, we used the pediatric video laryngoscope as useful alternative airway device in a child with CdLS and orotracheal intubation proceeded uneventfully.
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http://dx.doi.org/10.12701/yujm.2018.35.2.219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6784706PMC
December 2018

Effects of Blood Transfusion on Hepatic Ischemia-Reperfusion Injury-Induced Renal Tubular Injury.

Exp Clin Transplant 2020 02 11;18(1):19-26. Epub 2019 Oct 11.

From the Department of Anesthesiology and Pain Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.

Objectives: Hepatic ischemia-reperfusion injury and transfusion of red blood cells in liver surgery are wellknown risk factors to induce acute tubular injury. Transfusion of stored red blood cells may affect hepatic ischemia-reperfusion injury-induced acute tubular injury. Here, we hypothesized whether preischemic (due to increased severity of hepatic injury) and postischemic (due to renal uptake of free heme and iron) transfusion of stored red blood cells may potentiate acute tubular injury in rats subjected to hepatic ischemia-reperfusion injury.

Materials And Methods: Sprague Dawley rats (n = 24) were divided into 4 groups: sham operation (sham group), hepatic ischemia-reperfusion injury only (injury-only group), red blood cell transfusion before hepatic ischemia-reperfusion injury (preinjury transfusion group), and red blood celltransfusion after hepatic ischemia-reperfusion injury (postinjury transfusion group). Partial hepatic ischemia was induced for 90 minutes, with reperfusion allowed for 12 hours. Hepatic and renal tubular injury markers, renal mRNA levels of oxidant stress markers, and inflammatory markers were assessed. Renal cortex samples were examined under hematoxylin and eosin staining for tubular histopathologic score and immunohistochemical staining forinflammatory cells.

Results: With regard to hepatic and renal tubular injury markers, serum alanine aminotransferase, serum urea nitrogen, and histopathologic scores were increased in the preinjury and postinjury transfusion groups versus injury-only group, with moderate to strong correlation between alanine aminotransferase and tubular injury markers. Renal oxidative stress markers (heme oxygenase-1 and neutrophil gelatinaseassociated lipocalin) were correlated with increased alanine aminotransferase, with upregulation of oxidant stress markers in the preinjury transfusion group versus sham group (all markers), as well as in the injury-only and postinjury transfusion groups (heme oxygenase-1 only). We observed no changes in renal inflammatory responses among the groups.

Conclusions: Preischemic transfusion potentiated acute tubular injury without triggering renal inflammatory responses. Exacerbation of hepatic injury may induce acute tubular injury via renal oxidant stress.
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http://dx.doi.org/10.6002/ect.2019.0056DOI Listing
February 2020

Patterns of recurrence after radiation therapy for high-risk neuroblastoma.

Radiat Oncol J 2019 Sep 30;37(3):224-231. Epub 2019 Sep 30.

Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Purpose: To investigate the patterns of recurrence in patients with neuroblastoma treated with radiation therapy to the primary tumor site.

Materials And Methods: We retrospectively analyzed patients with high-risk neuroblastoma managed with definitive treatment with radiation therapy to the primary tumor site between January 2003 and June 2017. These patients underwent three-dimensional conformal radiation therapy or intensity-modulated radiation therapy. A total of 14-36 Gy was delivered to the planning target volume, which included the primary tumor bed and the selected metastatic site. The disease stage was determined according to the International Neuroblastoma Staging System (INSS). We evaluated the recurrence pattern (i.e., local or systemic), progression-free survival, and overall survival.

Results: A total of 40 patients with high-risk neuroblastoma were included in this study. The median patient age was 4 years (range, 1 to 11 years). Thirty patients (75%) had INSS stage 4 neuroblastoma. At the median follow-up of 58 months, there were 6 cases of local recurrence and 10 cases of systemic recurrence. Among the 6 local failure cases, 4 relapsed adjacent to the radiation field. The other 2 relapsed in the radiation field (i.e., para-aortic and retroperitoneal areas). The main sites of distant metastasis were the bone, lymph nodes, and bone marrow. The 5-year progression-free survival was 70.9% and the 5-year overall survival was 74.3%.

Conclusion: Radiation therapy directed at the primary tumor site provides good local control. It seems to be adequate for disease control in patients with high-risk neuroblastoma after chemotherapy and surgical resection.
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http://dx.doi.org/10.3857/roj.2019.00353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6790795PMC
September 2019

The value of prophylactic cranial irradiation in limited-stage small cell lung cancer: should it always be recommended?

Radiat Oncol J 2019 Sep 30;37(3):156-165. Epub 2019 Sep 30.

Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Purpose: Prophylactic cranial irradiation (PCI) is a standard treatment for limited-stage small cell lung cancer (LS-SCLC) showing a response to initial treatment, but many patients do not receive PCI due to comorbidities or refusal. This study aims to define the patient group for whom PCI can be omitted with minimal risk.

Materials And Methods: Patients with LS-SCLC who underwent radiotherapy with curative aim at our institution between January 2004 and December 2015 were retrospectively reviewed. Patients who did not receive PCI were evaluated for brain metastasis-free survival (BMFS), progression-free survival (PFS), overall survival (OS), and prognostic factors for survival, and treatment outcomes were compared with a patient cohort who received PCI.

Results: A total of 350 patients achieved a response following thoracic radiotherapy, and 190 of these patients did not receive PCI. Stage I-II and a complete response (CR) to initial therapy were good prognostic factors for BMFS and OS on univariate analysis. Patients with both stage I-II and a CR who declined PCI showed comparable 2-year BMFS to those who received PCI (92% vs. 89%). In patients who achieved CR, PCI did not significantly improve OS or PFS.

Conclusion: There should be less concern about omitting PCI in patients with comorbidities if they have stage I-II or a CR, with brain metastasis control being comparable to those patients who receive PCI.
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http://dx.doi.org/10.3857/roj.2019.00318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6790796PMC
September 2019

Acute baroreflex-mediated hemodynamic instability during thyroid surgery: A case report.

Saudi J Anaesth 2019 Oct-Dec;13(4):368-370

Department of Anesthesiology and Pain Medicine, Yeungnam University College of Medicine, Daegu, Korea.

During thyroid surgery, intraoperative hemodynamic instability can be attributed to episodic surges of thyroid hormones. Thyroid storms are emergency situations characterized by persistent hypertension, tachycardia, hyperthermia, and end-organ damage. However, baroreflex-mediated neurogenic phenomena due to surgical procedures near the carotid sinus are a likely cause of acute hemodynamic changes during thyroid surgery. We describe a case of sudden hemodynamic instability occurring after thyroid manipulation during thyroidectomy in a 61-year-old man who presented with a 6-cm-sized thyroid mass in a euthyroid state.
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http://dx.doi.org/10.4103/sja.SJA_76_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6753765PMC
October 2019

Patient-derived lung cancer organoids as in vitro cancer models for therapeutic screening.

Nat Commun 2019 09 5;10(1):3991. Epub 2019 Sep 5.

Asan Center for Cancer Genome Discovery, Asan Institute for Life Sciences, Seoul, South Korea.

Lung cancer shows substantial genetic and phenotypic heterogeneity across individuals, driving a need for personalised medicine. Here, we report lung cancer organoids and normal bronchial organoids established from patient tissues comprising five histological subtypes of lung cancer and non-neoplastic bronchial mucosa as in vitro models representing individual patient. The lung cancer organoids recapitulate the tissue architecture of the primary lung tumours and maintain the genomic alterations of the original tumours during long-term expansion in vitro. The normal bronchial organoids maintain cellular components of normal bronchial mucosa. Lung cancer organoids respond to drugs based on their genomic alterations: a BRCA2-mutant organoid to olaparib, an EGFR-mutant organoid to erlotinib, and an EGFR-mutant/MET-amplified organoid to crizotinib. Considering the short length of time from organoid establishment to drug testing, our newly developed model may prove useful for predicting patient-specific drug responses through in vitro patient-specific drug trials.
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http://dx.doi.org/10.1038/s41467-019-11867-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6728380PMC
September 2019
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