• IMMUNE NETWORK
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• v.3 no.2
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• pp.96-102
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• 2003

Background: Granulocyte-macrophage colony-stimulating factor (GM-CSF) gene-transduced tumor cell vaccines induce very potent systemic anti-tumor immunity in preclinical and clinical models. Our previous phase I clinical trial in patients with metastatic renal cell carcinoma (RCC) has demonstrated both immune cell infiltration at vaccine sites and T cell-mediated delayed-type hypersensitivity (DTH) response to whole tumor cell vaccines. Methods: To investigate the immune responses to autologous genetically- modified tumor cell vaccines, tumor-specific $CD8^+$ T cell lines were generated from peripheral blood lymphocytes (PBL) of a RCC patient 1.24 by repeated in vitro stimulation with either B7.1-transduced autologous RCC tumor cells or B7.1-transduced autologous tumor cells treated with interferon gamma ($IFN{\gamma}$), and cloned by limiting dilution. Results: Among several RCC-specific cytotoxic T lymphocytes (CTLs), a $CD4^+/CD8^+$ double positive T cell clone (17/A2) appeared to recognize $IFN{\gamma}$-treated autologous RCC restricted by HLA-B39. The 17/A2 also recognized other HLA-B39 positive RCC tumor cells after $IFN{\gamma}$ treatment. Conclusion: These results demonstrate that autologous RCC vaccination successfully generates the tumor-specific CTL 17/A2, and suggest that the presentation and recognition of the tumor antigen by the 17/A2 might be upregulated by $IFN{\gamma}$.

• Radiation Oncology Journal
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• v.20 no.1
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• pp.53-61
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• 2002

Purpose : To determine the optimal scheme of postoperative chemoradiotherapy in rectal cancer by comparing survival, Patterns of failure, toxicities in early and late radiotherapy groups using a Phase III randomized prospective clinical trial. Materials and Methods : From January 1996 to March 1999, 307 patients with curatively resected AJCC stage II and III rectal cancer were assigned randomly to an 'early (151 patients, arm 1)' or a 'late (156 patients, arm II)' and were administered combined chemotherapy (5-FU $375\;mg/m^2/day$, leucovorin $20\;mg/m^2$, IV bolus daily, for 3 days with RT, 5 days without RT, 8 cycles with 4 weeks interval) and radiation therapy (whole pelvis with 45 Gy/25 fractions/5 weeks). Patients of arm I received radiation therapy from day 1 of the first cycle of chemotherapy and those of arm II from day 57 with a third cycle of chemotherapy. The median follow-up period of living patients was 40 months. Results : Of the 307 patients enrolled, fifty patients did not receive scheduled radiation therapy or chemotherapy. The overall survival rate and disease free survival rate at 5 years were $78.3\%\;and\;68.7\%$ in arm I, and $78.4\%\;and\;67.5\%$ in arm II. The local recurrence rate was $6.6\%\;and\;6.4\%$ (p=0.46) in arms I and II, respectively, no significant difference was observed between the distant metastasis rates of the two arms ($23.8\%\;and\;29.5\%$, p=0.16). During radiation therapy, grade 3 diarrhea or more, by the NCI common toxicity criteria, was observed in $63.0\%\;and\;58.2\%$ of the respective arms (p=N.S.), but most were controlled with supportive care. Hematologic toxicity (leukopenia) greater than RTOG grade 2 was found in only $1.3\%\;and\;2.6\%$ of patients in each respective arm. Conclusion : There was no significant difference in survival, patterns of failure or toxicities between the early and late radiation therapy arms. Postoperative adjuvant chemoradiation was found to be a relatively safe treatment but higher compliance is needed.

• The Korean journal of internal medicine
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• v.33 no.6
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• pp.1224-1233
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• 2018

Background/Aims: The objective of this study was to determine the efficacy and safety of add-on therapy with certolizumab pegol (CZP) in active rheumatoid arthritis (RA) patients of a single ethnicity. Methods: In this 24-week, phase 3, randomized, double-blind, placebo-controlled trial, eligible patients (n = 127) were randomized 2:1 to subcutaneous CZP + methotrexate (MTX; 400 mg at week 0, 2, and 4 followed by 200 mg every 2 weeks) or placebo + MTX. Results: At week 24, the American College of Rheumatology criteria for 20% (ACR20) response rate was significantly greater with CZP + MTX than with placebo (66.7% vs. 27.5%, p < 0.001). Differences in ACR20 response rates for CZP vs. placebo were significant from week 1 (p < 0.05) and remained significant through week 24. The CZP group reported significant improvement in physical function and disability compared to the placebo group (p < 0.001) at week 24, as assessed by Korean Health Assessment Questionnaire-Disability Index (KHAQ-DI). Post hoc analysis indicated that the proportion of patients who had ACR70 responses, Disease Activity Score 28 (DAS28) low disease activity, and DAS28 remission at week 24 was greater in CZP + MTX-treated patients who achieved a decrease in DAS28 ${\geq}1.2$ (43.8%) at week 4 than in nonresponders. Among 18 (22.2%) and 14 patients (35.0%) in CZP and placebo groups who had latent tuberculosis (TB), none developed active TB. Most adverse events were mild or moderate. Conclusions: CZP treatment combined with MTX in active RA patients with moderate to severe disease activity and an inadequate response to MTX resulted in rapid onset of efficacy, which is associated with better clinical outcome at week 24 and has an acceptable safety profile, especially in an intermediate TB-burden population.

• Journal of Chest Surgery
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• v.35 no.4
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• pp.267-273
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• 2002

Background: We performed a phase IV clinical trial to examine the usefulness of a continuous infusion of nicardipine hydrochloride to control hypertension in patients with acute aortic dissection. material and Method: Systolic/diastolic blood pressure, and heart rate were monitored before and after the intravenous administration of nicardipine in 31 patients with aortic diseases. The period of nicardipine administration in each patient was from 3 to 14 days. Efficacy was evaluated by determining the average amount of blood pressure reduction on the 3rd day of drug administration. The dosage of another antihypertensive agent was slowly tapered down, and ultimately replaced by the test drug. Result: 28 patients were diagnosed as acute aortic dissection, 2 patients as rupture of the aortic arch aneurysm, and 1 patient as traumatic aortic rupture. Mean age was 53.9 $\pm$ 14.9(29~89) years, and 21 patients(67.7%) were male. 14 patients(32.3%) had complications associated with underlying aortic disease: aortic insufficiency in 7, hemopericardium in 6, acute renal failure in 1, paraplegia in 1, lower extremity ischemia in 1, and hemothorax in 1. The time needed to reach the target blood pressure was within 15 minutes in 16, from 15 to 30 minutes in 10, from 30 to 45 minutes in 3 and from 45 to 60 minutes in 2, and their baseline average systolic, diastolic, and mean arterial blood pressures(mmHg) were 147$\pm$23, 82.3$\pm$ 18.6, and 104 $\pm$ 18, respectively. Average systolic, diastolic, and mean arterial blood pressures(mmHg) on the third day of nicardipine infusion were 119$\pm$ 12, 69$\pm$9, and 86$\pm$8, and they all showed statistically significant decrease(p<0.05). The average systolic, diastolic, and mean arterial blood pressure(mmHg) after the discontinuation of the nicardipine infusion were 119 $\pm$ 15, 71 $\pm$ 14, and 86$\pm$ 13, respectively. No significant difference was observed between the average pressures measured on the third day and those measured after the discontinuation of the nicardipine infusion, and no definite side effects were observed during the study period. Conclusion: Nicardipine hydrochloride was both effective and safe at controlling blood pressure in patients with acute aortic dissection.

• Korean Journal of Radiology
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• v.25 no.2
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• pp.179-188
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• 2024

Objective: ¹⁷⁷Lutetium [Lu] Ludotadipep is a novel prostate-specific membrane antigen targeting therapeutic agent with an albumin motif added to increase uptake in the tumors. We assessed the biodistribution and dosimetry of [¹⁷⁷Lu]Ludotadipep in patients with metastatic castration-resistant prostate cancer (mCRPC). Materials and Methods: Data from 25 patients (median age, 73 years; range, 60-90) with mCRPC from a phase I study with activity escalation design of single administration of [¹⁷⁷Lu]Ludotadipep (1.85, 2.78, 3.70, 4.63, and 5.55 GBq) were assessed. Activity in the salivary glands, lungs, liver, kidneys, and spleen was estimated from whole-body scan and abdominal SPECT/CT images acquired at 2, 24, 48, 72, and 168 h after administration of [¹⁷⁷Lu]Ludotadipep. Red marrow activity was calculated from blood samples obtained at 3, 10, 30, 60, and 180 min, and at 24, 48, and 72 h after administration. Organand tumor-based absorbed dose calculations were performed using IDAC-Dose 2.1. Results: Absorbed dose coefficient (mean ± standard deviation) of normal organs was 1.17 ± 0.81 Gy/GBq for salivary glands, 0.05 ± 0.02 Gy/GBq for lungs, 0.14 ± 0.06 Gy/GBq for liver, 0.77 ± 0.28 Gy/GBq for kidneys, 0.12 ± 0.06 Gy/GBq for spleen, and 0.07 ± 0.02 Gy/GBq for red marrow. The absorbed dose coefficient of the tumors was 10.43 ± 7.77 Gy/GBq. Conclusion: [¹⁷⁷Lu]Ludotadipep is expected to be safe at the dose of 3.7 GBq times 6 cycles planned for a phase II clinical trial with kidneys and bone marrow being the critical organs, and shows a high tumor absorbed dose.

• The Journal of Internal Korean Medicine
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• v.40 no.3
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• pp.458-477
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• 2019

Objectives: This study aimed to investigate the trend in the research on alcoholic liver disease (ALD) using Korean traditional medicine. Methods: This review was conducted using six electronic databases (NDSL, KMBASE, Koreantk, KISS, KISTI, and KoreaMed) with no restrictions in year. The search terms were "alcoholic liver disease", "alcoholic fatty liver", "alcoholic hepatitis", "alcoholic cirrhosis", "herbal medicine", "acupuncture" and "traditional medicine". The searched studies were analyzed according to the type of research. Results: After screening, 37 studies were selected among 552. The types of studies were as follows: 8 in vivo studies, 17 case reports, 7 case series, 1 assessment scale study, 1 randomized controlled trial, and 3 research reviews. The in vivo studies reported the efficacy and its mechanism in the animal phase of single or complex herbal medicine. In the clinical research, interventions such as herbal medicine and acupuncture were most commonly used for ALD treatment. Conclusions: We analyzed the trends in ALD treatment using Korean traditional medicine through this review. The results showed that Korean traditional medicine could be an effective method for ALD treatment. Conducting related in-depth studies, such as well-designed randomized controlled trial based on the results of experimental research, is necessary.

• Biomolecules & Therapeutics
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• v.19 no.1
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• pp.126-133
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• 2011

The fruit of Actinidia arguta (AA) has been used mainly for the treatment of skin diseases, diuresis, diabetes mellitus and osteoporosis in Korean traditional medicine. It is known that AA (hardy kiwi) fruit extract has an effect on 2-chloro-1,3,5-trinitrobenzene-induced atopic dermatitis-like skin lesions in NC/Nga mice. Mode of action for it is associated with the modulation of biphasic Th1/Th2 cytokines. Furthermore, DA9102 containing AA is a herbal medicine currently under phase II clinical trial for atopic dermatitis in Korea. However, no active principles of AA on the decrease of Th2 cytokines including IL-4 and IL-10 have been identified. In this study, bioactivity-guided fractionation of an alcohol extract from the dried fruits of AA using ELISA assay for IL-4 production led to the isolation of $\alpha$-linolenic acid (I), linoleic acid (II), ethyl linolenate (III), ethyl linoleate (IV) and ethyl stearate (V) as the major active components. These compounds showed the down-regulatory effects of IL-4 production in A23187-stimulated RBL-2H3 cells without cytotoxicity.

• Molecules and Cells
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• v.41 no.2
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• pp.73-82
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• 2018

Cancer preventive activities of green tea and its main constituent, (-)-epigallocatechin gallate (EGCG) have been extensively studied by scientists all over the world. Since 1983, we have studied the cancer chemopreventive effects of EGCG as well as green tea extract and underlying molecular mechanisms. The first part of this review summarizes groundbreaking topics with EGCG and green tea extract: 1) Delayed cancer onset as revealed by a 10-year prospective cohort study, 2) Prevention of colorectal adenoma recurrence by a double-blind randomized clinical phase II trial, 3) Inhibition of metastasis of B16 melanoma cells to the lungs of mice, 4) Increase in the average value of Young's moduli, i.e., cell stiffness, for human lung cancer cell lines and inhibition of cell motility and 5) Synergistic enhancement of anticancer activity against human cancer cell lines with the combination of EGCG and anticancer compounds. In the second part, we became interested in cancer stem cells (CSCs). 1) Cancer stem cells in mouse skin carcinogenesis by way of introduction, after which we discuss two subjects from our review on human CSCs reported by other investigators gathered from a search of PubMed, 2) Expression of stemness markers of human CSCs compared with their parental cells, and 3) EGCG decreases or increases the expression of mRNA and protein in human CSCs. On this point, EGCG inhibited self-renewal and expression of pluripotency-maintaining transcription factors in human CSCs. Human CSCs are thus a target for cancer prevention and treatment with EGCG and green tea catechins.

• Radiation Oncology Journal
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• v.18 no.3
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• pp.167-176
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• 2000

The objective of recent radiation therapy is to improve the quality of treatment and the after treatment quality of life. In Korea, sharing the same objective, significant advancement was made due to the gradual increase of patient number and rapid increase of treatment facilities. The advancement includes generalization of three-dimensional conformal radiotherapy (3D-CRT), application of linac-based stereotactic radiosurgery (SRS), and furthermore, the introduction of intensity modulated radiation therapy (IMRT). Authors in this paper prospectively review the followings: the advancement of radiation oncology in Korea, the recent status of four-dimensional radiation therapy, IMRT, the concept of the treatment with biological conformity, the trend of combined chemoradiotherapy, the importance of internet and radiation oncology information management system as influenced by the revolution of information technology, and finally the global trend of telemedicine in radiation oncology. Additionally, we suggest the methods to improve radiotherapy treatment, which include improvement of quality assurance (QA) measures by developing Koreanized QA protocol and system, regional study about clinical protocol development for phase three clinical trial, suggestion of unified treatment protocol and guideline by academic or research societies, domestic generation of treatment equipment's or system, establishment of nationwide data base of radiation-oncology-related information, and finally patterns-of-care study about major cancers.

• Journal of Korean Neurosurgical Society
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• v.58 no.1
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• pp.1-8
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• 2015

Treatment of Leptomeningeal carcinomatosis (LMC) from solid cancers has not advanced noticeably since the introduction of intra-cerebrospinal fluid (CSF) chemotherapy in the 1970's. The marginal survival benefit and difficulty of intrathecal chemotherapy injection has hindered its wide spread use. Even after the introduction of intraventricular chemotherapy with Ommaya reservoir, frequent development of CSF flow disturbance, manifested as increased intracranial pressure (ICP), made injected drug to be distributed unevenly and thus, the therapy became ineffective. Systemic chemotherapy for LMC has been limited as effective CSF concentration can hardly be achieved except high dose methotrexate (MTX) intravenous administration. However, the introduction of small molecular weight target inhibitors for primary cancer treatment has changed the old concept of 'blood-brain barrier' as the ultimate barrier to systemically administered drugs. Conventional oral administration achieves an effective concentration at the nanomolar level. Furthermore, many studies report that a combined treatment of target inhibitor and intra-CSF chemotherapy significantly prolongs patient survival. Ventriculolumbar perfusion (VLP) chemotherapy has sought to increase drug delivery to the subarachnoid CSF space even in patients with disturbed CSF flow. Recently authors performed phase 1 and 2 clinical trial of VLP chemotherapy with MTX, and 3/4th of patients with increased ICP got controlled ICP and the survival was prolonged. Further trials are required with newly available drugs for CSF chemotherapy. Additionally, new LMC biologic/pharmacodynamic markers for early diagnosis and monitoring of the treatment response are to be identified with the help of advanced molecular biology techniques.