Thalidomide,an immunomodulatory drug,is widely recommended for the treatment of recurrent aphthous stomatitis(RAS).This review aimed to assess the reliability of thalidomide for managing RAS,oro-genital ulcers associa...Thalidomide,an immunomodulatory drug,is widely recommended for the treatment of recurrent aphthous stomatitis(RAS).This review aimed to assess the reliability of thalidomide for managing RAS,oro-genital ulcers associated with Behçet’s disease(BD),and RAS in individuals with HIV infection.A systematic review was conducted following PICOS(Patient,Intervention,Control,Outcome,Study design)principles.Given the heterogeneity across studies,a qualitative analysis was performed in place of a meta-analysis.Eight randomized controlled trials(RCTs)were deemed eligible for inclusion.In three RCTs focused on RAS,a dosage of thalidomide at 100 mg/d demonstrated efficacy,while a lower dose of 25 mg/d helped prolong the recurrence interval of RAS.For oro-genital ulcers of BD,two RCTs indicated that both 300 mg/d for 24 weeks and 200 mg/d for 28 d,preceded by an initial dose of 400 mg/d for 5 d,were effective.In three RCTs investigating RAS in HIV-infected patients,thalidomide at 200 mg/d for either 4 or 7 weeks,with an initial dose of 400 mg/d for the first week,proved effective.However,a regimen of 100 mg three times per week failed to prevent the recurrence of oral ulcers.Adverse reactions to thalidomide were generally tolerable within the dosage ranges used in these studies.Overall,thalidomide showed promising efficacy for treating RAS,oro-genital ulcers in BD,and RAS in HIV-infected individuals.However,the variability in trial designs,dosages,and treatment durations makes it challenging to recommend an optimal dose and course of therapy.Further high-quality RCTs are necessary to establish more definitive guidelines.展开更多
Thalidomide(THA)is renowned for its potent anti-inflammatory properties.This study aimed to elucidate its underlying mechanisms in the context of Crohn's disease(CD)development.Mouse colitis models were establishe...Thalidomide(THA)is renowned for its potent anti-inflammatory properties.This study aimed to elucidate its underlying mechanisms in the context of Crohn's disease(CD)development.Mouse colitis models were established by dextran sulfate sodium(DSS)treatment.Fecal microbiota and metabolites were analyzed by metagenomic sequencing and mass spectrometry,respectively.Antibiotic-treated mice served as models for microbiota depletion and transplantation.The expression of forkhead box P3+(FOXP3+)regulatory T cells(Tregs)was measured by flow cytometry and immunohistochemical assay in colitis model and patient cohort.THA inhibited colitis in DSS-treated mice by altering the gut microbiota profile,with an increased abundance of probiotics Bacteroides fragilis,while pathogenic bacteria were depleted.In addition,THA increased beneficial metabolites bile acids and significantly restored gut barrier function.Transcriptomic profiling revealed that THA inhibited interleukin-17(IL-17),IL-1βand cell cycle signaling.Fecal microbiota transplantation from THA-treated mice to microbiota-depleted mice partly recapitulated the effects of THA.Specifically,increased level of gut commensal B.fragilis was observed,correlated with elevated levels of the microbial metabolite 3alpha-hydroxy-7-oxo-5beta-cholanic acid(7-ketolithocholic acid,7-KA)following THA treatment.This microbial metabolite may stable FOXP3 expression by targeting the receptor FMR1 autosomal homolog 1(FXR1)to inhibit autophagy.An interaction between FOXP3 and FXR1 was identified,with binding regions localized to the FOXP3 domain(aa238-335)and the FXR1 domain(aa82-222),respectively.Conclusively,THA modulates the gut microbiota and metabolite profiles towards a more beneficial composition,enhances gut barrier function,promotes the differentiation of FOXP3+Tregs and curbs pro-inflammatory pathways.展开更多
Objectives:A common side effect of inflammatory bowel disease(IBD)is intestinal fibrosis,which frequently leads to intestinal blockage and stricture formation.Although Thalidomide(THD)has shown anti-fibrotic benefits ...Objectives:A common side effect of inflammatory bowel disease(IBD)is intestinal fibrosis,which frequently leads to intestinal blockage and stricture formation.Although Thalidomide(THD)has shown anti-fibrotic benefits in hepatic and renal models,little is known about how it affects intestinal fibrosis and the underlying processes.The present research examines the molecular targets of THD and its potential as a treatment for intestinal fibrosis brought on by colitis.Methods:Clinical samples from Crohn’s disease(CD)patients with intestinal strictures treated with infliximab(IFX)and THD combined with IFX were collected.Dextran sulfate sodium(DSS)was used to develop a mouse model of intestinal fibrosis in C57BL/6 mice.Anti-tumor necrosis factor-alpha(Anti-TNFα),THD,or a combination of the two were administered to the mice.Body weight,colon length,histology,and disease activity index were used to evaluate the disease’s severity.In vitro,THD was tested on colonic fibroblast lines(CCD-18Co and MPF)to assess its effects on cell proliferation,motility,and transdifferentiation.To examine changes in gene expression and signaling pathway modifications,namely in the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR)pathway,RNA sequencing,qRT-PCR,and Western blotting were carried out.Results:In DSS-induced colitis,THD therapy lowered fibrosis,as seen by downregulated fibrotic markers(α-smooth muscle actin(α-SMA),collagen I,and collagen III)and decreased collagen deposition.Mechanistically,THD prevented fibroblasts from transdifferentiating and decreased their vitality.Furthermore,THD inhitited the PI3K/AKT/mTOR pathway in vivo and in vitro.Conclusion:THD inhibits the PI3K/AKT/mTOR signaling cascade and suppresses colonic fibroblast transdifferentiation,which protects against DSS-induced colitis-associated fibrosis,especially when combined with anti-TNFαtherapy.展开更多
The aim of this study was to evaluate the protective effect of thalidomide derivative ZSN-12 on acute lung injury induced by oleic acid in mice, and to investigate the possible mechanisms. The results showed that ZSN-...The aim of this study was to evaluate the protective effect of thalidomide derivative ZSN-12 on acute lung injury induced by oleic acid in mice, and to investigate the possible mechanisms. The results showed that ZSN-12 （200 mg/kg） markedly improved the pathological changes of acute lung injury. The proportion of polymorphonuclear neutrophils （PMN） was reduced by 48% （P〈0.01） and the content of nitric oxide （NO） in bronchoalveolar lavage fluid （BALF） was decreased by 33% （P〈0.05）. ZSN-12 produced significant anti-inflammatory effects in the models of xylene induced ear edema and carrageenan induced paw edema, in which ZSN-12 inhibited ear edema and paw swelling in a dose-dependent manner. The inhibition rates by ZSN-12 dosed at 200, 100, 50 mg/kg were 62%, 43%, and 30% in ear edema, respectively and 60%, 47%, and 33% in paw edema, respectively, at 3 h. Meanwhile, ZSN-12 （10, 5, 1 μmol/L） significantly restrained the ConA-induced T lymphocyte proliferation, with the inhibition rates of 33%, 30% and 22%, respectively （P〈0.01）. In conclusion, the present study showed that administration of thalidomide derivative ZSN-12 exerted significant protective effect in acute lung injury induced by oleic acid in mice, which may be related to its anti-inflammation effect. ZSN-12 inhibited the effusion of PMN, reduced the release of NO, and suppressed the proliferation of T lymphocyte.展开更多
AIMTo examine the efficacy and safety of thalidomide and thalidomide analogues in induction and maintenance of remission in patients with inflammatory bowel disease （IBD）.METHODSA literature search was performed in ...AIMTo examine the efficacy and safety of thalidomide and thalidomide analogues in induction and maintenance of remission in patients with inflammatory bowel disease （IBD）.METHODSA literature search was performed in the following databases： PubMed, EMBASE, Web of Science, Ovid and the Cochrane Library, and Chinese databases such as the China National Knowledge Infrastructure, China Science and Technology Journal Database （VIP）, Wanfang Data. The randomized controlled analysis was performed to assess the effects of thalidomide therapy on infammatory bowel disease for patients who did show good response with other therapies.RESULTSThree studies （ n = 212） met the inclusion criteria were used in this Meta-analysis. No difference was found between thalidomide/thalidomide analogues and placebo in the induction of remission （RR = 1.36, 95%CI： 0.83-2.22, P = 0.22）, the induction of clinical response （RR = 1.14, 95%CI： 0.75-1.72, P = 0.54） and the induction of adverse events （RR = 1.41, 95%CI： 0.99-2.02, P = 0.06）.CONCLUSIONCurrently, there is not enough evidence to support use of thalidomide or its analogue for the treatment in patients of any age with IBD. However, it warrants a reanalysis when more data become available.展开更多
Thalidomide is widely used in the treatment of multiple myeloma (MM). In recent years, several cases of pulmonary hypertension have been reported following treatment with thalidomide. The aim of this review was to eva...Thalidomide is widely used in the treatment of multiple myeloma (MM). In recent years, several cases of pulmonary hypertension have been reported following treatment with thalidomide. The aim of this review was to evaluate the published literature on multiple myeloma patients with pulmonary hypertension following thalidomide treatment. A literature search was performed between 2000 and 2016. A total of 7 eligible studies were identified and deemed eligible, including 11 cases—approximately 37% (4 cases) with IgA (k), 27% (3 cases) with IgG (λ) MM, 27% (3 cases) with IgG (k) MM, and one case (9%) with primary plasma cell leukemia (PPCL). The vast majority of cases—82% (9 cases)—are associated with thalidomide, while only 18% (2 cases) are related to thalidomide derivatives (lenalidomide and pomalidomide). In conclusion, pulmonary hypertension induced by thalidomide or derivatives in multiple myeloma (MM) patients is related to a multifactorial etiology including the pathophysiology of the disease, thromboembolic events, preexisted cardiovascular conditions, comorbidities, and combination with other chemo- or bio-therapeutic agents. MM patients should be evaluated for signs and symptoms underlying cardiopulmonary disease before initiating, and during treatment with thalidomide.展开更多
AIM: To evaluate which patients with hepatocellular carcinoma (HCC) are most likely to respond to thalidomide treatment. METHODS: From July 2002 to July 2004, patients with HCC who received thalidomide treatment, were...AIM: To evaluate which patients with hepatocellular carcinoma (HCC) are most likely to respond to thalidomide treatment. METHODS: From July 2002 to July 2004, patients with HCC who received thalidomide treatment, were enrolled. We extracted relevant data from the patients’ medical records, including history and type of hepatitis, comorbidity, serum α-fetoprotein (α-FP) level, volumetric changes in tumor, length of survival, and the dose, duration, side effects of thalidomide treatment. The tumor response was evaluated. On the basis of these data, the patients were divided into two groups: those with either partial response or stable disease (PR + SD group) and those with progressive disease (PD group). RESULTS: Two of 42 (5%) patients had a partial tumor response after treatment with thalidomide, 200 mg/d, and 9 (21%) had stable disease. Patients in the PR + SD group all had cirrhosis. Comparing patients with and without cirrhosis, the former were more likely to respond to thalidomide therapy (PR + SD: 100% vs PD: 64.5%, P = 0.041 < 0.05). Thalidomide was significantly more likely to be effective in tumors smaller than 5 cm (PR + SD: 63.6% vs PD: 25.8%, P = 0.034 < 0.05). Compared with patients with progressive disease (PD), patients in the PR + SD group had a higher total dose of thalidomide (13 669.4 ± 8446.0 mg vs 22 022.7 ± 11 461.4 mg, P = 0.023 < 0.05) and a longer survival (181.0 ± 107.1 d vs 304.4 ± 167.1 d, P = 0.047 < 0.05). Patients with comorbid disease had a significantly greater incidence of adverse reactions than those without (93.8% vs 60.0%, P = 0.021 < 0.05). The average number of adverse reactions in each person with a comorbid condition was twice as high as in those without other diseases (2.2 ± 1.3 vs 1.1 ± 1.2; P = 0.022 < 0.05). CONCLUSION: Thalidomide therapy is most likely to beeffective in patients with early stage small HCC, espe- cially in those with other underlying diseases. A low dose (200 mg/d) of thalidomide is recommended to continue the treatment long enough to make it more effective.展开更多
AIM:To investigate the effects of thalidomide on angiogenesis,tumor growth and metastasis of hepatocellular carcinoma in nude mice.METHODS:Twenty-four nude mice were randomly divided into therapy group and control gro...AIM:To investigate the effects of thalidomide on angiogenesis,tumor growth and metastasis of hepatocellular carcinoma in nude mice.METHODS:Twenty-four nude mice were randomly divided into therapy group and control group,12 mice in each group.Thalidomide dissolved in 0.5%sodium carboxyl methyl cellulose(CMC)suspension was administered intraperitoneally once a day at the dose of 200 mg/kg in therapy group,and an equivalent volume of 0.5%CMC in control group.Mice were sacrificed on the 30th d,tumor size and weight and metastases in liver and lungs were measured.CD34 and VEGF mRNA in tumor tissue were detected by immunohistochemistry and semi-quantitative RT-PCR respectively and microvessel density(MVD)was counted.Serum concentrations of TNF-αand ALT and AFP were also tested.RESULTS:MVD and VEGF mRNA in therapy group were less than those in control group(31.08±16.23 vessels/HP vs 80.00±26.27 vessels/HP,0.0538±0.0165 vs 0.7373±0.1297,respectively,P<0.05).No statistical difference was observed in tumor size and weight and metastases in liver and lungs.TNF-αwas significantly lower in therapy group than in control group(28.64±4.64 ng/L vs42.69±6.99 ng/L,P<0.05).No statistical difference in ALT and AFP was observed between groups.CONCLUSION:Thalidomide can significantly inhibitangiogenesis and metastasis of hepatocellular carcinoma.Italso has inhibitory effects on circulating TNF-α.展开更多
AIM: To assess the efficacy and tolerability of thalidomide in pediatric Crohn's disease (CD). METHODS: Six patients with refractory CD received thalidomide at an initial dose of 2 mg/kg per day for one month, the...AIM: To assess the efficacy and tolerability of thalidomide in pediatric Crohn's disease (CD). METHODS: Six patients with refractory CD received thalidomide at an initial dose of 2 mg/kg per day for one month, then increased to 3 mg/kg per day or decreased to 1 mg/kg per day, and again further reduced to 0.5 mg/kg per day, according to the individual patient's response to the drug. RESULTS: Remission was achieved within three months. Dramatic clinical improvement was demonstrated after thalidomide treatment. Endoscopic and pathological improvements were also observed after thalidomide treatment, which was well tolerated by all patients. CONCLUSION: Thalidomide is a useful drug for pediatric refractory CD.展开更多
AIM: To determine whether thalidomide prevents microvascular injury in acute radiation proctitis in white rats. METHODS: Fourteen female Wistar rats were used: six in the radiation group, six in the thalidomide group,...AIM: To determine whether thalidomide prevents microvascular injury in acute radiation proctitis in white rats. METHODS: Fourteen female Wistar rats were used: six in the radiation group, six in the thalidomide group, and two in normal controls. The radiation and thalidomide groups were irradiated at the pelvic area using a single 30 Gy exposure. The thalidomide (150 mg/kg) was injected into the peritoneum for 7 d from the day of irradiation. All animals were sacrificed and the rectums were removed on day 8 after irradiation. The microvessels of resected specimens were immunohistochemically stained with thrombomodulin (TM), von Willebrand Factor (vWF), and vascular endothelial growth factor (VEGF). RESULTS: The microscopic scores did not differ significantly between the radiation and thalidomide groups, but both were higher than in the control group. Expression of TM was significantly lower inthe endothelial cells (EC) of the radiation group than in the control and thalidomide groups (P < 0.001). The number of capillaries expressing vWF in the EC was higher in the radiation group (15.3 ± 6.8) than in the control group (3.7 ± 1.7), and the number of capillaries expressing vWF was attenuated by thalidomide (10.8 ± 3.5, P < 0.001). The intensity of VEGF expression in capillaries was greater in the radiation group than in the control group and was also attenuated by thalidomide (P = 0.003). CONCLUSION: The mechanisms of acute radiation- induced proctitis in the rats are related to endothelial cell injury of microvessel, which may be attenuated with thalidomide.展开更多
AIM： To evaluate the efficacy of thalidomide in com- bination with other therapies to treat patients with ad- vanced hepatocellular carcinoma （HCC）. METHODS： We performed a retrospective analysis of all patients w...AIM： To evaluate the efficacy of thalidomide in com- bination with other therapies to treat patients with ad- vanced hepatocellular carcinoma （HCC）. METHODS： We performed a retrospective analysis of all patients with HCC who were treated with thalido- mide for at least two months. The medical records of patients with HCC who were treated at our institution between April 2003 and March 2008 were reviewed. Image studies performed before and after treatment, tumor response, overall survival, and the decrease in o-fetoprotein （AFP） levels were evaluated. RESULTS： A total of 53 patients with HCC received either 100 or 200 mg/d of thalidomide. The patient population consisted of 9 women and 44 men with a median age of 61 years. Thirty patients （56.6%） were classified as Child-Pugh A, and 12 patients （22.6%） were classified as Child-Pugh B. Twenty-six patients had portal vein thrombosis （49.1%）, and 25 patients had extrahepatic metastasis （47.1%）. The median duration of thalidomide treatment was 6.0 mo. Six of the 53 patients achieved a confirmed response （11.3%）, one achieved a complete response （1.9%） and 5 achieved a partial response （9.4%）. The disease control rate （CR ＋ PR ＋ SD） was 28.3% （95% CI： 17.8-42.4）, and the median overall survival rate was 10.5 too. The 1- and 2-year survival rates were 45% and 20%, respectively. Only one complete response patient showed an im- proved overall survival rate of 66.8 mo. Sixteen patients （30.2%） showed more than a 50% decrease in their serum AFP levels from baseline, indicating a better re- sponse rate （31.3%）, disease control rate （43.8%）, and overall survival time （20.7 mo）. The therapy was well tolerated, and no significant toxicities were observed. CONCLUSION： Thalidomide was found to be safe for advanced HCC patients, demonstrating anti-tumor ac- tivity including response, survival, and AFP decreases of greater than 50% from baseline.展开更多
Crohn's disease is a chronic inflammatory disorder of the gastrointestinal tract that is defi ned by relapsing and remitting episodes. Tumor necrosis factor alpha (TNF-α) appears to play a central role in the pat...Crohn's disease is a chronic inflammatory disorder of the gastrointestinal tract that is defi ned by relapsing and remitting episodes. Tumor necrosis factor alpha (TNF-α) appears to play a central role in the pathophysiology of the disease. Standard therapies for inflammatory bowel disease fail to induce remission in about 30% of patients. Biological therapies have been associated with an increased incidence of infections, especially infection by Mycobacterium tuberculosis (Mtb). Thalidomide is an oral immunomodulatory agent with anti-TNF-α properties. Recent studies have suggested that thalidomide is effective in refractory luminal and fistulizing Crohn's disease. Thalidomide costimulates T lymphocytes, with greater effect on CD8+ than on CD4+ T cells, which contributes to the protective immune response to Mtb infection. We present a case of Crohn's disease with gastric, ileal, colon and rectum involvement as well as steroid dependency, which progressed with loss of response to infliximabafter three years of therapy. The thorax computed tomography scan demonstrated a pulmonary nodule suspected to be Mtb infection. The patient was started on thalidomide therapy and exhibited an excellent response.展开更多
Objective To evaluate the efficacy and safety of the combination of XELOX regimen （oxaliplatin plus capecitabine） with thalidomide for the first-line treatment of metastatic colorectal cancer （MCRC）. Methods All o...Objective To evaluate the efficacy and safety of the combination of XELOX regimen （oxaliplatin plus capecitabine） with thalidomide for the first-line treatment of metastatic colorectal cancer （MCRC）. Methods All of the 89 patients with MCRC who fulfilled eligibility criteria were randomly assigned to treatment group （n=44） and control group （n=45）. The treatment group received a combination of XELOX with thalidomide and the control group received XELOX alone. Each patient received at least 2 cycles of treatment （1 cycle=21 d）. The primary endpoint was progression-free survival （PFS） and the secondary endpoints were objective response rate （ORR） as well as disease control rate （DCR）. Drug safety and quality of life were also assessed. Results The median PFS of the treatment and control groups were 5.6 and 5.2 months, respectively. The difference did not have a statistical significance （P=0.307）. The ORRs of the two groups also had no statistical difference （34.1% vs. 26.7%, P=0.446）. The addition of thalidomide to XELOX significantly improved the DCR （63.6% vs. 42.2%, P=0.043）. Among 24 patients with hepatic metastasis in the treatment group, 2 patients satisfied the surgical criteria after treatment but none of 23 patients in the control group did. Grade 3 or 4 constipation in patients treated with thalidomide was significantly increased （20.5% vs. 4.4%, P=0.022） but didn＇t result in treatment interruption. The rate of lethargy was increased but the difference between the two groups had no statistical significance （13,6% vs. 4.4%, P=0.130）. The quality of life had no statistical difference between the two groups. Conclusions The combination of XELOX with thalidomide for the first-line treatment of MCRC was well tolerated. Statistically significant improvement was achieved for time DCR but not for PFS.展开更多
AIM： To evaluated the therapeutic and prophylactic effect of thalidomide on 2, 4, 6-trinitrobenzene sulfonic acid （TNBS）-induced colitis. Thalidomide has been reported to downregulate the expression of tumor necros...AIM： To evaluated the therapeutic and prophylactic effect of thalidomide on 2, 4, 6-trinitrobenzene sulfonic acid （TNBS）-induced colitis. Thalidomide has been reported to downregulate the expression of tumor necrosis factor α （TNF-α）, IL-12, and vascular endothelial growth factor （VEGF）, hallmarks of intestinal inflammation in Crohn＇s disease （CD）. METHODS： Male Wistar rats were divided in five groups of ten animals each. Four groups received a rectal infusion of TNBS in ethanol. The first group was sacrificed 7 d after colitis induction. The second and third groups received either thalidomide or placebo by gavage and were sacrificed at 14 d. The fourth group received thalidomide 6 h before TNBS administration, and was sacrificed 7 d after induction. The fifth group acted as the control group and colitis was not induced. Histological inflammatory scores of the colon were performed and lamina propria CD4＋ T cells, macrophages, and VEGF＋ cells were detected by immunohistochemistry. TNF-α and IL-12 were quantified in the supernatant of organ cultures by ELISA. RESULTS： Significant reduction in the inflammatory score and in the percentage of VEGF＋ cells was observed in the group treated with thalidomide compared with animals not treated with thalidomide. Both TNF-α and IL-12 levels were significantly reduced among TNBS induced colitis animals treated with thalidomide compared with animals that did not receive thalidomide. TNF-α levels were also significantly reduced among the animals receiving thalidomide prophylaxis compared with untreated animals with TNBS-induced colitis. Intestinal levels of TNF-α and IL-12 were significantly correlated with the inflammatory score and the number of VEGF＋ cells. CONCLUSION： Thalidomide significantly attenuates TNBS-induced colitis by inhibiting the intestinal production of TNF-α, IL-12, and VEGF. This effect may support the use of thalidomide as an alternate approach in selected patients with CD.展开更多
For more than 50 years bleeding from gastrointestinal angiodysplasias has been treated by hormonal therapy with estrogens and progesterons. After a randomized study finally demonstrated that hormones have no effect on...For more than 50 years bleeding from gastrointestinal angiodysplasias has been treated by hormonal therapy with estrogens and progesterons. After a randomized study finally demonstrated that hormones have no effect on bleeding events and transfusion requirements, therapy has switched to endoscopic coagulation. However, angiodysplasias tend to recur over months to years and endoscopy often has to be repeated for long time periods. Thalidomide, which caused severe deformities in newborn children in the 1960 s, is now increasingly used after it was shown to suppress tumor necrosis factor alpha, inhibi t angiogenesis and to be also effective for treatment of multiple myeloma. In 2011 thalidomide was proven to be highly effective for treatment of bleeding from gastrointestinal angiodysplasias in a randomized study. Further evidence by uncontrolled studies exists that thalidomide is also useful for treatment of bleeding in hereditary hemorrhagic telangiectasia. In spite of this data, endoscopic therapy remains the treatment of choice in many hospitals, as thalidomide is still notorious for its teratogenicity. However, patients with gastrointestinal bleeding related to angiodysplasias are generally at an age in which women have no child-bearing potential. Teratogenicity is therefore no issue for these elderly patients. Other side-effects of thalidomide like neurotoxicity may limit treatment options but can be monitored safely.展开更多
Thalidomide is an effective drug for the treatment of ankylosing spondylitis but might induce peripheral neuropathy. This major adverse reaction has attracted much concern. The current study aimed to observe the incid...Thalidomide is an effective drug for the treatment of ankylosing spondylitis but might induce peripheral neuropathy. This major adverse reaction has attracted much concern. The current study aimed to observe the incidence of thalidomide-induced peripheral neuropathy among an- kylosing spondylitis patients for 1 year after treatment. In this study, 207 ankylosing spondylitis cases received thalidomide treatment, while 116 ankylosing spondylitis cases received other treat- ments. Results showed that the incidence of thalidomide-induced peripheral neuropathy in the thalidomide group was higher than that in the non-thalidomide group. There was no significant difference in the incidence of neuropathy between the 〈 6 months medication and 〉 6 months medication groups. There were no differences in the mean age, gender, or daily dose between the two groups. The incidence of peripheral neuropathy among patients receiving 25, 50, 75, or 100 mg thalidomide per day was 4.6%, 8.5%, 17.1%, 21.7%, respectively. The incidence was significantly different between the groups receiving 25 mg and 100 mg thalidomide. In conclu- sion, thalidomide can induce peripheral neuropathy within 1 year after treatment of ankylosing spondylitis; however, age and gender have no obvious impact on the incidence of peripheral neuropathy. The incidence of peripheral neuropathy is associated with increasing daily doses of thalidomide.展开更多
BACKGROUND Refractory gastrointestinal bleeding(GIB)secondary to gastrointestinal vascular malformations(GIVM)such as gastrointestinal angiodysplasia(GIAD)and gastric antral vascular ectasia(GAVE)remains challenging t...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 fails.Recently thalidomide has been suggested as a treatment option for refractory GIB.AIM To determine the outcome of patients treated with thalidomide for refractory GIB due to GIVM.METHODS IRB approved,single center,retrospective review of electronic medical records from January 2012 to November 2018.Patients 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 included.The primary endpoint was recurrence of GIB 6 mo after initiation of thalidomide.RESULTS Fifteen patients were included in the study,all with significant cardiac,hepatic,or renal comorbidities.The cause of GIB was GIAD in 10 patients and GAVE in 5 patients.Two patients were lost to follow up.Of the 13 patients followed,38.5%(n=5)had no recurrent GIB or transfusion requirement after treatment with thalidomide.Furthermore,84.6%(n=11)of patients had a reduction in transfusion requirements and hospitalizations for GIB.Thalidomide 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.展开更多
AIM To evaluate the efficacy of thalidomide for treating troublesome cases of pediatric Crohn's disease(CD) with tuberculosis infection.METHODS A retrospective study of clinical outcome among children treated with...AIM To evaluate the efficacy of thalidomide for treating troublesome cases of pediatric Crohn's disease(CD) with tuberculosis infection.METHODS 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 10.RESULTS 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 values.CONCLUSION Thalidomide is an effective and safe drug for remission of CD in pediatric patients who have been treated for tuberculosis.展开更多
文摘Thalidomide,an immunomodulatory drug,is widely recommended for the treatment of recurrent aphthous stomatitis(RAS).This review aimed to assess the reliability of thalidomide for managing RAS,oro-genital ulcers associated with Behçet’s disease(BD),and RAS in individuals with HIV infection.A systematic review was conducted following PICOS(Patient,Intervention,Control,Outcome,Study design)principles.Given the heterogeneity across studies,a qualitative analysis was performed in place of a meta-analysis.Eight randomized controlled trials(RCTs)were deemed eligible for inclusion.In three RCTs focused on RAS,a dosage of thalidomide at 100 mg/d demonstrated efficacy,while a lower dose of 25 mg/d helped prolong the recurrence interval of RAS.For oro-genital ulcers of BD,two RCTs indicated that both 300 mg/d for 24 weeks and 200 mg/d for 28 d,preceded by an initial dose of 400 mg/d for 5 d,were effective.In three RCTs investigating RAS in HIV-infected patients,thalidomide at 200 mg/d for either 4 or 7 weeks,with an initial dose of 400 mg/d for the first week,proved effective.However,a regimen of 100 mg three times per week failed to prevent the recurrence of oral ulcers.Adverse reactions to thalidomide were generally tolerable within the dosage ranges used in these studies.Overall,thalidomide showed promising efficacy for treating RAS,oro-genital ulcers in BD,and RAS in HIV-infected individuals.However,the variability in trial designs,dosages,and treatment durations makes it challenging to recommend an optimal dose and course of therapy.Further high-quality RCTs are necessary to establish more definitive guidelines.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.:82360112)the project supported by Jiangxi Provincial Natural Science Foundation,China(Grant No.:20232BAB216021)+2 种基金China Postdoctoral Science Foundation(Grant No.:2023M741522)the Key Laboratory Project of Digestive Diseases in Jiangxi Province,China(Program No.:2024SSY06101)Jiangxi Clinical Research Center for Gastroenterology,China(Program No.:20223BCG74011).
文摘Thalidomide(THA)is renowned for its potent anti-inflammatory properties.This study aimed to elucidate its underlying mechanisms in the context of Crohn's disease(CD)development.Mouse colitis models were established by dextran sulfate sodium(DSS)treatment.Fecal microbiota and metabolites were analyzed by metagenomic sequencing and mass spectrometry,respectively.Antibiotic-treated mice served as models for microbiota depletion and transplantation.The expression of forkhead box P3+(FOXP3+)regulatory T cells(Tregs)was measured by flow cytometry and immunohistochemical assay in colitis model and patient cohort.THA inhibited colitis in DSS-treated mice by altering the gut microbiota profile,with an increased abundance of probiotics Bacteroides fragilis,while pathogenic bacteria were depleted.In addition,THA increased beneficial metabolites bile acids and significantly restored gut barrier function.Transcriptomic profiling revealed that THA inhibited interleukin-17(IL-17),IL-1βand cell cycle signaling.Fecal microbiota transplantation from THA-treated mice to microbiota-depleted mice partly recapitulated the effects of THA.Specifically,increased level of gut commensal B.fragilis was observed,correlated with elevated levels of the microbial metabolite 3alpha-hydroxy-7-oxo-5beta-cholanic acid(7-ketolithocholic acid,7-KA)following THA treatment.This microbial metabolite may stable FOXP3 expression by targeting the receptor FMR1 autosomal homolog 1(FXR1)to inhibit autophagy.An interaction between FOXP3 and FXR1 was identified,with binding regions localized to the FOXP3 domain(aa238-335)and the FXR1 domain(aa82-222),respectively.Conclusively,THA modulates the gut microbiota and metabolite profiles towards a more beneficial composition,enhances gut barrier function,promotes the differentiation of FOXP3+Tregs and curbs pro-inflammatory pathways.
文摘Objectives:A common side effect of inflammatory bowel disease(IBD)is intestinal fibrosis,which frequently leads to intestinal blockage and stricture formation.Although Thalidomide(THD)has shown anti-fibrotic benefits in hepatic and renal models,little is known about how it affects intestinal fibrosis and the underlying processes.The present research examines the molecular targets of THD and its potential as a treatment for intestinal fibrosis brought on by colitis.Methods:Clinical samples from Crohn’s disease(CD)patients with intestinal strictures treated with infliximab(IFX)and THD combined with IFX were collected.Dextran sulfate sodium(DSS)was used to develop a mouse model of intestinal fibrosis in C57BL/6 mice.Anti-tumor necrosis factor-alpha(Anti-TNFα),THD,or a combination of the two were administered to the mice.Body weight,colon length,histology,and disease activity index were used to evaluate the disease’s severity.In vitro,THD was tested on colonic fibroblast lines(CCD-18Co and MPF)to assess its effects on cell proliferation,motility,and transdifferentiation.To examine changes in gene expression and signaling pathway modifications,namely in the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR)pathway,RNA sequencing,qRT-PCR,and Western blotting were carried out.Results:In DSS-induced colitis,THD therapy lowered fibrosis,as seen by downregulated fibrotic markers(α-smooth muscle actin(α-SMA),collagen I,and collagen III)and decreased collagen deposition.Mechanistically,THD prevented fibroblasts from transdifferentiating and decreased their vitality.Furthermore,THD inhitited the PI3K/AKT/mTOR pathway in vivo and in vitro.Conclusion:THD inhibits the PI3K/AKT/mTOR signaling cascade and suppresses colonic fibroblast transdifferentiation,which protects against DSS-induced colitis-associated fibrosis,especially when combined with anti-TNFαtherapy.
文摘The aim of this study was to evaluate the protective effect of thalidomide derivative ZSN-12 on acute lung injury induced by oleic acid in mice, and to investigate the possible mechanisms. The results showed that ZSN-12 （200 mg/kg） markedly improved the pathological changes of acute lung injury. The proportion of polymorphonuclear neutrophils （PMN） was reduced by 48% （P〈0.01） and the content of nitric oxide （NO） in bronchoalveolar lavage fluid （BALF） was decreased by 33% （P〈0.05）. ZSN-12 produced significant anti-inflammatory effects in the models of xylene induced ear edema and carrageenan induced paw edema, in which ZSN-12 inhibited ear edema and paw swelling in a dose-dependent manner. The inhibition rates by ZSN-12 dosed at 200, 100, 50 mg/kg were 62%, 43%, and 30% in ear edema, respectively and 60%, 47%, and 33% in paw edema, respectively, at 3 h. Meanwhile, ZSN-12 （10, 5, 1 μmol/L） significantly restrained the ConA-induced T lymphocyte proliferation, with the inhibition rates of 33%, 30% and 22%, respectively （P〈0.01）. In conclusion, the present study showed that administration of thalidomide derivative ZSN-12 exerted significant protective effect in acute lung injury induced by oleic acid in mice, which may be related to its anti-inflammation effect. ZSN-12 inhibited the effusion of PMN, reduced the release of NO, and suppressed the proliferation of T lymphocyte.
文摘AIMTo examine the efficacy and safety of thalidomide and thalidomide analogues in induction and maintenance of remission in patients with inflammatory bowel disease （IBD）.METHODSA literature search was performed in the following databases： PubMed, EMBASE, Web of Science, Ovid and the Cochrane Library, and Chinese databases such as the China National Knowledge Infrastructure, China Science and Technology Journal Database （VIP）, Wanfang Data. The randomized controlled analysis was performed to assess the effects of thalidomide therapy on infammatory bowel disease for patients who did show good response with other therapies.RESULTSThree studies （ n = 212） met the inclusion criteria were used in this Meta-analysis. No difference was found between thalidomide/thalidomide analogues and placebo in the induction of remission （RR = 1.36, 95%CI： 0.83-2.22, P = 0.22）, the induction of clinical response （RR = 1.14, 95%CI： 0.75-1.72, P = 0.54） and the induction of adverse events （RR = 1.41, 95%CI： 0.99-2.02, P = 0.06）.CONCLUSIONCurrently, there is not enough evidence to support use of thalidomide or its analogue for the treatment in patients of any age with IBD. However, it warrants a reanalysis when more data become available.
文摘Thalidomide is widely used in the treatment of multiple myeloma (MM). In recent years, several cases of pulmonary hypertension have been reported following treatment with thalidomide. The aim of this review was to evaluate the published literature on multiple myeloma patients with pulmonary hypertension following thalidomide treatment. A literature search was performed between 2000 and 2016. A total of 7 eligible studies were identified and deemed eligible, including 11 cases—approximately 37% (4 cases) with IgA (k), 27% (3 cases) with IgG (λ) MM, 27% (3 cases) with IgG (k) MM, and one case (9%) with primary plasma cell leukemia (PPCL). The vast majority of cases—82% (9 cases)—are associated with thalidomide, while only 18% (2 cases) are related to thalidomide derivatives (lenalidomide and pomalidomide). In conclusion, pulmonary hypertension induced by thalidomide or derivatives in multiple myeloma (MM) patients is related to a multifactorial etiology including the pathophysiology of the disease, thromboembolic events, preexisted cardiovascular conditions, comorbidities, and combination with other chemo- or bio-therapeutic agents. MM patients should be evaluated for signs and symptoms underlying cardiopulmonary disease before initiating, and during treatment with thalidomide.
文摘AIM: To evaluate which patients with hepatocellular carcinoma (HCC) are most likely to respond to thalidomide treatment. METHODS: From July 2002 to July 2004, patients with HCC who received thalidomide treatment, were enrolled. We extracted relevant data from the patients’ medical records, including history and type of hepatitis, comorbidity, serum α-fetoprotein (α-FP) level, volumetric changes in tumor, length of survival, and the dose, duration, side effects of thalidomide treatment. The tumor response was evaluated. On the basis of these data, the patients were divided into two groups: those with either partial response or stable disease (PR + SD group) and those with progressive disease (PD group). RESULTS: Two of 42 (5%) patients had a partial tumor response after treatment with thalidomide, 200 mg/d, and 9 (21%) had stable disease. Patients in the PR + SD group all had cirrhosis. Comparing patients with and without cirrhosis, the former were more likely to respond to thalidomide therapy (PR + SD: 100% vs PD: 64.5%, P = 0.041 < 0.05). Thalidomide was significantly more likely to be effective in tumors smaller than 5 cm (PR + SD: 63.6% vs PD: 25.8%, P = 0.034 < 0.05). Compared with patients with progressive disease (PD), patients in the PR + SD group had a higher total dose of thalidomide (13 669.4 ± 8446.0 mg vs 22 022.7 ± 11 461.4 mg, P = 0.023 < 0.05) and a longer survival (181.0 ± 107.1 d vs 304.4 ± 167.1 d, P = 0.047 < 0.05). Patients with comorbid disease had a significantly greater incidence of adverse reactions than those without (93.8% vs 60.0%, P = 0.021 < 0.05). The average number of adverse reactions in each person with a comorbid condition was twice as high as in those without other diseases (2.2 ± 1.3 vs 1.1 ± 1.2; P = 0.022 < 0.05). CONCLUSION: Thalidomide therapy is most likely to beeffective in patients with early stage small HCC, espe- cially in those with other underlying diseases. A low dose (200 mg/d) of thalidomide is recommended to continue the treatment long enough to make it more effective.
文摘AIM:To investigate the effects of thalidomide on angiogenesis,tumor growth and metastasis of hepatocellular carcinoma in nude mice.METHODS:Twenty-four nude mice were randomly divided into therapy group and control group,12 mice in each group.Thalidomide dissolved in 0.5%sodium carboxyl methyl cellulose(CMC)suspension was administered intraperitoneally once a day at the dose of 200 mg/kg in therapy group,and an equivalent volume of 0.5%CMC in control group.Mice were sacrificed on the 30th d,tumor size and weight and metastases in liver and lungs were measured.CD34 and VEGF mRNA in tumor tissue were detected by immunohistochemistry and semi-quantitative RT-PCR respectively and microvessel density(MVD)was counted.Serum concentrations of TNF-αand ALT and AFP were also tested.RESULTS:MVD and VEGF mRNA in therapy group were less than those in control group(31.08±16.23 vessels/HP vs 80.00±26.27 vessels/HP,0.0538±0.0165 vs 0.7373±0.1297,respectively,P<0.05).No statistical difference was observed in tumor size and weight and metastases in liver and lungs.TNF-αwas significantly lower in therapy group than in control group(28.64±4.64 ng/L vs42.69±6.99 ng/L,P<0.05).No statistical difference in ALT and AFP was observed between groups.CONCLUSION:Thalidomide can significantly inhibitangiogenesis and metastasis of hepatocellular carcinoma.Italso has inhibitory effects on circulating TNF-α.
文摘AIM: To assess the efficacy and tolerability of thalidomide in pediatric Crohn's disease (CD). METHODS: Six patients with refractory CD received thalidomide at an initial dose of 2 mg/kg per day for one month, then increased to 3 mg/kg per day or decreased to 1 mg/kg per day, and again further reduced to 0.5 mg/kg per day, according to the individual patient's response to the drug. RESULTS: Remission was achieved within three months. Dramatic clinical improvement was demonstrated after thalidomide treatment. Endoscopic and pathological improvements were also observed after thalidomide treatment, which was well tolerated by all patients. CONCLUSION: Thalidomide is a useful drug for pediatric refractory CD.
基金Supported by Leading Scientific Research Project of the Health Department of Jiangsu Province,China,No.Z201220Major Project of the Health Department of Changzhou,China,No.ZD201105Changzhou Sci-Tech Support Project for Social Development,No.CE20125021
文摘AIM: To investigate the short-term efficacy and tolerability of radiotherapy plus thalidomide in patients with esophageal cancer (EC).
文摘AIM: To determine whether thalidomide prevents microvascular injury in acute radiation proctitis in white rats. METHODS: Fourteen female Wistar rats were used: six in the radiation group, six in the thalidomide group, and two in normal controls. The radiation and thalidomide groups were irradiated at the pelvic area using a single 30 Gy exposure. The thalidomide (150 mg/kg) was injected into the peritoneum for 7 d from the day of irradiation. All animals were sacrificed and the rectums were removed on day 8 after irradiation. The microvessels of resected specimens were immunohistochemically stained with thrombomodulin (TM), von Willebrand Factor (vWF), and vascular endothelial growth factor (VEGF). RESULTS: The microscopic scores did not differ significantly between the radiation and thalidomide groups, but both were higher than in the control group. Expression of TM was significantly lower inthe endothelial cells (EC) of the radiation group than in the control and thalidomide groups (P < 0.001). The number of capillaries expressing vWF in the EC was higher in the radiation group (15.3 ± 6.8) than in the control group (3.7 ± 1.7), and the number of capillaries expressing vWF was attenuated by thalidomide (10.8 ± 3.5, P < 0.001). The intensity of VEGF expression in capillaries was greater in the radiation group than in the control group and was also attenuated by thalidomide (P = 0.003). CONCLUSION: The mechanisms of acute radiation- induced proctitis in the rats are related to endothelial cell injury of microvessel, which may be attenuated with thalidomide.
文摘AIM： To evaluate the efficacy of thalidomide in com- bination with other therapies to treat patients with ad- vanced hepatocellular carcinoma （HCC）. METHODS： We performed a retrospective analysis of all patients with HCC who were treated with thalido- mide for at least two months. The medical records of patients with HCC who were treated at our institution between April 2003 and March 2008 were reviewed. Image studies performed before and after treatment, tumor response, overall survival, and the decrease in o-fetoprotein （AFP） levels were evaluated. RESULTS： A total of 53 patients with HCC received either 100 or 200 mg/d of thalidomide. The patient population consisted of 9 women and 44 men with a median age of 61 years. Thirty patients （56.6%） were classified as Child-Pugh A, and 12 patients （22.6%） were classified as Child-Pugh B. Twenty-six patients had portal vein thrombosis （49.1%）, and 25 patients had extrahepatic metastasis （47.1%）. The median duration of thalidomide treatment was 6.0 mo. Six of the 53 patients achieved a confirmed response （11.3%）, one achieved a complete response （1.9%） and 5 achieved a partial response （9.4%）. The disease control rate （CR ＋ PR ＋ SD） was 28.3% （95% CI： 17.8-42.4）, and the median overall survival rate was 10.5 too. The 1- and 2-year survival rates were 45% and 20%, respectively. Only one complete response patient showed an im- proved overall survival rate of 66.8 mo. Sixteen patients （30.2%） showed more than a 50% decrease in their serum AFP levels from baseline, indicating a better re- sponse rate （31.3%）, disease control rate （43.8%）, and overall survival time （20.7 mo）. The therapy was well tolerated, and no significant toxicities were observed. CONCLUSION： Thalidomide was found to be safe for advanced HCC patients, demonstrating anti-tumor ac- tivity including response, survival, and AFP decreases of greater than 50% from baseline.
文摘Crohn's disease is a chronic inflammatory disorder of the gastrointestinal tract that is defi ned by relapsing and remitting episodes. Tumor necrosis factor alpha (TNF-α) appears to play a central role in the pathophysiology of the disease. Standard therapies for inflammatory bowel disease fail to induce remission in about 30% of patients. Biological therapies have been associated with an increased incidence of infections, especially infection by Mycobacterium tuberculosis (Mtb). Thalidomide is an oral immunomodulatory agent with anti-TNF-α properties. Recent studies have suggested that thalidomide is effective in refractory luminal and fistulizing Crohn's disease. Thalidomide costimulates T lymphocytes, with greater effect on CD8+ than on CD4+ T cells, which contributes to the protective immune response to Mtb infection. We present a case of Crohn's disease with gastric, ileal, colon and rectum involvement as well as steroid dependency, which progressed with loss of response to infliximabafter three years of therapy. The thorax computed tomography scan demonstrated a pulmonary nodule suspected to be Mtb infection. The patient was started on thalidomide therapy and exhibited an excellent response.
文摘Objective To evaluate the efficacy and safety of the combination of XELOX regimen （oxaliplatin plus capecitabine） with thalidomide for the first-line treatment of metastatic colorectal cancer （MCRC）. Methods All of the 89 patients with MCRC who fulfilled eligibility criteria were randomly assigned to treatment group （n=44） and control group （n=45）. The treatment group received a combination of XELOX with thalidomide and the control group received XELOX alone. Each patient received at least 2 cycles of treatment （1 cycle=21 d）. The primary endpoint was progression-free survival （PFS） and the secondary endpoints were objective response rate （ORR） as well as disease control rate （DCR）. Drug safety and quality of life were also assessed. Results The median PFS of the treatment and control groups were 5.6 and 5.2 months, respectively. The difference did not have a statistical significance （P=0.307）. The ORRs of the two groups also had no statistical difference （34.1% vs. 26.7%, P=0.446）. The addition of thalidomide to XELOX significantly improved the DCR （63.6% vs. 42.2%, P=0.043）. Among 24 patients with hepatic metastasis in the treatment group, 2 patients satisfied the surgical criteria after treatment but none of 23 patients in the control group did. Grade 3 or 4 constipation in patients treated with thalidomide was significantly increased （20.5% vs. 4.4%, P=0.022） but didn＇t result in treatment interruption. The rate of lethargy was increased but the difference between the two groups had no statistical significance （13,6% vs. 4.4%, P=0.130）. The quality of life had no statistical difference between the two groups. Conclusions The combination of XELOX with thalidomide for the first-line treatment of MCRC was well tolerated. Statistically significant improvement was achieved for time DCR but not for PFS.
文摘AIM： To evaluated the therapeutic and prophylactic effect of thalidomide on 2, 4, 6-trinitrobenzene sulfonic acid （TNBS）-induced colitis. Thalidomide has been reported to downregulate the expression of tumor necrosis factor α （TNF-α）, IL-12, and vascular endothelial growth factor （VEGF）, hallmarks of intestinal inflammation in Crohn＇s disease （CD）. METHODS： Male Wistar rats were divided in five groups of ten animals each. Four groups received a rectal infusion of TNBS in ethanol. The first group was sacrificed 7 d after colitis induction. The second and third groups received either thalidomide or placebo by gavage and were sacrificed at 14 d. The fourth group received thalidomide 6 h before TNBS administration, and was sacrificed 7 d after induction. The fifth group acted as the control group and colitis was not induced. Histological inflammatory scores of the colon were performed and lamina propria CD4＋ T cells, macrophages, and VEGF＋ cells were detected by immunohistochemistry. TNF-α and IL-12 were quantified in the supernatant of organ cultures by ELISA. RESULTS： Significant reduction in the inflammatory score and in the percentage of VEGF＋ cells was observed in the group treated with thalidomide compared with animals not treated with thalidomide. Both TNF-α and IL-12 levels were significantly reduced among TNBS induced colitis animals treated with thalidomide compared with animals that did not receive thalidomide. TNF-α levels were also significantly reduced among the animals receiving thalidomide prophylaxis compared with untreated animals with TNBS-induced colitis. Intestinal levels of TNF-α and IL-12 were significantly correlated with the inflammatory score and the number of VEGF＋ cells. CONCLUSION： Thalidomide significantly attenuates TNBS-induced colitis by inhibiting the intestinal production of TNF-α, IL-12, and VEGF. This effect may support the use of thalidomide as an alternate approach in selected patients with CD.
文摘For more than 50 years bleeding from gastrointestinal angiodysplasias has been treated by hormonal therapy with estrogens and progesterons. After a randomized study finally demonstrated that hormones have no effect on bleeding events and transfusion requirements, therapy has switched to endoscopic coagulation. However, angiodysplasias tend to recur over months to years and endoscopy often has to be repeated for long time periods. Thalidomide, which caused severe deformities in newborn children in the 1960 s, is now increasingly used after it was shown to suppress tumor necrosis factor alpha, inhibi t angiogenesis and to be also effective for treatment of multiple myeloma. In 2011 thalidomide was proven to be highly effective for treatment of bleeding from gastrointestinal angiodysplasias in a randomized study. Further evidence by uncontrolled studies exists that thalidomide is also useful for treatment of bleeding in hereditary hemorrhagic telangiectasia. In spite of this data, endoscopic therapy remains the treatment of choice in many hospitals, as thalidomide is still notorious for its teratogenicity. However, patients with gastrointestinal bleeding related to angiodysplasias are generally at an age in which women have no child-bearing potential. Teratogenicity is therefore no issue for these elderly patients. Other side-effects of thalidomide like neurotoxicity may limit treatment options but can be monitored safely.
基金financially supported by the Natural Science Foundation of Liaoning Province of China,No.2014021081
文摘Thalidomide is an effective drug for the treatment of ankylosing spondylitis but might induce peripheral neuropathy. This major adverse reaction has attracted much concern. The current study aimed to observe the incidence of thalidomide-induced peripheral neuropathy among an- kylosing spondylitis patients for 1 year after treatment. In this study, 207 ankylosing spondylitis cases received thalidomide treatment, while 116 ankylosing spondylitis cases received other treat- ments. Results showed that the incidence of thalidomide-induced peripheral neuropathy in the thalidomide group was higher than that in the non-thalidomide group. There was no significant difference in the incidence of neuropathy between the 〈 6 months medication and 〉 6 months medication groups. There were no differences in the mean age, gender, or daily dose between the two groups. The incidence of peripheral neuropathy among patients receiving 25, 50, 75, or 100 mg thalidomide per day was 4.6%, 8.5%, 17.1%, 21.7%, respectively. The incidence was significantly different between the groups receiving 25 mg and 100 mg thalidomide. In conclu- sion, thalidomide can induce peripheral neuropathy within 1 year after treatment of ankylosing spondylitis; however, age and gender have no obvious impact on the incidence of peripheral neuropathy. The incidence of peripheral neuropathy is associated with increasing daily doses of thalidomide.
文摘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 fails.Recently thalidomide has been suggested as a treatment option for refractory GIB.AIM To determine the outcome of patients treated with thalidomide for refractory GIB due to GIVM.METHODS IRB approved,single center,retrospective review of electronic medical records from January 2012 to November 2018.Patients 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 included.The primary endpoint was recurrence of GIB 6 mo after initiation of thalidomide.RESULTS Fifteen patients were included in the study,all with significant cardiac,hepatic,or renal comorbidities.The cause of GIB was GIAD in 10 patients and GAVE in 5 patients.Two patients were lost to follow up.Of the 13 patients followed,38.5%(n=5)had no recurrent GIB or transfusion requirement after treatment with thalidomide.Furthermore,84.6%(n=11)of patients had a reduction in transfusion requirements and hospitalizations for GIB.Thalidomide 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.
基金Supported by Medical Science and Technology Planning Project of Zhejiang Province,China,No.2015KYB430(to Hong Y)
文摘AIM To evaluate the efficacy of thalidomide for treating troublesome cases of pediatric Crohn's disease(CD) with tuberculosis infection.METHODS 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 10.RESULTS 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 values.CONCLUSION Thalidomide is an effective and safe drug for remission of CD in pediatric patients who have been treated for tuberculosis.
