• Journal of Korean Neurosurgical Society
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• v.67 no.4
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• pp.467-476
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• 2024

Objective : To evaluate the usefulness of a cranial implantable chemoport, the H-port, as an alternative to the Ommaya reservoir for intraventricular chemotherapy/cerebrospinal fluid (CSF) access in patients with leptomeningeal metastasis (LM). Methods : One hundred fifty-two consecutive patients with a diagnosis of LM and who underwent H-port installation between 2015 and 2021 were evaluated. Adverse events associated with installation and intraventricular chemotherapy, and the rate of increased intracranial pressure (ICP) control via the port were evaluated for safety and efficacy. These indices were compared with published data of Ommaya (n=89), from our institution. Results : Time-to-install and installation-related complications of intracranial hemorrhage (n=2) and catheter malposition (n=5) were not significantly different between the two groups. Intraventricular chemotherapy-related complications of CSF leakage occurred more frequently in the Ommaya than in the H-port group (13/89 vs. 3/152, respectively, p<0.001). Intracranial hemorrhage during chemotherapy occurred only in the Ommaya group (n=4). The CSF infection rate was not statistically different between groups (14/152 vs. 12/89, respectively). The ICP control rate according to reservoir type revealed a significantly higher ICP control rate with the H-port (40/67), compared with the Ommaya result (12/58, p<0.001). Analyzing the ICP control rate based on the CSF drainage method, continuous extraventricular drainage (implemented only with the H-port), found a significantly higher ICP control rate than with intermittent CSF drainage (33/40 vs. 6/56, respectively, p<0.0001). Conclusion : The H-port for intraventricular chemotherapy in patients with LM was superior for ICP control; it had equal or lower complication rates than the Ommaya reservoir.

• IMMUNE NETWORK
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• v.22 no.1
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• pp.8.1-8.20
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• 2022

Rheumatoid arthritis (RA) is a representative autoimmune disease that is primarily characterized by persistent inflammation and progressive destruction of synovial joints. RA has a complex and heterogeneous pathophysiology, involving interactions among various immune and joint stromal cells and a diverse network of cytokines and intracellular signaling pathways. With improved understanding of RA, over the past decades, therapeutic strategies have become considerably advanced and now included targeted molecular therapies, such as tumor necrosis factor inhibitors, IL-6 blockers, B-cell depletion agents, as well as inhibitors of T-cell co-stimulation and Janus kinases. However, a considerable proportion of RA patients experience refractory disease and interrupted treatment owing to the associated risk of developing serious infections and cancers. In contrast, although IL-1β, IL-17A, and p38α play significant roles in RA pathogenesis, several drugs targeting these factors have not been approved because of their low efficacy and severe adverse effects. In this review, we provide an overview of the working mechanism, advantages, and limitations of the currently available targeted drugs for RA. Additionally, we suggest potential mechanistic causes for clinically approved and failed drugs. Thus, this review provides perspectives on approaches for basic and translational studies that hold promise for identifying future next-generation therapeutics for RA.

• IMMUNE NETWORK
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• v.16 no.1
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• pp.75-84
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• 2016

Cancer is one of the leading causes of morbidity and mortality worldwide; therefore there is a need to discover new therapeutic modules with improved efficacy and safety. Immune-(cell) therapy is a promising therapeutic strategy for the treatment of intractable cancers. The effectiveness of certain chemotherapeutics in inducing immunogenic tumor cell death thus promoting cancer eradication has been reported. Ginsenoside Rg3 is a ginseng saponin that has antitumor and immunomodulatory activity. In this study, we treated tumor cells with Rg3 to verify the significance of inducing immunogenic tumor cell death in antitumor therapy, especially in DC-based immunotherapy. Rg3 killed the both immunogenic (B16F10 melanoma cells) and non-immunogenic (LLC: Lewis Lung Carcinoma cells) tumor cells by inducing apoptosis. Surface expression of immunogenic death markers including calreticulin and heat shock proteins and the transcription of relevant genes were increased in the Rg3-dying tumor. Increased calreticulin expression was directly related to the uptake of dying tumor cells by dendritic cells (DCs): the proportion of CRT⁺CD11c⁺cells was increased in the Rg3-treated group. Interestingly, tumor cells dying by immunogenic cell death secreted IFN-γ, an effector molecule for antitumor activity in T cells. Along with the Rg3-induced suppression of pro-angiogenic (TNF-α) and immunosuppressive cytokine (TGF-β) secretion, IFN-γ production from the Rg3-treated tumor cells may also indicate Rg3 as an effective anticancer immunotherapeutic strategy. The data clearly suggests that Rg3-induced immunogenic tumor cell death due its cytotoxic effect and its ability to induce DC function. This indicates that Rg3 may be an effective immunotherapeutic strategy.

• IMMUNE NETWORK
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• v.20 no.3
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• pp.27.1-27.11
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• 2020

Although various studies on predictive markers in the use of PD-1/PD-L1 inhibitors are in progress, only PD-L1 expression levels in tumor tissues are currently used. In the present study, we investigated whether baseline serum levels of IL-6 can predict the treatment response of patients with advanced non-small cell lung cancer (NSCLC) treated with PD-1/PD-L1 inhibitors. In our cohort of 125 NSCLC patients, the objective response rate (ORR) and disease control rate (DCR) were significantly higher in those with low IL-6 (<13.1 pg/ml) than those with high IL-6 (ORR 33.9% vs. 11.1%, p=0.003; DCR 80.6% vs. 34.9%, p<0.001). The median progression-free survival was 6.3 months (95% confidence interval [CI], 3.9-8.7) in the low IL-6 group, significantly longer than in the high IL-6 group (1.9 months, 95% CI, 1.6-2.2, p<0.001). The median overall survival in the low IL-6 group was significantly longer than in the high IL-6 group (not reached vs. 7.4 months, 95% CI, 4.8-10.0). Thus, baseline serum IL-6 levels could be a potential biomarker for predicting the efficacy and survival benefit of PD-1/PD-L1 inhibitors in NSCLC.

• Journal of Physiology & Pathology in Korean Medicine
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• v.38 no.1
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• pp.16-21
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• 2024

Haepyoijin-tang and its main components have been used for phlegm, cough and dyspnea. Using a respiratory inflammation model, we intend to reveal the anti-inflammatory effect and pharmacological mechanism of Haepyoijin-tang. We induced the respiratory inflammation model by Aspergillus oryzae protease and ovalbumin administration. Female Balb/c mice (8 weeks old) were classified into four groups as follows: saline control group, aspergillus oryzae protease and ovalbumin induced respiratory inflammation group (vehicle), inflammation with Haepyoijin-tang (200 mg/kg) administration group, inflammation with dexamethasone (5 mg/kg) administration group (n=7). To identify the anti-inflammatory effects of Haepyoijin-tang water extracts, we measured the inflammatory cell number in bronchoalveolar lavage fluid (BALF) and total live lung cell number. In addition, we checked eosinophil ratio and number in BALF. And Interleukin (IL)-5 level was also measured in lung cell culture supernatant. To confirm the mechanism of anti-inflammatory effects, we analyzed the activated helper T cell (CD4⁺CD25⁺ cell) and Th2 cell (CD4⁺GATA3⁺ cell) ratio and number in lung by using flow cytometry. Finally, we attempted to confirm the immune mechanism by measuring the ratio and number of regulatory T cells (CD4⁺Foxp3⁺ cell). Haepyoijin-tang extracts treatment diminished inflammatory cell, especially, eosinophil number in BALF and total live lung cell number. Moreover, IL-5 level was reduced in Haepyoijin-tang treated group. Surprisingly, Haepyoijin-tang extracts administration not only decreased the activated helper T cell but also Th2 cell population in lung. Additionally, regulatory T cell population was increased in Haepyoijin-tang administration group. Our findings proved that Haepyoijin-tang extract have anti-inflammatory efficacy by suppressing Th2 cell activation and promoting regulatory T cell population.

• Journal of Physiology & Pathology in Korean Medicine
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• v.38 no.2
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• pp.59-65
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• 2024

Rectal prolapse is a condition where the rectal wall protrudes outside the anus. While it is a rare condition, it can cause discomfort for patients due to the protrusion of the rectal structure, discharge of mucus and blood, fecal incontinence, constipation, and other inconveniences. In this review, we analyzed a randomized controlled trial (RCT) study that used the herbal medicine Bojungikgi-tang(Buzhongyiqi-tang) as a complementary therapy to improve the weaknesses and side effects of the standard treatment, surgical therapy, for rectal prolapse. The analysis included 12 RCT studies, and in all studies, the prescription involved the use of Astragali Radix at the highest dosage. Among the 11 studies that evaluated efficacy, 7 studies showed a significant effect compared to the control group. In all 3 studies that evaluating recurrence rates and all 5 studies investigating complications after surgery, the experimental group showed significant effects. Based on these findings, this study could be considered as a foundational evidence for the application of bojungikgi-tang(Buzhongyiqi-tang) in clinical practice in Korean medicine for patients with rectal prolapse. It could also serve as foundational data for future research.

• Korean Journal of Radiology
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• v.20 no.8
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• pp.1285-1292
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• 2019

Objective: To evaluate the safety and efficacy of the coil-protected technique for liquid embolization in neurovascular malformations. Materials and Methods: Twenty-two patients who underwent coil-protected liquid embolization for symptomatic cranial (n = 13) and spinal (n = 9) arteriovenous fistula (AVF) or arteriovenous malformations (AVMs) were identified. A total of 36 target feeder vessels were embolized with N-butyl cyanoacrylate and/or Onyx (Medtronic). This technique was used to promote delivery of a sufficient amount of liquid embolic agent into the target shunt or nidus in cases where tortuous feeding arteries preclude a microcatheter wedging techniqu and/or to prevent reflux of the liquid embolic agent in cases with a short safety margin. The procedure was considered technically successful if the target lesion was sufficiently filled with liquid embolic agent without unintentional reflux. Angiographic and clinical outcomes were retrospectively evaluated. Results: Technical success was achieved for all 36 target feeders. Post-embolization angiographies revealed complete occlusion in 16 patients and near-complete and partial occlusion in three patients each. There were no treatment-related complications. Of the six patients who showed near-complete or partial occlusion, five received additional treatments: two received stereotactic radiosurgery for cerebral AVM, two underwent surgical removal of cerebral AVM, and one underwent additional embolization by direct puncture for a mandibular AVM. Finally, all patients showed complete (n = 19) or near-complete (n = 3) occlusion of the target AVF or AVM on follow-up angiographies. The presenting neurological symptoms improved completely in 15 patients (68.2%) and partially in seven patients (31.8%). Conclusion: The coil-protected technique is a safe and effective method for liquid embolization, especially in patients with various neurovascular shunts or malformations who could not be successfully treated with conventional techniques.

• The Korean Journal of Physiology and Pharmacology
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• v.28 no.1
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• pp.21-30
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• 2024

The challenging clinical outcomes associated with advanced cervical cancer underscore the need for a novel therapeutic approach. Monensin, a polyether antibiotic, has recently emerged as a promising candidate with anti-cancer properties. In line with these ongoing efforts, our study presents compelling evidence of monensin's potent efficacy in cervical cancer. Monensin exerts a pronounced inhibitory impact on proliferation and anchorage-independent growth. Additionally, monensin significantly inhibited cervical cancer growth in vivo without causing any discernible toxicity in mice. Mechanism studies show that monensin's anti-cervical cancer activity can be attributed to its capacity to inhibit the Wnt/β-catenin pathway, rather than inducing oxidative stress. Monensin effectively reduces both the levels and activity of β-catenin, and we identify Akt, rather than CK1, as the key player involved in monensin-mediated Wnt/β-catenin inhibition. Rescue studies using Wnt activator and β-catenin-overexpressing cells confirmed that β-catenin inhibition is the mechanism of monensin's action. As expected, cervical cancer cells exhibiting heightened Wnt/β-catenin activity display increased sensitivity to monensin treatment. In conclusion, our findings provide pre-clinical evidence that supports further exploration of monensin's potential for repurposing in cervical cancer therapy, particularly for patients exhibiting aberrant Wnt/β-catenin activation.

• Molecules and Cells
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• v.47 no.1
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• pp.100004.1-100004.11
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• 2024

Insulin is essential for maintaining normoglycemia and is predominantly secreted in response to glucose stimulation by β-cells. Incretin hormones, such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide, also stimulate insulin secretion. However, as obesity and type 2 diabetes worsen, glucose-dependent insulinotropic polypeptide loses its insulinotropic efficacy, whereas GLP-1 receptor (GLP-1R) agonists continue to be effective owing to its signaling switch from Gs to Gq. Herein, we demonstrated that endoplasmic reticulum (ER) stress induced a transition from Gs to Gq in GLP-1R signaling in mouse islets. Intriguingly, chemical chaperones known to alleviate ER stress, such as 4-PBA and TUDCA, enforced GLP-1R's Gq utilization rather than reversing GLP-1R's signaling switch induced by ER stress or obese and diabetic conditions. In addition, the activation of X-box binding protein 1 (XBP1) or activating transcription factor 6 (ATF6), 2 key ER stress-associated signaling (unfolded protein response) factors, promoted Gs utilization in GLP-1R signaling, whereas Gq employment by ER stress was unaffected by XBP1 or ATF6 activation. Our study revealed that ER stress and its associated signaling events alter GLP-1R's signaling, which can be used in type 2 diabetes treatment.

• Microbiology and Biotechnology Letters
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• v.51 no.3
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• pp.223-242
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• 2023

In contrast to chemical medicines, biopharmaceuticals exhibit reduced side effects and enhanced therapeutic efficacy. Antibody therapies have significantly advanced since the first monoclonal antibody's approval in 1986, now dominating the pharmaceutical market with seven out of the top 10 biopharmaceuticals. The bispecific antibody has a distinct capability to bind to two antigens simultaneously, unlike conventional monoclonal antibodies that target just one antigen. The notion of bispecific antibodies was initially introduced in 1960, and by 1997, the first symmetrical form of bispecific antibody was successfully produced. Subsequently, extensive research has been conducted on bispecific antibodies, leading to a significant milestone in 2014 when blinatumomab became the first FDA-approved drug to treat acute lymphocytic leukemia. Despite having a relatively shorter history compared to monoclonal antibodies, bispecific antibodies have proven their potential by targeting two antigens simultaneously, thereby rendering them highly effective as anti-cancer drugs. As of 2023, there are a total of 11 globally approved bispecific antibodies, with six of them receiving approval from FDA. In light of the rapidly expanding market for bispecific antibodies, this review article comprehensively explores the attributes, historical background, applications, and market status of bispecific antibodies. Additionally, it sheds light on the present trends in bispecific antibody development, drawing insights from 96 research articles and 105 clinical studies. Excitingly, we anticipate further progress in the development of bispecific antibodies and clinical trials on a global scale, with the aspiration of utilizing them not only in cancer treatment but also for addressing diverse medical conditions.