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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Some cancer types are strongly associated with chronic inflammatory or infectious diseases whereas others are not, but an inflammatory component is present in most human neoplastic lesions. This review focuses on various aspects of thyroid cancer and inflammation. The incidence of thyroid cancer, in particular of well-differentiated papillary thyroid carcinomas (PTCs), is increased in autoimmune thyroid diseases such as Hashimoto's thyroiditis. Thyroid cancer often has an inflammatory cell infiltrate, which includes lymphocytes, macrophages, dendritic cells and mast cells, whose role in thyroid cancer is still not completely understood. However, most experimental evidence suggests these cells exert a protumorigenic function. Moreover, oncoproteins typically expressed in human PTCs, such as RET/PTC, RAS, and BRAF, trigger a proinflammatory programme in thyreocytes. These data suggest that inflammatory molecules are promising targets for thyroid cancer therapy.
Mol Cell Endocrinol 2010 May 28
PMID:Thyroid cancer and inflammation. 1983 28

The epidermal growth factor receptor family plays a critical role in the control of many physiological processes. Genetic alterations and/or variations in the gene encoding these receptors have been implicated in a variety of human cancers. In this study we evaluate the association of two single-nucleotide polymorphisms (SNP), R497K and I655V, of the EGFR and HER2 genes, respectively, with thyroid cancer risk. The analysis was performed with 302 healthy individuals and 106 thyroid cancer patients. No significant difference was found in the allelic and genotypic frequency distribution of the SNP R497K between the control and patient groups. While for the SNP I655V, the allele G is more frequent in patients than in controls and was associated with an increased risk of thyroid cancer (odds ratio = 1.88; 95% confidence intervals: 1.18-3.01; p = 0.007). We have also investigated the relationship between these two polymorphic sites and clinicopathological characteristics such as thyroid-stimulating hormone level, off-thyroxin, serum thyroglobulin, tumor histology, metastasis, tumor status, tumor stage, and survival. No significant association was observed. Tumor status was found significantly associated with HER2 I655V as well as with two previously studied markers in the thyroid hormone receptor A and estrogen receptor 1 (ESR1) genes (D17S2189 and D6S440, respectively). We also report a correlation between thyroglobulin level and genotypes for SNP rs2228480 in exon 8 of the ESR1 gene. In conclusion, our results suggest that the SNP HER2 I655V, but not the EGFR R497K, was associated with thyroid cancer risk.
Genet Test Mol Biomarkers 2009 Dec
PMID:Association of EGFR and HER2 polymorphisms with risk and clinical features of thyroid cancer. 1986 May 76

Thyroid cancer is the most common neoplasia of the endocrine system and accounts for approximately 1% of all newly diagnosed cancer cases. Its incidence has rapidly grown over the past few decades. Although most thyroid carcinomas are of the well-differentiated papillary histology, and respond well to treatment with surgical resection followed by radioactive iodine ablation, tumors with more aggressive phenotype, such as follicular, poorly differentiated, anaplastic, and medullary cancers, lead to almost 1500 patient deaths annually. Therefore, understanding molecular mechanisms that regulate the biology of these carcinomas could be helpful to identify new molecules acting as novel targets for therapeutic intervention. NF-kappaB has been recently shown to play an important role in thyroid cancer for its ability to control the proliferative and the anti-apoptotic signaling pathways of thyroid neoplastic cells. Oncogenic proteins RET/PTC, RAS and BRAF, that are involved in many aspects of thyroid carcinogenesis, can induce NF-kappaB activation in papillary, follicular, and medullary thyroid carcinomas, while constitutive de-regulated NF-kappaB activity has been found in anaplastic thyroid carcinomas. A number of NF-kappaB inhibitors have been demonstrated to induce anti-proliferative effects and/or massive apoptosis, especially in combination with radio- or chemo-therapy. The results obtained suggest that targeting NF-kappaB could be a promising strategy for advanced thyroid cancer treatment.
Mol Cell Endocrinol 2010 May 28
PMID:Role of NF-kappaB in thyroid cancer. 1987 19

Papillary thyroid cancer (PTC) is a common endocrine malignancy that frequently harbors the oncogenic T1799A BRAF mutation. As a novel prognostic molecular marker, this mutation has received considerable attention in recent years for its potential utility in the risk stratification and management of PTC. In PTC, BRAF mutation is closely associated with extrathyroidal extension, lymph node metastasis, advanced tumor stages, disease recurrence, and even patient mortality. Many of the responsible molecular derangements promoted by, or associated with, BRAF mutation have been identified, including over-expression of tumor-promoting genes, suppression of tumor-suppressor genes, and silencing of thyroid iodide-handling genes, resulting in impairment or loss of radioiodine avidity and hence the failure of radioiodine treatment of PTC. BRAF mutation can be readily tested on thyroid fine needle aspiration biopsy specimens, with high preoperative predictive probabilities for clinicopathological outcomes of PTC. As such, the knowledge of BRAF mutation status can facilitate more accurate risk stratification and better decision making at various steps in the management of PTC, from preoperative planning of initial surgical scale to postoperative decisions about appropriate radioiodine treatment and thyroid-stimulating hormone suppression, and to selections of appropriate surveillance modalities for PTC recurrence. The greatest utility of BRAF mutation status is in those cases where traditional clinicopathological criteria alone would otherwise be unreliable in the risk stratification and management of PTC. Use of this unique molecular marker, in conjunction with conventional clinicopathological risk factors, to assist the prognostication of PTC is likely to improve the efficiency of contemporary management of thyroid cancer.
Mol Cell Endocrinol 2010 May 28
PMID:Prognostic utility of BRAF mutation in papillary thyroid cancer. 1988 29

The phosphoinositide-3 (OH) kinase (PI3K) signaling cascade is involved in regulating glucose uptake and metabolism, growth, motility, and other essential functions for cell survival. Unregulated activation of this pathway commonly occurs in cancer through a variety of mechanisms, including genetic mutations of kinases and regulatory proteins, epigenetic alterations that alter gene expression and translation, and posttranslational modifications. In thyroid cancer, constitutive activation of PI3K signaling has been shown to play a role in the genetic predisposition for thyroid neoplasia in Cowden's syndrome, and is recognized to be frequently overactivated in sporadic forms of thyroid cancer including those with aggressive clinical behaviors. In this review, the key signaling molecules in the PI3K signaling cascade, the abnormalities known to occur in thyroid cancer, and the potential for therapeutic targeting of PI3K pathway members will be discussed.
Mol Cell Endocrinol 2010 May 28
PMID:The PI3K-Akt-mTOR pathway in initiation and progression of thyroid tumors. 1989 9

Thyroid cancer is the most common endocrine malignancy; it accounts for approximately 1% of all new case of cancer each year, and its incidence has increased significantly over the last few decades. The majority of thyroid tumors originate from follicular epithelial cells. Among them, papillary (PTC) and follicular carcinomas (FTC) represent the most common forms of differentiated thyroid cancer and account for approximately 80% and 15% of all cases, respectively. Specific genetic lesions are associated to each thyroid tumor histotype: BRAF mutations and RET/PTC and TRK oncogenes have been detected in PTC, whereas FTC is characterized by PAX8/PPARgamma rearrangements and RAS mutations. In this review we summarize studies on the molecular biology of the differentiated thyroid tumors, with particular interest in the associated genetic lesions and their role in thyroid carcinogenesis. We also report recent findings on gene expression and miRNA profiles of PTC and FTC.
Q J Nucl Med Mol Imaging 2009 Oct
PMID:Molecular pathology of differentiated thyroid cancer. 1991 Aug 97

A firm or hard consistency is associated with an increased risk of malignancy in thyroid nodules. Ultrasound (US) elastosonography is a new powerful diagnostic technique that assesses hardness as indicator of malignancy that was recently applied in the diagnostic approach of nodular thyroid disease. The basic principle of elastosonography is that tissue compression produces strain (displacement), that is less in hard than in soft tissues and is scored measuring the degree of distortion of US beam under the application of an external force, during the examination. The US elastogram is displayed over the B-mode image in a colour scale that corresponds to tissue elasticity. The US elastosonography performed on selected series of patients has displayed a sensitivity of 97%, a specificity of 100%, a positive predictive value of 100% and a negative predictive value of 98%. The predictivity of US elastographic measurement was independent from the nodule size, high sensitivity and specificity being observed also in nodules <1 cm. These data were also confirmed by other authors in smaller cytological series. Available data suggest that predictivity of US elastosonography is maintained in indeterminate lesions. Conventional US maintains a pivotal importance to define which nodules are suitable for elastographic characterization. Indeed, nodules in which US reveals the presence of calcified shell and cystic nodules have to be excluded from the US elastographic evaluation. Another limitation is that the nodule to be examined must be clearly distinguishable from other nodules present in the thyroid. Thus, multinodular goiters with coalescent nodules are not suitable for this analysis. US elastosonography seems to have a great potential as a new tool for the diagnosis of thyroid cancer, especially in nodules with indeterminate cytology.
Q J Nucl Med Mol Imaging 2009 Oct
PMID:Potential value of elastosonography in the diagnosis of malignancy in thyroid nodules. 1991 Aug 98

Differentiated thyroid cancer (DTC) is the most common endocrine malignancy with the highest mortality although with appropriate treatment has a good long-term prognosis and cure rate. Over the last 30 years there is a worldwide trend showing an increasing incidence of thyroid cancer. In DTC patients, total thyroidectomy has been for many decades routinely followed by the administration of radioiodine (131I) activity to destroy remnant thyroid tissue. Several reasons are in favour to routine ablation of postoperative thyroid remnants. The combination of both surgery and radioiodine has proven as a safe and effective treatment, resulting in improved life expectation and reduced recurrence rate for DTC patients. Recently, however, 131I ablation is not uniformly recommended for cancers smaller than 10 mm, and its use is debated for papillary tumours with diameter between 10 and 20 mm. Indeed, the decision about subsequent 131I thyroid remnant ablation is recommended as "individualized and selective". Even if new evidence has emerged that provides additional support for performing 131I treatment, the possible presence of radioiodine-associated side effects should be not overlooked. Moreover, a lot of discussion has taken place as to whether, and to what extent, 131I may cause secondary malignancies. Blood-based dosimetry is important to avoid surplus bone marrow toxicity while treating DTC patients. In this regard, the availability of a genetically engineered version of recombinant human TSH (rhTSH) provides an alternative tool to enhance serum TSH levels without inducing hypothyroidism. The administration of rhTSH to thyroid cancer patients still on LT4 therapy promotes radioiodine uptake and thyroglobulin production by thyroid cells to an extent comparable with hypothyroidism, preserving patients' quality of life, increasing the renal clearance of 131I and decreasing both the whole body and the blood dose. In this review the authors will discuss the pros and cons of postoperative radioiodine-induced thyroid remnant ablation.
Q J Nucl Med Mol Imaging 2009 Oct
PMID:Radioiodine ablation: when and how. 1991 Sep

Determination of thyroglobulin (Tg) in serum represents a key element in the follow-up of patients treated for differentiated thyroid cancer (DTC). The sensitivity and the specificity of the assay strongly affects the clinical impact. Most of patients are disease-free after thyroidectomy and iodine radioablation; 15% of them show over time persistent or recurrent disease; of these, 5% dies due to worsening of disease. This implies that the follow-up procedures should have a high negative predictive value to reduce as possible the unnecessary diagnostic tools and a high positive predictive value to identify the few patients with persistent/recurrent disease. The recent international guidelines are based on thyroglobulin measurement after thyroid-stimulating hormone (TSH) stimulation. More recent studies suggest that follow up based on serial measurements of basal (i.e. unstimulated) Tg show a higher predictive value than the single measurement after stimulation. Large and multicenter studies are necessary to modify the current guidelines.
Q J Nucl Med Mol Imaging 2009 Oct
PMID:Serum thyroglobulin measurement in the follow-up of patients treated for differentiated thyroid cancer. 1991 Sep 1

Thyrotropin stimulating hormone (TSH) exerts a physiological stimulus to growth, function and ability to take up iodine of both normal and malignant follicular cells. For this reason, the metastases deriving from well differentiated thyroid cancer (DTC) can be effectively treated with radioiodine but this procedure requires a strong TSH stimulus that can be obtained by withdrawing the L-thyroxine (LT4) therapy. However, both the social and personal life of patients while they are withdrawing the LT4 therapy are heavily affected by hypothyroidism. After more than a decade since the development of recombinant human TSH (rhTSH), this molecule has been introduced in the clinical practice (1998 in USA and 2001 in Europe) as a safe and reliable alternative to LT4 withdrawal. For several years the main clinical application of rhTSH was for diagnostic purposes (i.e. thyroglobulin stimulation) but, after the more recent demonstration of its efficacy in preparing DTC patients for radioiodine post surgical thyroid remnant ablation, also this application has been officially recognized worldwide. The validity of rhTSH has been also demonstrated in stimulating metastatic thyroid cancer cells but this employment is not yet officially approved and it can be used only in patients with contraindication to hypothyroidism (i.e. "compassionate use"). Other possible uses of rhTSH stimulation are related to its ability to enhance both 18FDG uptake during PET scan of metastatic DTC patients and the effectiveness of conventional chemotherapy. The aim of this review was to recall how the rhTSH has been developed and progressively introduced in the clinical management of DTC patients.
Q J Nucl Med Mol Imaging 2009 Oct
PMID:Recombinant human TSH (rhTSH) in 2009: new perspectives in diagnosis and therapy. 1991 Sep 2


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