• 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.

• 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.

• Clinical and Experimental Pediatrics
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• v.46 no.9
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• pp.939-943
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• 2003

Neonatal herpes simplex virus(HSV) infections result in significant morbidity and mortality. Although acyclovir treatment has improved survival, severe neurological sequelae can occur in the majority of survivors. HSV infections limited to the skin, eyes and mouth(SEM) can cause neurologic impairment. A direct correlation exists between the development of neurologic deficits and the frequency of cutaneous HSV recurrences. National Institutes of Allergy and Infectious Diseases(NIAID) Collaborative Antiviral Study Group conducted a phase I/II trial of continuous oral acyclovir therapy for the suppression of cutaneous recurrences. We describe a preterm infant who had two recurrences after neonatal SEM disease had been treated with intravenous acyclovir, and there were no more recurrences after continuous oral acyclovir suppressive therapy for six months. We report this case with a review of related literature.

• 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.1
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• pp.17-25
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• 2000

Purpose : To evaluate the side effects, pattern of failure, and survival rate according to the sequence of postoperative adjuvant radiotherapy and chemotherapy, patients with stages II and III rectal cancer who had undergone curative resection were randomized to 'early radiotherapy group (arm I)' or' late radiotherapy group (arm II)', then we intend to determine the most effective sequence of the radiotherapy and chemotherapy. Materials and Methods . From January 1996 to March 1999, 313 patients with curatively resected stages II and III rectal cancer have been randomized to' early' or' late' radiation therapy group and received combined chemotherapy (5-FU 375 mg/m$^{2}$/day, ieucovorin 20 mg/m$^{2}$, IV bolus daily Dl-5, 8 cycles) and radiation therapy (whole pelvis with 45 Gy/25 fractions/s weeks). Arm I received radiation therapy from day 1 with first cycle of chemotherapy and arm II received radiation therapy from day 57 with third cycle of chemotherapy after completion of first two cycles. Preliminary analysis was peformed with 228 patients registered up to Jun 1998. Two out of the 228 patients were excluded because of double primary cancer. Median follow-up period was 23 months. Results :Local recurrence occurred in 11 patients (9.7$\%$) for arm I and 9 patients (8$\%$) for arm 11. There was no significant difference between both groups ( p=0.64). However, distant metastasis was found in 22 patients (19.5$\%$) for arm I and 35 patients (31.0$\%$) for arm II and which showed statistically significant difference between the two groups ( p=0.046). And neither 3-year disease-free survival (70.2$\%$ vs 59.2$\%$, p=0.2) nor overall survival (89.4$\%$ vs 88.0$\%$, p=0.47) showed significant differences. The incidence of leukopenia during radiation therapy and chemotherapy was 78.3$\%$ and 79.9$\%$ respectively but leukopenia more than RTOG grade 3 was only 2.1$\%$ and 6.0$\%$ respectively. The incidence of diarrhea more than 10 times per day was significantly higher in the patients for arm I than for arm II (71.2$\%$ vs 41.6$\%$, p=0.02) but this complication was controlled with supportive cares. Conclusion : Regardless of the sequence of postoperative adjuvant radiation therapy and chemotherapy after curative resection for rectal cancer, local recurrence rate was low with combined chemoradlotherapy. But distant metastasis rate was lower in early radiation therapy group than in late radiation therapy group and the reason is unclear. Most patients completed these treatments without severe complication, so these were thought to be safe treatments but the treatment compliance should be improved.

• Nutrition Research and Practice
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• v.14 no.2
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• pp.102-108
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• 2020

BACKGROUND/OBJECTIVES: In Oriental medicine, certain foods may be beneficial or detrimental based on an individual's constitution; however, the scientific basis for this theory is insufficient. The purpose of this study was to investigate the effect of body constitution, based on the Sasang type of Korean traditional medical classification system, on the bioavailability of soy isoflavones of Cheonggukjang, a quick-fermented soybean paste. SUBJECTS/METHODS: A pilot study was conducted on 48 healthy Korean men to evaluate the bioavailability of isoflavone after ingestion of food based on constitution types classified by the Sasang typology. The participants were classified into the Taeeumin (TE; n = 15), Soyangin (SY; n = 15), and Soeumin (SE; n = 18) groups. Each participant ingested 50 g of Cheonggukjang per 60 kg body weight. Thereafter, blood was collected, and the soy isoflavone metabolites were analyzed by ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry. Ntrikinetic analysis of individual isoflavone-derived metabolites was performed. RESULTS: Our nutrikinetic analysis identified 21 metabolites derived from isoflavones in the blood samples from 48 healthy Korean men (age range, 21-29 years). Significant differences were observed in the time to maximum concentration (T_max) and elimination half-life (t_1/2) for nine metabolites among the three groups. The T_max and t_1/2 of the nine metabolites were higher in the SE group than in the other groups. Moreover, the absorption rates, as determined by the area under the plasma-level curve (AUC) values of intact isoflavone, were 5.3 and 9.4 times higher in the TE group than in the SY and SE groups, respectively. Additionally, the highest AUC values for phase I and II metabolites were observed in the TE group. CONCLUSIONS: These findings indicate that isoflavone bioavailability, following Cheonggukjang insgestion, is high in individuals with the TE constitution, and relatively lower in those with the SE and SY constitutions.

• Journal of Plant Biotechnology
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• v.32 no.4
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• pp.233-241
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• 2005

Plants have considerable advantages for the production of antigenic proteins because they provide an inexpensive source of protein and an easy administration of vaccine. Since a publication describing edible plant vaccine of HBsAg in 1992, a number of laboratories around the world have studied the use of plants as the bioreactor to produce antigenic proteins of human or animal pathogens. Over the last ten years, these works have been mainly focused on three major strategies for the production of antigenic proteins in plants: stable genetic transformation of either the nuclear or plastid genome, or transient expression in plants using viral vectors. As many antigenic proteins have been expressed in tobacco, also several laboratories have succeeded to express genes encoding antigenic proteins in other crop plants: potato, tomato, maize, carrot, soybean and spinach. At present many works for the production of edible plant vaccine against bacteria-mediated diseases have mostly performed the studies of enterotoxins and adhesion proteins. Also the development of new-type antigens (pili, flagella, surface protein, other enterotoxin and exotoxin etc.) is required for various targets and more efficacy to immunize against microorganism pathogens. Many works mostly studied in experimental animals had good results, and phase I clinical trial of LTB clearly indicated its immunogenic ability. On the other hand, edible plant vaccines have still problems remained to be solved. In addition to the accumulation of sufficient antigen in plants, human health, environment and agriculture regulation should be proven. Also oral tolerance, the physiological response to food antigens and commensal flora is the induction of a state of specific immunological unresponsiveness, needs to be addressed before plant-derived vaccine becomes a therapeutic option.

• Pediatric Infection and Vaccine
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• v.31 no.1
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• pp.12-24
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• 2024

The number of pediatric coronavirus disease 2019 (COVID-19) cases worldwide are increasing compared to the early phase of the pandemic, along with highly transmissible severe acute respiratory syndrome coronavirus variant and the increase in adult COVID-19 vaccination. We conducted a rapid systematic review and meta-analysis of published randomized clinical trials (RCTs) of the COVID-19 vaccines and the observational retrospective studies on adverse events after COVID-19 vaccination in adolescents. Seventeen studies were finally included in this systematic review. Meta-analysis showed that although vaccination in adolescents was significantly effective to prevent COVID-19 infection in retrospective studies (risk ratio [RR], 0.29; 95% confidence interval [CI], 0.22-0.37; I² =100%), however the effect of preventing COVID-19 infection was lower than in RCTs (RR, 0.05; 95% CI, 0.01-0.27). In five retrospective studies, the pooled estimated proportion of participants with myocarditis and/or pericarditis was 2.33 per 100,000 of the population (95% CI, 0.97-5.61 per 100,000). Sub-group analysis with sex and vaccine doses showed that male (5.35 per 100,000) and the second dose (9.71 per 100,000) had significantly higher incidence of myocarditis and/or pericarditis than female (1.09 per 100,000) and the first dose (1.61 per 100,000), respectively. Our study showed that mRNA COVID-19 vaccines in adolescent recipients were favorable and effective against COVID-19 in RCT as well as observational studies. The safety findings of BNT162b2 vaccine in adolescents were explored and we found the difference of safety according to sex and vaccine doses. The occurrence of adverse events after mRNA COVID-19 vaccination should be monitored.

• Radiation Oncology Journal
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• v.16 no.3
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• pp.311-323
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• 1998

Purpose : Prospective, single arm, Phase I/II clinical trial was performed to assess the efficacy and toxicity of the concurrent chemotherapy and definitive radiotherapy (RT) in patients with previously untreated locally advanced carcinoma of the uterine cervix. Methods and Materials : From Mar 1992 to January 1997, a total of 73 patients with advanced cervical carcinoma were entered on the protocol but 5 patients were excluded in analysis because of patients' refusal of treatment. Their ages ranged from 31 to 77 years, median 58 years. The International Federation of Gynecology and Obstetrics (FIGO) stage distribution was as follows: IIB 46, IIIA 2, IIIB 15 and IVA 5. RT consisted of external beam irradiation to 4,140-5,040 cGy/23-28 fractions plus high dose rate intracavitary treatments to deliver a dose of 30-35 Gy to point A in 6-7 fractions. During the intracavitary treatments parametrial boost was delivered for point B dose of 60 Gy in stage IIB and 65 Gy in stage IIIB. Two cycles of concurrent 5-fluorouracil and cisplatin (FP) chemotherapy (5-fluorouracil 1,000 mg/$m^2$/day continuous infusion for 4 days, day 1-4, 29-32 and cisplatin 20 mg/$m^2$/day intravenous bolus for 3 days day 1-3, 29-31) administered starting on day 1 of RT. Results : The median follow-up was 24 months (range 4-68+). Sixty-four patients were evaluable for survival rate in this protocol: The 5-year actuarial and disease-free survival rate were 52$\%$ and 64$\%$, respectively. The 5-rear actuarial survival for stage IIB and III+IVA patients were 58$\%$ and 36$\%$, respectively The 5-year disease-free survival rate for stage IIB and III+IVA patients were 71$\%$ and 40$\%$, respectively. Of the 68 patients evaluated for patterns of failure, overall recurrence rate was 27.9$\%$ (19/68) : local failure in 5.9$\%$ (4/68), distant metastasis in 10.3$\%$ (7/68) and both in 11.8$\%$ (8/68). Of the 64 patients evaluated for response at one month after the completion of treatment the complete response rate was 78$\%$ (50/64). Concurrent chemoradiation appear to be a well-tolerated regimen but there were two treatment-related deaths. Conclusion : Concurrent chemotherapy of FP with high-dose definitive RT in locally advanced carcinoma of the uterine cervix is feasible and effective with acceptable toxicities. This chemoradiation regimen may offer a modest survival benefit for advanced stage. Further follow-up of these patients will evaluate the impact of this regimen on the long-term local control and their survival.