• Bulletin of the Korean Chemical Society
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• v.35 no.7
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• pp.1939-1943
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• 2014

Solid dispersion (SD) system of everolimus (EVR) with Gelucire 50/13 (Stearoyl polyoxyl-32 glycerides) was prepared using melt granulation technique with the aim of improving the physicochemical properties and dissolution rate. The solid state characterization using scanning electron microscopy and X-ray powder diffraction, indicated that the drug was homogeneously distributed in the surfactant carrier in a stable amorphous form. The dissolution rate of EVR from the optimized SD composed of the drug, Gelucire 50/13 and microcrystalline cellulose in a weight ratio of 1:5:10, was markedly rapid and higher than that from the drug powder and the market product (Afinitor$^{(R)}$, Novartis Pharmaceuticals) in all dissolution mediums tested from pH 3.0 to pH 6.8. The results of this study suggest that formulation of SD with Gelucire 50/13 using melt granulation procedure may be a simple and promising approach for improving the dissolution rate and oral absorption of the anti-cancer agent without the need for using an organic solvent.

• Korean Journal of Clinical Pharmacy
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• v.31 no.1
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• pp.44-52
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• 2021

Background: Post-transplant immunosuppression with calcineurin inhibitors (CNIs) is associated with kidney function impairment while mammalian target of rapamycin (mTOR) inhibitors, such as everolimus, can be used for its renal-sparing effects. In this study, we compared the efficacy and safety of everolimus with low dose tacrolimus (EVR+Low TAC) and conventional dose tacrolimus (TAC) in liver transplantation recipients. Methods: Medical records of recipients who received liver transplantation at Seoul National University Bundang Hospital from January 1st 2009 to December 31st 2018 were retrospectively reviewed. Cohort entry date was defined as the day everolimus was initiated and tacrolimus dosage was reduced. All patients were followed up for 1 year. Indicator of efficacy was the incidence of rejection and safety was evaluated by incidence of drug adverse events including renal function. Results: Among 118 patients, there were 40 patients (33.9%) in EVR+Low TAC group. Incidence of rejection, including both biopsy proven acute rejection and clinical rejection, was similar in two groups [7.5% (n=3) vs. 6.4% (n=5), p=1.000]. Renal dysfunction was less frequent in EVR+Low TAC [17.5% (n=7) vs. 35.9% (n=28), p=0.038]. However, incidence rates of dyslipidemia, oral ulcer were more frequent in EVR+Low TAC [45.0% (n=18) vs. 21.8% (n=17), p=0.009; 15.0% (n=6) vs. 1.3% (n=1), p=0.006]. Conclusions: In terms of prevention of rejection, EVR+Low TAC was as effective as TAC and had renal-sparing effect but was associated with increased risk of dyslipidemia and oral ulcer. This study demonstrates that EVR+Low TAC could be an alternative to liver transplant recipients with nephrotoxicity after administration of conventional dose tacrolimus.

• Journal of Biomedical Engineering Research
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• v.34 no.2
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• pp.69-72
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• 2013

The goal of this study is to develop test method for evaluating the drug eluting properties of drug eluting stents (DES). PBS and the detergent solutions, presented by each DES manufacturer, were used for drug release of DES coated with paclitaxel, zotarolimus and everolimus. The drugs which are coating DES were not released by PBS but released by the detergent solutions, finally paclitaxel 83.38%, zotarolimus 103.85% and everolimus 115.78%. It seems that the use of the detergents is necessary in order to release the drugs because those drugs are extremely hydrophobic. In conclusion, using of detergent solutions presented by each manufacturer were suitable for evaluating the drug eluting property of drug eluting stent.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.24 no.5
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• pp.413-422
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• 2021

Intestinal lymphangiectasia is a rare disease which is causing protein-losing enteropathy. Treatment of intestinal lymphangiectasia can be a challenge for clinicians because of the lack of specific guidelines regarding pharmacological indications. We sought to introduce a diagnostic approach and suggest guidelines for treatment. After exclusion of secondary intestinal lymphangiectasia, magnetic resonance lymphangiography is a promising tool for the assessment of abnormal lymphatic lesions in primary intestinal lymphangiectasia. Determining the extent of the lesion provides direction for treatment options. Focal short-segment intestinal lymphangiectasia can be treated via intestinal resection or radiologic embolization after dietary therapy failure. Diffuse intestinal lymphangiectasia and extensive lymphangiectasia should be treated with several drugs with a full understanding of their mechanisms.

• Journal of Physiology & Pathology in Korean Medicine
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• v.26 no.2
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• pp.228-233
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• 2012

Two years ago, a 75-year-old female was diagnosed left renal cancer and went on radical nephrectomy. Recently, metastatized lesions on lumbar spine and various lymph nodes including paraaortic lymph node of which diameter was about 5.5 cm was identified. She suffered from extreme low back pain despite using opioid agents of fentanyl patch and oral oxycodone. During about one month, Korean medicine therpies including herbal medicine(Yang-He tang), acupuncture with her conventional medications were co-administered. However her pain didn't improved and gradual cough and dyspnea developed. So she transferred to the hemato-oncology part for 2 weeks under the diagnosis of everolimus-induced noninfectious pneumonitis. After quitting everolimus her pneumonitis was improved and she came back our ward and started another herbal medicine, Ai-Tong-Ning tang for about 2 months. During this period, her pain was well managed without oral opioid agents and her paraaortic lymph node was regressed to about 2.2cm in diameter.

• Journal of the Korean Child Neurology Society
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• v.26 no.4
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• pp.284-287
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• 2018

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutation of one of two genes, TSC1 (encoding hamartin, 9q34) and TSC2 (encoding tuberin, 16p13). It invades the central nervous system and various parts of the body, causing various symptoms. Crohn's disease (CD) is a chronic immune-mediated disease that has not been clearly elucidated. It is thought to be caused by an excessive immune response of the body to bacteria that normally exist in the digestive tract with genetic factors. No cases have been reported in which both of the above-mentioned diseases occurred simultaneously. We report a case of CD in a patient with TSC. A 12-year-old boy was brought to our hospital because of abdominal pain. Skin lesions were observed in the TSC. Fundus examination revealed a hamartoma in the right retina. Brain magnetic resonance imaging revealed a subendothelial giant cell astrocytoma (SEGA). On the basis of these findings, he was diagnosed as having TSC. Blood test results showed increased levels of inflammatory markers. On abdominal ultrasonography, his colon walls were observed to be thickened with increased vascularity of the proximal ascending colon, ileocecal valve, and terminal ileum. Colonoscopy revealed discontinuous ulcerations and inflammations of the ileum, IC valve, and cecum, similar to those found in CD. Everolimus was administered orally for the SEGA but was discontinued frequently owing to the exacerbation of CD. The possibility of CD should be kept in mind in patients with TSC considering to undergo treatment for SEGA.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2151-2159
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• 2015

Pancreatic neuroendocrine tumors (pNETs) are rare and heterogenous tumors and surgery to remove the primary tumor is the mainstay of treatment for resectable disease. However, curative surgery is often not feasible, because half of patients with pNET have metastases at the time of diagnosis. Palliative dubulking surgery and liver-directed therapies are appropriate options for these patients. Streptozocin-based regimens are standard, although temozolamide-based treatments are rapidly gaining wide clinical application. Somatostatin analogs are mainly indicated in hormonally active tumors to ameliorate symptoms. In addition, anti-tumoral activity has been proven in well-differentiated NETs. Recently, there has been tremendous progress in the molecular biology of pNETs; thereby, the efficacy of sunitinib and everolimus in the treatment of patients with metastatic pNETs has been proven by large placebo-controlled phase III trials. Currently, there are no definitively proven predictive biomarkers to evaluate response to medical therapies in patients with pNET. Therefore, further studies are needed to individualize and optimize their management. This article reviews systemic chemotherapy, targeted therapies, and anti-secretory treatments for the management of patients with unresectable or metastatic pNETs, summarized in the light of recent advances.

• Journal of Oral Medicine and Pain
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• v.42 no.1
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• pp.20-24
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• 2017

Drug-induced gingival overgrowth (DIGO) is an adverse drug reaction mainly described with three types of commonly prescribed drugs, namely, calcium channel blockers (CCBs) (nifedipine, diltiazem, and verapamil), anti-convulsants (phenytoin), and immunosuppressive agents (cyclosporine). Numerous reports have associated gingival overgrowth with the newer generation of immunosuppressive agents (tacrolimus, sirolimus, and everolimus), and CCBs (amlodipine, felodipine, nicardipine, and manidipine). Especially, patients concomitantly medicated with an immunosuppressive agent and CCB have a higher DIGO chance. Dentists need to be aware of drugs that induce gingival overgrowth, the possibility of DIGO, and risk factors, and also prevent the progression of DIGO by early detection of DIGO, consultation about the drug change, and the maintenance of strict dental hygiene regimes.

• Journal of Digestive Cancer Research
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• v.4 no.2
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• pp.51-57
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• 2016

The epidemiology of pancreatic neuroendocrine neoplasms (PNENs) in Asia has been clarified through epidemiological studies, including one conducted in Japan, and subsequently another in South Korea. As endoscopic ultrasonography (EUS) has become more widely accessible, endoscopic ultrasound-fine needle aspiration (EUS-FNA) has been performed in pancreatic tumors for which the clinical course was only monitored previously. This has enabled accurate diagnosis of pancreatic tumors based on the 2010 WHO classification; as a result, the number of patients with an accurate diagnosis has increased. Although surgery has been the standard therapy for PNENs, new treatment options have become available in Japan for the treatment of advanced or inoperable PNENs; of particular note is the recent introduction of molecular target drugs (such as everolimus and sunitinib) and streptozocin. Treatment for progressive PNENs needs to be selected for each patient with consideration of the performance status, degree of tumor differentiation, tumor mass, and proliferation rate. Somatostatin receptor (SSTR)-2 is expressed in many patients with neuroendocrine tumor. Somatostatin receptor scintigraphy (SRS), which can visualize SSTR-2 expression, has been approved in Japan. The SRS will be a useful diagnostic tool for locating neuroendocrine neoplasms, detecting distant metastasis, and evaluating therapy outcomes. In this manuscript, we review the latest diagnostic methods and treatments for PNENs.

• Journal of the Korean Society of Radiology
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• v.14 no.3
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• pp.319-336
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• 2020

The purpose of this study was to compare the outcomes of two interventional methods, overlapping drug-eluting stents (DES) and long DES, for long-term clinical outcomes in patients with acute myocardial infarction (AMI). A total of 438 patients with AMI (65.9±11.0 years, 306 males) from June 2008 to March 2019 who had diffuse long coronary artery lesion, more than 30mm were divided into two groups; group I (overlapped DES group; n=140) and group II (long DES group; n=298). We compared the incidences of major adverse cardiac events [MACEs; cardiac death, myocardial infaction (MI), target lesion revascularization (TLR) and stent thrombosis (ST)] during 12 months between the two groups. Everolimus-eluting stent was more commonly used in group II than in group I (28.1% vs. 51.8% p<0.001). Mean lesion diameter was slightly longer in group II (3.1±0.3mm vs. 3.2±0.3mm, p=0.042), and prevalence of ACC/AHA lesion type C was higher in group I (41.7% vs. 25.4%, p<0.001). Incidences of MACEs during 12 months were higher in group I than group II (18.5% vs. 14.4%, p=0.034). The rates of cardiac death (2.1% vs. 4.4%, p=0.667), MI (5.0% vs. 2.7%, p=0.260) and stent thrombosis rate (0.7% vs. 1.7%, p=0.669) were similar between the two groups. However, TLR rate was higher in group I (10.7% vs. 5.6%, p=0.041). In multivariate logistic regression analysis, presence of diabetes mellitus [Hazard ratio (HR) 2.383, 95% confidence interval (CI) 1.332-4.260, p=0.003] and use of paclitaxel-eluting stent (HR) 2.367, 95% CI 1.371-4.086, p=0.002) were independent predictors of 12-month MACEs, without significant differences in prevalence between the two groups. In AMI patients with diffuse long lesion, TLR rate was higher in the overlapped DES group during 12-month follow-up. Presence of diabetes and use of paclitaxel-eluting stent were independent predictors of MACEs.