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이형곤,김웅모,윤명하,A Reum Park,최정일 대한마취통증의학회 2013 Korean Journal of Anesthesiology Vol.65 No.4
Background: Thalidomide has been recognized as having an anti-allodynic effect against neuropathic pain induced by spinal nerve ligation. Its clinical beneficial effects are mainly derived from its immune-modulating property, which is known to influence the analgesic action of morphine. The possible characteristics of systemic interactions between thalidomide and morphine in the context of spinal nerve ligation-induced neuropathic pain were examined in rats. Methods: Neuropathic pain was induced by ligation of the L5/6 spinal nerves in male Sprague-Dawley rats and mechanical allodynia was assessed using von Frey filaments. The ED50 was calculated for thalidomide and for morphine, and the mixture of both drugs was intraperitoneally administered at different doses of ED50 of each drug (1/8, 1/4, 1/2, 1/1 of ED50) to obtain the experimental ED50 value for the combination of thalidomide and morphine. Isobolographic analysis was used to evaluate the characteristics of drug interactions between morphine and thalidomide. Results: The ED50 of thalidomide was three-fold higher than that of morphine. The experimental ED50 value of the mixture of thalidomide and morphine was significantly lower than the calculated theoretical ED50 value. Isobolographic analysis revealed a synergistic interaction for anti-allodynic effect after intraperitoneal delivery of the thalidomide-morphine mixture. Conclusions: These results suggest that thalidomide acts synergistically with morphine to produce an anti-allodynic effect in neuropathic pain induced by spinal nerve ligation in rats. Thus, the combination of thalidomide with morphine may be one of the useful strategies in the management of neuropathic pain.
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누드마우스에 이종이식된 구강편평상피세포암종에 대한 thalidomide의 항암효과와 혈관형성억제에 관한 연구
김수곤,명훈,김명진,Kim, Su-Gon,Myoung, Hoon,Kim, Myung-Jin 대한구강악안면외과학회 2001 대한구강악안면외과학회지 Vol.27 No.4
Angiogenesis is an essential process for the growth, invasion and metastasis of cancer. However, it is uncertain that antiangiogenic effects can be a major treatment strategy of oral cancer. The aim of this study was to investigate whether thalidomide, which is known to be a potent inhibitor of angiogenesis, have inhibitory effect on the growth and antiangiogenic effects of oral squamous cell carcinoma(OSCC) xenografted in nude mice and whether antiangiogenesis of thalidomide can be included as a major treatment strategy of oral cancer. After human oral squamous cell carcinoma strain KB was subcutaneously implanted in 20 nude mice, the volume of tumor was measured every three days. When the tumor mass reached $75{\sim}100mm^3$, thalidomide(200mg/kg/d) was administered into 10 experimental nude mice and the same volume of distilled water was administered into 10 control nude mice and the tumor volume was measured every three days. The excised tumor masses on the 30th day after administration were frozen and processed for immunohistochemistry using vascular endothelial growth factor(VEGF) and CD31. We evaluated microvessel density and VEGF expression. The results were as follows ; 1. Thalidomide retarded the growth of human OSCC as compared with the control group, but it was not statistically significant. 2. A statistically significant lower microvessel density was observed in the thalidomide-treated group than in the control group(p<0.01) and thalidomide significantly reduced VEGF expression (p<0.01). Thalidomide exhibited significantly antiangiogenic effect, but did not inhibit the growth of human OSCC effectively. Antiangiogenic therapy of thalidomide alone is not likely to be effective in the treatment of human OSCC, but might be regarded as adjuvant chemotherapeutic strategy.
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한국인 베체트 장염 환자에서 Thalidomide의 치료 경험: 단일 기관의 초기 경험
이현정 ( Hyun Jung Lee ),천재희 ( Jae Hee Cheon ),이경주 ( Kyong Joo Lee ),장희원 ( Hui Won Jang ),정규식 ( Kyu Sik Jung ),정은석 ( Eun Suk Jung ),이진하 ( Jin Ha Lee ),전승민 ( Seung Min Jeon ),홍성필 ( Sung Pil Hong ),김태일 ( T 대한장연구학회 2010 Intestinal Research Vol.8 No.1
Intestinal Behcet’s disease (BD) often leads to severe complications, such as perforation or massive bleeding, and therefore is one of the major causes of morbidity and mortality. As thalidomide has been identified and its anti-inflammatory and immunomodulatory properties clarified, this drug has been used in cases of systemic BD with some success. Herein we report a case series of four patients with intestinal BD to share our clinical experience with thalidomide treatment. We studied the effects of thalidomide in four patients who had a chronic relapse of intestinal BD requiring the frequent use of systemic steroids due to refractoriness to prior treatments, such as 5-aminosalycylic acid and immunosuppressants. Pre- and post-treatment clinical and laboratory data, including clinical symptoms, laboratory data, disease activity index for intestinal BD, and thalidomide toxicity were recorded. Three of the four patients had a clinical and radiologic improvement after thalidomide treatment and all of the patients discontinued steroid therapy. Although two patients tolerated thalidomide, two patients could not continue the treatment because they suffered from edema and neutropenia. Thalidomide could be considered a therapeutic option for the treatment of intestinal BD. (Intest Res 2010;8:63-69)
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Kim, Ki-Hoon,Choi, Chang-Bon,Kim, Jong-Yeon Yeungnam University College of Medicine 2018 Yeungnam University Journal of Medicine Vol.35 No.2
Background: Body fats, especially both of abdominal fat pad mass and skeletal muscle fat content, are inversely related to insulin action. Therefore, methods for decreasing visceral fat mass and muscle triglyceride content may be helpful for the prevention of insulin resistance. Methods: Thalidomide, used for its anti-angiogenic and anti-inflammatory properties, was administered to rats for 4 weeks. A 10% solution of thalidomide in dimethyl sulfoxide was injected daily into the peritoneal cavity as much as 100 mg/kg of body weight. Results: The total visceral fat pad mass in the thalidomide-treated group was 11% lower than in the control group. The size of adipocytes of the epididymal fat pad mass in the thalidomide-treated group was smaller than in the control group. The intraperitoneal thalidomide treatment increased triglyceride concentrations by 16% in the red muscle, but not in the white muscle. Conclusion: The results suggested that intraperitoneal thalidomide treatment inhibited abdominal fat accumulation, and that the free fatty acids in the blood were preferentially accumulated in the red muscle rather than in the white muscle.
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김기훈,최창본,김종연 영남대학교 의과대학 2018 Yeungnam University Journal of Medicine Vol.35 No.2
Background: Body fats, especially both of abdominal fat pad mass and skeletal muscle fat content, are inversely related to insulin action. Therefore, methods for decreasing visceral fat mass and muscle triglyceride content may be helpful for the prevention of insulin resistance. Methods: Thalidomide, used for its anti-angiogenic and anti-inflammatory properties, was administered to rats for 4 weeks. A 10% solution of thalidomide in dimethyl sulfoxide was injected daily into the peritoneal cavity as much as 100 mg/kg of body weight. Results: The total visceral fat pad mass in the thalidomide-treated group was 11% lower than in the control group. The size of adipocytes of the epididymal fat pad mass in the thalidomide-treated group was smaller than in the control group. The intraperitoneal thalidomide treatment increased triglyceride concentrations by 16% in the red muscle, but not in the white muscle. Conclusion: The results suggested that intraperitoneal thalidomide treatment inhibited abdominal fat accumulation, and that the free fatty acids in the blood were preferentially accumulated in the red muscle rather than in the white muscle.
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( Ki-hoon Kim ),( Chang-bon Choi ),( Jong-yeon Kim ) 영남대학교 의과대학 2018 Yeungnam University Journal of Medicine Vol.35 No.2
Background: Body fats, especially both of abdominal fat pad mass and skeletal muscle fat content, are inversely related to insulin action. Therefore, methods for decreasing visceral fat mass and muscle triglyceride content may be helpful for the prevention of insulin resistance. Methods: Thalidomide, used for its anti-angiogenic and anti-inflammatory properties, was administered to rats for 4 weeks. A 10% solution of thalidomide in dimethyl sulfoxide was injected daily into the peritoneal cavity as much as 100 mg/kg of body weight. Results: The total visceral fat pad mass in the thalidomide-treated group was 11% lower than in the control group. The size of adipocytes of the epididymal fat pad mass in the thalidomide-treated group was smaller than in the control group. The intraperitoneal thalidomide treatment increased triglyceride concentrations by 16% in the red muscle, but not in the white muscle. Conclusion: The results suggested that intraperitoneal thalidomide treatment inhibited abdominal fat accumulation, and that the free fatty acids in the blood were preferentially accumulated in the red muscle rather than in the white muscle.
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Peng Lv,Qingshun Meng,Jie Liu,Chuanfang Wang 연세대학교의과대학 2015 Yonsei medical journal Vol.56 No.6
Purpose: The degradation of the extracellular matrix has been shown to play an important role in the treatment of hepatic cirrhosis. In this study, the effect of thalidomide on the degradation of extracellular matrix was evaluated in a rat model of hepatic cirrhosis. Materials and Methods: Cirrhosis was induced in Wistar rats by intraperitoneal injection of carbon tetrachloride (CCl4) three times weekly for 8 weeks. Then CCl4 was discontinued and thalidomide (100 mg/kg) or its vehicle was administered daily by gavagefor 6 weeks. Serum hyaluronic acid, laminin, procollagen type III, and collagen type IV were examined by using a radioimmunoassay. Matrix metalloproteinase-13 (MMP-13), tissue inhibitor of metalloproteinase-1 (TIMP-1), and α-smooth muscle actin(α-SMA) protein in the liver, transforming growth factor β1 (TGF-β1) protein in cytoplasm by using immunohistochemistry and Western blot analysis, and MMP-13, TIMP-1, and TGF-β1 mRNA levels in the liver were studied using reverse transcriptase polymerase chain reaction. Results: Liver histopathology was significantly better in rats given thalidomide than in the untreated model group. The levels of TIMP-1 and TGF-β1 mRNA and protein expressions were decreased significantly and MMP-13 mRNA and protein in the liver were significantly elevated in the thalidomide-treated group. Conclusion: Thalidomide may exert its effects on the regulation of MMP-13 and TIMP-1 via inhibition of the TGF-β1 signaling pathway, which enhances the degradation of extracellular matrix and accelerates the regression of hepatic cirrhosis in rats.
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Thalidomide Combined with Chemotherapy in Treating Patients with Advanced lung Cancer
Li, Li,Huang, Xin-En Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.5
Objectives: To evaluate efficacy and toxicity in patients with advanced lung cancer, including non-small cell and small cell variants (NSCLC and SCLC), treated with thalidomide plus chemotherapy. Methods: Fourteen patients with advanced lung cancer were scheduled to receive chemotherapy combined with thalidomide. All patients in this study received thalidomide (100 mg orally per night before sleeping, produced by Changzhou Pharmaceutical Factory Co.Ltd) after the start of chemotherapy for at least 14 days. Chemotherapy was administered according to the condition of patients. After at least 14 days of treatment, efficacy and toxicity were evaluated. Results: There were 6 female and 8 male patients with advanced lung cancer recruited into this study, including 2 with SCLC and 12 with NSCLC. The median age was 56.7 (44-65) years. Progressive disease was observed in 12 patients (12/14), and stable disease in 2 (2/14). Grade 1 to 2 myelosuppression was observed in 4/14 patients, and Grade 1 to 2 elevation of hepatic enzymes was recorded in 5/14 patients. Adverse effects on the gastrointestinal tract were documented in 2/14 patients, all beingGrade 1. No Grade 3-4 toxicity was recorded. No treatment related deaths occurred. Conclusions: Our results demonstrate that thalidomide combined with chemotherapy is mildly effective and safe for treating patients with advanced lung cancer. However, further evaluation of this combination is warranted.
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다발성골수종 환자의 일차 치료제로서 탈리도마이드 병합요법의 임상적 효능
정성훈,이제중,손상균,신호진,양덕환,김여경,김상기,백진호,김동환,김종광,정주섭,조군제,김형준 대한혈액학회 2006 Blood Research Vol.41 No.2
배경: 본 연구에서는 새로이 진단된 다발성골수종 환자를 대상으로 thalidomide를 포함한 복합 항암요법을 시행하여서 그 임상적인 유효성과 안전성, 또한 말초혈액 조혈모세포 채집에 미치는 영향을 알아보고자 하였다. 방법: 새로 진단된 다발성골수종 환자에 TD 요법(thalidomide와 dexamethasone) 또는 TCD 요법(thalidomide, cyclophosphamide, dexamethasone)을 투여한 후 치료에 대한 반응을 평가하였으며, G-CSF±cyclophosphamide로 조혈모세포를 가동화시킨 후 말초혈액 조혈모세포를 채집하였다. 결과: 2003년 6월부터 2005년 12월까지 새로 진단된 다발성골수종 환자 60예를 대상으로 상기 요법이 투여되었으며, 이 중 4주기 이상 투여되어서 평가 가능한 56예를 대상으로 치료에 대한 반응과 독성을 분석하였다. 중앙연령은 65.5세(범위: 39~80세)였다. 치료에 대한 전체반응률은 85.5%를 보였고, TD 요법을 시행받은 12예의 환자 중에서 완전반응은 3예(25%), 부분반응은 6예(50%)를 보였으며, TCD 요법을 시행받은 44예의 환자 중에서 완전반응은 17예(38.6%), 부분반응은 21예(47.7%)를 보였다. NCI-CTC 기준 3도 이상 치료 독성은 호중구감소증 7예(12.5%), 혈소판감소증 4예(7.1%), 감염 6예(10.7%), 신경병증 10예(17.8%)가 발생하였고, 또한 혈전증이 2예(3.6%)에서 발생하였다. 부분반응 이상을 보인 환자 중 13예에서 자가 조혈모세포를 채집하였으며, 채집한 CD34 양성 세포의 중앙치는 3.8×106/kg을 보였다.
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