Journal of Thyroid Research 

About: Journal of Thyroid Research is an academic journal published by Hindawi Publishing Corporation. The journal publishes majorly in the area(s): Thyroid & Thyroid cancer. It has an ISSN identifier of 2042-0072. It is also open access. Over the lifetime, 264 publications have been published receiving 7386 citations.

Antitumor Activity of Lenvatinib (E7080): An Angiogenesis Inhibitor That Targets Multiple Receptor Tyrosine Kinases in Preclinical Human Thyroid Cancer Models

Abstract: 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.

The Link between Thyroid Function and Depression.

Abstract: The relation between thyroid function and depression has long been recognized. Patients with thyroid disorders are more prone to develop depressive symptoms and conversely depression may be accompanied by various subtle thyroid abnormalities. Traditionally, the most commonly documented abnormalities are elevated T4 levels, low T3, elevated rT3, a blunted TSH response to TRH, positive antithyroid antibodies, and elevated CSF TRH concentrations. In addition, thyroid hormone supplements appear to accelerate and enhance the clinical response to antidepressant drugs. However, the mechanisms underlying the interaction between thyroid function and depression remain to be further clarified. Recently, advances in biochemical, genetic, and neuroimaging fields have provided new insights into the thyroid-depression relationship.

Thyroid disorders and diabetes mellitus.

Abstract: Studies have found that diabetes and thyroid disorders tend to coexist in patients. Both conditions involve a dysfunction of the endocrine system. Thyroid disorders can have a major impact on glucose control, and untreated thyroid disorders affect the management of diabetes in patients. Consequently, a systematic approach to thyroid testing in patients with diabetes is recommended.

Autoimmune Thyroid Disorders

Abstract: Thyroid autoimmunity, as reflected by the presence in serum of autoantibodies directed against the thyroid autoantigens thyroglobulin (Tg) and thyroid peroxidase (TPO), is present in >10% of the US population over 12 years of age [1] and is the most common cause of endocrine dysfunction in iodine-sufficient populations [2]. The underlying mechanism is a failure of T-cell tolerance leading to lymphocytic infiltration of the thyroid gland [3] and to a complex sequence of humoral and cellular immune responses to thyroid antigens, presumably in response to an environmental trigger [4]. In chronic lymphocytic thyroiditis (CLT), the predominant immunologic mechanisms are T-cell- and cytokine-mediated thyroid cell damage and apoptotic cell death whereas in Graves' disease (GD) generation of thyrotropin (TSH) receptor autoantibodies leads to thyroid cell stimulation [5], but significant overlap exists. Seven susceptibility genes, in addition to the major histocompatibility gene (HLA-DR3), have now been identified [6]. Some of these genes affect the immune response in general (CD40, CTLA-4, and PTPN22), while others are thyroid specific (thyroglobulin, thyrotropin (TSH) receptor). Some are common to both CLT and GD, while others are specific for GD. In view of the importance of AITD as well as the diverse array of new information, it is only fitting that this special issue of the Journal of Thyroid Research is devoted entirely to this complex subject. Four of the papers we have selected are focused on clinical topics, including AITD in childhood, during pregnancy, in the postpartum period, and in patients with type 1 diabetes mellitus. The fifth paper addresses the potential role of NKT cells in an animal model of thyroiditis. We conclude this special edition with a discussion of thyroid autoimmunity in patients with papillary thyroid cancer (PTC). The association of AI and thyroid cancer was first reported by Dailey et al. [7]. In general, patients with AI appear more likely to have PTC than follicular thyroid cancer (FTC), but a lower frequency of extrathyroidal extension, nodal and distant metastases when compared with patients without AI. In some but not all series, patients with autoimmune thyroiditis (AT) and PTC have improved survival when compared to those with PTC alone, suggesting that thyroid autoimmunity might contribute to improved survival [8–10]. In contrast, other data suggest that AI might actually increase the risk to develop thyroid cancer [10–12]. Several theories have been proposed to explain how AI might increase the risk for thyroid malignancy. Thyrocyte apoptosis and proliferation are increased in AI suggesting that thyrocytes rapidly progressing through the cell cycle might accumulate increased DNA damage resulting in malignant transformation [13]. Russell et al. hypothesized that thyroid cells predestined to become cancers might secrete proinflammatory cytokines that affect immune cells [14]. They showed that thyrocytes of ret/PTC3 transgenic mice express increased levels of interleukins, tumor necrosis factor-α, and cyclooxygenase-2 [14] that could attract and/or activate cells of the immune system. Finally, the ret/PTC recombinant genes have been detected in samples of AI [15–17] suggesting that ret/PTC rearrangements might be present in AI and could be precursors to PTC. From these papers, it is clear that thyroid autoimmunity is a frequent problem in the population and that thyroid autoimmunity can lead to a variety of thyroid disorders including alterations in thyroid hormone synthesis and possibly even neoplasia. Focused research in this area is beginning to illuminate some of the molecular mechanisms that help to explain these associations. Rosalind Brown Gary L. Francis

Differentiated thyroid cancer: management of patients with radioiodine nonresponsive disease.

Abstract: Differentiated thyroid carcinoma (papillary and follicular) has a favorable prognosis with an 85% 10-year survival. The patients that recur often require surgery and further radioactive iodine to render them disease-free. Five percent of thyroid cancer patients, however, will eventually succumb to their disease. Metastatic thyroid cancer is treated with radioactive iodine if the metastases are radioiodine avid. Cytotoxic chemotherapies for advanced or metastatic noniodine avid thyroid cancers show no prolonged responses and in general have fallen out of favor. Novel targeted therapies have recently been discovered that have given rise to clinical trials for thyroid cancer. Newer aberrations in molecular pathways and oncogenic mutations in thyroid cancer together with the role of angiogenesis in tumor growth have been central to these discoveries. This paper will focus on the management and treatment of metastatic differentiated thyroid cancers that do not take up radioactive iodine.