Busulfan is an antineoplastic agent with a narrow therapeutic window. A post-hoc population pharmacokinetic analysis of a prospective randomized trial for comparison of four-times daily versus once-daily intravenous busulfan was carried out to search for predictive factors of intravenous busulfan (iBu) pharmacokinetics (PK). In this study the population PK of iBu was characterized to provide suitable dosing recommendations. Patients were randomized to receive iBu, either as 0.8 mg/kg every 6 h or 3.2 mg/kg daily over 4 days prior to hematopoietic stem cell transplantation. In total, 295 busulfan concentrations were analyzed with NONMEM. Actual body weight and sex were significant covariates affecting the PK of iBu. Sixty patients were included in the study (all Korean; 23 women, 37 men; mean [SD] age, 36.5 [10.9] years; weight, 66.5 [11.3] kg). Population estimates for a typical patient weighing 65 kg were: clearance (CL) 7.6 l/h and volume of distribution (Vd) 32.2 l for men and 29.1 L for women. Inter-individual random variabilities of CL and $V_d$ were 16% and 9%. Based on a CL estimate from the final PK model, a simple dosage scheme to achieve the target $AUC_{0-inf}$ (defined as median AUC0-inf with a once-daily dosage) of 26.18 $mg/l{\cdot}hr$, was proposed: $24.79{\cdot}ABW^{0.5}mg$ q24h, where ABW represents the actual body weight in kilograms. The dosing scheme reduced the unexplained interindividual variabilities of CL and Vd of iBu with ABW being a significant covariate affecting clearance of iBU. We propose a new simple dosing scheme for iBu based only on ABW.
Kim, Seung Gu;Kang, Gun Hi;Kim, Jun Jae;Park, Hyun;Baek, Na Na;Choi, Sang Bong;Shin, Eun Ah;Kim, Joung Sook;Park, I Nae;Jeung, Hoon;Hur, Jin Won;Lee, Sung Soon;Lee, Hyun Kyung;Kim, Joo In;Lee, Young Min;Lee, Hyuk Pyo;Yum, Ho Kee;Choi, Soo Jeon
Tuberculosis and Respiratory Diseases
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v.65
no.5
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pp.416-420
/
2008
Many classes of drug, such as antineoplastic drugs and antiarrhythmic drugs, have potential to induce interstitial lung disease. Herbal medicines are also believed to have the potential to induce pneumonitis. However, to our knowledge, there are no reports of pneumonitis caused by herbal medications in the Korean medical database. We report a case of recurrent pneumonitis caused by a self rechallenge of the Herbal medicine Bojungikgitang (Bu-Zhong-Yi-Qi-Tang : Hochu-ekki-to).
Background: The aim of this study was to explore the efficacy and adverse reactions of CT-guided radioactive 125I-seed implantation treatment combined with chemotherapy for platinum-resistant recurrent ovarian carcinoma. Materials and Methods: From September 2010 to December 2012, 23 patients with platinum-resistant recurrent ovarian carcinoma were enrolled. All the patients refused, could not bear, or were not suitable for surgery. They all had no more than 3 lesions, which were detected and could also be measured by CT. All were clarified as single-lesion or multiple-lesion groups. A total of 41 lesions underwent implantation of from 8 to 106 125I seeds (median=43). Multi-plane implanting was adopted and 125I-seeds of (0.4-0.7)mCi were placed at intervals of (0.5-1.0) cm. After implantation treatment, all patients underwent 4 cycles of chemotherapy with gemcitabine $800mg/m^2$ (days 1, 8 and 15). Results: The outcome was evaluated with CT 3 weeks and every 3 months after implantation treatment. After 6 months, the volume of 32 out of 41 lesions (78.0%) was reduced at least 30%, within which 9 lesions completely disappeared(22.0%). Complete response was observed in 7 cases (30.4%), with a partial response in 4 cases (17.4%), 4 cases stable(17.4%)and 8 cases showing progression (34.8%). The total clinical remission rate was 47.8% (11/23). The clinical remission rate was 77.8% (7/9) in the single-lesion group and 28.6% (4/14) in the multiple-lesion group with a significant difference between the two(P=0.036). The common side effects observed were mild gastrointestinal reactions. Conclusions: 125I-seed implantation combined with chemotherapy applies an effective way in the treatment of platinum-resistant recurrent ovarian epithelial carcinoma with the advantages of high local control rates, good short-term effects, little trauma and less side effects.
Traditionally, the larvae of Allomyrina dichotoma (AD), a species of the rhinoceros beetle, have been widely used for their antidiabetic, antihepatofibrotic, antineoplastic, and antiobesity effects. The United Nations' Food and Agriculture Organization has reported on the possibility of using edible insects in human dietary supplements in the future. However, despite the growing interest in insect-based bio-active products, the biological activities of these products have rarely been studied. Previously, we reported that AD larvae inhibit the in vitro differentiation of adipocytes via transcription factor downregulation. In this study, our objective was to evaluate the effects of a hot-water extract of AD larvae on allergy and inflammation. To investigate the inhibitory effect of the extract on allergic reactions, we measured the levels of ${\beta}-hexosaminidase$, tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), interleukin-4 (IL-4), and cyclooxygenase-2 (COX-2) after activation of RBL-2H3 cells using Compound 48/80. In addition, the inhibitory effect of the extract on inflammation was determined using Raw 264.7 cells after lipopolysaccharide (LPS) stimulation. The extract significantly inhibited the ${\beta}-hexosaminidase$, $TNF-{\alpha}$, IL-4, and COX-2 levels in RBL-2H3 cells. Furthermore, it effectively inhibited the inflammatory cytokine IL-6, nitric oxide, and inducible nitric oxide synthase expression in LPS-stimulated Raw 264.7 cells. These results suggest that AD larval extract can be potentially developed as an antiallergic and anti-inflammatory therapeutic agent.
Journal of the Korean Association of Oral and Maxillofacial Surgeons
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v.27
no.5
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pp.468-473
/
2001
Castleman's disease or angiofollicular lymph node hyperplasia, is a rare lymphoproliferative disorder. It may be appear as a local or generalized tumor-like condition, usually in chest or abdomen and may involve both lymph nodes and non-nodal tissues. Castleman's disease is an unusal entity which may at times mimic malignancy but is entirely benign in nature. It is topical as it has been noted to occur with AIDS and Kaposi's sarcoma. Careful interpretation of radiogram may help to distinguish Castleman's disease from other tumor condition, such as lymphoma, neurogenic tumor, or even angiofibroma, etc. But exact diagnosis must be made on the basis of histologic confirmation. In addition to histologic features, clinical distinction between the localized and multicentric form is important in selecting appropriate management. Surgical excision of an localized mass is the first choice of treatment. Partial resection, radiotherapy or observation alone may avoid the need for exessively aggressive therapy. Patients with multicentric disease don't benefit by surgical management because of systemic manifestation and rapid deterioration. Thus, antineoplastic agents and steroids may offer an alternative form of therapy. We report a case of female patient with Castleman's disease in oral and maxillofacial region, treated by surgical excision with good results.
Kim, Gyoo-Cheon;Lee, Kyoung-Duk;Park, Jae-Hyun;Kim, Duk-Han;Park, Jeong-Kil;Park, June-Sang;Park, Bong-Soo
Journal of Oral Medicine and Pain
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v.30
no.2
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pp.231-238
/
2005
Anti-cancer drugs have been shown to target diverse cellular functions in mediation cell death in chemosensitive tumors. Most antineoplastic drugs used in chemotherapy of leukemias and solid tumors induce apoptosis in drug-sensitive target cells. However, the precise molecular requirements that are central for drug-induced cell death are largely unknown. Etoposide is used for the treatment of lung and testicular cancer. This study was performed to examine whether etoposide promote apoptosis in human oral squamous carcinoma cells (OSC9) as well as in lung and testicular cancer. Etoposide had a significant dose- and time-dependent inhibitory effect on the viability of OSC9 cells. TUNEL assay showed the positive reaction on condensed nuclei. Hoechst stain demonstrated that etoposide induced a change in nuclear morphology. The expression of p53 was increased at 48 hour, suggesting that the nuclear of OSC9 cell was damaged, thereby inducing apoptosis. Etoposide treatment induced caspase-3 cleavage and activation. Intact PARP protein 116-kDa and 85-kDa cleaved product were observed. The activated caspase-3 led cleavage of the PARP. These results demonstrate that etoposide-induced apoptosis in OSC9 cells is associated with caspase-3 activation.
Hyun, Ja-Kyoung;Kwon, O Jun;Lee, Joo Young;Roh, Seong-Soo;Seo, Young-Bae
Journal of Applied Biological Chemistry
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v.59
no.2
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pp.113-124
/
2016
Red ginseng is known to have many beneficial effects. Cisplatin, an effective antineoplastic drug, can cause many side effects like irreversible sensorineural hearing loss and serious tinnitus in humans. This study is aimed to reduce a cisplatin's side effect, nephrotoxicity by fermentated korean red ginseng. Korea ginseng was produced by steaming and dring and fermentation. And mice were divided into 4 groups- (A) normal mice, (B) Vehicle treated cisplatin mice, (C) RG0F0-treated cisplatin mice, (D) RG8F3-treated cisplatin mice. C and D groups were feed each material 200 mg/kg/day during 4 days. And cisplatin 20 mg/kg injected to B, C, and D groups as abdominal injection. After 24 h, blood sample was collected. The kidneys were harvested for histological, immuno histochemical and western blot analysis. 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging activity was depended on steaming hours. RG0F0 and RG8F3 (ginseng-8 h steamed and fermented by Saccharomyces cerevisiae) were showed antioxidants effect in DPPH and ABTS radical scavenging activity. Component amounts according to steaming hours. 8 h steamed red ginseng had the most ingredients of ginsenoside. Treatments with RG8F3 reduced cisplatin-induced nephrotoxicity in the mice resulting in increase of GSH and decrease of ROS, BUN, creatinine, and inflammatory mediators. This result seems to be involved with the restriction of the inflammation in the kidney. Therefore, fermented red ginseng might have therapeutic efficacy in reduce kidney injury induced by cisplatin treatment.
Kim, Minjoo;Kim, Eun-Mi;Oh, Phil-Sun;Lim, Seok Tae;Sohn, Myung-Hee;Song, Eun-Kee;Park, Keon Uk;Kim, Jin Young;Won, Kyoung Sook;Jeong, Hwan-Jeong
The Korean Journal of Pain
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v.34
no.4
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pp.427-436
/
2021
Background: Pharmacological and non-pharmacological therapies have been used to treat patients with chemotherapy-induced peripheral neuropathy (CIPN). However, the effect of therapies in cancer patients has yet to be investigated comprehensively. We hypothesized that cyclic thermal therapy would improve blood flow and microcirculation and improve the symptoms driven by CIPN. Methods: The criteria of assessment were blood volume in region of interest (ROI) in the images, and European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20 questionnaire scores. The blood volume was quantified by using red blood cell (RBC) scintigraphy. All patients were treated 10 times during 10 days. The thermal stimulations, between 15° and 41°, were repeatedly delivered to the patient's hands. Results: The total score of the questionnaires, the score of questions related to the upper limbs, the score of questions closely related to the upper limbs, and the score excluding the upper limbs questions was decreased. The blood volume was decreased, and the variance of blood volume was decreased. During cooling stimulation, the blood volume was decreased, and its variance was decreased. During warming stimulation, the blood volume was decreased, and its variance was decreased. Conclusions: We suggest that cyclic thermal therapy is useful to alleviate CIPN symptoms by blood circulation improvement. RBC scintigraphy can provide the quantitative information on blood volume under certain conditions such as stress, as well as rest, in peripheral tissue.
Journal of the korean academy of Pediatric Dentistry
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v.46
no.3
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pp.239-246
/
2019
The purpose of this study was to examine dental complications and to evaluate the effects of initial treatment age, treatment modalities, and treatment duration on the disorder after radiation and chemotherapy in pediatric cancer patients. For 93 children with clinical and radiographic data, the number of teeth, the morphology of teeth, the shape of the roots, and development status of the dentition were evaluated. Dental development disorders were found in 61.3% of the children. The mostly found abnormality was root deformity with the prevalence of 31.2%. In children submitted to the therapy before the age of 6, the number of missing teeth (p = 0.029) and microdontia (p = 0.003) were greater compared to the children who started to receive the treatment after the age of 6. The combination of radiation and chemotherapy showed significantly greater incidences of missing teeth (p = 0.030), microdontia (p = 0.046), and root deformity (p = 0.009) when compared with the sole application of chemotherapy. When the children were submitted to anticancer therapy for 18 months or longer duration, greater number of missing teeth (p = 0.032), microdontia (p = 0.011), root deformity (p = 0.025), and total number of teeth affected (p = 0.036) were observed compared with duration less than 18 months. The number of dental abnormalities increased when the children were treated at earlier ages, with combination of radiation and chemotherapy, and for longer period of time.
Colon cancer is one of the most common malignancies in the western world and the second leading cause of cancer death in Korea. Epidemiology studies have shown a reduced incidence of colon cancer among populations consuming a large quantity of ${\omega}3$-polyunsaturated fatty acids (${\omega}3$-PUFA) of marine origin. Recently, it has been found that ${\omega}3$-PUFA has an antineoplastic effect in several cancers. This study was designed to investigate the mechanism of the anti-invasive effect of ${\omega}3$-PUFA in colon cancer. ${\omega}3$-PUFA, docosahexaenoic acids (DHA) and eicosapentaenoic acid (EPA) treatment resulted in a dose-dependent inhibition of cell growth in SW480 human colon cancer cells. In contrast, arachidonic acid (AA), a ${\omega}6$-PUFA, exhibited no significant effect. This action likely involves apoptosis, given that DHA treatment increased apoptotic cells in TUNEL assay. Moreover, invasiveness of SW480 cells was inhibited following treatment of DHA in a dose-dependent manner; in contrast, AA had no effect. The levels of MMP-9 and MMP-2 mRNA decreased after DHA pretreatment. MMP-9 and MMP-2 promoter activities were also inhibited by DHA treatment. The levels of NF-kB and p-IkB protein were down-regulated by DHA pretreatment in a dose dependent manner. In addition, DHA inhibited NF-kB promoter reporter activities. These findings suggest that ${\omega}3$-PUFA may inhibit cancer cell invasion by inhibition of MMPs via reduction of NF-kB in colon cancer. In conclusion, ${\omega}3$-PUFA could be used for chemoprevention and treatment of human colon cancer.
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