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Differential profile of ultrasound findings associated with malignancy in mixed and solid thyroid nodules in an elderly female population. 老年女性混合甲状腺结节和实性甲状腺结节的超声表现与恶性肿瘤的差异分析。
IF 2.1 Q4 ENDOCRINOLOGY & METABOLISM Pub Date : 2014-01-01 Epub Date: 2014-06-23 DOI: 10.1155/2014/761653
María Inés Vera, Tomás Meroño, María Agustina Urrutia, Carina Parisi, Yanina Morosan, Melanie Rosmarin, Marta Schnitman, Fernando Brites, Silvio Grisendi, María Sol Serrano, Wilfredo Luciani, Leonardo Serrano, Carlos Zuk, Guillermo De Barrio, Claudia Cejas, María Cristina Faingold, Gabriela Brenta

Objective. Ultrasonographic characteristics are associated with thyroid malignancy. Our aim was to compare the diagnostic value of ultrasound features in the detection of thyroid malignancy in both solid and mixed nodules. Methods. We prospectively studied female patients (≥50 years) referred to ultrasound-guided fine needle aspiration biopsy. Ultrasound features considered suspicious were hypoechogenicity, microcalcifications, irregular margins, high anteroposterior (AP)/axial-ratio, and absent halo. Associations were separately assessed in mixed and solid nodules. Results. In a group of 504 elderly female patients (age = 69 ± 8 years), the frequency of malignant cytology was 6%. Thirty-one percent of nodules were mixed and 60% were solid. The rate of malignant cytology was similar for mixed and solid nodules (7.4 versus 5.8%, P: 0.56). While in mixed nodules none of the ultrasound characteristics were associated with malignant cytology, in solid nodules irregular margins and microcalcifications were significant (all P < 0.05). The combination of irregular margins and/or microcalcifications significantly increased the association with malignant cytology only in solid nodules (OR: 2.76 (95% CI: 1.25-6.10), P: 0.012). Conclusions. Ultrasound features were of poor diagnostic value in mixed nodules, which harbored malignant lesions as often as solid nodules. Our findings challenge the recommended minimal size for ultrasound-guided fine needle aspiration biopsy in mixed nodules.

目标。超声特征与甲状腺恶性肿瘤有关。我们的目的是比较超声特征在检测甲状腺恶性肿瘤的固体和混合结节的诊断价值。方法。我们前瞻性研究了超声引导下细针穿刺活检的女性患者(≥50岁)。可疑的超声特征为低回声、微钙化、边缘不规则、高正轴比和无晕。在混合性和实性结节中分别评估相关性。结果。504例老年女性患者(年龄= 69±8岁),恶性细胞学检出率为6%。31%为混合性结节,60%为实性结节。混合性结节和实性结节的恶性细胞学发生率相似(7.4%对5.8%,P: 0.56)。在混合性结节中,超声特征与恶性细胞学无关,而在实性结节中,边缘不规则和微钙化显著(P < 0.05)。不规则边缘和/或微钙化的结合仅在实性结节中显著增加了恶性细胞学的相关性(or: 2.76 (95% CI: 1.25-6.10), P: 0.012)。结论。超声特征对混合性结节的诊断价值较差,混合性结节与实性结节一样常伴有恶性病变。我们的研究结果挑战了超声引导下对混合性结节进行细针穿刺活检时推荐的最小尺寸。
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引用次数: 9
Association between TSH-Receptor Autoimmunity, Hyperthyroidism, Goitre, and Orbitopathy in 208 Patients Included in the Remission Induction and Sustenance in Graves' Disease Study. 巴塞杜氏病缓解诱导和维持研究》中208名患者的TSH受体自身免疫、甲状腺功能亢进、甲状腺肿和眼眶病之间的关系
IF 2.1 Q4 ENDOCRINOLOGY & METABOLISM Pub Date : 2014-01-01 Epub Date: 2014-02-18 DOI: 10.1155/2014/165487
Peter Laurberg, Birte Nygaard, Stig Andersen, Allan Carlé, Jesper Karmisholt, Anne Krejbjerg, Inge Bülow Pedersen, Stine Linding Andersen

Background. Graves' disease may have a number of clinical manifestations with varying degrees of activity that may not always run in parallel. Objectives. To study associations between serum levels of TSH-receptor autoantibodies and the three main manifestations of Graves' disease (hyperthyroidism, goiter, and presence of orbitopathy) at the time of diagnosis of hyperthyroidism. Methods. We describe a cohort of 208 patients with newly diagnosed Graves' hyperthyroidism. Patients were enrolled in a multiphase study of antithyroid drug therapy of Graves' hyperthyroidism, entitled "Remission Induction and Sustenance in Graves' Disease (RISG)." Patients were systematically tested for degree of biochemical hyperthyroidism, enlarged thyroid volume by ultrasonography, and the presence of orbitopathy. Results. Positive correlations were found between the levels of TSH-receptor autoantibodies in serum and the three manifestations of Graves' disease: severeness of hyperthyroidism, presence of enlarged thyroid, and presence of orbitopathy, as well as between the different types of manifestations. Only around half of patients had enlarged thyroid gland at the time of diagnosis of hyperthyroidism, whereas 25-30% had orbitopathy. Conclusions. A positive but rather weak correlation was found between TSH-receptor antibodies in serum and the major clinical manifestation of Graves' disease. Only half of the patients had an enlarged thyroid gland at the time of diagnosis.

背景。巴塞杜氏病可能有多种临床表现,活动程度各不相同,而且不一定总是同时发生。研究目的研究确诊甲状腺功能亢进症时血清中 TSH 受体自身抗体水平与巴塞杜氏病三种主要表现(甲状腺功能亢进症、甲状腺肿和眼眶病)之间的关系。方法。我们对208名新确诊的巴塞杜氏甲亢患者进行了研究。患者参加了一项名为 "巴塞杜氏病缓解诱导与维持(RISG)"的多阶段巴塞杜氏甲亢抗甲状腺药物治疗研究。研究人员对患者的生化甲状腺功能亢进程度、超声波检查显示的甲状腺肿大程度以及是否存在眶病进行了系统检测。结果显示结果发现,血清中 TSH 受体自身抗体的水平与巴塞杜氏病的三种表现(甲状腺功能亢进的严重程度、甲状腺肿大和眼眶病)以及不同类型的表现之间存在正相关。只有约一半的患者在确诊甲状腺功能亢进症时有甲状腺肿大,而25%-30%的患者有眼眶病。结论是血清中的促甲状腺激素受体抗体与巴塞杜氏病的主要临床表现呈正相关,但相关性较弱。只有一半的患者在确诊时甲状腺肿大。
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引用次数: 0
There is no elevation of immunoglobulin e levels in Albanian patients with autoimmune thyroid diseases. 阿尔巴尼亚自身免疫性甲状腺疾病患者的免疫球蛋白e水平没有升高。
IF 2.1 Q4 ENDOCRINOLOGY & METABOLISM Pub Date : 2014-01-01 Epub Date: 2014-05-14 DOI: 10.1155/2014/283709
Hatixhe Latifi-Pupovci, Besa Gacaferri-Lumezi, Violeta Lokaj-Berisha

Background. Studies in several ethnic groups reported high incidence of elevated levels of immunoglobulin E (IgE) in patients with autoimmune thyroid diseases (ATD), especially in patients with Graves' disease. Objective. To study association between serum levels of IgE and thyroid stimulating hormone receptor antibodies (TRAb) in Albanian patients with ATD. Material and Methods. Study was performed in 40 patients with Graves' disease, 15 patients with Hashimoto's thyroiditis, and 14 subjects in the control group. The IgE levels were measured by immunoradiometric assay, whereas the TRAb levels were measured by radioreceptor assay. Results. In all groups of subjects the IgE levels were within reference values (<200 kIU/L). Significant difference in mean concentration of IgE was found between two groups of Graves' disease patients, and those with normal and elevated TRAb levels (22.57 versus 45.03, P < 0.05). Positive correlation was found between TRAb and IgE only in Graves' disease patients (r = 0.43, P = 0.006). Conclusion. In Albanian patients with ATD there is no elevation of IgE levels. This could be the result of low prevalence of allergic diseases in Albanian population determined by genetic and environmental factors.

背景。针对多个种族群体的研究报告显示,自身免疫性甲状腺疾病(ATD)患者,尤其是巴塞杜氏病患者中免疫球蛋白 E(IgE)水平升高的发生率很高。研究目的研究阿尔巴尼亚 ATD 患者血清中 IgE 水平与促甲状腺激素受体抗体(TRAb)之间的关系。材料与方法。研究对象包括40名巴塞杜氏病患者、15名桥本氏甲状腺炎患者和14名对照组受试者。IgE水平通过免疫放射测定法进行测量,而TRAb水平则通过放射受体测定法进行测量。结果显示所有组别的受试者的 IgE 水平都在参考值范围内(见图 1)。
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引用次数: 0
The Beneficial Effects of Valproic Acid in Thyroid Cancer Are Mediated through Promoting Redifferentiation and Reducing Stemness Level: An In Vitro Study. 丙戊酸对甲状腺癌的有益作用是通过促进再分化和降低干细胞水平介导的:一项体外研究
IF 2.1 Q4 ENDOCRINOLOGY & METABOLISM Pub Date : 2014-01-01 Epub Date: 2014-05-15 DOI: 10.1155/2014/218763
Vahid Haghpanah, Mohsen Malehmir, Bagher Larijani, Shahin Ahmadian, Kamran Alimoghaddam, Ramin Heshmat, Ardeshir Ghavamzadeh, Khadijeh Adabi, Seyed H Ghaffari

Valproic acid (VPA) has been identified as a histone deacetylase inhibitor, inducing differentiation in transformed cells. However, no study has shown the effect of VPA in the redifferentiation induction and stemness of anaplastic thyroid. The main objective of this study was to evaluate the efficacy of VPA as a differentiation therapy agent in human thyroid cancer based on its effect on stemness and differentiation process. Indications for differentiation of 8305C and B-CPAP cell lines following VPA treatment were obtained by analyzing cell proliferation rate, morphological changes, adherent-dependent colony formation, and Hoechst 33342 staining. The expressions of stemness, differentiation, and aggressiveness specific marker genes were measured by quantitative RT-PCR. VPA treatment effectively showed growth inhibition in both cell lines. The high nuclear-cytoplasmic (N : C) ratio of 8305C cells markedly decreased and treated cells became more epithelial-like. Treated cells showed stronger Hoechst 33342 fluorescence compared with control cells. The hTERT and OCT-4 reduction was paralleled with adherent-dependent colony formation decrement in both cell lines. VPA effectively induced NIS and TTF-1 in anaplastic cells, it whereas showed no clear pattern in papillary cell line. VPA treatment also resulted in the reduction of MMP-2 and MMP-9. These finding suggest that VPA could redifferentiate the anaplastic thyroid cancer cells.

丙戊酸(VPA)是一种组蛋白去乙酰化酶抑制剂,可诱导转化细胞分化。然而,没有研究显示VPA在间变性甲状腺的再分化诱导和干性中的作用。本研究的主要目的是基于VPA对人甲状腺癌干细胞和分化过程的影响,评价其作为分化治疗剂对人甲状腺癌的疗效。通过分析VPA处理后8305C和B-CPAP细胞株的增殖率、形态变化、贴壁依赖性菌落形成及Hoechst 33342染色,获得VPA处理后8305C和B-CPAP细胞株的分化适应症。采用定量RT-PCR法检测干性、分化性和侵袭性特异性标记基因的表达。VPA处理有效抑制了两种细胞系的生长。8305C细胞的高核质比(N: C)明显降低,处理后的细胞更接近上皮样。与对照细胞相比,处理细胞显示出更强的Hoechst 33342荧光。在两种细胞系中,hTERT和OCT-4的减少与粘附依赖性集落形成的减少是平行的。VPA对间变性细胞有诱导NIS和TTF-1的作用,而对乳头状细胞系无明显的诱导作用。VPA处理也导致MMP-2和MMP-9的减少。提示VPA对甲状腺间变性癌细胞具有再分化作用。
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引用次数: 12
Symptoms and signs associated with postpartum thyroiditis. 产后甲状腺炎的相关症状和体征。
IF 2.1 Q4 ENDOCRINOLOGY & METABOLISM Pub Date : 2014-01-01 Epub Date: 2014-10-27 DOI: 10.1155/2014/531969
Maureen Groer, Cecilia Jevitt
Background. Postpartum thyroiditis (PPT) is a common triphasic autoimmune disease in women with thyroid peroxidase (TPO) autoantibodies. This study evaluated women's thyroid disease symptoms, physical findings, stress levels, and thyroid stimulating hormone (TSH) levels across six postpartum months in three groups, TPO negative, TPO positive, and PPT positive women. Methods. Women were recruited in midpregnancy (n = 631) and TPO status was determined which then was used to form the three postpartum groups. The three groups were compared on TSH levels, thyroid symptoms, weight, blood pressure, heart rate, a thyroid exam, and stress scores. Results. Fifty-six percent of the TPO positive women developed PPT. Hypothyroid group (F (2, 742) = 5.8, P = .003) and hyperthyroid group (F (2, 747) = 6.6, P = .001) subscale scores differed by group. Several symptoms and stress scores were highest in the PPT group. Conclusions. The normal postpartum is associated with many symptoms that mimic thyroid disease symptoms, but severity is greater in women with either TPO or PPT positivity. While the most severe symptoms were generally seen in PPT positive women, even TPO positive women seem to have higher risk for these signs and symptoms.
背景。产后甲状腺炎(PPT)是甲状腺过氧化物酶(TPO)自身抗体妇女常见的三期自身免疫性疾病。本研究评估了三组(TPO阴性、TPO阳性和PPT阳性)妇女产后6个月的甲状腺疾病症状、身体检查结果、压力水平和促甲状腺激素(TSH)水平。方法。在怀孕中期招募妇女(n = 631),并确定TPO状态,然后用于组成三个产后组。比较三组的TSH水平、甲状腺症状、体重、血压、心率、甲状腺检查和压力评分。结果。TPO阳性的女性中有56%患有PPT。甲状腺功能减退组(F (2,742) = 5.8, P = 0.003)和甲状腺功能亢进组(F (2,747) = 6.6, P = 0.001)亚量表评分组间存在差异。PPT组的一些症状和压力得分最高。结论。正常的产后有许多类似甲状腺疾病的症状,但在TPO或PPT阳性的妇女中,严重程度更大。虽然最严重的症状通常出现在PPT阳性的女性身上,但即使是TPO阳性的女性似乎也有更高的风险出现这些症状和体征。
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引用次数: 11
Urinary Iodine Clearance following Iodinated Contrast Administration: A Comparison of Euthyroid and Postthyroidectomy Subjects. 碘造影剂给药后尿碘清除率:甲状腺功能正常和甲状腺切除术后受试者的比较。
IF 2.1 Q4 ENDOCRINOLOGY & METABOLISM Pub Date : 2014-01-01 Epub Date: 2014-11-12 DOI: 10.1155/2014/580569
Janice D Ho, James F Tsang, Kylie A Scoggan, William D Leslie

Purpose. To compare iodine clearance following iodinated contrast administration in thyroidectomised thyroid cancer patients and euthyroid individuals. Methods. A convenience population (6 thyroidectomised thyroid cancer patients and 7 euthyroid controls) was drawn from patients referred for iodinated contrast-enhanced computed tomography (CT) studies. Subjects had sequential urine samples collected up to 6 months (50 samples from the thyroidectomised and 63 samples from the euthyroid groups). t-tests and generalised estimating equations (GEE) were used to test for group differences in urinary iodine creatinine ratios. Results. Groups had similar urinary iodine creatinine ratios at baseline, with a large increase 2 weeks following iodinated contrast (P = 0.005). Both groups had a return of urinary iodine creatinine ratios to baseline by 4 weeks, with no significant group differences overall or at any time point. Conclusions. Thyroidectomised patients did not have a significantly different urinary iodine clearance than euthyroid individuals following administration of iodinated contrast. Both had a return of urinary iodine creatinine ratios to baseline within 4 weeks.

目的。比较甲状腺癌切除患者和甲状腺功能正常个体碘造影剂使用后的碘清除率。方法。方便人群(6名甲状腺癌切除术患者和7名甲状腺正常对照)从接受碘化对比增强计算机断层扫描(CT)研究的患者中抽取。受试者连续收集了6个月的尿液样本(50份来自甲状腺切除术组,63份来自甲状腺功能正常组)。采用t检验和广义估计方程(GEE)来检验尿碘肌酐比值的组间差异。结果。各组在基线时尿碘肌酐比值相似,碘化对比2周后显著升高(P = 0.005)。两组的尿碘肌酐比在4周后恢复到基线水平,总体上或在任何时间点上没有明显的组间差异。结论。甲状腺切除术患者在给予碘造影剂后,尿碘清除率与甲状腺功能正常的患者没有显著差异。两人均在4周内尿碘肌酐恢复到基线水平。
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引用次数: 9
Histopathological Changes of the Thyroid and Parathyroid Glands in HIV-Infected Patients. hiv感染患者甲状腺和甲状旁腺的组织病理学变化。
IF 2.1 Q4 ENDOCRINOLOGY & METABOLISM Pub Date : 2014-01-01 Epub Date: 2014-01-22 DOI: 10.1155/2014/364146
Rabia Cherqaoui, K M Mohamed Shakir, Babak Shokrani, Sujay Madduri, Faria Farhat, Vinod Mody

Objective. To study histopathology of the thyroid and parathyroid glands in HIV-infected African Americans in the United States. Methods. A retrospective review of 102 autopsy cases done by the Department of Pathology at Howard University Hospital from 1980 through 2007 was conducted. The histopathological findings of the thyroid and parathyroid glands were reviewed, both macroscopically and microscopically. A control group of autopsy patients with chronic non-HIV diseases was examined. Results. There were 71 males (70%) and 31 females (30%) with an average age of 38 years (range: 20-71 y). Thirteen patients with abnormal thyroid findings were identified. Interstitial fibrosis was the most common histological finding (4.9%), followed by thyroid hyperplasia (1.9%). Infectious disease affecting the thyroid gland was limited to 2.9% and consisted of mycobacterium tuberculosis, Cryptococcus neoformans, and cytomegalovirus. Kaposi sarcoma of the thyroid gland was present in only one case (0.9%). Parathyroid hyperplasia was the most common histological change noted in the parathyroid glands. Comparing the histological findings of cases and controls, we found a similar involvement of the thyroid, with a greater prevalence of parathyroid hyperplasia in HIV patients. Conclusion. Thyroid and parathyroid abnormalities are uncommon findings in the HIV-infected African American population.

目标。目的:研究美国hiv感染非裔美国人甲状腺和甲状旁腺的组织病理学。方法。回顾性分析了1980年至2007年间由霍华德大学医院病理学部完成的102例尸检病例。本文综述了甲状腺和甲状旁腺的组织病理学表现,包括宏观和微观。以非hiv慢性疾病尸检患者为对照。结果。男性71例(70%),女性31例(30%),平均年龄38岁(20 ~ 71岁)。13例患者有甲状腺异常表现。间质纤维化是最常见的组织学表现(4.9%),其次是甲状腺增生(1.9%)。影响甲状腺的传染病限于2.9%,包括结核分枝杆菌、新型隐球菌和巨细胞病毒。甲状腺卡波西肉瘤仅1例(0.9%)。甲状旁腺增生是甲状旁腺最常见的组织学改变。比较病例和对照组的组织学结果,我们发现甲状腺也有类似的病变,在HIV患者中甲状旁腺增生的患病率更高。结论。甲状腺和甲状旁腺异常是罕见的发现在艾滋病毒感染的非洲裔美国人。
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引用次数: 11
Parathyroid gland involvement by thyroid cancer: results from a large series of thyroidectomies performed in two italian university hospitals and review of the literature. 甲状腺癌累及甲状旁腺:意大利两所大学医院进行的大量甲状腺切除术的结果和文献回顾。
IF 2.1 Q4 ENDOCRINOLOGY & METABOLISM Pub Date : 2014-01-01 Epub Date: 2014-11-11 DOI: 10.1155/2014/685425
Giampaolo Papi, Stefania Corrado, Guido Fadda, Antonino Maiorana, Livia Maccio, Salvatore Maria Corsello, Alfredo Pontecorvi

Objectives.Parathyroid involvement by thyroid cancer (TC) has not been frequently investigated in thyroidectomy-based studies. We aimed to detect cases of parathyroid invasion by TC in a large series of thyroidectomies and to review the literature on this topic. Study Design. A 10-yr period database research was made from the files of the Section of Pathology of two Italian University Hospitals. Out of 22,310 thyroidectomies, 10 patients with parathyroid involvement by TC were found. Results. The 10 patients, 7 females and 3 males, aged 55 ± 14 years (range 34-76, median 56) had papillary thyroid carcinoma and accounted for 0.4% of subjects affected by all TCs and submitted to thyroidectomy. The tumor invaded perithyroid soft tissues in 6 patients and central neck (level VI) lymph nodes in 3. Parathyroid involvement by TC occurred by infiltration in 6 cases, extension through an intervening pseudocapsule in 1, and both patterns in 3. All patients are alive and disease free at 5.6 ± 3-yr follow-up. Conclusion. Limited to thyroidectomy series, our results and literature data suggest that parathyroid involvement by TC has a 0.4-3.9% incidence rate; mainly affects women in their sixth-seventh decade of life; is associated to a good prognosis, unless massive extrathyroid extension of TC occurs.

目标。在以甲状腺切除术为基础的研究中,甲状腺癌(TC)累及甲状旁腺的研究并不频繁。我们的目的是在大量甲状腺切除术中发现TC侵犯甲状旁腺的病例,并回顾有关这一主题的文献。研究设计。对意大利两所大学医院病理科的档案进行了为期10年的数据库研究。在22,310例甲状腺切除术中,发现10例甲状腺旁腺受累于TC。结果。10例患者,女性7例,男性3例,年龄55±14岁(范围34-76岁,中位56岁),均为甲状腺乳头状癌,占所有TCs患者并行甲状腺切除术的0.4%。肿瘤侵袭甲状腺周围软组织6例,颈部中央(VI层)淋巴结3例。TC累及甲状旁腺6例为浸润,1例为假包膜延伸,3例为两种情况。随访5.6±3年,所有患者均存活且无疾病。结论。限于甲状腺切除术系列,我们的结果和文献资料表明,TC累及甲状旁腺的发生率为0.4-3.9%;主要影响六、七十岁的妇女;除非TC发生大量甲状腺外展,否则预后良好。
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引用次数: 2
Antitumor activity of lenvatinib (e7080): an angiogenesis inhibitor that targets multiple receptor tyrosine kinases in preclinical human thyroid cancer models. lenvatinib (e7080)的抗肿瘤活性:一种在临床前人甲状腺癌模型中靶向多种受体酪氨酸激酶的血管生成抑制剂。
IF 2.1 Q4 ENDOCRINOLOGY & METABOLISM Pub Date : 2014-01-01 Epub Date: 2014-09-10 DOI: 10.1155/2014/638747
Osamu Tohyama, Junji Matsui, Kotaro Kodama, Naoko Hata-Sugi, Takayuki Kimura, Kiyoshi Okamoto, Yukinori Minoshima, Masao Iwata, Yasuhiro Funahashi

Inhibition of tumor angiogenesis by blockading the vascular endothelial growth factor (VEGF) signaling pathway is a promising therapeutic strategy for thyroid cancer. Lenvatinib mesilate (lenvatinib) is a potent inhibitor of VEGF receptors (VEGFR1-3) and other prooncogenic and prooncogenic receptor tyrosine kinases, including fibroblast growth factor receptors (FGFR1-4), platelet derived growth factor receptor α (PDGFRα), KIT, and RET. We examined the antitumor activity of lenvatinib against human thyroid cancer xenograft models in nude mice. Orally administered lenvatinib showed significant antitumor activity in 5 differentiated thyroid cancer (DTC), 5 anaplastic thyroid cancer (ATC), and 1 medullary thyroid cancer (MTC) xenograft models. Lenvatinib also showed antiangiogenesis activity against 5 DTC and 5 ATC xenografts, while lenvatinib showed in vitro antiproliferative activity against only 2 of 11 thyroid cancer cell lines: that is, RO82-W-1 and TT cells. Western blot analysis showed that cultured RO82-W-1 cells overexpressed FGFR1 and that lenvatinib inhibited the phosphorylation of FGFR1 and its downstream effector FRS2. Lenvatinib also inhibited the phosphorylation of RET with the activated mutation C634W in TT cells. These data demonstrate that lenvatinib provides antitumor activity mainly via angiogenesis inhibition but also inhibits FGFR and RET signaling pathway in preclinical human thyroid cancer models.

通过阻断血管内皮生长因子(VEGF)信号通路抑制肿瘤血管生成是一种很有前景的甲状腺癌治疗策略。甲磺酸Lenvatinib (Lenvatinib)是一种有效的VEGF受体(VEGFR1-3)和其他促癌和促癌受体酪氨酸激酶抑制剂,包括成纤维细胞生长因子受体(FGFR1-4)、血小板衍生生长因子受体α (PDGFRα)、KIT和RET。我们在裸鼠身上检测了Lenvatinib对人甲状腺癌异种移植模型的抗肿瘤活性。口服lenvatinib对5例分化型甲状腺癌(DTC)、5例间变性甲状腺癌(ATC)和1例甲状腺髓样癌(MTC)异种移植模型均有显著的抗肿瘤活性。Lenvatinib对5种DTC和5种ATC异种移植物也显示出抗血管生成活性,而Lenvatinib对11种甲状腺癌细胞系中的2种,即RO82-W-1和TT细胞显示出体外抗增殖活性。Western blot分析显示,培养的RO82-W-1细胞过表达FGFR1, lenvatinib抑制FGFR1及其下游效应物FRS2的磷酸化。Lenvatinib还抑制TT细胞中RET的磷酸化,激活突变C634W。这些数据表明lenvatinib在临床前人甲状腺癌模型中主要通过抑制血管生成提供抗肿瘤活性,但也抑制FGFR和RET信号通路。
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引用次数: 348
Frequency of Adverse Events of Antithyroid Drugs Administered during Pregnancy. 妊娠期间使用抗甲状腺药物不良事件的频率。
IF 2.1 Q4 ENDOCRINOLOGY & METABOLISM Pub Date : 2014-01-01 Epub Date: 2014-01-09 DOI: 10.1155/2014/952352
Ai Yoshihara, Jaeduk Yoshimura Noh, Natsuko Watanabe, Kenji Iwaku, Sakiko Kobayashi, Miho Suzuki, Hidemi Ohye, Masako Matsumoto, Yo Kunii, Koji Mukasa, Kiminori Sugino, Koichi Ito

The frequency and types of adverse events after initial antithyroid drug (ATD) therapy during pregnancy have never been reported, nor has whether the frequency of adverse events is the same as among nonpregnant subjects ever been investigated. We investigated retrospectively the frequency of adverse events after initial ATD administration to previously untreated Graves' disease (GD) patients during pregnancy. We reviewed the charts of cases of 91 untreated pregnant women who came to our hospital for the first time and were newly diagnosed with GD during the period between January 1, 1999, and December 31, 2011. Thiamazole (MMI) was used to treat 40 patients and 51 patients were treated with propylthiouracil (PTU). Adverse events occurred in 5 patients (5/40; 12.5%) treated with MMI, and they consisted of cutaneous reactions in 5 patients. Adverse events occurred in five patients (5/51; 9.8%) treated with PTU, and they consisted of hepatotoxicity in two patients and cutaneous reactions in three patients. No patients experienced agranulocytosis or ANCA-related vasculitis. Comparison with the expected rate of adverse events in nonpregnant individuals showed that the frequency of adverse events in pregnant individuals was low.

妊娠期初始抗甲状腺药物(ATD)治疗后不良事件的频率和类型从未报道过,也没有调查过不良事件的频率是否与非妊娠受试者相同。我们回顾性调查了妊娠期未经治疗的Graves病(GD)患者首次服用ATD后不良事件的频率。我们回顾了1999年1月1日至2011年12月31日期间91例首次来我院未经治疗并新诊断为GD的孕妇的病例图。用噻马唑(MMI)治疗40例,用丙硫脲嘧啶(PTU)治疗51例。不良事件发生5例(5/40;12.5%)用MMI治疗,其中5例为皮肤反应。5例患者发生不良事件(5/51;9.8%),其中2例为肝毒性,3例为皮肤反应。没有患者出现粒细胞缺乏症或与anca相关的血管炎。与非妊娠个体不良事件预期发生率比较,妊娠个体不良事件发生率较低。
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引用次数: 13
期刊
Journal of Thyroid Research
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