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thalidomide for refractory gastrointestinal bleeding from vascular malformations in patients with significant comorbidities

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World Journal of Clinical Cases 2020年第15期8卷 3218-3229页

作者： Alexis Mae Bayudan Chien-Huan Chen Department of Medicine Washington University School of MedicineSt.LouisMO 63108United States Division of Gastroenterology Department of Internal MedicineWashington University School of MedicineSt.LouisMO 63110United States

BACKGROUND Refractory gastrointestinal bleeding(GIB)secondary to gastrointestinal vascular malformations(GIVM)such as gastrointestinal angiodysplasia(GIAD)and gastric antral vascular ectasia(GAVE)remains challenging to treat when endoscopic therapy *** thalidomide has been suggested as a treatment option for refractory *** To determine the outcome of patients treated with thalidomide for refractory GIB due to *** IRB approved,single center,retrospective review of electronic medical records from January 2012 to November *** age>18 years old,who had>3 episodes of GIB refractory to medical or endoscopic therapy,and who had been treated with thalidomide for at least 3 mo were *** primary endpoint was recurrence of GIB 6 mo after initiation of *** Fifteen patients were included in the study,all with significant cardiac,hepatic,or renal *** cause of GIB was GIAD in 10 patients and GAVE in 5 *** patients were lost to follow *** the 13 patients followed,38.5%(n=5)had no recurrent GIB or transfusion requirement after treatment with ***,84.6%(n=11)of patients had a reduction in transfusion requirements and hospitalizations for *** was discontinued in 2 patients due to cost(n=1)and medication interaction(n=1).Reported adverse reactions included fatigue(n=3),neuropathy(n=2),dizziness(n=1),and constipation(n=1).Six patients died during follow up due to unknown cause(n=4)and sepsis(n=2).CONCLUSION thalidomide appears to be an effective treatment for refractory GIB due to GIAD or GAVE in a Western population with significant comorbidities.

关键词： Vascular malformation thalidomide Refractory gastrointestinal bleeding Gastric antral vascular ectasia Angiodysplasia

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thalidomide ameliorates portal hypertension via nitric oxide synthase independent reduced systolic blood pressure

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World Journal of Gastroenterology 2015年第14期21卷 4126-4135页

作者： Nicholas G Theodorakis Yining N Wang Vyacheslav A Korshunov Mary A Maluccio Nicholas J Skill Division of Transplant Surgery Department of SurgerySchool of MedicineIndiana University School of Medicine University of Rochester

AIM: Portal hypertension is a common complication of liver cirrhosis and significantly increases mortality and *** reports have suggested that the compound thalidomide attenuates portal hypertension(PHT).However, the mechanism for this action is not fully *** hypothesis is that thalidomide destabilizes tumor necrosis factor α(TNFα) mR NA and therefore diminishes TNFα induction of nitric oxide synthase(NOS) and the production of nitric oxide(NO).To examine this hypothesis, we utilized the murine partial portal vein ligation(PVL) PHT model in combination with endothelial or inducible NOS isoform gene knockout ***: Wild type, inducible nitric oxide synthase(i NOS)-/- and endothelial nitric oxide synthase(e NOS)-/-mice received either PVL or sham surgery and were given either thalidomide or *** nitrate(total nitrate, NOx) was measured daily for 7 d as a surrogate of NO *** TNFα level was quantified by enzyme-linked immunosorbent ***α m RNA was quantified in liver and aorta tissue by reverse transcription-polymerase chain *** was determined by recording splenic pulp pressure(SPP) and abdominal aortic flow after 0-7 *** to thalidomide was determined by measurement of SPP and mean arterial pressure(MAP).RESULTS: SPP, abdominal aortic flow(Qao) and plasma NOx were increased in wild type and i NOS-/-PVL mice when compared to sham operated control *** contrast, SPP, Qao and plasma NOx were not increased in e NOS-/- PVL mice when compared to sham *** TNFα level in both sham and PVL mice was below the detection limit of the commercial ELISA ***, the effect of thalidomide on serum TNFα levels was undetermined in wild type, e NOS-/-or i NOS-/- *** acutely increased plasma NOx in wild type and e NOS-/- mice but not i NOS-/-***, thalidomide temporarily(0-90 min) decreased mean arterial pressure, SPP and Qao in wild type, e NOS-/- and i NOS-/- PVL mice, aft

关键词： Portal hypertension thalidomide Nitric oxide Knock

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thalidomide combined with endoscopy in the treatment of Cronkhite-Canada syndrome:A case report

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World Journal of Clinical Cases 2022年第28期10卷 10366-10374页

作者： Jia-Mei Rong Meng-Lin Shi Jun-Kun Niu Juan Luo Ying-Lei Miao Department of Gastroenterology The First Affiliated Hospital of Kunming Medical UniversityKunming 650032Yunnan ProvinceChina

BACKGROUND Cronkhite-Canada syndrome(CCS)is a rare non-hereditary disease with a poor prognosis and a mortality rate of up to 55%.Currently,there is no standard treatment for *** department of gastroenterology of our hospital admitted a patient with CCS whose symptoms improved significantly after treatment with thalidomide combined with endoscopy,and there was no obvious adverse reaction during the 2-year *** SUMMARY A 47-year-old Chinese man presented with diarrhea for more than 4 mo,accompanied by loss of taste,fatigue,and weight *** examination demonstrated that the patient’s skin and hands were hyperpigmented,the front edges of the nails of both hands were notably thickened and yellow,and the nails were partially *** endoscopy identified a diffuse polypoid bulge,and the patient bore an albumin level of 27.3 g/*** level of the calcium correction amount was(2.164 m M)which allowed for a comprehensive diagnosis of Cronkhite-Canada syndrome,combined with hypoalbuminemia and *** of 150 mg per day was administered to regulate immunity,and the symptoms were relieved after 1 *** the follow-up period,polyps were still found that had not been resolved by thalidomide treatment,and endoscopic therapy was *** resulted in further improvement of his condition and no particular discomfort during the 2 years of *** The patient’s symptoms were significantly relieved by thalidomide 2 years after treatment,proposing it as a potential treatment for CCS.

关键词： Cronkhite-Canada syndrome Diarrhea Polyp thalidomide Endoscopic therapy Case report

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Preparation of thalidomide nano-flakes by supercritical antisolvent with enhanced mass transfer

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Particuology 2012年第1期10卷 17-23页

作者： HeyangJin Melinda Hemingway Ram B. Gupta Fei Xia Yaping Zhao School of Chemistry and Chemical Engineering ShanghaiJiaotong University Shanghai China Department of Chemical Engineering Auburn University Auburn AL USA

thalidomide treats multiple myeloma and protracts life-span of patient, but its bioavailability is limited as it is poorly water soluble. thalidomide nano-flakes are produced to improve the drug dissolution rate. Two nanoflake production methods are utilized for a comparative study： a supercritical antisolvent （SAS） method and a supercritical antisolvent with enhanced mass transfer （SAS-EM）. SAS-EM utilizes ultrasonication to improve dispersion upon injection within the supercritical carbon dioxide. Comparative study of SAS and SAS-EM thalidomide confirmed that the application of ultrasonication improved the micro/nano particles produced by SAS. The effects of ultrasound power on the formation of thalidomide particles are examined. The particle size and morphology were characterized by SEM. The thalidomide nano-flakes produced by SAS-EM were smaller than the particles produced by SAS. Dissolution rates of the produced particles, evaluated by HPLC, demonstrated an increase in the thalidomide dissolution rate for the SAS-EM produced particles, The polymorphs and crystallinity of thalidomide particles （flakes） were observed by FTIR and XRD. In this research, the supercritical processing significantly modified the crystal formation of thalidomide from an original state of a β-polymorph to the amorphous state α-polymorph after suoercritical orocessing.

关键词： Supercritical Anti-solventUltrasound thalidomide Nano-flakes Polymorph

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Therapeutic effects of thalidomide in hematologic disorders:a review

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Frontiers of Medicine 2013年第3期7卷 290-300页

作者： Miao Xu Yu Hou Lei Sheng Jun Peng Department of Hematology Qilu HospitalShandong UniversityJinan 250012China Shandong University School of Medicine JinanShandong250012China Department of General Surgery Qilu HospitalShandong UniversityJinan 250012China

The extensive autoimmune,anti-inflammatory,and anticancer applications of thalidomide have inspired a growing number of studies and clinical *** an inexpensive agent with relatively low toxicity,thalidomide is regarded as a promising therapeutic candidate,especially for malignant *** review its therapeutic effects in hematology,including those on multiple myeloma,Waldenstroem macroglobulinemia,lymphoma,mantle-cell lymphoma,myelodysplastic syndrome,hereditary hemorrhagic telangiectasia,and graft-versus-host *** studies have shown satisfactory results,although several have reported the *** from optimal outcomes,the toxicities and adverse effects of thalidomide should also be *** current work includes a discussion of the mechanisms through which the novel biological effects of thalidomide occur,although more studies should be devoted to this *** appropriate safeguards,thalidomide may benefit patients suffering from a broad variety of disorders,particularly refractory and resistant diseases.

关键词： thalidomide multiple myeloma lymphoma

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Safety and efficacy of thalidomide in patients with transfusiondependentβ-thalassemia:a randomized clinical trial

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Signal Transduction and Targeted Therapy 2021年第12期6卷 3723-3729页

作者： Jiang-Ming Chen Wei-Jian Zhu Jie Liu Gui-Zhen Wang Xiao-Qin Chen Yun Tan Wei-Wei Xu Li-Wei Qu Jin-Yan Li Huan-Ju Yang Lan Huang Ning Cai Wei-Da Wang Ken Huang Jian-Quan Xu Guo-Hui Li Sheng He Tian-Ying Luo Yi Huang Song-Hua Liu Wen-Qiang Wu Qi-Yang Lu Mei-Guang Zhou Shu-Ying Chen Rong-Lan Li Mei-Ling Hu Ying Huang Jin-Hua Wei Jun-Min Li Sai-Juan Chen Guang-Biao Zhou Department of Hematology Wuzhou Gongren HospitalWuzhou 543001 GuangxiChina Department of Hematology Zhuhai People’s Hospital(Zhuhai Hospital Affiliated with Jinan University)Zhuhai 541000 GuangdongChina State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Reproductive Medicine The First Affiliated Hospital of Hebei North UniversityZhangjiakou 075000 HebeiChina State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineMedical Oncology DepartmentSun Yat-Sen University Cancer CenterGuangzhou 510060 GuangdongChina State Key Laboratory of Medical Genomics Shanghai Institute of HematologyNational Research Center for Translational MedicineRuijin Hospital Affiliated with Shanghai Jiao Tong University School of MedicineShanghai 200025China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of Sciences&University of Chinese Academy of SciencesBeijing 100101China Department of Pediatrics Affiliated Hospital of Youjiang Medical University for NationalitiesBaise City 533000 GuangxiChina Department of Hematology Yulin Guinan HospitalYulin 537005 GuangxiChina Department of neurology Wuzhou Gongren HospitalWuzhou 543001 GuangxiChina Guangxi Key Laboratory of Basic Research on Birth Defects Prevention and Treatment Guangxi Zhuang Autonomous Region Women and Children Health Care HospitalNanning 530000 GuangxiChina Department of Hematology Guigang People’s HospitalGuigang 537100 GuangxiChina Department of Hematology Hospital of Traditional Chinese Medicine of Wuzhou CityWuzhou 543002 GuangxiChina Department of Hematology Wuzhou Red Cross HospitalWuzhou 543002 GuangxiChina Department of Hematology Hechi People’s HospitalHechi City 547000 GuangxiChina

thalidomide inducesγ-globin expression in erythroid progenitor cells,but its efficacy on patients with transfusion-dependentβ-thalassemia(TDT)remains *** this phase 2,multi-center,randomized,double-blind clinical trial,we aimed to determine the safety and efficacy of thalidomide in TDT patients.A hundred patients of 14 years or older were randomly assigned to receive placebo or thalidomide for 12 weeks,followed by an extension phase of at least 36 *** primary endpoint was the change of hemoglobin(Hb)level in the *** secondary endpoints included the red blood cell(RBC)units transfused and adverse *** the placebo-controlled period,Hb concentrations in patients treated with thalidomide achieved a median elevation of 14.0(range,2.5 to 37.5)g/L,whereas Hb in patients treated with placebo did not significantly *** the 12 weeks,the mean RBC transfusion volume for patients treated with thalidomide and placebo was 5.4±5.0 U and 10.3±6.4 U,respectively(Pthalidomide than *** the extension phase,treatment with thalidomide for 24 weeks resulted in a sustainable increase in Hb concentrations which reached 104.9±19.0 g/L,without blood *** increase in Hb concentration and reduction in RBC transfusions were associated with nonβ0/β0 and HBS1L-MYB(rs9399137 C/T,C/C;rs4895441 A/G,G/G)*** results demonstrated that thalidomide is effective in patients with TDT.

关键词： transfusion patients thalidomide

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Synthesis and biological evaluation of novel thalidomide analogues as potential anticancer drugs

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Chinese Chemical Letters 2008年第8期19卷 928-930页

作者： Tao Wang Yi Hua Zhang Shan Yu Hui Ji Yi Sheng Lai Si Xun Peng a Center of Drug Discovery China Pharmaceutical University Nanjing 210009 China Department of Pharmacology China Pharmaceutical University Nanjing 210009 China

In search of novel anticancer agents, a series of thalidomide analogs （6a-j） were designed and synthesized. Cytotoxicity of these compounds against human hepatoma cells （HepG2） was evaluated by MTT method. Compoun... 详细信息

关键词： thalidomide 1,3,4-Thiadiazole Anti-tumor activity HepG2

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Physics, chemistry, and Hirshfeld surface analyses of gamma-irradiated thalidomide to evaluate behavior under sterilization doses

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Journal of Pharmaceutical Analysis 2018年第3期8卷 194-201页

作者： Valner A.F.S.N.Mussel Max R Ferreira Maria B.E Marques Maria I.Yoshida Mariana R.Almeida Bernardo L.Rodrigues Wagner N.Mussel Departamento de Quimica ICExUniversidade Federal de Minas Gerais-UFMGAv.Antonio Carlos 662731270-901 Belo HorizonteMGBrazil CNEN-CDTN Comissao Nacional de Energia Nuclear-Centro de Desenvolvimento da Tecnologia NuclearAv.Antonio Carlos6627 Belo HorizonteMGBrazil

thalidomide was indicated as a sedative and antiemetic and prescribed for pregnant women. Its tragic teratogenic effects culminated in withdrawal from the market. Since the discovery of its anti-angiogenic and anti-inflammatory actions, thalidomide has been used in the treatment of leprosy and multiple myeloma, which justify studies of its stability. We investigated the effects of irradiation of thalidomide up to 100 kGy （fourfold the usual sterilizing dose for pharmaceutics）. The polymorph of thalidomide was obtained in an isothermal experiment at 270℃. All samples underwent gamma irradiation for specific times. At different doses, decomposition of the pharmaceutical was not observed up to 100 kGy. The observed effect was angle turning between the phthalimide and glutarimide rings modulated by repulsion towards the carbonyl group, leading to a stable energetic configuration, as measured by the equilibrium in the torsion angle after irradiation. The thalidomide molecule has a center of symmetry, so a full turn starting from 57.3° will lead to an identical molecule. Further irradiation will start the process again. Samples irradiated at 30 and 100 kGy have more compact unit cells and a lower volume, which leads to an increase in the intermolecular hydrogen interaction within the unit cell, resulting in higher thermal stability for polymorph α.

关键词： thalidomide Thermal stability Polymorphs Gamma irradiation Hirshfeld

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Clinical trial of thalidomide combined with radiotherapy in patients with esophageal cancer

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World Journal of Gastroenterology 2014年第17期20卷 5098-5103页

作者： Jing-Ping Yu Su-Ping Sun Zhi-Qiang Sun Xin-Chu Ni Jian Wang Yi Li Li-Jun Hu Dong-Qing Li Department of Radiation Oncology Changzhou Second People’s HospitalAffiliated to Nanjing Medical University

AIM: To investigate the short-term efficacy and tolerability of radiotherapy plus thalidomide in patients with esophageal cancer (EC).

关键词： thalidomide Radiotherapy Esophageal cancer Vascular endothelial growth factor

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Efficacy of thalidomide therapy in pediatric Crohn's disease with evidence of tuberculosis

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World Journal of Gastroenterology 2017年第43期23卷 7727-7734页

作者： Lin Wang Yan Hong Jie Wu Ying-Kit Leung Ying Huang Department of Gastroenterology Pediatric Inflammatory Bowel Disease Research CenterChildren’s Hospital of Fudan University Department of Pediatrics Taizhou Women’s and Children’s Hospital of Wenzhou Medical University

AIM To evaluate the efficacy of thalidomide for treating troublesome cases of pediatric Crohn's disease(CD) with tuberculosis *** A retrospective study of clinical outcome among children treated with thalidomide was conducted. All patients had evidence of tuberculosis infection with a failure of anti-tuberculosis treatment for more than one year,and were subsequently diagnosed with CD. All the patients received thalidomide treatment with a starting dose of 1.2-2.5 mg/kg per day. Remission was defined as pediatric CD activity index less than or equal to *** Ten patients with CD were treated with thalidomide at an average age of 7.2 years and followed up for a median of 22.2 mo. Clinical remission rate was 60% after 9-12 mo of thalidomide treatment. One patient with no response had an interleukin-10 receptor alpha gene mutation. Erythrocyte sedimentation rate,C-reactive protein and platelet count showed a dramatic decrease; hemoglobin level and weight improved significantly after thalidomide treatment when compared with the baseline *** thalidomide is an effective and safe drug for remission of CD in pediatric patients who have been treated for tuberculosis.

关键词： Inflammatory bowel disease Intestinal tuberculosis Anti-tubercular treatment thalidomide Children

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