• Biomolecules & Therapeutics
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• 제24권4호
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• pp.402-409
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• 2016

It has been found that 4-isopropyl-2,6-bis(1-phenylethyl)phenol (KTH-13), a novel compound isolated from Cordyceps bassiana, is able to suppress tumor cell proliferation by inducing apoptosis. To mass-produce this compound, we established a total synthesis method. Using those conditions, we further synthesized various analogs with structural similarity to KTH-13. In this study, we aimed to test their anti-cancer activity by measuring anti-proliferative and pro-apoptotic activities. Of 8 compounds tested, 4-methyl-2,6-bis(1-phenylethyl)phenol (KTH-13-Me) exhibited the strongest anti-proliferative activity toward MDA-MB 231 cells. KTH-13-Me also similarly suppressed the survival of various cancer cell lines, including C6 glioma, HCT-15, and LoVo cells. Treatment of KTH-13-Me induced several apoptotic signs in C6 glioma cells, such as morphological changes, induction of apoptotic bodies, and nuclear fragmentation and chromatin condensation. Concordantly, early-apoptotic cells were also identified by staining with FITC-Annexin V/PI. Moreover, KTH-13-Me highly enhanced the activation of caspase-3 and caspase-9, and decreased the protein level of Bcl-2. In addition, the phosphorylation levels of Src and STAT3 were diminished in KTH-13-Me-treated C6 cells. Therefore, these results suggest that KTH-13-Me can be developed as a novel anti-cancer drug capable of blocking proliferation, inducing apoptosis, and blocking cell survival signaling in cancer cells.

• 한국식품영양학회지
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• 제21권4호
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• pp.397-402
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• 2008

Over the past few years, anthocyanin has been demonstrated to exert potentially anti-oxidative and bioavailability effects including anti-cardiovascular disease and cancer-preventive effects in humans. This study was conducted to assess the toxicity of anthocyanin extracts from black soybean seed coats via oral administration in a mice feeding test. The final anthocyanin-containing products induced signs of toxicity on mortality in the 4-week feeding test. The incidence of clinical signs and changes in body and organ weight were also not observed in all anthocyanin-treated groups as compared with the control groups. In hematology analysis, RBC indices concluding MCV, MCH, and MCHC and WBC differential counting such a NEU, LYM, MONO, EOS, and BASO evidenced no significant differences between the anthocyanin treatment and control groups. The biochemical parameters in serum analysis - ALT, AST, BUN, Crea etc.- were also not significantly altered in those groups. Absolute and relative organ weights were not increased after 4 weeks of treatment with anthocyanin extracts in mice. In conclusion, anthocyanin extracts from the black soybean has biological activity without any toxic effects, which also suggests that the consumption of soy containing anthocyanin products may be a good source for health and medical supplies.

• 약학회지
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• 제49권4호
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• pp.317-322
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• 2005

Isoflavones are reported to playa role in menopausal women as a phytoestrogen, which can replace estradiols in hormone replacement therapy (HRT). Recently; due to the risk of breast cancer by HRT, phytoestrogens (e.g. isoflavones) have been focused as an alternative therapy in menopause. In the study, we investigated whether isoflavones derived from Sophorae fructus (SISO) have more benefit than that of soybean isoflavones in estrogen deficient rats. We found that SISO effectively controled $H_2O_2$ comparing with the baseline (p<0.01 vs. post value of OVX-Cont), and the blood sugar and weight were also controlled with decreasing patterns. Additionally, in LDH assay for cytoprotective effect in Neuro-2a cell line, SISO protected cells from the damage by SNAP (p<0.05). In conclusion, SISO may have more beneficial effect in enhancing the menopausal signs than that of soybean isoflavones and the cytoprotective effect in neuron cells suggests that SISO can play a certain role in neuroprotection after menopause.

• 대한약침학회지
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• 제22권3호
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• pp.147-153
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• 2019

Objectives: Many studies have been reported the efficacy of intravenous lipid emulsion (ILE) as an antidote on acute lipophilic drug toxicity. Clozapine, highly lipophilic dibenzodiazepine neuroleptics, is an important medication in the schizophrenia therapy regimen. Acute intoxication with antipsychotics is one of the main reasons for the referral of poisoned patients to the hospital. We expected that ILE could be used for the therapy of acute clozapine intoxicated patients. Methods: We used two groups of consisting of six male rats. Both groups received a toxic dose of clozapine (40 mg/kg) intravenously, via the tail vein. After 15 minutes, they were treated with intravenous infusion of 18.6 mg/kg normal saline (NS group), or 18.6 mg/kg ILE 20% (ILE group). We evaluated blood pressure (BP) and heart rate by power lab apparatus through the tail artery, ataxia by a rat rotary circle, seizure scores and death in multiple times after starting clozapine administration. For biochemical and pathological evaluations the samples of tissue and blood were taken. Results: Our results demonstrated that ILE 20% could return hypotension-induced clozapine better than normal saline. Furthermore, ataxia and seizure have rectified more rapidly and deaths reduced. Clozapine administration causes pancreatitis and lung injury but fat emulsion did not show an optimal effect on tissue damages caused by clozapine toxicity. Conclusion: In conclusion, ILE can remove toxic signs of clozapine same as other lipophilic medicines, however, clinical uses of ILE for this intention requires more appraisement to determine the precise implication and safety.

• Journal of Acupuncture Research
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• 제39권4호
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• pp.310-316
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• 2022

Background: Verbenalin is an iridoid glucoside, which is among the active components of some medicinal herbs such as Verbena officinalis Linn, and Cornus officinalis Siebold and Zucc. Previous studies have confirmed the antioxidant activity and neuroprotective potential of verbenalin. To confirm the safety of verbenalin, an approximate lethal dose was determined based on a single oral dose toxicity study. Methods: Institute of Cancer Research mice were randomly assigned to three verbenalin exposure groups (250, 500, and 1,000 mg/kg) and a control group (5% methylcellulose solution). There were (5 male and 5 female mice per group). Mortality, clinical signs, and body weight were monitored for 14 days, and necropsies were conducted. Results: No mortalities were observed in the control group or the verbenalin 250 mg/kg group, whereas mortalities were observed in the 500 mg/kg and 1,000 mg/kg verbenalin groups. During the observation period, stool abnormalities such as mucous stools were observed. Clinical signs such as loss of locomotor activity were observed in the 500 mg/kg and 1,000 mg/kg verbenalin groups. During the study period, significant changes in body weight were observed in the 500 mg/kg and 1,000 mg/kg verbenalin groups; however, no gross abnormalities were observed at necropsy. Overall, no toxicity was found in the 250 mg/kg group. Conclusion: The approximate lethal dose of verbenalin was estimated to be 500 mg/kg. For a more accurate assessment of the safety of verbenalin, other types of studies such as repeated-dose toxicity studies should also be conducted.

• 대한본초학회지
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• 제29권4호
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• pp.29-34
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• 2014

Objectives : Ulcerative colitis (UC) is an inflammatory bowel disease, which is one of chronic gastrointestinal disorders. Orostachys japonicus (OJ) has been used as a traditional medicine for various diseases including gastric cancer, gastric ulcers and intoxication. However, the regulatory effect of OJ on intestinal inflammation has not been fully understood, yet. The aim of this study was to investigate the effect of OJ on dextran sulfate sodium (DSS)-induced colitis in mice. Methods : To ascertain the pharmacological effects of OJ, the colitis mice were induced by drinking water containing 5% DSS for 7 days. Mice were randomized into groups receiving OJ (100 mg/kg), sulfasalazine (150 mg/kg) as a positive control, or water as a negative control. We evaluated the effects of OJ on DSS-induced the clinical signs, measuring weight loss and colon length. In addition, the inhibitory effect of OJ on the tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) level was determined by enzyme-linked immunosorbent assay in colitis tissue. Results : The results indicated that mice treated with DSS showed remarkable clinical signs, including weight loss, and reduced colon length. However, treatment with OJ significantly improved the weight loss and DAI as clinical symptoms. Moreover, OJ reduced the TNF-${\alpha}$ levels in DSS-treated colon tissues. Conclusions : Collectively, the findings of this study provide us with novel insights into the pharmacological actions of OJ as a potential medicine for use in the treatment of ulcerative colitis.

• Radiation Oncology Journal
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• 제18권4호
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• pp.314-320
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• 2000

목적 :폐암으로 확진되어 근치적 방사선 치료를 받은 환자에서 방사선페렴이 발생할 수 있는 위험군을 사전에 예측해 보고자 혈장내 TGF-$\beta$1, TNF-$\alpha$, IL-6의 농도를 측정하여 페렴 발생과의 상관관계를 분석하고자 하였다. 재료 및 방법 : 1998년 5월부터 1999년 7월까지 폐암으로 확진되어 근치적 방사선 치료를 받은 17명의 환자(비소세포암 11명, 소세포암 6명)을 대상으로 하였다. 방사선 치료는 주 5회 매일 1.8 Gy씩 실시하였고 비소세포암과 소세포암에서 각각 평균 60 Gy와 져 Gy를 조사하였다. 모든 환자에서 방사선치료 전, 방사선치료 중 주 1회, 치료 후 추적관찰로 내원시마다 혈액을 채취하여 혈장 TGF-$\beta$1, TNF-$\alpha$ 및 IL-6의 양을 ELISA법으로 측정하였다. 모든 환자에서 단순흉부촬영(치료중 주1회, 치료 후 추적관찰 시마다 촬영) 및 방사선 폐렴과 연관된 증세를 관찰하여 방사선 페렴의 징후가 발견되면 즉시 고해상도 컴퓨터 단층 촬영(HRCT)를 촬영하여 방사선 폐렴 발생여부를 확진하고자 하였다. 결과: 17명의 환자 중 13명에서 방사선 폐렴과 연관된 증세가 발현되었고 단순 흉부 촬영과 고해상도 컴퓨터 단층 찰영에서 이를 확인할 수 있었다. 방사선 폐렴이 발생한 환자에서 측정한 TGF-$\beta$1의 경우 특징적인 수치 변화를 보여 치료 전 평균값은 38.45 ng/ml로 방사선 페렴이 발생하지 않은 군에 비해 상승되어 나타났고(0.7T ng/ml) 방사선치료 중 13.66 ng/ml의 평균값을 보인 후 다시 점진적으로 상승하여 치료 2$\~$4주 후까지 평균 60.63 ng/ml로 상승되어 유지되었고 이 수치는 폐렴이 발생하지 않은 군과 비교할 때(12.77 ng/ml) 통계적으로 의미가 있었다(p<0.05). TNF-$\alpha$와 IL-6의 수치도 방사선 폐렴군에서 더 높게 측정되었으나 수치변화의 양상은 특징적이지 못하였으며 통계학적 의미도 찾을 수 없었다. 결론: 방사선 치료를 받은 폐암환자에서 치료 전과 치료 기간 중 및 치료 후 측정한 혈장 TGF-$\beta$1,의 수치는 향후 방사선 페렴이 발생할 위험군을 예측할 수 있는 지표로 사용할 수 있을 것으로 사료된다.

• 대한약침학회지
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• 제5권1호
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• pp.7-26
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• 2002

Objective: The purpose of this study was to investigate acute and subacute toxicity and sarcoma-180 anti-cancer effects of herbal acupuncture with Carthami- Tinctorii fructus (CF) in mice and rats. Method: Balb/c mice were injected intraperitoneally with Carthami - Tinctorii fructus (CF) for $LD_{50}$ and acute toxicity test. Sprague Dawley rats were injected intraperitoneally with Carthami- Tinctorii fructus (CF) for subacute toxicity test. The Carthami- Tinctorii fructus herbal-acupuncture was injected on Chung-wan (CV12) of mice with Sarcoma-180 cancer cell line. Results: 1. $LD_{50}$ was uncountable as none of the subjects expired during the test. 2. In acute toxicity test, toxic symptoms were not detected, but the body weight of mice was increased in treatment Ⅰ, treatment Ⅱ groups, compared to the normal group.(p<0.05) 3. In acute toxicity test of serum biochemical values of mice, glucose was increased in treatment Ⅰ and treatment Ⅱ groups, total cholesterol was increased in treatment I group, GOT was decreased in treatment Ⅱ group, and GPT was decreased in treatment Ⅰ group, compared to the normal group.(p<0.05) 4. The clinical signs and the body weight of mice treated with 0.1 cc, 0.2cc Carthami- Tinctorii fructus (CF) were not affected during the subacute toxicity test. 5. In subacute toxicity test, treatment groups didn't show significant changes in complete blood count test (CBC) of rats, compared to the nonnal group.(p<0.05) 6. In subacute toxicity test of serum biochemical values of rats, uric acid was decreased in treatment Ⅰ and treatment Ⅱ groups, compared to the nonnal group, triglyceride was decreased in treatment I group, compared to the normal group, GOT and GPT were decreased in treatment I and treatment Ⅱ groups, and alkaline phosphatase was decreased in treatment Ⅰ and treatment Ⅱ groups, compared to the normal group.(p<0.05) 7. Median survival time was increased in all the treatment groups for Sarcoma-180 cancer cell treated with Carthmni- Tinctorii fructus (CF).(p<0.05) 8. Natural killer cell activity was significantly increased in all the treatment groups compared to the normal group.(p<0.05) 9. Interleukin-2 productivity was decreased in treatment Ⅰ and treatment Ⅱ groups.(p<0.05) Conclusion: According to the results, we can conclude herbal-acupuncture of Carthami-Tinctoriifructus (CF) caused negligible toxkity, and had anti-tumor effects in mice.

• Tuberculosis and Respiratory Diseases
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• 제39권1호
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• pp.55-61
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• 1992

연구배경 : 폐장은 악성종양이 가장 잘 전이하는 장기로 대부분은 혈행성으로 하나 또는 다수의 결절형태로 나타나나, 드물게는 림프관을 따라 전파되어 흉부 X선 검사상 미만성 간질성 폐침윤 양상으로 나타나기도한다. 때로는 이러한 림프관성 전이가 원발성암의 증상이 뚜렷치 않으면서 호흡기 증상과 흉부 X선 검사상 미만성 간질성 폐침윤이 보여 다른 간질성 폐질환과의 감별을 요하는데 이러한 경우를 경기관지 폐생검으로 암종성 림프관염이 진단되었던 5예를 경험하였기에 보고하는 바이다. 방법 : 임상소견, 폐기능검사, 흉부 전산화 단층촬영, 기관지 폐포 세척술과 경기관지 폐생검 검사로 진단을 얻었다. 결과 : 종양의 원발병소는 5명중 3명이 위암이었고, 2명은 폐암으로 생각되었다. 폐기능검사상 2명의 환자에서는 폐확산능이 감소된 제한성 환기장애를 보인 반면 한명에서는 폐쇄성 환기장애를 보였다. 기관지 폐포 세척술에서는 4명의 환자에서 모두 림프구 증가소견을 보였고 세포학적 검사상 이중 한명에서는 암세포도 관찰되었다. 경기관지 폐생검 검사에서 림프관에만 국한된 암세포가 관찰되었고, 이들의 cell type은 4명이 선암종이었고, 1명은 편평 상피 암종이었다. 결론 : 드물게, 암종성 림프관염은 원발성암의 증상이 없이 미만성 간질성 폐질환으로 발현될 수 있으며, 경기관지 폐생검 검사로 쉽게 진단되어 질수 있다.

• Asian Pacific Journal of Cancer Prevention
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• 제17권sup3호
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• pp.81-85
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• 2016

Globally, the burden of breast cancer (BC) continues to increase. BC related lymphedema (BCRL) is currently non curable and as a life time risk it affects at least 25% of BC patients. Knowing more about BCRL and appropriate control of its modifiable risk factors can improve quality of life (QOL) of the affected patients. In this case control study to detect factors, 400 women with BCRL (as the case group) and 283 patients with BC without lymphedema (as the control group) that were referred to Shiraz University of Medical Sciences affiliated BC clinic center were assessed. The data were analyzed in SPSS. The mean age of the case group was $52.3{\pm}11.0years$ and of the control group was $50.1{\pm}10.9years$. In patients with BCRL, 203(50.7%) had left (Lt) side BC and in non- lymphedema group 151 (53.3%) had Lt side BC. Out of all BCRL patients, 204 (51%) had lymphedema in all parts of their affected upper extremities, 100 (25%) had swelling in the arm and forearm and 23 (5.7%) had edema in both the upper extremity and trunk. Edema, heaviness, concern about changing body image, pain and paresthesia were the most common signs/symptoms among patients with BCRL. In BCRL patients, the difference of circumference between the affected upper limb and non-affected limb was $4.4{\pm}2.5cm$ and the difference in volume displacement was $528.7{\pm}374.4milliliters$. Multiple variable analysis showed that moderate to severe activity (OR; odds ratio =14, 95% CI :2.6-73.3), invasiveness of BC (OR =13.7, 95% CI :7.3-25.6), modified radical mastectomy (OR=4.3, 95% CI :2.3-7.9), BMI =>25 (OR=4.2, 95% CI :2-8.7), radiotherapy (OR=3.9, 95% CI :1.8-8.2), past history of limb damage (OR=1.7, 95% CI :0.9-3.1) and the number of excised lymph nodes (OR=1.06, 95% CI :1.02-1.09) were the significant predictors of lymphedema in women with BC. Modifiable risk factors of BCRL such as non-guided moderate to severe physical activity, high BMI and trauma to the limb should be controlled as early as possible in BC patients to prevent development of BCRL and improve QOL of these patients.