沙利度胺对人肝癌细胞株SMMC-7721荷瘤鼠移植瘤作用

目的 研究沙利度胺对人肝癌细胞株SMMG7721荷瘤鼠移植瘤的生长抑制作用及可能机制.方法 建立肝癌细胞株SMMC-7721的荷瘤鼠模型,观察沙利度胺组与对照组瘤体变化,应用免疫组化方法测定瘤体组织中微血管密度,ELISA法测定荷瘤鼠外周血血管内皮生长因子(VEGF)表达,并采用流式细胞仪测定瘤体组织细胞凋亡指数及瘤...     

BDT和VADT方案治疗多发性骨髓瘤的临床研究

目的比较BDT与VADT方案治疗多发性骨髓瘤(MM)的疗效及不良反应。方法回顾分析72例MM病人,其中24例病人(初治13例,复发难治11例)接受BDT(硼替佐米联合地塞米松、沙利度胺)方案治疗,48例病人(初治36例,复发难治12例)接受VADT(长春地辛联合表柔比星、地塞米松、沙利度胺)方案化疗。所有病人均接受4～6个疗程治疗后进行全面评价,自动放弃治疗、疗程不符合标准以及失访病人不计入。结果 BDT组和VADT组的总完全缓解(TR)率分别为68.42%和35.42%,初治病人TR率分别为80.00%、44.44%,复发难治病人TR率分别为55.56%、8.33%,两组比较差异均有显著性(2χ=3.965～5.996,P<0.05);两组的总体有效(RR)率分别为89.47%和70.83%,两组比较差异无显著性(P>0.05)。两组初治病人达到最大反应中位疗程数分别为3和5个,复发难治病人分别为4和7个。常见的不良反应有骨髓抑制、消化道症状、肝肾功能损害、周围神经病变、乏力、血栓形成、血凝异常、带状疱疹病毒感染、精神症状、皮疹等,两组比较差异无显著意义(P>0.05)。结论 BDT方案治疗MM比VADT方案有较高的TR率,对复发难治性MM效果明确,且起效更快,副作用多可耐受,值得临床推广。     

Rosai‐Dorfman disease successfully treated with thalidomide: A case report

Rosai‐Dorfman disease (RDD) is a rare disease which characterized by proliferation and overproduction of histiocytes in the lymph nodes appearing as lymphadenopathy, however, it may also occur in extranodal sites. The occurrence of unusual manifestations of the disease such as the appearance of the mass in an unusual area may increase the probability of misdiagnosis. Herein, we describe a case of RDD in an old woman with an unusual appearance of RDD in the leg that was successfully treated by thalidomide.     

沙利度胺联合英夫利西治疗克罗恩病患者的临床效果

目的研究沙利度胺联合英夫利西治疗克罗恩病患者的临床效果。方法选择2017年9月至2018年9月我院收治的106例克罗恩病患者为研究对象,采用随机数字法将其分为英夫利西组(53例,英夫利西)和沙利度胺+英夫利西组(53例,沙利度胺联合英夫利西)。比较两组的临床疗效。结果治疗2个月后,沙利度胺+英夫利西组的IFN-γ、TNF-ɑ、IL-8、CRP、VEGF水平、CDAI评分、ESR、CD4^+、CD3^+及不良反应总发生率明显低于英夫利西组,CD8^+和临床治疗总有效率明显高于英夫利西组(P<0.05)。结论克罗恩病患者应用沙利度胺联合英夫利西治疗的效果显著,可推广应用。     

多发性骨髓瘤维持治疗的研究进展

多发性骨髓瘤(multiple mfeloma,MM)是第二常见的血液肿瘤病,目前仍无法治愈。诱导治疗后序贯自体干细胞移植（ASCT）已经成为一种标准化治疗,但依然可能存在复发。使用维持治疗的目的是通过增加无进展生存期（PFS）,加深缓解,进而增加总生存期(OS)。本文主要对新药时代MM的维持治疗的进展作一综述。     

Complex Anatomic Abnormalities of the Lower Leg Muscles and Tendons Associated With Phocomelia: A Case Report

Musculoskeletal anatomy is widely known to have components that stray from the norm in the form of variant muscle and tendon presence, absence, origin, insertion, and bifurcation. Although these variant muscles and tendons might be deemed incidental and insignificant findings by most, they can be important contributors to pathologic physiology or, more importantly, an option for effective treatment. In the present case report, we describe a patient with phocomelia and Müllerian abnormalities secondary to in utero thalidomide exposure. The patient had experienced recurrent bilateral foot pain accompanied by numbness, stiffness, swelling, and longstanding pes planus. These symptoms persisted despite conservative treatment with orthotics, steroids, and nonsteroidal anti-inflammatory drugs. Radiographic imaging showed dysmorphic and degenerative changes of the ankle and foot joints. Further investigation with magnetic resonance imaging revealed complex anatomic abnormalities, including the absence of the posterior tibialis and peroneus brevis, lateralization of the peroneus longus, and the presence of a variant anterior compartment muscle. The variant structure was likely a previously described anterior compartment variant, anterior fibulocalcaneus, and might have been a source of the recurrent pain. Also, the absence of the posterior tibialis might have caused the pes planus in the present patient, considering that posterior tibialis tendon dysfunction is the most common cause of acquired pes planus. Although thalidomide infrequently affects the lower extremities, its effects on growth and development were likely the cause of this rare array of anatomic abnormalities and resulting ankle and foot pathologic features.     

沙利度胺治疗多发性骨髓瘤前后血清TNF-α水平变化的观察

为观察沙利度胺治疗多发性骨髓瘤(MM)前后TNF-α水平。选择20例沙利度胺治疗的难治、复发性多发性骨髓瘤患者,所有病例均于治疗前留取血浆标本,治疗有效组在最大反应率时留取标本,治疗无效组在治疗结束后留取标本。采用酶联免疫吸附法测定血浆TNF-α水平。结果显示沙利度胺治疗有效组、无效组治疗前TNF-α水平无明显差异。沙利度胺治疗有效组,治疗前后血浆TNF-α水平分别是(55.2854±11.3558)pg/ml和(29.2842±11.5684)pg/ml,治疗前血浆TNF-α水平明显高于治疗后(P=0.0001);治疗无效组,治疗前后血浆TNF-α水平分别是(54.0688±6.4732)pg/ml和(54.4672±3.3512)pg/ml,无明显差异(P=0.87310)。结论:沙利度胺治疗有效组可明显减少MM患者TNF-α水平,进一步支持TNF-α在多发性骨髓瘤发生、发展中的作用,同时说明TNF-α水平可以作为判断疗效的指标。     

沙利度胺及其类似物治疗炎症性肠病的系统性回顾

目的 评价沙利度胺及其类似物在炎症性肠病（IBD）治疗中的有效性以及安全性。方法 检索PubMed、Cochrane Center Register of Controlled Trails、Embase、Web of Science、中国期刊全文数据库、万方数据库、维普数据库,系统性评价沙利度胺及其类似物治疗IBD的有效性及安全性,就诱导缓解率、维持缓解率、不良反应事件进行总结分析。结果 共纳入16篇文献（3篇RCT,13篇病例系列研究）,333例IBD患者。2篇RCT显示在克罗恩病（Crohn’s disease,CD）和溃疡性结肠炎（ulcerative colitis,UC）患者中,沙利度胺均能够显著提高诱导缓解率（46.4% vs 11.5%,P=0.010;83.3% vs 18.8%,P=0.005）。病例系列研究显示沙利度胺能够诱导CD缓解,合并缓解率为50%（95%CI＝36%~65%）。沙利度胺不良反应中神经系统不良反应最为常见（207/316,65.5%）,周围神经病变是患者停药的最常见原因。结论 沙利度胺治疗IBD疗效理想,在CD诱导缓解治疗中效果尤为显著。     

Administrations of thalidomide into the rostral ventromedial medulla produce antinociceptive effects in a rat model of postoperative pain

The rostral ventromedial medulla (RVM) is highly involved in pain signal transmissions. Previous studies have shown that thalidomide is anti‐nociceptive. Thus, we evaluated the neurobiological mechanisms of thalidomide in the RVM in the regulation of postoperative pain. We used a rat model of postoperative pain to investigate the effects of intra‐RVM thalidomide treatments on postoperative pain, and evaluate the role of cannabinoid receptors in the effects of intra‐RVM thalidomide treatments on GABAergic neurotransmission in the RVM neurons. We found intra‐RVM thalidomide treatments reduced incisional surgery induced mechanical allodynia. This phenomenon was associated with attenuation of the frequency and amplitude of miniature inhibitory postsynaptic currents (mIPSCs) and spontaneous IPSCs (sIPSCs) in RVM neurons. Furthermore, applications of WIN 55,212‐3 mesylate, a non‐selective cannabinoid receptor antagonist reversed the effects of repeated thalidomide treatment on the frequency but not the amplitude of mIPSCs and sIPSCs. Finally, we found that repeated thalidomide treatment robustly enhanced CB2 receptor expression, but slightly reduced CB1 receptor expression, in the RVM. These results suggested that the antinociceptive effects of thalidomide in the RVM likely involve the attenuation of GABA release, which are critically regulated by cannabinoid receptors.     

Vinca alkaloids,thalidomide and eribulin‐induced peripheral neurotoxicity: From pathogenesis to treatment

Vinca alkaloids, thalidomide, and eribulin are widely used to treat patients with childhood acute lymphoblastic leukemia (ALL), adults affected by multiple myeloma and locally invasive or metastatic breast cancer, respectively. However, soon after their introduction into clinical practice, chemotherapy‐induced peripheral neurotoxicity (CIPN) emerged as their main non‐hematological and among dose‐limiting adverse events. It is generally perceived that vinca alkaloids and the antiangiogenic agent thalidomide are more neurotoxic, compared to eribulin. The exposure to these chemotherapeutic agents is associated with an axonal, length‐dependent, sensory polyneuropathy of mild to moderate severity, whereas it is considered that the peripheral nerve damage, unless severe, usually resolves soon after treatment discontinuation. Advanced age, high initial and prolonged dosing, coadministration of other neurotoxic chemotherapeutic agents and pre‐existing neuropathy are the common risk factors. Pharmacogenetic biomarkers might be used to define patients at increased susceptibility of CIPN. Currently, there is no established therapy for CIPN prevention or treatment; symptomatic treatment for neuropathic pain and dose reduction or withdrawal in severe cases is considered, at the cost of reduced cancer therapeutic efficacy. This review critically examines the pathogenesis, epidemiology, risk factors (both clinical and pharmacogenetic), clinical phenotype and management of CIPN as a result of exposure to vinca alkaloids, thalidomide and its analogue lenalidomide as also eribulin.