• Journal of Gastric Cancer
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• v.23 no.1
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• pp.224-249
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• 2023

Gastric cancer is heterogeneous in morphology, biology, genomics, and treatment response. Alterations in human epidermal growth factor receptor 2 (HER2) overexpression, microsatellite instability (MSI) status, programmed death-ligand 1 (PD-L1) levels, and fibroblast growth factor receptor 2 (FGFR2) can be used as biomarkers. Since the combination of fluoropyrimidine/platinum plus trastuzumab that was investigated in the ToGA trial was approved as a standard of care in HER2-positive patients in 2010, no other agents showed efficacy in the first- (HELOISE, LOGiC, JACOB trials) and second- (TyTAN, GATSBY, T-ACT trials) line treatments. Despite the success in treating breast cancer, various anti-HER2 agents, including a monoclonal antibody (pertuzumab), an antibody-drug conjugate (ADC; trastuzumab emtansine [T-DM1]), and a small molecule (lapatinib) failed to translate into clinical benefits until the KEYNOTE-811 (first-line) and DESTINY-Gastri01 (≥second-line) trials were conducted. The incorporation of HER2-directed treatment with immune checkpoint inhibitors in the form of a monoclonal antibody or ADC is now approved as a standard treatment. Despite the promising results of new agents (engineered monoclonal antibodies, bi-specific antibodies, fusion proteins, and small molecules) in the early phase of development, the management of HER2-positive gastric cancer requires further optimization to achieve precision medicine with a chemotherapeutic backbone. Treatment resistance is a complex process that can be overcome using a combination of chemotherapy, targeted agents, and immune checkpoint inhibitors, including novel agents. HER2 status must be reassessed in patients undergoing anti-HER2 treatment with disease progression after the first-line treatment. As a general guideline, patients who need systemic treatment should receive chemotherapy plus targeted agents, anti-angiogenic agents, immune checkpoint inhibitors, or their combinations.

• Molecules and Cells
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• v.45 no.12
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• pp.923-934
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• 2022

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have great potential in applications such as regenerative medicine, cardiac disease modeling, and in vitro drug evaluation. However, hPSC-CMs are immature, which limits their applications. During development, the maturation of CMs is accompanied by a decline in their proliferative capacity. This phenomenon suggests that regulating the cell cycle may facilitate the maturation of hPSC-CMs. Aurora kinases are essential kinases that regulate the cell cycle, the role of which is not well studied in hPSC-CM maturation. Here, we demonstrate that CYC116, an inhibitor of Aurora kinases, significantly promotes the maturation of CMs derived from both human embryonic stem cells (H1 and H9) and iPSCs (induced PSCs) (UC013), resulting in increased expression of genes related to cardiomyocyte function, better organization of the sarcomere, increased sarcomere length, increased number of mitochondria, and enhanced physiological function of the cells. In addition, a number of other Aurora kinase inhibitors have also been found to promote the maturation of hPSC-CMs. Our data suggest that blocking aurora kinase activity and regulating cell cycle progression may promote the maturation of hPSC-CMs.

• Journal of Ginseng Research
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• v.47 no.1
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• pp.65-73
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• 2023

Background: Age-related macular degeneration (AMD) is a significant visual disease that induces impaired vision and irreversible blindness in the elderly. However, the effects of ginseng berry extract (GBE) on the retina have not been studied. Therefore, this study aimed to investigate the protective effects of GBE on blue light (BL)-induced retinal damage and elucidate its underlying mechanisms in human retinal pigment epithelial cells (ARPE-19 cells) and Balb/c retina. Methods: To investigate the effects and underlying mechanisms of GBE on retinal damage in vitro, we performed cell viability assay, pre-and post-treatment of sample, reactive oxygen species (ROS) assay, quantitative real-time PCR (qRT-PCR), and western immunoblotting using A2E-laden ARPE-19 cells with BL exposure. In addition, Balb/c mice were irradiated with BL to induce retinal degeneration and orally administrated with GBE (50, 100, 200 mg/kg). Using the harvested retina, we performed histological analysis (thickness of retinal layers), qRT-PCR, and western immunoblotting to elucidate the effects and mechanisms of GBE against retinal damage in vivo. Results: GBE significantly inhibited BL-induced cell damage in ARPE-19 cells by activating the SIRT1/PGC-1α pathway, regulating NF-kB translocation, caspase 3 activation, PARP cleavage, expressions of apoptosis-related factors (BAX/BCL-2, LC3-II, and p62), and ROS production. Furthermore, GBE prevented BL-induced retinal degeneration by restoring the thickness of retinal layers and suppressed inflammation and apoptosis via regulation of NF-kB and SIRT1/PGC-1α pathway, cleavage of caspase 3 and PARP, and expressions of apoptosis-related factors in vivo. Conclusions: GBE could be a potential agent to prevent dry AMD and progression to wet AMD.

• Journal of Chest Surgery
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• v.56 no.5
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• pp.353-358
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• 2023

Background: Malignant pleural effusion affects many patients with advanced cancer. When chemotherapy or radiotherapy fails to relieve malignant pleural effusion and related symptoms, drainage and pleurodesis can help. Although surgical talc pleurodesis is the most widely used method, Viscum album, which has been recently used in surgical or bedside procedures, has demonstrated significant results and is as effective as talc. This study aimed to determine the most effective agent and procedure. Methods: Between January 2015 and July 2022, chemical pleurodesis was performed in 137 patients with malignant pleural effusion, using a V. album surgical procedure in 48, a V. album bedside procedure in 55, and a talc surgical procedure in 34 patients. We reviewed patients' clinical responses and disease progression after chemical pleurodesis. Results: The success rate was not significantly different among the V. album surgical procedures (91.7%), V. album bedside procedures (83.6%), and talc surgical procedures (91.2%). However, the total drainage amount and tube insertion duration in both Viscum groups were more effective than those in the talc group. Furthermore, the bedside Viscum group showed significantly lower post-pleurodesis pain scores than the other 2 groups. Conclusion: According to our results, talc and V. album can be considered ideal agents for chemical pleurodesis. However, Viscum pleurodesis showed safer outcomes in terms of ensuring quality of life than talc. Additionally, the bedside Viscum group showed significantly lower pain scores than the other groups. Hence, patients for whom surgical procedures are inappropriate can undergo bedside Viscum pleurodesis without diminishing the therapeutic effect.

• BMB Reports
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• v.56 no.2
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• pp.114-119
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• 2023

Liver fibrosis is caused by chronic liver damage and results in the aberrant accumulation of extracellular matrix during disease progression. Despite the identification of the HAT enzyme p300 as a major factor for liver fibrosis, the development of therapeutic agents targeting the regulation of p300 has not been reported. We validated a novel p300 inhibitor (A6) on the improvement of liver fibrosis using two mouse models, mice on a choline-deficient high-fat diet and thioacetamide-treated mice. We demonstrated that pathological hall-marks of liver fibrosis were significantly diminished by A6 treatment through Masson's trichrome and Sirius red staining on liver tissue and found that A6 treatment reduced the expression of matricellular protein genes. We further showed that A6 treatment improved liver fibrosis by reducing the stability of p300 protein via disruption of p300 binding to AKT. Our findings suggest that targeting p300 through the specific inhibitor A6 has potential as a major therapeutic avenue for treating liver fibrosis.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.2
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• pp.167-176
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• 2023

This study aims to explore the impact of Rehmannioside D (RD) on ovarian functions of rats with diminished ovarian reserve (DOR) and its underlying mechanisms of action. A single injection of cyclophosphamide was performed to establish a DOR rat model, and fourteen days after the injection, the rats were intragastrically administrated with RD for two weeks. Rat estrus cycles were tested using vaginal smears. Ovarian tissues were histologically evaluated, the number of primordial, mature, and atretic follicles was calculated, and the apoptotic rate of granulosa cells. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E₂) levels were determined by ELISA assays. Protein levels of Forkhead Box O1 (FOXO1), KLOTHO, Bcl-2, and Bax were investigated in ovarian tissues of DOR rats. The binding between FOXO1 and KLOTHO was verified by ChIP assay. High-dose administration of RD into DOR rats improved their estrus cycles, increased ovarian index, enhanced the number of primordial and mature follicles, reduced the number of atretic follicle number, and ovarian granulosa cell apoptosis in addition to inhibiting FSH and LH levels and upregulating E₂ expression. FOXO1 and KLOTHO were significantly suppressed in DOR rats. FOXO1 knockdown partially suppressed the protective effects of RD on DOR rats, and KLOTHO overexpression could restore RD-induced blockade of DOR development despite knocking down FOXO1. FOXO1 antibody enriched KLOTHO promoter, and the binding between them was reduced in DOR group compared to that in sham group. RD improved ovarian functions in DOR rats and diminished granulosa cell apoptosis via the FOXO1/KLOTHO axis.

• Korean Journal of Exercise Nutrition
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• v.23 no.3
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• pp.39-44
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• 2019

[Purpose] Weight loss can reduce obesity-induced arterial stiffening that is attributed to decreased inflammation. Angiopoietin-like protein 2 (ANGPTL2) is a pro-inflammatory adipokine that is upregulated in obesity and is important in the progression of atherosclerosis and cardiovascular disease. The purpose of this study is to investigate the effects of dietary modification on circulating ANGPTL2 levels and arterial stiffness in overweight and obese men. [Methods] Twenty-two overweight and obese men (with mean age of 56 ± 2 years and body mass index of 28.6 ± 2.6 kg/m²) completed a 12-week dietary modification program. We measured the arterial compliance and β-stiffness index (as the indices of arterial stiffness) and serum ANGPTL2 levels before and after the program. [Results] After the 12-week dietary modification, body mass and daily energy intake were significantly reduced. Arterial compliance was significantly increased and β-stiffness index was significantly decreased after the 12-week dietary modification program. Serum ANGPTL2 levels were significantly decreased. Also, the changes in arterial compliance were negatively correlated with the changes in serum ANGPTL2 levels, whereas the changes in β-stiffness index were positively correlated with the changes in serum ANGPTL2 levels. [Conclusion] These results suggest that the decrease in circulating ANGPTL2 levels can be attributed to the dietary modification-induced reduction of arterial stiffness in overweight and obese men.

• Journal of Digestive Cancer Research
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• v.6 no.2
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• pp.73-77
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• 2018

A 70-year-old female diagnosed with pancreatic ductal adenocarcinoma was treated by pylorus-preserving pancreaticoduodenectomy (PPPD) and adjuvant concurrent chemoradiotherapy with 5-fluorouracil. Pancreatic ductal adenocarcinoma pT3N0 (stage IIA) was pathologically confirmed. Abdominal computed tomography (CT) findings 14 months after PPPD showed 10 mm sized solitary liver metastasis in segment 3. After 12 cycles of gemcitabine and 9 cycles of capecitabine plus oxaliplatin, the metastatic nodule increased in size to 27 mm. Tumorectomy at segment 3 of liver was done. 25 months after tumorectomy, chest CT showed 23 mm sized cavitary nodule in right upper lobe of lung. The result of percutaneous biopsy favored metastatic adenocarcinoma. Two sets of stereotactic body radiation therapy were done and the patient has survived without further disease progression for 6 years after initial diagnosis. This case suggests that selected population of recurrent pancreatic cancer patients with solitary liver or pulmonary metastasis can be treated by resection of metastatic site and ablative therapies.

• Journal of Digestive Cancer Research
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• v.5 no.1
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• pp.66-69
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• 2017

Approximately 40% of patients with colorectal cancer have metastatic lesions at the time of diagnosis, and chemotherapy is generally prescribed for these patients. Though several drugs are used, 5-FU has long been the backbone of chemotherapy for colorectal cancer. Capecitabine is an oral 5-FU prodrug approved by the FDA in 2005 and is used alone or in combination for treatment of colorectal cancer. Recently, capecitabine has been used for a number of off-label indications, including the treatment of advanced or metastatic colorectal cancer. Here, we report a rare case of a 59-year-old woman, diagnosed with metastatic colorectal cancer who first presented with abdominal discomfort and dyspepsia. She showed a partial response to palliative first line FOLFOX chemotherapy, which had to be stopped due to peripheral neuropathy, as a side effect. She was next put on a second line chemotherapy regimen with capecitabine alone, since then she showed good treatment response without any disease progression.

• Journal of the Korean Society of Radiology
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• v.82 no.1
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• pp.261-266
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• 2021

Ischemic stroke is one of the manifestations of reversible cerebral vasoconstriction syndrome (RCVS). Many precipitants and associated disorders of RCVS have been suggested. However, few case reports have indicated an association between anemia and RCVS. Here, we report a case of a 66-year-old female with severe iron deficiency anemia (IDA), who presented with ischemic stroke and cerebral vasoconstriction, which gradually improved with conservative treatment. High-resolution vessel wall magnetic resonance imaging findings and reversibility suggested the possibility of RCVS. In patients with RCVS and ischemic stroke, IDA should be considered. Prompt management should be delivered to prevent disease progression and recurrence.