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Sample records for advanced thyroid cancers

  1. Advances in the management of thyroid cancer.

    PubMed

    Shaha, Ashok R

    2005-01-01

    The incidence of thyroid cancer is rapidly increasing in the United States. A large number of incidentalomas are found during routine head and neck evaluations. The diagnostic workup still revolves around fine needle aspiration biopsy. Ultrasound guided fine needle aspiration biopsy is likely to yield the best results. Surgical resection offers the best treatment choice. Controversy continues in relation to total versus less than total thyroidectomy. The incidence of complications is inversely proportional to the extent of surgery and obviously related to the experience of the operating surgeon. The decision regarding the extent of thyroidectomy should be based on prognostic factors and risk groups. Prognostic factors are well defined, such as age, grade of the tumor, extrathyroidal extension, size, distant metastasis, and histology. Nodal metastasis has minimal implications. Based on prognostic factors, thyroid cancer can be divided into low, intermediate and high risk groups. In the high risk group and in selected intermediate risk patients, radioactive iodine dosimetry and ablation should be considered after total thyroidectomy. PET scanning and the use of recombinant TSH have been major advances in follow-up care for patients with thyroid cancer. Thyroglobulin appears to be a very good tumor marker for follow-up. No major breakthrough is noted in the management of anaplastic thyroid cancer, however, identification of RET mutation has been extremely helpful in evaluating the family members of the patient with medullary thyroid cancer with strong consideration given to total thyroidectomy. PMID:17462286

  2. Advanced thyroid cancers: new era of treatment.

    PubMed

    Mohammed, Amrallah A; El-Shentenawy, Ayman

    2014-07-01

    Since chemotherapy has been shown to be unsuccessful in case of advanced thyroid carcinomas, the research for new therapies is fundamental. Clinical trials of many tyrosine kinase inhibitors as well as anti-angiogenic inhibitors suggest that patients with thyroid cancer could have an advantage with new target therapy. Recently, Food and Drug Administration approved two targeted therapies, vandetanib and cabozantinib for the treatment of metastatic thyroid carcinomas with acceptable outcome. We summarized the results and the toxic effects associated with these treatments reported in clinical trials. Future trials should aim at combinations of targeted agents with or without other treatment modalities to obtain a more effective result in thyroid carcinoma treatment. PMID:24908065

  3. Management of advanced medullary thyroid cancer.

    PubMed

    Hadoux, Julien; Pacini, Furio; Tuttle, R Michael; Schlumberger, Martin

    2016-01-01

    Medullary thyroid cancer arises from calcitonin-producing C-cells and accounts for 3-5% of all thyroid cancers. The discovery of a locally advanced medullary thyroid cancer that is not amenable to surgery or of distant metastases needs careful work-up, including measurement of serum calcitonin and carcinoembryonic antigen (and their doubling times), in addition to comprehensive imaging to determine the extent of the disease, its aggressiveness, and the need for any treatment. In the past, cytotoxic chemotherapy was used for treatment but produced little benefit. For the past 10 years, tyrosine kinase inhibitors targeting vascular endothelial growth factor receptors and RET (rearranged during transfection) have been used when a systemic therapy is indicated for large tumour burden and documented disease progression. Vandetanib and cabozantinib have shown benefits on progression-free survival compared with placebo in this setting, but their toxic effect profiles need thorough clinical management in specialised centres. This Review describes the management and treatment of patients with advanced medullary thyroid cancer with emphasis on current targeted therapies and perspectives to improve patient care. Most treatment responses are transient, emphasising that mechanisms of resistance need to be better understood and that the efficacy of treatment approaches should be improved with combination therapies or other drugs that might be more potent or target other pathways, including immunotherapy. PMID:26608066

  4. Treatment of advanced thyroid cancer: role of molecularly targeted therapies.

    PubMed

    Covell, Lorinda L; Ganti, Apar Kishor

    2015-09-01

    Advanced thyroid cancer is not amenable to therapy with conventional cytotoxic chemotherapy. However, newer advances in the understanding of the molecular pathogenesis of different subtypes of thyroid cancer have provided new opportunities for the evaluation of molecularly targeted therapies. This has led to multiple clinical trials using various multi-kinase inhibitors and the subsequent US FDA approval of sorafenib for differentiated thyroid cancer and vandetanib and cabozantinib for medullary thyroid carcinoma. This review provides a summary of the current literature for the treatment of advanced thyroid carcinoma and future directions in this disease. PMID:26335853

  5. Thyroid cancer

    MedlinePlus

    ... cancer is a cancer that starts in the thyroid gland. The thyroid gland is located inside the front of your lower ... thyroid cells that are normally present in the thyroid gland. This form of thyroid cancer tends to occur ...

  6. Treatment of advanced medullary thyroid cancer.

    PubMed

    Smit, Johannes

    2013-03-14

    Therapy decisions in advanced medullary thyroid carcinoma should be guided by a critical appraisal of the natural disease course (slowly progressive vs. aggressive) and benefits and side effects of therapy. Therapy goals should be distinguished between curative and palliative. Local treatments are mainly palliative and may add to quality of life. The advent of novel systemic therapies opens promising perspectives but its place in the therapeutic arsenal must be further determined. PMID:23514632

  7. [Thyroid cancer].

    PubMed

    Nagayama, Yuji

    2012-03-01

    The thyroid glands are a vulnerable organ to ionizing radiation. Indeed the epidemiological studies have revealed an increase in the incidences of thyroid cancer among atomic bomb survivors in Hiroshima and Nagasaki and radiation casualties in Chernobyl. The carcinogenic risk for the thyroids is dependent on radiation dose, and higher in younger people. Recent advances in molecular biology contribute to clarify the mechanisms for thyroid carcinogenesis at genetic and molecular levels. Here radiation-induced thyroid carcinogenesis is reviewed from epidemiological data to basic research. PMID:22514922

  8. Evolving molecularly targeted therapies for advanced-stage thyroid cancers.

    PubMed

    Bible, Keith C; Ryder, Mabel

    2016-07-01

    Increased understanding of disease-specific molecular targets of therapy has led to the regulatory approval of two drugs (vandetanib and cabozantinib) for the treatment of medullary thyroid cancer (MTC), and two agents (sorafenib and lenvatinib) for the treatment of radioactive- iodine refractory differentiated thyroid cancer (DTC) in both the USA and in the EU. The effects of these and other therapies on overall survival and quality of life among patients with thyroid cancer, however, remain to be more-clearly defined. When applied early in the disease course, intensive multimodality therapy seems to improve the survival outcomes of patients with anaplastic thyroid cancer (ATC), but salvage therapies for ATC are of uncertain benefit. Additional innovative, rationally designed therapeutic strategies are under active development both for patients with DTC and for patients with ATC, with multiple phase II and phase III randomized clinical trials currently ongoing. Continued effort is being made to identify further signalling pathways with potential therapeutic relevance in thyroid cancers, as well as to elaborate on the complex interactions between signalling pathways, with the intention of translating these discoveries into effective and personalized therapies. Herein, we summarize the progress made in molecular medicine for advanced-stage thyroid cancers of different histotypes, analyse how these developments have altered - and might further refine - patient care, and identify open questions for future research. PMID:26925962

  9. Thyroid Cancer

    MedlinePlus

    ... are here Home > Types of Cancer > Thyroid Cancer Thyroid Cancer This is Cancer.Net’s Guide to Thyroid Cancer. Use the menu below to choose the ... social workers, and patient advocates. Cancer.Net Guide Thyroid Cancer Overview Statistics Medical Illustrations Risk Factors Symptoms ...

  10. Thyroid Cancer

    MedlinePlus

    ... body work normally. There are several types of cancer of the thyroid gland. You are at greater ... imaging tests, and a biopsy to diagnose thyroid cancer. Treatment depends on the type of cancer you ...

  11. Recent Advances in Molecular Biology of Thyroid Cancer and Their Clinical Implications

    PubMed Central

    Xing, Mingzhao

    2009-01-01

    Synopsis Thyroid cancer is the most common endocrine malignancy with a rapid rising incidence in recent years. Novel efficient management strategies are increasingly needed for this cancer. Remarkable advances have occurred in recent years in understanding the molecular biology of thyroid cancer. This is reflected in several major biological areas of thyroid cancer, including the molecular alterations for the loss of radioiodine avidity of thyroid cancer, the pathogenic role of the MAP kinase and PI3K/Akt pathways and their related genetic alterations, and the aberrant methylation of functionally important genes in thyroid tumorigenesis and pathogenesis. These exciting advances in molecular biology of thyroid cancer provide unprecedented opportunities for the development of molecular-based novel diagnostic, prognostic, and therapeutic strategies for this cancer. PMID:19040974

  12. Thyroid cancer

    MedlinePlus

    ... known prevention. Awareness of risk (such as previous radiation therapy to the neck) can allow earlier diagnosis and treatment. Sometimes, people with family histories and genetic mutations related to thyroid cancer will have their thyroid ...

  13. Suberoylanilide Hydroxamic Acid in Treating Patients With Metastatic and/or Locally Advanced or Locally Recurrent Thyroid Cancer

    ClinicalTrials.gov

    2014-07-23

    Insular Thyroid Cancer; Recurrent Thyroid Cancer; Stage II Follicular Thyroid Cancer; Stage II Papillary Thyroid Cancer; Stage IV Follicular Thyroid Cancer; Stage IV Papillary Thyroid Cancer; Thyroid Gland Medullary Carcinoma

  14. Pazopanib Hydrochloride in Treating Patients With Advanced Thyroid Cancer

    ClinicalTrials.gov

    2016-08-31

    Recurrent Thyroid Gland Carcinoma; Stage III Differentiated Thyroid Gland Carcinoma; Stage III Thyroid Gland Medullary Carcinoma; Stage IVA Differentiated Thyroid Gland Carcinoma; Stage IVA Thyroid Gland Medullary Carcinoma; Stage IVA Thyroid Gland Undifferentiated (Anaplastic) Carcinoma; Stage IVB Differentiated Thyroid Gland Carcinoma; Stage IVB Thyroid Gland Medullary Carcinoma; Stage IVB Thyroid Gland Undifferentiated (Anaplastic) Carcinoma; Stage IVC Differentiated Thyroid Gland Carcinoma; Stage IVC Thyroid Gland Medullary Carcinoma; Stage IVC Thyroid Gland Undifferentiated (Anaplastic) Carcinoma; Thyroid Gland Undifferentiated (Anaplastic) Carcinoma

  15. Thyroid cancer - medullary carcinoma

    MedlinePlus

    Thyroid - medullary carcinoma; Cancer - thyroid (medullary carcinoma); MTC; Thyroid nodule - medullary ... The cause of medullary carcinoma of the thyroid (MTC) is unknown. ... and adults. Unlike other types of thyroid cancer, MTC is less ...

  16. Advances in thyroid cancer treatment: latest evidence and clinical potential

    PubMed Central

    Alonso-Gordoa, T.; Díez, J.J.; Durán, M.

    2015-01-01

    Advanced thyroid carcinoma is an infrequent tumor entity with limited treatment possibilities until recently. The extraordinary improvement in the comprehension of genetic and molecular alterations involving the RAS/RAF/mitogen-activated protein kinase and phosphatidylinositide 3-kinase/Akt/mammalian target of rapamycin signaling and interacting pathways that are involved in tumor survival, proliferation, differentiation, motility and angiogenesis have been the rationale for the development of new effective targeted therapies. Data coming from phase II clinical trials have confirmed the efficacy of those targeted agents against receptors in cell membrane and cytoplasmic molecules. Moreover, four of those investigational drugs, vandetanib, cabozantinib, sorafenib and lenvatinib, have reached a phase III clinical trial with favorable results in progression-free survival and overall survival in medullary thyroid carcinoma and differentiated thyroid carcinoma. Further analysis for an optimal approach has been conducted according to mutational profile and tumor subtypes. However, consistent results are still awaited and the research for adequate prognostic and predictive biomarkers is ongoing. The following report offers a comprehensive review from the rationale to the basis of targeted agents in the treatment of thyroid carcinoma. In addition, current and future therapeutic developments by the inhibition of further molecular targets are discussed in this setting. PMID:25553081

  17. Advances in the management of differentiated thyroid cancer with follicular cell strain.

    PubMed

    Ben Slimène, Faouzi; Mhiri, Aida; Ben Ali, Moez; Slimène, Hédia; Ben Raies, Nouzha; Karboua, Esma; Schlumberger, Martin

    2016-03-01

    The management of nodules and thyroid cancer is evolving. The aim is to individualize the treatment, decreasing aggression in the forms low risk and instead seeking new therapeutic options in advanced disease. This update shows the main recent advances in this field. PMID:27575497

  18. [Advances in thyroglobulin assays and their impact on the management of differentiated thyroid cancers].

    PubMed

    d'Herbomez, Michèle; Lion, Georges; Béron, Amandine; Wémeau, Jean-Louis; DoCao, Christine

    2016-01-01

    Thyroglobulin (Tg) is a high molecular weight glycoprotein located mainly in thyroid follicles, where thyroid hormones are synthesized and stored. In patients with differentiated thyroid cancer of follicular origin, serum Tg levels become undetectable following total thyroidectomy and iodine-131 remnant ablation. It is a key biomarker to follow-up patients with differentiated thyroid cancer, in combination with neck ultrasound monitoring. The measurement of Tg in the wash-out of the needle used for fine needle aspiration biopsy is a valuable aid to the diagnosis of lymph node metastasis. The presence of anti-thyroglobulin antibodies affects reliability of Tg results measured in serum or plasma. Systematic investigation of such antibodies is required to validate any Tg assay. Elevated or rising levels of anti-thyroglobulin antibodies can in turn be used as a surrogate tumor marker of thyroid cancer. The development of second-generation Tg assay (automated, highly sensitive) has enabled significant advances in the management of differentiated thyroid cancer: early detection of persistent or recurrent disease and follow-up care simplified in low-risk patients. Testing of serum Tg can also be useful in evaluating other clinical situations such as congenital hypothyroidism, endemic goiter and thyrotoxicosis factitia. PMID:26711165

  19. Treatment of advanced thyroid cancer with targeted therapies: ten years of experience.

    PubMed

    Viola, David; Valerio, Laura; Molinaro, Eleonora; Agate, Laura; Bottici, Valeria; Biagini, Agnese; Lorusso, Loredana; Cappagli, Virginia; Pieruzzi, Letizia; Giani, Carlotta; Sabini, Elena; Passannati, Paolo; Puleo, Luciana; Matrone, Antonio; Pontillo-Contillo, Benedetta; Battaglia, Valentina; Mazzeo, Salvatore; Vitti, Paolo; Elisei, Rossella

    2016-04-01

    Thyroid cancer is rare, but it is the most frequent endocrine malignancy. Its prognosis is generally favorable, especially in cases of well-differentiated thyroid cancers (DTCs), such as papillary and follicular cancers, which have survival rates of approximately 95% at 40 years. However, 15-20% of cases became radioiodine refractory (RAI-R), and until now, no other treatments have been effective. The same problems are found in cases of poorly differentiated (PDTC) and anaplastic (ATC) thyroid cancers and in at least 30% of medullary thyroid cancer (MTC) cases, which are very aggressive and not sensitive to radioiodine. Tyrosine kinase inhibitors (TKIs) represent a new approach to the treatment of advanced cases of RAI-R DTC, MTC, PDTC, and, possibly, ATC. In the past 10 years, several TKIs have been tested for the treatment of advanced, progressive, and RAI-R thyroid tumors, and some of them have been recently approved for use in clinical practice: sorafenib and lenvatinib for DTC and PDTC and vandetanib and cabozantinib for MTC. The objective of this review is to present the current status of the treatment of advanced thyroid cancer with the use of innovative targeted therapies by describing both the benefits and the limits of their use based on the experiences reported so far. A comprehensive analysis and description of the molecular basis of these therapies, as well as new therapeutic perspectives, are reported. Some practical suggestions are given for both the choice of patients to be treated and their management, with particular regard to the potential side effects. PMID:27207700

  20. Key Statistics for Thyroid Cancer

    MedlinePlus

    ... cancer? Next Topic Thyroid cancer risk factors Key statistics for thyroid cancer How common is thyroid cancer? ... remains very low compared with most other cancers. Statistics on survival rates for thyroid cancer are discussed ...

  1. Chemotherapy for Thyroid Cancer

    MedlinePlus

    ... cancer Next Topic Targeted therapy for thyroid cancer Chemotherapy for thyroid cancer Chemotherapy (chemo) uses anti-cancer drugs that are injected ... vein or muscle, or are taken by mouth. Chemotherapy is systemic therapy, which means that the drug ...

  2. [Radiotherapy for Thyroid Cancer].

    PubMed

    Jingu, Keiichi; Maruoka, Shin; Umezawa, Rei; Takahashi, Noriyoshi

    2015-06-01

    Radioactive 131I therapy for differentiated thyroid cancer has been used since the 1940s and is an established and effective treatment. In contrast, external beam radiotherapy (EBRT) was considered to be effective for achieving local control but not for prolonging survival. Although clinicians were hesitant to administer EBRT owing to the potential radiation-induced adverse effects of 2 dimensional (2D)-radiotherapy until 2000, it is expected that adverse effects will be reduced and treatment efficacy improved through the introduction of more advanced techniques for delivering radiation (eg, 3D-radiotherapy and intensity modulated radiotherapy [IMRT]). The prognosis of undifferentiated thyroid cancer is known to be extremely bad, although in very rare cases, multimodality therapy (total or subtotal resection, chemotherapy, and radiotherapy) has allowed long-term survival. Here, we report the preliminary results of using hypofractionated radiotherapy for undifferentiated thyroid cancer in our institution. PMID:26199238

  3. Sorafenib for Metastatic Thyroid Cancer

    Cancer.gov

    A summary of results from an international phase III trial that compared sorafenib (Nexavar®) and a placebo for the treatment of locally advanced or metastatic differentiated thyroid cancer that is no longer responding to treatment with radioactive iodine

  4. [Autoimmune thyroiditis and thyroid cancer].

    PubMed

    Krátký, Jan; Jiskra, Jan

    2015-10-01

    Association between autoimmune thyroiditis (CLT) and thyroid cancer remains not clear. Although both diseases often occur simultaneously in histological samples, it is not yet clear whether CLT can be regarded as a risk factor for thyroid malignancy. This review focus on the known epidemiological and molecular genetics links between both diseases. Most studies have shown a significant association between thyroid cancer and positive antibodies to thyroglobulin and histological evidence of CLT, as well. Both disorders share some risk factors (greater incidence in women, in areas with adequate supply of iodine and in patients after radiotherapy of the neck) and molecular genetics linkage. For example: RET/PTC rearrangements could be more often found in carcinomas associated with CLT, but this mutation could be found in benign lesions such as CLT, as well. CLT seems to be a positive prognostic factor in patients with differentiated thyroid cancer. It is associated with less invasive forms of tumor, lower occurrence of infiltrated lymphatic nodes and a lower risk of recurrence. PMID:26486481

  5. Thyroid cancer in childhood

    SciTech Connect

    Gorlin, J.B.; Sallan, S.E. )

    1990-09-01

    The incidence, clinical presentation, and types of thyroid cancers presenting in childhood are reviewed. The role of antecedent radiation in papillary and follicular thyroid cancers and genetics of medullary thyroid carcinoma are discussed. Unique aspects of therapy and prognosis for the pediatric patient with thyroid carcinoma are addressed as well as a diagnostic approach to the child who presents with a neck mass.59 references.

  6. Thyroid Cancer

    MedlinePlus

    ... of treatments. They may include surgery, radioactive iodine, hormone treatment, radiation therapy, chemotherapy, or targeted therapy. Targeted therapy uses substances that attack cancer cells without harming normal cells. NIH: National Cancer Institute

  7. Thyroid cancer around Chernobyl

    SciTech Connect

    Beral, V.

    1997-03-01

    The author`s presentation on thyroid cancer around Chernobyl will focus on four different things. First will be the time trends, or the pattern of thyroid cancer occurrence before and after the accident. It is now very well known that the increase in thyroid cancer in children in several areas has been unprecedented. Second, the author discusses thyroid cancer in general and patterns of thyroid cancer around the world before the Chernobyl accident, including differences by age and pathology. Third, the author presents relatively crude analyses of risk according to dose to the thyroid gland. And last, the author attempts to contrast the findings for thyroid cancer in relation to the internal radioiodine dose in Chernobyl studies with analyses of the effects of external dose on thyroid cancer incidence. The bottom line to be developed is similar to that presented by Elaine Ron with regard to effects of external dose on thyroid cancer. The similarities between the childhood finding from Chernobyl studies and external radiation studies appear more remarkable than the differences.

  8. Thyroid cancer in children.

    PubMed

    Rivera, Gabriel; Lugo-Vicente, Humberto

    2014-01-01

    Cancer of the thyroid gland in pediatric patients is rare and if left untreated spreads and become lethal. Thyroid nodules in pediatric patients are four times more likely being malignant than adult nodules. The incidence of thyroid cancer in children increases with age, sex, race and nodule size. Exposures to low level of head and neck irradiation at young age, cancer survivors, family history of thyroid cancer and iodine deficiency are specific risk factors to develop thyroid cancer. Thyroid cancer is subdivided into papillary, follicular and medullary thyroid cancer varying in histological characteristics. Children who present with thyroid nodules should undergo ultrasound and fine needle aspiration biopsy to evaluate malignant potential. If biopsy results are positive for malignancy best option is complete surgical resection of the thyroid gland with central lymph node dissection followed by radioactive iodine treatment. Surgeons need to take certain precaution to avoid postoperative complications like hypoparathyroidism or recurrent laryngeal nerve damage. Follow-up is essential in order to evaluate remission or recurrence. An excellent prognosis in pediatric patients is the result of such an aggressive approach that can be supported by the low complications rate and low recurrence rate following surgery. PMID:25470911

  9. Thyroid cancer in children.

    PubMed

    Rivera, Gabriel; Lugo-Vicente, Humberto

    2014-01-01

    Cancer of the thyroid gland in pediatric patients is rare and if left untreated spreads and become lethal. Thyroid nodules in pediatric patients are four times more likely being malignant than adult nodules. The incidence of thyroid cancer in children increases with age, sex, race and nodule size. Exposures to low level of head and neck irradiation at young age, cancer survivors, family history of thyroid cancer and iodine deficiency are specific risk factors to develop thyroid cancer. Thyroid cancer is subdivided into papillary, follicular and medullary thyroid cancer varying in histological characteristics. Children who present with thyroid nodules should undergo ultrasound and fine needle aspiration biopsy to evaluate malignant potential. If biopsy results are positive for malignancy best option is complete surgical resection of the thyroid gland with central lymph node dissection followed by radioactive iodine treatment. Surgeons need to take certain precaution to avoid postoperative complications like hypoparathyroidism or recurrent laryngeal nerve damage. Follow-up is essential in order to evaluate remission or recurrence. An excellent prognosis in pediatric patients is the result of such an aggressive approach that can be supported by the low complications rate and low recurrence rate following surgery. PMID:25508538

  10. Thyroid Growth and Cancer.

    PubMed

    Williams, Dillwyn

    2015-09-01

    It is proposed that most papillary thyroid cancers originate in infancy and childhood, based on the early rise in sporadic thyroid carcinoma incidence, the pattern of radiation-induced risk (highest in those exposed as infants), and the high prevalence of sporadic papillary thyroid cancers in children and adolescents (ultrasound screening after the Fukushima accident). The early origin can be linked to the growth pattern of follicular cells, with a high mitotic rate in infancy falling to very low replacement levels in adult life. The cell of origin of thyroid cancers, the differentiated follicular cell, has a limited growth potential. Unlike cancers originating in stem cells, loss of the usually tight link between differentiation and replicative senescence is required for immortalisation. It is suggested that this loss distinguishes larger clinically significant papillary thyroid cancers from micro-papillary thyroid cancers of little clinical significance. Papillary carcinogenesis can then be divided into 3 stages: (1) initiation, the first mutation in the carcinogenic cascade, for radiation-induced papillary thyroid cancers usually a RET rearrangement, (2) progression, acquisition of the additional mutations needed for low-grade malignancy, and (3) escape, further mutations giving immortality and a higher net growth rate. Most papillary thyroid cancers will not have achieved full immortality by adulthood, and remain as so-called micro-carcinomas with a very low growth rate. The use of the term 'cancer' to describe micro-papillary thyroid cancers in older patients encourages overtreatment and alarms patients. Invasive papillary thyroid tumours show a spectrum of malignancy, which at its lowest poses no threat to life. The treatment protocols and nomenclature for small papillary carcinomas need to be reconsidered in the light of the new evidence available, the continuing discovery of smaller lesions, and the model of thyroid carcinogenesis proposed. PMID:26558233

  11. Thyroid Growth and Cancer

    PubMed Central

    Williams, Dillwyn

    2015-01-01

    It is proposed that most papillary thyroid cancers originate in infancy and childhood, based on the early rise in sporadic thyroid carcinoma incidence, the pattern of radiation-induced risk (highest in those exposed as infants), and the high prevalence of sporadic papillary thyroid cancers in children and adolescents (ultrasound screening after the Fukushima accident). The early origin can be linked to the growth pattern of follicular cells, with a high mitotic rate in infancy falling to very low replacement levels in adult life. The cell of origin of thyroid cancers, the differentiated follicular cell, has a limited growth potential. Unlike cancers originating in stem cells, loss of the usually tight link between differentiation and replicative senescence is required for immortalisation. It is suggested that this loss distinguishes larger clinically significant papillary thyroid cancers from micro-papillary thyroid cancers of little clinical significance. Papillary carcinogenesis can then be divided into 3 stages: (1) initiation, the first mutation in the carcinogenic cascade, for radiation-induced papillary thyroid cancers usually a RET rearrangement, (2) progression, acquisition of the additional mutations needed for low-grade malignancy, and (3) escape, further mutations giving immortality and a higher net growth rate. Most papillary thyroid cancers will not have achieved full immortality by adulthood, and remain as so-called micro-carcinomas with a very low growth rate. The use of the term ‘cancer’ to describe micro-papillary thyroid cancers in older patients encourages overtreatment and alarms patients. Invasive papillary thyroid tumours show a spectrum of malignancy, which at its lowest poses no threat to life. The treatment protocols and nomenclature for small papillary carcinomas need to be reconsidered in the light of the new evidence available, the continuing discovery of smaller lesions, and the model of thyroid carcinogenesis proposed. PMID

  12. Thyroid cancer - papillary carcinoma

    MedlinePlus

    ... non-cancerous childhood conditions Radiation exposure from nuclear plant disasters Radiation given through a vein (through an IV) during medical tests and treatments does not increase the risk of developing thyroid cancer.

  13. Decitabine in Treating Patients With Metastatic Papillary Thyroid Cancer or Follicular Thyroid Cancer Unresponsive to Iodine I 131

    ClinicalTrials.gov

    2014-08-20

    Recurrent Thyroid Cancer; Stage IVA Follicular Thyroid Cancer; Stage IVA Papillary Thyroid Cancer; Stage IVB Follicular Thyroid Cancer; Stage IVB Papillary Thyroid Cancer; Stage IVC Follicular Thyroid Cancer; Stage IVC Papillary Thyroid Cancer

  14. Follicular cell-derived thyroid cancer.

    PubMed

    Dralle, Henning; Machens, Andreas; Basa, Johanna; Fatourechi, Vahab; Franceschi, Silvia; Hay, Ian D; Nikiforov, Yuri E; Pacini, Furio; Pasieka, Janice L; Sherman, Steven I

    2015-01-01

    Follicular cell-derived thyroid cancers are derived from the follicular cells in the thyroid gland, which secrete the iodine-containing thyroid hormones. Follicular cell-derived thyroid cancers can be classified into papillary thyroid cancer (80-85%), follicular thyroid cancer (10-15%), poorly differentiated thyroid cancer (<2%) and undifferentiated (anaplastic) thyroid cancer (<2%), and these have an excellent prognosis with the exception of undifferentiated thyroid cancer. The advent and expansion of advanced diagnostic techniques has driven and continues to drive the epidemic of occult papillary thyroid cancer, owing to overdiagnosis of clinically irrelevant nodules. This transformation of the thyroid cancer landscape at molecular and clinical levels calls for the modification of management strategies towards personalized medicine based on individual risk assessment to deliver the most effective but least aggressive treatment. In thyroid cancer surgery, for instance, injuries to structures outside the thyroid gland, such as the recurrent laryngeal nerve in 2-5% of surgeries or the parathyroid glands in 5-10% of surgeries, negatively affect quality of life more than loss of the expendable thyroid gland. Furthermore, the risks associated with radioiodine ablation may outweigh the risks of persistent or recurrent disease and disease-specific mortality. Improvement in the health-related quality of life of survivors of follicular cell-derived thyroid cancer, which is decreased despite the generally favourable outcome, hinges on early tumour detection and minimization of treatment-related sequelae. Future opportunities include more widespread adoption of molecular and clinical risk stratification and identification of actionable targets for individualized therapies. PMID:27188261

  15. Cancer of the Thyroid

    MedlinePlus

    ... at a Glance Show More At a Glance Estimated New Cases in 2016 64,300 % of All New Cancer Cases 3.8% Estimated Deaths in 2016 1,980 % of All Cancer ... of This Cancer : In 2013, there were an estimated 637,115 people living with thyroid cancer in ...

  16. Drugs Approved for Thyroid Cancer

    MedlinePlus

    ... Ask about Your Treatment Research Drugs Approved for Thyroid Cancer This page lists cancer drugs approved by ... that are not listed here. Drugs Approved for Thyroid Cancer Cabozantinib-S-Malate Caprelsa (Vandetanib) Cometriq (Cabozantinib-S-Malate) ...

  17. Thyroid cancer - papillary carcinoma

    MedlinePlus

    ... some noncancerous childhood conditions Radiation exposure from nuclear plant disasters Radiation given through a vein (through an IV) during medical tests and treatments does not increase the risk of developing thyroid cancer.

  18. General Information about Thyroid Cancer

    MedlinePlus

    ... Research Thyroid Cancer Treatment (PDQ®)–Patient Version General Information About Thyroid Cancer Go to Health Professional Version ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  19. Post-laryngectomy voice rehabilitation with a voice prosthesis in a young girl with advanced thyroid cancer.

    PubMed

    Fukuhara, Takahiro; Miyoshi, Masayuki; Fujii, Taihei; Miyake, Naritomo; Taira, Kenkichiro; Koyama, Satoshi; Taguchi, Daizo; Fujiwara, Kazunori; Kataoka, Hideyuki; Kitano, Hiroya; Takeuchi, Hiromi

    2016-10-01

    The aim of this report is to evaluate the effects of voice rehabilitation with a voice prosthesis in a young patient with thyroid cancer. A 17-year-old girl underwent voice restoration with a voice prosthesis after laryngectomy to treat thyroid cancer. She completed voice-related questionnaires (the Voice Handicap Index-10 and Voice-Related Quality Of Life Survey) at ages 17 and 21 and underwent phonetic functional evaluation. The sound spectrograms of her phonation using the voice prosthesis showed low frequency sounds without an obvious basic frequency. She was ashamed of her hoarse voice and did not use her voice prosthesis during high school. However, after beginning to work at age 20, she used her voice to communicate in the workplace. At age 21, her questionnaire scores, especially those related to the physical and functional domains, improved compared with those at age 17. Voice restoration with a voice prosthesis is recommended for young patients who undergo laryngectomy for advanced thyroid cancer. The advantages of voice restoration with a voice prosthesis may increase when the patient reaches working age, and it may improve post-laryngectomy quality of life considerably. PMID:26960746

  20. Occupation and Thyroid Cancer

    PubMed Central

    Aschebrook-Kilfoy, Briseis; Ward, Mary H.; Valle, Curt T. Della; Friesen, Melissa C.

    2014-01-01

    Objectives Numerous occupational and environmental exposures have been shown to disrupt thyroid hormones, but much less is known about their relationships with thyroid cancer. Here we review the epidemiology studies of occupations and occupational exposures and thyroid cancer incidence to provide insight into preventable risk factors for thyroid cancer. Methods The published literature was searched using the Web of Knowledge database for all articles through August 2013 that had in their text “occupation” “job” ”employment” or “work” and “thyroid cancer”. After excluding 10 mortality studies and 4 studies with less than 5 exposed incident cases, we summarized the findings of 30 articles that examined thyroid cancer incidence in relation to occupations or occupational exposure. The studies were grouped by exposure/occupation category, study design, and exposure assessment approach. Where available, gender stratified results are reported. Results The most studied (19 of 30 studies) and the most consistent associations were observed for radiation-exposed workers and health care occupations. Suggestive, but inconsistent, associations were observed in studies of pesticide-exposed workers and agricultural occupations. Findings for other exposures and occupation groups were largely null. The majority of studies had few exposed cases and assessed exposure based on occupation or industry category, self-report, or generic (population-based) job exposure matrices. Conclusion The suggestive, but inconsistent findings for many of the occupational exposures reviewed here indicate that more studies with larger numbers of cases and better exposure assessment are necessary, particularly for exposures known to disrupt thyroid homeostasis. PMID:24604144

  1. Mitochondrial Energy Metabolism and Thyroid Cancers.

    PubMed

    Lee, Junguee; Chang, Joon Young; Kang, Yea Eun; Yi, Shinae; Lee, Min Hee; Joung, Kyong Hye; Kim, Kun Soon; Shong, Minho

    2015-06-01

    Primary thyroid cancers including papillary, follicular, poorly differentiated, and anaplastic carcinomas show substantial differences in biological and clinical behaviors. Even in the same pathological type, there is wide variability in the clinical course of disease progression. The molecular carcinogenesis of thyroid cancer has advanced tremendously in the last decade. However, specific inhibition of oncogenic pathways did not provide a significant survival benefit in advanced progressive thyroid cancer that is resistant to radioactive iodine therapy. Accumulating evidence clearly shows that cellular energy metabolism, which is controlled by oncogenes and other tumor-related factors, is a critical factor determining the clinical phenotypes of cancer. However, the role and nature of energy metabolism in thyroid cancer remain unclear. In this article, we discuss the role of cellular energy metabolism, particularly mitochondrial energy metabolism, in thyroid cancer. Determining the molecular nature of metabolic remodeling in thyroid cancer may provide new biomarkers and therapeutic targets that may be useful in the management of refractory thyroid cancers. PMID:26194071

  2. What Causes Thyroid Cancer?

    MedlinePlus

    ... not yet known. Certain changes in a person’s DNA can cause thyroid cells to become cancerous. DNA is the chemical in each of our cells ... parents because they are the source of our DNA. But DNA affects more than just how we ...

  3. Sunitinib Malate in Treating Patients With Iodine-Refractory Recurrent or Metastatic Thyroid Cancer

    ClinicalTrials.gov

    2015-09-28

    Recurrent Thyroid Cancer; Stage IVA Follicular Thyroid Cancer; Stage IVA Papillary Thyroid Cancer; Stage IVB Follicular Thyroid Cancer; Stage IVB Papillary Thyroid Cancer; Stage IVC Follicular Thyroid Cancer; Stage IVC Papillary Thyroid Cancer; Thyroid Gland Medullary Carcinoma

  4. Unusual CNS presentation of thyroid cancer.

    PubMed

    Heery, Christopher R; Engelhard, Herbert H; Slavin, Konstantin V; Michals, Edward A; Villano, J Lee

    2012-09-01

    As advanced therapies allow cancer patients to live longer, disease failure in the central nervous system increases from limited therapeutic penetration. Primary thyroid malignancies rarely metastasize to the brain and have a small number of investigations in literature on the subject. The majority of brain metastases involve the brain parenchyma, reflecting the mass and blood distribution within the brain and central nervous system. Here, we report two cases of the most common differentiated thyroid cancers; follicular thyroid cancer having brain involvement from extra-axial growth and papillary thyroid cancer having brain involvement from a single intraventricular metastasis, presumed as metastasis from the vascular choroid plexus. Both of our cases had widespread systemic involvement. For our follicular thyroid cancer, brain involvement was a result of extra-axial growth from cavarial bone, and our papillary thyroid cancer had brain involvement from a single intraventricular metastasis that was initially resected and nearly a year later developed extensive brain involvement. Unlike the usual gray-white junction metastases seen in the majority of metastatic brain tumors, including thyroid, our cases are uncommon. They reflect differences in tumor biology that allows for spread and growth in the brain. Although there is growing genetic knowledge on tumors that favor brain metastases, little is known about tumors that rarely involve the brain. PMID:22296651

  5. Role of External Beam Radiotherapy in Patients With Advanced or Recurrent Nonanaplastic Thyroid Cancer: Memorial Sloan-Kettering Cancer Center Experience

    SciTech Connect

    Terezakis, Stephanie A. Lee, Kyungmouk S.; Ghossein, Ronald A.; Rivera, Michael; Tuttle, Robert M.; Wolden, Suzanne L.; Zelefsky, Michael J.; Wong, Richard J.; Patel, Snehal G.; Pfister, David G.; Shaha, Ashok R.; Lee, Nancy Y.

    2009-03-01

    Purpose: External beam radiotherapy (EBRT) plays a controversial role in the management of nonanaplastic thyroid cancer. We reviewed our institution's outcomes in patients treated with EBRT for advanced or recurrent nonanaplastic thyroid cancer. Methods and Materials: Between April 1989 and April 2006, 76 patients with nonanaplastic thyroid cancer were treated with EBRT. The median follow-up for the surviving patients was 35.3 months (range, 4.2-178.4). The lesions were primarily advanced and included Stage T2 in 5 (7%), T3 in 5 (7%), and T4 in 64 (84%) patients. Stage N1 disease was present in 60 patients (79%). Distant metastases before EBRT were identified in 27 patients (36%). The median total EBRT dose delivered was 6,300 cGy. The histologic features examined included medullary in 12 patients (16%) and nonmedullary in 64 (84%). Of the 76 patients, 71 (93%) had undergone surgery before RT, and radioactive iodine treatment was used in 56 patients (74%). Results: The 2- and 4-year overall locoregional control rate for all histologic types was 86% and 72%, respectively, and the 2- and 4-year overall survival rate for all patients was 74% and 55%, respectively. No significant differences were found in locoregional control, overall survival, or distant metastases-free survival for patients with complete resection, microscopic residual disease, or gross residual disease. Grade 3 acute mucositis and dysphagia occurred in 14 (18%) and 24 (32%) patients, respectively. Late adverse toxicity was notable for percutaneous endoscopic gastrostomy tube use in 4 patients (5%). Conclusion: The results of our study have shown that EBRT is effective for locoregional control of selected locally advanced or recurrent nonanaplastic thyroid malignancies, with acceptable acute toxicity.

  6. Sorafenib treatment of radioiodine-refractory advanced thyroid cancer in daily clinical practice: a cohort study from a single center.

    PubMed

    Gallo, Marco; Michelon, Federica; Castiglione, Anna; Felicetti, Francesco; Viansone, Alessandro Adriano; Nervo, Alice; Zichi, Clizia; Ciccone, Giovannino; Piovesan, Alessandro; Arvat, Emanuela

    2015-08-01

    Treatment options for recurrent or metastatic differentiated thyroid cancer (DTC) refractory to radioactive iodine (RAI) are inadequate. Multitargeted kinase inhibitors have recently shown promising results in phase 2-3 studies. This retrospective study aimed to document our clinical experience on the effects of sorafenib in the setting of daily clinical practice. Retrospective study evaluating the efficacy and safety of sorafenib in a cohort of patients consecutively treated with sorafenib at a single center. Twenty patients with advanced RAI-refractory thyroid carcinoma were enrolled (March 2011-March 2014). Patients generally started with 400 mg of sorafenib twice daily, tapering the dose in case of side effects. Radiological response and toxicity were measured during follow-up, together with safety parameters. CT scans were performed by a single experienced radiologist every 3-4 months. Five patients stopped sorafenib within 90 days due to severe toxicities. Median progression-free survival was 248 days. Five patients had a partial response (PR), achieved in all cases within 3 months, whereas 5 had stable disease (SD) at 12 months. Durable response rate (PR plus SD) for at least 6 months was 50 %, among those who received sorafenib for at least 3 months. Commonest adverse events included skin toxicity, gastrointestinal and constitutional symptoms. In our cohort of patients with advanced RAI-refractory thyroid carcinoma, sorafenib confirmed antitumor activity leading to SD or PR in the majority of cases, at the expense of clinically relevant side effects. More effective and tolerable agents are still needed in the treatment of RAI-refractory DTC. PMID:25414068

  7. New technologies in thyroid cancer surgery.

    PubMed

    Dhepnorrarat, Rataphol Chris; Witterick, Ian J

    2013-07-01

    Several new technologies have advanced the practice of thyroid surgery in recent years, with some centers implementing substantial changes in the way thyroid surgery is performed. As many thyroid cancers are diagnosed at an early stage the treatment is quite effective, and the prognosis is good for most patients with differentiated thyroid cancer. With excellent long term survival, advancements in the treatment of patients with thyroid cancers are focusing on reducing complications of surgery, improving quality-of-life and delivering care in a cost-effective way. The LigaSure electrothermal bipolar vessel sealing system and Harmonic scalpel have been designed to aid in dissection with less thermal spread than conventional electrocautery. Alternative access approaches to the thyroid allow for improved cosmetic outcomes and potentially improve the view of the surgical field. The intraoperative use of gamma-probe for the localization of metastases and sentinel lymph nodes are being increasingly reported on. Surgeon performed ultrasound is promoted for improving the detection of disease, and intraoperative nerve monitoring is now widespread, aiding in laryngeal nerve detection and protection. The assay of parathyroid hormone is also in common use for predicting patients at risk for developing postoperative hypocalcemia. This article reviews the current literature on new technologies for thyroid surgery and discusses some of the implications for the future of this field of surgery. PMID:23578371

  8. Thyroid Cancer in Pediatrics.

    PubMed

    Machac, Josef

    2016-06-01

    Well differentiated thyroid cancer (DTC) in children is characterized by a high rate of response to treatment and low disease-specific mortality. Treatment of children with DTC has evolved toward a greater reliance on evaluation and monitoring with serial serum thyroglobulin measurements and ultrasound examinations. Radioiodine therapy is recommended for thyroid remnant ablation in high-risk patients, treatment of demonstrated radioiodine-avid local-regional disease not amenable to surgical resection, or distant radioiodine-avid metastatic disease. Sufficient time should be given for benefits of radioiodine therapy to be realized, with follow-up monitoring. Re-treatment with radioiodine can be deferred until progression of significant disease manifests. PMID:27241970

  9. Update on external beam radiation therapy in thyroid cancer.

    PubMed

    Brierley, James D

    2011-08-01

    Surgery is the mainstay of treatment for thyroid cancer. The role for external beam radiotherapy (EBRT) as an adjuvant to surgery or as the primary therapy is established in anaplastic thyroid cancer but is controversial in differentiated thyroid cancer and uncertain in medullary thyroid cancer. This update reviews the recent reported success of combining EBRT with taxanes in anaplastic thyroid cancer. Also discussed are the recent reports from large single institutions that support the recommendations of the American and British Thyroid Associations on the use of EBRT in high-risk differentiated thyroid cancer. Further evidence on the role of EBRT in MTC is discussed. The important advances in the delivery of EBRT using intensity-modulated radiation and image-guided radiation that result in more accurate and potentially more effective radiation therapy with less toxicity are also discussed. PMID:21816795

  10. NEW DEVELOPMENTS IN THE DIAGNOSIS AND TREATMENT OF THYROID CANCER

    PubMed Central

    Schneider, David F.; Chen, Herbert

    2013-01-01

    Thyroid cancer exists in several forms. Differentiated thyroid cancers include papillary and follicular histologies. These tumors exist along a spectrum of differentiation, and their incidence continues to climb. A number of advances in the diagnosis and treatment of differentiated thyroid cancers now exist. These include molecular diagnostics and more advanced strategies for risk stratification. Medullary cancer arises from the parafollicular cells and not the follicular cells. Therefore, diagnosis and treatment differs from differentiated thyroid tumors. Genetic testing and newer adjuvant therapies has changed the diagnosis and treatment of medullary thyroid cancer. This review will focus on the epidemiology, diagnosis, work-up, and treatment of both differentiated and medullary thyroid cancers, focusing specifically on newer developments in the field. PMID:23797834

  11. What Is Thyroid Cancer?

    MedlinePlus

    ... Having too much thyroid hormone (a condition called hyperthyroidism ) can cause a rapid or irregular heartbeat, trouble ... nodules make too much thyroid hormone and cause hyperthyroidism. Nodules that produce increased thyroid hormone are almost ...

  12. Stages of Thyroid Cancer

    MedlinePlus

    ... glands make hormones. The thyroid uses iodine , a mineral found in some foods and in iodized salt, ... Fine-needle aspiration biopsy of the thyroid : The removal of thyroid tissue using a thin needle. The ...

  13. Thyroid Hormone, Cancer, and Apoptosis.

    PubMed

    Lin, Hung-Yun; Chin, Yu-Tan; Yang, Yu-Chen S H; Lai, Husan-Yu; Wang-Peng, Jacqueline; Liu, Leory F; Tang, Heng-Yuan; Davis, Paul J

    2016-01-01

    Thyroid hormones play important roles in regulating normal metabolism, development, and growth. They also stimulate cancer cell proliferation. Their metabolic and developmental effects and growth effects in normal tissues are mediated primarily by nuclear hormone receptors. A cell surface receptor for the hormone on integrin [alpha]vβ3 is the initiation site for effects on tumor cells. Clinical hypothyroidism may retard cancer growth, and hyperthyroidism was recently linked to the prevalence of certain cancers. Local levels of thyroid hormones are controlled through activation and deactivation of iodothyronine deiodinases in different organs. The relative activities of different deiodinases that exist in tissues or organs also affect the progression and development of specific types of cancers. In this review, the effects of thyroid hormone on signaling pathways in breast, brain, liver, thyroid, and colon cancers are discussed. The importance of nuclear thyroid hormone receptor isoforms and of the hormone receptor on the extracellular domain of integrin [alpha]vβ3 as potential cancer risk factors and therapeutic targets are addressed. We analyze the intracellular signaling pathways activated by thyroid hormones in cancer progression in hyperthyroidism or at physiological concentrations in the euthyroid state. Determining how to utilize the deaminated thyroid hormone analog (tetrac), and its nanoparticulate derivative to reduce risks of cancer progression, enhance therapeutic outcomes, and prevent cancer recurrence is also deliberated. © 2016 American Physiological Society. Compr Physiol 6:1221-1237, 2016. PMID:27347891

  14. Anaplastic thyroid cancer

    MedlinePlus

    ... or MRI of the neck may show a tumor growing from the thyroid gland. A thyroid biopsy makes the diagnosis. An examination ... the thyroid Images ... Saunders; 2016:chap 226. Lai SY, Mandel SJ, Weber RS. Management of thyroid neoplasms. In: Flint PW, Haughey BH, Lund LJ, et ...

  15. Efficacy and safety of vascular endothelial growth factor receptor tyrosine kinase inhibitors in the treatment of advanced thyroid cancer: a meta-analysis of randomized controlled trials

    PubMed Central

    Yimaer, Wufuer; Abudouyimu, Aizizi; Tian, Ye; Magaoweiya, Sailike; Bagedati, Duman; Wen, Hao

    2016-01-01

    Background We performed a systematic review and meta-analysis to determine the efficacy and safety of the US Food and Drug Administration approved vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) in the treatment of advanced thyroid cancer. Patients and methods We included prospective randomized controlled trials that compared VEGFR-TKIs with placebo for advanced thyroid cancer. The endpoints included safety (fatal adverse events [FAEs], treatment discontinuation, and any severe [grade 3 or 4] adverse events [AEs]) and efficacy (objective response rate, progression-free survival, and overall survival). The pooled relative risk (RR) or hazard ratio (HR) was calculated by using either random-effects or fixed-effects models according to the heterogeneity of included studies. Results A total of 1,614 advanced thyroid cancer patients from five randomized controlled trials were identified for analysis. Compared with placebo alone, VEGFR-TKIs significantly increased the risk of treatment discontinuation (RR: 3.80, 95% confidence interval [CI]: 2.56–5.65, P<0.001) and any severe AEs (RR: 2.63, 95% CI: 1.72–4.03, P<0.001), but not of FAEs (RR: 1.24, 95% CI: 0.65–2.39, P=0.52). The use of VEGFR-TKIs in advanced thyroid cancer was associated with a significant improvement in objective response rate (RR: 8.73, 95% CI: 1.72–44.4, P=0.009) and progression-free survival (HR: 0.41, 95% CI: 0.27–0.61, P<0.001), with a tendency to improve overall survival (HR: 0.83, 95% CI: 0.68–1.01, P=0.06). Conclusion The use of small-molecule VEGFR-TKIs in advanced thyroid cancer did significantly increase the risk of treatment discontinuation and any severe AEs, but not of FAEs, compared with placebo alone. It is important for physicians to weigh the risk of toxicities as well as the potential survival benefits associated with VEGFR-TKI treatment in advanced thyroid cancer patients. PMID:27022276

  16. Can Thyroid Cancer Be Prevented?

    MedlinePlus

    ... look for the gene mutations found in familial medullary thyroid cancer (MTC). Because of this, most of the familial cases of MTC can be prevented or treated early by removing the thyroid gland. Once the disease is discovered in a family, the rest of ...

  17. Thyroid Cancer Statistics | Did You Know?

    Cancer.gov

    Thyroid cancer represents the 8th most common cancer in the United States. Did you know that this cancer, located at the base of the throat in the thyroid gland, is highly treatable and usually curable?

  18. Technological Innovations in Surgical Approach for Thyroid Cancer

    PubMed Central

    Lang, Brian Hung-Hin; Lo, Chung-Yau

    2010-01-01

    Over the last decade, surgeons have witnessed dramatic changes in surgical practice as a result of the introduction of new technological advancement. Some of these changes include refinement of techniques in thyroid cancer surgery. The development of various endoscopic thyroidectomy techniques, the addition of the da Vinci robot, and the use of operative adjuncts in thyroid surgery, such as intraoperative neuromonitoring and quick intraoperative parathyroid hormone, have made thyroid cancer surgery not only safer and better accepted by patients with thyroid cancer but also offer them more surgical treatment options. PMID:20798772

  19. Medullary thyroid cancer.

    PubMed

    Clayman, Gary L; el-Baradie, Tarek S

    2003-02-01

    Medullary thyroid cancer is a rare neoplasm that arises from the parafollicular C cells. It occurs in a sporadic form, or less commonly as a hereditary form, as part of multiple endocrine neoplasia syndromes types 2A and 2B. The RET proto-oncogene is currently the primary factor that is implicated in the hereditary forms of this neoplasm. The knowledge about the genetic makeup of the neoplasm impacts upon management as it allows for screening, early detection, and prophylactic treatment. Surgery is the main modality that offers a cure. This entails a total thyroidectomy and vigilant management and surveillance of the neck. Prognosis of patients with MTC is variable, but the more constant factors that affect it are the stage of disease and the age of the patient. The emerging molecular genetic understanding of this malignancy will provide the foundation for prognostic and therapeutic decision-making in the future. Interdisciplinary management by surgeons, endocrinologists, pathologists, radiotherapists, radiologists, and medical oncologists should be sought. PMID:12803011

  20. Cancer Stem Cells in the Thyroid

    PubMed Central

    Nagayama, Yuji; Shimamura, Mika; Mitsutake, Norisato

    2016-01-01

    The cancer stem cell (CSC) model posits that CSCs are a small, biologically distinct subpopulation of cancer cells in each tumor that have self-renewal and multi-lineage potential, and are critical for cancer initiation, metastasis, recurrence, and therapy-resistance. Numerous studies have linked CSCs to thyroid biology, but the candidate markers and signal transduction pathways that drive thyroid CSC growth are controversial, the origin(s) of thyroid CSCs remain elusive, and it is unclear whether thyroid CSC biology is consistent with the original hierarchical CSC model or the more recent dynamic CSC model. Here, we critically review the thyroid CSC literature with an emphasis on research that confirmed the presence of thyroid CSCs by in vitro sphere formation or in vivo tumor formation assays with dispersed cells from thyroid cancer tissues or bona fide thyroid cancer cell lines. Future perspectives of thyroid CSC research are also discussed. PMID:26973599

  1. Cancer Stem Cells in the Thyroid.

    PubMed

    Nagayama, Yuji; Shimamura, Mika; Mitsutake, Norisato

    2016-01-01

    The cancer stem cell (CSC) model posits that CSCs are a small, biologically distinct subpopulation of cancer cells in each tumor that have self-renewal and multi-lineage potential, and are critical for cancer initiation, metastasis, recurrence, and therapy-resistance. Numerous studies have linked CSCs to thyroid biology, but the candidate markers and signal transduction pathways that drive thyroid CSC growth are controversial, the origin(s) of thyroid CSCs remain elusive, and it is unclear whether thyroid CSC biology is consistent with the original hierarchical CSC model or the more recent dynamic CSC model. Here, we critically review the thyroid CSC literature with an emphasis on research that confirmed the presence of thyroid CSCs by in vitro sphere formation or in vivo tumor formation assays with dispersed cells from thyroid cancer tissues or bona fide thyroid cancer cell lines. Future perspectives of thyroid CSC research are also discussed. PMID:26973599

  2. Pediatric Thyroid Cancer

    MedlinePlus

    ... isthmus). The thyroid secretes three main hormones: 1) Thyroxine, that contains iodine, needed for growth and metabolism; ... also contains iodine and similar in function to Thyroxine; and 3) Calcitonin, which decreases the concentration of ...

  3. Incidental thyroid nodules and thyroid cancer: considerations before determining management.

    PubMed

    Tufano, Ralph P; Noureldine, Salem I; Angelos, Peter

    2015-06-01

    The worldwide incidence of thyroid cancer is increasing substantially, almost exclusively attributable to small papillary thyroid cancers. Increased use of diagnostic imaging is considered the most likely explanation for this reported rise, but other factors may also be contributing. The increase in health care expenditures related to managing these presumably low-risk cancers, without a clear patient benefit, has resulted in a backlash against the early detection of thyroid cancer. Currently, there is no way to confidently predict which incidentally detected thyroid nodule may be the precursor to a more aggressive process. Predictions such as these would require more accurate characterization of the biology of individual thyroid cancers than is currently possible. With time, we might prove our ability to confidently differentiate low-risk from high-risk thyroid cancers, but until that happens, routine screening for thyroid cancer by imaging billed as a "health checkup" should not be performed. However, incidentally detected thyroid nodules should be reported, and a clear medical team management plan should be developed. Our ethical responsibility is to provide patients with objective, evidence-based information about their disease status, not to assume that we know what is best for them by selectively withholding information. In addition, providing patients with psychosocial assistance will help them process the information necessary to make informed decisions that will provide them with the most value when a small thyroid nodule or cancer is incidentally identified. Herein, we summarize the epidemiological data for disease incidence, discuss some controversies in disease management, and outline the key elements and ethical considerations of informed decision making as they apply to managing incidentally detected thyroid nodules and thyroid cancer. PMID:25928353

  4. Thyroid Cancer Metabolism: A Review

    PubMed Central

    Gill, Kurren S; Tassone, Patrick; Hamilton, James; Hjelm, Nikolaus; Luginbuhl, Adam; Cognetti, David; Tuluc, Madalina; Martinez-Outschoorn, Ubaldo; Johnson, Jennifer M; Curry, Joseph M

    2016-01-01

    Metabolic dysregulation within the tumor microenvironment (TME) is critical to the process of tumorigenesis in various cancer types. Thyrocyte metabolism in papillary and anaplastic thyroid cancer, however, remains poorly characterized, and studies analyzing the role of multicompartment metabolism in thyrocyte oncogenesis are sparse. We present a review of the current knowledge on cellular metabolism in non-cancerous and cancerous thyroid tissues, focusing on the monocarboxylate transporters MCT1 and MCT4, and on a transporter of the outer mitochondrial membrane TOMM20. Understanding the metabolic phenotype of tumor cells and associated stromal cells in thyroid cancer can have profound implications on the use of biomarker staining in detecting subclinical cancer, imaging as it relates to expression of various transport proteins, and therapeutic interventions that manipulate this dysregulated tumor metabolism to halt tumorigenesis and eradicate the cancer. Future studies are required to confirm the prognostic significance of these biomarkers and their correlation with existing staging schemas such as the AGES, AMES, ATA and MACIS scoring systems. PMID:27213120

  5. Mutation Profile of Well-Differentiated Thyroid Cancer in Asians

    PubMed Central

    Song, Young Shin; Lim, Jung Ah

    2015-01-01

    Recent advances in molecular diagnostics have led to significant insights into the genetic basis of thyroid tumorigenesis. Among the mutations commonly seen in thyroid cancers, the vast majority are associated with the mitogen-activated protein kinase pathway. B-Raf proto-oncogene (BRAF) mutations are the most common mutations observed in papillary thyroid cancers (PTCs), followed by RET/PTC rearrangements and RAS mutations, while follicular thyroid cancers are more likely to harbor RAS mutations or PAX8/peroxisome proliferator-activated receptor γ (PPARγ) rearrangements. Beyond these more common mutations, alterations in the telomerase reverse transcriptase (TERT) promoter have recently been associated with clinicopathologic features, disease prognosis, and tumorigenesis in thyroid cancer. While the mutations underlying thyroid tumorigenesis are well known, the frequency of these mutations is strongly associated with geography, with clear differences reported between Asian and Western countries. Of particular interest is the prevalence of BRAF mutations, with Korean patients exhibiting the highest rate of BRAF-associated thyroid cancers in the world. Here, we review the prevalence of each of the most common mutations in Asian and Western countries, and identify the characteristics of well-differentiated thyroid cancer in Asians. PMID:26435130

  6. Thyroid Cancer Risk Factors

    MedlinePlus

    ... and radiation fallout from power plant accidents or nuclear weapons. Having had head or neck radiation treatments in childhood is a risk factor for ... should be done using the lowest dose of radiation that still provides a clear ... from nuclear weapons or power plant accidents. For instance, thyroid ...

  7. Thyroid Hormones as Renal Cell Cancer Regulators

    PubMed Central

    Matak, Damian; Bartnik, Ewa; Szczylik, Cezary; Czarnecka, Anna M.

    2016-01-01

    It is known that thyroid hormone is an important regulator of cancer development and metastasis. What is more, changes across the genome, as well as alternative splicing, may affect the activity of the thyroid hormone receptors. Mechanism of action of the thyroid hormone is different in every cancer; therefore in this review thyroid hormone and its receptor are presented as a regulator of renal cell carcinoma. PMID:27034829

  8. Novel molecular targeted therapies for refractory thyroid cancer.

    PubMed

    Perez, Cesar A; Santos, Edgardo S; Arango, Belisario A; Raez, Luis E; Cohen, Ezra E W

    2012-05-01

    The incidence of thyroid cancer continues to increase and this neoplasia remains the most common endocrine malignancy. No effective systemic treatment currently exists for iodine-refractory differentiated or medullary thyroid carcinoma, but recent advances in the pathogenesis of these diseases have revealed key targets that are now being evaluated in the clinical setting. RET (rearranged during transfection)/PTC (papillary thyroid carcinoma) gene rearrangements, B-Raf gene mutations, and vascular endothelial growth factor receptor 2 (VEGFR-2) angiogenesis pathways are some of the known genetic alterations playing a crucial role in the development of thyroid cancer. Several novel agents have demonstrated promising responses. Of the treatments studied, multi-kinase inhibitors such as axitinib, sorafenib, motesanib, and XL-184 have shown to be the most effective by inducing clinical responses and stabilizing the disease process. Randomized clinical trials are currently evaluating these agents, results that may soon change the management of thyroid cancer. PMID:21544895

  9. Thyroid cancer in children and adolescents

    SciTech Connect

    Ceccarelli, C.; Pacini, F.; Lippi, F.; Elisei, R.; Arganini, M.; Miccoli, P.; Pinchera, A.

    1988-12-01

    We report on 49 patients younger than 18 years at diagnosis, of 776 patients with thyroid cancer, seen in our institution in the last 17 years. Female/male ratio was 2.2:1. Histologic type was papillary in 44, follicular in 4, and medullary in 1. Initial treatment was near-total thyroidectomy with or without neck dissection. Surgical complications (vocal cord palsy, permanent hypoparathyroidism, or both) were found in 25 patients and were usually associated with more advanced primary tumors. At surgery, node metastases were present in 73% of the patients and lung metastases, detected by chest x ray films, in 6%. Patients were treated with thyroid suppressive therapy and, except the one with medullary cancer, with radioiodine (131I) therapy. After a mean follow-up of 7.7 +/- 4.4 years (range, 1 to 17 years), one patient with lung metastases died of respiratory failure. Of 36 patients who have been followed up more than 4 years, 22 (61.1%) are now cured, and 14 have metastases (to lymph nodes, 2; to nodes and lung, 10; and to lung, 2). Since 1977 serum thyroglobulin (Tg) was used routinely as a tumor marker for differentiated thyroid cancer. After operation, Tg was elevated in all patients both not receiving (mean +/- SE, 902 +/- 380 ng/ml) and receiving (44 +/- 15 ng/ml) suppressive therapy; after 131I treatment, serum Tg dropped to 104 +/- 50 and 7.3 +/- 1.7 ng/ml, without and with suppressive therapy, respectively. Of 11 patients with lung metastases treated with 131I, respiratory function, as assessed by means of spirometry, was normal in three, mildly reduced in six, and severely impaired in two (including the one who died). In conclusion, our study indicates that thyroid cancer in young patients is rather advanced at initial examination and usually associated with node and, less frequently, lung metastases.

  10. The treatment landscape in thyroid cancer: a focus on cabozantinib

    PubMed Central

    Weitzman, Steven P; Cabanillas, Maria E

    2015-01-01

    Although patients with thyroid cancer generally fare well, there is a subset for which this is not necessarily true. Progress in understanding the molecular aberrations in thyroid cancer has led to a change in the management of these cases. Since 2011, four multikinase inhibitors (MKIs) have been approved by the US Food and Drug Administration for thyroid cancer – cabozantinib and vandetanib for medullary thyroid cancer and sorafenib and lenvatinib for differentiated thyroid cancer. This change in the treatment landscape has raised challenges for practitioners who may not be familiar with the use of MKIs or with the treatment and natural history of advanced thyroid cancer in general. This article reviews the epidemiology, molecular drivers, and initial treatment of patients with thyroid cancer and offers practical guidance to assist with the determination of when to appropriately start an MKI. As an example, cabozantinib and its efficacy are discussed in detail. Close monitoring is required for all patients on targeted agents to assess for adverse effects and response to therapy. An approach to managing drug-related adverse events is detailed. Since these drugs are not curative and have not yet proven to prolong overall survival, it is critical to weigh the risks and benefits of treatment at every visit. The potential value of changing to a different agent following failure of an MKI is also addressed. PMID:26316818

  11. What's New in Thyroid Cancer Research and Treatment?

    MedlinePlus

    ... Next Topic References: Thyroid cancer detailed guide What’s new in thyroid cancer research and treatment? Important research ... RAI) therapy. Doctors and researchers are looking for new ways to treat thyroid cancer that are more ...

  12. Overview of the 2015 American Thyroid Association guidelines for managing thyroid nodules and differentiated thyroid cancer.

    PubMed

    Matti, Bashar; Cohen-Hallaleh, Ruben

    2016-01-01

    The last few years have witnessed numerous publications addressing the management of thyroid nodules and differentiated thyroid cancers. The purpose of this review is to provide a simplified summary of the newly released guidelines by the American Thyroid Association. A systematic approach has been recommended to evaluate a thyroid nodule through clinical assessment, measurement of serum Thyroid Stimulating Hormone, neck ultrasonography and Fine Needle Aspiration where appropriate. This is followed by cytology analysis using the Bethesda scoring system to detect malignancy. Once diagnosed, thyroid cancers need to be staged and risk stratification needs to be applied to develop further treatment plans. Lastly, several recommendations have been presented to assure proper follow-up and support for thyroid cancer patients regardless of the treatment received. PMID:27607088

  13. Thyroid Cancer and Tumor Collaborative Registry (TCCR).

    PubMed

    Shats, Oleg; Goldner, Whitney; Feng, Jianmin; Sherman, Alexander; Smith, Russell B; Sherman, Simon

    2016-01-01

    A multicenter, web-based Thyroid Cancer and Tumor Collaborative Registry (TCCR, http://tccr.unmc.edu) allows for the collection and management of various data on thyroid cancer (TC) and thyroid nodule (TN) patients. The TCCR is coupled with OpenSpecimen, an open-source biobank management system, to annotate biospecimens obtained from the TCCR subjects. The demographic, lifestyle, physical activity, dietary habits, family history, medical history, and quality of life data are provided and may be entered into the registry by subjects. Information on diagnosis, treatment, and outcome is entered by the clinical personnel. The TCCR uses advanced technical and organizational practices, such as (i) metadata-driven software architecture (design); (ii) modern standards and best practices for data sharing and interoperability (standardization); (iii) Agile methodology (project management); (iv) Software as a Service (SaaS) as a software distribution model (operation); and (v) the confederation principle as a business model (governance). This allowed us to create a secure, reliable, user-friendly, and self-sustainable system for TC and TN data collection and management that is compatible with various end-user devices and easily adaptable to a rapidly changing environment. Currently, the TCCR contains data on 2,261 subjects and data on more than 28,000 biospecimens. Data and biological samples collected by the TCCR are used in developing diagnostic, prevention, treatment, and survivorship strategies against TC. PMID:27168721

  14. Thyroid Cancer and Tumor Collaborative Registry (TCCR)

    PubMed Central

    Shats, Oleg; Goldner, Whitney; Feng, Jianmin; Sherman, Alexander; Smith, Russell B.; Sherman, Simon

    2016-01-01

    A multicenter, web-based Thyroid Cancer and Tumor Collaborative Registry (TCCR, http://tccr.unmc.edu) allows for the collection and management of various data on thyroid cancer (TC) and thyroid nodule (TN) patients. The TCCR is coupled with OpenSpecimen, an open-source biobank management system, to annotate biospecimens obtained from the TCCR subjects. The demographic, lifestyle, physical activity, dietary habits, family history, medical history, and quality of life data are provided and may be entered into the registry by subjects. Information on diagnosis, treatment, and outcome is entered by the clinical personnel. The TCCR uses advanced technical and organizational practices, such as (i) metadata-driven software architecture (design); (ii) modern standards and best practices for data sharing and interoperability (standardization); (iii) Agile methodology (project management); (iv) Software as a Service (SaaS) as a software distribution model (operation); and (v) the confederation principle as a business model (governance). This allowed us to create a secure, reliable, user-friendly, and self-sustainable system for TC and TN data collection and management that is compatible with various end-user devices and easily adaptable to a rapidly changing environment. Currently, the TCCR contains data on 2,261 subjects and data on more than 28,000 biospecimens. Data and biological samples collected by the TCCR are used in developing diagnostic, prevention, treatment, and survivorship strategies against TC. PMID:27168721

  15. Robotic thyroidectomy and cervical neck dissection for thyroid cancer.

    PubMed

    Paek, Se Hyun; Kang, Kyung Ho

    2016-06-01

    A robotic approach for thyroid surgery was developed to overcome the limitations of endoscopic thyroidectomy and provide many technical advantages. This approach facilitates the surgeon's control through a magnified three-dimensional view, decreased tremor, and freedom of motion with articulated instruments. Robotic thyroidectomy is safe and technically feasible in patients with well-differentiated, low-risk thyroid cancer. Furthermore, robotic thyroidectomy may become a good surgical alternative option for patients with more advanced thyroid cancer. Our modified bilateral axillo-breast approach (BABA) for central and lateral cervical neck lymph node (LN) dissection has yielded excellent surgical outcomes as an open procedure. The incorporation of robotics in thyroid cancer surgery will continue to evolve, and the surgical indications for robotic thyroidectomy will continue to expand. Further analyses that include long-term outcomes and randomized comparative trials remain important. PMID:27294043

  16. Robotic thyroidectomy and cervical neck dissection for thyroid cancer

    PubMed Central

    Paek, Se Hyun

    2016-01-01

    A robotic approach for thyroid surgery was developed to overcome the limitations of endoscopic thyroidectomy and provide many technical advantages. This approach facilitates the surgeon’s control through a magnified three-dimensional view, decreased tremor, and freedom of motion with articulated instruments. Robotic thyroidectomy is safe and technically feasible in patients with well-differentiated, low-risk thyroid cancer. Furthermore, robotic thyroidectomy may become a good surgical alternative option for patients with more advanced thyroid cancer. Our modified bilateral axillo-breast approach (BABA) for central and lateral cervical neck lymph node (LN) dissection has yielded excellent surgical outcomes as an open procedure. The incorporation of robotics in thyroid cancer surgery will continue to evolve, and the surgical indications for robotic thyroidectomy will continue to expand. Further analyses that include long-term outcomes and randomized comparative trials remain important. PMID:27294043

  17. Lenvatinib: Role in thyroid cancer and other solid tumors.

    PubMed

    Cabanillas, Maria E; Habra, Mouhammed Amir

    2016-01-01

    Despite recent breakthroughs in treatment of advanced thyroid cancers, prognoses remain poor. Treatment of advanced, progressive disease remains challenging, with limited treatment options. Small-molecule tyrosine kinase inhibitors, including vandetanib, cabozantinib, sorafenib, and lenvatinib, which are now FDA-approved for thyroid cancer, have shown clinical benefit in advanced thyroid cancer. Lenvatinib is approved for treatment of locally recurrent or metastatic, progressive, radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC). It has been studied in phase II and III trials for treatment of advanced RAI-refractory DTC, and in a phase II trial for medullary thyroid cancer (MTC). Lenvatinib targets vascular endothelial growth factor receptors 1-3 (VEGFR1-3), fibroblast growth factor receptors 1-4 (FGFR-1-4), RET, c-kit, and platelet-derived growth factor receptor α (PDGFRα). Its antitumor activity may be due to antiangiogenic properties and direct antitumor effects. Lenvatinib has demonstrated antitumor activity in a variety of solid tumors, including MTC, in phase I and II clinical trials. In a phase II study in advanced RAI-refractory DTC, lenvatinib-treated patients achieved a 50% response rate (RR), with median progression-free survival (PFS) of 12.6 months. In a phase III trial in RAI-refractory DTC, median PFS in lenvatinib-treated patients was 18.3 months, with a 65% overall RR, versus 3.6 months in placebo-treated patients, with a 2% RR. Adverse events occurring in >50% of patients included hypertension, diarrhea, fatigue/asthenia, and decreased appetite. Lenvatinib is a promising new agent for treatment of patients with advanced thyroid cancer. PMID:26678514

  18. Medical exposure to radiation and thyroid cancer.

    PubMed

    Schonfeld, S J; Lee, C; Berrington de González, A

    2011-05-01

    In 2008, the worldwide estimated age-standardised incidence rates for thyroid cancer incidence were 4.7 and 1.5 per 100,000 women and men, respectively. Thyroid cancer's overall contribution to the worldwide cancer burden is relatively small, but incidence rates have increased over the last three decades throughout the world. This trend has been hypothesised to reflect a combination of technological advances enabling increased detection, but also changes in environmental factors, including population exposure to ionising radiation from fallout, diagnostic tests and treatment for benign and malignant conditions. Studies of the atomic bomb survivors and populations treated with radiotherapy have established radiation as a risk factor for thyroid cancer, particularly from early life exposure. About 0.62 mSv (20%) of the global annual per caput effective radiation dose comes from diagnostic medical and dental radiation for the period of 1997-2007, increased from 0.4 mSv for the years 1991-1996. This international trend of increasing population exposure to medical diagnostic sources of radiation, attributed in large part to the growing use of computed tomography scans, but also interventional radiology procedures, has raised concerns about exposure to radiosensitive organs such as the thyroid. Worldwide, medical and dental X-rays constitute the most common type of diagnostic medical exposures, but their contribution to the cumulative effective dose is relatively low, whereas computed tomography scans account for 7.9% of diagnostic radiology examinations but 47% of the collective effective dose from diagnostic radiation procedures in parts of the world. Although the radiation exposure from computed tomography scans is substantially lower than that from radiotherapy, multiple computed tomography scans could result in non-trivial cumulative doses to the thyroid. Studies are currently underway to assess the incidence of cancer in large cohorts of children who received

  19. Treatment Option Overview (Thyroid Cancer)

    MedlinePlus

    ... glands make hormones. The thyroid uses iodine , a mineral found in some foods and in iodized salt, ... Fine-needle aspiration biopsy of the thyroid : The removal of thyroid tissue using a thin needle. The ...

  20. The 'rings of fire' and thyroid cancer.

    PubMed

    Duntas, Leonidas H; Doumas, Christos

    2009-01-01

    Several studies have revealed an increased incidence of thyroid cancer in volcanic areas around the world. Hawaii and the Philippines on the rim of the Pacific Ocean, where the greatest number of volcanoes are located at convergent plate boundaries, are among the regions with the highest incidence of thyroid carcinoma worldwide. Iceland is another region also rich in volcanoes in which the highest incidence of thyroid cancer in Europe is found. The common denominator of these regions is their numerous volcanoes and the fact that several constituents of volcanic lava have been postulated as being involved in the pathogenesis of thyroid cancer. This article aims at presenting pertinent data that could link a volcanic environment to thyroid cancer. PMID:20045797

  1. Novel Approaches in Anaplastic Thyroid Cancer Therapy

    PubMed Central

    Hsu, Kun-Tai; Yu, Xiao-Min; Audhya, Anjon W.; Jaume, Juan C.; Lloyd, Ricardo V.; Miyamoto, Shigeki; Prolla, Tomas A.

    2014-01-01

    Anaplastic thyroid cancer (ATC), accounting for less than 2% of all thyroid cancer, is responsible for the majority of death from all thyroid malignancies and has a median survival of 6 months. The resistance of ATC to conventional thyroid cancer therapies, including radioiodine and thyroid-stimulating hormone suppression, contributes to the very poor prognosis of this malignancy. This review will cover several cellular signaling pathways and mechanisms, including RET/PTC, RAS, BRAF, Notch, p53, and histone deacetylase, which are identified to play roles in the transformation and dedifferentiation process, and therapies that target these pathways. Lastly, novel approaches and agents involving the Notch1 pathway, nuclear factor κB, Trk-fused gene, cancer stem-like cells, mitochondrial mutation, and tumor immune microenvironment are discussed. With a better understanding of the biological process and treatment modality, the hope is to improve ATC outcome in the future. PMID:25260367

  2. Recurrent thyroid cancer with changing histologic features

    PubMed Central

    Konduri, Kartik; Harshman, Leeanne K.; Welch, Brian J.; O'Brien, John C.

    2010-01-01

    We present the case of a 57-year-old woman diagnosed with breast cancer and a thyroid mass that was suspicious for cancer. The breast cancer was estrogen and progesterone receptor negative, HER2/neu borderline, with a high proliferative index. Treatment of this cancer took precedence. Nine months later, a total thyroidectomy was done for papillary thyroid cancer with metastases to 2 of 8 perithyroid lymph nodes. Postoperative radioactive iodine ablation was given. Recurrent thyroid disease was found in the right neck 1 year later and was resected; no radioactive iodine was given at that time. After 2½ years, the cancer recurred as a more highly aggressive, undifferentiated anaplastic thyroid carcinoma. Treatment is discussed. PMID:21240322

  3. Thyroid Hormone Replacement in Patients Following Thyroidectomy for Thyroid Cancer

    PubMed Central

    Hannoush, Zeina C.; Weiss, Roy E.

    2016-01-01

    Thyroid hormone replacement therapy in patients following thyroidectomy for thyroid cancer, although a potentially straightforward clinical problem, can present the clinician and patient with a variety of challenges. Most often the problems are related to the dose and preparation of thyroid hormone (TH) to use. Some patients feel less well following thyroidectomy and/or radioiodine ablation than they did before their diagnosis. We present evidence that levothyroxine (L-T4) is the preparation of choice, and keeping the thyroid-stimulating hormone (TSH) between detectable and 0.1 mU/L should be the standard of care in most cases. In unusual circumstances, when the patient remains clinically hypothyroid despite a suppressed TSH, we acknowledge there may be as yet unidentified factors influencing the body’s response to TH, and individualized therapy may be necessary in such patients. PMID:26886951

  4. Management of Thyroid Nodules and Surgery for Differentiated Thyroid Cancer

    PubMed Central

    Iyer, N. Gopalakrishna; Shaha, A.R.

    2016-01-01

    The incidence of well-differentiated thyroid cancer has seen a worldwide increase in the last three decades. Whether this is due to a ‘true increase’ in incidence or simply increased detection of otherwise subclinical disease remains unclear. The treatment of thyroid cancer revolves around appropriate surgical intervention, minimising complications and the use of adjuvant therapy in select circumstances. Prognostic features and risk stratification are crucial in determining the appropriate treatment. There continues to be considerable debate in several aspects of management in these patients. Level 1 evidence is lacking, and there are limited prospective data to direct therapy, hence limiting decision-making to retrospective analyses, treatment guidelines based on expert opinion and personal philosophies. This overview focuses on the major issues associated with the investigation of thyroid nodules and the extent of surgery. As overall survival in well-differentiated thyroid cancer exceeds 95%, it is important to reduce over-treating the large majority of patients, and focus limited resources on high-risk patients who require aggressive treatment and closer attention. The onus is on the physician to avoid treatment-related complications from thyroid surgery and to offer the most efficient and cost-effective therapeutic option. PMID:20381323

  5. Signaling Pathways in Thyroid Cancer and Their Therapeutic Implications

    PubMed Central

    Jin, Shan; Borkhuu, Oyungerel; Bao, Wuyuntu; Yang, Yun-Tian

    2016-01-01

    Thyroid cancer is a common malignancy of endocrine system, and has now become the fastest increasing cancer among all the malignancies. The development, progression, invasion, and metastasis are closely associated with multiple signaling pathways and the functions of related molecules, such as Src, Janus kinase (JAK)-signal transducers and activators of transcription (STAT), mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K)/Akt, NF-κB, thyroid stimulating hormone receptor (TSHR), Wnt-β-catenin and Notch signaling pathways. Each of the signaling pathways could exert its function singly or through network with other pathways. These pathways could cooperate, promote, antagonize, or interact with each other to form a complex network for the regulation. Dysfunction of this network could increase the development, progression, invasion, and metastasis of thyroid cancer. Inoperable thyroid cancer still has a poor prognosis. However, signaling pathway-related targeted therapies offer the hope of longer quality of meaningful life for this small group of patients. Signaling pathway-related targets provide unprecedented opportunities for further research and clinical development of novel treatment strategies for this cancer. In the present work, the advances in these signaling pathways and targeted treatments of thyroid cancer were reviewed. PMID:26985248

  6. The Surgical Approach to Differentiated Thyroid Cancer

    PubMed Central

    Nixon, Iain

    2015-01-01

    The incidence of thyroid cancer is increasing rapidly. A large percentage of new cases identified fall into a low-risk category. As the incidence has increased, clinical experience has confirmed that the majority of patients will have excellent outcomes and that those at risk of doing badly can be reliably identified. Treatment for thyroid cancer is predominantly surgical. The decision about how aggressively this disease should be managed has remained controversial due to the excellent outcomes irrespective of the nature of surgical procedure chosen. This article reviews the developments in our understanding of the biology of thyroid cancer and the evidence that supports the approach to management. PMID:26918146

  7. [Thyroid cancer following exposure to ionising radiation].

    PubMed

    Schlumberger, M; Chevillard, S; Ory, K; Dupuy, C; Le Guen, B; de Vathaire, F

    2011-08-01

    Exposure to ionising radiations during childhood increases the risk of thyroid cancer. Similar risk factors have been found after external radiation exposure or internal contamination with radioactive iodine isotopes. In case of contamination with radioiodines, administration of potassium iodide can prevent thyroid irradiation. PMID:21723770

  8. Thyroid Adenomas After Solid Cancer in Childhood

    SciTech Connect

    Haddy, Nadia; El-Fayech, Chiraz; Guibout, Catherine; Adjadj, Elisabeth; Thomas-Teinturier, Cecile; Oberlin, Odile; Veres, Cristina; Pacquement, Helene; Jackson, Angela; Munzer, Martine; N'Guyen, Tan Dat; Bondiau, Pierre-Yves; Berchery, Delphine; Laprie, Anne; Bridier, Andre; Lefkopoulos, Dimitri; Schlumberger, Martin; Rubino, Carole; Diallo, Ibrahima; Vathaire, Florent de

    2012-10-01

    Purpose: Very few childhood cancer survivor studies have been devoted to thyroid adenomas. We assessed the role of chemotherapy and the radiation dose to the thyroid in the risk of thyroid adenoma after childhood cancer. Methods and Materials: A cohort of 3254 2-year survivors of a solid childhood cancer treated in 5 French centers before 1986 was established. The dose received by the isthmus and the 2 lobes of the thyroid gland during each course of radiation therapy was estimated after reconstruction of the actual radiation therapy conditions in which each child was treated as well as the dose received at other anatomical sites of interest. Results: After a median follow-up of 25 years, 71 patients had developed a thyroid adenoma. The risk strongly increased with the radiation dose to the thyroid up to a few Gray, plateaued, and declined for high doses. Chemotherapy slightly increased the risk when administered alone but also lowered the slope of the dose-response curve for the radiation dose to the thyroid. Overall, for doses up to a few Gray, the excess relative risk of thyroid adenoma per Gray was 2.8 (90% CI: 1.2-6.9), but it was 5.5 (90% CI: 1.9-25.9) in patients who had not received chemotherapy or who had received only 1 drug, and 1.1 (90% CI: 0.4-3.4) in the children who had received more than 1 drug (P=.06, for the difference). The excess relative risk per Gray was also higher for younger children at the time of radiation therapy than for their older counterparts and was higher before attaining 40 years of age than subsequently. Conclusions: The overall pattern of thyroid adenoma after radiation therapy for a childhood cancer appears to be similar to that observed for thyroid carcinoma.

  9. Thyroid cancer: a lethal endocrine neoplasm

    SciTech Connect

    Robbins, J.; Merino, M.J.; Boice, J.D. Jr.; Ron, E.; Ain, K.B.; Alexander, H.R.; Norton, J.A.; Reynolds, J.

    1991-07-15

    This conference focuses on the controversies about managing thyroid cancer, emphasizing the possibility that the treatment of patients with potentially fatal thyroid cancer may be improved. Although the mortality rate from thyroid cancer is low, it is the highest among cancers affecting the endocrine glands (excluding the ovary). Exposure to radiation during childhood in the 1930s and 1940s increased the incidence of but not the mortality from thyroid cancer, because these tumors are mainly papillary cancers developing in young adults. These rates may change as the exposed cohort ages. Risk factors that increase mortality include older patient age and the growth characteristics of the tumor at diagnosis, the presence of distant metastases, and cell type (for example, the tall-cell variants of papillary cancer, follicular cancer (to be distinguished from the more benign follicular variant of papillary cancer), medullary cancer, and anaplastic cancer). Local metastases in lymph nodes do not seem to increase the risk for death from papillary cancer, but they do increase the risk for death from follicular and medullary cancer. In the latter, mortality is decreased by the early detection and treatment of patients with the familial multiple endocrine neoplasia syndrome 2a. There are excellent tumor markers for differentiated cancer of the parafollicular and of the follicular cells. Measuring the calcitonin level allows early diagnosis of familial medullary cancer, whereas measuring the thyroglobulin level, although useful only after total thyroidectomy, allows early recognition of recurrence or metastases of papillary or follicular cancer. Initial surgery, protocols for follow-up, and the use of radioiodine for the ablation of any residual thyroid and the treatment of metastatic cancer are discussed.128 references.

  10. Application of Metabolomics in Thyroid Cancer Research

    PubMed Central

    Wojakowska, Anna; Chekan, Mykola; Widlak, Piotr; Pietrowska, Monika

    2015-01-01

    Thyroid cancer is the most common endocrine malignancy with four major types distinguished on the basis of histopathological features: papillary, follicular, medullary, and anaplastic. Classification of thyroid cancer is the primary step in the assessment of prognosis and selection of the treatment. However, in some cases, cytological and histological patterns are inconclusive; hence, classification based on histopathology could be supported by molecular biomarkers, including markers identified with the use of high-throughput “omics” techniques. Beside genomics, transcriptomics, and proteomics, metabolomic approach emerges as the most downstream attitude reflecting phenotypic changes and alterations in pathophysiological states of biological systems. Metabolomics using mass spectrometry and magnetic resonance spectroscopy techniques allows qualitative and quantitative profiling of small molecules present in biological systems. This approach can be applied to reveal metabolic differences between different types of thyroid cancer and to identify new potential candidates for molecular biomarkers. In this review, we consider current results concerning application of metabolomics in the field of thyroid cancer research. Recent studies show that metabolomics can provide significant information about the discrimination between different types of thyroid lesions. In the near future, one could expect a further progress in thyroid cancer metabolomics leading to development of molecular markers and improvement of the tumor types classification and diagnosis. PMID:25972898

  11. The immune network in thyroid cancer.

    PubMed

    Galdiero, Maria Rosaria; Varricchi, Gilda; Marone, Gianni

    2016-06-01

    The immune system plays critical roles in tumor prevention, but also in its initiation and progression. Tumors are subjected to immunosurveillance, but cancer cells generate an immunosuppressive microenvironment that favors their escape from immune-mediated elimination. During chronic inflammation, immune cells can contribute to the formation and progression of tumors by producing mitogenic, prosurvival, proangiogenic and lymphangiogenic factors. Thyroid cancer is the most frequent type of endocrine neoplasia and is the most rapidly increasing cancer in the US. In this review, we discuss recent findings on how different immune cells and mediators can contribute to thyroid cancer development and progression. PMID:27471646

  12. Risk of Thyroid Cancer in Euthyroid Asymptomatic Patients with Thyroid Nodules with an Emphasis on Family History of Thyroid Cancer

    PubMed Central

    Hwang, Shin Hye; Kim, Eun-Kyung; Moon, Hee Jung; Yoon, Jung Hyun

    2016-01-01

    Objective To determine the factors associated with thyroid cancer, focusing on first-degree family history and ultrasonography (US) features, in euthyroid asymptomatic patients with thyroid nodules. Materials and Methods This retrospective study included 1310 thyroid nodules of 1254 euthyroid asymptomatic patients who underwent US-guided fine-needle aspiration biopsy between November 2012 and August 2013. Nodule size and clinical risk factors–such as patient age, gender, first-degree family history of thyroid cancer, multiplicity on US and serum thyroid stimulating hormone (TSH) levels–were considered together with US features to compare benign and malignant nodules. Multiple logistic regression analysis was performed to assess the risk of thyroid malignancy according to clinical and US characteristics. Results Although all of the clinical factors and US findings were significantly different between patients with benign and malignant nodules, a solitary lesion on US (p = 0.041–0.043), US features and male gender (p < 0.001) were significant independent risk factors for thyroid malignancy in a multivariate analysis. Patient age, a first-degree family history of thyroid cancer and high normal serum TSH levels did not independently significantly increase the risk of thyroid cancer. However, multicollinearity existed between US assessment and patient age, first-degree family history of thyroid cancer and serum TSH values. Conclusion Ultrasonography findings should be the primary criterion used to decide the management of euthyroid asymptomatic patients with thyroid nodules. The concept of first-degree family history as a risk factor for thyroid malignancy should be further studied in asymptomatic patients. PMID:26957911

  13. Sorafenib in the treatment of thyroid cancer.

    PubMed

    Ferrari, Silvia Martina; Politti, Ugo; Spisni, Roberto; Materazzi, Gabriele; Baldini, Enke; Ulisse, Salvatore; Miccoli, Paolo; Antonelli, Alessandro; Fallahi, Poupak

    2015-01-01

    Sorafenib has been evaluated in several Phase II and III studies in patients with locally advanced/metastatic radioactive iodine-refractory differentiated thyroid carcinomas (DTCs), reporting partial responses, stabilization of the disease and improvement of progression-free survival. Best responses were observed in lung metastases and minimal responses in bone lesions. On the basis of these studies, sorafenib was approved for the treatment of metastatic DTC in November 2013. Few studies suggested that reduction of thyroglobulin levels, or of average standardized uptake value at the fluorodeoxyglucose-PET, could be helpful for the identification of responding patients; but further studies are needed to confirm these results. Tumor genetic marker levels did not have any prognostic or predictive role in DTC patients.The most common adverse events observed included skin toxicity and gastrointestinal and constitutional symptoms. Encouraging results have also been observed in patients with medullary thyroid cancer. Many studies are ongoing to evaluate the long-term efficacy and tolerability of sorafenib in DTC patients. PMID:26152651

  14. Propranolol sensitizes thyroid cancer cells to cytotoxic effect of vemurafenib.

    PubMed

    Wei, Wei-Jun; Shen, Chen-Tian; Song, Hong-Jun; Qiu, Zhong-Ling; Luo, Quan-Yong

    2016-09-01

    Treatment options for advanced metastatic or progressive thyroid cancers are limited. Although targeted therapy specifically inhibiting intracellular kinase signaling pathways has markedly changed the therapeutic landscape, side-effects and resistance of single agent targeted therapy often leads to termination of the treatment. The objective of the present study was to identify the antitumor property of the non-selective β-adrenergic receptor antagonist propranolol for thyroid cancers. Human thyroid cancer cell lines 8505C, K1, BCPAP and BHP27 were used in the present study. Broad β-blocker propranolol and β2-specific antagonist ICI118551, but not β1-specific antagonist atenolol, inhibited the growth of 8505C and K1 cells. Propranolol treatment inhibited growth and induced apoptosis of 8505C cells in vitro and in vivo, which are closely associated with decreased expressions of cyclin D1 and anti-apoptotic Bcl-2. Expression of hexokinase 2 (HK2) and glucose transporter 1 (GLUT1) also decreased following propranolol intervention. 18F-FDG PET/CT imaging of the 8505C xenografts validated shrinkage of the tumors in the propranolol-treated group when compared to the phosphate‑buffered saline treated group. Finally, we found that propranolol can amplify the cytotoxicity of vemurafenib and sensitize thyroid cancer cells to cytotoxic effect of vemurafenib. Our present results suggest that propranolol has potential activity against thyroid cancers and investigation of the combination with targeted molecular therapy for progressive thyroid cancers could be beneficial. PMID:27432558

  15. Advances in the management of patients with thyroid disease.

    PubMed

    Dworkin, H J; Meier, D A; Kaplan, M

    1995-07-01

    Discoveries related to thyroid immunology, especially concerning the thyroid-stimulating hormone (TSH) receptor, may facilitate new immunologic approaches to the therapy of Graves' disease and the thyroiditis syndromes. Advances in genetics are being applied to the thyroid hormone resistance syndromes and papillary and medullary carcinomas. The development of ever more sensitive TSH assays has led to the detection of subclinical thyroid disease, which has special implications for the sick and elderly patients. Sensitive TSH assays also allow more precise titration of levothyroxine (T4) dosages, especially for patients with a past history of thyroid cancer. Evidence continues to accumulate suggesting that postmenopausal women on T4 doses that suppress the TSH level below 0.1 ulU/mL have lower bone mineral density than matched patients with healthy TSH levels. Also, pregnant hypothyroid women need higher T4 doses to normalize the TSH levels. In the evaluation of thyroid nodules, fine-needle aspiration biopsy is the single most definitive modality in selecting the patients for surgery. Scintigraphy provides a complimentary role, especially in defining autonomously functioning thyroid adenomas (AFTA), because these should not be treated with T4 suppression. Ultrasound-guided needle biopsy is occasionally helpful with nodules that are difficult to palpate. Concern for possible tracheal compression after treatment of toxic multinodular goiter with large doses of radioactive iodine (I-131) in the range of 50 to 150 mCi (1.85 to 5.5 GBq) does not seem warranted. Work, primarily out of Italy, suggests AFTA can be ablated with repeat ethanol injections. Residual tissues after thyroidectomy for differentiated carcinoma can be "stunned" by tracer doses of 131I greater than 3.0 mCi (111 MBq), which diminishes the uptake and effectiveness of a subsequent therapy dose. Positron emission tomograph, imaging with thallium-201, and Technetium 99m Sestamibi can identify a small number

  16. Survival discriminants for differentiated thyroid cancer

    SciTech Connect

    Cunningham, M.P.; Duda, R.B.; Recant, W.; Chmiel, J.S.; Sylvester, J.A.; Fremgen, A. )

    1990-10-01

    Since 1975, the American Cancer Society, Illinois Division, has published end results of major cancer sites drawn from patient data contributed voluntarily by hospital cancer registries throughout the state. The current study was undertaken, in part, to apprehend information regarding contested areas in the management of patients having differentiated (papillary/follicular) thyroid cancer. A total of 2,282 patients with either papillary or follicular carcinoma of the thyroid from 76 different Illinois hospitals and providing 10 years of follow-up information (life-table analysis) were retrospectively analyzed for demographic, disease, and treatment-related predictors of survival. Multivariate analysis using the Cox proportional hazards method was made for stage, age, race, sex, morphology, history of radiation exposure, presence of positive lymph nodes, initial surgical treatment, postoperative iodine 131 therapy, and replacement/suppressive thyroid hormone treatment. Statistically significant (p less than or equal to 0.05) predictors of favorable survival after thyroid cancer were low stage (I and II), young age (less than 50 years), white race, female sex, and the administration, postoperatively, of either thyroid hormone or radioactive iodine. Factors that had no influence on survival were lymph node status, choice of initial surgical treatment, and a history of prior irradiation. We suggest that where a prospective clinical trial is impracticable, a retrospective analysis of a large and detailed database, such as that available from cooperating hospital-based tumor registries, may yet provide useful insights to solutions of cancer management problems.

  17. Scans Not Worthwhile for Most Thyroid Cancers: Study

    MedlinePlus

    ... fullstory_160009.html Scans Not Worthwhile for Most Thyroid Cancers: Study Doctors found checking for recurrences with ... News) -- Having scans after treatment does not improve thyroid cancer patients' chances of survival, a new study ...

  18. Agent Orange Linked to Bladder Cancer, Thyroid Problems, Panel Says

    MedlinePlus

    ... 157716.html Agent Orange Linked to Bladder Cancer, Thyroid Problems, Panel Says Herbicide was used during Vietnam ... the herbicide Agent Orange and bladder cancer and thyroid problems among U.S. military personnel exposed to the ...

  19. Cancer stem-like cells and thyroid cancer.

    PubMed

    Guo, Zhenying; Hardin, Heather; Lloyd, Ricardo V

    2014-10-01

    Thyroid cancer is one of the most rapidly increasing malignancies. The reasons for this increase is not completely known, but increases in the diagnosis of papillary thyroid microcarcinomas and follicular variant of papillary thyroid carcinomas along with the enhanced detection of well-differentiated thyroid carcinomas are probably all contributing factors. Although most cases of well-differentiated thyroid carcinomas are associated with an excellent prognosis, a small percentage of patients with well-differentiated thyroid carcinomas as well as most patients with poorly differentiated and anaplastic thyroid carcinomas have recurrent and/or metastatic disease that is often fatal. The cancer stem-like cell (CSC) model suggests that a small number of cells within a cancer, known as CSCs, are responsible for resistance to chemotherapy and radiation therapy, as well as for recurrent and metastatic disease. This review discusses current studies about thyroid CSCs, the processes of epithelial-to-mesenchymal transition (EMT), and mesenchymal-to-epithelial transition that provide plasticity to CSC growth, in addition to the role of microRNAs in CSC development and regulation. Understanding the biology of CSCs, EMT and the metastatic cascade should lead to the design of more rational targeted therapies for highly aggressive and fatal thyroid cancers. PMID:24788702

  20. Molecular pathogenesis and mechanisms of thyroid cancer

    PubMed Central

    Xing, Mingzhao

    2013-01-01

    Thyroid cancer is a common endocrine malignancy. There has been exciting progress in understanding its molecular pathogenesis in recent years, as best exemplified by the elucidation of the fundamental role of several major signalling pathways and related molecular derangements. Central to these mechanisms are the genetic and epigenetic alterations in these pathways, such as mutation, gene copy-number gain and aberrant gene methylation. Many of these molecular alterations represent novel diagnostic and prognostic molecular markers and therapeutic targets for thyroid cancer, which provide unprecedented opportunities for further research and clinical development of novel treatment strategies for this cancer. PMID:23429735

  1. Early clinical studies of novel therapies for thyroid cancers.

    PubMed

    Sherman, Steven I

    2008-06-01

    Historically, systemic therapies for advanced, metastatic thyroid carcinomas have been poorly effective. However, as a result of a confluence of increasing knowledge of the biologic basis for thyroid cancer development and progression, identification of therapeutic agents that could target these biologic abnormalities, and enthusiasm for research by both funding agencies as well as patients, multiple clinical trials have been initiated and successfully completed during the past several years. This article focuses on findings from key studies that reflect the new paradigms for treatment. PMID:18502340

  2. A New Aurora in Anaplastic Thyroid Cancer Therapy

    PubMed Central

    Baldini, Enke; D'Armiento, Massimino

    2014-01-01

    Anaplastic thyroid cancers (ATC) are among the most aggressive human neoplasms with a dire prognosis and a median survival time of few months from the diagnosis. The complete absence of effective therapies for ATC renders the identification of novel therapeutic approaches sorely needed. Chromosomal instability, a feature of all human cancers, is thought to represent a major driving force in thyroid cancer progression and a number of mitotic kinases showing a deregulated expression in malignant thyroid tissues are now held responsible for thyroid tumor aneuploidy. These include the three members of the Aurora family (Aurora-A, Aurora-B, and Aurora-C), serine/threonine kinases that regulate multiple aspects of chromosome segregation and cytokinesis. Over the last few years, several small molecule inhibitors targeting Aurora kinases were developed, which showed promising antitumor effects against a variety of human cancers, including ATC, in preclinical studies. Several of these molecules are now being evaluated in phase I/II clinical trials against advanced solid and hematological malignancies. In the present review we will describe the structure, expression, and mitotic functions of the Aurora kinases, their implications in human cancer progression, with particular regard to ATC, and the effects of their functional inhibition on malignant cell proliferation. PMID:25097550

  3. [Association of hyperthyroidism with differentiated thyroid cancer].

    PubMed

    Haraj, Nassim Essabah; Ahandar, Hayat; El Aziz, Siham; Chadli, Asma

    2016-01-01

    The presence of hyperthyroidism is no longer an insurance against the occurrence of thyroid cancer. The combination of the two is common. This is a retrospective study of 355 files of patients followed for differentiated thyroid cancer in the endocrinology department at CHU IBN ROCHD from 1986 to 2014. 12 of those patients were followed for hyperthyroidism, and a fortuitous association with differentiated thyroid cancer was found during the anatomopathological exam, giving us a 3.38% prevalence. The average age of discovery is 44.8 years, with a marked female predominance (8/12). Eight patients had a toxic nodule, 3 had Basedow's goiters, and one had Graves' disease. All underwent total thyroidectomy. In all patients, the cancer was a papillary carcinoma. Microcarcinoma was the most predominant (6 patients). An insular carcinoma was found in a patient with spinal and retro-orbital metastases. Treatment with radioactive iodine was prescribed to five patients. The diagnosis of hyperthyroidism does not eliminate the possibility of an associated thyroid cancer. Malignancy should always be kept in mind and therefore lead to a diagnostic approach comparable to that for any thyroid nodule. PMID:27583082

  4. Iodine I 131 and Pazopanib Hydrochloride in Treating Patients With Recurrent and/or Metastatic Thyroid Cancer Previously Treated With Iodine I 131 That Cannot Be Removed By Surgery

    ClinicalTrials.gov

    2015-11-04

    Recurrent Thyroid Cancer; Stage IVA Follicular Thyroid Cancer; Stage IVA Papillary Thyroid Cancer; Stage IVB Follicular Thyroid Cancer; Stage IVB Papillary Thyroid Cancer; Stage IVC Follicular Thyroid Cancer; Stage IVC Papillary Thyroid Cancer

  5. Upregulation of long noncoding RNA LOC100507661 promotes tumor aggressiveness in thyroid cancer.

    PubMed

    Kim, Daham; Lee, Woo Kyung; Jeong, Seonhyang; Seol, Mi-Youn; Kim, Hyunji; Kim, Kyung-Sup; Lee, Eun Jig; Lee, Jandee; Jo, Young Suk

    2016-08-15

    Recent advances in next-generation sequencing have revealed a variety of long noncoding RNAs (lncRNAs). However, studies of lncRNAs are at a very early stage, our knowledge of the biological functions and clinical implications remains limited. To investigate the roles of lncRNAs in thyroid cancers, we verified 56 lncRNAs identified as potential cancer-promoting genes in a previous study that analyzed 2394 tumor SNP arrays from 12 types of cancer. Based on verified sequence information in NCBI and Ensembl, we ultimately selected three candidate lncRNAs for detailed analysis. One of the candidates, LOC100507661, was strongly upregulated in thyroid cancer tissues relative to paired contralateral normal tissue. LOC100507661 was easily detectable in papillary and anaplastic thyroid cancer cell lines such as TPC1, BCPAP, C643, and 8505C, but not in the follicular thyroid cancer cell line FTC133. Stable overexpression of LOC100507661 promoted cell proliferation, migration, and invasion of thyroid cancer cells. Lymph node metastasis and BRAF V600E mutations were more frequent in papillary thyroid cancers with high LOC100507661 expression. Our data demonstrate that LOC100507661 expression is elevated in human thyroid cancer and may play a critical role in thyroid carcinogenesis. PMID:27151833

  6. Cancer-Related Worry in Canadian Thyroid Cancer Survivors

    PubMed Central

    Bresner, Lauren; Banach, Rita; Rodin, Gary; Thabane, Lehana; Ezzat, Shereen

    2015-01-01

    Context: Little is known about cancer-related worry in thyroid cancer survivors. Objectives: We quantified cancer-related worry in Canadian thyroid cancer survivors and explored associated factors. Design, Setting, and Participants: We performed a cross-sectional, self-administered, written survey of thyroid cancer survivor members of the Thyroid Cancer Canada support group. Independent factors associated with cancer-related worry were identified using a multivariable linear regression analysis. Main Outcome Measure: We used the Assessment of Survivor Concerns (ASC) questionnaire, which includes questions on worry about diagnostic tests, second primary malignancy, recurrence, dying, health, and children's health. Results: The response rate for eligible members was 60.1% (941 of 1567). Most respondents were women (89.0%; 837 of 940), and the age was < 50 years in 54.0% of participants (508 of 941). Thyroid cancer was diagnosed within ≤ 5 years in 66.1% of participants (622 of 940). The mean overall ASC score was 15.34 (SD, 4.7) (on a scale from 6 [least worry] to 24 [most worry]). Factors associated with increased ASC score included: younger age (P < .001), current suspected or proven recurrent/persistent disease (ie, current proven active disease or abnormal diagnostic tests) (P < .001), partnered marital status (P = .021), having children (P = .029), and ≤5 years since thyroid cancer diagnosis (P = .017). Conclusions: In a population of Canadian thyroid cancer survivors, cancer-related worry was greatest in younger survivors and those with either confirmed or suspected disease activity. Family status and time since thyroid cancer diagnosis were also associated with increased worry. More research is needed to confirm these findings and to develop effective preventative and supportive strategies for those at risk. PMID:25393643

  7. Controversies in the Management and Followup of Differentiated Thyroid Cancer: Beyond the Guidelines

    PubMed Central

    Ahmadieh, Hala; Azar, Sami T.

    2012-01-01

    Thyroid cancer is among the most common endocrine malignancies. Genetic and environmental factors play an important role in the pathogenesis of differentiated thyroid cancer. Both have good prognosis but with frequent recurrences. Cancer staging is an essential prognostic part of cancer management. There are multiple controversies in the management and followup of differentiated thyroid cancer. Debate still exists with regard to the optimal surgical approach but trends toward a more conservative approach, such as lobectomy, are being more favored, especially in papillary thyroid cancer, of tumor sizes less than 4 cm, in the absence of other high-risk suggestive features. Survival of patients with well-differentiated thyroid cancer was adversely affected by lymph node metastases. Prophylactic central LN dissection did improve accuracy in staging and decrease postop TG level, but it had no effect on small-sized tumors. Conservative approach was more applied with regard to the need and dose of radioiodine given postoperatively. There have been several advancements in the management of radioiodine resistant advanced differentiated thyroid cancers. Appropriate followup is required based on risk stratification of patients postoperatively. Many studies are still ongoing in order to reach the optimal management and followup of differentiated thyroid cancer. PMID:23326756

  8. Testosterone regulates thyroid cancer progression by modifying tumor suppressor genes and tumor immunity

    PubMed Central

    Zhang, Lisa J.; Xiong, Yin; Nilubol, Naris; He, Mei; Bommareddi, Swaroop; Zhu, Xuguang; Jia, Li; Xiao, Zhen; Park, Jeong-Won; Xu, Xia; Patel, Dhaval; Willingham, Mark C.; Cheng, Sheue-yann; Kebebew, Electron

    2015-01-01

    Cancer gender disparity has been observed for a variety of human malignancies. Thyroid cancer is one such cancer with a higher incidence in women, but more aggressive disease in men. There is scant evidence on the role of sex hormones on cancer initiation/progression. Using a transgenic mouse model of follicular thyroid cancer (FTC), we found castration led to lower rates of cancer in females and less advanced cancer in males. Mechanistically, less advanced cancer in castrated males was due to increased expression of tumor suppressor (Glipr1, Sfrp1) and immune-regulatory genes and higher tumor infiltration with M1 macrophages and CD8 cells. Functional study showed that GLIPR1 reduced cell growth and increased chemokine secretion (Ccl5) that activates immune cells. Our data demonstrate that testosterone regulates thyroid cancer progression by reducing tumor suppressor gene expression and tumor immunity. PMID:25576159

  9. Involvement of Aberrant Glycosylation in Thyroid Cancer

    PubMed Central

    Miyoshi, Eiji; Ito, Yasuhiro; Miyoshi, Yoko

    2010-01-01

    Glycosylation is one of the most common posttranslational modification reactions and nearly half of all known proteins in eukaryotes are glycosylated. In fact, changes in oligosaccharides structures are associated with many physiological and pathological events, including cell growth, migration and differentiation, and tumor invasion. Therefore, functional glycomics, which is a comprehensive study of the structures and functions of glycans, is attracting the increasing attention of scientists in various fields of life science. In cases of thyroid cancer, the biological characters and prognosis are completely different in each type of histopathology, and their oligosaccharide structures as well as the expression of glycosyltransferases are also different. In this review, we summarized our previous papers on oligosaccharides and thyroid cancers and discussed a possible function of oligosaccharides in the carcinogenesis in thyroid cancer. PMID:20652009

  10. Molecular Targeted Therapies of Aggressive Thyroid Cancer

    PubMed Central

    Ferrari, Silvia Martina; Fallahi, Poupak; Politti, Ugo; Materazzi, Gabriele; Baldini, Enke; Ulisse, Salvatore; Miccoli, Paolo; Antonelli, Alessandro

    2015-01-01

    Differentiated thyroid carcinomas (DTCs) that arise from follicular cells account >90% of thyroid cancer (TC) [papillary thyroid cancer (PTC) 90%, follicular thyroid cancer (FTC) 10%], while medullary thyroid cancer (MTC) accounts <5%. Complete total thyroidectomy is the treatment of choice for PTC, FTC, and MTC. Radioiodine is routinely recommended in high-risk patients and considered in intermediate risk DTC patients. DTC cancer cells, during tumor progression, may lose the iodide uptake ability, becoming resistant to radioiodine, with a significant worsening of the prognosis. The lack of specific and effective drugs for aggressive and metastatic DTC and MTC leads to additional efforts toward the development of new drugs. Several genetic alterations in different molecular pathways in TC have been shown in the past few decades, associated with TC development and progression. Rearranged during transfection (RET)/PTC gene rearrangements, RET mutations, BRAF mutations, RAS mutations, and vascular endothelial growth factor receptor 2 angiogenesis pathways are some of the known pathways determinant in the development of TC. Tyrosine kinase inhibitors (TKIs) are small organic compounds inhibiting tyrosine kinases auto-phosphorylation and activation, most of them are multikinase inhibitors. TKIs act on the aforementioned molecular pathways involved in growth, angiogenesis, local, and distant spread of TC. TKIs are emerging as new therapies of aggressive TC, including DTC, MTC, and anaplastic thyroid cancer, being capable of inducing clinical responses and stabilization of disease. Vandetanib and cabozantinib have been approved for the treatment of MTC, while sorafenib and lenvatinib for DTC refractory to radioiodine. These drugs prolong median progression-free survival, but until now no significant increase has been observed on overall survival; side effects are common. New efforts are made to find new more effective and safe compounds and to personalize the therapy in

  11. How Is Thyroid Cancer Diagnosed?

    MedlinePlus

    ... test. This leads to low thyroid hormone levels (hypothyroidism) and causes the pituitary gland to release more ... is that it can cause the symptoms of hypothyroidism, including tiredness, depression, weight gain, sleepiness, constipation, muscle ...

  12. Germline HABP2 Mutation Causing Familial Nonmedullary Thyroid Cancer

    PubMed Central

    Gara, Sudheer Kumar; Jia, Li; Merino, Maria J.; Agarwal, Sunita K.; Zhang, Lisa; Cam, Maggie; Patel, Dhaval; Kebebew, Electron

    2015-01-01

    SUMMARY Familial nonmedullary thyroid cancer accounts for 3 to 9% of all cases of thyroid cancer, but the susceptibility genes are not known. Here, we report a germline variant of HABP2 in seven affected members of a kindred with familial nonmedullary thyroid cancer and in 4.7% of 423 patients with thyroid cancer. This variant was associated with increased HABP2 protein expression in tumor samples from affected family members, as compared with normal adjacent thyroid tissue and samples from sporadic cancers. Functional studies showed that HABP2 has a tumor-suppressive effect, whereas the G534E variant results in loss of function. PMID:26222560

  13. A phase 2 trial of lenvatinib (E7080) in advanced progressive radioiodine-refractory differentiated thyroid cancer: a clinical outcomes and biomarker assessment

    PubMed Central

    Cabanillas, Maria E.; Schlumberger, Martin; Jarzab, Barbara; Martins, Renato G.; Pacini, Furio; Robinson, Bruce; McCaffrey, Judith C.; Shah, Manisha H.; Bodenner, Donald L.; Topliss, Duncan; Andresen, Corina; O'Brien, James P.; Ren, Min; Funahashi, Yasuhiro; Allison, Roger; Elisei, Rossella; Newbold, Kate; Licitra, Lisa F.; Sherman, Steven I.; Ball, Douglas W.

    2016-01-01

    Background Lenvatinib is an oral, multitargeted tyrosine kinase inhibitor of VEGFR1–3, FGFR1–4, PDGFRα, RET, and KIT signaling networks implicated in tumor angiogenesis. Positive phase 1 results in solid tumors prompted a phase 2 trial in advanced radioiodine-refractory differentiated thyroid cancer (RR-DTC). Methods Fifty-eight patients with RR-DTC and disease progression during the prior 12 months were administered lenvatinib 24-mg once daily in 28-day cycles until disease progression, unmanageable toxicity, withdrawal, or death. Prior VEGFR-targeted therapy was permitted. The primary endpoint was objective response rate (ORR) based upon independent imaging review (IIR). Secondary endpoints included progression-free survival (PFS) and safety. Serum levels of 51 circulating cytokines and angiogenic factors were also assessed. Results After ≥14 months of follow-up, patients had ORR of 50% (95% confidence interval [CI] 37–63) with only partial responses reported. Median time to response was 3.6 months; median duration of response was 12.7 months; median PFS was 12.6 months (95% CI 9.9–16.1). ORR for patients with prior VEGF therapy (n=17) was 59% (95% CI 33–82). Lower baseline levels of angiopoietin-2 were suggestive of tumor response and longer PFS. Grade 3/4 treatment-emergent adverse events regardless of relation to treatment occurred in 72% of patients, most frequently weight loss (12%), hypertension (10%), proteinuria (10%), and diarrhea (10%). Conclusion In patients with and without prior exposure to VEGF therapy, the encouraging response rates, median time to response, and PFS for lenvatinib have prompted further investigation in a phase 3 trial. PMID:25913680

  14. Management of Differentiated Thyroid Cancer in Children: Focus on the American Thyroid Association Pediatric Guidelines.

    PubMed

    Parisi, Marguerite T; Eslamy, Hedieh; Mankoff, David

    2016-03-01

    First introduced in 1946, radioactive iodine (I-131) produces short-range beta radiation with a half-life of 8 days. The physical properties of I-131 combined with the high degree of uptake in the differentiated thyroid cancers (DTCs) led to the use of I-131 as a therapeutic agent for DTC in adults. There are two indications for the potential use of I-131 therapy in pediatric thyroid disorders: nonsurgical treatment of hyperthyroidism owing to Graves' disease and the treatment of children with intermediate- and high-risk DTC. However, children are not just miniature adults. Not only are children and the pediatric thyroid gland more sensitive to radiation than adults but also the biologic behavior of DTC differs between children and adults as well. As opposed to adults, children with DTC typically present with advanced disease at diagnosis; yet, they respond rapidly to therapy and have an excellent prognosis that is significantly better than that in adult counterparts with advanced disease. Unfortunately, there are also higher rates of local and distant disease recurrence in children with DTC compared with adults, mandating lifelong surveillance. Further, children have a longer life expectancy during which the adverse effects of I-131 therapy may become manifest. Recognizing the differences between adults and children with DTC, the American Thyroid Association commissioned a task force of experts who developed and recently published a guideline to address the unique issues related to the management of thyroid nodules and DTC in children. This article reviews the epidemiology, diagnosis, staging, treatment, therapy-related effects, and suggestions for surveillance in children with DTC, focusing not only on the differences between adults and children with this disease but also on the latest recommendations from the inaugural pediatric management guidelines of the American Thyroid Association. PMID:26897719

  15. Diagnosis and Management of Hereditary Thyroid Cancer.

    PubMed

    Bano, Gul; Hodgson, Shirley

    2016-01-01

    Thyroid cancers are largely divided into medullary (MTC) and non-medullary (NMTC) cancers , depending on the cell type of origin. Familial non-medullary thyroid cancer (FNMTC) comprises about 5-15% of NMTC and is a heterogeneous group of diseases, including both non-syndromic and syndromic forms. Non-syndromic FNMTC tends to manifest papillary thyroid carcinoma , usually multifocal and bilateral . Several high-penetrance genes for FNMTC have been identified, but they are often confined to a few or single families, and other susceptibility loci appear to play a small part, conferring only small increments in risk. Familial susceptibility is likely to be due to a combination of genetic and environmental influences. The current focus of research in FNMTC is to characterise the susceptibility genes and their role in carcinogenesis. FNMTC can also occur as a part of multitumour genetic syndromes such as familial adenomatous polyposis , Cowden's disease , Werner's syndrome and Carney complex . These tend to present at an early age and are multicentric and bilateral with distinct pathology. The clinical evaluation of these patients is similar to that for most patients with a thyroid nodule. Medullary thyroid cancer (MTC) arises from the parafollicular cells of the thyroid which release calcitonin. The familial form of MTC accounts for 20-25% of cases and presents as a part of the multiple endocrine neoplasia type 2 (MEN 2) syndromes or as a pure familial MTC (FMTC). They are caused by germline point mutations in the RET oncogene on chromosome 10q11.2. There is a clear genotype-phenotype correlation, and the aggressiveness of FMTC depends on the specific genetic mutation, which should determine the timing of surgery. PMID:27075347

  16. Diagnostic imaging techniques in thyroid cancer

    SciTech Connect

    Friedman, M.; Toriumi, D.M.; Mafee, M.F.

    1988-02-01

    With the refinement of fine-needle aspiration, the specific applications of thyroid imaging techniques need to be reevaluated for efficiency and cost containment. No thyroid imaging test should be routinely obtained. Radionuclide scanning is most beneficial in evaluating the functional status of thyroid nodules when fine-needle aspiration is inadequate, the findings are benign, or when there is no discrete nodule that is palpated in an enlarged gland. When fine-needle aspiration is unavailable or unreliable, radionuclide scanning becomes a first-line diagnostic tool. Ultrasonography should be used primarily for identifying a solid component of a cystic nodule, determining the size of nodules on thyroxine suppression that are not easily palpable, or for performing guided fine-needle aspiration. Computerized tomography and magnetic resonance imaging both have a definite role in the evaluation of thyroid tumors. Magnetic resonance imaging is superior to computerized tomography for the evaluation of metastatic, retrotracheal, or mediastinal involvement of large thyroid tumors or goiters. Careful selection of the diagnostic techniques will ensure more accurate diagnosis and reduce unnecessary patient costs in the treatment of thyroid cancer.

  17. NADPH oxidases: new actors in thyroid cancer?

    PubMed

    Ameziane-El-Hassani, Rabii; Schlumberger, Martin; Dupuy, Corinne

    2016-08-01

    Hydrogen peroxide (H2O2) is a crucial substrate for thyroid peroxidase, a key enzyme involved in thyroid hormone synthesis. However, as a potent oxidant, H2O2 might also be responsible for the high level of oxidative DNA damage observed in thyroid tissues, such as DNA base lesions and strand breakages, which promote chromosomal instability and contribute to the development of tumours. Although the role of H2O2 in thyroid hormone synthesis is well established, its precise mechanisms of action in pathological processes are still under investigation. The NADPH oxidase/dual oxidase family are the only oxidoreductases whose primary function is to produce reactive oxygen species. As such, the function and expression of these enzymes are tightly regulated. Thyrocytes express dual oxidase 2, which produces most of the H2O2 for thyroid hormone synthesis. Thyrocytes also express dual oxidase 1 and NADPH oxidase 4, but the roles of these enzymes are still unknown. Here, we review the structure, expression, localization and function of these enzymes. We focus on their potential role in thyroid cancer, which is characterized by increased expression of these enzymes. PMID:27174022

  18. Anaplastic Transformation of Papillary Thyroid Cancer in the Retroperitoneum

    PubMed Central

    Solomon, James P.; Wen, Fang; Jih, Lily J.

    2015-01-01

    Anaplastic thyroid carcinoma is an aggressive variant of thyroid cancer that in most cases arises from anaplastic transformation of terminally differentiated thyroid carcinomas. This process usually occurs in the thyroid or cervical lymph nodes. Anaplastic transformation in distant metastatic sites is exceedingly rare, only previously documented in a few case reports. We report a rare case of anaplastic transformation of papillary thyroid carcinoma within a large retroperitoneal metastasis in a 64-year-old male 30 years after the initial diagnosis. PMID:26351607

  19. Sorafenib Tosylate in Treating Younger Patients With Relapsed or Refractory Rhabdomyosarcoma, Wilms Tumor, Liver Cancer, or Thyroid Cancer

    ClinicalTrials.gov

    2015-05-14

    Childhood Hepatocellular Carcinoma; Papillary Thyroid Cancer; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Childhood Liver Cancer; Recurrent Childhood Rhabdomyosarcoma; Recurrent Thyroid Cancer; Recurrent Wilms Tumor and Other Childhood Kidney Tumors

  20. Sorafenib in locally advanced or metastatic, radioactive iodine-refractory, differentiated thyroid cancer: a randomized, double-blind, phase 3 trial

    PubMed Central

    Brose, Marcia S; Nutting, Christopher M; Jarzab, Barbara; Elisei, Rossella; Siena, Salvatore; Bastholt, Lars; de la Fouchardiere, Christelle; Pacini, Furio; Paschke, Ralf; KeeShong, Young; Sherman, Steven I; Smit, Johannes WA; Chung, John; Kappeler, Christian; Pena, Carol; Molnár, István; Schlumberger, Martin J

    2015-01-01

    Background Patients with radioactive iodine (131I, RAI)-refractory locally advanced or metastatic differentiated thyroid cancer (DTC) have a poor prognosis due to the lack of effective treatment options. Methods This multicentre, randomized (1:1), double-blind, placebo-controlled, phase 3 study (DECISION; NCT00984282) investigated sorafenib (400 mg orally twice-daily) in patients with RAI-refractory locally advanced or metastatic DTC progressing within the past 14 months. The primary endpoint was progression-free survival (PFS) by central independent review. Patients receiving placebo could crossover to open-label sorafenib upon progression. Archival tumour tissue was examined for BRAF and RAS mutations. Serum thyroglobulin was measured at baseline and each visit. Findings A total of 417 patients were randomized to sorafenib (n=207) or placebo (n=210). Sorafenib treatment significantly improved PFS compared with placebo (hazard ratio, 0·59; 95% confidence interval, 0·45–0·76; P<0·0001; median 10·8 vs. 5·8 months, respectively). PFS improvement was seen in all pre-specified clinical and genetic biomarker subgroups irrespective of mutation status. There was no statistically significant difference in overall survival (hazard ratio, 0·80; 95% confidence interval, 0·54–1·19; P=0·14); median overall survival had not been reached and 150 (71%) patients receiving placebo crossed over to sorafenib upon progression. Response rates (all partial responses) were 12·2% (24/196; sorafenib) and 0·5% (1/201; placebo; p<0·0001). Median thyroglobulin levels increased in the placebo group, and decreased, then paralleled treatment responses in the sorafenib group. Most adverse events were grade 1 or 2. The most common treatment-emergent adverse events in the sorafenib arm were hand–foot skin reaction (76·3%), diarrhoea (68·6%), alopecia (67·1%), and rash/desquamation (50·2%). Interpretation Sorafenib significantly improved PFS compared with placebo in patients

  1. Editorial: Thyroid cancer and the Chernobyl accident

    SciTech Connect

    Williams, D.

    1996-01-01

    The accident at the Chernobyl power station nearly 10 years ago was unprecedented in the exposure of a very large population to high levels of fallout including high levels of isotopes of iodine, predominantly {sup 131}I. An increase in incidence of childhood thyroid cancer was first observed in 1990 in Belarus and in the Ukraine, and the first reports in the Western literature were published in 1992. At a symposium in Nagasaki in June 1994, the numbers of cases that had occurred between 1990 and 1993 in Belarus, a country with a population of just over 10 million, was reported to be 233, and in the heavily contaminated northern parts of the Ukraine, with a population of about 7 million, 36 cases occurred in the same period. To put these figures into perspective, the number of childhood thyroid cancers registered in England and Wales over a 30-year period was 154, an average of 5 cases per yr in a population of 50 million people, with about 10 million children under 15 yr of age. The initial reports of such a great increase in childhood thyroid cancers in the areas exposed to fallout from Chernobyl were at first greeted in the West with some skepticism. The latent period between exposure and development of thyroid cancer was surprisingly short, based on experience with thyroid carcinomas developing after external radiation to the neck. The reliability of the figures based on the pathological diagnosis was questioned because the cases had not been confirmed by Western pathologists, and because the known high frequency of papillary microcarcinoms in adults raised the possibility that the reported incidence was resulted form increased ascertainment and not a true increase in incidence. 14 refs.

  2. Induction of thyroid cancer by ionizing radiation

    SciTech Connect

    Not Available

    1985-01-01

    This report assesses the potential for cancer induction in the thyroid gland after exposure of the gland to external x radiation and gamma radiation and/or some internally deposited radionuclides. Data and assumptions from existing human and animal studies are used to develop average risk estimates for populations over various ranges of radiation dose to the thyroid. The carcinogenicity of various iodine isotopes is examined. A specific model for risk estimation is developed which involves numerous modifications of an absolute risk model for factors such as age at exposure, sex, ethnic background, radiation source, exposure range, and time since exposure. Risk estimates are presented which are considered to be application to the population of the US for mean thyroidal doses in the range from 6 to 1500 rads. 146 references, 1 figures, 18 tables.

  3. Resistance of papillary thyroid cancer stem cells to chemotherapy

    PubMed Central

    GIUFFRIDA, RAFFAELLA; ADAMO, LUANA; IANNOLO, GIOACCHIN; VICARI, LUISA; GIUFFRIDA, DARIO; ERAMO, ADRIANA; GULISANO, MASSIMO; MEMEO, LORENZO; CONTICELLO, CONCETTA

    2016-01-01

    Thyroid carcinoma is the most common endocrine neoplasm, with the highest mortality rate of all the endocrine cancers. Among the endocrine malignancies, ~80% are papillary thyroid carcinomas (PTCs). In the initiation and progression of this tumor, genetic alterations in the mitogen-associated protein kinase pathway, including RAS point mutations, RET/PTC oncogene rearrangements and BRAF point mutations, play an important role, particularly in deciding targeted therapy. In the present study, a small population of thyroid tumor cells, known as tumor spheres, were isolated and characterized from PTC surgical samples. These spheres can be expanded indefinitely in vitro and give rise to differentiated adherent cells when cultivated in differentiative conditions. The present study showed by reverse transcription-polymerase chain reaction and flow cytometric analysis that the undifferentiated PTC cells exhibited a characteristic antigen expression profile of adult progenitor/stem cells. The cells were more resistant to chemotherapeutics, including bortezomib, taxol, cisplatin, etoposide, doxorubicin and vincristine, than differentiated PTC cells and the majority possessed a quiescent status, as revealed by the various cell cycle characteristics and anti-apoptotic protein expression. Such advances in cancer thyroid stem cell biology may provide relevant information for future targeted therapies. PMID:27347201

  4. Radiofrequency Ablation of Benign Thyroid Nodules and Recurrent Thyroid Cancers: Consensus Statement and Recommendations

    PubMed Central

    Na, Dong Gyu; Lee, Jeong Hyun; Jung, So Lyung; Kim, Ji-hoon; Sung, Jin Yong; Shin, Jung Hee; Kim, Eun-Kyung; Lee, Joon Hyung; Kim, Dong Wook; Park, Jeong Seon; Kim, Kyu Sun; Baek, Seon Mi; Lee, Younghen; Chong, Semin; Sim, Jung Suk; Huh, Jung Yin; Bae, Jae-Ik; Kim, Kyung Tae; Han, Song Yee; Bae, Min Young; Kim, Yoon Suk

    2012-01-01

    Thermal ablation using radiofrequency is a new, minimally invasive modality employed as an alternative to surgery in patients with benign thyroid nodules and recurrent thyroid cancers. The Task Force Committee of the Korean Society of Thyroid Radiology has developed recommendations for the optimal use of radiofrequency ablation for thyroid nodules. These recommendations are based on a comprehensive analysis of the current literature, the results of multicenter studies, and expert consensus. PMID:22438678

  5. Increased Pleiotrophin Concentrations in Papillary Thyroid Cancer

    PubMed Central

    Jee, Youn Hee; Sadowski, Samira M.; Celi, Francesco S.; Xi, Liqiang; Raffeld, Mark; Sacks, David B.; Remaley, Alan T.; Wellstein, Anton; Kebebew, Electron; Baron, Jeffrey

    2016-01-01

    Background Thyroid nodules are common, and approximately 5% of these nodules are malignant. Pleiotrophin (PTN) is a heparin-binding growth factor which is overexpressed in many cancers. The expression of PTN in papillary thyroid cancer (PTC) is unknown. Method and Findings 74 subjects (age 47 ± 12 y, 15 males) who had thyroidectomy with a histological diagnosis: 79 benign nodules and 23 PTCs (10 classic, 6 tall cell, 6 follicular variant and 1 undetermined). Fine-needle aspiration (FNA) samples were obtained ex vivo from surgically excised tissue and assayed for PTN and thyroglobulin (Tg). Immunohistochemistry (IHC) was performed on tissue sections. In FNA samples, PTN concentration normalized to Tg was significantly higher in PTC than in benign nodules (16 ± 6 vs 0.3 ± 0.1 ng/mg, p < 0.001). In follicular variant of PTC (n = 6), the PTN/Tg ratio was also higher than in benign nodules (1.3 ± 0.6 vs 0.3 ± 0.1 ng/mg, P < 0.001, respectively). IHC showed cytoplasmic localization of PTN in PTC cells. Conclusion In ex vivo FNA samples, the PTN to thyroglobulin ratio was higher in PTCs, including follicular variant PTC, than in benign thyroid nodules. The findings raise the possibility that measurement of the PTN to Tg ratio may provide useful diagnostic and/or prognostic information in the evaluation of thyroid nodules. PMID:26914549

  6. Responses to Overdiagnosis in Thyroid Cancer Screening among Korean Women

    PubMed Central

    Lee, Sangeun; Lee, Yoon Young; Yoon, Hyo Joong; Choi, Eunji; Suh, Mina; Park, Boyoung; Jun, Jae Kwan; Kim, Yeol; Choi, Kui Son

    2016-01-01

    Purpose Communicating the harms and benefits of thyroid screening is necessary to help individuals decide on whether or not to undergo thyroid cancer screening. This study was conducted to assess changes in thyroid cancer screening intention in response to receiving information about overdiagnosis and to determine factors with the greatest influence thereon. Materials and Methods Data were acquired from subjects included in the 2013 Korean National Cancer Screening Survey (KNCSS), a nationwide, population-based, cross-sectional survey. Of the 4,100 respondents in the 2013 KNCSS, women were randomly subsampled and an additional face-to-face interview was conducted. Finally, a total of 586 female subjects were included in this study. Intention to undergo thyroid cancer screening was assessed before and after receiving information on overdiagnosis. Results Prior awareness of overdiagnosis in thyroid cancer screening was 27.8%. The majority of subjects intended to undergo thyroid cancer screening before and after receiving information on overdiagnosis (87% and 74%, respectively). Only a small number of subjects changed their intention to undergo thyroid cancer screening from positive to negative after receiving information on overdiagnosis. Women of higher education level and Medical Aid Program recipients reported being significantly more likely to change their intention to undergo thyroid cancer screening afterreceiving information on overdiagnosis,whilewomen with stronger beliefs on the efficacy of cancer screening were less likely to change their intention. Conclusion Women in Korea appeared to be less concerned about overdiagnosis when deciding whether or not to undergo thyroid cancer screening. PMID:26727718

  7. TERT Promoter Mutations in Thyroid Cancer.

    PubMed

    Alzahrani, Ali S; Alsaadi, Rawan; Murugan, Avaniyapuram Kannan; Sadiq, Bakr Bin

    2016-06-01

    Two mutations (C228T and C250T) in the promoter region of the telomerase reverse transcriptase (TERT) have recently been described in different types of cancer including follicular cell-derived thyroid cancer (TC). In this paper, we reviewed the rates of these mutations in different types and subtypes of TC, their association with a number of clinical and histopathological features and outcome of TC, and their potential diagnostic and prognostic roles in TC. The overall rate of these mutations in TC is about 14 % with least prevalence in the well-differentiated subtypes of papillary thyroid cancer (10-13 %). Their rates increase significantly with increasing aggressiveness of TC reaching about 40 % in the undifferentiated and anaplastic thyroid cancers. There is also clear association with increasing age of patients at the time of diagnosis of TC. The evidence is compelling but with some conflicting results for associations between TERT promoter mutations and tumor size, extrathyroidal invasion, distant metastases, high tumor TNM stage, BRAF (V600E) mutation, recurrence, and mortality. A couple of studies reported a potential diagnostic role for TERT promoter mutations in thyroid nodules with indeterminate cytology of fine needle aspiration biopsy. These studies showed 100 % specificity but very low sensitivity of 7-10 %. The sensitivity increases significantly when TERT promoter mutation testing is combined with other gene mutations, particularly BRAF (V600E) and RAS mutations. Although TERT promoter mutations seem to play significant roles in the pathogenesis of TC, the mechanisms by which they contribute to carcinogenesis remain elusive and future work is needed to fully assess the roles, interactions, and impact of these mutations on the pathogenesis, diagnosis, prognosis, and therapeutics of TC. PMID:26902827

  8. Targeted Therapy Shows Benefit in Rare Type of Thyroid Cancer

    Cancer.gov

    Treatment with the multitargeted agent vandetanib (Caprelsa) improved progression-free survival in patients with medullary thyroid cancer (MTC), according to findings from a randomized clinical trial.

  9. Thyroid nodule

    MedlinePlus

    ... 2016:chap 14. Read More Chronic thyroiditis (Hashimoto disease) Laryngeal nerve damage Multiple endocrine neoplasia (MEN) II Thyroid cancer Thyroid cancer - medullary carcinoma Thyroid gland removal Patient Instructions Thyroid gland ...

  10. Thyroid cancer following radiotherapy for Hodgkin's disease: a case report and review of the literature

    SciTech Connect

    Moroff, S.V.; Fuks, J.Z.

    1986-01-01

    Improved survival resulting from advances in therapy in patients with Hodgkin's disease is associated with long-term morbidity, including the potential for the development of a second solid malignancy. We report a 44-year-old man with an unusually aggressive course of thyroid carcinoma 15 years after treatment for Hodgkin's disease. In a review of the English-language literature, we found 21 cases of thyroid cancer following radiotherapy for Hodgkin's disease, with latency periods ranging from 6 to 48 years. The development of secondary thyroid cancer after high-dose neck irradiation may be related to hypothyroidism, itself a complication of radiotherapy. Thyroid function should be measured at least once a year in all patients given neck irradiation, with initiation of thyroid hormone replacement if there is evidence of sustained hypothyroidism.

  11. h-prune affects anaplastic thyroid cancer invasion and metastasis.

    PubMed

    Nambu, Junko; Kobayashi, Tsuyoshi; Hashimoto, Masakazu; Tashiro, Hirotaka; Sugino, Keizo; Shimamoto, Fumio; Kikuchi, Akira; Ohdan, Hideki

    2016-06-01

    Anaplastic thyroid cancer is one of the most aggressive human malignancies and is resistant to multimodal treatments. The expression of h-prune, the human homologue of Drosophila prune, has been reported to be correlated with progression and aggressiveness in various cancers including breast, colorectal and pancreatic cancers. We examined the role of h-prune in anaplastic thyroid cancer cell migration, invasion and metastasis. Immunohistochemical analysis of h-prune was performed with 15 surgically resected specimens of anaplastic thyroid cancers. To investigate cell motility, Boyden chamber, wound healing and matrigel invasion assays were performed using cells from anaplastic thyroid cancer cell lines. A murine orthotopic thyroid cancer model was used to investigate metastatic ability. In the immunohistochemical analysis, only weak focal or no staining of h-prune was observed in non-tumor tissue. In contrast, diffuse staining of h-prune was observed in anaplastic thyroid cancer and lymph node metastasis samples. Both inhibition of h-prune phosphodiesterase activity with dipyridamole and small interfering RNA for h-prune suppressed 8505C and KTC-3 cell motility. In addition, treatment with dipyridamole and decreased expression of h-prune suppressed tumor invasion and pulmonary metastasis in a NOD/Shi-scid, IL-2Rγnull (NOG) mouse orthotopic thyroid cancer model. In conclusion, h-prune is frequently expressed in anaplastic thyroid cancer cells and lymph nodes metastasis, and promotes migration and invasion of anaplastic thyroid cancer cells and metastasis in an anaplastic thyroid cancer model. Thus, h-prune shows promise as a targeting candidate against anaplastic thyroid cancer. PMID:27109060

  12. Mitochondrial Metabolism as a Treatment Target in Anaplastic Thyroid Cancer.

    PubMed

    Johnson, Jennifer M; Lai, Stephen Y; Cotzia, Paolo; Cognetti, David; Luginbuhl, Adam; Pribitkin, Edmund A; Zhan, Tingting; Mollaee, Mehri; Domingo-Vidal, Marina; Chen, Yunyun; Campling, Barbara; Bar-Ad, Voichita; Birbe, Ruth; Tuluc, Madalina; Martinez Outschoorn, Ubaldo; Curry, Joseph

    2015-12-01

    Anaplastic thyroid cancer (ATC) is one of the most aggressive human cancers. Key signal transduction pathways that regulate mitochondrial metabolism are frequently altered in ATC. Our goal was to determine the mitochondrial metabolic phenotype of ATC by studying markers of mitochondrial metabolism, specifically monocarboxylate transporter 1 (MCT1) and translocase of the outer mitochondrial membrane member 20 (TOMM20). Staining patterns of MCT1 and TOMM20 in 35 human thyroid samples (15 ATC, 12 papillary thyroid cancer [PTC], and eight non-cancerous thyroid) and nine ATC mouse orthotopic xenografts were assessed by visual and Aperio digital scoring. Staining patterns of areas involved with cancer versus areas with no evidence of cancer were evaluated independently where available. MCT1 is highly expressed in human anaplastic thyroid cancer when compared to both non-cancerous thyroid tissues and papillary thyroid cancers (P<.001 for both). TOMM20 is also highly expressed in both ATC and PTC compared to non-cancerous thyroid tissue (P<.01 for both). High MCT1 and TOMM20 expression is also found in ATC mouse xenograft tumors compared to non-cancerous thyroid tissue (P<.001). These xenograft tumors have high (13)C- pyruvate uptake. ATC has metabolic features that distinguish it from PTC and non-cancerous thyroid tissue, including high expression of MCT1 and TOMM20. PTC has low expression of MCT1 and non-cancerous thyroid tissue has low expression of both MCT1 and TOMM20. This work suggests that MCT1 blockade may specifically target ATC cells presenting an opportunity for a new drug target. PMID:26615136

  13. Personalized Medicine Based on Theranostic Radioiodine Molecular Imaging for Differentiated Thyroid Cancer

    PubMed Central

    2016-01-01

    Molecular imaging based personalized therapy has been a fascinating concept for individualized therapeutic strategy, which is able to attain the highest efficacy and reduce adverse effects in certain patients. Theranostics, which integrates diagnostic testing to detect molecular targets for particular therapeutic modalities, is one of the key technologies that contribute to the success of personalized medicine. Although the term “theranostics” was used after the second millennium, its basic principle was applied more than 70 years ago in the field of thyroidology with radioiodine molecular imaging. Differentiated thyroid cancer, which arises from follicular cells in the thyroid, is the most common endocrine malignancy, and theranostic radioiodine has been successfully applied to diagnose and treat differentiated thyroid cancer, the applications of which were included in the guidelines published by various thyroid or nuclear medicine societies. Through better pathophysiologic understanding of thyroid cancer and advancements in nuclear technologies, theranostic radioiodine contributes more to modern tailored personalized management by providing high therapeutic effect and by avoiding significant adverse effects in differentiated thyroid cancer. This review details the inception of theranostic radioiodine and recent radioiodine applications for differentiated thyroid cancer management as a prototype of personalized medicine based on molecular imaging. PMID:27239470

  14. Personalized Medicine Based on Theranostic Radioiodine Molecular Imaging for Differentiated Thyroid Cancer.

    PubMed

    Ahn, Byeong-Cheol

    2016-01-01

    Molecular imaging based personalized therapy has been a fascinating concept for individualized therapeutic strategy, which is able to attain the highest efficacy and reduce adverse effects in certain patients. Theranostics, which integrates diagnostic testing to detect molecular targets for particular therapeutic modalities, is one of the key technologies that contribute to the success of personalized medicine. Although the term "theranostics" was used after the second millennium, its basic principle was applied more than 70 years ago in the field of thyroidology with radioiodine molecular imaging. Differentiated thyroid cancer, which arises from follicular cells in the thyroid, is the most common endocrine malignancy, and theranostic radioiodine has been successfully applied to diagnose and treat differentiated thyroid cancer, the applications of which were included in the guidelines published by various thyroid or nuclear medicine societies. Through better pathophysiologic understanding of thyroid cancer and advancements in nuclear technologies, theranostic radioiodine contributes more to modern tailored personalized management by providing high therapeutic effect and by avoiding significant adverse effects in differentiated thyroid cancer. This review details the inception of theranostic radioiodine and recent radioiodine applications for differentiated thyroid cancer management as a prototype of personalized medicine based on molecular imaging. PMID:27239470

  15. A review on thyroid cancer during pregnancy: Multitasking is required.

    PubMed

    Khaled, Hussein; Al Lahloubi, Nasr; Rashad, Noha

    2016-07-01

    Thyroid cancer is the second most common cancer diagnosed during pregnancy after breast cancer. The goal of management is to control malignancy and prevent maternal and fetal complications as a result of maternal hypothyroidism. The role of female sex hormones as an etiologic factor was investigated, with no clear association. Pregnancy can cause an increase in size of a previously existed thyroid nodule through the structural similarity between TSH and BHCG, and the normally expressed estrogen receptors on thyroid gland cells. Effect of pregnancy on development and prognosis of differentiated thyroid malignancies (papillary and follicular) has also been studied. The prognosis of thyroid cancer is not worse in patients diagnosed during pregnancy or those who got pregnant after curative treatment. Termination of pregnancy is not indicated at all, surgery can be delayed till after delivery except in rapidly growing aggressive tumors. While radioactive iodine ablation is absolutely contra-indicated, the new systemic therapies are not well studied during pregnancy. However, almost all these new agents are classified as FDA category C or D and are better to be avoided. The effect of pregnancy on other types of thyroid cancer (medullary and anaplastic thyroid tumors) is not well studied because of very low incidence with pregnancy. The endocrinological management of thyroid cancer during pregnancy is of utmost importance. The hypothyroidism after total thyroidectomy can cause fetal hypothyroidism. Therefore, the management of thyroid cancer related to pregnancy needs a multidisciplinary team. PMID:27408758

  16. Anaplastic thyroid cancer: multimodal treatment results

    PubMed Central

    Aslan, Zaki Antonio Taissoun; Granados-García, Martín; Luna-Ortiz, Kuauhyama; Guerrero-Huerta, Francisco Javier; Gómez-Pedraza, Antonio; Ñamendys-Silva, Silvio A; Meneses-García, Abelardo; Ordoñez-Mosquera, Juliana María

    2014-01-01

    Background Anaplastic thyroid cancer is a rare and lethal disease. It accounts for 1–2% of thyroid malignancies, but specific mortality is higher than 90%. It is an aggressive locoregional disease with a high metastatic capacity. There is no agreement with regards to the best treatment. We analysed the results of treatment in a mestizo population treated in the National Cancer Institute (Mexico). Methods We reviewed 1,581 files of thyroid carcinomas; of these, 29 (1.83%) had anaplastic thyroid carcinoma. Demographic variables, clinical manifestations, tumour characteristics, and treatments were analysed. Results The median age was 64.5 ± 13.2 years. Females were more affected (female/male ratio: 2.6:1); 21 cases occurred in women (72.4%), and eight in males (27.6%). The most common manifestations were neck enlargement (93.10%) and hoarseness (71.31%). The median tumour size was 8 cm (range: 4–20 cm). The percentage of cases which presented in clinical stage IVA was 10.3%, with 62.1% presenting in clinical stage IVb and 27.6% presenting in clinical stage VIc. Complete resection (R0) (p = 0.05), radiation doses of higher than 33.1 Gy (p = 0.04), and multimodal therapy were associated with better survival. Surgery plus radiotherapy with or without systemic treatment (p = 0.006). The median overall survival was 119 days (IC 95%, 36.3–201.6). Six-month, one-year and two-year survival was 37.9%, 21% and 13%, respectively. Conclusion Complete surgical resection is associated with better survival but is very difficult to achieve due to aggressive biological behaviour. Multimodal therapy is associated with better survival and a better quality of life. There is a need for more effective systemic treatments as extensive surgical resections have little overall benefit in highly invasive and metastatic disease. PMID:25114721

  17. Molecular profiles of cancer stem-like cell populations in aggressive thyroid cancers.

    PubMed

    Dima, Mariavittoria; Pecce, Valeria; Biffoni, Mauro; Di Gioia, Cira Rosaria Tiziana; Tallini, Giovanni; Biffoni, Marco; Rosignolo, Francesca; Verrienti, Antonella; Sponziello, Marialuisa; Damante, Giuseppe; Russo, Diego; Durante, Cosimo

    2016-07-01

    A substantial proportion of patients with advanced thyroid carcinoma fail to respond to or at some point become refractory to conventional therapies. This resistance and the phenomena of thyroid cancer progression and metastasis themselves are thought to be related to tumor-cell sub-populations with stem-like properties. We isolated thyrospheres from four advanced thyroid carcinomas that were resistant to radioiodine therapy and analyzed their molecular profiles. ALDH activity and proteomic profile of main stem cell markers were used to assess stem cell properties. The TaqMan Low Density Array approach was used to evaluate the expression of several genes involved in the EMT process. The phosphorylation status of tyrosine kinase receptors (RTKs) was analyzed to identify potential markers for targeted therapies. We then investigated the effects of the EMT-inhibitor crizotinib on both cell proliferation and phosphorylation status of RTK targets. The cancer stem-like properties of a subset of cells from primary cultures of each tumor were demonstrated. A wide variability among thyrospheres arising from the four thyroid cancers in terms of ALDH activity, stem cell marker expression, and phosphoproteome profiling was present. Dysregulated expression of genes involved in the EMT was observed in all four thyrosphere lines. Treatment with crizotinib was ineffective in cancer stem-like cells, suggesting the presence of a mechanism of resistance in thyrospheres. Collectively, our data indicate that thyroid cancer stem-like populations vary markedly from tumor to tumor and require detailed molecular and biological characterization if they are to be used as the basis of "personalized" treatment of aggressive disease. PMID:26370117

  18. Neutron therapy for salivary and thyroid gland cancer

    NASA Astrophysics Data System (ADS)

    Gribova, O. V.; Musabaeva, L. I.; Choynzonov, E. L.; Lisin, V. A.; Novikov, V. A.

    2016-08-01

    The purpose of this study was to analyze the results of the combined modality treatment and radiation therapy using 6.3 MeV fast neutrons for salivary gland cancer and prognostically unfavorable thyroid gland cancer. The study group comprised 127 patients with salivary gland cancer and 46 patients with thyroid gland cancer, who received neutron therapy alone and in combination with surgery. The results obtained demonstrated that the combined modality treatment including fast neutron therapy led to encouraging local control in patients with salivary and thyroid gland cancers.

  19. Thyroid scan

    MedlinePlus

    ... Read More Anaplastic thyroid cancer Cancer Goiter - simple Hyperthyroidism Multiple endocrine neoplasia (MEN) II PET scan Skin ... A.M. Editorial team. Related MedlinePlus Health Topics Hyperthyroidism Hypothyroidism Nuclear Scans Thyroid Cancer Thyroid Diseases Thyroid ...

  20. Trends of Thyroid Cancer in Israel: 1980–2012

    PubMed Central

    Keinan-Boker, Lital; Silverman, Barbara G.

    2016-01-01

    Objectives: Thyroid cancer incidence is increasing worldwide, while mortality from thyroid cancer is stable or decreasing. Consequently, survival rates are rising. We describe time trends in the incidence, mortality, and 5-year survival of thyroid cancer in Israel in 1980–2012, in light of the global trends. Methods: Israel National Cancer Registry database provided information regarding thyroid cancer incidence and vital status, which enabled computation of survival rates. The Central Bureau of Statistics database provided information on thyroid cancer mortality. Incidence and mortality rates were age-adjusted and presented by population group (Jews/Arabs) and gender. Relative 5-year survival rates which account for the general population survival in the corresponding time period were presented by population group and gender. Joinpoint analyses were used to assess incidence trends over time. Results: In 1980–2012 significant increases in the incidence of thyroid cancer were observed, with an annual percent change (APC) range of 3.98–6.93, driven almost entirely by papillary carcinoma (APCs 5.75–8.86), while rates of other types of thyroid cancer remained stable or decreased. Furthermore, higher rates of early detection were noted. In 1980–2012, a modest reduction in thyroid cancer mortality was observed in Jewish women (APC −1.07) with no substantial change in Jewish men. The 5-year relative survival after thyroid cancer diagnosis has increased to ≥90% in both population groups and both genders. Conclusions: The Israeli secular trends of thyroid cancer incidence (increasing), mortality (mostly stable), and survival (modestly increasing) closely follow reported global trends. PMID:26886958

  1. Predicting Malignancy in Thyroid Nodules: Molecular Advances

    PubMed Central

    Melck, Adrienne L.; Yip, Linwah

    2016-01-01

    Over the last several years, a clearer understanding of the genetic alterations underlying thyroid carcinogenesis has developed. This knowledge can be utilized to tackle one of the greatest challenges facing thyroidologists: management of the indeterminate thyroid nodule. Despite the accuracy of fine needle aspiration cytology, many patients undergo invasive surgery in order to determine if a follicular or Hurthle cell neoplasm is malignant, and better diagnostic tools are required. A number of biomarkers have recently been studied and show promise in this setting. In particular, BRAF, RAS, PAX8-PPARγ, microRNAs and loss of heterozygosity have each been demonstrated as useful molecular tools for predicting malignancy and can thereby guide decisions regarding surgical management of nodular thyroid disease. This review summarizes the current literature surrounding each of these markers and highlights our institution’s prospective analysis of these markers and their subsequent incorporation into our management algorithms for thyroid nodules. PMID:21818817

  2. Treatment Options by Stage (Thyroid Cancer)

    MedlinePlus

    ... glands make hormones. The thyroid uses iodine , a mineral found in some foods and in iodized salt, ... Fine-needle aspiration biopsy of the thyroid : The removal of thyroid tissue using a thin needle. The ...

  3. Radioiodine and radiotherapy in the management of thyroid cancers

    SciTech Connect

    Simpson, W.J. )

    1990-06-01

    Radioiodine is an important adjuvant treatment in the management of resectable papillary and follicular thyroid cancers in all patients except those with the best prognostic features. External radiation is also an important adjuvant therapy in these patients, especially those with tumors that extend beyond the thyroid gland and invade the trachea, esophagus, nerves, and blood vessels; it is especially important in treating patients whose tumors do not concentrate radioiodine. Radioiodine may be curative in patients with microscopic distant metastases demonstrated by radioiodine scanning. Even unresectable primary papillary and follicular cancers may be eradicated by combined therapy with radioiodine and radiotherapy. Radioiodine plays no significant role in the treatment of medullary or anaplastic thyroid cancers, but external radiation may eradicate microscopic thyroid bed or nodal disease when persistent disease is indicated by elevated calcitonin levels in medullary thyroid cancer patients. Anaplastic thyroid cancers are usually unresectable and are not eradicated by conventional radiotherapy or by any of the novel radiation techniques, with or without chemotherapy. In all types of thyroid cancer, external radiotherapy may produce beneficial palliative results in patients with distant metastases, but the use of radioiodine should always be explored in papillary and follicular thyroid cancer patients. 30 references.

  4. Dietary Factors and the Risk of Thyroid Cancer: A Review

    PubMed Central

    Choi, Wook Jin

    2014-01-01

    In the past few decades, the incidence of thyroid cancer has rapidly increased worldwide. Thyroid cancer incidence is relatively high in regions where the population's daily iodine intake is insufficient. While low dietary iodine has been considered as a risk factor for thyroid cancer development, previous studies found controversial results across different food types. Among different ethnic groups, dietary factors are influenced by various dietary patterns, eating habits, life-styles, nutrition, and other environmental factors. This review reports the association between dietary factors and thyroid cancer risk among ethnic groups living in different geologic regions. Iodine-rich food such as fish and shellfish may provide a protective role in populations with insufficient daily iodine intake. The consumption of goitrogenic food, such as cruciferous vegetables, showed a positive association with risk. While considered to be a risk factor for other cancers, alcohol intake showed a protective role against thyroid cancer. High consumption of meat such as chicken, pork, and poultry showed a positive association with the risk, but dairy products showed no significant association. Regular use of multivitamins and dietary nitrate and nitrite also showed a positive association with thyroid cancer risk. However, the study results are inconsistent and investigations into the mechanism for how dietary factors change thyroid hormone levels and influence thyroid function are required. PMID:25136535

  5. Thyroid Fine-Needle Aspiration Biopsy and Thyroid Cancer Diagnosis: A Nationwide Population-Based Study

    PubMed Central

    Huang, Li-Ying; Lee, Ya-Ling; Chou, Pesus; Chiu, Wei-Yih; Chu, Dachen

    2015-01-01

    Background Thyroid cancer is the most common endocrine gland malignancy and fine-needle aspiration biopsy is widely used for thyroid nodule evaluation. Repeated aspiration biopsies are needed due to plausible false-negative results. This study aimed to investigate the overall relationship between aspiration biopsy and thyroid cancer diagnosis, and to explore factors related to shorter diagnostic time. Methods This nationwide retrospective cohort study retrieved data from the Longitudinal Health Insurance Database in Taiwan. Subjects without known thyroid malignancies and who received the first thyroid aspiration biopsy after 2004 were followed-up from 2004 to 2009 (n = 7700). Chi-square test, Kaplan-Meier survival analysis, and Cox proportional hazards model were used for data analysis. Results Of 7700 newly-aspirated patients, 276 eventually developed thyroid cancer (malignancy rate 3.6%). Among the 276 patients with thyroid cancer, 61.6% underwent only one aspiration biopsy and 81.2% were found within the first year after the initial aspiration. Cox proportional hazards model revealed that aspiration frequency (HR 1.07, 95% CI 1.06–1.08), ultrasound frequency (HR 1.02, 95% CI 1.01–1.03), older age, male sex, and aspiration biopsies arranged by surgery, endocrinology or otolaryngology subspecialties were all associated with shorter time to thyroid cancer diagnosis. Conclusions About 17.4% of thyroid cancer cases received more than two aspiration biopsies and 18.8% were diagnosed one year after the first biopsy. Regular follow-up with repeated aspiration or ultrasound may be required for patients with clinically significant thyroid nodules. PMID:26020790

  6. Thyroid cancer incidence in relation to volcanic activity

    SciTech Connect

    Arnbjoernsson, E.A.; Arnbjoernsson, A.O.; Olafsson, A.

    1986-01-01

    Environmental or genetic factors are sought to explain the high incidence of thyroid cancer in Iceland. At present, it is impossible to cite any environmental factor, particularly one related to the volcanic activity in the country, which could explain the high incidence of thyroid cancer in Iceland. However, the thyroid gland in Icelanders is very small due to the high intake of iodine from seafood. It is, therefore, easier for physicians to find thyroid tumors. Furthermore, genetic factors are very likely to be of great importance in the small, isolated island of Iceland.

  7. Spotlight on lenvatinib in the treatment of thyroid cancer: patient selection and perspectives

    PubMed Central

    Costa, Ricardo; Carneiro, Benedito A; Chandra, Sunandana; Pai, Sachin G; Chae, Young Kwang; Kaplan, Jason B; Garrett, Hannah B; Agulnik, Mark; Kopp, Peter A; Giles, Francis J

    2016-01-01

    Thyroid cancer is the most common endocrine malignancy, with over 60,000 cases reported per year in the US alone. The incidence of thyroid cancer has increased in the last several years. Patients with metastatic differentiated thyroid cancer (DTC) generally have a good prognosis. Metastatic DTC can often be treated in a targeted manner with radioactive iodine, but the ability to accumulate iodine is lost with decreasing differentiation. Until recently, chemotherapy was the only treatment in patients with advanced thyroid cancer, which is no longer amenable to therapy with radioactive iodine. The modest efficacy and significant toxicity of chemotherapy necessitated the need for urgent advances in the medical field. New insights in thyroid cancer biology propelled the development of targeted therapies for this disease, including the tyrosine kinase inhibitor sorafenib as salvage treatment for DTC. In 2015, the US Food and Drug Administration approved a second tyrosine kinase inhibitor, lenvatinib, for the treatment of radioiodine-refractory thyroid cancer. Although associated with a significant progression-free survival improvement as compared to placebo in a large Phase III study (median progression-free survival 18.2 vs 3.6 months; hazard ratio 0.21; 99% confidence interval 0.14–0.31; P<0.001), the benefit of lenvatinib needs to be proved in the context of associated moderate to severe toxicities that require frequent dose reduction and delays. This article reviews the evidence supporting the use of lenvatinib as salvage therapy for radioactive iodine-refractory thyroid cancer, with a focus on the toxicity profile of this new therapy. PMID:27013865

  8. Standardized Thyroid Cancer Mortality in Korea between 1985 and 2010

    PubMed Central

    Choi, Yun Mi; Jang, Eun Kyung; Kwon, Hyemi; Jeon, Min Ji; Kim, Won Gu; Shong, Young Kee; Kim, Won Bae

    2014-01-01

    Background The prevalence of thyroid cancer has increased very rapidly in Korea. However, there is no published report focusing on thyroid cancer mortality in Korea. In this study, we aimed to evaluate standardized thyroid cancer mortality using data from Statistics Korea (the Statistical Office of Korea). Methods Population and mortality data from 1985 to 2010 were obtained from Statistics Korea. Age-standardized rates of thyroid cancer mortality were calculated according to the standard population of Korea, as well as World Health Organization (WHO) standard population and International Cancer Survival Standard (ICSS) population weights. Results The crude thyroid cancer mortality rate increased from 0.1 to 0.7 per 100,000 between 1985 and 2010. The pattern was the same for both sexes. The age-standardized mortality rate (ASMR) for thyroid cancer for Korean resident registration population increased from 0.19 to 0.67 between 1985 and 2000. However, it decreased slightly, from 0.67 to 0.55, between 2000 and 2010. When mortality was adjusted using the WHO standard population and ICSS population weights, the ASMR similarly increased until 2000, and then decreased between 2000 and 2010. Conclusion Thyroid cancer mortality increased until 2000 in Korea. It started to decrease from 2000. PMID:25559576

  9. Selective use of sorafenib in the treatment of thyroid cancer

    PubMed Central

    Pitoia, Fabián; Jerkovich, Fernando

    2016-01-01

    Sorafenib is a multiple kinase inhibitor (MKI) approved for the treatment of primary advanced renal cell carcinoma and advanced primary liver cancer. It was recently approved by several health agencies around the world as the first available MKI treatment for radioactive iodine-refractory advanced and progressive differentiated thyroid cancer. Sorafenib targets C-RAF, B-RAF, VEGF receptor-1, -2, -3, PDGF receptor-β, RET, c-kit, and Flt-3. As a multifunctional inhibitor, sorafenib has the potential of inhibiting tumor growth, progression, metastasis, and angiogenesis and downregulating mechanisms that protect tumors from apoptosis and has shown to increase the progression-free survival in several Phase II trials. This led to the Phase III trial (DECISION) which showed that there was an improvement in progression-free survival of 5 months for patients on sorafenib when compared to those on placebo. Adverse events with this drug are common but usually manageable. The development of resistance after 1 or 2 years is almost a rule in most patients who showed partial response or stabilization of the disease while on sorafenib, which makes it necessary to think of a plan for subsequent therapies. These may include the use of another MKI, such as lenvatinib, the second approved MKI for advanced differentiated thyroid cancer, or include patients in clinical trials or the off-label use of other MKIs. Given sorafenib’s earlier approval, most centers now have access to its prescription. The goal of this review was to improve the care of these patients by describing key aspects that all prescribers will need to master in order to optimize outcomes. PMID:27042004

  10. Medical Management of Metastatic Medullary Thyroid Cancer

    PubMed Central

    Maxwell, Jessica E.; Sherman, Scott K.; O’Dorisio, Thomas M.; Howe, James R.

    2014-01-01

    Medullary thyroid cancer (MTC) is an aggressive form of thyroid cancer, which occurs in both heritable and sporadic forms. Discovery that mutations in the RET protooncogene predispose to familial cases of this disease has allowed for presymptomatic identification of gene carriers and prophylactic surgery to improve the prognosis of these patients. A significant number of patients with the sporadic type of MTC and even with familial disease, still present with nodal or distant metastases, making surgical cure difficult. Over the past several decades, many different types of therapy for metastatic disease have been attempted, with limited success. Improved understanding of the molecular defects and pathways involved in both familial and sporadic MTC has resulted in new hope for these patients with the development of drugs targeting the specific alterations responsible. This new era of targeted therapy with kinase inhibitors represents a significant step forward from previous trials of chemotherapy, radiotherapy, and hormonal therapy. Although much progress has been made, additional agents and strategies are needed to achieve durable, long-term responses in patients with metastatic MTC. This article reviews the history and results of medical management for metastatic MTC from the early 1970s up until the present day. PMID:24942936

  11. Tumour suppressive function of HUWE1 in thyroid cancer.

    PubMed

    Ma, Weiyuan; Zhao, Pengxin; Zang, Leilei; Zhang, Kaili; Liao, Haiying; Hu, Zhigang

    2016-09-01

    HUWE1 (the HECT, UBA, and WWE domain-containing protein 1) is an ubiquitin E3 ligase which plays an important role in coordinating diverse cellular processes. It has been found to be dysregulated in various cancer type and its functions in tumorigenesis remain controversial. The potential tumour suppressive role of HUWE1 in thyroid cancer development was investigated by knocking down HUWE1 in three authentic thyroid cancer cell lines, WRO, FTC133 and BCPAP, followed by various functional assays, including cell proliferation, scratch wound healing and invasion assays. Xenograft experiment was performed to examine in vivo tumour suppressive properties of HUWE1. Small-interfering RNA mediated knockdown of HUWE1 promoted cell proliferation, cell migration and invasion in thyroid cancer cells. Overexpression of HUWE1 conferred partial sensitivity to chemo drugs interfering with DNA replication in these cells. Moreover, HUWE1 was found to be down-regulated in human thyroid cancer tissues compared with matched normal thyroid tissues. In addition, overexpression of HUWE1 significantly inhibited tumour growth in vivo using xenograft mouse models. Mechanistic investigation revealed that HUWE1 can regulate p53 protein level through its stabilization. HUWE1 functions as a tumour suppressor in thyroid cancer progression, which may represent a novel therapeutic target for prevention or intervention of thyroid cancer. PMID:27581931

  12. Selective use of vandetanib in the treatment of thyroid cancer

    PubMed Central

    Fallahi, Poupak; Di Bari, Flavia; Ferrari, Silvia Martina; Spisni, Roberto; Materazzi, Gabriele; Miccoli, Paolo; Benvenga, Salvatore; Antonelli, Alessandro

    2015-01-01

    Vandetanib is a once-daily orally available tyrosine kinase inhibitor that works by blocking RET (REarranged during Transfection), vascular endothelial growth factor receptor (VEGFR-2, VEGFR-3), and epidermal growth factor receptor and to a lesser extent VEGFR-1, which are important targets in thyroid cancer (TC). It is emerging as a potentially effective option in the treatment of advanced medullary thyroid cancer (MTC) and in dedifferentiated papillary thyroid cancer not responsive to radioiodine. The most important effect of vandetanib in aggressive MTC is a prolongation of progression-free survival and a stabilization of the disease. Significant side effects have been observed with the vandetanib therapy (as fatigue, hypertension, QTc prolongation, cutaneous rash, hand-and-foot syndrome, diarrhea, etc), and severe side effects can require the suspension of the drug. Several studies are currently under way to evaluate the long-term efficacy and tolerability of vandetanib in MTC and in dedifferentiated papillary TC. The efficacy of vandetanib in patients with MTC in long-term treatments could be overcome by the resistance to the drug. However, the effectiveness of the treatment could be ameliorated by the molecular characterization of the tumor and by the possibility to test the sensitivity of primary TC cells from each subject to different tyrosine kinase inhibitor. Association studies are evaluating the effect of the association of vandetanib with other antineoplastic agents (such as irinotecan, bortezomib, etc). Further research is needed to determine the ideal therapy to obtain the best response in terms of survival and quality of life. PMID:26170630

  13. Determinants of papillary cancer of the thyroid

    SciTech Connect

    Wingren, G.; Hatschek, T.; Axelson, O. )

    1993-10-01

    Determinants of papillary thyroid cancer were evaluated in a questionnaire-based case-control study from southeastern Sweden. A total of 104 cases, diagnosed from 1977 to 1987, and 387 randomly selected controls were included in the analyses. Female subjects with papillary cancer reported a work history as dentists/dental assistants, telephone operators, teachers, and day nursery personnel, and an occupational contact with chemicals and video display terminals more often than did controls. The 11 male cases more often reported working as mechanics and metal workers and having occupational contact with solvents. Other factors associated with increased risk for female papillary cancer were having private well water at the birth address; leisure time exposure to combustion smoke; low intake of cruciferous vegetables and seafood; and a family history of goiter, heart disease, biliary disorder, or female genital cancer. Diagnostic radiographic examinations, especially to the head, neck, or upper back/chest area, or repeated dental examinations, were also found to be associated with this form of cancer. With regard to the possible influence from hormonal factors among women less than age 50 years at time of diagnosis, an increased risk was found for a pregnancy soon after puberty. Tendencies toward a decreasing risk with increasing age at first pregnancy as well as an increasing risk with increasing number of pregnancies were found as well. Multiparity seemed to potentiate the effect from prior radiographic examinations.

  14. Radiation Exposure and the Risk of Pediatric Thyroid Cancer

    PubMed Central

    Miyakawa, Megumi

    2014-01-01

    Abstract It has been more than three years since the unprecedentedly massive earthquake and tsunami struck eastern Japan on March 11, 2011, and the large accident occurred at the Fukushima Daiichi Nuclear Power Plant. To investigate the influence of radiation exposure, thyroid ultrasonography has been provided preliminarily for 360,000 children who lived in Fukushima Prefecture at the time of the accident. As of September 2013, 59 children had been diagnosed with thyroid cancer by fine-needle aspiration cytology, and 34 children had been treated surgically and ultimately diagnosed with papillary thyroid cancer. Here, I would like to describe the characteristics of pediatric thyroid cancer and typical thyroid images obtained by ultrasonography. PMID:25110391

  15. Immune Response in Thyroid Cancer: Widening the Boundaries

    PubMed Central

    Ward, Laura Sterian

    2014-01-01

    The association between thyroid cancer and thyroid inflammation has been repeatedly reported and highly debated in the literature. In fact, both molecular and epidemiological data suggest that these diseases are closely related and this association reinforces that the immune system is important for thyroid cancer progression. Innate immunity is the first line of defensive response. Unlike innate immune responses, adaptive responses are highly specific to the particular antigen that induced them. Both branches of the immune system may interact in antitumor immune response. Major effector cells of the immune system that directly target thyroid cancer cells include dendritic cells, macrophages, polymorphonuclear leukocytes, mast cells, and lymphocytes. A mixture of immune cells may infiltrate thyroid cancer microenvironment and the balance of protumor and antitumor activity of these cells may be associated with prognosis. Herein, we describe some evidences that immune response may be important for thyroid cancer progression and may help us identify more aggressive tumors, sparing the vast majority of patients from costly unnecessary invasive procedures. The future trend in thyroid cancer is an individualized therapy. PMID:25328756

  16. Exhaled breath volatile biomarker analysis for thyroid cancer.

    PubMed

    Guo, Lei; Wang, Changsong; Chi, Chunjie; Wang, Xiaoyang; Liu, Shanshan; Zhao, Wei; Ke, Chaofu; Xu, Guowang; Li, Enyou

    2015-08-01

    Compared with other types of cancer, thyroid cancer incidence rates have increased rapidly worldwide in the past few decades. In recent years, potential thyroid cancer biomarkers have been studied, but these biomarkers have neither specificity nor good positive predictive value. Exhaled breath analysis is a recently developed convenient and noninvasive method for screening and diagnosing the disease. In this study, potential thyroid cancer biomarkers in volatile organic compounds (VOCs) were detected. Exhaled breath was collected from 64 patients with histologically confirmed cases of thyroid disease (including 39 individuals with papillary thyroid carcinoma and 25 individuals with nodular goiters) and 32 healthy volunteers. Solid-phase microextraction-gas chromatography and mass spectrometry was used to assess the exhaled VOCs of the study participants. The statistical methods of principal component analysis and partial least-squares discriminant analysis were performed to process the final data. The VOCs exhibited significant differences between nodular goiter patients and normal controls, papillary thyroid carcinoma patients and normal controls, and papillary thyroid carcinoma patients and nodular goiter patients; 7, 7, and 3 characteristic metabolites played decisive roles in sample classification, respectively. Breath analysis may provide a new, noninvasive, and directly qualitative method for the clinical diagnosis of thyroid disease. PMID:25666355

  17. Thyroid Hormones, Autoantibodies, Ultrasonography, and Clinical Parameters for Predicting Thyroid Cancer

    PubMed Central

    He, Lin-zheng; Zeng, Tian-shu; Pu, Lin; Pan, Shi-xiu; Xia, Wen-fang; Chen, Lu-lu

    2016-01-01

    Our objective was to evaluate thyroid nodule malignancy prediction using thyroid function tests, autoantibodies, ultrasonographic imaging, and clinical data. We conducted a retrospective cohort study in 1400 patients with nodular thyroid disease (NTD). The thyroid stimulating hormone (TSH) concentration was significantly higher in patients with differentiated thyroid cancer (DTC) versus benign thyroid nodular disease (BTND) (p = 0.004). The receiver operating characteristic curve of TSH showed an AUC of 0.58 (95% CI 0.53–0.62, p = 0.001), sensitivity of 74%, and specificity of 57% at a cut-off of 1.59 mIU/L. There was an incremental increase in TSH concentration along with the increasing tumor size (p < 0.001). Thyroglobulin antibody (TgAb) concentration was associated with an increased risk of malignancy (p = 0.029), but this association was lost when the effect of TSH was taken into account (p = 0.11). Thyroid ultrasonographic characteristics, including fewer than three nodules, hypoechoic appearance, solid component, poorly defined margin, intranodular or peripheral-intranodular flow, and punctate calcification, can be used to predict the risk of thyroid cancer. In conclusion, our study suggests that preoperative serum TSH concentration, age, and ultrasonographic features can be used to predict the risk of malignancy in patients with NTD. PMID:27313612

  18. Thyroid cancer incidence in simultaneous thyroidectomy with parathyroid surgery

    PubMed Central

    Emirikçi, Selman; Özçınar, Beyza; Öner, Gizem; Omarov, Nail; Ağcaoğlu, Orhan; Soytaş, Yiğit; Aksakal, Nihat; Yanar, Fatih; Barbaros, Umut; Erbil, Yeşim

    2015-01-01

    Objective: Primary hyperparathyroidism (PHPT) is often seen in conjunction with an underlying thyroid disorder. Imaging methods that are used to localize the parathyroid adenoma also detect associated thyroid nodules and thyroid cancer. The aim of this study was to detect the rate of thyroid cancer identified while performing parathyroidectomy and thyroidectomy in patients with PHPT. Material and Methods: Files of all patients who were operated for PHPT and who underwent simultaneous thyroidectomy were analyzed. Data regarding parathyroid pathology, surgical procedures, indications of thyroid surgery, and pathology results were retrospectively recorded. The indications for thyroid surgery included presence of suspicious thyroid nodules in ultrasonography, increase in size of thyroid nodules in follow-up ultrasound, or presence of suspicious thyroid fine needle aspiration biopsy (FNAB) findings. Rates of thyroid cancer detection were investigated according to definite pathology reports. Results: Eighty-three patients who underwent parathyroidectomy with a diagnosis of PHPT with concurrent thyroidectomy in Department of General Surgery, İstanbul University İstanbul Faculty of Medicine were included in the study. Eighteen patients were male (22%) and 65 were female (78%). The median age was 53 (18–70) years. The primary indication for parathyroidectomy was primary hyperparathyroidism in all patients. The thyroid procedures applied in addition to parathyroidectomy were lobectomy + isthmusectomy in 29 patients (35%), bilateral subtotal thyroidectomy in 20 patients (24%), bilateral total thyroidectomy in 23 patients (28%), and total thyroidectomy on one side and near total thyroidectomy to the other side in 11 patients (13%). The only indication for thyroidectomy was the presence of thyroid nodules until 2000 (20 patients, 24%). Indications in the remaining 63 patients included the presence of multiple nodules that cannot be followed up by ultrasonography in 25

  19. Peptide Receptor Radionuclide Therapy (PRRT) of Medullary and Nonmedullary Thyroid Cancer Using Radiolabeled Somatostatin Analogues.

    PubMed

    Salavati, Ali; Puranik, Ameya; Kulkarni, Harshad R; Budiawan, Hendra; Baum, Richard P

    2016-05-01

    As therapeutic options in advanced medullary and non-iodine avid differentiated (nonmedullary) thyroid cancers are limited and associated with significant toxicity, targeting of somatostatin receptors (SSTRs) for internal radiation therapy provides a promising option. Theranostics (therapy and diagnosis) using radiolabeled somatostatin analogues has proved to be a milestone in the management of SSTR-expressing tumors. Peptide receptor radionuclide therapy using (177)Lu-labeled or (90)Y-labeled somatostatin analogues may have a significant role in the management of medullary and nonmedullary thyroid cancers in those patients where PET/CT with (68)Ga-labeled somatostatin analogues demonstrates significant SSTR expression. PMID:27067502

  20. Thyroid cancer after diagnostic administration of iodine-131

    SciTech Connect

    Hall, P.; Mattsson, A.; Boice, J.D. Jr.

    1996-01-01

    To provide quantitative data on the risk of thyroid cancer after exposure to {sup 131}I, 34,104 patients administered {sup 131}I for diagnostic purposes were followed for up to 40 years. The mean thyroid dose was estimated as 1.1 Gy, and 67 thyroid cancers occurred in contrast to 49.7 expected (standardized incidence ratio = 1.35; 95% confidence interval 1.05-1.71). Excess cancers were apparent only among patients referred because of a suspected thyroid tumor, and no increased risk was seen among those referred for other reasons. Further, risk was not related to radiation dose to the thyroid gland, time since exposure or age at exposure. The slight excess of thyroid cancer thus appeared to be due to the underlying thyroid condition and not radiation exposure. Among those under age 20 years when {sup 131}I was administered, a small excess risk (3 cancers compared to 1.8 expected) was about 2-10 times lower than that predicted from data for the A-bomb survivors. These data suggest that protraction of dose may result in a lower risk than an acute X-ray exposure of the same total dose. 34 refs., 5 tabs.

  1. Cancer in Canada fact sheet series #1 - thyroid cancer in Canada.

    PubMed

    Shaw, A; Semenciw, R; Mery, L

    2014-02-01

    The incidence of thyroid cancer is increasing more rapidly than that of any other cancer in Canada, while mortality has remained low and stable. In the last 10 years the number of thyroid cancer cases has increased 144% from 1709 to 4172 cases per year. Thyroid cancer is three times more common in females than males. 40% of thyroid cancers are diagnosed in Canadians under 45 years of age. Some of the apparent increase in incidence is likely due to improved and more widely available diagnostic techniques. PMID:24618383

  2. Radionuclide imaging and treatment of thyroid cancer.

    PubMed

    Wang, Xiu Juan; Li, XianFeng; Ren, Yuan

    2016-01-01

    Over the past decades, the diagnostic methods and therapeutic tools for thyroid cancer (TC) have been greatly improved. In addition to the classical method of ingestion of radioactive iodine-131 (I131) and subsequent I123 and I124 positron emission tomography (PET) in therapy and examination, I124 PET-based 3-dimensional imaging, Ga68-labeled [1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid]-1-NaI(3)-octreotide (DOTANOC) PET/computed tomography (CT), Tc99m tetrofosmin, pre-targeted radioimmunotherapy, and peptide receptor radionuclide therapy have all been used clinically. These novel methods are useful in diagnosis and therapy of TC, but also have unavoidable adverse effects. In this review, we will discuss the development of nuclear medicine in TC examination and treatment. PMID:27100499

  3. IRF5 promotes the proliferation of human thyroid cancer cells

    PubMed Central

    2012-01-01

    Background Interferon Regulatory Factor 5 is a transcription factor that regulates the expression of genes involved in the response to viral infection and in the stimulation of the immune system. Moreover, multiple studies have demonstrated that it negatively regulates cell growth and oncogenesis, favoring cell differentiation and apoptosis. Thyroid carcinoma represents 98% of all thyroid malignancies and has shown a steady increase in incidence in both the USA and western European countries. Findings We investigated the expression, localization and function of IRF5 in thyroid cancer cells and found that it is highly expressed in both primary and immortalized thyroid carcinomas but not in normal thyrocytes. IRF5 levels were variably modulated by Interferon alpha but IRF5 only localized in the cytoplasmic compartment, thus failing to induce p21 expression as previously reported in different cell models. Furthermore, ectopic IRF5 increased both the proliferation rate and the clonogenic potential of malignant thyroid cells, protecting them from the cytotoxic effects of DNA-damaging agents. These results were directly attributable to IRF5, as demonstrated by the reduction in colony-forming ability of thyroid cancer cells after IRF5 silencing. An IRF5-dependent induction of endogenous B-Raf observed in all thyroid cancer cells might contribute to these unexpected effects. Conclusions These findings suggest that, in thyroid malignancies, IRF5 displays tumor-promoting rather than tumor-suppressor activities. PMID:22507190

  4. TCGA study improves understanding of thyroid cancer genetics - TCGA

    Cancer.gov

    A comprehensive analysis of the genomes of nearly 500 papillary thyroid carcinomas has provided new insights into the roles of frequently mutated cancer genes and other genomic alterations that drive disease development.

  5. Global tyrosine kinome profiling of human thyroid tumors identifies Src as a promising target for invasive cancers

    SciTech Connect

    Cho, Nancy L.; Lin, Chi-Iou; Du, Jinyan; Whang, Edward E.; Ito, Hiromichi; Moore, Francis D.; Ruan, Daniel T.

    2012-05-11

    . Conclusion: Global kinome analysis enables the discovery of novel targets for thyroid cancer therapy. Further investigation of Src targeted therapy for advanced thyroid cancer is warranted.

  6. Concurrent papillary thyroid cancer and parathyroid adenoma as a rare condition: a case report.

    PubMed

    Javadi, Hamid; Jallalat, Sara; Farrokhi, Shokrollah; Semnani, Shahriar; Mogharrabi, Mehdi; Riazi, Ahmad; Nabipour, Iraj; Moshtaghi, Darab; Assadi, Majid

    2012-01-01

    Although the pathological relationship between parathyroid and thyroid diseases is common, an association between parathyroid adenoma and thyroid cancer is rare. Concomitant thyroid cancer in patients with primary hyperparathyroidism (pHPT) has been reported at varying frequencies. WE present here a 23-year-old man who had papillary thyroid carcinoma in the right thyroid lobe and a parathyroid adenoma in the left thyroid lobe, which were confirmed surgically. PMID:22936512

  7. Herpes and polyoma family viruses in thyroid cancer

    PubMed Central

    STAMATIOU, DIMITRIS P.; DERDAS, STAVROS P.; ZORAS, ODYSSEAS L.; SPANDIDOS, DEMETRIOS A.

    2016-01-01

    Thyroid cancer is considered the most common malignancy that affects the endocrine system. Generally, thyroid cancer derives from follicular epithelial cells, and thyroid cancer is divided into well-differentiated papillary (80% of cases) and follicular (15% of cases) carcinoma. Follicular thyroid cancer is further divided into the conventional and oncocytic (Hürthle cell) type, poorly differentiated carcinoma and anaplastic carcinoma. Both poorly differentiated and anaplastic carcinoma can arise either de novo, or secondarily from papillary and follicular thyroid cancer. The incidence of thyroid cancer has significantly increased for both males and females of all ages, particularly for females between 55–64 years of age, from 1999 through 2008. The increased rates refer to tumors of all stages, though they were mostly noted in localized disease. Recently, viruses have been implicated in the direct regulation of epithelial-mesenchymal transition (EMT) and the development of metastases. More specifically, Epstein-Barr virus (EBV) proteins may potentially lead to the development of metastasis through the regulation of the metastasis suppressor, Nm23, and the control of Twist expression. The significant enhancement of the metastatic potential, through the induction of angiogenesis and changes to the tumor microenvironment, subsequent to viral infection, has been documented, while EMT also contributes to cancer cell permissiveness to viruses. A number of viruses have been identified to be associated with carcinogenesis, and these include lymphotropic herpesviruses, namely EBV and Kaposi's sarcoma-associated herpesvirus [KSHV, also known as human herpesvirus type 8 (HHV8)]; two hepatitis viruses, hepatitis B virus (HBV) and hepatitis C virus (HCV); human papillomaviruses (HPVs); human T cell lymphoma virus (HTLV); and a new polyomavirus, Merkel cell polyomavirus identified in 2008. In this review, we examined the association between thyroid cancer and two oncogenic

  8. Increasing thyroid cancer incidence in Lithuania in 1978–2003

    PubMed Central

    Smailyte, Giedre; Miseikyte-Kaubriene, Edita; Kurtinaitis, Juozas

    2006-01-01

    Background The aim of this paper is to analyze changes in thyroid cancer incidence trends in Lithuania during the period 1978–2003 using joinpoint regression models, with special attention to the period 1993–2003. Methods The study was based on all cases of thyroid cancer reported to the Lithuanian Cancer Registry between 1978 and 2003. Age group-specific rates and standardized rates were calculated for each gender, using the direct method (world standard population). The joinpoint regression model was used to provide estimated annual percentage change and to detect points in time where significant changes in the trends occur. Results During the study period the age-standardized incidence rates increased in males from 0.7 to 2.5 cases per 100 000 and in females from 1.5 to 11.4 per 100 000. Annual percentage changes during this period in the age-standardized rates were 4.6% and 7.1% for males and females, respectively. Joinpoint analysis showed two time periods with joinpoint in the year 2000. A change in the trend occurred in which a significant increase changed to a dramatic increase in thyroid cancer incidence rates. Papillary carcinoma and stage I thyroid cancer increases over this period were mainly responsible for the pattern of changes in trend in recent years. Conclusion A moderate increase in thyroid cancer incidence has been observed in Lithuania between the years 1978 and 2000. An accelerated increase in thyroid cancer incidence rates took place in the period 2000–2003. It seems that the increase in thyroid cancer incidence can be attributed mainly to the changes in the management of non palpable thyroid nodules with growing applications of ultrasound-guided fine needle aspiration biopsy in clinical practice. PMID:17156468

  9. Zinc finger E-box-binding homeobox 1: its clinical significance and functional role in human thyroid cancer

    PubMed Central

    Zhang, Yan; Liu, Gang; Wu, Shihe; Jiang, Futing; Xie, Jiangping; Wang, Yuhong

    2016-01-01

    Objective Transcription factor zinc finger E-box-binding homeobox 1 (ZEB1), as one of the key inducers of epithelial-mesenchymal transition, has been reported to be regulated by microRNA-144 and Bcl-2-associated athanogene 3, which both promote thyroid cancer cell invasion. However, the involvement of ZEB1 in thyroid cancer has not been fully elucidated. In this study, we aimed to investigate the role and clinical implication of ZEB1 in this disease. Methods Immunohistochemistry was performed to examine the subcellular localization and the expression level of ZEB1 protein in 82 self-pairs of formalin-fixed and paraffin-embedded cancerous and adjacent noncancerous tissues obtained from patients with thyroid cancer. The roles of ZEB1 in thyroid cancer cell migration, invasion, and proliferation were also detected by transwell and MTT analyses, respectively. Results Immunohistochemistry showed that ZEB1 was predominantly localized in the nucleus of thyroid cancer cells. Its immunoreactive score in thyroid cancer tissues was significantly higher than that in adjacent noncancerous tissues (P=0.01). In addition, ZEB1 overexpression was significantly associated with the advanced tumor node metastasis staging (P=0.008), the positive lymph node metastasis (P=0.01) and distant metastasis (P=0.02). Furthermore, ZEB1 knockdown by siRNA could efficiently inhibit the migration, invasion, and proliferation abilities of thyroid cancer cells in vitro. Conclusion These findings indicated that ZEB1 might function as an oncogene, the overexpression of which was associated with the aggressive tumor progression of human thyroid cancer. Interestingly, ZEB1 also could promote thyroid cancer cell migration, invasion, and proliferation, suggesting that the inhibition of this protein might be a therapeutic strategy for the treatment of this malignancy. PMID:27099512

  10. Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer

    PubMed Central

    Waguespack, Steven G.; Bauer, Andrew J.; Angelos, Peter; Benvenga, Salvatore; Cerutti, Janete M.; Dinauer, Catherine A.; Hamilton, Jill; Hay, Ian D.; Luster, Markus; Parisi, Marguerite T.; Rachmiel, Marianna; Thompson, Geoffrey B.; Yamashita, Shunichi

    2015-01-01

    Background: Previous guidelines for the management of thyroid nodules and cancers were geared toward adults. Compared with thyroid neoplasms in adults, however, those in the pediatric population exhibit differences in pathophysiology, clinical presentation, and long-term outcomes. Furthermore, therapy that may be recommended for an adult may not be appropriate for a child who is at low risk for death but at higher risk for long-term harm from overly aggressive treatment. For these reasons, unique guidelines for children and adolescents with thyroid tumors are needed. Methods: A task force commissioned by the American Thyroid Association (ATA) developed a series of clinically relevant questions pertaining to the management of children with thyroid nodules and differentiated thyroid cancer (DTC). Using an extensive literature search, primarily focused on studies that included subjects ≤18 years of age, the task force identified and reviewed relevant articles through April 2014. Recommendations were made based upon scientific evidence and expert opinion and were graded using a modified schema from the United States Preventive Services Task Force. Results: These inaugural guidelines provide recommendations for the evaluation and management of thyroid nodules in children and adolescents, including the role and interpretation of ultrasound, fine-needle aspiration cytology, and the management of benign nodules. Recommendations for the evaluation, treatment, and follow-up of children and adolescents with DTC are outlined and include preoperative staging, surgical management, postoperative staging, the role of radioactive iodine therapy, and goals for thyrotropin suppression. Management algorithms are proposed and separate recommendations for papillary and follicular thyroid cancers are provided. Conclusions: In response to our charge as an independent task force appointed by the ATA, we developed recommendations based on scientific evidence and expert opinion for the

  11. The role of surgery in the management of thyroid cancer.

    PubMed Central

    Mustard, R. A.

    1975-01-01

    This is a review of one surgeon's personal experience with 85 patients with thyroid cancer treated over a 20-year period. The data confirm that for papillary thyroid tumours, with rare exceptions, the prognosis is excellent. Anaplastic lesions, however, are consistently lethal. Follicular carcinoma and medullary carcinoma fall between these extremes. A simple clinical classification is offered as a guide to operative management and a reliable index of prognosis. Patients with clinically apparent, "manifest cancer" have serious, life-threatening disease; many such patients die of their disease. Patients with "neck lumps not yet diagnosed" usually have papillary carcinoma; their prognosis is excellent. Patients whose thyroid tumours fall into the category of "malignant nodule" or "pathologist's cancer" are particularly fortunate: in this series no such patient has died. The importance of age in relation to thyroid cancer is also confirmed: non of the patients first treated before the age of 40 years has died of cancer. For young patients with favourable disease the author recommends conservative surgical treatment, which avoids cosmetic deformity or functional disability, to be followed by administration of levothyroxine to suppress production of thyroid=stimulating hormone. For patients with "unfavourable" thyroid cancer valuable palliation can often be achieved by a combination of surgery and irradiation. Survival rates for the total series are 76% at 5 years and 60% at 10 years. PMID:1139493

  12. Complementary and Alternative Medicine Use Among Patients with Thyroid Cancer

    PubMed Central

    Gardiner, Paula; Saper, Robert B.; Filippelli, Amanda C.; White, Laura F.; Pearce, Elizabeth N.; Gupta-Lawrence, Rebecca L.; Lee, Stephanie L.

    2013-01-01

    Background To report on the incidence and predictors of use of complementary and alternative medicine (CAM) among patients with thyroid cancer. Methods Data were collected using a web-based online anonymous survey under Institutional Review Board approval from Boston University. This report is based on 1327 responses from subjects with thyroid cancer. Patient factors were compared by univariate and multivariate analyses. Results After excluding multivitamin and prayer use, 74% (n=941) used CAM. Respondents were primarily over age 40, white, and female and held a college degree. The top five modalities were massage therapy, chiropraxy, special diets, herbal tea, and yoga. Few patients reported perceiving a particular modality had a negative effect on treatment. CAM was more often used for treatment of symptoms (73%) than as part of thyroid cancer treatment (27%). Multivariable logistic regression demonstrated that patients reporting a poor health status, higher education, cardiovascular disease, pulmonary symptoms, or persistent, recurrent, or metastatic disease were more likely to use CAM for treatment of thyroid cancer symptoms. Nearly one third of respondents reported their CAM use was not known, prescribed, or asked about by their physicians. Conclusions In comparison to national surveys of the general U.S. population, patients with thyroid cancer use CAM therapies twice as often and report their use far less often. Physicians who treat patients with thyroid cancer should be aware of these data to further assist in their assessment and care. PMID:23350883

  13. The Accuracy of Thyroid Nodule Ultrasound to Predict Thyroid Cancer: Systematic Review and Meta-Analysis

    PubMed Central

    Gionfriddo, Michael R.; Al Nofal, Alaa; Boehmer, Kasey R.; Leppin, Aaron L.; Reading, Carl; Callstrom, Matthew; Elraiyah, Tarig A.; Prokop, Larry J.; Stan, Marius N.; Murad, M. Hassan; Morris, John C.; Montori, Victor M.

    2014-01-01

    Context: Significant uncertainty remains surrounding the diagnostic accuracy of sonographic features used to predict the malignant potential of thyroid nodules. Objective: The objective of the study was to summarize the available literature related to the accuracy of thyroid nodule ultrasound (US) in the prediction of thyroid cancer. Methods: We searched multiple databases and reference lists for cohort studies that enrolled adults with thyroid nodules with reported diagnostic measures of sonography. A total of 14 relevant US features were analyzed. Results: We included 31 studies between 1985 and 2012 (number of nodules studied 18 288; average size 15 mm). The frequency of thyroid cancer was 20%. The most common type of cancer was papillary thyroid cancer (84%). The US nodule features with the highest diagnostic odds ratio for malignancy was being taller than wider [11.14 (95% confidence interval 6.6–18.9)]. Conversely, the US nodule features with the highest diagnostic odds ratio for benign nodules was spongiform appearance [12 (95% confidence interval 0.61–234.3)]. Heterogeneity across studies was substantial. Estimates of accuracy depended on the experience of the physician interpreting the US, the type of cancer and nodule (indeterminate), and type of reference standard. In a threshold model, spongiform appearance and cystic nodules were the only two features that, if present, could have avoided the use of fine-needle aspiration biopsy. Conclusions: Low- to moderate-quality evidence suggests that individual ultrasound features are not accurate predictors of thyroid cancer. Two features, cystic content and spongiform appearance, however, might predict benign nodules, but this has limited applicability to clinical practice due to their infrequent occurrence. PMID:24276450

  14. Uptake of I-131 MIBG by medullary thyroid cancer

    SciTech Connect

    Endo, K.; Koizumi, M.; Sakahara, H.; Nakashima, T.; Ohta, H.; Kasagi, K.; Konishi, J.; Miyauchi, A.; Kuma, K.; Torizuka, K.

    1985-05-01

    I-131 MIBG scans are useful for the localization of pheochromocytoma and neuroblastoma with high catecholamine levels. Recently the authors have found that medullary thyroid cancer also showed an uptake of I-131 MIBG in both primary neck tumors and metastatic sites. Up to now scintigraphic studies were performed in 5 patients with medullary thyroid cancer. Scintigraphy was done at 24 and 48 hours after the administration of 0.5 mCi of I-131 MIBG, thyroid uptake of dissociated I-131 being prevented by Lugol's solution. Four out of 5 cases were familial type and uptake of I-131 MIBG was similarly observed in medullary thyroid cancer as well as in pheochromocytoma. Bone metastasis of medullary thyroid cancer was also detected with I-131 MIBG. However, one case of sporadic form was negative with I-131 MIBG, whereas there was a high uptake of Tc(V)-99m dimercaptosuccinic acid: a newly developed radiopharmaceutical for medullary thyroid cancer, visualizing a different uptake mechanism of both reagents (J Nucl Med 25: 323-325, 1984). After adrenalectomy high uptake of I-131 MIBG was still observed in medullary thyroid cancer, in spite of normal catecholamine levels. The tumor to blood ratio was estimated in vivo to be about several hundreds at 24 hours after the administration. These cells are of neural crest origin and the mechanism of uptake of I-131 MIBG may not be related to the catechamine uptake mechanism. This paper concludes that I-131 MIBG is useful not only for the localization but also for the treatment of medullary thyroid cancer, as preliminary performed in pheochromocytoma and neuroblastoma.

  15. New drugs for medullary thyroid cancer: new promises?

    PubMed

    Spitzweg, Christine; Morris, John C; Bible, Keith C

    2016-06-01

    Medullary thyroid cancer (MTC) is a rare tumor arising from the calcitonin-producing parafollicular C cells of the thyroid gland, occurring either sporadically or alternatively in a hereditary form based on germline RET mutations in approximately one-third of cases. Historically, patients with advanced, metastasized MTC have had a poor prognosis, partly due to limited response to conventional chemotherapy and radiation therapy. In the past decade, however, considerable progress has been made in identifying key genetic alterations and dysregulated signaling pathways paving the way for the evaluation of a series of multitargeted kinase inhibitors that have started to meaningfully impact clinical practice. Two drugs, vandetanib and cabozantinib, are now approved in the US and EU for use in advanced, progressive MTC, with additional targeted agents also showing promise or awaiting results from clinical trials. However, the potential for toxicities with significant reduction in quality of life and lack of curative outcomes has to be carefully weighed against potential for benefit. Despite significant PFS prolongation observed in randomized clinical trials, most patients even with metastatic disease enjoy indolent courses with slow progression observed over years, wherein watchful waiting is still the preferred strategy. As advanced, progressive MTC is a rare and complex disease, a multidisciplinary approach centered in specialized centers providing interdisciplinary expertise in the individualization of available therapeutic options is preferred. In this review, we summarize current concepts of the molecular pathogenesis of advanced MTC and discuss results from clinical trials of targeted agents and also cytotoxic chemotherapy in the context of clinical implications and future perspectives. PMID:27185870

  16. Therapeutic Outcome of Second Primary Malignancies in Patients with Well-Differentiated Thyroid Cancer

    PubMed Central

    Liou, Miaw-Jene; Tsang, Ngan-Ming; Hsueh, Chuen; Chao, Tzu-Chieh; Lin, Jen-Der

    2016-01-01

    Background. The aims of this study were to analyze the clinical characteristics of SPM in patients with well-differentiated thyroid cancer and to determine the long-term prognosis in patients with double malignancies. Materials and Methods. We retrospectively analyzed 2,864 patients with well-differentiated thyroid cancer and a mean age of 44.0 ± 14.4 years. Of these, 200 (7.0%) were diagnosed with SPM, 115 of which were diagnosed with metachronous SPM. Results. Of 2,864 patients, 163 (5.7%) patients died of thyroid cancer and 301 (10.5%) died of any cause by the end of the follow-up period. Multivariate analysis identified age, SPM, external radiotherapy, TNM stage, and postoperative serum Tg level to be factors independently associated with decreased survival. Of 200 patients with SPM, 74 (37.0%) died. In comparison to the anachronous and synchronous groups, the metachronous SPM group had a higher mean age; more advanced tumor, node, and metastasis stage; lower remission rate; higher postoperative radioactive iodide (131I) accumulated dose; a higher proportion of patients who underwent external radiotherapy; and higher thyroid cancer and total mortality rates. Conclusions. Patients with well-differentiated thyroid carcinoma and metachronous SPM had worse prognoses compared to patients without SPM. PMID:27118971

  17. Normal vs cancer thyroid stem cells: the road to transformation.

    PubMed

    Zane, M; Scavo, E; Catalano, V; Bonanno, M; Todaro, M; De Maria, R; Stassi, G

    2016-02-18

    Recent investigations in thyroid carcinogenesis have led to the isolation and characterisation of a subpopulation of stem-like cells, responsible for tumour initiation, progression and metastasis. Nevertheless, the cellular origin of thyroid cancer stem cells (SCs) remains unknown and it is still necessary to define the process and the target population that sustain malignant transformation of tissue-resident SCs or the reprogramming of a more differentiated cell. Here, we will critically discuss new insights into thyroid SCs as a potential source of cancer formation in light of the available information on the oncogenic role of genetic modifications that occur during thyroid cancer development. Understanding the fine mechanisms that regulate tumour transformation may provide new ground for clinical intervention in terms of prevention, diagnosis and therapy. PMID:25961919

  18. Imaging for staging and management of thyroid cancer

    PubMed Central

    2008-01-01

    Abstract The management of thyroid cancer has been controversial and, as a result, the routine use of imaging in this disease, especially for pre-operative staging, has lagged behind other head and neck cancers. However, as more is known about the natural history of thyroid cancer, the role of imaging is becoming more established. This review focuses on how imaging now influences the staging and management of the primary cancer, nodal metastases and distant metastases. This is followed by a brief review of the role of imaging in planning post-operative radiotherapy and post-treatment surveillance. PMID:18390389

  19. Use of ultrasound in the management of thyroid cancer.

    PubMed

    Lew, John I; Solorzano, Carmen C

    2010-01-01

    The use of ultrasound for thyroid cancer has evolved dramatically over the last few decades. Since the late 1960s, ultrasound has become essential in the examination of the thyroid gland with the increased availability of high-frequency linear array transducers and computer-enhanced imaging capabilities of modern day portable ultrasound equipment in a clinic- or office-based setting. As a noninvasive, rapid, and easily reproducible imaging study, ultrasound has been demonstrated to have a broadened utility beyond the simple confirmation of thyroid nodules and their sizes. Recently, office-based ultrasound has become an integral part of clinical practice, where it has demonstrated overwhelming benefits to patients being evaluated and treated for thyroid cancer. Ultrasound has become useful in the qualitative characterization of thyroid nodules based on benign or malignant features. On the basis of such classifications and the relative risk for thyroid malignancy, the need for ultrasound-guided fine-needle aspiration, preoperative and intraoperative staging, lymph node mapping, and the extent of surgery can subsequently be determined. Furthermore, ultrasound has additional value in the surveillance of patients treated for thyroid cancer. PMID:20215358

  20. Thyroid cancer following nuclear tests in French Polynesia

    PubMed Central

    de Vathaire, F; Drozdovitch, V; Brindel, P; Rachedi, F; Boissin, J-L; Sebbag, J; Shan, L; Bost-Bezeaud, F; Petitdidier, P; Paoaafaite, J; Teuri, J; Iltis, J; Bouville, A; Cardis, E; Hill, C; Doyon, F

    2010-01-01

    Background: Between 1966 and 1974, France conducted 41 atmospheric nuclear tests in Polynesia, but their potential health effects have not previously been investigated. Methods: In a case–control study, we compared the radiation exposure of almost all the French Polynesians diagnosed with differentiated thyroid carcinoma between 1981 and 2003 (n=229) to the exposure of 373 French Polynesian control individuals without cancer from the general population. Radiation exposures were estimated using measurements after the nuclear tests, age at time of each test, residential and dietary information. Results: The average thyroid dose before 15 years of age was about 1.8 mGy, and 5% of the cases and 3% of the controls received a dose above 10 mGy. Despite this low level of dose, and after adjusting for ethnic group, level of education, body surface area, family history of thyroid cancer and number of pregnancies for women, we observed an increasing risk (P=0.04) of thyroid cancer with increasing thyroid dose received before age of 15 years, which remained after excluding non-aggressive differentiated thyroid micro-carcinomas. This increase of risk per unit of thyroid radiation dose was higher (P=0.03) in women who later experienced four or more pregnancies than among other women. Conclusion: The risk estimate is low, but is based on limited exposure data. The release of information on exposure, currently classified, would greatly improve the reliability of the risk estimation. PMID:20808313

  1. Thyroid-specific ablation of the Carney complex gene, PRKAR1A, results in hyperthyroidism and follicular thyroid cancer.

    PubMed

    Pringle, Daphne R; Yin, Zhirong; Lee, Audrey A; Manchanda, Parmeet K; Yu, Lianbo; Parlow, Alfred F; Jarjoura, David; La Perle, Krista M D; Kirschner, Lawrence S

    2012-06-01

    Thyroid cancer is the most common endocrine malignancy in the population, and the incidence of this cancer is increasing at a rapid rate. Although genetic analysis of papillary thyroid cancer (PTC) has identified mutations in a large percentage of patients, the genetic basis of follicular thyroid cancer (FTC) is less certain. Thyroid cancer, including both PTC and FTC, has been observed in patients with the inherited tumor predisposition Carney complex, caused by mutations in PRKAR1A. In order to investigate the role of loss of PRKAR1A in thyroid cancer, we generated a tissue-specific knockout of Prkar1a in the thyroid. We report that the resulting mice are hyperthyroid and developed follicular thyroid neoplasms by 1 year of age, including FTC in over 40% of animals. These thyroid tumors showed a signature of pathway activation different from that observed in other models of thyroid cancer. In vitro cultures of the tumor cells indicated that Prkar1a-null thyrocytes exhibited growth factor independence and suggested possible new therapeutic targets. Overall, this work represents the first report of a genetic mutation known to cause human FTC that exhibits a similar phenotype when modeled in the mouse. In addition to our knowledge of the mechanisms of human follicular thyroid tumorigenesis, this model is highly reproducible and may provide a viable mechanism for the further clinical development of therapies aimed at FTC. PMID:22514108

  2. The effect of low level laser on anaplastic thyroid cancer

    NASA Astrophysics Data System (ADS)

    Rhee, Yun-Hee; Moon, Jeon-Hwan; Ahn, Jin-Chul; Chung, Phil-Sang

    2015-02-01

    Low-level laser therapy (LLLT) is a non-thermal phototherapy used in several medical applications, including wound healing, reduction of pain and amelioration of oral mucositis. Nevertheless, the effects of LLLT upon cancer or dysplastic cells have been so far poorly studied. Here we report that the effects of laser irradiation on anaplastic thyroid cancer cells leads to hyperplasia. 650nm of laser diode was performed with a different time interval (0, 15, 30, 60J/cm2 , 25mW) on anaplastic thyroid cancer cell line FRO in vivo. FRO was orthotopically injected into the thyroid gland of nude mice and the irradiation was performed with the same method described previously. After irradiation, the xenograft evaluation was followed for one month. The thyroid tissues from sacrificed mice were undergone to H&E staining and immunohistochemical staining with HIF-1α, Akt, TGF-β1. We found the aggressive proliferation of FRO on thyroid gland with dose dependent. In case of 60 J/ cm2 of energy density, the necrotic bodies were found in a center of the thyroid. The phosphorylation of HIF-1α and Akt was detected in the thyroid gland, which explained the survival signaling of anaplastic cancer cell was turned on the thyroid gland. Furthermore, TGF-β1 expression was decreased after irradiation. In this study, we demonstrated that insufficient energy density irradiation occurred the decreasing of TGF-β1 which corresponding to the phosphorylation of Akt/ HIF-1α. This aggressive proliferation resulted to the hypoxic condition of tissue for angiogenesis. We suggest that LLLT may influence to cancer aggressiveness associated with a decrease in TGF-β1 and increase in Akt/HIF-1α.

  3. [CME: Radioactive iodine therapy in thyroid cancer].

    PubMed

    Steinert, Hans C; Aberle, Susanne

    2015-11-11

    Differentiated thyroid carcinomas represent about 90% of all thyroid tumors and are divided in papillary and follicular carcinomas. Their prognosis is good, however, recurrences are not rare. Their ability to accumulate iodine is used for the radioactive iodine treatment. The aim of the postoperative radioactive iodine ablation therapy is the complete elimination of remnant thyroid cells and sensitive staging (Fig. 1). The recurrence rate decreases after a complete thyroid ablation. Furthermore, thyroglobulin can be used as a sensitive tumor marker. Radioactive iodine treatment by itself describes the therapy of metastases. An exception is the papillary microcarcinoma, which in general is treated by a lobectomy alone. PMID:26558927

  4. Novel Approaches to Thyroid Cancer Treatment and Response Assessment.

    PubMed

    Grewal, Ravinder K; Ho, Alan; Schöder, Heiko

    2016-03-01

    The incidence of thyroid cancer has been increasing. After total thyroidectomy of well-differentiated thyroid tumors with intermediate- or high-risk features on pathology, radioiodine remains one of the mainstays of therapy for both thyroid remnant ablation as well as for treatment of metastatic disease. SPECT/CT, a relatively new modality, has been shown to play a pivotal role predominantly in the post-therapy setting by changing the risk stratification of patients with thyroid cancer. In the case of radioiodine treatment failure, FDG-PET/CT may provide prognostic information based on extent and intensity of metabolically active metastatic sites as well as serve as an important imaging test for response assessment in patients treated with chemotherapy, targeted therapies, or radiotherapy, thereby affecting patient management in multiple ways. The role of newer redifferentiation drugs has been evaluated with the use of I-124 PET/CT. PMID:26897715

  5. Thyroid Cancer Cases in U.S. Level Off, Perhaps Reflecting Diagnostic Changes

    MedlinePlus

    ... nlm.nih.gov/medlineplus/news/fullstory_158319.html Thyroid Cancer Cases in U.S. Level Off, Perhaps Reflecting ... 2016 THURSDAY, April 14, 2016 (HealthDay News) -- Fewer thyroid cancers are diagnosed in the United States now ...

  6. What Should You Ask Your Health Care Team About Thyroid Cancer?

    MedlinePlus

    ... thyroid cancer survivor What should you ask your health care team about thyroid cancer? As you deal with ... only ones who can give you information. Other health care professionals, such as nurses and social workers, may ...

  7. Detecting and Treating Thyroid Nodules and Cancer Before, During, and After Pregnancy

    MedlinePlus

    ... cancer have their own risk factors. For instance, “medullary” thyroid cancer (an uncommon type) can run in ... most common to least common, are papillary, follicular, medullary, and anaplastic. (See the Hormone Health Network’s Thyroid ...

  8. Thyroid scan

    MedlinePlus

    ... is done to: Check for thyroid cancer Evaluate thyroid nodules or goiter Find the cause of an overactive ... the thyroid appears lighter, it could be a thyroid problem. Nodules that are darker can be overactive and may ...

  9. Alpha lipoic acid inhibits proliferation and epithelial mesenchymal transition of thyroid cancer cells.

    PubMed

    Jeon, Min Ji; Kim, Won Gu; Lim, Seonhee; Choi, Hyun-Jeung; Sim, Soyoung; Kim, Tae Yong; Shong, Young Kee; Kim, Won Bae

    2016-01-01

    The naturally occurring short-chain fatty acid, α-lipoic acid (ALA) is a powerful antioxidant which is clinically used for treatment of diabetic neuropathy. Recent studies suggested the possibility of ALA as a potential anti-cancer agent, because it could activate adenosine monophosphate activated protein kinase (AMPK) and inhibit transforming growth factor-β (TGFβ) pathway. In this study, we evaluate the effects of ALA on thyroid cancer cell proliferation, migration and invasion. We performed in vitro cell proliferation analysis using BCPAP, HTH-83, CAL-62 and FTC-133 cells. ALA suppressed thyroid cancer cell proliferation through activation of AMPK and subsequent down-regulation of mammalian target of rapamycin (mTOR)-S6 signaling pathway. Low-dose ALA, which had minimal effects on cell proliferation, also decreased cell migration and invasion of BCPAP, CAL-62 and HTH-83 cells. ALA inhibited epithelial mesenchymal transition (EMT) evidently by increase of E-cadherin and decreases of activated β-catenin, vimentin, snail, and twist in these cells. ALA suppressed TGFβ production and inhibited induction of p-Smad2 and twist by TGFβ1 or TGFβ2. These findings indicate that ALA reduces cancer cell migration and invasion through suppression of TGFβ production and inhibition of TGFβ signaling pathways in thyroid cancer cells. ALA also significantly suppressed tumor growth in mouse xenograft model using BCPAP and FTC-133 cells. This is the first study to show anti-cancer effect of ALA on thyroid cancer cells. ALA could be a potential therapeutic agent for treatment of advanced thyroid cancer, possibly as an adjuvant therapy with other systemic therapeutic agents. PMID:26463583

  10. Access, excess, and overdiagnosis: the case for thyroid cancer

    PubMed Central

    Hall, Stephen F; Irish, Jonathan; Groome, Patti; Griffiths, Rebecca

    2014-01-01

    The incidence of thyroid cancer in women is increasing at an epidemic rate. Numerous studies have proposed that the cause is increasing detection due to availability and use of medical diagnostic ultrasound. Our objective was to compare rates of diagnosis across different health-care regions to rates of diagnostic tests and to features of both health and access of the regional populations. This is a population-based retrospective ecological observational study of 12,959 patients with thyroid cancer between January 1, 2000 and December 31, 2008 in Ontario Canada based on the health-care utilization regions (Local Health Integration Networks) of the province of Ontario Canada. We found that some regions of Ontario had four times the rates of diagnosis of thyroid cancer compared to other regions. The regions with the highest use of discretionary medical tests (pelvic ultrasound, abdominal ultrasound, neck ultrasound, echocardiogram, resting electrocardiogram, cardiac nuclear perfusion tests, and bone scan), highest population density, and better education had the highest rates of thyroid cancer diagnoses. Differences in the rates of the ordering of discretionary diagnostic medical tests, such as diagnostic ultrasound, in different geographic regions of Ontario lead to differences in the rates of diagnosis of thyroid cancer. PMID:24408145

  11. Myxedema madness complicating postoperative follow-up of thyroid cancer.

    PubMed

    Morosán Allo, Yanina J; Rosmarin, Melanie; Urrutia, Agustina; Faingold, Maria Cristina; Musso, Carla; Brenta, Gabriela

    2015-08-01

    Although hypothyroidism is associated with an increased prevalence of psychiatric manifestations, myxedema madness is rarely observed. We report the case of a 62-year-old woman with no prior history of psychiatric disorders, who presented to the emergency department with psychomotor agitation 6 weeks after total thyroidectomy for papillary thyroid cancer. Serum thyroid stimulating hormone (TSH) on admission was 62.9 mIU/L and free T4 was < 0.35 ng/dL, indicating severe hypothyroidism. After ruling out other possible causes, the diagnosis of myxedema madness was considered; hence, antipsychotic drug treatment and intravenous levothyroxine were prescribed. Behavioral symptoms returned to normal within 4 days of presentation, while levels of thyroid hormones attained normal values 1 week after admission. Recombinant TSH (Thyrogen®) was used successfully to prevent new episodes of mania due to thyroid hormone withdrawal in further controls for her thyroid cancer. This case illustrates that myxedema madness can occur in the setting of acute hypothyroidism, completely reverting with levothyroxine and antipsychotic treatment. Recombinant TSH may be a useful tool to prevent myxedema madness or any severe manifestation of levothyroxine withdrawal for the follow-up of thyroid cancer. PMID:26331326

  12. Profile of thyroid hormones in breast cancer patients.

    PubMed

    Saraiva, P P; Figueiredo, N B; Padovani, C R; Brentani, M M; Nogueira, C R

    2005-05-01

    Estrogen involvement in breast cancer has been established; however, the association between breast cancer and thyroid diseases is controversial. Estrogen-like effects of thyroid hormone on breast cancer cell growth in culture have been reported. The objective of the present study was to determine the profile of thyroid hormones in breast cancer patients. Serum aliquots from 26 patients with breast cancer ranging in age from 30 to 85 years and age-matched normal controls (N = 22) were analyzed for free triiodothyronine (T3F), free thyroxine (T4F), thyroid-stimulating hormone (TSH), antiperoxidase antibody (TPO), and estradiol (E2). Estrogen receptor ss (ERss) was determined in tumor tissues by immunohistochemistry. Thyroid disease incidence was higher in patients than in controls (58 vs 18%, P < 0.05). Subclinical hyperthyroidism was the most frequent disorder in patients (31%); hypothyroidism (8%) and positive anti-TPO antibodies (19%) were also found. Subclinical hypothyroidism was the only dysfunction (18%) found in controls. Hyperthyroidism was associated with postmenopausal patients, as shown by significantly higher mean T3 and T4 values and lower TSH levels in this group of breast cancer patients than in controls. The majority of positive ERss tumors were clustered in the postmenopausal patients and all cases presenting subclinical hyperthyroidism in this subgroup concomitantly exhibited Erss-positive tumors. Subclinical hyperthyroidism was present in only one of 6 premenopausal patients. We show here that postmenopausal breast cancer patients have a significantly increased thyroid hormone/E2 ratio (P < 0.05), suggesting a possible tumor growth-promoting effect caused by this misbalance. PMID:15917958

  13. FAP Associated Papillary Thyroid Carcinoma: A Peculiar Subtype of Familial Nonmedullary Thyroid Cancer

    PubMed Central

    Cetta, Francesco

    2015-01-01

    Familial Nonmedullary Thyroid Carcinoma (FNMTC) makes up to 5–10% of all thyroid cancers, also including those FNMTC occurring as a minor component of familial cancer syndromes, such as Familial Adenomatous Polyposis (FAP). We give evidence that this extracolonic manifestation of FAP is determined by the same germline mutation of the APC gene responsible for colonic polyps and cancer but also shows some unusual features (F : M ratio = 80 : 1, absence of LOH for APC in the thyroid tumoral tissue, and indolent biological behaviour, despite frequent multicentricity and lymph nodal involvement), suggesting that the APC gene confers only a generic susceptibility to thyroid cancer, but perhaps other factors, namely, modifier genes, sex-related factors, or environmental factors, are also required for its phenotypic expression. This great variability is against the possibility of classifying all FNMTC as a single entity, not only with a unique or prevalent causative genetic factor, but also with a unique or common biological behavior and a commonly dismal prognosis. A new paradigm is also suggested that could be useful (1) for a proper classification of FAP associated PTC within the larger group of FNMTC and (2) for making inferences to sporadic carcinogenesis, based on the lesson from FAP. PMID:26697262

  14. Focal Lymphocytic Thyroiditis Nodules Share the Features of Papillary Thyroid Cancer on Ultrasound

    PubMed Central

    Hwang, Sena; Shin, Dong Yeob; Kim, Eun Kyung; Yang, Woo Ick; Byun, Jung Woo; Lee, Su Jin; Kim, Gyuri; Im, Soo Jung

    2015-01-01

    Purpose It is often difficult to discriminate focal lymphocytic thyroiditis (FLT) or adenomatous hyperplasia (AH) from thyroid cancer if they both have suspicious ultrasound (US) findings. We aimed to make a predictive model of FLT from papillary thyroid cancer (PTC) in suspicious nodules with benign cytologic results. Materials and Methods We evaluated 214 patients who had undergone fine-needle aspiration biopsy (FNAB) and had shown thyroid nodules with suspicious US features. PTC was confirmed by surgical pathology. FLT and AH were confirmed through more than two separate FNABs. Clinical and biochemical findings, as well as US features, were evaluated. Results Of 214 patients, 100 patients were diagnosed with PTC, 55 patients with FLT, and 59 patients with AH. The proportion of elevated thyrotropin (TSH) levels (p=0.014) and thyroglobulin antibody (Tg-Ab) or thyroid peroxidase antibody (TPO-Ab) positivity (p<0.001) in the FLT group was significantly higher than that in the PTC group. Regarding US features, absence of calcification (p=0.006) and "diffuse thyroid disease" (DTD) pattern on US (p<0.001) were frequently seen in the FLT group. On multivariate analysis, Tg-Ab positivity, presence of a DTD pattern on US, and absence of calcification in nodules were associated with FLT with the best specificity of 99% and positive predictive value of 96%. In contrast, a taller than wide shape of nodules was the only variable significant for differentiating AH from PTC. Conclusion Suspicious thyroid nodules with cytologic benign results could be followed up with US rather than repeat FNAB, if patients exhibit Tg-Ab positivity, no calcifications in nodules, and a DTD pattern on US. PMID:26256977

  15. Thyroid

    MedlinePlus

    Thyroid is used to treat the symptoms of hypothyroidism (a condition where the thyroid gland does not produce enough thyroid hormone). Symptoms of hypothyroidism include lack of energy, depression, constipation, weight gain, ...

  16. Thyroiditis

    MedlinePlus

    ... Hashimoto’s thyroiditis is the most common cause of hypothyroidism in the United States. Postpartum thyroiditis, which causes ... hormone levels in the blood) followed by temporary hypothyroidism, is a common cause of thyroid problems after ...

  17. Retinoic acid inhibits angiogenesis and tumor growth of thyroid cancer cells.

    PubMed

    Hoffmann, Sebastian; Rockenstein, Andreas; Ramaswamy, Anette; Celik, Ilhan; Wunderlich, Anette; Lingelbach, Susanne; Hofbauer, Lorenz C; Zielke, Andreas

    2007-01-29

    The anti-proliferative effect of retinoic acid (RA) has been documented for various tumors. Some 40% of patients with advanced and poorly differentiated thyroid cancer have been shown to respond to RA with increased uptake of radioiodine. It has been suggested that these effects may be caused by redifferentiation. Presently, little is known about the effects of RA on tumor angiogenesis, a prerequisite for growth and metastatic spread. The aim of the current study was to determine, whether tumor-induced angiogenesis of thyroid cancer is affected by RA. In vitro, the effect of 0.1/10 microM 13-cis RA on tumor cell number (MTT assay) and secretion of VEGF (ELISA) was analyzed in three thyroid cancer cell lines (FTC 236, C634 and XTC), as well as in endothelial cells (HUVEC) over several passages. In vivo, tumor growth, VEGF-expression and microvessel density (VSD) of RA treated thyroid cancer cells after xenotransplantation to nude mice was evaluated by morphometric analysis. In vitro, thyroid cancer cell lines responded to RA with reduced proliferation, ranging from 26 to 34% after 2 weeks of treatment and with up to 80% reduced secretion of VEGF. In vivo, tumor volumes of animals receiving RA were reduced by 33% (FTC 236), 27% (C643) and 6% (XTC), respectively. VSD of experimental tumors was diminished in the FTC 236 (25%) and the C643 cell line (15%), and almost unchanged in XTC tumors (7%). In vivo, VEGF-expression and apoptosis were not significantly affected by RA. In vitro, proliferation of HUVEC was inhibited by conditioned medium of C643 cells pretreated with RA (0.1/10 microM), as well as by administration of RA (0.1/10 microM). This study confirms thyroid tumor cell growth to be inhibited by RA. It demonstrates a decrease of in vitro VEGF accumulation and reduction of VSD in experimental undifferentiated thyroid carcinoma, suggesting that reduced angiogenesis may be an important mechanism responsible for the therapeutic effect of RA in thyroid cancer

  18. Differentiated thyroid cancer-personalized therapies to prevent overtreatment.

    PubMed

    Luster, Markus; Weber, Theresia; Verburg, Frederik A

    2014-09-01

    The concept of individualized therapy is rapidly gaining recognition in the management of patients with differentiated thyroid cancer (DTC). This Review provides an overview of the most important elements of this paradigm shift in DTC management and discusses the implications for clinical practice. In the majority of patients with DTC who have an inherently good prognosis, the extent of surgery, the dosage of (131)I therapy and the use of levothyroxine therapy are all aspects suitable for individualization, on the basis of both the stage of disease and the response to treatment. In individuals with advanced disease, newer imaging techniques, advances in (131)I therapy and the use of targeted molecular therapies (such as multitargeted kinase inhibitors) have provided new options for the personalized care of patients, for whom until recently no effective therapies were available. Individualized therapies could reduce adverse effects, including the sometimes debilitating hypothyroidism that used to be required before initiation of (131)I treatment, and major salivary gland damage, a common and unpleasant side effect of (131)I therapy. Highly individualized interdisciplinary treatment of patients with DTC might lead to improved outcomes with reduced severity and frequency of complications and adverse effects. However, in spite of ongoing research, personalized therapies remain in their infancy. PMID:24981455

  19. Aggressive thyroid cancer in low-risk age population

    SciTech Connect

    Rosen, I.B.; Bowden, J.; Luk, S.C.; Simpson, J.A.

    1987-12-01

    Seventy-eight patients under the age of 40 (low-risk patients) who had undergone surgical treatment for well-differentiated thyroid carcinoma were referred from 1979 to 1986 to our hospital for adjuvant therapy. A subgroup of 37 patients, 14 with apparent aggressive cancer, was studied. This study group consisted of 27 female and 10 male patients with mixed papillary and follicular cancer, who ranged in age from 11 to 40 years. Nodal disease occurred in 27 (73%) patients and invasiveness in 30 (81%) patients and involved multiple areas in 9 (24%) patients. Recurrence occurred in 14 (38%) patients and visceral metastases occurred in eight (22%) patients. All patients underwent appropriate surgery, but microscopic residual disease was seen in 15 patients and gross residual disease in seven patients, so that 31 patients underwent iodine-131 therapy, and 17 of these patients also underwent external radiation therapy. Three patients died of their disease, whereas 24 (65%) patients are free of disease and 9 (24%) patients are alive with disease. An additional 7 (19%) patients were initially seen in the fifth to seventh decade after decades of neglected thyroid disease, which culminated in residual cancer and death. Although low-risk categorization for thyroid cancer appears valid, its rigid application in support of conservative treatment may lead to inadequate primary treatment and underdiagnosis of cancer in thyroid nodule disease in the low-risk age population.

  20. Hyperactive ERK and persistent mTOR signaling characterize vemurafenib resistance in papillary thyroid cancer cells

    PubMed Central

    Hanly, Elyse K.; Tuli, Neha Y.; Bednarczyk, Robert B.; Suriano, Robert; Geliebter, Jan; Moscatello, Augustine L.; Darzynkiewicz, Zbigniew; Tiwari, Raj K.

    2016-01-01

    Clinical studies evaluating targeted BRAFV600E inhibitors in advanced thyroid cancer patients are currently underway. Vemurafenib (BRAFV600E inhibitor) monotherapy has shown promising results thus far, although development of resistance is a clinical challenge. The objective of this study was to characterize development of resistance to BRAFV600E inhibition and to identify targets for effective combination therapy. We created a line of BCPAP papillary thyroid cancer cells resistant to vemurafenib by treating with increasing concentrations of the drug. The resistant BCPAP line was characterized and compared to its sensitive counterpart with respect to signaling molecules thought to be directly related to resistance. Expression and phosphorylation of several critical proteins were analyzed by Western blotting and dimerization was evaluated by immunoprecipitation. Resistance to vemurafenib in BCPAP appeared to be mediated by constitutive overexpression of phospho-ERK and by resistance to inhibition of both phospho-mTOR and phospho-S6 ribosomal protein after vemurafenib treatment. Expression of potential alternative signaling molecule, CRAF, was not increased in the resistant line, although formation of CRAF dimers appeared increased. Expression of membrane receptors HER2 and HER3 was greatly amplified in the resistant cancer cells. Papillary thyroid cancer cells were capable of overcoming targeted BRAFV600E inhibition by rewiring of cell signal pathways in response to prolonged vemurafenib therapy. Our study suggests that in vitro culture of cancer cells may be useful in assessing molecular resistance pathways. Potential therapies in advanced thyroid cancer patients may combine vemurafenib with inhibitors of CRAF, HER2/HER3, ERK, and/or mTOR to delay or abort development of resistance. PMID:26735176

  1. Well-Differentiated Thyroid Cancer: The Philippine General Hospital Experience

    PubMed Central

    Uy, Abigail T.; Maningat, Patricia Deanna D.

    2016-01-01

    Background Well-differentiated thyroid cancer (WDTC) is the most common form of thyroid malignancy. While it is typically associated with good prognosis, it may exhibit higher recurrence and mortality rates in selected groups, particularly Filipinos. This paper aims to describe the experience of a Philippine Hospital in managing patients with differentiated thyroid cancer. Methods We performed a retrospective cohort study of 723 patients with WDTC (649 papillary and 79 follicular), evaluating the clinicopathologic profiles, ultrasound features, management received, tumor recurrence, and eventual outcome over a mean follow-up period of 5 years. Results The mean age at diagnosis was 44±13 years (range, 18 to 82), with a majority of cases occurring in the younger age group (<45 years). Most tumors were between 2 and 4 cm in size. The majority of papillary thyroid cancers (PTCs, 63.2%) and follicular thyroid cancers (FTCs, 54.4%) initially presented as stage 1, with a greater proportion of FTC cases (12.7% vs. 3.7%) presenting with distant metastases. Nodal metastases at presentation were more frequent among patients with PTC (29.9% vs. 7.6%). A majority of cases were treated by complete thyroidectomy, followed by radioactive iodine therapy and thyroid stimulating hormone suppression, resulting in a disease-free state. Excluding patients with distant metastases at presentation, the recurrence rates for papillary and FTC were 30.1% and 18.8%, respectively. Conclusion Overall, PTC among Filipinos was associated with a more aggressive and recurrent behavior. FTC among Filipinos appeared to behave similarly with other racial groups. PMID:26754584

  2. External radiotherapy prior to thyroid cancer: A case-control study

    SciTech Connect

    Hallquist, A.; Loefroth, P.O. ); Hardell, L. )

    1993-12-01

    The aim of this investigation was to study previous radiotherapy of malignant diseases as a risk factor for thyroid cancer. By using the Swedish Cancer Registry all cases of thyroid cancer with another malignant disease at least one year previously and living within the catchment area of the hospital were traced. During 1959-1989 a total of 1056 cases of thyroid cancer were identified. Of these, 37 had had another previous malignant disease and they constituted the cases in this study. As controls four persons with at least two malignant diseases, thyroid cancer excluded, were selected for each case from the same cancer registry. Ten (27.0%) of the 37 patients with thyroid cancer as a second tumor had earlier been irradiated with the treatment dose including the thyroid gland as compared with 34 (24.5%) of the 139 control patients. Eight of the ten cases with previous irradiation of the thyroid gland had papillary cancer. The median latency was 13 years. The estimated radiation dose in the thyroid varied between 3 and 40 Gy. External radiotherapy gave a crude odds ratio of 1.1 with 95% confidence interval = 0.5-2.8 for thyroid cancer. The weighted odds ratio was calculated to 2.3 with confidence interval = 0.5-8.9. This case-control study gave a nonsignificantly increased odds ratio for thyroid cancer in patients with external radiotherapy including the thyroid gland. 26 refs., 4 tabs.

  3. Genetics and epigenetics of sporadic thyroid cancer

    PubMed Central

    Vu-Phan, Dang; Koenig, Ronald J.

    2013-01-01

    Thyroid carcinoma is the most common endocrine malignancy, and although the disease generally has an excellent prognosis, therapeutic options are limited for patients not cured by surgery and radioiodine. Thyroid carcinomas commonly contain one of a small number of recurrent genetic mutations. The identification and study of these mutations has led to a deeper understanding of the pathophysiology of this disease and is providing new approaches to diagnosis and therapy. Papillary thyroid carcinomas usually contain an activating mutation in the RAS cascade, most commonly in BRAF and less commonly in RAS itself or through gene fusions that activate RET. A chromosomal translocation that results in production of a PAX8-PPARG fusion protein is found in follicular carcinomas. Anaplastic carcinomas may contain some of the above changes as well as additional mutations. Therapies that are targeted to these mutations are being used in patient care and clinical trials. PMID:23933154

  4. Evaluation of Serum Vascular Adhesion Protein-1 as a Potential Biomarker in Thyroid Cancer

    PubMed Central

    Zhao, Pengxin; Zhang, Kaili

    2016-01-01

    Vascular adhesion protein-1 (VAP-1) is a glycoprotein that mediates tissue-selective lymphocyte adhesion. The prognostic value of VAP-1 has been determined in gastric cancer. The aim of this study was to evaluate the changes and the predictive value of serum VAP-1 in patients with thyroid cancer. A total of 126 patients with thyroid nodules and 53 healthy controls participated in this study. The patients were further divided into subgroup 1 (69 cases with benign thyroid nodules) and subgroup 2 (57 cases with thyroid cancer). Serum VAP-1 was measured by time-resolved immunofluorometric assay. Diagnostic value of presurgical VAP-1 for thyroid cancer was conducted by receiver operating characteristic (ROC) curves. Serum levels of VAP-1 were significantly lower in thyroid cancer group than in healthy control and benign thyroid nodule groups. VAP-1 concentrations negatively correlated with serum thyroglobulin (Tg) levels in thyroid cancer patients (r = −0.81; p < 0.001). The optimum cut-off value of VAP-1 was 456.6 ng/mL with a 77.4% specificity and 66.7% sensitivity for thyroid cancer diagnosis. Serum VAP-1 decreased in thyroid cancer patients and VAP-1 could be a potential useful adjunct biomarker in the diagnosis of thyroid cancer. PMID:27446209

  5. Transmembrane Protease Serine 4 Promotes Thyroid Cancer Proliferation via CREB Phosphorylation

    PubMed Central

    Guan, Hongyu; Liang, Weiwei; Liu, Juan; Wei, Guohong; Li, Hai; Xiu, Lingling; Xiao, Haipeng

    2015-01-01

    Background: Transmembrane protease serine 4 (TMPRSS4), one of the type II transmembrane serine proteases (TTSPs), is elevated in various cancers and is associated with multiple malignant phenotypes. However, the expression pattern and biologic significance of TMPRSS4 in thyroid cancer are largely unknown. In this study, we investigated the expression of TMPRSS4 in thyroid cancer and assessed the pro-proliferative role of TMPRSS4 in thyroid cancer. Methods: Immunohistochemistry and real-time reverse transcription-polymerase chain reaction (RT-PCR) assays were performed to assess the expression of TMPRSS4 in thyroid cancer. We evaluated in vitro cell proliferation using MTT, colony formation, anchorage-independent growth, flow cytometry analysis, and 5-ethynyl-2'-deoxyuridine (EdU) incorporation assays. Western blot, real-time RT-PCR, and luciferase assays were conducted to reveal the underlying mechanisms. Results: TMPRSS4 is overexpressed in thyroid cancer and is associated with the grade of malignancy. Depletion of TMPRSS4 in thyroid cancer cells significantly suppressed proliferation. Moreover, the proliferation of thyroid cancer cells with TMPRSS4 overexpression was significantly enhanced. We also show that cyclic adenosine monophosphate response element-binding protein (CREB)-cyclin D1 signaling mediates, at least partially, the role of TMPRSS4 in thyroid cancer cell proliferation. Conclusions: TMPRSS4 is overexpressed in thyroid cancer and TMPRSS4-CREB signaling is needed to sustain thyroid cancer cell proliferation. PMID:25244400

  6. Thyroid Hormone Receptor-β (TRβ) Mediates Runt-Related Transcription Factor 2 (Runx2) Expression in Thyroid Cancer Cells: A Novel Signaling Pathway in Thyroid Cancer.

    PubMed

    Carr, Frances E; Tai, Phillip W L; Barnum, Michael S; Gillis, Noelle E; Evans, Katherine G; Taber, Thomas H; White, Jeffrey H; Tomczak, Jennifer A; Jaworski, Diane M; Zaidi, Sayyed K; Lian, Jane B; Stein, Janet L; Stein, Gary S

    2016-08-01

    Dysregulation of the thyroid hormone receptor (TR)β is common in human cancers. Restoration of functional TRβ delays tumor progression in models of thyroid and breast cancers implicating TRβ as a tumor suppressor. Conversely, aberrant expression of the runt-related transcription factor 2 (Runx2) is established in the progression and metastasis of thyroid, breast, and other cancers. Silencing of Runx2 diminishes tumor invasive characteristics. With TRβ as a tumor suppressor and Runx2 as a tumor promoter, a compelling question is whether there is a functional relationship between these regulatory factors in thyroid tumorigenesis. Here, we demonstrated that these proteins are reciprocally expressed in normal and malignant thyroid cells; TRβ is high in normal cells, and Runx2 is high in malignant cells. T3 induced a time- and concentration-dependent decrease in Runx2 expression. Silencing of TRβ by small interfering RNA knockdown resulted in a corresponding increase in Runx2 and Runx2-regulated genes, indicating that TRβ levels directly impact Runx2 expression and associated epithelial to mesenchymal transition molecules. TRβ specifically bound to 3 putative thyroid hormone-response element motifs within the Runx2-P1 promoter ((-)105/(+)133) as detected by EMSA and chromatin immunoprecipitation. TRβ suppressed Runx2 transcriptional activities, thus confirming TRβ regulation of Runx2 at functional thyroid hormone-response elements. Significantly, these findings indicate that a ratio of the tumor-suppressor TRβ and tumor-promoting Runx2 may reflect tumor aggression and serve as biomarkers in biopsy tissues. The discovery of this TRβ-Runx2 signaling supports the emerging role of TRβ as a tumor suppressor and reveals a novel pathway for intervention. PMID:27253998

  7. Incidence of thyroid cancer in women in relation to previous exposure to radiation therapy and history of thyroid disease.

    PubMed

    McTiernan, A M; Weiss, N S; Daling, J R

    1984-09-01

    Female residents of 13 counties of Western Washington, in whom papillary, follicular, or mixed papillary-follicular thyroid carcinomas had been diagnosed between 1974 and 1979 were interviewed regarding their medical and reproductive histories and past exposure to radiation treatments. For comparison, a random sample of women from the same population was interviewed. Women who had received radiation treatments to the head or neck prior to 5 years before interview were 16.5 times (95% confidence interval = 8.1-33.5) more likely than unexposed women to develop cancer. The relative risk (RR) was highest for papillary cancer (19.4) but also was elevated substantially for follicular and mixed papillary-follicular tumors. Women first irradiated at age 19 years or younger had a much higher RR than did women irradiated at age 20 or older. Regardless of prior radiation exposure, women who ever had had a goiter were at increased risk of developing thyroid cancer. Women who had ever developed a goiter had 17 times the risk of developing follicular cancer and almost 7 times the risk of developing papillary cancer as compared with women who never had had a goiter. Risk of thyroid cancer was elevated even among women who had had a history of goiter many years prior to diagnosis. A history of thyroid nodules was also a risk factor for papillary and mixed thyroid cancer. Neither a history of hypothyroidism nor hyperthyroidism was found to increase the risk of thyroid cancer. PMID:6590909

  8. Incidence of thyroid cancer in women in relation to previous exposure to radiation therapy and history of thyroid disease

    SciTech Connect

    McTiernan, A.M.; Weiss, N.S.; Daling, J.R.

    1984-09-01

    Female residents of 13 counties of Western Washington, in whom papillary, follicular, or mixed papillary-follicular thyroid carcinomas had been diagnosed between 1974 and 1979 were interviewed regarding their medical and reproductive histories and past exposure to radiation treatments. For comparison, a random sample of women from the same population was interviewed. Women who had received radiation treatments to the head or neck prior to 5 years before interview were 16.5 times (95% confidence interval . 8.1-33.5) more likely than unexposed women to develop cancer. The relative risk (RR) was highest for papillary cancer (19.4) but also was elevated substantially for follicular and mixed papillary-follicular tumors. Women first irradiated at age 19 years or younger had a much higher RR than did women irradiated at age 20 or older. Regardless of prior radiation exposure, women who ever had had a goiter were at increased risk of developing thyroid cancer. Women who had ever developed a goiter had 17 times the risk of developing follicular cancer and almost 7 times the risk of developing papillary cancer as compared with women who never had had a goiter. Risk of thyroid cancer was elevated even among women who had had a history of goiter many years prior to diagnosis. A history of thyroid nodules was also a risk factor for papillary and mixed thyroid cancer. Neither a history of hypothyroidism nor hyperthyroidism was found to increase the risk of thyroid cancer.

  9. Genetic Alterations in Hungarian Patients with Papillary Thyroid Cancer.

    PubMed

    Tobiás, Bálint; Halászlaki, Csaba; Balla, Bernadett; Kósa, János P; Árvai, Kristóf; Horváth, Péter; Takács, István; Nagy, Zsolt; Horváth, Evelin; Horányi, János; Járay, Balázs; Székely, Eszter; Székely, Tamás; Győri, Gabriella; Putz, Zsuzsanna; Dank, Magdolna; Valkusz, Zsuzsanna; Vasas, Béla; Iványi, Béla; Lakatos, Péter

    2016-01-01

    The incidence of thyroid cancers is increasing worldwide. Some somatic oncogene mutations (BRAF, NRAS, HRAS, KRAS) as well as gene translocations (RET/PTC, PAX8/PPAR-gamma) have been associated with the development of thyroid cancer. In our study, we analyzed these genetic alterations in 394 thyroid tissue samples (197 papillary carcinomas and 197 healthy). The somatic mutations and translocations were detected by Light Cycler melting method and Real-Time Polymerase Chain Reaction techniques, respectively. In tumorous samples, 86 BRAF (44.2%), 5 NRAS (3.1%), 2 HRAS (1.0%) and 1 KRAS (0.5%) mutations were found, as well as 9 RET/PTC1 (4.6%) and 1 RET/PTC3 (0.5%) translocations. No genetic alteration was seen in the non tumorous control thyroid tissues. No correlation was detected between the genetic variants and the pathological subtypes of papillary cancer as well as the severity of the disease. Our results are only partly concordant with the data found in the literature. PMID:26259532

  10. Hypertrophic Osteoarthropathy and Follicular Thyroid Cancer: A Rare Paraneoplastic Syndrome

    PubMed Central

    Tavarelli, Martina; Sarfati, Julie; De Gennes, Christian; Haroche, Julien; Buffet, Camille; Ghander, Cécile; Simon, Jean Marc; Ménégaux, Fabrice; Leenhardt, Laurence

    2015-01-01

    Background Hypertrophic osteoarthropathy (HOA) is a rare condition characterized by bone and joint pain and digital clubbing usually associated with bronchopulmonary diseases. Primary HOA is rare and the pathogenesis remains unclear. Objectives Cases of HOA as a paraneoplastic syndrome associated with thyroid carcinoma are very rare – only 2 cases have been described in the literature. Results We present the first case of a 40-year-old patient affected by HOA associated with invasive differentiated follicular thyroid carcinoma operated in 2 stages. Both operations were followed by radioiodine ablation, and then a rapid unresectable local recurrence developed requiring cervical radiotherapy (70 Gy). A second treatment with 100 mCi of 131I confirmed it was a refractory thyroid cancer. Further surgery confirmed a poorly differentiated follicular cancer and 12 cycles of chemotherapy by gemcitabine and oxaliplatin followed. During the 8 years of follow-up, cervical recurrence was stable, but severe episodes of hemoptysis occurred requiring iterative embolization of the bronchial and tracheal arteries. Other lung diseases were excluded. Digital clubbing appeared, which was associated with arthritis, bone pain and inflammatory syndrome. X-rays and magnetic resonance imaging found periosteal apposition in the long bones; bone scintigraphy confirmed the HOA diagnosis. Other causes of arthritis were eliminated. She was treated with colchicine, corticosteroids and nonsteroidal anti-inflammatory drugs, but only the combination of methotrexate and hydroxychloroquine reduced the morphine requirements. Conclusion HOA is exceptionally associated with thyroid cancer and we raised the hypothesis of the secretion of a circulating factor in a patient with invasive and recurrent follicular thyroid cancer, refractory to radioiodine. PMID:26835431

  11. Cervical distribution of iodine 131 following total thyroidectomy for thyroid cancer

    SciTech Connect

    Fratkin, M.J.; Newsome, H.H. Jr.; Sharpe, A.R. Jr.; Tatum, J.L.

    1983-07-01

    The use of postoperative radioiodine thyroid scanning has questioned whether total thyroidectomy is surgically possible. Similar to earlier studies, we have found functioning iodine 131 (/sup 131/I)-avid thyroid tissue in our patients following total thyroidectomy for thyroid cancer. Preoperative and postoperative thyroid scans were compared in 24 patients to study the cervical location of postthyroidectomy residual thyroid tissue. Thyroid scanning detected 44 distinct sites of uptake. Thirty-eight of these foci were located either at the extremes of the upper poles of the thyroid gland (24) or along the embryonic thyroid descent tract (14). We conclude that these foci of /sup 131/I uptake represent incomplete resection of normal thyroid tissue, and that surgical attention to these areas should result more frequently in extirpation of the entire thyroid gland.

  12. The Breast-Thyroid Cancer Link: A Systematic Review and Meta-analysis.

    PubMed

    Nielsen, Sarah M; White, Michael G; Hong, Susan; Aschebrook-Kilfoy, Briseis; Kaplan, Edwin L; Angelos, Peter; Kulkarni, Swati A; Olopade, Olufunmilayo I; Grogan, Raymon H

    2016-02-01

    Rates of thyroid cancer in women with a history of breast cancer are higher than expected. Similarly, rates of breast cancer in those with a history of thyroid cancer are increased. Explanations for these associations include detection bias, shared hormonal risk factors, treatment effect, and genetic susceptibility. With increasing numbers of breast and thyroid cancer survivors, clinicians should be particularly cognizant of this association. Here, we perform a systematic review and meta-analysis of the literature utilizing PubMed and Scopus search engines to identify all publications studying the incidence of breast cancer as a secondary malignancy following a diagnosis of thyroid cancer or thyroid cancer following a diagnosis of breast cancer. This demonstrated an increased risk of thyroid cancer as a secondary malignancy following breast cancer [OR = 1.55; 95% confidence interval (CI), 1.44-1.67] and an increased risk of breast cancer as a secondary malignancy following thyroid cancer (OR = 1.18; 95% CI, 1.09-1.26). There is a clear increase in the odds of developing either thyroid or breast cancer as a secondary malignancy after diagnosis with the other. Here, we review this association and current hypothesis as to the cause of this correlation. Cancer Epidemiol Biomarkers Prev; 25(2); 231-8. ©2016 AACR. PMID:26908594

  13. Iodine and thyroid cancer risk among women in a multiethnic population: the Bay Area Thyroid Cancer Study.

    PubMed

    Horn-Ross, P L; Morris, J S; Lee, M; West, D W; Whittemore, A S; McDougall, I R; Nowels, K; Stewart, S L; Spate, V L; Shiau, A C; Krone, M R

    2001-09-01

    Research on the relationship between iodine exposure and thyroid cancer risk is limited, and the findings are inconclusive. In most studies, fish/shellfish consumption has been used as a proxy measure of iodine exposure. The present study extends this research by quantifying dietary iodine exposure as well as incorporating a biomarker of long-term (1 year) exposure, i.e., from toenail clippings. This study is conducted in a multiethnic population with a wide variation in thyroid cancer incidence rates and substantial diversity in exposure. Women, ages 20-74, residing in the San Francisco Bay Area and diagnosed with thyroid cancer between 1995 and 1998 (1992-1998 for Asian women) were compared with women selected from the general population via random digit dialing. Interviews were conducted in six languages with 608 cases and 558 controls. The established risk factors for thyroid cancer were found to increase risk in this population: radiation to the head/neck [odds ratio (OR), 2.3; 95% confidence interval (CI), 0.97-5.5]; history of goiter/nodules (OR, 3.7; 95% CI, 2.5-5.6); and a family history of proliferative thyroid disease (OR, 2.5; 95% CI, 1.6-3.8). Contrary to our hypothesis, increased dietary iodine, most likely related to the use of multivitamin pills, was associated with a reduced risk of papillary thyroid cancer. This risk reduction was observed in "low-risk" women (i.e., women without any of the three established risk factors noted above; OR, 0.53; 95% CI, 0.33-0.85) but not in "high-risk" women, among whom a slight elevation in risk was seen (OR, 1.4; 95% CI, 0.56-3.4). However, no association with risk was observed in either group when the biomarker of exposure was evaluated. In addition, no ethnic differences in risk were observed. The authors conclude that iodine exposure appears to have, at most, a weak effect on the risk of papillary thyroid cancer. PMID:11535551

  14. Thyroid nodularity and cancer among Chernobyl cleanup workers from Estonia

    SciTech Connect

    Inskip, P.D.; Boice, J.D. Jr.; Tekkel, M.

    1997-02-01

    Thyroid examinations, including palpation, ultrasound and, selectively, fine-needle aspiration biopsy, were conducted on nearly 2,000 Chernobyl cleanup workers from Estonia to evaluate the occurrence of thyroid cancer and nodular thyroid disease among men with protracted exposure to ionizing radiation. The examinations were conducted in four cities in Estonia during March-April 1995, 9 years after the reactor accident. The study population was selected from a predefined cohort of 4,833 cleanup workers from Estonia under surveillance for cancer incidence. These men had been sent to Chernobyl between 1986 and 1991 to entomb the damaged reactor, remove radioactive debris and perform related cleanup activities. A total of 2,997 men were invited for thyroid screening and 1,984 (66%) were examined. Estimates of radiation dose from external sources were obtained from military or other institutional records, and details about service dates and types of work performed while at Chernobyl were obtained from a self-administered questionnaire. Blood samples were collected for assay of chromosomal translocations in circulating lymphocytes and loss of expression of the glycophorin A (GPA) gene in erythrocytes. The primary outcome measure was the presence or absence of thyroid nodules as determined by the ultrasound examination. Of the screened workers, 1,247 (63%) were sent to Chernobyl in 1986, including 603 (30%) sent in April or May, soon after the accident. Workers served at Chernobyl for an average of 3 months. The average age was 32 years at the time of arrival at Chernobyl and 40 years at the time of thyroid examination. The mean documented radiation dose from external sources was 10.8 cGy. Biological indicators of exposure showed low correlations with documented dose, but did not indicate that the mean dose for the population was higher than the average documented dose. 47 refs., 1 fig., 9 tabs.

  15. Thyroid dose and thyroid cancer incidence after the Chernobyl accident: assessments for the Zhytomyr region (Ukraine).

    PubMed

    Goulko, G M; Chepurny, N I; Jacob, P; Kairo, I A; Likhtarev, I A; Pröhl, G; Sobolev, B G

    1998-02-01

    In the Zhytomyr region, about 52,000 measurements of the 131I activity in thyroids were performed. On the basis of these measurements, individual doses have been assessed for the people monitored and age-dependent average doses have been estimated for those settlements with more than 11 direct measurements. In order to estimate the pattern of thyroid exposure in the Zhytomyr region, these doses have been interpolated or extrapolated to population groups who were not monitored during May-June 1986. For this purpose, a model has been developed based on a correlation between thyroid dose estimates with the 137Cs deposition and the co-ordinates of the settlements relative to Chernobyl. Collective doses of people who were born in the years 1968 to 1986 were calculated. The radiation-induced thyroid cancer incidence in the period 1991 to 1995 was assessed by subtracting the spontaneous incidence from the observed incidence. The result is considerably lower than that observed in longer periods after external exposures. Possible reasons for this difference are discussed. PMID:9523343

  16. Completion thyroidectomy for initially misdiagnosed thyroid cancer

    SciTech Connect

    Auguste, L.J.; Attie, J.N. )

    1990-06-01

    Intraoperative frozen sections fails to diagnose thyroid carcinoma accurately in 16% of cases. In such instances, we recommend that completion thyroidectomy be performed in the patient who has invasive carcinoma, is less than 70 years old, and has a reasonable life expectancy. The procedure should be carried out immediately if the error in diagnosis is discovered within a week; otherwise the procedure should be delayed until 3 to 4 months later. At that time, the recurrent laryngeal nerves and at least two parathyroid glands should be dissected and preserved. A paratracheal lymph node dissection should also be performed and the lower jugular lymph nodes should be sampled. If these jugular lymph nodes are found to be positive, a modified radical neck dissection should be added. The morbidity associated with the completion thyroidectomy is minimal. Postoperatively, a 131I scan of the neck should be carried out and ablative doses of radioactive iodine can be given if the uptake in the thyroid bed is greater than 1.5%. Subsequently, all patients are given thyroid suppressive therapy and are monitored closely. This approach will reduce the local recurrence rate and improve the long-term survival. 19 references.

  17. Surgical approach to thyroid nodules and cancer.

    PubMed

    Oertli, D; Harder, F

    2000-12-01

    Fine needle aspiration cytology is the mainstay of the diagnostic work-up of solitary thyroid nodules. Together with the patient's history and the clinical findings, cytology determines the indication for surgery. The minimal intervention for a suspicious nodule consists of thyroid lobectomy. If a diagnosis of malignancy is established, then we recommend total thyroidectomy for all follicular lesions that are larger than 1.5 cm and for high-risk papillary tumours. Near-total thyroidectomy may be appropriate for low-risk patients with papillary carcinoma in whom it is not intended to use radioactive iodine ablation. Whereas ipsilateral lymphadenectomy of the central (primary) compartment should routinely be performed, modified radical neck dissection is only indicated in evident nodal disease of the lateral (secondary) compartment(s). Patients with incidentally discovered differentiated thyroid carcinomas generally do not require complete thyroidectomy unless the tumours are larger than 1.5 cm in diameter or nodal involvement is present. A detailed description of the surgical technique for thyroidectomy and lymphadenectomy is given and an overview of surgical complications is provided. PMID:11289740

  18. Secretome-based identification and characterization of potential biomarkers in thyroid cancer.

    PubMed

    Kashat, Lawrence; So, Anthony K-C; Masui, Olena; Wang, X Simon; Cao, Jun; Meng, Xianwang; Macmillan, Christina; Ailles, Laurie E; Siu, K W Michael; Ralhan, Ranju; Walfish, Paul G

    2010-11-01

    In search of thyroid cancer biomarkers, proteins secreted by thyroid cancer cell lines, papillary-derived TPC-1 and anaplastic-derived CAL62, were analyzed using liquid chromatography-tandem mass spectrometry. Of 46 high-confidence identifications, 6 proteins were considered for verification in thyroid cancer patients' tissue and blood. The localization of two proteins, nucleolin and prothymosin-α (PTMA), was confirmed in TPC-1 and CAL62 cells by confocal microscopy and immunohistochemically in xenografts of TPC-1 cells in NOD/SCID/γ mice and human thyroid cancers (48 tissues). Increased nuclear and cytoplasmic expression of PTMA was observed in anaplastic compared to papillary and poorly differentiated carcinomas. Nuclear expression of nucleolin was observed in all subtypes of thyroid carcinomas, along with faint cytoplasmic expression in anaplastic cancers. Importantly, PTMA, nucleolin, clusterin, cysteine-rich angiogenic inducer 61, enolase 1, and biotinidase were detected in thyroid cancer patients' sera, warranting future analysis to confirm their potential as blood-based thyroid cancer markers. In conclusion, we demonstrated the potential of secretome analysis of thyroid cancer cell lines to identify novel proteins that can be independently verified in cell lines, xenografts, tumor tissues, and blood samples of thyroid cancer patients. These observations support their potential utility as minimally invasive biomarkers for thyroid carcinomas and their application in management of these diseases upon future validation. PMID:20873772

  19. [Current Advances and Future Development of Thyroid Ultrasound Examination--Steps toward State-of-the-Art Laboratory Medicine in Fukushima].

    PubMed

    Shimura, Hiroki

    2015-03-01

    Since the accidents at the Fukushima Daiichi Nuclear Power Plant after the Great East Japan Earthquake on March 11, 2011, large quantities of radionuclides have leaked into the surrounding environment. Fukushima Prefecture started the Fukushima Health Management Survey Project including Thyroid Ultrasound Examination to screen for thyroid cancer in all residents aged 0 to 18 years at the time of the nuclear accident. This accident also led to increased interest in thyroid ultrasound examination in Japan. This article reviews the studies to establish ultrasound diagnostic criteria for thyroid nodules and the clinical guidelines of thyroid nodule management, both of which are fundamental to Thyroid Ultrasound Examination in Fukushima. This article also reviews a study designed to clarify the actual frequency of sonographically detected thyroid nodular lesions among Japanese children, which will become appropriate reference data to interpret the results from Thyroid Ultrasound Examination. Further advances in the screening and management of thyroid diseases are important responsibilities of clinicians and researchers in Fukushima. PMID:26524862

  20. Engineering Multi-Walled Carbon Nanotube Therapeutic Bionanofluids to Selectively Target Papillary Thyroid Cancer Cells

    PubMed Central

    Paliouras, Miltiadis; Mitmaker, Elliot J.; Trifiro, Mark A.

    2016-01-01

    Background The incidence of papillary thyroid carcinoma (PTC) has risen steadily over the past few decades as well as the recurrence rates. It has been proposed that targeted ablative physical therapy could be a therapeutic modality in thyroid cancer. Targeted bio-affinity functionalized multi-walled carbon nanotubes (BioNanofluid) act locally, to efficiently convert external light energy to heat thereby specifically killing cancer cells. This may represent a promising new cancer therapeutic modality, advancing beyond conventional laser ablation and other nanoparticle approaches. Methods Thyroid Stimulating Hormone Receptor (TSHR) was selected as a target for PTC cells, due to its wide expression. Either TSHR antibodies or Thyrogen or purified TSH (Thyrotropin) were chemically conjugated to our functionalized Bionanofluid. A diode laser system (532 nm) was used to illuminate a PTC cell line for set exposure times. Cell death was assessed using Trypan Blue staining. Results TSHR-targeted BioNanofluids were capable of selectively ablating BCPAP, a TSHR-positive PTC cell line, while not TSHR-null NSC-34 cells. We determined that a 2:1 BCPAP cell:α-TSHR-BioNanofluid conjugate ratio and a 30 second laser exposure killed approximately 60% of the BCPAP cells, while 65% and >70% of cells were ablated using Thyrotropin- and Thyrogen-BioNanofluid conjugates, respectively. Furthermore, minimal non-targeted killing was observed using selective controls. Conclusion A BioNanofluid platform offering a potential therapeutic path for papillary thyroid cancer has been investigated, with our in vitro results suggesting the development of a potent and rapid method of selective cancer cell killing. Therefore, BioNanofluid treatment emphasizes the need for new technology to treat patients with local recurrence and metastatic disease who are currently undergoing either re-operative neck explorations, repeated administration of radioactive iodine and as a last resort external beam

  1. Minimally invasive surgical techniques in the management of differentiated thyroid cancer

    PubMed Central

    Tucker, N.; Mitchem, J.; Gillanders, W.

    2015-01-01

    Thyroid cancer is the fifth most common cancer in women with approximately 60,220 expected new cases in the United States in 2013, and the incidence continues to increase each year. Fortunately, the majority are well-differentiated thyroid cancers with excellent overall prognosis. Controversy persists regarding the optimal surgical management of differentiated thyroid cancer in terms of the extent of thyroid resection (thyroid lobectomy vs total thyroidectomy) and the utility of prophylactic central neck dissection (pCND) in low-risk PTC, and papillary thyroid microcarcinoma (PTMC, defined as <10 mm). Thyroid surgical approaches have progressed from the Kocher open incision to minimally invasive techniques that include endoscopic and robotic thyroidectomy. Overall, these minimally invasive techniques have been shown to be safe, and appear to be associated with improved cosmesis and decreased pain compared to open thyroidectomy. PMID:26504264

  2. Quadruple Cancers of Non-producing Multiple Myeloma, Cholangiocellular Carcinoma, and Two Different Thyroid Cancers.

    PubMed

    Mizutani, Shinsuke; Kuroda, Junya; Sasaki, Nana; Kiyota, Miki; Tatekawa, Shotaro; Tsukamoto, Taku; Maegawa, Saori; Chinen, Yoshiaki; Shimura, Yuji; Nagoshi, Hisao; Kobayashi, Tsutomu; Horiike, Shigeo; Tando, So; Fushiki, Shinji; Taniwaki, Masafumi

    2016-01-01

    We report the case of a 72-year-old man who presented with non-producing multiple myeloma (MM) with three additional concomitant solid tumors that were identified by postmortem autopsy. The disease was refractory to anti-MM therapy including bortezomib and lenalidomide, and he finally died of bacterial pneumonia with diffuse alveolar damage 8 months after the diagnosis. An autopsy revealed that he was also affected by three other solid cancers, cholangiocellular carcinoma, medullary thyroid cancer and papillary thyroid cancer that were clinically asymptomatic and remained undiagnosed before death. A review of the literature suggests that primary quadruple cancers including MM are extremely rare. PMID:27150876

  3. Current Concepts in the Molecular Genetics and Management of Thyroid Cancer: An Update for Radiologists.

    PubMed

    Kelil, Tatiana; Keraliya, Abhishek R; Howard, Stephanie A; Krajewski, Katherine M; Braschi-Amirfarzan, Marta; Hornick, Jason L; Ramaiya, Nikhil H; Tirumani, Sree Harsha

    2016-01-01

    Substantial improvement in the understanding of the oncogenic pathways in thyroid cancer has led to identification of specific molecular alterations, including mutations of BRAF and RET in papillary thyroid cancer, mutation of RAS and rearrangement of PPARG in follicular thyroid cancer, mutation of RET in medullary thyroid cancer, and mutations of TP53 and in the phosphatidylinositol 3'-kinase (PI3K)/AKT1 pathway in anaplastic thyroid cancer. Ultrasonography (US) and US-guided biopsy remain cornerstones in the initial workup of thyroid cancer. Surgery is the mainstay of treatment, with radioactive iodine (RAI) therapy reserved for differentiated subtypes. Posttreatment surveillance of thyroid cancer is done with US of the thyroid bed as well as monitoring of tumor markers such as serum thyroglobulin and serum calcitonin. Computed tomography (CT), magnetic resonance imaging, and fluorine 18 fluorodeoxyglucose positron emission tomography/CT are used in the follow-up of patients with negative iodine 131 imaging and elevated tumor markers. Certain mutations, such as mutations of BRAF in papillary thyroid carcinoma and mutations in RET codons 883, 918, and 928, are associated with an aggressive course in medullary thyroid carcinoma, and affected patients need close surveillance. Treatment options for metastatic RAI-refractory thyroid cancer are limited. Currently, Food and Drug Administration-approved molecularly targeted therapies for metastatic RAI-refractory thyroid cancer, including sorafenib, lenvatinib, vandetanib, and cabozantinib, target the vascular endothelial growth factor receptor and RET kinases. Imaging plays an important role in assessment of response to these therapies, which can be atypical owing to antiangiogenic effects. A wide spectrum of toxic effects is associated with the molecularly targeted therapies used in thyroid cancer and can be detected at restaging scans. (©)RSNA, 2016. PMID:27618325

  4. Signs and Symptoms of Thyroid Cancer

    MedlinePlus

    ... Local Offices Volunteer Employment Become a Supplier Report Fraud or ... reserved. The American Cancer Society is a qualified 501(c)(3) tax-exempt organization. Cancer.org is provided courtesy of ...

  5. Destabilizing RET in targeted treatment of thyroid cancers

    PubMed Central

    Gild, M L; Bullock, M; Pon, C K; Robinson, B G; Clifton-Bligh, R J

    2015-01-01

    Metastatic differentiated thyroid cancers (DTC) are resistant to traditional chemotherapy. Kinase inhibitors have shown promise in patients with progressive DTC, but dose-limiting toxicity is commonplace. HSP90 regulates protein degradation of several growth-mediating kinases such as RET, and we hypothesized that HSP90 inhibitor (AUY922) could inhibit RET-mediated medullary thyroid cancer (MTC) as well as papillary thyroid cancer (PTC) cell growth and also radioactive iodine uptake by PTC cells. Studies utilized MTC cell lines TT (C634W) and MZ-CRC-1 (M918T) and the PTC cell line TPC-1 (RET/PTC1). Cell viability was assessed with MTS assays and apoptosis by flow cytometry. Signaling target expression was determined by western blot and radioiodine uptake measured with a gamma counter. Prolonged treatment of both MTC cell lines with AUY922 simultaneously inhibited both MAPK and mTOR pathways and significantly induced apoptosis (58.7 and 78.7% reduction in MZ-CRC-1 and TT live cells respectively, following 1 μM AUY922; P<0.02). Similarly in the PTC cell line, growth and signaling targets were inhibited, and also a 2.84-fold increase in radioiodine uptake was observed following AUY922 administration (P=0.015). AUY922 demonstrates in vitro activity against MTC and PTC cell lines. We observed a potent dose-dependent increase in apoptosis in MTC cell lines following drug administration confirming its anti-tumorigenic effects. Western blots confirm inhibition of pro-survival proteins including AKT suggesting this as the mechanism of cell death. In a functional study, we observed an increase in radioiodine uptake in the PTC cell line following AUY922 treatment. We believe HSP90 inhibition could be a viable alternative for treatment of RET-driven chemo-resistant thyroid cancers. PMID:26574568

  6. Thyroid cancer incidence due to technogenic exposure in childhood.

    PubMed

    Koshurnikova, Nina Alexandrovna; Kaigorodova, Larissa Y; Rabinovich, Evgenya I; Martinenko, Irina I; Okatenko, Pavel A; Khokhryakov, Victor V; Mosharova, Elena P; Mokrov, Juri; Fomin, Evgeny; Alekseyev, Valery S; Panteleyev, Nikolay T; Sannikova, Lubov A; Ryzhykh, Tatyana V

    2012-07-01

    Thyroid cancer incidence was studied in the cohort of residents of Ozyorsk and Kyshtym, the nearest upwind cities to the Mayak Production Association (Mayak PA), Russia's first plutonium production facility, which has been in operation since 1948. Radioactive contamination of areas around the Mayak PA were from unmonitored releases of inert gases produced by industrial reactors and also from the release of uranium fission products from a radiochemical plant stack where irradiated uranium blocks were refined. Iodine-131 (131I) was the main contributor to the technogenic dose from atmospheric releases. Routine monitoring of gaseous releases began in the mid-1960s, when a gas purification system was perfected. Children were a critical group due to their higher radiosensitivity and specific diet (dairy products and vegetables). Both cities maintain Registries containing over 100,000 individuals born from 1934-2006. Among this group, more than 100 cases of thyroid cancer were registered during 1948-2009. The relative risk of thyroid cancer incidence is 1.5 times higher than in the Chelyabinsk. PMID:22647908

  7. Putative BRAF activating fusion in a medullary thyroid cancer

    PubMed Central

    Kasaian, Katayoon; Wiseman, Sam M.; Walker, Blair A.; Schein, Jacqueline E.; Hirst, Martin; Moore, Richard A.; Mungall, Andrew J.; Marra, Marco A.; Jones, Steven J.M.

    2016-01-01

    Medullary thyroid cancer (MTC) is a malignancy of the calcitonin-producing parafollicular cells of the thyroid gland. Surgery is the only curative treatment for this cancer. External beam radiation therapy is reserved for adjuvant treatment of MTC with aggressive features. Targeted therapeutics vandetanib and cabozantinib are approved for the treatment of aggressive and metastatic tumors that are not amenable to surgery. The use of these multikinase inhibitors are supported by the observed overactivation of the RET oncoprotein in a large subpopulation of MTCs. However, not all patients carry oncogenic alterations of this kinase. Hence, there is still a need for comprehensive molecular characterization of MTC utilizing whole-genome and transcriptome-sequencing methodologies with the aim of identifying targetable mutations. Here, we describe the genomic profiles of two medullary thyroid cancers and report the presence of a putative oncogenic BRAF fusion in one. Such alterations, previously observed in other malignancies and known targets of available drugs, can benefit patients who currently have no treatment options. PMID:27148585

  8. Putative BRAF activating fusion in a medullary thyroid cancer.

    PubMed

    Kasaian, Katayoon; Wiseman, Sam M; Walker, Blair A; Schein, Jacqueline E; Hirst, Martin; Moore, Richard A; Mungall, Andrew J; Marra, Marco A; Jones, Steven J M

    2016-03-01

    Medullary thyroid cancer (MTC) is a malignancy of the calcitonin-producing parafollicular cells of the thyroid gland. Surgery is the only curative treatment for this cancer. External beam radiation therapy is reserved for adjuvant treatment of MTC with aggressive features. Targeted therapeutics vandetanib and cabozantinib are approved for the treatment of aggressive and metastatic tumors that are not amenable to surgery. The use of these multikinase inhibitors are supported by the observed overactivation of the RET oncoprotein in a large subpopulation of MTCs. However, not all patients carry oncogenic alterations of this kinase. Hence, there is still a need for comprehensive molecular characterization of MTC utilizing whole-genome and transcriptome-sequencing methodologies with the aim of identifying targetable mutations. Here, we describe the genomic profiles of two medullary thyroid cancers and report the presence of a putative oncogenic BRAF fusion in one. Such alterations, previously observed in other malignancies and known targets of available drugs, can benefit patients who currently have no treatment options. PMID:27148585

  9. High-throughput drug library screening identifies colchicine as a thyroid cancer inhibitor

    PubMed Central

    Zhang, Le; Yang, Zhaoying; Granieri, Letizia; Pasculescu, Adrian; Datti, Alessandro; Asa, Sylvia L.; Xu, Zheli; Ezzat, Shereen

    2016-01-01

    We employed a high-throughput drug library screening platform to identify novel agents affecting thyroid cancer cells. We used human thyroid cancer cell lines to screen a collection of approximately 5200 small molecules with biological and/or pharmacologial properties. Parallel primary screens yielded a number of hits differentially active between thyroid and melanoma cells. Amongst compounds specifically targeting thyroid cancer cells, colchicine emerged as an effective candidate. Colchicine inhibited cell growth which correlated with G2 cell cycle arrest and apoptosis. These effects were hampered through inhibition of MEK1/2 and JNK. In contrast, inhibition of p38-MAPK had little effect, and AKT had no impact on colchicine action. Systemic colchicine inhibited thyroid cancer progression in xenografted mice. These findings demonstrate that our screening platform is an effective vehicle for drug reposition and show that colchicine warrants further attention in well-defined clinical niches such as thyroid cancer. PMID:26942566

  10. High-throughput drug library screening identifies colchicine as a thyroid cancer inhibitor.

    PubMed

    Zhang, Le; Yang, Zhaoying; Granieri, Letizia; Pasculescu, Adrian; Datti, Alessandro; Asa, Sylvia L; Xu, Zheli; Ezzat, Shereen

    2016-04-12

    We employed a high-throughput drug library screening platform to identify novel agents affecting thyroid cancer cells. We used human thyroid cancer cell lines to screen a collection of approximately 5200 small molecules with biological and/or pharmacologial properties. Parallel primary screens yielded a number of hits differentially active between thyroid and melanoma cells. Amongst compounds specifically targeting thyroid cancer cells, colchicine emerged as an effective candidate. Colchicine inhibited cell growth which correlated with G2 cell cycle arrest and apoptosis. These effects were hampered through inhibition of MEK1/2 and JNK. In contrast, inhibition of p38-MAPK had little effect, and AKT had no impact on colchicine action. Systemic colchicine inhibited thyroid cancer progression in xenografted mice. These findings demonstrate that our screening platform is an effective vehicle for drug reposition and show that colchicine warrants further attention in well-defined clinical niches such as thyroid cancer. PMID:26942566

  11. Medullary carcinoma of thyroid

    MedlinePlus

    Thyroid - medullary carcinoma; Cancer - thyroid (medullary carcinoma); MTC ... The cause of medullary carcinoma of the thyroid (MTC) is unknown. Unlike other types of thyroid cancer, MTC is less likely to be caused by radiation therapy to the neck given ...

  12. Fibroblast-Mediated Collagen Remodeling Within the Tumor Microenvironment Facilitates Progression of Thyroid Cancers Driven by BrafV600E and Pten Loss.

    PubMed

    Jolly, Lee Ann; Novitskiy, Sergey; Owens, Phillip; Massoll, Nicole; Cheng, Nikki; Fang, Wei; Moses, Harold L; Franco, Aime T

    2016-04-01

    Contributions of the tumor microenvironment (TME) to progression in thyroid cancer are largely unexplored and may illuminate a basis for understanding rarer aggressive cases of this disease. In this study, we investigated the relationship between the TME and thyroid cancer progression in a mouse model where thyroid-specific expression of oncogenic BRAF and loss of Pten (Braf(V600E)/Pten(-/-)/TPO-Cre) leads to papillary thyroid cancers (PTC) that rapidly progress to poorly differentiated thyroid cancer (PDTC). We found that fibroblasts were recruited to the TME of Braf(V600E)/Pten(-/-)/TPO-Cre thyroid tumors. Conditioned media from cell lines established from these tumors, but not tumors driven by mutant H-ras, induced fibroblast migration and proliferation in vitro Notably, the extracellular matrix of Braf(V600E)/Pten(-/-)/TPO-Cre tumors was enriched with stromal-derived fibrillar collagen, compared with wild-type or Hras-driven tumors. Further, type I collagen enhanced the motility of Braf(V600E)/Pten(-/-)/TPO-Cre tumor cells in vitro In clinical specimens, we found COL1A1 and LOX to be upregulated in PTC and expressed at highest levels in PDTC and anaplastic thyroid cancer. Additionally, increased expression levels of COL1A1 and LOX were associated with decreased survival in thyroid cancer patients. Overall, our results identified fibroblast recruitment and remodeling of the extracellular matrix as pivotal features of the TME in promoting thyroid cancer progression, illuminating candidate therapeutic targets and biomarkers in advanced forms of this malignancy. Cancer Res; 76(7); 1804-13. ©2016 AACR. PMID:26818109

  13. Thyroid dysfunction associated with immunotherapy for patients with cancer.

    PubMed

    Schwartzentruber, D J; White, D E; Zweig, M H; Weintraub, B D; Rosenberg, S A

    1991-12-01

    The authors performed a prospective study to evaluate thyroid dysfunction in 130 patients with cancer who were receiving interleukin-2 (IL-2)-based immunotherapy. Primary hypothyroidism was the most common abnormality, occurring in 12% of patients before, 38% during, and 23% after immunotherapy. Hyperthyroidism occurred in 1%, 4%, and 7% of patients at those time intervals. Among patients initially euthyroid (n = 111), primary hypothyroidism developed in 32% during and 14% after immunotherapy, persisting a median of 54 days. Three patients required levothyroxine. Hyperthyroidism developed in 2% of patients during immunotherapy and 6% after. Thyroid dysfunction was not a function of sex, diagnosis, type of treatment, or response to immunotherapy. Elevated titers of antithyroglobulin and antithyroid microsomal antibodies were detected after treatment in 9% and 7%, respectively, of all patients without prior antibody abnormalities and did not correlate with response to therapy. The high incidence of therapy-induced thyroid dysfunction suggests that thyroid function should be carefully monitored in all patients receiving IL-2-based immunotherapy. PMID:1933775

  14. Generation of Novel Thyroid Cancer Stem-Like Cell Clones: Effects of Resveratrol and Valproic Acid.

    PubMed

    Hardin, Heather; Yu, Xiao-Min; Harrison, April D; Larrain, Carolina; Zhang, Ranran; Chen, Jidong; Chen, Herbert; Lloyd, Ricardo V

    2016-06-01

    Anaplastic thyroid cancer is an aggressive and highly lethal cancer for which conventional therapies have proved ineffective. Cancer stem-like cells (CSCs) represent a small fraction of cells in the cancer that are resistant to chemotherapy and radiation therapy and are responsible for tumor reoccurrence and metastasis. We characterized CSCs in thyroid carcinomas and generated clones of CSC lines. Our study showed that anaplastic thyroid cancers had significantly more CSCs than well-differentiated thyroid cancers. We also showed that Aldefluor-positive cells revealed significantly higher expression of stem cell markers, self-renewal properties, thyrosphere formation, and enhanced tumorigenicity. In vivo passaging of Aldefluor-positive cells resulted in the growth of larger, more aggressive tumors. We isolated and generated two clonal spheroid CSC lines derived from anaplastic thyroid cancer that were even more enriched with stem cell markers and more tumorigenic than the freshly isolated Aldefluor-positive cells. Resveratrol and valproic acid treatment of one of the CSC lines resulted in a significant decrease in stem cell markers, Aldefluor expression, proliferation, and invasiveness, with an increase in apoptosis and thyroid differentiation markers, suggesting that these cell lines may be useful for discovering new adjuvant therapies for aggressive thyroid cancers. For the first time, we have two thyroid CSC lines that will be useful tools for the study of thyroid CSC targeted therapies. PMID:27060227

  15. Randomization to Screening for Prostate, Lung, Colorectal and Ovarian Cancers and Thyroid Cancer Incidence in Two Large Cancer Screening Trials

    PubMed Central

    O'Grady, Thomas J.; Kitahara, Cari M.; DiRienzo, A. Gregory; Boscoe, Francis P.; Gates, Margaret A.

    2014-01-01

    Background Thyroid cancer incidence has increased significantly over the past three decades due, in part, to incidental detection. We examined the association between randomization to screening for lung, prostate, colorectal and/or ovarian cancers and thyroid cancer incidence in two large prospective randomized screening trials. Methods We assessed the association between randomization to low-dose helical CT scan versus chest x-ray for lung cancer screening and risk of thyroid cancer in the National Lung Screening Trial (NLST). In the Prostate Lung Colorectal and Ovarian Cancer Screening Trial (PLCO), we assessed the association between randomization to regular screening for said cancers versus usual medical care and thyroid cancer risk. Over a median 6 and 11 years of follow-up in NLST and PLCO, respectively, we identified 60 incident and 234 incident thyroid cancer cases. Cox proportional hazards regression was used to calculate the cause specific hazard ratios (HR) and 95% confidence intervals (CI) for thyroid cancer. Results In NLST, randomization to lung CT scan was associated with a non-significant increase in thyroid cancer risk (HR  = 1.61; 95% CI: 0.96–2.71). This association was stronger during the first 3 years of follow-up, during which participants were actively screened (HR  = 2.19; 95% CI: 1.07–4.47), but not subsequently (HR  = 1.08; 95% CI: 0.49–2.37). In PLCO, randomization to cancer screening compared with usual care was associated with a significant decrease in thyroid cancer risk for men (HR  = 0.61; 95% CI: 0.49–0.95) but not women (HR  = 0.91; 95% CI: 0.66–1.26). Similar results were observed when restricting to papillary thyroid cancer in both NLST and PLCO. Conclusion Our study suggests that certain medical encounters, such as those using low-dose helical CT scan for lung cancer screening, may increase the detection of incidental thyroid cancer. PMID:25192282

  16. Cell surface and secreted protein profiles of human thyroid cancer cell lines reveal distinct glycoprotein patterns.

    PubMed

    Arcinas, Arthur; Yen, Ten-Yang; Kebebew, Electron; Macher, Bruce A

    2009-08-01

    Cell surface proteins have been shown to be effective therapeutic targets. In addition, shed forms of these proteins and secreted proteins can serve as biomarkers for diseases, including cancer. Thus, identification of cell surface and secreted proteins has been a prime area of interest in the proteomics field. Most cell surface and secreted proteins are known to be glycosylated, and therefore, a proteomics strategy targeting these proteins was applied to obtain proteomic profiles from various thyroid cancer cell lines that represent the range of thyroid cancers of follicular cell origin. In this study, we oxidized the carbohydrates of secreted proteins and those on the cell surface with periodate and isolated them via covalent coupling to hydrazide resin. The glycoproteins obtained were identified from tryptic peptides and N-linked glycopeptides released from the hydrazide resin using two-dimensional liquid chromatography-tandem mass spectrometry in combination with the gas phase fractionation. Thyroid cancer cell lines derived from papillary thyroid cancer (TPC-1), follicular thyroid cancer (FTC-133), Hurthle cell carcinoma (XTC-1), and anaplastic thyroid cancer (ARO and DRO-1) were evaluated. An average of 150 glycoproteins were identified per cell line, of which more than 57% are known cell surface or secreted glycoproteins. The usefulness of the approach for identifying thyroid cancer associated biomarkers was validated by the identification of glycoproteins (e.g., CD44, galectin 3 and metalloproteinase inhibitor 1) that have been found to be useful markers for thyroid cancer. In addition to glycoproteins that are commonly expressed by all of the cell lines, we identified others that are only expressed in the more well-differentiated thyroid cancer cell lines (follicular, Hurthle cell and papillary), or by cell lines derived from undifferentiated tumors that are uniformly fatal forms of thyroid cancer (i.e., anaplastic). On the basis of the results obtained, a

  17. Activation of the RhoB Signaling Pathway by Thyroid Hormone Receptor β in Thyroid Cancer Cells

    PubMed Central

    Ichijo, Sayaka; Furuya, Fumihiko; Shimura, Hiroki; Hayashi, Yoshitaka; Takahashi, Kazuya; Ohta, Kazuyasu; Kobayashi, Tetsuro; Kitamura, Kenichiro

    2014-01-01

    Thyroid hormone receptor (TR) mediates the crucial effects of the thyroid hormone (T3) on cellular growth, development, and differentiation. Decreased expression or inactivating somatic mutations of TRs have been found in human cancers of the liver, breast, lung, and thyroid. The mechanisms of TR-associated carcinogenesis are still not clear. To establish the function of TRβ in thyroid cancer cell proliferation, we constructed a recombinant adenovirus vector, AdTRβ, which expresses human TRβ1 cDNA. Thyroid cancer cell lines in which TRβ protein levels were significantly decreased as compared to intact thyroid tissues were infected with AdTRβ and the function of TRβ on cell proliferation and migration was analyzed. Ligand-bound TRβ induced HDAC1 and HDAC3 dissociation from, and histone acetylation associated with the RhoB promoter and enhanced the expression of RhoB mRNA and protein. In AdTRβ-infected cells, T3 and farnesyl transferase inhibitor (FTI)-treatment induced the distribution of RhoB on the cell membrane and enhanced the abundance of active GTP-bound RhoB. This RhoB protein led to p21-associated cell-cycle arrest in the G0/G1 phase, following inhibition of cell proliferation and invasion. Conversely, lowering cellular RhoB by small interfering RNA knockdown in AdTRβ-infected cells led to downregulation of p21 and inhibited cell-cycle arrest. The growth of BHP18-21v tumor xenografts in vivo was significantly inhibited by AdTRβ injection with FTIs-treatment, as compared to control virus-injected tumors. This novel signaling pathway triggered by ligand-bound TRβ provides insight into possible mechanisms of proliferation and invasion of thyroid cancer and may provide new therapeutic targets for thyroid cancers. PMID:25548921

  18. Cytokine production in patients with papillary thyroid cancer and associated autoimmune Hashimoto thyroiditis.

    PubMed

    Zivancevic-Simonovic, Snezana; Mihaljevic, Olgica; Majstorovic, Ivana; Popovic, Suzana; Markovic, Slavica; Milosevic-Djordjevic, Olivera; Jovanovic, Zorica; Mijatovic-Teodorovic, Ljiljana; Mihajlovic, Dusan; Colic, Miodrag

    2015-08-01

    Hashimoto thyroiditis (HT) is the most frequent thyroid autoimmune disease, while papillary thyroid cancer (PTC) is one of the most common endocrine malignancies. A few patients with HT also develop PTC. The aim of this study was to analyze cytokine profiles in patients with PTC accompanied with autoimmune HT in comparison with those in patients with PTC alone or HT alone and healthy subjects. Cytokine levels were determined in supernatants obtained from phytohemagglutinin (PHA)-stimulated whole blood cultures in vitro. The concentrations of selected cytokines: Th1-interferon gamma (IFN-γ); Th2-interleukin 4 (IL-4), interleukin 5 (IL-5), interleukin 6 (IL-6), interleukin 10 (IL-10) and interleukin 13 (IL-13); Th9-interleukin 9 (IL-9); and Th17-interleukin 17 (IL-17A) were measured using multiplex cytokine detection systems for human Th1/Th2/Th9/Th17/Th22. We found that PTC patients with HT produced significantly higher concentrations of IL-4, IL-6, IL-9, IL-13 and IFN-γ than PTC patients without HT. In conclusion, autoimmune HT affects the cytokine profile of patients with PTC by stimulating secretion of Th1/Th2/Th9 types of cytokines. Th1/Th2 cytokine ratios in PTC patients with associated autoimmune HT indicate a marked shift toward Th2 immunity. PMID:25971541

  19. Differentiated thyroid cancer: feasibility of loboisthmectomy in an endemic region

    PubMed Central

    CALÒ, P.G.; ERDAS, E.; MEDAS, F.; GORDINI, L.; LONGHEU, A.; PISANO, G.; NICOLOSI, A.

    2015-01-01

    Aim The aim of the present retrospective study was to assess the feasibility of loboisthmectomy for the treatment of differentiated thyroid cancer in a endemic area, evaluating the histopathological features and the results of a case series of 1154 patients. Patients and Methods The clinical records of 1154 patients submitted to total thyroidectomy in our Department were retrospectively reviewed to analyze the histopathological characters and the results. Results In 1044 cases (90.5%) a papillary cancer was observed, in 110 (9.5%) a follicular carcinoma; microcarcinomas were 399 (34.5%). Multifocality was present in 323 cases (28%), in 142 unilateral (12.3%) and in 181 bilateral (15.7%). Thyroiditis coexisted in 472 patients (40.9%), multinodular goiter in 404 (35%), Graves’ disease in 48 (4.1%), and multinodular toxic goiter in 38 (3.3%). Complications were: postoperative bleeding in 20 patients (1.7%), transient unilateral vocal cord paralysis in 20 (1.7%) definitive in 10 (0.86%), a transient bilateral paralysis in 1 (0.08%), a transient hypoparathyroidism in 351 (30.4%), and a definitive in 24 (2.07%). Nodal recurrence occurred in 25 patients (2.16%). Conclusions Total thyroidectomy remains the safest treatment in differentiated thyroid cancer, especially if performed in high volume centers in which complications can be minimized. Loboisthmectomy can be a viable and safe alternative in small (< 1 cm) unifocal tumors in patients at low risk. Loboisthmectomy is limited in endemic areas by the association with other thyroid diseases. A correct and detailed information of the patient is essential before planning surgery. PMID:26888701

  20. Risk Stratification in Differentiated Thyroid Cancer: An Ongoing Process

    PubMed Central

    Omry-Orbach, Gal

    2016-01-01

    Thyroid cancer is an increasingly common malignancy, with a rapidly rising prevalence worldwide. The social and economic ramifications of the increase in thyroid cancer are multiple. Though mortality from thyroid cancer is low, and most patients will do well, the risk of recurrence is not insignificant, up to 30%. Therefore, it is important to accurately identify those patients who are more or less likely to be burdened by their disease over years and tailor their treatment plan accordingly. The goal of risk stratification is to do just that. The risk stratification process generally starts postoperatively with histopathologic staging, based on the AJCC/UICC staging system as well as others designed to predict mortality. These do not, however, accurately assess the risk of recurrence/persistence. Patients initially considered to be at high risk may ultimately do very well yet be burdened by frequent unnecessary monitoring. Conversely, patients initially thought to be low risk, may not respond to their initial treatment as expected and, if left unmonitored, may have higher morbidity. The concept of risk-adaptive management has been adopted, with an understanding that risk stratification for differentiated thyroid cancer is dynamic and ongoing. A multitude of variables not included in AJCC/UICC staging are used initially to classify patients as low, intermediate, or high risk for recurrence. Over the course of time, a response-to-therapy variable is incorporated, and patients essentially undergo continuous risk stratification. Additional tools such as biochemical markers, genetic mutations, and molecular markers have been added to this complex risk stratification process such that this is essentially a continuum of risk. In recent years, additional considerations have been discussed with a suggestion of pre-operative risk stratification based on certain clinical and/or biologic characteristics. With the increasing prevalence of thyroid cancer but stable mortality

  1. Effects of thyroid hormones on human breast cancer cell proliferation.

    PubMed

    Hall, Linda C; Salazar, Eddie P; Kane, Staci R; Liu, Nan

    2008-03-01

    The involvement of estrogens in breast cancer development and growth has been well established. However, the effects of thyroid hormones and their combined effects with estrogens are not well studied. We investigated the response of human breast cancer cells to thyroid hormone, particularly the role of T3 in mediating cell proliferation and gene expression. We demonstrated that 17beta-estradiol (E2) or triiodothyronine (T3) promoted cell proliferation in a dose-dependent manner in both MCF-7 and T47-D cell lines. The E2- or T3-dependent cell proliferation was suppressed by co-administration of the ER antagonist ICI. We also demonstrated that T3 could enhance the effect of E2 on cell proliferation in T47-D cells. Using an estrogen response element (ERE)-mediated luciferase assay, we determined that T3 was able to induce the activation of ERE-mediated gene expression in MCF-7 cells, although the effects were much weaker than that induced by E2. These results suggest that T3 can promote breast cancer cell proliferation and increase the effect of E2 on cell proliferation in some breast cancer cell lines and thus that T3 may play a role in breast cancer development and progression. PMID:18328691

  2. Thyroid hormone replacement one day before 131I therapy in patients with well-differentiated thyroid cancer

    PubMed Central

    Kayano, Daiki; Taki, Junichi; Inaki, Anri; Wakabayashi, Hiroshi; Nakamura, Ayane; Fukuoka, Makoto; Kinuya, Seigo

    2013-01-01

    Objective: The current study aimed to determine the efficacy of radioiodine-131 (131I) ablation therapy with thyroid hormone replacement one day before 131I administration in patients with well-differentiated thyroid cancer (DTC). Methods: This retrospective study included 29 patients who underwent 131I therapies twice for DTC during 6-12 months. Since all the patients obviously had residual lesions by their serum thyroglobulin levels or their scintigrams at the first therapies, they underwent the second 131I therapies without diagnostic scintigraphy after the first therapies. After confirming the sufficient elevation of TSH concentration, thyroid hormone replacement was resumed one day before 131I administration (3.7-7.4GBq). The ablation rate of thyroid remnant at the first 131I therapy was evaluated by comparing 131I post-therapeutic images of the two treatments. Results: Three patients were administrated thyroid hormone after 131I therapy because of insufficient TSH concentration under thyroid hormone withdrawal. In the remaining 26 patients, 41 thyroid remnant accumulations were detected in all 26 patients at the first 131I therapy. Based on the second 131I post-therapeutic images, successful ablation was confirmed in 24 of 26 patients (92.3%) and 38 of 41 sites (92.7%), which was comparable with historically reported ablation rates. Conclusion: Thyroid hormone replacement one day before 131I therapy could provide a sufficiently high ablation rate in patients with DTC.

  3. The relationship of thyroid cancer with radiation exposure from nuclear weapon testing in the Marshall Islands.

    PubMed

    Takahashi, Tatsuya; Schoemaker, Minouk J; Trott, Klaus R; Simon, Steven L; Fujimori, Keisei; Nakashima, Noriaki; Fukao, Akira; Saito, Hiroshi

    2003-03-01

    The US nuclear weapons testing program in the Pacific conducted between 1946 and 1958 resulted in radiation exposure in the Marshall Islands. The potentially widespread radiation exposure from radio-iodines of fallout has raised concerns about the risk of thyroid cancer in the Marshallese population. The most serious exposures and its health hazards resulted from the hydrogen-thermonuclear bomb test, the Castle BRAVO, on March 1, 1954. Between 1993 and 1997, we screened 3,709 Marshallese for thyroid disease who were born before the BRAVO test. It was 60% of the entire population at risk and who were still alive at the time of our examinations. We diagnosed 30 thyroid cancers and found 27 other study participants who had been operated for thyroid cancer before our screening in this group. Fifty-seven Marshallese born before 1954 (1.5%) had thyroid cancer or had been operated for thyroid cancer. Nearly all (92%) of these cancers were papillary carcinoma. We derived estimates of individual thyroid dose proxy from the BRAVO test in 1954 on the basis of published age-specific doses estimated on Utirik atoll and 137Cs deposition levels on the atolls where the participants came from. There was suggestive evidence that the prevalence of thyroid cancer increased with category of estimated dose to the thyroid. PMID:12675119

  4. The Noninvestigational Use of Tyrosine Kinase Inhibitors in Thyroid Cancer: Establishing a Standard for Patient Safety and Monitoring

    PubMed Central

    Carhill, Aubrey A.; Cabanillas, Maria E.; Jimenez, Camilo; Waguespack, Steven G.; Habra, Mouhammed A.; Hu, Mimi; Ying, Anita; Vassilopoulou-Sellin, Rena; Gagel, Robert F.; Sherman, Steven I.

    2013-01-01

    Context: The increasing use of tyrosine kinase inhibitor therapy outside of the context of the clinical trial for treatment of advanced thyroid cancer has highlighted the need for a systematic approach to the clinical application of these agents in order to improve patient safety and monitoring promote consistency among providers, and ensure compliance with both institutional and industry standards. Evidence: We reviewed professional thyroid cancer guidelines, the National Comprehensive Cancer Network task force reports, American Society of Clinical Oncology safety standards, review articles, and clinical trials published within the past 10 yr and also included relevant older studies. Conclusions: Review of available published data and the collective experience prescribing tyrosine kinase inhibitors at The University of Texas MD Anderson Cancer Center have highlighted the need for a systematic, comprehensive, and uniform approach to managing these patients. This paper discusses the approach adopted by the Department of Endocrine Neoplasia at the MD Anderson Cancer Center and illustrates practice patterns, experience, and our standardized approach related to prescribing commercially available tyrosine kinase inhibitors outside of the context of a clinical trial for patients with advanced thyroid cancer. PMID:23185034

  5. miR-126-3p Inhibits Thyroid Cancer Cell Growth and Metastasis, and Is Associated with Aggressive Thyroid Cancer

    PubMed Central

    Xiong, Yin; Kotian, Shweta; Zeiger, Martha A.; Zhang, Lisa; Kebebew, Electron

    2015-01-01

    Background Previous studies have shown that microRNAs are dysregulated in thyroid cancer and play important roles in the post-transcriptional regulation of target oncogenes and/or tumor suppressor genes. Methodology/Principal Findings We studied the function of miR-126-3p in thyroid cancer cells, and as a marker of disease aggressiveness. We found that miR-126-3p expression was significantly lower in larger tumors, in tumor samples with extrathyroidal invasion, and in higher risk group thyroid cancer in 496 papillary thyroid cancer samples from The Cancer Genome Atlas study cohort. In an independent sample set, lower miR-126-3p expression was observed in follicular thyroid cancers (which have capsular and angioinvasion) as compared to follicular adenomas. Mechanistically, ectopic overexpression of miR-126-3p significantly inhibited thyroid cancer cell proliferation, in vitro (p<0.01) and in vivo (p<0.01), colony formation (p<0.01), tumor spheroid formation (p<0.05), cellular migration (p<0.05), VEGF secretion and endothelial tube formation, and lung metastasis in vivo. We found 14 predicted target genes, which were significantly altered upon miR-126-3p transfection in thyroid cancer cells, and which are involved in cancer biology. Of these 14 genes, SLC7A5 and ADAM9 were confirmed to be inhibited by miR-126-3p overexpression and to be direct targets of miR-136-3p. Conclusions/Significance To our knowledge, this is the first study to demonstrate that miR-126-3p has a tumor-suppressive function in thyroid cancer cells, and is associated with aggressive disease phenotype. PMID:26244545

  6. Investigation of excess thyroid cancer incidence in Los Alamos County

    SciTech Connect

    Athas, W.F.

    1996-04-01

    Los Alamos County (LAC) is home to the Los Alamos National Laboratory, a U.S. Department of Energy (DOE) nuclear research and design facility. In 1991, the DOE funded the New Mexico Department of Health to conduct a review of cancer incidence rates in LAC in response to citizen concerns over what was perceived as a large excess of brain tumors and a possible relationship to radiological contaminants from the Laboratory. The study found no unusual or alarming pattern in the incidence of brain cancer, however, a fourfold excess of thyroid cancer was observed during the late-1980`s. A rapid review of the medical records for cases diagnosed between 1986 and 1990 failed to demonstrate that the thyroid cancer excess had resulted from enhanced detection. Surveillance activities subsequently undertaken to monitor the trend revealed that the excess persisted into 1993. A feasibility assessment of further studies was made, and ultimately, an investigation was conducted to document the epidemiologic characteristics of the excess in detail and to explore possible causes through a case-series records review. Findings from the investigation are the subject of this report.

  7. Cost-Effectiveness Analysis of Papillary Thyroid Cancer Surveillance

    PubMed Central

    Wang, Laura Y.; Roman, Benjamin R.; Migliacci, Jocelyn C.; Palmer, Frank L.; Tuttle, R. Michael; Shaha, Ashok R.; Shah, Jatin P.; Patel, Snehal G.; Ganly, Ian

    2016-01-01

    BACKGROUND The recent overdiagnosis of subclinical, low-risk papillary thyroid cancer (PTC) coincides with a growing national interest in cost-effective health care practices. The aim of this study was to measure the relative cost-effectiveness of disease surveillance of low-risk PTC patients versus intermediate- and high-risk patients in accordance with American Thyroid Association risk categories. METHODS Two thousand nine hundred thirty-two patients who underwent thyroidectomy for differentiated thyroid cancer between 2000 and 2010 were identified from the institutional database; 1845 patients were excluded because they had non-PTC cancer, underwent less than total thyroidectomy, had a secondary cancer, or had <36 months of follow-up. In total, 1087 were included for analysis. The numbers of postoperative blood tests, imaging scans and biopsies, clinician office visits, and recurrence events were recorded for the first 36 months of follow-up. Costs of surveillance were determined with the Physician Fee Schedule and Clinical Lab Fee Schedule of the Centers for Medicare and Medicaid Services. RESULTS The median age was 44 years (range, 7–83 years). In the first 36 months after thyroidectomy, there were 3, 44, and 22 recurrences (0.8%, 7.8%, and 13.4%) in the low-, intermediate-, and high-risk categories, respectively. The cost of surveillance for each recurrence detected was US $147,819, US $22,434, and US $20,680, respectively. CONCLUSIONS The cost to detect a recurrence in a low-risk patient is more than 6 and 7 times greater than the cost for intermediate- and high-risk PTC patients. It is difficult to justify this allocation of resources to the surveillance of low-risk patients. Surveillance strategies for the low-risk group should, therefore, be restructured. PMID:26280253

  8. The adverse effects of sorafenib in patients with advanced cancers.

    PubMed

    Li, Ye; Gao, Zu-Hua; Qu, Xian-Jun

    2015-03-01

    Sorafenib is the first multi-kinase inhibitor (TKI) approved for the treatment of advanced hepatocellular cancer (HCC) and metastatic renal cell cancer (RCC) and is increasingly being used to treat patients with well-differentiated radioiodine-resistant thyroid cancer (DTC). Sorafenib demonstrates targeted activity on several families of receptor and non-receptor tyrosine kinases that are involved in angiogenesis, tumour growth and metastatic progression of cancer. Sorafenib treatment results in long-term efficacy and low incidence of life-threatening toxicities. Although sorafenib has demonstrated many benefits in patients, the adverse effects cannot be ignored. The most common treatment-related toxicities include diarrhoea, fatigue, hand-foot skin reaction and hypertension. Most of these toxicities are considered mild to moderate and manageable to varying degrees; however, cardiovascular events might lead to death. In this MiniReview, we summarize the adverse effects of sorafenib that commonly occur in patients with advanced cancers. PMID:25495944

  9. A loss-of-function genetic screening identifies novel mediators of thyroid cancer cell viability.

    PubMed

    Cantisani, Maria Carmela; Parascandolo, Alessia; Perälä, Merja; Allocca, Chiara; Fey, Vidal; Sahlberg, Niko; Merolla, Francesco; Basolo, Fulvio; Laukkanen, Mikko O; Kallioniemi, Olli Pekka; Santoro, Massimo; Castellone, Maria Domenica

    2016-05-10

    RET, BRAF and other protein kinases have been identified as major molecular players in thyroid cancer. To identify novel kinases required for the viability of thyroid carcinoma cells, we performed a RNA interference screening in the RET/PTC1(CCDC6-RET)-positive papillary thyroid cancer cell line TPC1 using a library of synthetic small interfering RNAs (siRNAs) targeting the human kinome and related proteins. We identified 14 hits whose silencing was able to significantly reduce the viability and the proliferation of TPC1 cells; most of them were active also in BRAF-mutant BCPAP (papillary thyroid cancer) and 8505C (anaplastic thyroid cancer) and in RAS-mutant CAL62 (anaplastic thyroid cancer) cells. These included members of EPH receptor tyrosine kinase family as well as SRC and MAPK (mitogen activated protein kinases) families. Importantly, silencing of the identified hits did not affect significantly the viability of Nthy-ori 3-1 (hereafter referred to as NTHY) cells derived from normal thyroid tissue, suggesting cancer cell specificity. The identified proteins are worth exploring as potential novel druggable thyroid cancer targets. PMID:27058903

  10. Do Polybrominated Diphenyl Ethers (PBDEs) Increase the Risk of Thyroid Cancer?

    PubMed Central

    Zhang, Yawei; Guo, Grace L.; Han, Xuesong; Zhu, Cairong; Kilfoy, Briseis A.; Zhu, Yong; Boyle, Peter; Zheng, Tongzhang

    2008-01-01

    An increased incidence of thyroid cancer has been reported in many parts of the world including the United States during the past several decades. Recently emerging evidence has demonstrated that polyhalogenated aromatic hydrocarbons (PHAHs), particularly polybrominated diphenyl ethers (PBDEs), alter thyroid hormone homeostasis and cause thyroid dysfunction. However, few studies have been conducted to test whether exposure to PBDEs and other PHAHs increases the risk of thyroid cancer. Here, we hypothesize that elevated exposure to PHAHs, particularly PBDEs, increases the risk of thyroid cancer and may explain part of the increase in incidence of thyroid cancer during the past several decades. In addition, genetic and epigenetic variations in metabolic pathway genes may alter the expression and function of metabolic enzymes which are involved in the metabolism of endogenous thyroid hormones and the detoxification of PBDEs and other PHAHs. Such variation may result in different individual susceptibilities to PBDEs and other PHAHs and the subsequent development of thyroid cancer. The investigation of this hypothesis will lead to an improved understanding of the role of PBDEs and other PHAHs in thyroid tumorigenesis and may provide a real means to prevent this deadly disease. PMID:19122824

  11. Primary surgery for differentiated thyroid cancer in the new millennium.

    PubMed

    Dralle, H; Machens, A

    2012-01-01

    Differentiated thyroid cancers (DTC) are malignancies of follicular cell derivation. Histopathologically and oncologically, DTC fall into two broad tumor categories: papillary (PTC) and follicular thyroid cancer (FTC). These major tumor categories, based on clinical manifestation and biological behavior, are further subdivided into low-risk [papillary microcarcinoma (mPTC); minimally invasive follicular cancer (MIFTC)] and high-risk DTC [PTC>1 cm or metastatic; MIFTC with histopathological angioinvasion; widely invasive FTC (WIFTC)]. Recently, a surgical approach has been adopted that differentiates between low-risk and high-risk DTC. The rationale behind this new concept is to better balance oncologic risk (high vs low) with the surgical morbidity attendant to the procedure (recurrent laryngeal nerve palsy and hypoparathyroidism). This surgical risk is larger with routine total thyroidectomy (TT) and central node dissection (CND) than with less than TT or TT without CND.Whereas TT with CND remains the treatment of choice for high-risk DTC with metastases, the extent of thyroid resection and lymph node dissection can be reduced in low-risk PTC and FTC without demonstrable loss of oncological benefit. In the new millennium, the surgical approach to DTC, especially low-risk PTC and FTC, has undergone considerable change, resulting in less extensive procedures. This risk-adapted strategy relies not only on the skillful histopathologic detection of multifocality in PTC and vascular invasion in MIFTC, but likewise necessitates diligent follow-up to spot and adequately treat local recurrences and distant metastases as they become clinically apparent. PMID:23014068

  12. Controversies in the Management of Papillary Thyroid Cancer Revisited

    PubMed Central

    Guerrero, Marlon A.; Clark, Orlo H.

    2011-01-01

    The debate on the appropriate treatment of patients with papillary thyroid cancer (PTC) has persisted for several decades. The main controversies focus on the extent of surgery, the timing of central neck dissection, and the indications for radioactive iodine ablation. These controversies continue, for the most part, due to the good prognosis of PTC patients and the questionable effect these treatment modalities have on patient survival. This paper addresses these three controversies and the role of molecular tumor markers in the appropriate treatment selection. PMID:22091417

  13. IMRT versus 3D-CRT for thyroid cancer

    NASA Astrophysics Data System (ADS)

    Gizynska, Marta K.; Zawadzka, Anna

    2008-01-01

    A 3D-CRT involving a 4-field (5-field, 6-field, etc.) technique (photon and electron beams) and an alternative IMRT 7-field technique with 6 MV photon fields for thyroid cancer were compared. The IMRT allows reduction in the dose to the spinal cord of about 12 Gy and permits better coverage of the target volume with smaller standard deviation (average 4.65% for 3D-CRT as compared with 1.81% for IMRT). The time needed to prepare therapy (TPS, dosimetry, preparing boluses and electron aperture) and the session time are about the same for both techniques.

  14. The incidence of thyroid cancer is affected by the characteristics of a healthcare system.

    PubMed

    Lee, Tae-Jin; Kim, Sun; Cho, Hong-Jun; Lee, Jae-Ho

    2012-12-01

    The aim of this study was to investigate the associations between the incidence of thyroid cancer and the characteristics of healthcare systems in OECD countries and to demonstrate that the increasing incidence of thyroid cancer is mainly due to overdiagnosis. We used a random effects panel model to regress the incidence of thyroid cancer on the characteristics of healthcare systems (i.e., share of public expenditure on health, mode of health financing, existence of referral system to secondary care, mode of payment to primary care physicians), controlling for macro context variables (i.e., GDP per capita, educational level) on a country level. Data were derived from 34 OECD countries for 2002 and 2008. The share of public expenditure on health was negatively associated with the incidence of thyroid cancer. However, it had no statistically significant effect on the mortality of thyroid cancer and on the incidence of stomach and lung cancer. In the case of colorectal cancer, it had a positive effect on the incidence rate. The upward trend of the incidence of thyroid cancer is closely related to the healthcare system that permits overdiagnosis. Increases in the proportion of public financing may help reduce the overdiagnosis of thyroid cancer. PMID:23255848

  15. Recurrence of papillary thyroid cancer after optimized surgery

    PubMed Central

    2015-01-01

    Recurrence of papillary thyroid cancer (PTC) after optimized surgery requires a full understanding of the disease, especially as it has changed in the last 15 years, what comprises optimized surgery, and the different types and implications of disease relapse that can be encountered. PTC has evolved to tumors that are much smaller than previously seen, largely due to various high quality imaging studies obtained for different reasons, but serendipitously identifying thyroid nodules that prove to be papillary thyroid microcarcinomas (PTMC). With rare exception, these cancers are cured by conservative surgery without additional therapy, and seldom result in recurrent disease. PTC is highly curable in 85% of cases because of its rather innocent biologic behavior. Therefore, the shift in emphasis from disease survival to recurrence is appropriate. As a result of three technologic advances—high-resolution ultrasound (US), recombinant TSH, and highly sensitive thyroglobulin (Tg)—disease relapse can be discovered when it is subclinical. Endocrinologists who largely control administration of radioactive iodine have used it to ablate barely detectable or even biochemically apparent disease, hoping to reduce recurrence and perhaps improve survival. Surgeons, in response to this new intense postoperative surveillance that has uncovered very small volume disease, have responded by utilizing US preoperatively to image this disease, and incorporated varying degrees of lymphadenectomy into their initial treatment algorithm. Bilateral thyroid resection—either total or near-total thyroidectomy—remains the standard for PTC >1 cm, although recent data has re-emphasized the value of unilateral lobectomy in treating even some PTC measuring 1-4 cm. Therapeutic lymphadenectomy has universal approval, but when lymph nodes in the central neck are not worrisome to the surgeon’s intraoperative assessment, although that judgment in incorrect up to 50%, whether they should be excised

  16. A Genomic Alternative to Identify Medullary Thyroid Cancer Preoperatively in Thyroid Nodules with Indeterminate Cytology

    PubMed Central

    Monroe, Robert J.; Traweek, S. Thomas; Lanman, Richard B.; Kennedy, Giulia C.

    2016-01-01

    Background: The use of calcitonin screening for the rare medullary thyroid cancer (MTC) is controversial due to questions of efficacy, accuracy, and cost-effectiveness. This study reports the results of a large prospective validation using a machine-trained algorithm (MTC Classifier) to preoperatively identify MTC in fine-needle aspiration biopsies in lieu of calcitonin measurements. Methods: Cytology analysis on a prospective consecutive series of 50,430 thyroid nodule biopsies yielded a total of 7815 indeterminate (Bethesda categories III/IV) cases, which were tested with the MTC classifier. A prospective, consecutively submitted series of 2673 Bethesda III–VI cases with cytology determined locally was also evaluated. RNA was isolated and tested for the MTC Classifier using microarrays. Results: Forty-three cases were positive by the MTC Classifier among 10,488 tested nodules (0.4%), consistent with the low prevalence of MTC. Of these, all but one was histologically or biochemically confirmed as MTC, yielding a positive predictive value (PPV) of 98%. Of the positive cases, only 19 (44%) had been specifically suspected of MTC by cytology, highlighting the limitations of light microscopy to detect this disease. Three surgically confirmed MTC cases that were detected by the MTC Classifier had low basal serum calcitonin values, indicating these would have been missed by traditional calcitonin screening methods. A pooled analysis of three independent validation sets demonstrates high test sensitivity (97.9%), specificity (99.8%), PPV (97.9%), and negative predictive value (99.8%). Conclusions: A clinical paradigm is proposed, whereby cytologically indeterminate thyroid nodules being tested for common malignancies using gene expression can be simultaneously tested for MTC using the same genomic assay at no added cost. PMID:26992356

  17. Early diagnosis by FNA cytology should not influence the outcome of differentiated thyroid cancer.

    PubMed

    Trimboli, Pierpaolo; Nigri, Giuseppe; Guidobaldi, Leo; Romanelli, Francesco; Aurello, Paolo; Crescenzi, Anna; Appetecchia, Marialuisa; Giovanella, Luca; Valabrega, Stefano

    2016-04-25

    In oncology, the early cancer detection is recognized as associated with good patient's prognosis. Then, one could expect that differentiated thyroid carcinoma (DTC) undergone fine-needle aspiration cytology (FNA) early have better outcome. Aim of this study was to investigate if DTC prognosis is improved by early FNA diagnosis. DTCs followed-up at our institution were included. Information about initial management of thyroid lesion, FNA, surgery, and postoperative follow-up was collected. Cytologies were classified according to British Thyroid Association (BTA). The final series comprised 219 DTCs, of which 22 (10%) recurred. The length of time between nodule appearance and cancer treatment was significantly (p<0.0001) shorter in patients who had undergone FNA than those who had not. In the FNA group, 73 patients underwent biopsy within six months, 25 at 7-12 months, and 43 after at least one year. Regardless of this highly significant (p<0.0001) difference, the results of TNM staging and cancer recurrence rate were no different between these three subgroups. This result was confirmed in DTCs larger than 1 cm submitted to FNA within 12 months or later. When we evaluated the impact of nodule's presentation on DTC outcome, clinically discovered cancers were significantly associated with relapse (OR 2.81) and advanced TNM stages (p=0.03). These data show a lack of clinical impact of the delayed diagnosis of DTC. Also, the postoperative outcome of these patients should not be influenced by the timing of FNA. Instead, DTC patients with preoperative clinical nodule appearance should be considered at higher risk of relapse. PMID:26821685

  18. Thyroid dysfunction and neoplasia in children receiving neck irradiation for cancer

    SciTech Connect

    Fleming, I.D.; Black, T.L.; Thompson, E.I.; Pratt, C.; Rao, B.; Hustu, O.

    1985-03-15

    The reported relationship of radiation exposure and thyroid carcinoma stimulated this retrospective study of 298 patients treated at St. Jude Children's Hospital with radiation therapy to the neck for childhood cancer to identify patients who developed subsequent thyroid abnormalities. This series includes 153 patients with Hodgkin's disease, 95 with acute lymphocytic leukemia, 28 with lymphoepithelioma, and 22 with miscellaneous tumors. Inclusion in the study required 5 years of disease-free survival following therapy for their original tumor, which included thyroid irradiation. Follow-up has been 100%. Most patients also received chemotherapy. Seventeen patients were found to have decreased thyroid reserve with normal levels of free triiodothyroxine (T3) or free thyroxin, (T4) and an elevated level of thyroid-stimulating hormone (TSH). In nine patients hypothyroidism developed, with decreased T3 or T4 levels and an elevated level of TSH. One hyperthyroid patient was identified. Two patients had thyroiditis, and seven had thyroid neoplasms: (carcinoma in two, adenoma in two, colloid nodule in one, and undiagnosed nodules in two). This survey has demonstrated an increased incidence of thyroid dysfunction and thyroid neoplasia when compared to the general population. The importance of long-term follow-up for thyroid disease is emphasized in patients who have received thyroid irradiation. The possible role of subclinical hypothyroidism with TSH elevation coupled with radiation damage to the thyroid gland as a model for the development of neoplastic disease is discussed.

  19. Thyroid Nodules and Shear Wave Elastography: A New Tool in Thyroid Cancer Detection.

    PubMed

    Azizi, Ghobad; Keller, James M; Mayo, Michelle L; Piper, Kelé; Puett, David; Earp, Karly M; Malchoff, Carl D

    2015-11-01

    This study determines the performance of virtual touch imaging quantification (VTIQ), a non-invasive shear wave elastography method for measuring thyroid nodule (TN) stiffness, in distinguishing benign from malignant TNs. This prospective study evaluates 707 TNs in 676 patients with fine-needle aspiration biopsy (FNAB). Before FNAB, both conventional B-mode ultrasound and shear wave elastography were performed. Surgical resection was recommended for FNAB results that were not clearly benign. Surgical pathology confirmed 82 malignant TNs. The receiver operating curve identified a single cut-off of 3.54 m/s as the maximum shear wave velocity (SWV) for predicting thyroid cancer (TC). The sensitivity and specificity were 79.27% and 71.52%, respectively. Positive predictive value (PPV) was 26.75% and negative predictive value (NPV) was 96.34%. Compared with B-mode US features for predicting malignancy, SWV ≥3.54 m/s has a higher sensitivity, specificity, PPV and NPV. TN stiffness measured by VTIQ-generated shear wave elastography is an independent predictor of TC. PMID:26277203

  20. Small cell lung cancer with metastasis to the thyroid in a patient with toxic multinodular goiter.

    PubMed

    Ozgu, Eylem Sercan; Gen, Ramazan; Ilvan, Ahmet; Ozge, Cengiz; Polat, Ayşe; Vayisoglu, Yusuf

    2012-11-01

    Thyroid metastasis of lung cancer is rarely observed in clinical practice. The primary cancers which metastasize to the thyroid gland are mostly renal cell carcinoma, lung cancer, and breast cancer. Transient destructive thyrotoxicosis is caused by massive metastasis of extrathyroid tumors. We herein present a case report of a patient with small cell carcinoma of lung with metastasis to the thyroid and thyrotoxicosis due to toxic multinodular goiter. A 66-year-old man complained of swelling around the right side of the neck, dyspnea, progressive weight loss, and palpitation starting since 3 months before his admission. The patient was diagnosed with small cell carcinoma of lung with metastasis to the thyroid and thyrotoxicosis due to toxic multinodular goiter. The case report presented here illustrates the challenge of making a definitive and adequate diagnosis, particularly if the patient presents with 2 potential causes of thyrotoxicosis. Thyroid scintigraphy is an important tool for differential diagnosis of thyrotoxicosis. PMID:23172496

  1. A prospective study of medical diagnostic radiography and risk of thyroid cancer.

    PubMed

    Neta, Gila; Rajaraman, Preetha; Berrington de Gonzalez, Amy; Doody, Michele M; Alexander, Bruce H; Preston, Dale; Simon, Steven L; Melo, Dunstana; Miller, Jeremy; Freedman, D Michal; Linet, Martha S; Sigurdson, Alice J

    2013-04-15

    Although diagnostic x-ray procedures provide important medical benefits, cancer risks associated with their exposure are also possible, but not well characterized. The US Radiologic Technologists Study (1983-2006) is a nationwide, prospective cohort study with extensive questionnaire data on history of personal diagnostic imaging procedures collected prior to cancer diagnosis. We used Cox proportional hazard regressions to estimate thyroid cancer risks related to the number and type of selected procedures. We assessed potential modifying effects of age and calendar year of the first x-ray procedure in each category of procedures. Incident thyroid cancers (n = 251) were diagnosed among 75,494 technologists (1.3 million person-years; mean follow-up = 17 years). Overall, there was no clear evidence of thyroid cancer risk associated with diagnostic x-rays except for dental x-rays. We observed a 13% increase in thyroid cancer risk for every 10 reported dental radiographs (hazard ratio = 1.13, 95% confidence interval: 1.01, 1.26), which was driven by dental x-rays first received before 1970, but we found no evidence that the relationship between dental x-rays and thyroid cancer was associated with childhood or adolescent exposures as would have been anticipated. The lack of association of thyroid cancer with x-ray procedures that expose the thyroid to higher radiation doses than do dental x-rays underscores the need to conduct a detailed radiation exposure assessment to enable quantitative evaluation of risk. PMID:23529772

  2. International patterns and trends in thyroid cancer incidence, 1973–2002

    PubMed Central

    Kilfoy, Briseis A.; Zheng, Tongzhang; Holford, Theodore R.; Han, Xuesong; Ward, Mary H.; Sjodin, Andreas; Zhang, Yaqun; Bai, Yana; Zhu, Cairong; Guo, Grace L.; Rothman, Nathaniel; Zhang, Yawei

    2009-01-01

    During the past several decades, an increasing incidence of thyroid cancer has been reported in many parts of the world. To date, no study has compared trends in thyroid cancer incidence across continents. We examined incidence data from Cancer Incidence in Five Continents (CI5) over the 30-year period 1973–2002 from 19 populations in the Americas, Asia, Europe and Oceania. Thyroid cancer rates have increased from 1973–1977 to 1998–2002 for most of the populations except for Sweden, in which the incidence rates decreased about 18% for both males and females. The average increase was 48.0% among males and 66.7% among females. More recently, the age-adjusted international thyroid cancer incidence rates from 1998–2002 varied 5-fold by geographic region for males and nearly 10-fold for females by geographic region. Considerable variation in thyroid cancer incidence was present for every continent but Africa, in which the incidence rates were generally low. Our analysis of published CI5 data suggests that thyroid cancer rates increased between 1973 and 2002 in most populations worldwide and that the increase does not appear to be restricted to a particular region of the world or by the underlying rates of thyroid cancer. PMID:19016336

  3. PSMA Expression in Papillary Thyroid Carcinoma: Opening a New Horizon in Management of Thyroid Cancer?

    PubMed

    Taywade, Sameer Kamalakar; Damle, Nishikant Avinash; Bal, Chandrasekhar

    2016-05-01

    Prostate-specific membrane antigen (PSMA) is a type 2 transmembrane protein highly expressed in prostate cancer cells. We present the case of a 50-year-old man with metastatic papillary carcinoma of the thyroid, with rising thyroglobulin level and negative whole-body radioiodine scan after total thyroidectomy. Considering the limited treatment options available, it was decided to perform Ga-PSMA-HBED-CC PET/CT scan. It revealed intense radiotracer uptake in mediastinal and left supraclavicular lymph nodes, brain metastases, bilateral lung nodules, and skeletal sites. Patient also underwent F-FDG PET/CT. It demonstrated similar findings; however, the number of lesions detected in brain was less compared with Ga-PSMA PET/CT. PMID:26914556

  4. Postoperative Complications of Thyroid Cancer in a Single Center Experience

    PubMed Central

    Lee, Yong Sang; Nam, Kee-Hyun; Chung, Woong Youn; Park, Cheong Soo

    2010-01-01

    The aim of this study was to investigate the complications following surgical treatment of thyroid cancer and the association between the extent of surgery and complication rates. A total of 2,636 patients who underwent surgery due to thyroid cancer were retrospectively reviewed to identify surgical complications. Complication rates were assessed according to the extent of surgery, which was classified as follows; less-than-total thyroidectomy with central compartment node dissection (CCND) (Group I, n=636), total thyroidectomy with CCND (Group II, n=1,390), total thyroidectomy plus ipsilateral neck dissection (Group III, n=513), and total thyroidectomy plus bilateral neck dissection (Group IV, n=97). The most common surgical complication was symptomatic hypoparathyroidism, of which 28.4% of cases were transient and 0.3% permanent. The other surgical complications included vocal cord palsy (0.7% transient, and 0.2% permanent), hematoma (0.5%), seroma (4.7%), chyle fistula (1.8%), and Horner's syndrome (0.2%). The complication rates increased significantly with increasing the extent of surgery from Group I to Group IV. The more extensive surgery makes more complications, such as hypoparathyroidism, seroma, and others. PMID:20357995

  5. Municipal mortality due to thyroid cancer in Spain

    PubMed Central

    Lope, Virginia; Pollán, Marina; Pérez-Gómez, Beatriz; Aragonés, Nuria; Ramis, Rebeca; Gómez-Barroso, Diana; López-Abente, Gonzalo

    2006-01-01

    Background Thyroid cancer is a tumor with a low but growing incidence in Spain. This study sought to depict its spatial municipal mortality pattern, using the classic model proposed by Besag, York and Mollié. Methods It was possible to compile and ascertain the posterior distribution of relative risk on the basis of a single Bayesian spatial model covering all of Spain's 8077 municipal areas. Maps were plotted depicting standardized mortality ratios, smoothed relative risk (RR) estimates, and the posterior probability that RR > 1. Results From 1989 to 1998 a total of 2,538 thyroid cancer deaths were registered in 1,041 municipalities. The highest relative risks were mostly situated in the Canary Islands, the province of Lugo, the east of La Coruña (Corunna) and western areas of Asturias and Orense. Conclusion The observed mortality pattern coincides with areas in Spain where goiter has been declared endemic. The higher frequency in these same areas of undifferentiated, more aggressive carcinomas could be reflected in the mortality figures. Other unknown genetic or environmental factors could also play a role in the etiology of this tumor. PMID:17173668

  6. Serum thyroglobulin in the management of patients with thyroid cancer

    SciTech Connect

    Barsano, C.P.; Skosey, C.; DeGroot, L.J.; Refetoff, S.

    1982-04-01

    We have reviewed our experience with the management of patients with thyroid cancer to assess the potential benefits of employing the serum thyroglobulin assay in patient management programs and to determine the optimal conditions for this application. Serum thyroglobulin levels were found to be more reliable when obtained from hypothyroid patients. Levels of thyroglobulin greater than 10 ng/mL appeared to be abnormally elevated in both thyroidectomized patients prior to radioactive iodine therapy (group 1) and in thyroidectomized patients after radioactive iodine therapy (group 2). Elevated thyroglobulin levels were found to be useful indicators of the presence of metastatic disease, whereas normal thyroglobulin levels were reliable indicators of the absence of metastases. In group 1 patients, elevated thyroglobulin levels reliably predicted the presence of important total body scan uptake. In group 2 patients, normal thyroglobulin levels reliably predicted the absence of total body scan uptake. The serum thyroglobulin assay can substantially reduce the need for repetitive total body scanning in the follow-up of group 2 patients with thyroid cancer.

  7. A new appraisal of iodine refractory thyroid cancer.

    PubMed

    Vaisman, Fernanda; Carvalho, Denise P; Vaisman, Mario

    2015-12-01

    Thyroid cancer incidence is increasing all over the world - mostly due to an increase in the detection of small tumors that were previously undetected. A small percentage of these tumors lose the ability to uptake and/or to respond to radioiodine (RAI) therapy, especially in metastatic patients. There are several new therapeutic options that have emerged in the last 5 years to treat RAI refractory thyroid cancer patients, however, it is very important to properly identify RAI refractory patients and to clarify those appropriate for these treatments. In this review, we discuss the RAI refractory definitions and the criteria that have been suggested based on RAI uptake in the post therapy scan, as well as the response after RAI therapy and the possible molecular mechanisms involved in this process. We offer a review of the therapeutic options available at the moment and the therapeutic considerations based on a patient's individualized personal characteristics, primary tumor histology, tumor burden and location and velocity of lesion growth. PMID:26307020

  8. Effects of the chernobyl disaster on thyroid cancer incidence in Turkey after 22 years.

    PubMed

    Acar, Hasan; Cakabay, Bahri; Bayrak, Ferit; Evrenkaya, Tülay

    2011-01-01

    Background. Separate studies involving people who survived atomic bombs have shown that the risk for cancer remains high after 40 years, compared with the risk in the general population. An elevated risk may also remain in regions of Turkey near the Chernobyl disaster. Patients and Methods. A multidisciplinary study conducted in 2008, 22 years after the Chernobyl disaster, examined the thyroid cancer incidence in Rize, a province of Turkey located on the shore of the middle Black Sea. Approximately 100,000 people were screened, and a fine-needle aspiration biopsy was performed in 89 patients. Results. Based on postoperative histopathological examinations, thyroid cancer was diagnosed in six of the 100,000 people screened. Conclusion. Given a thyroid cancer frequency of approximately 8 in 100,000 in the Turkish population, according to the Turkish Cancer Research Association, the rate in Rize reflects no increase in the thyroid cancer incidence 22 years after the Chernobyl disaster. PMID:22229102

  9. IQGAP1 Plays an Important Role in the Invasiveness of Thyroid Cancer

    PubMed Central

    Liu, Zhi; Liu, Dingxie; Bojdani, Ermal; El-Naggar, Adel K.; Vasko, Vasily; Xing, Mingzhao

    2010-01-01

    Purpose This study was designed to explore the role of IQGAP1 in the invasiveness of thyroid cancer and its potential as a novel prognostic marker and therapeutic target in this cancer. Experimental Design We examined IQGAP1 copy gain and its relationship with clinicopathological outcomes of thyroid cancer and investigated its role in cell invasion and molecules involved in the process. Results We found IQGAP1 copy number gain ≥ 3 in 1/30 (3%), 24/74 (32%), 44/107 (41%), 8/16 (50%), and 27/41 (66%) of benign thyroid tumor, follicular variant papillary thyroid cancer (FVPTC), follicular thyroid cancer (FTC), tall cell PTC, and anaplastic thyroid cancer, respectively, in the increasing order of invasiveness of these tumors. A similar tumor distribution trend of copy number ≥ 4 was also seen. IQGAP1 copy gain was positively correlated with IQGAP1 protein expression. It was significantly associated with extrathyroidal and vascular invasion of FVPTC and FTC and, remarkably, a 50–60% rate of multifocality and recurrence of BRAF mutation-positive PTC (P = 0.01 and 0.02, respectively). siRNA knockdown of IQGAP1 dramatically inhibited thyroid cancer cell invasion and colony formation. Co-immunoprecipitation assay demonstrated direct interaction of IQGAP1 with E-cadherin, a known invasion-suppressing molecule, which was up-regulated when IQGAP1 was knocked down. This provided a mechanism for the invasive role of IQGAP1 in thyroid cancer. In contrast, IQGAP3 lacked all these functions. Conclusions IQGAP1, through genetic copy gain, plays an important role in the invasiveness of thyroid cancer and may represent a novel prognostic marker and therapeutic target for this cancer. PMID:20959410

  10. Risk of Thyroid Cancer in a Nationwide Cohort of Patients with Biopsy-Verified Celiac Disease

    PubMed Central

    Lebwohl, Benjamin; Kämpe, Olle; Murray, Joseph A.; Green, Peter H.; Ekbom, Anders

    2013-01-01

    Background In earlier studies based on selected populations, the relative risk for thyroid cancer in celiac disease has varied between 0.6 and 22.5. We aimed to test this relationship in a population-based setting. Methods We collected small intestinal biopsy report data performed in 1969–2008 from all 28 Swedish pathology departments. 29,074 individuals with celiac disease (villous atrophy; Marsh histopathology stage III) were matched for sex, age, calendar year, and county to 144,440 reference individuals from the Swedish general population. Through Cox regression, we then estimated hazard ratios (HRs) and confidence intervals (CIs) for any thyroid cancer and papillary thyroid cancer (defined according to relevant pathology codes in the Swedish Cancer Register) in patients with celiac disease. Results During follow-up, any thyroid cancer developed in seven patients with celiac disease (expected=12) and papillary thyroid cancer developed in five patients (expected=7). Celiac disease was not associated with an increased risk of any thyroid cancer (HR 0.6 [CI 0.3–1.3]) or of papillary thyroid cancer (HR 0.7 [CI 0.3–1.8]). All cases of thyroid cancer in celiac disease occurred in female patients. Risk estimates were similar before and after the year 2000 and independent of age at celiac diagnosis (≤24 years vs. ≥25 years). Conclusions We conclude that, in the Swedish population, there is no increased risk of thyroid cancer in patients with celiac disease. This differs from what has been reported in smaller studies in Italy and the United States. PMID:23281890

  11. Follicular Thyroid Cancer Incidence Patterns in the United States, 1980–2009

    PubMed Central

    Grogan, Raymon H.; Ward, Mary H.; Kaplan, Edwin; Devesa, Susan S.

    2013-01-01

    Background The increases in thyroid cancer overall and in the predominant papillary type have been well documented, but trends for follicular thyroid cancer, a less common but more aggressive variant, have not been as well characterized. In this study, we determined the incidence patterns for follicular thyroid cancer and compared trends between the follicular and papillary thyroid cancers in the United States. Methods We used the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program to examine incidence in the United States during 1980–2009, stratified by demographic and tumor characteristics. Incidence rates (IR) were calculated, relative risks were expressed as incidence rate ratios (IRR), and temporal trends were expressed as percentage changes and plotted. Results Overall we observed a modest increase in age-adjusted follicular thyroid cancer rates among women (31.89%) and men (35.88%). Rates increased most dramatically for regional stage tumors compared to localized tumors in women, whereas the rates for all tumor sizes rose. These findings reveal increases in more aggressive tumors in women in addition to small and localized tumors. The trends for males were different from those among females. Among males, the largest increase was observed for regional and smaller size tumors. The papillary-to-follicular IRR overall was 7.07 [95% confidence interval 6.91–7.24], which varied from 7.37 among Whites to 3.86 among Blacks (SEER race/ethnicity categories), and increased significantly from 3.98 during 1980–1984 to 9.88 during 2005–2009. Conclusion The different trends for follicular and papillary types of thyroid cancer illustrate that thyroid cancer is a heterogeneous disease. Our results do not support the hypothesis that increasing thyroid cancer rates are largely due to improvements in detection, and suggest the importance of evaluating thyroid cancer types separately in future studies. PMID:23360496

  12. Worldwide Increasing Incidence of Thyroid Cancer: Update on Epidemiology and Risk Factors

    PubMed Central

    Frasca, Francesco; Regalbuto, Concetto; Squatrito, Sebastiano; Vigneri, Riccardo

    2013-01-01

    Background. In the last decades, thyroid cancer incidence has continuously and sharply increased all over the world. This review analyzes the possible reasons of this increase. Summary. Many experts believe that the increased incidence of thyroid cancer is apparent, because of the increased detection of small cancers in the preclinical stage. However, a true increase is also possible, as suggested by the observation that large tumors have also increased and gender differences and birth cohort effects are present. Moreover, thyroid cancer mortality, in spite of earlier diagnosis and better treatment, has not decreased but is rather increasing. Therefore, some environmental carcinogens in the industrialized lifestyle may have specifically affected the thyroid. Among potential carcinogens, the increased exposure to medical radiations is the most likely risk factor. Other factors specific for the thyroid like increased iodine intake and increased prevalence of chronic autoimmune thyroiditis cannot be excluded, while other factors like the increasing prevalence of obesity are not specific for the thyroid. Conclusions. The increased incidence of thyroid cancer is most likely due to a combination of an apparent increase due to more sensitive diagnostic procedures and of a true increase, a possible consequence of increased population exposure to radiation and to other still unrecognized carcinogens. PMID:23737785

  13. A case report of hyperfunctioning metastatic thyroid cancer and rare I-131 avid liver metastasis

    PubMed Central

    Kunawudhi, Anchisa; Promteangtrong, Chetsadaporn; Chotipanich, Chanisa

    2016-01-01

    Thyroid cancer is usually, relatively hypofunctional; most patients with thyroid cancer are clinically euthyroid. The combination of thyroid cancer and thyrotoxicosis is not common. We herein, report a case of follicular thyroid cancer with hyperfunctioning metastasis in a 43-year-old woman who presented with thyrotoxicosis, a cold right thyroid nodule, and low I-131 uptake at the thyroid bed. An additional total body scan with I-131 revealed a large radioiodine avid osteolytic bone metastasis with soft tissue masses and liver metastasis. The patient received treatment with total thyroidectomy, methimazole, and I-131 at a cumulative dose of 600 mCi along with recombinant human thyroid-stimulating hormone before the first I-131 treatment and palliative radiation. The patient had normal liver function test and experienced a mild degree of bone marrow suppression after I-131. At the 2-year follow-up, the patient was still alive with the progression of bone metastases but was doing well with less severe thyrotoxicosis, good ambulation, and an Eastern Cooperative Oncology Group performance status of 2. Clinicians should be aware of the unusual concurrent presentation of thyrotoxicosis and thyroid cancer, a differential diagnosis in patients with thyrotoxicosis and low or normal radioiodine uptake over the neck and also potential pitfalls during radionuclide treatment. PMID:27385894

  14. A case report of hyperfunctioning metastatic thyroid cancer and rare I-131 avid liver metastasis.

    PubMed

    Kunawudhi, Anchisa; Promteangtrong, Chetsadaporn; Chotipanich, Chanisa

    2016-01-01

    Thyroid cancer is usually, relatively hypofunctional; most patients with thyroid cancer are clinically euthyroid. The combination of thyroid cancer and thyrotoxicosis is not common. We herein, report a case of follicular thyroid cancer with hyperfunctioning metastasis in a 43-year-old woman who presented with thyrotoxicosis, a cold right thyroid nodule, and low I-131 uptake at the thyroid bed. An additional total body scan with I-131 revealed a large radioiodine avid osteolytic bone metastasis with soft tissue masses and liver metastasis. The patient received treatment with total thyroidectomy, methimazole, and I-131 at a cumulative dose of 600 mCi along with recombinant human thyroid-stimulating hormone before the first I-131 treatment and palliative radiation. The patient had normal liver function test and experienced a mild degree of bone marrow suppression after I-131. At the 2-year follow-up, the patient was still alive with the progression of bone metastases but was doing well with less severe thyrotoxicosis, good ambulation, and an Eastern Cooperative Oncology Group performance status of 2. Clinicians should be aware of the unusual concurrent presentation of thyrotoxicosis and thyroid cancer, a differential diagnosis in patients with thyrotoxicosis and low or normal radioiodine uptake over the neck and also potential pitfalls during radionuclide treatment. PMID:27385894

  15. Papillary thyroid cancer in a young woman affected by giant congenital melanocytic nevus, ultrasound diagnosis.

    PubMed

    Manganaro, L; Onesti, M G; Sergi, M E; Vinci, V; Maruccia, M; Soda, G; Marini, M

    2011-01-01

    Data literatures report numerous association between giant congenital nevus and development alteration; only two cases describe its coexistence with thyroid disorders. However, we report the association of papillary thyroid cancer and giant congenital nevus. Papillary thyroid cancer is the most common differentiated thyroid cancer and has high prevalence in young women. In this paper we report: the case of a 18 years-old woman, affected by giant congenital melanocytic nevus on her back, who came to our observation because of one month of fever and increased volume of latero-cervical lymph nodes. Negative serologic tests allowed us to exclude lymphoma and mononucleosis. Because of the high risk (6%) that giant congenital melanocytic nevi could transform into malignant melanoma, we performed an ultrasound examination (US) of the cervical lymph nodes. The examination extended to the thyroid gland enabled us to visualize the same parenchyma alteration in both thyroid gland and lymph nodes. At last, fine-needle percoutaneus aspiration on thyroid lesion confirmed the presence of papillary carcinoma. In our case, thank to the optimal visualization of the parenchyma structure, US was diriment allowing a diagnosis of primitive thyroid lesion with an involvement of all lymph nodes in the neck. This findings legitimate the role of US as an accurate, noninvasive, radiation free and low-cost imaging technique in detecting differential diagnosis in the cervical lymphadenopathy, as well in preoperative staging thyroid carcinoma. PMID:22041799

  16. Recombinant Human Thyroid Stimulating Hormone versus Thyroid Hormone Withdrawal for Radioactive Iodine Treatment of Differentiated Thyroid Cancer with Nodal Metastatic Disease

    PubMed Central

    Wolfson, Robert M.; Rachinsky, Irina; Morrison, Deric; Driedger, Al; Spaic, Tamara; Van Uum, Stan H. M.

    2016-01-01

    Introduction. Recombinant human thyroid stimulating hormone (rhTSH) is approved for preparation of thyroid remnant ablation with radioactive iodine (RAI) in low risk patients with well differentiated thyroid cancer (DTC). We studied the safety and efficacy of rhTSH preparation for RAI treatment of thyroid cancer patients with nodal metastatic disease. Methods. A retrospective analysis was performed on 108 patients with histopathologically confirmed nodal metastatic DTC, treated with initial RAI between January 1, 2000, and December 31, 2007. Within this selected group, 31 and 42 patients were prepared for initial and all subsequent RAI treatments by either thyroid hormone withdrawal (THW) or rhTSH protocols and were followed up for at least 3 years. Results. The response to initial treatment, classified as excellent, acceptable, or incomplete, was not different between the rhTSH group (57%, 21%, and 21%, resp.) and the THW group (39%, 13%, and 48%, resp.; P = 0.052). There was no significant difference in the final clinical outcome between the groups. The rhTSH group received significantly fewer additional doses of RAI than the THW group (P = 0.03). Conclusion. In patients with nodal-positive DTC, preparation for RAI with rhTSH is a safe and efficacious alternative to THW protocol. PMID:26977148

  17. Role of metallothioneins in benign and malignant thyroid lesions

    PubMed Central

    2012-01-01

    Recent findings in the past two decades have brought many insights into the biology of thyroid benign and malignant lesions, in particular the papillary and follicular thyroid cancers. Although, much progress have been made, thyroid cancers still pose diagnostic problems regarding differentiation of follicular lesions in relation to their aggressiveness and the treatment of advanced and undifferentiated thyroid cancers. Metallothioneins (MTs) were shown to induce cancer cells proliferation, mediate resistance to apoptosis, certain chemotherapeutics and radiotherapy. Therefore, MTs may be of utility in diagnosis and management of patients with benign and malignant lesions of the thyroid. PMID:23273222

  18. Clinical guidelines for management of thyroid nodule and cancer during pregnancy.

    PubMed

    Galofré, Juan Carlos; Riesco-Eizaguirre, Garcilaso; Alvarez-Escolá, Cristina

    2014-03-01

    Special considerations are warranted in management of thyroid nodule and thyroid cancer during pregnancy. The diagnostic and therapeutic approach of thyroid nodules follows the standard practice in non-pregnant women. On the other hand, differentiated thyroid cancer management during pregnancy poses a number of challenges for the mother and fetus. The available data show that pregnancy is not a risk factor for thyroid cancer development or recurrence, although flare-ups cannot be completely ruled out in women with active disease. If surgery is needed, it should be performed during the second term or, preferably, after delivery. A majority of pregnant patients with low-risk disease only need adjustment in levothyroxine therapy. However, women with increased serum thyroglobulin levels before pregnancy or structural disease require regular thyroglobulin measurements and neck ultrasound throughout pregnancy. Pregnancy is an absolute contraindication for radioactive iodine administration. PMID:24176541

  19. Cancer risk estimation in Belarussian children due to thyroid irradiation as a consequence of the Chernobyl nuclear accident

    SciTech Connect

    Buglova, E.; Kenigsberg, J.E.; Sergeeva, N.V.

    1996-07-01

    The thyroid doses received by the juvenile population of Belarus following the Chernobyl accident ranged up to about 10 Gy. The thyroid cancer risk estimate recommended in NCRP Report No. 80 was used to predict the number of thyroid cancer cases among children during 1990-1992 in selected Belarussian regions and cities. The results obtained using this risk estimate show an excess of thyroid cancer cases being registered vs. the predicted cases. Thyroid cancer incidence rate among boys under investigation is higher than among girls in the postaccident period. The excess of the observed over the expected incidence in the general juvenile population is caused by the high thyroid cancer incidence rate among boys. These results, which can be considered part of the first stage of a thorough thyroid cancer risk estimation after the Chernobyl accident, demonstrate the critical need to complete these studies in depth. 6 refs., 5 figs., 3 tabs.

  20. Charting a course through the CEAs: diagnosis and management of medullary thyroid cancer.

    PubMed

    Rowe, Christopher W; Bendinelli, Cino; McGrath, Shaun

    2016-09-01

    Medullary thyroid cancer (MTC) is an uncommon thyroid cancer that requires a high index of suspicion to facilitate diagnosis of early-stage disease amenable to surgical cure. The challenges of diagnosis, as well as management in the setting of persistent disease, are explored in the context of a case presenting with the incidental finding of elevated carcinoembryonic antigen (CEA) and an (18) F-fluorodeoxyglucose positron emission tomography ((18) F-FDG-PET)-positive thyroid incidentaloma detected following treatment of colorectal cancer. Strategies to individualize prognosis, and emerging PET-based imaging modalities, particularly the potential role of (18) F-DOPA-PET in staging, are reviewed. PMID:27230389

  1. Coping with Advanced Cancer

    MedlinePlus

    ... Currents Blog Research Findings Drug Approvals Precision Medicine Leadership Views All Press Releases 2016 2015 2014 2013 ... NCI NCI Overview History Contributing to Cancer Research Leadership Director's Page Previous NCI Directors NCI Organization Advisory ...

  2. Expression and function of CXCL12/CXCR4/CXCR7 in thyroid cancer

    PubMed Central

    ZHU, XIAOLI; BAI, QIANMING; LU, YONGMING; LU, YIQIONG; ZHU, LINLIN; ZHOU, XIAOYAN; WU, LIJING

    2016-01-01

    The contribution of CXCL12/CXCR4/CXCR7 axis to cancer progression has been increasingly recognized. However, its role in thyroid cancer development remains unclear. The present study aimed to examine the expression and function of CXCL12 and its receptors in thyroid cancer. The expression of CXCL12/CXCR4/CXCR7 in human tissue specimens of papillary, follicular, medullary, and anaplastic thyroid carcinoma, follicular adenoma, Hashimoto's thyroiditis and nodular goiter were examined by immunohistochemistry using a tissue microarray. CXCR4 and CXCR7 were over-expressed in human thyroid cancer cells K1 by transduction of recombinant lentivirus. The effect of overexpression of CXCR4 and CXCR7 on K1 cell proliferation and invasion and the molecular mechanism underlying the effect were investigated. CXCL12 was exclusively expressed in papillary thyroid carcinoma tissue but absent in other types of thyroid malignancies and benign lesions. CXCR7 was widely expressed in the endothelial cells of all types of malignancy but only occasionally detected in benign lesions. CXCR4 was expressed in 62.5% of papillary thyroid carcinoma tissue specimens and in 30–40% of other types of malignancy, and it was either absent or weakly expressed in benign lesions. CXCL12 stimulated the invasion and migration of K1 cells overexpressing CXCR4, but did not affect K1 cells overexpressing CXCR7. K1 cell proliferation was not affected by overexpression of CXCR4 or CXCR7. Overexpression of CXCR4 in K1 cells significantly increased AKT and ERK phosphorylation and markedly induced the expression and activity of matrix metalloproteinase-2 (MMP-2). Thus, CXCL12 may be an effective diagnostic marker for papillary thyroid carcinoma, and CXCL12/CXCR4/CXCR7 axis may contribute to thyroid cancer development by regulating cancer cell migration and invasion via AKT and ERK signaling and MMP-2 activation. PMID:27082011

  3. Expression and function of CXCL12/CXCR4/CXCR7 in thyroid cancer.

    PubMed

    Zhu, Xiaoli; Bai, Qianming; Lu, Yongming; Lu, Yiqiong; Zhu, Linlin; Zhou, Xiaoyan; Wu, Lijing

    2016-06-01

    The contribution of CXCL12/CXCR4/CXCR7 axis to cancer progression has been increasingly recognized. However, its role in thyroid cancer development remains unclear. The present study aimed to examine the expression and function of CXCL12 and its receptors in thyroid cancer. The expression of CXCL12/CXCR4/CXCR7 in human tissue specimens of papillary, follicular, medullary, and anaplastic thyroid carcinoma, follicular adenoma, Hashimoto's thyroiditis and nodular goiter were examined by immunohistochemistry using a tissue microarray. CXCR4 and CXCR7 were over-expressed in human thyroid cancer cells K1 by transduction of recombinant lentivirus. The effect of overexpression of CXCR4 and CXCR7 on K1 cell proliferation and invasion and the molecular mechanism underlying the effect were investigated. CXCL12 was exclusively expressed in papillary thyroid carcinoma tissue but absent in other types of thyroid malignancies and benign lesions. CXCR7 was widely expressed in the endothelial cells of all types of malignancy but only occasionally detected in benign lesions. CXCR4 was expressed in 62.5% of papillary thyroid carcinoma tissue specimens and in 30-40% of other types of malignancy, and it was either absent or weakly expressed in benign lesions. CXCL12 stimulated the invasion and migration of K1 cells overexpressing CXCR4, but did not affect K1 cells overexpressing CXCR7. K1 cell proliferation was not affected by overexpression of CXCR4 or CXCR7. Overexpression of CXCR4 in K1 cells significantly increased AKT and ERK phosphorylation and markedly induced the expression and activity of matrix metalloproteinase-2 (MMP‑2). Thus, CXCL12 may be an effective diagnostic marker for papillary thyroid carcinoma, and CXCL12/CXCR4/CXCR7 axis may contribute to thyroid cancer development by regulating cancer cell migration and invasion via AKT and ERK signaling and MMP-2 activation. PMID:27082011

  4. Genetic and Pharmacological Targeting of CSF-1/CSF-1R Inhibits Tumor-Associated Macrophages and Impairs BRAF-Induced Thyroid Cancer Progression

    PubMed Central

    Ryder, Mabel; Gild, Matti; Hohl, Tobias M.; Pamer, Eric; Knauf, Jeff; Ghossein, Ronald; Joyce, Johanna A.; Fagin, James A.

    2013-01-01

    Advanced human thyroid cancers are densely infiltrated with tumor-associated macrophages (TAMs) and this correlates with a poor prognosis. We used BRAF-induced papillary thyroid cancer (PTC) mouse models to examine the role of TAMs in PTC progression. Following conditional activation of BRAFV600E in murine thyroids there is an increased expression of the TAM chemoattractants Csf-1 and Ccl-2. This is followed by the development of PTCs that are densely infiltrated with TAMs that express Csf-1r and Ccr2. Targeting CCR2-expressing cells during BRAF-induction reduced TAM density and impaired PTC development. This strategy also induced smaller tumors, decreased proliferation and restored a thyroid follicular architecture in established PTCs. In PTCs from mice that lacked CSF-1 or that received a c-FMS/CSF-1R kinase inhibitor, TAM recruitment and PTC progression was impaired, recapitulating the effects of targeting CCR2-expressing cells. Our data demonstrate that TAMs are pro-tumorigenic in advanced PTCs and that they can be targeted pharmacologically, which may be potentially useful for patients with advanced thyroid cancers. PMID:23372702

  5. Quality of life aspects in the management of thyroid cancer.

    PubMed

    Duan, H; Gamper, E; Becherer, A; Hoffmann, M

    2015-06-01

    While there is agreement that quality of life (QoL) is a central aim of medical treatment, the methods of its evaluation as well as its role in the patient's overall treatment experience are under continuous scrutiny. Different perspectives on patients' QoL have emerged; from the treating physician, from the psychologist, and naturally from the patient him/herself. This article provides insights into each of these views within the context of thyroid cancer where, as a consequence of increasing incidence and decreasing mortality rates, QoL aspects deserve close attention. Physicians often find themselves in situations where they perform a balancing act between what they know is best from a somatic point of view and learning about what is best for the individual patient. For psychologists in the field of oncology, a main area of interest is the incorporation of the patient's perspective into research by using patient-reported outcomes (PROs) which include QoL assessment. PROs can also be used in clinical practice as a way to start a conversation about symptoms and QoL aspects that perhaps patients might not volunteer, and this allows physicians to address QoL issues more directly. Patients usually appreciate being asked about all aspects of QoL, and need sound information about how their QoL might be affected by the disease and its treatment. By examining and understanding the different perspectives on QoL, and how QoL differs in patients with thyroid cancer compared with other cancers, it is hoped that the QoL can be enhanced in this particular patient group. PMID:25920747

  6. Volumetric modulated arc radiotherapy sparing the thyroid gland for early-stage glottic cancer: A dosimetrical analysis

    PubMed Central

    KIM, EUN SEOK; YEO, SEUNG-GU

    2014-01-01

    Previous studies on advanced radiotherapy (RT) techniques for early stage glottic cancer have focused on sparing the carotid artery. However, the aim of the present study was to evaluate the dosimetric advantages of volumetric modulated arc therapy (VMAT) in terms of sparing the thyroid gland in early-stage glottic cancer patients. In total, 15 cT1N0M0 glottic cancer patients treated with definitive RT using VMAT were selected, and for dosimetric comparison, a conventional RT plan comprising opposed-lateral wedged fields was generated for each patient. The carotid artery, thyroid gland and spinal cord were considered organs at risk. The prescription dose was 63 Gy at 2.25 Gy per fraction. For the thyroid gland and carotid artery, all compared parameters were significantly lower with VMAT compared with conventional RT. For the thyroid gland, the median reduction rates of the mean dose (Dmean), the volume receiving ≥30% of the prescription dose (V30) and the V50 were 32.6, 40.9 and 46.0%, respectively. The Dmean was 14.7±2.6 Gy when using VMAT compared with 22.2±3.9 Gy when using conventional RT. The differences between the techniques in terms of planning target volume coverage and dose homogeneity were not significant. When considering a recent normal tissue complication probability model, which indicated the mean thyroid gland dose as the most significant predictor of radiation-induced hypothyroidism, the dosimetric advantage shown in this study may be valuable in reducing hypothyroidism following RT for early stage glottic cancer patients. PMID:24932276

  7. DNA damage among thyroid cancer and multiple cancer cases, controls, and long-lived individuals

    SciTech Connect

    Sigurdson, A J; Hauptmann, M; Alexander, B J; Doody, M M; Thomas, C B; Struewing, J P; Jones, I M

    2004-08-24

    Variation in the detection, signaling, and repair of DNA damage contributes to human cancer risk. To assess capacity to modulate endogenous DNA damage among radiologic technologists who had been diagnosed with breast cancer and another malignancy (breast-other; n=42), early-onset breast cancer (early-onset, age {<=} 35; n=38), thyroid cancer (n=68), long-lived cancer-free individuals (hyper-normals; n=20) and cancer-free controls (n=49) we quantified DNA damage (single strand breaks and abasic sites) in untreated lymphoblastoid cell lines using the alkaline comet assay. Komet{trademark} software provided comet tail length, % DNA in tail (tail DNA), comet distributed moment (CDM), and Olive tail moment (OTM) summarized as the geometric mean of 100 cells. Category cut-points (median and 75th percentile) were determined from the distribution among controls. Tail length (for {>=} 75% vs. below the median, age adjusted) was most consistently associated with the highest odds ratios in the breast-other, early-onset, and thyroid cancer groups (with risk increased 10-, 5- or 19-fold, respectively, with wide confidence intervals) and decreased risk among the hyper-normal group. For the other three Comet measures, risk of breast-other was elevated approximately three-fold. Risk of early-onset breast cancer was mixed and risk of thyroid cancer ranged from null to a two-fold increase. The hyper-normal group showed decreased odds ratios for tail DNA and OTM, but not CDM. DNA damage, as estimated by all Comet measures, was relatively unaffected by survival time, reproductive factors, and prior radiation treatment. We detected a continuum of endogenous DNA damage that was highest among cancer cases, less in controls, and suggestively lowest in hyper-normal individuals. Measuring this DNA damage phenotype may contribute to the identification of susceptible sub-groups. Our observations require replication in a prospective study with a large number of pre-diagnostic samples.

  8. Cancer risks after diagnostic doses of 131I with special reference to thyroid cancer

    SciTech Connect

    Holm, L.E. )

    1991-01-01

    Between 1951 and 1969 a total of 35,074 patients less than 75 years of age (mean = 44 years) were examined with diagnostic doses of 131I. The mean administered activity of 131I was 52 microCi and the radiation dose to the thyroid gland was on the average of 0.5 Gy. The cohort was matched with the Swedish Cancer Register for the years 1958-1984. During this period, 3746 cancers occurred more than 5 years after the 131I examination, and the resulting standardized incidence ratio (SIR) was 1.01 (95% confidence interval (CI) = 0.98 to 1.04). SIR for thyroid cancer was 1.18 (95% CI = 0.88 to 1.56). The risks for both cancer of all sites and for thyroid cancer were highest 5 to 9 years after examination (SIR = 1.07 and 2.06, respectively) and did not differ from unity thereafter. With greater than or equal to 10 years of follow-up, risk was not statistically associated with the dose of 131I.

  9. A population-based case-control study of thyroid cancer.

    PubMed

    Ron, E; Kleinerman, R A; Boice, J D; LiVolsi, V A; Flannery, J T; Fraumeni, J F

    1987-07-01

    A population-based case-control interview study of thyroid cancer (159 cases and 285 controls) was conducted in Connecticut. Prior radiotherapy to the head or neck was reported by 12% of the cases and 4% of the controls [odds ratio (OR) = 2.8; 95% confidence interval = 1.2-6.9]. Risk was inversely related to age at irradiation and was highest among children exposed under age 10. Few persons born after 1945 received prior radiotherapy, consistent with the declining use of radiation to treat benign conditions in the 1950's. Among females the radiogenic risk appeared to be potentiated by the number of subsequent live-births. Other significant risk factors included a history of benign thyroid nodules (OR = 33) or goiter (OR = 5.6). Miscarriage and multiparity increased risk but only among women who developed thyroid cancer before age 35 years. Consumption of shellfish (a rich source of iodine) seemed to increase the risk of follicular thyroid cancer, whereas consumption of goitrogen-containing vegetables appeared to reduce risk of total thyroid cancer, possibly because of their cruciferous nature. A significantly low risk was observed among persons of English descent, whereas Italian ancestry appeared to increase risk. No significant associations were found with a number of suspected risk factors: diagnostic x-rays, radioactive isotope scans, occupational radiation exposure, tonsillectomy, Jewish ethnicity, alcohol intake, cigarette smoking, oral contraceptives, lactation suppressants, menopausal estrogens, most other common medications, and water source. New associations were suggested for obesity among females (OR = 1.5), surgically treated benign breast disease (OR = 1.6), use of spironolactone (OR = 4.3) or vitamin D supplements (OR = 1.8), and a family history of thyroid cancer (OR = 5.2). About 9% of the incident thyroid cancers could be attributed to prior head and neck irradiation, 4% to goiter, and 17% to thyroid nodular disease, leaving the etiology of most

  10. cabozantinib (COMETRIQ⁰). In medullary thyroid cancer: more harmful than beneficial, as is vandetanib.

    PubMed

    2016-01-01

    Surgery is the mainstay of treatment for medullary thyroid cancer. Cytotoxic chemotherapy is generally ineffective in patients with progressive, inoperable, advanced-stage or metastatic tumours. Vandetanib is also authorised in this setting, but it has more harms than benefits. Cabozantinib, like vandetanib, inhibits several tyrosine kinases involved in angiogenesis. Cabozantinib has been authorised in the European Union for use in this setting. In a randomised, placebo-controlled trial in 330 patients, adding cabozantinib to tailored symptomatic treatment did not prolong survival or improve symptoms, despite a favourable effect on tumour imaging and certain laboratory parameters. On the contrary, cabozantinib appeared to undermine quality of life and aggravate diarrhoea. The known adverse effects of cabozantinib are numerous and often severe: diarrhoea, hand-foot syndrome, hypertension, venous and arterial thrombosis, bleeding and fistulae. Deaths unrelated to tumour progression were more frequent with cabozantinib than with placebo. Cabozantinib carries a risk of multiple pharmacokinetic interactions by interfering with cytochrome P450 isoenzyme CYP3A4 and P-glycoprotein. In animals, cabozantinib is teratogenic and also impairs male and female fertility. Contraception is required for women, and also for the partners of treated men, who must use condoms. These precautions must be maintained for at least 4 months after the end of treatment. In practice, in mid-2015, cabozantinib, like vandetanib, has an unfavourable harm-benefit balance in medullary thyroid cancer. The focus should remain on tailored symptomatic care. PMID:26942253

  11. Transaxillary single-incision robotic neck dissection for metastatic thyroid cancer

    PubMed Central

    Kang, Sang-Wook

    2015-01-01

    In head and neck area, neck dissection (ND) is one of the most complex and precision-needed procedure. The long cervical scar and post-operative neck discomfort have been also inevitable brands after this procedure. Heretofore, few dare to try endoscopic surgical technique to the ND mainly due to its complexity and jeopardy of complication. Although, there have been several reports about the endoscopic approaches for functional ND or ND, they had so many technical and instrumental limitations. The dexterities of the surgical robotics have advanced the techniques of endoscopic surgery, and have facilitated the most precise and delicate endoscopic surgical procedure in head and neck area. The technical feasibility and early surgical outcomes of robotic ND using the transaxillary approach for the management of metastatic thyroid cancer have already been reported as satisfactory. Robotic ND can allow complete compartment-oriented lymph node (LN) dissection without any fatal complications, or compromising oncologic principles. We previously described a novel method of robotic thyroidectomy with ND using a gasless transaxillary approach for metastatic thyroid cancer, and here, we firstly introduce a less invasive robotic procedure which has been modified from the original one, which we refer to as the transaxillary single-incision robotic ND. PMID:26425451

  12. Colon cancer metastasis to the thyroid gland: report of a case with unique molecular profile.

    PubMed

    Roloff, Gregory W; Yang, Zhiming; Wood, Lauren V; Neychev, Vladimir K

    2016-06-01

    A high index of suspicion is needed when a patient presents with thyroid mass in the settings of an advanced CRC. Secondary thyroid malignancy should be considered unless proven otherwise. reatment should be determined considering extent of CRC metastasis, patient's general condition, and presence of local symptoms. PMID:27398194

  13. The Role of Podoplanin in the Biology of Differentiated Thyroid Cancers

    PubMed Central

    Rudzińska, Magdalena; Gaweł, Damian; Sikorska, Justyna; Karpińska, Kamila M.; Kiedrowski, Mirosław; Stępień, Tomasz; Marchlewska, Magdalena; Czarnocka, Barbara

    2014-01-01

    Podoplanin (PDPN), a mucin-type transmembrane glycoprotein specific to the lymphatic system is expressed in a variety of human cancers, and is regarded as a factor promoting tumor progression. The purpose of this study was to elucidate the molecular role of PDPN in the biology of thyroid cancer cells. PDPN expression was evaluated in primary thyroid carcinomas and thyroid carcinoma cell lines by RT-qPCR, Western blotting, IF and IHC. To examine the role of podoplanin in determining a cell's malignant potential (cellular migration, invasion, proliferation, adhesion, motility, apoptosis), a thyroid cancer cell line with silenced PDPN expression was used. We observed that PDPN was solely expressed in the cancer cells of 40% of papillary thyroid carcinoma (PTC) tissues. Moreover, PDPN mRNA and protein were highly expressed in PTC-derived TPC1 and BcPAP cell lines but were not detected in follicular thyroid cancer derived cell lines. PDPN knock-down significantly decreased cellular invasion, and modestly reduced cell migration, while proliferation and adhesion were not affected. Our results demonstrate that PDPN mediates the invasive properties of cells derived from papillary thyroid carcinomas, suggesting that podoplanin might promote PTC progression. PMID:24797369

  14. Advances in cancer immunology and cancer immunotherapy.

    PubMed

    Voena, Claudia; Chiarle, Roberto

    2016-02-01

    After decades of setbacks, cancer immunology is living its Golden Age. Recent advances in cancer immunology have provided new therapeutic approaches to treat cancer. The objective clinical response observed in patients treated with antibodies that block the immune checkpoints, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell-death protein 1 (PD-1)/programmed cell-death 1 ligand 1 (PD-L1) pathways, has led to their FDA approval for the treatment of melanoma in 2011 and in 2014, respectively. The anti-PD-1 antibody nivolumab has received the FDA-approval in March 2015 for squamous lung cancer treatment. In addition, antibodies targeting PD-1 or PD-L1 have demonstrated their efficacy and safety in additional tumors, including non-small cell lung carcinoma (NSCLC), renal cell carcinoma (RCC), bladder cancer, and Hodgkin's lymphoma. Almost at the same time, the field of adoptive cell transfer has exploded. The chimeric antigen receptor (CAR) T technology has provided strong evidence of efficacy in the treatment of B cell malignancies, and different T cell based treatments are currently under investigation for different types of tumors. In this review we will discuss the latest advances in cancer immunology and immunotherapy as well as new treatments now under development in the clinic and potential strategies that have shown promising results in preclinical models. PMID:27011048

  15. Increased risk of papillary thyroid cancer related to hormonal factors in women.

    PubMed

    Wang, Ping; Lv, Long; Qi, Feng; Qiu, Feng

    2015-07-01

    Strikingly higher rates of papillary thyroid cancer in women compared with men suggest that hormonal factors may be involved in the development of this cancer. A number of independent studies have investigated the association between hormonal factors and papillary thyroid cancer risk in women but yielded conflicting and inconclusive findings. We performed a meta-analysis of all currently published studies to provide better estimates for the risk of papillary thyroid cancer related to menstrual, reproductive, and other hormonal factors in women. Six cohort studies and three case-control ones were included into our study after a comprehensive literature search. The pooled relative risk (RR) with 95 % confidence interval (95 % CI) implicated that late age at menopause was associated with an increased risk of papillary thyroid cancer (RR = 1.39, 95 % CI 1.03-1.89, P = 0.032). No significant association was demonstrated between papillary thyroid cancer risk and other hormone-related factors, including oral contraceptive, hormone replacement therapy, age at menarche, parity, age at first birth, menopausal status, and breast feeding. Subgroup analysis by study design confirmed those associations. Sensitivity analysis did not materially alter the pooled results. The meta-analysis firstly suggests that late age at menopause is a risk factor for papillary thyroid cancer. PMID:25669169

  16. The impact of marital status at diagnosis on cancer survival in patients with differentiated thyroid cancer.

    PubMed

    Shi, Rong-Liang; Qu, Ning; Lu, Zhong-Wu; Liao, Tian; Gao, Yi; Ji, Qing-Hai

    2016-08-01

    Previous studies have revealed that marital status influences the prognosis of patients with various types of cancer. We evaluated the influence of marriage on the survival outcomes in differentiated thyroid cancer (DTC). The Surveillance, Epidemiology and End Results (SEER) database between 2002 and 2012 was used to compare cancer-specific mortality in different marital status, and in each sex, age, and stage stratification by multivariate Cox regression model. In total, 61,077 eligible patients were identified. The widowed group had the highest proportion of women, elderly patients (≥45 years), and advanced stage III/IV tumor (P = 0.001), but the total thyroidectomy (TT) performed and radioisotopes therapy rates were lower than those in the married group. Married patients had a better cancer-specific survival (CSS) than the unmarried (P < 0.05). Further analysis showed that widowed patients always presented the lowest CSS compared with other groups. Widowed patients had a significant increased risk for CSS compared with married patients in males [hazard ratio (HR) 2.72, 95% confidence interval (CI): 1.59-4.65, P = 0.001], females (HR 2.02, 95% CI: 2.24-4.06, P = 0.001), young patients (<45, HR 28.12, 95% CI: 3.48-227.25, P = 0.002), elderly patients (≥45, HR 28.12, 95% CI: 2.97, 95% CI: 2.30-3.83, P = 0.001), stage I (HR 8.44, 95% CI: 4.05-17.59, P = 0.001), stage II (HR 3.64, 95% CI: 1.30-10.20, P = 0.014), stage III (HR 2.27, 95% CI: 1.08-4.78, P = 0.031), and stage IV (HR 2.63, 95% CI: 1.94-3.57, P = 0.001). These results showed that unmarried status, especially for widowhood, increased the risk of cancer mortality in DTC patients. PMID:27264532

  17. CHIP promotes thyroid cancer proliferation via activation of the MAPK and AKT pathways.

    PubMed

    Zhang, Li; Liu, Lianyong; He, Xiaohua; Shen, Yunling; Liu, Xuerong; Wei, Jing; Yu, Fang; Tian, Jianqing

    2016-08-26

    The carboxyl terminus of Hsp70-interacting protein (CHIP) is a U box-type ubiquitin ligase that plays crucial roles in various biological processes, including tumor progression. To date, the functional mechanism of CHIP in thyroid cancer remains unknown. Here, we obtained evidence of upregulation of CHIP in thyroid cancer tissues and cell lines. CHIP overexpression markedly enhanced thyroid cancer cell viability and colony formation in vitro and accelerated tumor growth in vivo. Conversely, CHIP knockdown impaired cell proliferation and tumor growth. Notably, CHIP promoted cell growth through activation of MAPK and AKT pathways, subsequently decreasing p27 and increasing cyclin D1 and p-FOXO3a expression. Our findings collectively indicate that CHIP functions as an oncogene in thyroid cancer, and is therefore a potential therapeutic target for this disease. PMID:27342662

  18. Genomic and transcriptomic hallmarks of poorly differentiated and anaplastic thyroid cancers

    PubMed Central

    Ibrahimpasic, Tihana; Boucai, Laura; Shah, Ronak H.; Dogan, Snjezana; Ricarte-Filho, Julio C.; Krishnamoorthy, Gnana P.; Schultz, Nikolaus; Berger, Michael F.; Sander, Chris; Taylor, Barry S.; Ghossein, Ronald; Ganly, Ian; Fagin, James A.

    2016-01-01

    BACKGROUND. Poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC) are rare and frequently lethal tumors that so far have not been subjected to comprehensive genetic characterization. METHODS. We performed next-generation sequencing of 341 cancer genes from 117 patient-derived PDTCs and ATCs and analyzed the transcriptome of a representative subset of 37 tumors. Results were analyzed in the context of The Cancer Genome Atlas study (TCGA study) of papillary thyroid cancers (PTC). RESULTS. Compared to PDTCs, ATCs had a greater mutation burden, including a higher frequency of mutations in TP53, TERT promoter, PI3K/AKT/mTOR pathway effectors, SWI/SNF subunits, and histone methyltransferases. BRAF and RAS were the predominant drivers and dictated distinct tropism for nodal versus distant metastases in PDTC. RAS and BRAF sharply distinguished between PDTCs defined by the Turin (PDTC-Turin) versus MSKCC (PDTC-MSK) criteria, respectively. Mutations of EIF1AX, a component of the translational preinitiation complex, were markedly enriched in PDTCs and ATCs and had a striking pattern of co-occurrence with RAS mutations. While TERT promoter mutations were rare and subclonal in PTCs, they were clonal and highly prevalent in advanced cancers. Application of the TCGA-derived BRAF-RAS score (a measure of MAPK transcriptional output) revealed a preserved relationship with BRAF/RAS mutation in PDTCs, whereas ATCs were BRAF-like irrespective of driver mutation. CONCLUSIONS. These data support a model of tumorigenesis whereby PDTCs and ATCs arise from well-differentiated tumors through the accumulation of key additional genetic abnormalities, many of which have prognostic and possible therapeutic relevance. The widespread genomic disruptions in ATC compared with PDTC underscore their greater virulence and higher mortality. FUNDING. This work was supported in part by NIH grants CA50706, CA72597, P50-CA72012, P30-CA008748, and 5T32-CA160001; the Lefkovsky Family

  19. An Unusual Case of Cauda Equina Secondary to Spinal Metastasis of Thyroid Cancer

    PubMed Central

    Akhtar, Shabbir; Adeel, Mohammad

    2016-01-01

    Introduction: Cauda equina secondary to metastatic follicular thyroid cancer of the lumbosacral area is a rare entity. Case Report: We report an unusual case of a 52-year-old male who presented with backache, lower limb weakness, and perianal numbness. A CT-scan of the lumbosacral area showed an enhancing mass at the L4, L5 and S1 vertebrae. Histopathology after excision revealed a metastatic thyroid cancer. Hence, a CT scan of the neck and chest was performed which showed a nodule in the left lobe of the thyroid and a mass in the left chest wall. A total thyroidectomy and excision of the chest wall lesion was undergone, which was diagnosed as a follicular carcinoma of the thyroid. Conclusion: Metastatic workup of spinal metastasis should include evaluation of the thyroid gland. PMID:26878006

  20. Tumor-Associated Mast Cells in Thyroid Cancer

    PubMed Central

    Visciano, Carla; Prevete, Nella; Liotti, Federica; Marone, Gianni

    2015-01-01

    There is compelling evidence that the tumor microenvironment plays a major role in mediating aggressive features of cancer cells, including invasive capacity and resistance to conventional and novel therapies. Among the different cell populations that infiltrate cancer stroma, mast cells (MCs) can influence several aspects of tumor biology, including tumor development and progression, angiogenesis, lymphangiogenesis, and tissue remodelling. Thyroid cancer (TC), the most frequent neoplasia of the endocrine system, is characterized by a MC infiltrate, whose density correlates with extrathyroidal extension and invasiveness. Recent evidence suggests the occurrence of epithelial-to-mesenchymal transition (EMT) and stemness in human TC. The precise role of immune cells and their mediators responsible for these features in TC remains unknown. Here, we review the relevance of MC-derived mediators (e.g., the chemokines CXCL1/GRO-α, CXCL10/IP-10, and CXCL8/IL-8) in the context of TC. CXCL1/GRO-α and CXCL10/IP-10 appear to be involved in the stimulation of cell proliferation, while CXCL8/IL-8 participates in the acquisition of TC malignant traits through its ability to induce/enhance the EMT and stem-like features of TC cells. The inhibition of chemokine signaling may offer novel therapeutic approaches for the treatment of refractory forms of TC. PMID:26379707

  1. Repositioning therapy for thyroid cancer: new insights on established medications.

    PubMed

    Kushchayeva, Yevgeniya; Jensen, Kirk; Burman, Kenneth D; Vasko, Vasyl

    2014-06-01

    Repositioning of established non-cancer pharmacotherapeutic agents with well-known activity and side-effect profiles is a promising avenue for the development of new treatment modalities for multiple cancer types. We have analyzed some of the medications with mechanism of action that may have relevance to thyroid cancer (TC). Experimental in vitro and in vivo evidences, as well as results of clinical studies, have indicated that molecular targets for medications currently available for the treatment of mood disorders, sexually transmitted diseases, metabolic disorders, and diabetes may be active and relevant in TC. For instance, the derivatives of cannabis and an anti-diabetic agent, metformin, both are able to inhibit ERK, which is commonly activated in TC cells. We present here several examples of well-known medications that have the potential to become new therapeutics for patients with TC. Repositioning of established medications for the treatment of TC could broaden the scope of current therapeutic strategies. These diverse treatment choices could allow physicians to provide an individualized approach to optimize treatment for patients with TC. PMID:24446492

  2. Thyroid cancer detected by ultrasound-guided fine-needle aspiration biopsy.

    PubMed

    Yokozawa, T; Fukata, S; Kuma, K; Matsuzuka, F; Kobayashi, A; Hirai, K; Miyauchi, A; Sugawara, M

    1996-09-01

    A greater percentage of thyroid cancers can be detected by ultrasound-guided fine-needle aspiration biopsy (UG-FNAB) than by ordinary FNAB. A group of 678 patients were selected sequentially as having been diagnosed with benign nodules by the conventional FNAB method. We reexamined these patients by UG-FNAB and investigated the types of thyroid cancer that were missed by the conventional FNAB. Of the 678 patients diagnosed with benign nodules (using conventional FNAB), 571 (84.2%) demonstrated the same diagnosis when UG-FNAB was used. The remaining 107 patients (15.8%) studied were suspected of having a malignancy after UG-FNAB had been performed. Surgical specimen histology proved thyroid cancer in 99 of the 107 patients: 93 had papillary carcinoma, 4 had follicular carcinoma, 1 had medullary carcinoma and 1 had anaplastic carcinoma. Two drawbacks were noted when conventional FNAB was used: (1) cancer lesions difficult to palpate (n = 55) (e.g., small cancers with or without benign lesions or cancers associated with Hashimoto's thyroiditis or Graves' disease); and (2) palpable cancers with insufficient cell material for analysis (n = 44) (e.g., cystic carcinoma and cancers with calcified lesions. UG-FNAB is a powerful technique for detecting microcancers, cystic carcinomas, cancers associated with benign nodules, Hashimoto's thyroiditis, or coarse calcifications. PMID:8678961

  3. 2013 European Thyroid Association Guidelines for Cervical Ultrasound Scan and Ultrasound-Guided Techniques in the Postoperative Management of Patients with Thyroid Cancer

    PubMed Central

    Leenhardt, L.; Erdogan, M.F.; Hegedus, L.; Mandel, S.J.; Paschke, R.; Rago, T.; Russ, G.

    2013-01-01

    Cervical ultrasound scanning (US) is considered a key examination, by all major thyroid and endocrine specialist societies for the postoperative follow-up of thyroid cancer patients to assess the risk of recurrence. Neck US imaging is readily available, non-invasive, relatively easy to perform, cost-effective, and can guide diagnostic and therapeutic procedures with low complication rates. Its main shortcoming is its operator-dependency. Because of the pivotal role of US in the care of thyroid cancer patients, the European Thyroid Association convened a panel of international experts to review technical aspects, indications, results, and limitations of cervical US in the initial staging and follow-up of thyroid cancer patients. The main aim is to establish guidelines for both a cervical US scanning protocol and US-guided diagnostic and therapeutic procedures in patients with thyroid cancer. This report presents (1) standardization of the US scanning procedure, techniques of US-guided fine-needle aspiration, and reporting of findings; (2) definition of criteria for classification of malignancy risk based on cervical US imaging characteristics of neck masses and lymph nodes; (3) indications for US-guided fine-needle aspiration and for biological in situ assessments; (4) proposal of an algorithm for the follow-up of thyroid cancer patients based on risk stratification following histopathological and cervical US findings, and (5) discussion of the potential use of US-guided localization and ablation techniques for locoregional thyroid metastases. PMID:24847448

  4. A case of polymyositis associated with papillary thyroid cancer: a case report

    PubMed Central

    Kalliabakos, Dimitrios; Pappas, Apostolos; Lagoudianakis, Emmanuel; Papadima, Artemisia; Chrysikos, John; Basagiannis, Christos; Tsakoumagou, Maria; Skanelli, Yasemi; Manouras, Andreas

    2008-01-01

    Differentiated thyroid cancer is rarely associated with paraneoplastic events. Polymyositis, an autoimmune inflammatory myopathy, can be manifested as a paraneoplastic syndrome (PS). We report a case of a young woman who developed progressive proximal muscle weakness one and a half year after a total thyroidectomy for papillary thyroid cancer. Clinical features, laboratory results and muscle biopsy led us to the diagnosis of polymyositis, possibly related to her previous malignancy. A search for recurrence of the thyroid carcinoma or other underlying malignancy was fruitless. The patient improved slowly but almost completely after about 6 months of immunosupressive therapy, which she is still receiving. PMID:18973692

  5. Chernobyl-related thyroid cancer in children of Belarus: a case-control study.

    PubMed

    Astakhova, L N; Anspaugh, L R; Beebe, G W; Bouville, A; Drozdovitch, V V; Garber, V; Gavrilin, Y I; Khrouch, V T; Kuvshinnikov, A V; Kuzmenkov, Y N; Minenko, V P; Moschik, K V; Nalivko, A S; Robbins, J; Shemiakina, E V; Shinkarev, S; Tochitskaya, S I; Waclawiw, M A

    1998-09-01

    The accident at the Chernobyl nuclear power plant on April 26, 1986, released approximately 2 EBq of 131I and other radioiodine isotopes that heavily contaminated southern Belarus. An increase in thyroid cancer reported in 1992 and attributed to the Chernobyl accident was challenged as possibly the result of intensive screening. We began a case-control study to test the hypothesis that the Chernobyl accident caused the increase in thyroid cancer. Records of childhood thyroid cancer in the national therapy centers in Minsk in 1992 yielded 107 individuals with confirmed pathology diagnoses and available for interview. Pathways to diagnosis were (1) routine endocrinological screening in 63, (2) presentation with enlarged or nodular thyroid in 25 and (3) an incidental finding in 19. Two sets of controls were chosen, one matched on pathway to diagnosis, the other representing the area of heavy fallout, both matched on age, sex and rural/urban residence in 1986. The 131I dose to the thyroid was estimated from ground deposition of 137Cs, ground deposition of 131I, a data bank of 1986 thyroid radiation measurements, questionnaires and interviews. Highly significant differences were observed between cases and controls (both sets) with respect to dose. The differences persisted within pathway to diagnosis, gender, age and year of diagnosis, and level of iodine in the soil, and were most marked in the southern portion of the Gomel region. The case-control comparisons indicate a strong relationship between thyroid cancer and estimated radiation dose from the Chernobyl accident. PMID:9728663

  6. Off Target Effects of c-MET Inhibitors on Thyroid Cancer Cells

    PubMed Central

    Zhou, Yan; Zhao, Conghui; Gery, Sigal; Braunstein, Glenn D.; Okamoto, Ryoko; Alvarez, Rocio; Miles, Steven A.; Doan, Ngan B.; Said, Jonathan W.; Gu, Jiang; Koeffler, H. Phillip

    2013-01-01

    Aberrantly activated c-MET signaling occurs in several cancers, promoting the development of c-MET inhibitors. In this study, we found that eight of 8 thyroid cancer cell lines (including six anaplastic thyroid cell lines) have prominent expression of c-MET protein. Fifty percent of the thyroid cancer cell lines (four of 8) were growth-inhibited by two small molecule c-MET inhibitors (Tivantinib and Crizotinib), associated with apoptosis and G2/M cell cycle arrest. However, Crizotinib did not inhibit 50% proliferation of thyroid cancer cells (SW1736 and TL3) at a concentration at which the drug completely inhibited ligand-stimulated c-MET phosphorylation. On the other hand, Tivantinib was less potent than Crizotinib at inhibiting c-MET phosphorylation, but was more potent than Crizotinib at decreasing cell growth. Suppressing c-MET protein expression and phosphorylation using siRNA targeting c-MET did not induce cell cycle arrest and apoptosis. Taken together, Tivantinib and Crizotinib have off target(s) activity, contributing to their anti-tumor activity. In vivo study showed that Crizotinib markedly inhibited the growth of thyroid cancer cells (SW1736) in immunodeficient mice. In summary, c-MET inhibitors (Tivantinib and Crizotinib) suppress the growth of aggressive thyroid cancer cells, and this potential therapeutic benefit results from their non-MET-targeting effects. PMID:24170771

  7. Molecular profiling of thyroid cancer subtypes using large-scale text mining

    PubMed Central

    2014-01-01

    Background Thyroid cancer is the most common endocrine tumor with a steady increase in incidence. It is classified into multiple histopathological subtypes with potentially distinct molecular mechanisms. Identifying the most relevant genes and biological pathways reported in the thyroid cancer literature is vital for understanding of the disease and developing targeted therapeutics. Results We developed a large-scale text mining system to generate a molecular profiling of thyroid cancer subtypes. The system first uses a subtype classification method for the thyroid cancer literature, which employs a scoring scheme to assign different subtypes to articles. We evaluated the classification method on a gold standard derived from the PubMed Supplementary Concept annotations, achieving a micro-average F1-score of 85.9% for primary subtypes. We then used the subtype classification results to extract genes and pathways associated with different thyroid cancer subtypes and successfully unveiled important genes and pathways, including some instances that are missing from current manually annotated databases or most recent review articles. Conclusions Identification of key genes and pathways plays a central role in understanding the molecular biology of thyroid cancer. An integration of subtype context can allow prioritized screening for diagnostic biomarkers and novel molecular targeted therapeutics. Source code used for this study is made freely available online at https://github.com/chengkun-wu/GenesThyCan. PMID:25521965

  8. Inhibition of BRD4 suppresses tumor growth and enhances iodine uptake in thyroid cancer.

    PubMed

    Gao, Xuemei; Wu, Xinchao; Zhang, Xiao; Hua, Wenjuan; Zhang, Yajing; Maimaiti, Yusufu; Gao, Zairong; Zhang, Yongxue

    2016-01-15

    Thyroid cancer is a common malignancy of the endocrine system. Although radioiodine (131)I treatment on differentiated thyroid cancer is widely used, many patients still fail to benefit from (131)I therapy. Therefore, exploration of novel targeted therapies to suppress tumor growth and improve radioiodine uptake remains necessary. Bromodomain-containing protein 4 (BRD4) is an important member of the bromodomain and extra terminal domain family that influences transcription of downstream genes by binding to acetylated histones. In the present study, we found that BRD4 was up-regulated in thyroid cancer tissues and cell lines. Inhibition of BRD4 in thyroid cancer cells by JQ1 resulted in cell cycle arrest at G0/G1 phase and enhanced (131)I uptake in vitro and suppressed tumor growth in vivo. Moreover, JQ1 treatment suppressed C-MYC but enhanced NIS expression. We further demonstrated that BRD4 was enriched in the promoter region of C-MYC, which could be markedly blocked by JQ1 treatment. In conclusion, our findings revealed that the aberrant expression of BRD4 in thyroid cancer is possibly involved in tumor progression, and JQ1 is potentially an effective chemotherapeutic agent against human thyroid cancer. PMID:26707881

  9. 2012 European Thyroid Association Guidelines for Genetic Testing and Its Clinical Consequences in Medullary Thyroid Cancer

    PubMed Central

    Elisei, R.; Alevizaki, M.; Conte-Devolx, B.; Frank-Raue, K.; Leite, V.; Williams, G.R.

    2013-01-01

    Twenty-five percent of medullary thyroid cancers (MTC) are familial and inherited as an autosomal dominant trait. Three different phenotypes can be distinguished: multiple endocrine neoplasia (MEN) types 2A and 2B, in which the MTC is associated with other endocrine neoplasias, and familial MTC (FMTC), which occurs in isolation. The discovery that germline RET oncogene activating mutations are associated with 95–98% of MEN 2/FMTC syndromes and the availability of genotyping to identify mutations in affected patients and their relatives has revolutionized the diagnostic and therapeutic strategies available for the management of these patients. All patients with MTC, both those with a positive familial history and those apparently sporadic, should be submitted to RET genetic screening. Once an RET mutation has been confirmed in an index patient, first-degree relatives should be screened rapidly to identify the 50% who inherited the mutation and are therefore at risk for development of MTC. Relatives in whom no RET mutation is identified can be reassured and discharged from further follow-up, whereas RET-positive subjects (i.e. gene carriers) must be investigated and a therapeutic strategy initiated. These guideline recommendations are derived from the most recent studies identifying phenotype-genotype correlations following the discovery of causative RET gene mutations in MEN 2 eighteen years ago. Three major points will be discussed: (a) identification of patients and relatives who should have genetic screening for RET mutations, (b) management of asymptomatic gene carriers, and (c) ethics. PMID:24783025

  10. microRNA-141 inhibits thyroid cancer cell growth and metastasis by targeting insulin receptor substrate 2

    PubMed Central

    Dong, Su; Meng, Xianying; Xue, Shuai; Yan, Zewen; Ren, Peiyou; Liu, Jia

    2016-01-01

    microRNA-141 (miR-141), a member of the miR-200 family, and has been reported to involve in tumor initiation and development in many types of cancers. However, the function and underlying molecular mechanism of miR-141 in thyroid cancer remains unclear. Therefore, the aim of this study is to identify its expression, function, and molecular mechanism in thyroid cancer. In this study, we found that miR-141 expression levels were downregulated in human thyroid cancer specimens compared to the adjacent normal tissues, and its expression were strongly correlated with clinical stages and lymph node metastases. Function assays showed that overexpression of miR-141 inhibited cell proliferation, induced cell apoptosis, and decreased migration, invasion in thyroid cancer cells, as well as tumor growth in nude mice. Moreover, insulin receptor substrate 2 (IRS2), a known oncogene, was confirmed as a direct target of miR-141, and IRS2 expression levels were upregulated in thyroid cancer, and its expression were inversely correlated with miR-141 expression levels in human thyroid cancer specimens. Forced expression of IRS2 reversed the inhibition effect induced by miR-141 overexpression in thyroid cancer cells. Taken together, our study provides the first evidence that miR-141 suppressed thyroid cancer cell growth and metastasis through inhibition of IRS2. Thus, miR-141 might serve as a promising therapeutic strategy for thyroid cancer treatment. PMID:27186273

  11. Zn(II)-curc targets p53 in thyroid cancer cells

    PubMed Central

    GARUFI, ALESSIA; D'ORAZI, VALERIO; CRISPINI, ALESSANDRA; D'ORAZI, GABRIELLA

    2015-01-01

    TP53 mutation is a common event in many cancers, including thyroid carcinoma. Defective p53 activity promotes cancer resistance to therapies and a more malignant phenotype, acquiring oncogenic functions. Rescuing the function of mutant p53 (mutp53) protein is an attractive anticancer therapeutic strategy. Zn(II)-curc is a novel small molecule that has been shown to target mutp53 protein in several cancer cells, but its effect in thyroid cancer cells remains unclear. Here, we investigated whether Zn(II)-curc could affect p53 in thyroid cancer cells with both p53 mutation (R273H) and wild-type p53. Zn(II)-curc induced mutp53H273 downregulation and reactivation of wild-type functions, such as binding to canonical target promoters and target gene transactivation. This latter effect was similar to that induced by PRIMA-1. In addition, Zn(II)-curc triggered p53 target gene expression in wild-type p53-carrying cells. In combination treatments, Zn(II)-curc enhanced the antitumor activity of chemotherapeutic drugs, in both mutant and wild-type-carrying cancer cells. Taken together, our data indicate that Zn(II)-curc promotes the reactivation of p53 in thyroid cancer cells, providing in vitro evidence for a potential therapeutic approach in thyroid cancers. PMID:26314369

  12. Restoration of Brain Acid Soluble Protein 1 Inhibits Proliferation and Migration of Thyroid Cancer Cells

    PubMed Central

    Guo, Run-Sheng; Yu, Yue; Chen, Jun; Chen, Yue-Yu; Shen, Na; Qiu, Ming

    2016-01-01

    Background: Brain acid soluble protein 1 (BASP1) is identified as a novel potential tumor suppressor in several cancers. However, its role in thyroid cancer has not been investigated yet. In the present study, the antitumor activities of BASP1 against the growth and migration of thyroid cancer cells were evaluated. Methods: BASP1 expression in thyroid cancer tissues and normal tissues were examined by immunohistochemical staining and the association between its expression and prognosis was analyzed. pcDNA-BASP1 carrying full length of BASP1 cDNA was constructed to restore the expression of BASP1 in thyroid cancer cell lines (BHT-101 and KMH-2). The cell proliferation in vitro and in vivo was evaluated by WST-1 assay and xenograft tumor models, respectively. Cell cycle distribution after transfection was analyzed using flow cytometry. Cell apoptosis after transfection was examined by annexin V/propidium iodide assay. The migration was examined using transwell assay. Results: BASP1 expression was abundant in normal tissues while it is significantly decreased in cancer tissues (P = 0.000). pcDNA-BASP1 restored the expression of BASP1 and significantly inhibited the growth of BHT-101 and KMH-2 cells as well as xenograft tumors in nude mice (P = 0.000). pcDNA-BASP1 induced G1 arrest and apoptosis in BHT-101 and KMH-2 cells. In addition, pcDNA-BASP1 significantly inhibited the cell migration. Conclusions: Downregulation of BASP1 expression may play a role in the tumorigenesis of thyroid cancer. Restoration of BASP1 expression exerted extensive antitumor activities against growth and migration of thyroid cancer cells, which suggested that BASP1 gene might act as a potential therapeutic agent for the treatment of thyroid cancer. PMID:27270539

  13. Papillary thyroid cancer in a struma ovarii: a report of a rare case.

    PubMed

    Monti, Eleonora; Mortara, Lorenzo; Zupo, Simonetta; Dono, Mariella; Minuto, Francesco; Truini, Mauro; Naseri, Mehrdad; Giusti, Massimo

    2015-01-01

    After removal of an ovarian mass in a 43-year-old woman, a struma ovarii was diagnosed. Within this teratoma, a papillary thyroid cancer was found. The tumor was negative for BRAF, NRAS, KRAS, PIK3CA and c-KIT mutations on molecular analysis. Thyroid function and morphology were normal. Thyroidectomy, L-T4 TSH-suppressive therapy and rhTSH-induced radioiodine ablation were performed. So far, the follow-up has been favorable. This is the first case of thyroid cancer in a struma ovarii in which mutations of PIK3CA exons 9 and 20, and c-KIT exons 9, 11 and 13 have been evaluated and the third in which ablation has been performed under rhTSH. The prognosis of patients with thyroid cancer in a struma ovarii is generally poor. In our patient, as in those who undergo ablative radioactive iodine therapy, this was not the case. PMID:25402391

  14. Metabolomic analysis of percutaneous fine-needle aspiration specimens of thyroid nodules: Potential application for the preoperative diagnosis of thyroid cancer

    PubMed Central

    Ryoo, Inseon; Kwon, Hyuknam; Kim, Soo Chin; Jung, Seung Chai; Yeom, Jeong A; Shin, Hwa Seon; Cho, Hye Rim; Yun, Tae Jin; Choi, Seung Hong; Sohn, Chul-Ho; Park, Sunghyouk; Kim, Ji-hoon

    2016-01-01

    Thyroid nodules are a very common problem. Since malignant thyroid nodules should be treated surgically, preoperative diagnosis of thyroid cancer is very crucial. Cytopathologic analysis of percutaneous fine-needle aspiration (FNA) specimens is the current gold standard for diagnosing thyroid nodules. However, this method has led to high rates of inconclusive results. Metabolomics has emerged as a useful tool in medical fields and shown great potential in diagnosing various cancers. Here, we evaluated the potential of nuclear magnetic resonance (NMR) analysis of percutaneous FNA specimens for preoperative diagnosis of thyroid cancer. We analyzed metabolome of FNA samples of papillary thyroid carcinoma (n = 35) and benign follicular nodule (n = 69) using a proton NMR spectrometer. The metabolomic profiles showed a considerable discrimination between benign and malignant nodules. Receiver operating characteristic (ROC) curve analysis indicated that seven metabolites could serve as discriminators (area under ROC curve value, 0.64–0.85). These findings demonstrated that NMR analysis of percutaneous FNA specimens of thyroid nodules can be potentially useful in the accurate and rapid preoperative diagnosis of thyroid cancer. PMID:27440433

  15. Efficacy of pazopanib in progressive, radioiodine-refractory, metastatic differentiated thyroid cancers: results of a phase 2 consortium study

    PubMed Central

    Bible, Keith C; Suman, Vera J; Molina, Julian R; Smallridge, Robert C; Maples, William J; Menefee, Michael E; Rubin, Joseph; Sideras, Kostandinos; Morris, John C; McIver, Bryan; Burton, Jill K; Webster, Kevin P; Bieber, Carolyn; Traynor, Anne M; Flynn, Patrick J; Goh, Boon Cher; Tang, Hui; Ivy, Susan Percy; Erlichman, Charles

    2011-01-01

    Summary Background Chemotherapy has historically proven ineffective in advanced differentiated thyroid cancers, but the realisation that various tyrosine kinases are activated in the disease suggested a potential therapeutic role for tyrosine-kinase inhibitors. We investigated the safety and efficacy of pazopanib. Methods This phase 2 trial was done from Feb 22, 2008, to Jan 31, 2009, in patients with metastatic, rapidly progressive, radioiodine-refractory differentiated thyroid cancers. Each patient received 800 mg continuous pazopanib daily in 4-week cycles until disease progression, drug intolerance, or both occurred. Up to two previous therapies were allowed, and measurable disease with radiographic progression in the 6-month period before enrolment was a requirement for inclusion. The primary endpoint was any tumour response, according to the Response Evaluation Criteria in Solid Tumors 1.0. This study is registered with ClinicalTrials.gov, number NCT00625846. Findings 39 patients were enrolled. One patient had received no previous radioiodine therapy and another withdrew consent before treatment. Clinical outcomes could, therefore, be assessed in 37 patients (19 [51%] men, median age 63 years). The study is closed to accrual of new patients, but several enrolled patients are still being treated. Patients received a median of 12 cycles (range 1 to >23, total >383). Confirmed partial responses were recorded in 18 patients (response rate 49%, 95% CI 35–68), with likelihood of response lasting longer than 1 year calculated to be 66%. Maximum concentration of pazopanib in plasma during cycle one was significantly correlated with radiographic response (r=−0·40, p=0·021). 16 (43%) patients required dose reductions owing to adverse events, the most frequent of which (any grade) were fatigue (29 patients), skin and hair hypopigmentation (28), diarrhoea (27), and nausea (27). Two patients who died during treatment had pre-existing contributory disorders

  16. Trends in Thyroid Cancer Incidence in Korean Children (1999-2012) Based on Palpation and Nonpalpation Detection Methods

    PubMed Central

    Cho, Yoon Young; Jang, Hye Won; Joung, Ji Young; Park, Sun-Mi; Jeong, Dae Joon; Kim, Sun Wook; Chung, Jae Hoon

    2015-01-01

    Background The incidence of childhood thyroid cancer is increasing in several populations; however, contributing factors have not been adequately discussed. Objectives Our aim was to identify trends of childhood thyroid cancer based on the Korea Central Cancer Registry (KCCR) database and to elucidate changes in detection methods of cancers using a single-center database. Methods Data from the KCCR and Statistics Korea between 1999 and 2012 were used to calculate the crude incidence of thyroid cancer in children. To analyze detection methods for cancers, pediatric patients (aged 0-19 years, n = 126) who underwent thyroid surgery for thyroid cancers at our institution were identified. Subjects were divided into two groups by detection method: (1) palpation group and (2) screening group. Results The crude incidence of childhood thyroid cancer increased from 0.5 per 100,000 in 1999 to 1.7 in 2012. The proportion of thyroid cancer among total cancers also increased from 4.4% in 1999 to 10.6% in 2012. Among 126 children from our institution, 91 cases (72%) were identified as palpable neck masses, and the remainder were discovered during imaging studies. The numbers in both groups gradually increased during the study period. Conclusions The incidence of childhood thyroid cancer has steadily increased in Korea. Regarding the detection methods of cancers, most tumors are detected by palpation rather than screening, although the rate of masses identified during screening has increased. PMID:26835429

  17. Novel analogs targeting histone deacetylase suppress aggressive thyroid cancer cell growth and induce re-differentiation.

    PubMed

    Jang, S; Yu, X-M; Odorico, S; Clark, M; Jaskula-Sztul, R; Schienebeck, C M; Kupcho, K R; Harrison, A D; Winston-McPherson, G N; Tang, W; Chen, H

    2015-08-01

    To develop novel therapies for aggressive thyroid cancers, we have synthesized a collection of histone deacetylase (HDAC) inhibitor analogs named AB1 to AB13, which have different linkers between a metal chelating group and a hydrophobic cap. The purpose of this study was to screen out the most effective compounds and evaluate the therapeutic efficacy. AB2, AB3 and AB10 demonstrated the lowest half-maximal inhibitory concentration (IC50) values in one metastatic follicular and two anaplastic thyroid cancer cell lines. Treatment with each of the three ABs resulted in an increase in apoptosis markers, including cleaved poly adenosine diphosphate ribose polymerase (PARP) and cleaved caspase 3. Additionally, the expression of cell-cycle regulatory proteins p21(WAF1) and p27(Kip1) increased with the treatment of ABs while cyclin D1 decreased. Furthermore, AB2, AB3 and AB10 were able to induce thyrocyte-specific genes in the three thyroid cancer cell lines indicated by increased expression levels of sodium iodide symporter, paired box gene 8, thyroid transcription factor 1 (TTF1), TTF2 and thyroid-stimulating hormone receptors. AB2, AB3 and AB10 suppress thyroid cancer cell growth via cell-cycle arrest and apoptosis. They also induce cell re-differentiation, which could make aggressive cancer cells more susceptible to radioactive iodine therapy. PMID:26251030

  18. miR-195 is a key regulator of Raf1 in thyroid cancer

    PubMed Central

    Wang, Fangzheng; Jiang, Chuner; Sun, Quanquan; Yan, Fenqin; Wang, Lei; Fu, Zhenfu; Liu, Tongxin; Hu, Fujun

    2015-01-01

    Proto-oncogene Raf1 serves as a part of the mitogen-activated protein kinases/extracellular signal-regulated kinase signal transduction pathway and regulates cell migration, apoptosis, and differentiation. Although a large number of studies have shown that Raf1 is overexpressed in various kinds of cancer, little is known about the association between Raf1 and miRNAs in thyroid carcinoma. This study proves that Raf1 is overexpressed in thyroid cancer, which has been confirmed by many other studies. Besides, we identify that Raf1 is a direct target of miR-15a/b, miR-16, and miR-195 by dual luciferase reporter assay. We also find that the expression of miR-195 is downregulated in 50 pairs of thyroid tumor tissues compared to the adjacent nontumor tissues, while there is no difference in the expression of miR-15a/b and miR-16 between the groups. Furthermore, exogenous overexpression of miR-195 significantly inhibits the protein expression of Raf1 and blocks the thyroid cancer cell proliferation. Our findings delineate a novel mechanism for the regulation of Raf1 in thyroid cancer, which may help to provide a new direction for the treatment of thyroid cancer. PMID:26527888

  19. Thyroid Cancer after Childhood Exposure to External Radiation: An Updated Pooled Analysis of 12 Studies.

    PubMed

    Veiga, Lene H S; Holmberg, Erik; Anderson, Harald; Pottern, Linda; Sadetzki, Siegal; Adams, M Jacob; Sakata, Ritsu; Schneider, Arthur B; Inskip, Peter; Bhatti, Parveen; Johansson, Robert; Neta, Gila; Shore, Roy; de Vathaire, Florent; Damber, Lena; Kleinerman, Ruth; Hawkins, Michael M; Tucker, Margaret; Lundell, Marie; Lubin, Jay H

    2016-05-01

    Studies have causally linked external thyroid radiation exposure in childhood with thyroid cancer. In 1995, investigators conducted relative risk analyses of pooled data from seven epidemiologic studies. Doses were mostly <10 Gy, although childhood cancer therapies can result in thyroid doses >50 Gy. We pooled data from 12 studies of thyroid cancer patients who were exposed to radiation in childhood (ages <20 years), more than doubling the data, including 1,070 (927 exposed) thyroid cancers and 5.3 million (3.4 million exposed) person-years. Relative risks increased supralinearly through 2-4 Gy, leveled off between 10-30 Gy and declined thereafter, remaining significantly elevated above 50 Gy. There was a significant relative risk trend for doses <0.10 Gy (P < 0.01), with no departure from linearity (P = 0.36). We observed radiogenic effects for both papillary and nonpapillary tumors. Estimates of excess relative risk per Gy (ERR/Gy) were homogeneous by sex (P = 0.35) and number of radiation treatments (P = 0.84) and increased with decreasing age at the time of exposure. The ERR/Gy estimate was significant within ten years of radiation exposure, 2.76 (95% CI, 0.94-4.98), based on 42 exposed cases, and remained elevated 50 years and more after exposure. Finally, exposure to chemotherapy was significantly associated with thyroid cancer, with results supporting a nonsynergistic (additive) association with radiation. PMID:27128740

  20. Serum thyroglobulin in the monitoring of differentiated thyroid cancer.

    PubMed

    Evans, Carol; Tennant, Sarah; Perros, Petros

    2016-01-01

    Patients with differentiated thyroid cancer (DTC) usually have an excellent prognosis. Following surgical and radioiodine treatment to remove the cancer cells and suppressive doses of levothyroxine, long-term follow-up, including measurement of serum thyroglobulin (Tg) using a sensitive assay is required to detect recurrence. To interpret Tg results clinicians need to know the corresponding serum TSH concentration, have an appreciation of the clearance of Tg from patient serum following various interventions and the limitations of its measurement. The limitations of Tg immunoassay are well described and include potential interference from TgAb. For the majority of patients with DTC who are TgAb-negative, Tg measurement remains the most useful method of follow-up. For the TgAb-positive minority, interference and the possibility of producing erroneous results is a concern. Some assays are less badly affected than others and laboratories are advised to choose their assays carefully. Laboratories have sought to identify interferences using measurement of TgAb, lack of concordance between RIAs and immunometric assays and recovery of added Tg. More recently LC-MSMS assays to quantify Tg have been developed. They are not currently as sensitive as Tg immunoassays and it is likely these assays will, like immunoassays, be limited by Tg heterogeneity and standardization issues, although initial evaluations indicate that they may have value in the clinical setting as a second line test in antibody-positive DTC patients in whom Tg is unmeasurable by immunoassay. PMID:27542000

  1. In Thyroidectomized Thyroid Cancer Patients, False-Positive I-131 Whole Body Scans Are Often Caused by Inflammation Rather Than Thyroid Cancer

    PubMed Central

    Garger, Yana Basis; Winfeld, Mathew; Friedman, Kent; Blum, Manfred

    2016-01-01

    Objective. To show that I-131 false-positive results on whole-body scans (WBSs) after thyroidectomy for thyroid cancer may be a result of inflammation unassociated with the cancer. Methods. We performed a retrospective image analysis of our database of thyroid cancer patients who underwent WBS from January 2008 to January 2012 to identify and stratify false positives. Results. A total of 564 patients underwent WBS during the study period; 96 patients were referred for 99 I-131 single-photon emission computed tomography (SPECT/CT) scans to better interpret cryptic findings. Among them, 73 scans were shown to be falsely positive; 40/73 or 54.7% of false-positive findings were a result of inflammation. Of the findings, 17 were in the head, 1 in the neck, 4 in the chest, 3 in the abdomen, and 14 in the pelvis; 1 had a knee abscess. Conclusions. In our series, inflammation caused the majority of false-positive WBSs. I-131 SPECT/CT is powerful in the differentiation of inflammation from thyroid cancer. By excluding metastatic disease, one can properly prognosticate outcome and avoid unnecessary, potentially harmful treatment of patients with thyroid cancer. PMID:26977418

  2. Thyroid hormone autoantibodies: are they a better marker to detect early thyroid damage in patients with hematologic cancers receiving tyrosine kinase inhibitor or immunoregulatory drug treatments?

    PubMed Central

    Mondello, P.; Mian, M.; Pitini, V.; Cuzzocrea, S.; Sindoni, A.; Galletti, M.; Mandolfino, M.; Santoro, D.; Mondello, S.; Aloisi, C.; Altavilla, G.; Benvenga, S.

    2016-01-01

    Background Unlike cytotoxic agents, novel antineoplastic drugs can variably affect thyroid function and so impair patient outcomes. However, the widely used standard thyroid tests have demonstrated low sensitivity for detecting early thyroid damage that leads to dysfunction of the gland. To find a more reliable thyroid marker, we assessed the presence of antibodies binding thyroid hormones (thAbs) in a cancer population undergoing potentially thyrotoxic treatment. Methods From April 2010 to September 2013, 82 patients with hematologic malignancies treated with tyrosine kinase inhibitors or immunoregulatory drugs were recruited. Healthy volunteers (n = 104) served as control subjects. Thyroid function, autoimmunity tests, thAbs, and thyroid sonography were assessed once during treatment. Results Overall, thAb positivity was recorded in 13% of the entire cohort. In most cases, the thAbs were of a single type, with a predominance of T3 immunoglobulin G. More specifically, thAbs were detected in 11 cancer patients; and abnormal levels of thyroid-stimulating hormone, thyroglobulin antibody, and thyroperoxidase antibody were detected in 6 (p = 0.05), 0 (p = 0.0006), and 2 cancer patients (p = 0.001) respectively. Ultrasonographic alterations of the thyroid were observed in 12 cancer patients. In contrast, of the 104 healthy control subjects, only 1 was positive for thAbs (1%). Conclusions We have demonstrated for the first time that thAbs are a reliable marker of early thyroid dysfunction when compared with the widely used standard thyroid tests. A confirmatory prospective trial aiming at evaluating thAbs at various time points during treatment could clarify the incidence and timing of antibody appearance. PMID:27330353

  3. Real-time Imaging of Tumor Progression in a Fluorescent Orthotopic Mouse Model of Thyroid Cancer

    PubMed Central

    TRAN CAO, HOP S.; KAUSHAL, SHARMEELA; SNYDER, CYNTHIA S.; ONGKEKO, WEG M.; HOFFMAN, ROBERT M.; BOUVET, MICHAEL

    2015-01-01

    There is a need for a clinically relevant mouse model of thyroid cancer that enables real-time, non-invasive monitoring of tumor growth, progression, and drug response over time. Human thyroid cancer cell lines NPA (papillary) and KAK-1 (anaplastic) were stably transfected to express either red or green fluorescent protein. Cancer cells were injected into the thyroid glands of 8-week-old athymic mice. The animals were imaged with whole-body fluorescence imaging weekly and sacrificed when premorbid. At necropsy, the primary tumor was resected en bloc with the respiratory system for processing and analysis. Histology was performed on fixed tissue specimens for review of morphologic findings. Both anaplastic and papillary thyroid cancer cell lines led to robust development of orthotopic fluorescent tumors in nude mice. Injection of 5×105 cancer cells was sufficient for tumor development. Tumors were visualized for both cell lines via non-invasive imaging as early as 3 weeks post-implantation and were monitored over time. Time to premorbid condition varied between mice and was associated with a primary tumor growth pattern (early local compression of the esophagus vs. late metastatic disease) rather than tumor size. At necropsy, tumor fluorescence demonstrated metastases in the lungs, lymph nodes and vessels that were not visible under white light. Thus an orthotopic mouse model of thyroid cancer has been developed that replicates the major clinical features of thyroid cancer and enables real-time, non-invasive monitoring of tumor progression. This model should permit preclinical evaluation of novel thyroid cancer therapeutics. PMID:21115887

  4. Postoperative Nomogram for Predicting Cancer-Specific Mortality in Medullary Thyroid Cancer

    PubMed Central

    Ho, Allen S.; Wang, Lu; Palmer, Frank L.; Yu, Changhong; Toset, Arnbjorn; Patel, Snehal; Kattan, Michael W.; Tuttle, R. Michael; Ganly, Ian

    2016-01-01

    Background Medullary thyroid cancer (MTC) is a rare thyroid cancer accounting for 5 % of all thyroid malignancies. The purpose of our study was to design a predictive nomogram for cancer-specific mortality (CSM) utilizing clinical, pathological, and biochemical variables in patients with MTC. Methods MTC patients managed entirely at Memorial Sloan-Kettering Cancer Center between 1986 and 2010 were identified. Patient, tumor, and treatment characteristics were recorded, and variables predictive of CSM were identified by univariable analyses. A multivariable competing risk model was then built to predict the 10-year cancer specific mortality of MTC. All predictors of interest were added in the starting full model before selection, including age, gender, pre- and postoperative serum calcitonin, pre- and postoperative CEA, RET mutation status, perivascular invasion, margin status, pathologic T status, pathologic N status, and M status. Stepdown method was used in model selection to choose predictive variables. Results Of 249 MTC patients, 22.5 % (56/249) died from MTC, whereas 6.4 % (16/249) died secondary to other causes. Mean follow-up period was 87 ± 67 months. The seven variables with the highest predictive accuracy for cancer specific mortality included age, gender, postoperative calcitonin, perivascular invasion, pathologic T status, pathologic N status, and M status. These variables were used to create the final nomogram. Discrimination from the final nomogram was measured at 0.77 with appropriate calibration. Conclusions We describe the first nomogram that estimates cause-specific mortality in individual patients with MTC. This predictive nomogram will facilitate patient counseling in terms of prognosis and subsequent clinical follow up. PMID:25366585

  5. AZD6244 in Treating Patients With Papillary Thyroid Cancer That Did Not Respond to Radioactive Iodine

    ClinicalTrials.gov

    2016-09-02

    Recurrent Thyroid Gland Carcinoma; Stage I Thyroid Gland Papillary Carcinoma; Stage II Thyroid Gland Papillary Carcinoma; Stage III Thyroid Gland Papillary Carcinoma; Stage IV Thyroid Gland Papillary Carcinoma

  6. Targeting Thyroid Hormone Receptor Beta in Triple Negative Breast Cancer

    PubMed Central

    Gu, Guowei; Gelsomino, Luca; Covington, Kyle R.; Beyer, Amanda R.; Wang, John; Rechoum, Yassine; Huffman, Kenneth; Carstens, Ryan; Ando, Sebastiano; Fuqua, Suzanne A.W.

    2015-01-01

    Purpose Discover novel nuclear receptor targets in triple negative breast cancer Methods Expression microarray, western blot, qRT-PCR, MTT growth assay, soft agar anchorage-independent growth assay, TRE reporter transactivation assay, statistical analysis. Results We performed microarray analysis using 227 triple negative breast tumors, and clustered the tumors into five groups according to their nuclear receptor expression. Thyroid hormone receptor beta (TRβ) was one of the most differentially expressed nuclear receptors in group 5 compared to other groups. TRβ low expressing patients were associated with poor outcome. We evaluated the role of TRβ in triple negative breast cancer cell lines representing group 5 tumors. Knockdown of TRβ increased soft agar colony and reduced sensitivity to docetaxel and doxorubicin treatment. Docetaxel or doxorubicin long-term cultured cell lines also expressed decreased TRβ protein. Microarray analysis revealed cAMP/PKA signaling was the only KEGG pathways upregulated in TRβ knockdown cells. Inhibitors of cAMP or PKA, in combination with doxorubicin further enhanced cell apoptosis and restored sensitivity to chemotherapy. TRβ-specific agonists enhanced TRβ expression, and further sensitized cells to both docetaxel and doxorubicin. Sensitization was mediated by increased apoptosis with elevated cleaved PARP and caspase 3. Conclusions TRβ represents a novel nuclear receptor target in triple negative breast cancer; low TRβ levels were associated with enhanced resistance to both docetaxel and doxorubicin treatment. TRβ-specific agonists enhance chemosensitivity to these two agents. Mechanistically enhanced cAMP/PKA signaling was associated with TRβ’s effects on response to chemotherapy. PMID:25820519

  7. Familial Adenomatous Polyposis-Associated Papillary Thyroid Cancer

    PubMed Central

    Abdullah Suhaimi, Shahrun Niza; Nazri, Nadzrin; Nani Harlina, Mat Latar; Md. Isa, Nurismah; Muhammad, Rohaizak

    2015-01-01

    Papillary thyroid carcinoma (PTC) associated with familial adenomatous polyposis (FAP) is rare. It is usually associated with the cribriform-morular variant of PTC, with unusual patterns on detailed histology examination. This variant is known to have a good prognosis. Papillary thyroid carcinoma associated with FAP commonly occurs in females in their 30s and rarely in the elderly. We report a case of a 69-year-old female presenting with thyroid swelling and a history of FAP. PMID:26715910

  8. AZD1480 blocks growth and tumorigenesis of RET- activated thyroid cancer cell lines.

    PubMed

    Couto, Joana P; Almeida, Ana; Daly, Laura; Sobrinho-Simões, Manuel; Bromberg, Jacqueline F; Soares, Paula

    2012-01-01

    Persistent RET activation is a frequent event in papillary thyroid carcinoma (PTC) and medullary thyroid carcinoma (MTC). In these cancers, RET activates the ERK/MAPK, the PI3K/AKT/mTOR and the JAK/STAT3 pathways. Here, we tested the efficacy of a JAK1/2- inhibitor, AZD1480, in the in vitro and in vivo growth of thyroid cancer cell lines expressing oncogenic RET. Thyroid cancer cell lines harboring RET/PTC1 (TPC-1), RET M918T (MZ-CRC1) and RET C634W (TT) alterations, as well as TPC-1 xenografts, were treated with JAK inhibitor, AZD1480. This inhibitor led to growth inhibition and/or apoptosis of the thyroid cancer cell lines in vitro, as well as to tumor regression of TPC-1 xenografts, where it efficiently blocked STAT3 activation in tumor and stromal cells. This inhibition was associated with decreased proliferation, decreased blood vessel density, coupled with increased necrosis. However, AZD1480 repressed the growth of STAT3- deficient TPC-1 cells in vitro and in vivo, demonstrating that its effects in this cell line were independent of STAT3 in the tumor cells. In all cell lines, the JAK inhibitor reduced phospho-Y1062 RET levels, and mTOR effector phospho-S6, while JAK1/2 downregulation by siRNA did not affect cell growth nor RET and S6 activation. In conclusion, AZD1480 effectively blocks proliferation and tumor growth of activated RET- thyroid cancer cell lines, likely through direct RET inhibition in cancer cells as well as by modulation of the microenvironment (e.g. via JAK/phospho-STAT3 inhibition in endothelial cells). Thus, AZD1480 should be considered as a therapeutic agent for the treatment of RET- activated thyroid cancers. PMID:23056499

  9. Prospective study of seaweed consumption and thyroid cancer incidence in women: the Japan collaborative cohort study.

    PubMed

    Wang, Chaochen; Yatsuya, Hiroshi; Li, Yuanying; Ota, Atsuhiko; Tamakoshi, Koji; Fujino, Yoshihisa; Mikami, Haruo; Iso, Hiroyasu; Tamakoshi, Akiko

    2016-05-01

    Excess intake of iodine is a suspected risk factor for thyroid cancer. Previous epidemiological research from Japan reported that daily intake of seaweed was associated with a four-fold higher risk in postmenopausal women, whereas others reported a null association. A major source of iodine intake in Japan is from edible seaweeds, and it is reported to be among the highest in the world. We examined the association between seaweed intake frequency and the risk of thyroid cancer in women in the Japan Collaborative Cohort Study followed from 1988 to 2009. Seaweed intake, together with other lifestyle-related information was collected using a self-administered questionnaire at baseline. Seaweed intake frequency was categorized as follows: 1-2 times/week or less, 3-4 times/week, and almost daily. Hazard ratios and the 95% confidence intervals of thyroid cancer incidence according to seaweed intake frequency were estimated using Cox proportional hazards regression. During 447 876 person-years of follow-up (n=35 687), 94 new cases of thyroid cancer were identified. The crude incidence rate was 20.9 per 100 000 person-years. The hazard ratio of thyroid cancer in women who consumed seaweed daily compared with women who ate it 1-2 times/week or less was 1.15 (95% confidence interval: 0.69-1.90, P for trend=0.59). Further analyses did not indicate any association between seaweed intake and the risk of thyroid cancer on statistically adjusting for potential confounding variables as well as on stratification by menopausal status. The present study did not find an association between seaweed intake and thyroid cancer incidence in premenopausal or in postmenopausal women. PMID:26011104

  10. Notch and TGF-β/Smad3 pathways are involved in the interaction between cancer cells and cancer-associated fibroblasts in papillary thyroid carcinoma.

    PubMed

    Zhang, Jie; Wang, Yuan; Li, Dan; Jing, Shanghua

    2014-01-01

    Accumulating evidence suggests that cancer-associated stromal fibroblasts (CAFs) contribute to tumor growth by actively communicating with cancer cells. Our aim was to identify the signaling pathways that are involved in tumor-stromal cell interactions in human papillary thyroid carcinoma (PTC). Immunohistochemical analyses were performed with 127 archived formalin-fixed and paraffin-embedded thyroid tissue samples that included 70 cases of PTC, 35 cases of nodular goiter (NG), and 22 cases of normal thyroid tissues. The results showed that the expression levels of Notch1, transforming growth factor β (TGF-β1), and p-Smad3 in PTC cells and α-smooth muscle actin (α-SMA) in the stroma of PTC were all significantly higher than in NG and normal thyroid tissues. Further analysis showed that in PTC, higher expression levels of Notch1 and TGF-β1 were closely related with lymph node metastasis (P < 0.05), whereas for α-SMA and p-Smad3, the percent expression increased significantly with advanced tumor stages (P < 0.05). Correlation analysis revealed that TGF-β1 expression increased with increased Notch1 and p-Smad3 levels in PTC cells (P < 0.05). Moreover, a significant correlation was found between higher TGF-β1 expression in PTC cells and increased α-SMA levels in the fibroblasts surrounding the cancer cells (P < 0.05). We identified TGF-β1 as an important factor from PTC cells that act in a paracrine manner to influence the activation of stromal fibroblasts. These data suggest that the activation of Notch and TGF-β/Smad3 pathways in cancer cells influence tumor growth. Moreover, cancer cell-derived-TGF-β ligands also affect stromal cells in a paracrine fashion and enhance tumor growth. PMID:23918305

  11. The influence of dietary patterns on the development of thyroid cancer.

    PubMed

    Markaki, I; Linos, D; Linos, A

    2003-09-01

    To elucidate the role of diet in the development of thyroid cancer, we conducted a case-control study of 113 persons with histologically-verified thyroid cancer and 138 controls, matched by age, gender and health unit. Socio-economic data, known risk factors and food consumption of more than 100 items were recorded by interviewer-administered prestructured questionnaire. Factor analysis was used to identify possible dietary patterns and logistic regression analysis was used to explore the effect of food items or dietary patterns on thyroid cancer. After adjustment for age, gender, body mass index (BMI), and total energy intake, significant positive associations were observed for pork consumption, while negative ones were observed for tomatoes, lemons and pasta. Dietary patterns of fruits, raw vegetables and mixed raw vegetables and fruits, led to a reduced risk (corresponding odds ratios (ORs) 0.68, 0.71, 0.73) for all thyroid cancers and similar figures were obtained for papillary thyroid cancers. A dietary pattern of fish and cooked vegetables led to an increased risk (OR 2.79) of follicular cancer. PMID:12932671

  12. Chernobyl-related thyroid cancer: what evidence for role of short-lived iodines?

    PubMed Central

    Bleuer, J P; Averkin, Y I; Abelin, T

    1997-01-01

    Over 500 cases of thyroid cancer were diagnosed in Belarus between 1986 and 1995 among persons exposed as children (under 15 years of age) to radioactive contamination from the Chernobyl nuclear accident. There is little doubt that radioactive iodine isotopes emitted during the nuclear explosion and subsequent fire were instrumental in causing malignancy in this particular organ. Comparison of the observed geographic distribution of Chernobyl-associated thyroid cancer incidence rates by districts with contamination maps of radioactive fallout shows a better fit for estimated 131I contamination than for 137Cs. Because 131I used for medical purposes had not been considered carcinogenic in humans in the past, and in view of the unusually short latency period between exposure and clinical manifestation of cancer, it is suspected that not only 131I but also energy-rich shorter-lived radioiodines may have played a role in post-Chernobyl thyroid carcinogenesis. Measurements of iodine isotopes are not available, but reconstruction of geographic distributions and estimations of radioactive fallout based on meteorological observations immediately following the accident could provide a basis for comparison with the distribution of thyroid cancer cases. In this paper, data from the Epidemiological Cancer Register for Belarus will be used to show geographic and time trends of thyroid cancer incidence rates in the period from 1986 to 1995 among persons who were exposed as children, and these will be compared with the estimated contamination by radioiodines. Tentative conclusions are drawn from the available evidence and further research requirements discussed. PMID:9467068

  13. Aberrant Expression of Posterior HOX Genes in Well Differentiated Histotypes of Thyroid Cancers

    PubMed Central

    Cantile, Monica; Scognamiglio, Giosuè; La Sala, Lucia; La Mantia, Elvira; Scaramuzza, Veronica; Valentino, Elena; Tatangelo, Fabiana; Losito, Simona; Pezzullo, Luciano; Chiofalo, Maria Grazia; Fulciniti, Franco; Franco, Renato; Botti, Gerardo

    2013-01-01

    Molecular etiology of thyroid cancers has been widely studied, and several molecular alterations have been identified mainly associated with follicular and papillary histotypes. However, the molecular bases of the complex pathogenesis of thyroid carcinomas remain poorly understood. HOX genes regulate normal embryonic development, cell differentiation and other critical processes in eukaryotic cell life. Several studies have shown that HOX genes play a role in neoplastic transformation of several human tissues. In particular, the genes belonging to HOX paralogous group 13 seem to hold a relevant role in both tumor development and progression. We have identified a significant prognostic role of HOX D13 in pancreatic cancer and we have recently showed the strong and progressive over-expression of HOX C13 in melanoma metastases and deregulation of HOX B13 expression in bladder cancers. In this study we have investigated, by immunohistochemisty and quantitative Real Time PCR, the HOX paralogous group 13 genes/proteins expression in thyroid cancer evolution and progression, also evaluating its ability to discriminate between main histotypes. Our results showed an aberrant expression, both at gene and protein level, of all members belonging to paralogous group 13 (HOX A13, HOX B13, HOX C13 and HOX D13) in adenoma, papillary and follicular thyroid cancers samples. The data suggest a potential role of HOX paralogous group 13 genes in pathogenesis and differential diagnosis of thyroid cancers. PMID:24189220

  14. Vaccine Therapy With or Without Sargramostim in Treating Patients With Advanced or Metastatic Cancer

    ClinicalTrials.gov

    2013-01-24

    Adenocarcinoma of the Colon; Adenocarcinoma of the Gallbladder; Adenocarcinoma of the Pancreas; Adenocarcinoma of the Rectum; Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Gallbladder; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Male Breast Cancer; Mixed Adenocarcinoma of the Stomach; Ovarian Endometrioid Adenocarcinoma; Paget Disease of the Breast With Intraductal Carcinoma; Paget Disease of the Breast With Invasive Ductal Carcinoma; Recurrent Adult Primary Liver Cancer; Recurrent Breast Cancer; Recurrent Colon Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Salivary Gland Cancer; Salivary Gland Adenocarcinoma; Stage II Malignant Testicular Germ Cell Tumor; Stage II Pancreatic Cancer; Stage III Colon Cancer; Stage III Gastric Cancer; Stage III Malignant Testicular Germ Cell Tumor; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Stage III Salivary Gland Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IV Breast Cancer; Stage IV Colon Cancer; Stage IV Gastric Cancer; Stage IV Pancreatic Cancer; Stage IV Rectal Cancer; Stage IV Salivary Gland Cancer; Thyroid Gland Medullary Carcinoma; Unresectable Gallbladder Cancer

  15. Clinical Outcome, Role of BRAFV600E, and Molecular Pathways in Papillary Thyroid Microcarcinoma: Is It an Indolent Cancer or an Early Stage of Papillary Thyroid Cancer?

    PubMed Central

    Nucera, Carmelo; Pontecorvi, Alfredo

    2012-01-01

    Most human thyroid cancers are differentiated papillary carcinomas (PTC). Papillary thyroid microcarcinomas (PTMC) are tumors that measure 1 cm or less. This class of small tumors has proven to be a very common clinical entity in endocrine diseases. PTMC may be present in 30–40% of human autopsies and is often identified incidentally in a thyroid removed for benign clinical nodules. Although PTMC usually has an excellent long-term prognosis, it can metastasize to neck lymph nodes; however deaths related to this type of thyroid tumor are very rare. Few data exist on molecular pathways that play a role in PTMC development; however, two molecules have been shown to be associated with aggressive PTMC. S100A4 (calcium-binding protein), which plays a role in angiogenesis, extracellular matrix remodeling, and tumor microenvironment, is over-expressed in metastatic PTMC. In addition, the BRAFV600E mutation, the most common genetic alteration in PTC, is present in many PTMC with extra thyroidal extension and lymph node metastasis. Importantly, recently developed selective [e.g., PLX4720, PLX4032 (Vemurafenib, also called RG7204)] or non-selective (e.g., Sorafenib) inhibitors of BRAFV600E may be an effective treatment for patients with BRAFV600E-expressing PTMCs with aggressive clinical–pathologic features. Here, we summarize the clinical outcome, cancer genetics, and molecular mechanisms of PTMC. PMID:22649416

  16. Thyroid cancer. Reevaluation of an experimental model for radiogenic endocrine carcinogenesis

    SciTech Connect

    Clifton, K.H.

    1984-11-01

    The status of experimental studies of radiogenic thyroid cancer is appraised, and some older data are reinterpreted in the light of more recent findings. Problems of thyroid dosimetry, particularly the dosimetry of internal radioiodides, are discussed. The steps in radiation carcinogenesis during the acute phase, the latent phase, and the phase of tumor growth are discussed in terms of thyroid epithelial cell population changes. The roles of three cell populations (undamaged or completely repaired epithelial cells, oncogenically initiated cells, and terminally damaged but functionally competent cells) in neoplasia are described. Finally, the implications for man of these experimental results and conclusions are discussed. 89 refs., 4 figs.

  17. Contactin 1 as a potential biomarker promotes cell proliferation and invasion in thyroid cancer

    PubMed Central

    Shi, Kaiyuan; Xu, Dong; Yang, Chen; Wang, Liping; Pan, Weiyun; Zheng, Chuanming; Fan, Linyin

    2015-01-01

    Contactin 1 (CNTN1) as a member of the immunoglobulin superfamily plays important role in the development of nervous system. Recent studies find that elevated CNTN1 can promote the metastasis of cancer. However, the expression and function of CNTN1 in thyroid cancer are still unknown. Here, we firstly find CNTN1 is a new gene which can be regulated by RET/PTC3 (Ret proto-oncogene and Ret-activating protein ELE1) rearrangement gene and the protein level of CNTN1 is increasing in thyroid cancer. Besides this change is positively associated with the TNM stage and tumor size. Moreover, we confirm that knockdown of CNTN1 significantly inhibits the tumor proliferation, invasiveness and represses the expression of cyclin D1 (CCND1). In conclusion, CNTN1 will be a poteintial diagnosis biomarker and therapy target for thyroid cancer. PMID:26722434

  18. BRAF Inhibitors: Experience in Thyroid Cancer and General Review of Toxicity

    PubMed Central

    Cabanillas, M.E.; Patel, A.; Danysh, B. P.; Dadu, R.; Kopetz, S.; Falchook, G.

    2014-01-01

    The U.S. Food and Drug Administration–approved BRAF inhibitors, vemurafenib and dabrafenib, have demonstrated superior efficacy in patients with BRAF-mutant melanomas but have limited efficacy in BRAF-mutant colorectal cancer. Little is known at this time regarding BRAF inhibitors in thyroid cancer. Initial reports in patients with progressive, radioactive iodine–refractory BRAF-mutant papillary thyroid cancer suggest response rates of approximately 30–40%. In this review, we discuss BRAF inhibitors in the context of thyroid cancer, the toxicities associated with BRAF inhibitors, and the suggested management of those toxicities. The management of vemurafenib and dabrafenib toxicities is applicable across all tumor types and may serve as a practical guide to their use. PMID:25467940

  19. The Impact of Thyroid Cancer and Post-Surgical Radioactive Iodine Treatment on the Lives of Thyroid Cancer Survivors: A Qualitative Study

    PubMed Central

    Sawka, Anna M.; Goldstein, David P.; Brierley, James D.; Tsang, Richard W.; Rotstein, Lorne; Ezzat, Shereen; Straus, Sharon; George, Susan R.; Abbey, Susan; Rodin, Gary; O'Brien, Mary Ann; Gafni, Amiram; Thabane, Lehana; Goguen, Jeannette; Naeem, Asima; Magalhaes, Lilian

    2009-01-01

    Background Adjuvant treatment with radioactive iodine (RAI) is often considered in the treatment of well-differentiated thyroid carcinoma (WDTC). We explored the recollections of thyroid cancer survivors on the diagnosis of WDTC, adjuvant radioactive iodine (RAI) treatment, and decision-making related to RAI treatment. Participants provided recommendations for healthcare providers on counseling future patients on adjuvant RAI treatment. Methods We conducted three focus group sessions, including WDTC survivors recruited from two Canadian academic hospitals. Participants had a prior history of WDTC that was completely resected at primary surgery and had been offered adjuvant RAI treatment. Open-ended questions were used to generate discussion in the groups. Saturation of major themes was achieved among the groups. Findings There were 16 participants in the study, twelve of whom were women (75%). All but one participant had received RAI treatment (94%). Participants reported that a thyroid cancer diagnosis was life-changing, resulting in feelings of fear and uncertainty. Some participants felt dismissed as not having a serious disease. Some participants reported receiving conflicting messages from healthcare providers on the appropriateness of adjuvant RAI treatment or insufficient information. If RAI-related side effects occurred, their presence was not legitimized by some healthcare providers. Conclusions The diagnosis and treatment of thyroid cancer significantly impacts the lives of survivors. Fear and uncertainty related to a cancer diagnosis, feelings of the diagnosis being dismissed as not serious, conflicting messages about adjuvant RAI treatment, and treatment-related side effects, have been raised as important concerns by thyroid cancer survivors. PMID:19142227

  20. Treatment strategies for radioactive iodine-refractory differentiated thyroid cancer

    PubMed Central

    2014-01-01

    Until recently, no truly effective treatment options have existed for patients with radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC), a serious disease with poor prognosis. In November 2013, the targeted multikinase inhibitor, sorafenib, was approved for use in these patients based on substantially improved progression-free survival compared with placebo. A number of other targeted agents, including lenvatinib, are being investigated in phase II and phase III trials. With the advent of these new treatment options, practitioners are faced with making important decisions in determining which patients are candidates for systemic treatment and the optimal timing for treatment initiation. Since patients may remain asymptomatic for a protracted period of time, tumor size and growth rate are the primary considerations for making these choices. Proactive management of side effects is also critical in optimizing the effectiveness of treatment. Here we review targeted systemic agents that are either in use or are under investigation for RAI-refractory DTC and provide recommendations on the rationale for initiating systemic treatment and on managing adverse events. Four illustrative case studies are provided. PMID:25364392

  1. Carfilzomib potentiates CUDC-101-induced apoptosis in anaplastic thyroid cancer

    PubMed Central

    Zhang, Lisa; Boufraqech, Myriem; Lake, Ross; Kebebew, Electron

    2016-01-01

    Anaplastic thyroid cancer (ATC) is one of the most aggressive human malignancies, with no effective treatment currently available. Previously, we identified agents active against ATC cells, both in vitro and in vivo, using quantitative high-throughput screening of 3282 clinically approved drugs and small molecules. Here, we report that combining two of these active agents, carfilzomib, a second-generation proteasome inhibitor, and CUDC-101, a histone deacetylase and multi-kinase inhibitor, results in increased, synergistic activity in ATC cells. The combination of carfilzomib and CUDC-101 synergistically inhibited cellular proliferation and caused cell death in multiple ATC cell lines harboring various driver mutations observed in human ATC tumors. This increased anti-ATC effect was associated with a synergistically enhanced G2/M cell cycle arrest and increased caspase 3/7 activity induced by the drug combination. Mechanistically, treatment with carfilzomib and CUDC-101 increased p21 expression and poly (ADP-ribose) polymerase protein cleavage. Our results suggest that combining carfilzomib and CUDC-101 would offer an effective therapeutic strategy to treat ATC. PMID:26934320

  2. Carfilzomib potentiates CUDC-101-induced apoptosis in anaplastic thyroid cancer.

    PubMed

    Zhang, Lisa; Boufraqech, Myriem; Lake, Ross; Kebebew, Electron

    2016-03-29

    Anaplastic thyroid cancer (ATC) is one of the most aggressive human malignancies, with no effective treatment currently available. Previously, we identified agents active against ATC cells, both in vitro and in vivo, using quantitative high-throughput screening of 3282 clinically approved drugs and small molecules. Here, we report that combining two of these active agents, carfilzomib, a second-generation proteasome inhibitor, and CUDC-101, a histone deacetylase and multi-kinase inhibitor, results in increased, synergistic activity in ATC cells. The combination of carfilzomib and CUDC-101 synergistically inhibited cellular proliferation and caused cell death in multiple ATC cell lines harboring various driver mutations observed in human ATC tumors. This increased anti-ATC effect was associated with a synergistically enhanced G2/M cell cycle arrest and increased caspase 3/7 activity induced by the drug combination. Mechanistically, treatment with carfilzomib and CUDC-101 increased p21 expression and poly (ADP-ribose) polymerase protein cleavage. Our results suggest that combining carfilzomib and CUDC-101 would offer an effective therapeutic strategy to treat ATC. PMID:26934320

  3. Radiologic and Pathologic Findings of a Follicular Variant of Papillary Thyroid Cancer with Extensive Stromal Fat: A Case Report

    PubMed Central

    Choi, Jin Woo; Kim, Tae Hyung; Roh, Hong Gee; Moon, Won-Jin; Lee, Sang Hwa; Hwang, Tae Sook

    2015-01-01

    Thyroid cancer may have small adipose structures detected by microscopy. However, there are no reports of thyroid cancer with gross fat evaluated by radiological methods. We reported a case of a 58-year-old woman with a fat containing thyroid mass. The mass was hyperechoic and ovoid in shape with a smooth margin on ultrasonography. On computed tomography, the mass had markedly low attenuation suggestive of fat, and fine reticular and thick septa-like structures. The patient underwent a right lobectomy. The mass was finally diagnosed as a follicular variant of papillary thyroid cancer with massive stromal fat. PMID:26576126

  4. Down-regulation of SOSTDC1 promotes thyroid cancer cell proliferation via regulating cyclin A2 and cyclin E2

    PubMed Central

    He, Xiaoying; Ke, Weijian; Xu, Lijuan; Liu, Liehua; Xiao, Haipeng; Li, Yanbing

    2015-01-01

    Sclerostin domain containing protein 1 (SOSTDC1) is down-regulated and acts as a tumor suppressor in some kinds of cancers. However, the expression pattern and biological significance of SOSTDC1 in thyroid cancer are largely unknown. We demonstrated that SOSTDC1 was significantly down-regulated in thyroid cancer. Ectopic over-expression of SOSTDC1 inhibited proliferation and induced G1/S arrest in thyroid cancer cells. Moreover, SOSTDC1 over-expression suppressed the growth of tumor xenografts in nude mice. We also found that elevated SOSTDC1 led to inhibition of cyclin A2 and cyclin E2. Together, our results demonstrate that SOSTDC1 is down-regulated in thyroid cancer and might be a potential therapeutic target in the treatment of thyroid cancer. PMID:26378658

  5. Downregulation of Notch-regulated Ankyrin Repeat Protein Exerts Antitumor Activities against Growth of Thyroid Cancer

    PubMed Central

    Chu, Bing-Feng; Qin, Yi-Yu; Zhang, Sheng-Lai; Quan, Zhi-Wei; Zhang, Ming-Di; Bi, Jian-Wei

    2016-01-01

    Background: The Notch-regulated ankyrin repeat protein (NRARP) is recently found to promote proliferation of breast cancer cells. The role of NRARP in carcinogenesis deserves extensive investigations. This study attempted to investigate the expression of NRARP in thyroid cancer tissues and assess the influence of NRARP on cell proliferation, apoptosis, cell cycle, and invasion in thyroid cancer. Methods: Thirty-four cases with thyroid cancer were collected from the Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine between 2011 and 2012. Immunohistochemistry was used to detect the level of NRARP in cancer tissues. Lentivirus carrying NRARP-shRNA (Lenti-NRARP-shRNA) was applied to down-regulate NRARP expression. Cell viability was tested after treatment with Lenti-NRARP-shRNA using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis and cell cycle distribution were determined by flow cytometry. Cell invasion was tested using Transwell invasion assay. In addition, expressions of several cell cycle-associated and apoptosis-associated proteins were examined using Western blotting after transfection. Student's t-test, one-way analysis of variance (ANOVA), or Kaplan–Meier were used to analyze the differences between two group or three groups. Results: NRARP was highly expressed in thyroid cancer tissues. Lenti-NRARP-shRNA showed significantly inhibitory activities against cell growth at a multiplicity of infection of 10 or higher (P < 0.05). Lenti-NRARP-shRNA-induced G1 arrest (BHT101: 72.57% ± 5.32%; 8305C: 75.45% ± 5.26%) by promoting p21 expression, induced apoptosis by promoting bax expression and suppressing bcl-2 expression, and inhibited cell invasion by suppressing matrix metalloproteinase-9 expression. Conclusion: Downregulation of NRARP expression exerts significant antitumor activities against cell growth and invasion of thyroid cancer, that suggests a potential role of NRARP in

  6. The diagnosis of cancer in thyroid fine needle aspiration biopsy. Surgery, repeat biopsy or specimen consultation?

    PubMed

    Stanek-Widera, A; Biskup-Frużyńska, M; Zembala-Nożyńska, E; Śnietura, M; Lange, D

    2016-03-01

    Fine needle aspiration biopsy (FNA) is the only diagnostic method that allows a preoperative diagnosis of thyroid carcinoma. An unequivocal diagnosis of a malignant change is achievable only in cases in which all cytological criteria of carcinoma are met. The aim of the study was to evaluate the necessity of repeat thyroid FNA in patients with papillary thyroid carcinoma verified on consultative examination (CE). We analyzed cytology reports of thyroid FNA and CE that resulted in the diagnosis of papillary carcinoma. Evaluation of the correlation of the cytological diagnosis with the histopathology report was based on data obtained after the surgery. Between 2010 and 2015 in the Institute of Oncology (IO) there were 184 cancers diagnosed on CE or in thyroid FNA performed primarily in IO. Additionally, 74 patients were subjected to repeat biopsy after confirmation of cancer in CE. Histopathological diagnosis of cancer was obtained in 62 (100%) cases that were doubly confirmed with cytological examination. The remaining 12 patients were operated on outside the institute. From 110 FNA primarily performed in the IO, histopathological verification was achievable in 92 cases, from which 92 (100%) provided a confirmation of cancer, and the remaining 18 patients were operated on outside the institute. High (100%) specificity of cancer diagnosis in FNA established primarily and verified on CE (second independent assessment) indicates that repeat FNA in order to confirm the diagnosis is unnecessary. PMID:27179270

  7. Targeted near infrared hyperthermia combined with immune stimulation for optimized therapeutic efficacy in thyroid cancer treatment

    PubMed Central

    Zhou, Le; Zhang, Mengchao; Fu, Qingfeng; Li, Jingting; Sun, Hui

    2016-01-01

    Treatment of thyroid cancer has incurred much focus because of its high prevalency. As a new strategy treating thyroid cancer, hyperthermia takes several advantages compared with surgery or chemotherapy, including minimal invasion, low systematic toxicity and the ability to enhance the immunogenicity of cancer cells with the expression Hsp70 which serves as Toll-like receptors-4 (TLR-4 agonist). However, Hsp70 as a molecular chaperone can protect cells from heat induced apoptosis and therefore compromise the tumor killing effect of hyperthermia. In this study, to solve this problem, a combined hyperthermia therapy was employed to treat thyroid cancer. We prepared a probe with the tumor targeting agent AG to monitor thyroid tumor issue and generate heat to kill tumor cells in vivo. At the same time Quercetin (inhibitor of HSP70) and lipopolysaccharide (LPS) (agonist of TLR-4) were used for the combined hyperthermia therapy. The results showed that compared with free IR820, AG modification facilitated much enhanced cellular uptake and greatly pronounced tumor targeting ability. The combined therapy exhibited the most remarkable tumor inhibition compared with the single treatments both in vitro and in vivo. These findings verified that the new therapeutic combination could significantly improve the effect of hyperthermia and shed light on a novel clinical strategy in thyroid cancer treatment. PMID:26769848

  8. Hypothyroidism in Pancreatic Cancer: Role of Exogenous Thyroid Hormone in Tumor Invasion—Preliminary Observations

    PubMed Central

    Sarosiek, Konrad; Gandhi, Ankit V.; Saxena, Shivam; Kang, Christopher Y.; Chipitsyna, Galina I.; Yeo, Charles J.; Arafat, Hwyda A.

    2016-01-01

    According to the epidemiological studies, about 4.4% of American general elderly population has a pronounced hypothyroidism and relies on thyroid hormone supplements daily. The prevalence of hypothyroidism in our patients with pancreatic cancer was much higher, 14.1%. A retrospective analysis was performed on patients who underwent pancreaticoduodenectomy (Whipple procedure) or distal pancreatectomy and splenectomy (DPS) at Thomas Jefferson University Hospital, Philadelphia, from 2005 to 2012. The diagnosis of hypothyroidism was correlated with clinicopathologic parameters including tumor stage, grade, and survival. To further understand how thyroid hormone affects pancreatic cancer behavior, functional studies including wound-induced cell migration, proliferation, and invasion were performed on pancreatic cancer cell lines, MiaPaCa-2 and AsPC-1. We found that hypothyroid patients taking exogenous thyroid hormone were more than three times likely to have perineural invasion, and about twice as likely to have higher T stage, nodal spread, and overall poorer prognostic stage (P < 0.05). Pancreatic cancer cell line studies demonstrated that exogenous thyroid hormone treatment increased cell proliferation, migration, and invasion (P < 0.05). We conclude that exogenous thyroid hormone may contribute to the progression of pancreatic cancer. PMID:27123358

  9. Increasing incidence of thyroid cancer in Shanghai, China, 1983-2007.

    PubMed

    Wang, Youxin; Wang, Wei

    2015-03-01

    Increasing incidence of thyroid cancer has been observed in some countries such as the United States, United Kingdom, France, and so on. Joinpoint regression was used to analyze the incidence of thyroid cancer in Shanghai, China, from 1983 to 2007. The results showed that there were 2 distinct slopes: in men, representing a significant annual percentage change (APC) of 2.6% from 1983 to 2000 (P < .001) followed by a sharp APC of 14.4% (P < .001), and in women, representing a significant APC of 4.9% from 1983 to 2003 (P < .001) followed by a sharp APC of 19.9% (P = .001). The sharp increase in thyroid cancer occurred 5 and 8 years after the iodine supplementation by salt, for men and women, respectively, suggesting that either the developed screening techniques or iodine supplementation might have contributed to the rapid increase in the incidence of thyroid cancer. The burden of thyroid cancer cases is expected to be substantial, based on predictions through 2020. PMID:22345304

  10. The BRAFV600E mutation: what is it really orchestrating in thyroid cancer?

    PubMed Central

    Nucera, Carmelo; Lawler, Jack; Hodin, Richard; Parangi, Sareh

    2010-01-01

    BRAFV600E is a constitutively active onco-kinase and is the most common genetic alteration in papillary thyroid carcinoma (PTC), and in anaplastic thyroid carcinoma as well, albeit at a lower frequency. The BRAFV600E mutation in some studies has been significantly associated with extra-thyroidal extension, metastases, recurrence, and mortality in patients with PTC. A recent genome-wide expression profiling approach (Gene Set Enrichment Analysis (GSEA)) and in vitro and in vivo functional studies revealed that BRAFV600E affects extracellular matrix composition (i.e. increased expression of some collagens and laminins) and promotes thyroid cancer migration and invasion. BRAFV600E through the phospho-MEK1/2 and phospho-ERK1/2 pathway may control a network of genes crucial in integrating and regulating the extracellular and intracellular signaling in thyroid cancer cells, which may be fundamental to trigger an abnormal cell differentiation/totipotency and shape/polarity, and contribute to tumor aggressiveness mechanisms (i.e. cell adhesion, migration, and invasion). Increasing our knowledge of BRAFV600E-modulated ECM genes and targeting the subset of genes essential for tumor aggressiveness will help establish a novel paradigm for treatment of thyroid cancers harboring BRAFV600E. Furthermore, identifying downstream events from the BRAFV600E/ERK1/2 pathway will eventually identify novel biomarkers that can be used to correlate with disease outcome and overall survival. PMID:21321384

  11. Genome-Wide Methylation Patterns in Papillary Thyroid Cancer Are Distinct Based on Histological Subtype and Tumor Genotype

    PubMed Central

    Ellis, Ryan J.; Wang, Yonghong; Stevenson, Holly S.; Boufraqech, Myriem; Patel, Dhaval; Nilubol, Naris; Davis, Sean; Edelman, Daniel C.; Merino, Maria J.; He, Mei; Zhang, Lisa; Meltzer, Paul S.

    2014-01-01

    Context: Aberrant DNA methylation is known to be a major factor in oncogenesis and cancer progression, but effects of methylation in papillary thyroid cancer (PTC) are not well defined. Objective: The objective of the study was to identify altered methylation patterns, which may be associated with PTC disease behavior. Design: This study was a genome-wide methylation analysis of PTC. Setting: The study was conducted at the National Institutes of Health Clinical Center. Patients: PTC tissue from 51 patients were analyzed and compared with normal thyroid tissue from seven patients. Interventions: CpG methylation status was assessed using advanced genome-wide methylation bead chips. Outcome Measures: Altered methylation patterns in PTC were analyzed by stage, recurrence, histological subtype of tumor, and tumor genotype. Results: PTC is globally hypomethylated compared with normal thyroid with 2837 differentially methylated CpG sites. The follicular variant of PTC demonstrated less differential methylation with only 569 differentially methylated CpG sites. Tumors with mutations in BRAF, RET/PTC, and RAS demonstrated a 3.6-fold increase in the number of differentially methylated sites compared with wild-type tumors. The differentially methylated genes were associated with oncological pathways including cellular movement, growth, and proliferation. Conclusion: PTC is epigenetically distinct from the follicular variant of PTC and by gene mutation status (BRAF, RET/PTC, and RAS). PMID:24423287

  12. Influence of iodine deficiency and iodine prophylaxis on thyroid cancer histotypes and incidence in endemic goiter area.

    PubMed

    Huszno, B; Szybiński, Z; Przybylik-Mazurek, E; Stachura, J; Trofimiuk, M; Buziak-Bereza, M; Gołkowski, F; Pantoflinski, J

    2003-01-01

    The aim of the study was to evaluate the correlation between thyroid cancer histotype and incidence rate (IR) and iodine nutrition level in two endemic goiter areas: the districts of Krakow and Nowy Sacz. The suspension of iodine prophylaxis in Poland in 1980 resulted in increased goiter prevalence in schoolchildren and adults and elevated TSH levels in newborns in the early 1990s. Since 1992 a rise in thyroid cancer IR was observed. Thyroid cancer IR in the Krakow population was 2.22 in 1986; 3.62 in 1995 and 6.02 in 2001; in Nowy Sacz: 1.52; 2.59 and 3.88 respectively. In 1986 papillary/follicular cancer ratio in both areas was about 1.0--the value typical of iodine deficient areas. After restoring the obligatory iodine prophylaxis in 1997, a significant decrease in elevated TSH concentration in newborns and urinary iodine concentration increase in schoolchildren were observed. A relative rise in the incidence of papillary thyroid cancer and decrease in follicular cancer, resulting in rise in papillary/follicular thyroid cancer ratio up to 5.9 in 2001 was also observed. Since 1999 no further thyroid cancer IR increase was noted. In conclusion, a significant increase in differentiated thyroid cancer IR was observed in association with the iodine prophylaxis suspension. Changes in thyroid cancer histotypes in 1986-2001 and a significant decrease in incremental rate of differentiated thyroid cancer probably reflect the influence of effective iodine prophylaxis. The significant difference between IR of thyroid cancer incidence in the districts of Krakow and Nowy Sacz may be related to differences in the exposure to radiation after the Chernobyl accident. PMID:12762644

  13. Cediranib Maleate With or Without Lenalidomide in Treating Patients With Thyroid Cancer

    ClinicalTrials.gov

    2016-07-20

    Recurrent Thyroid Gland Carcinoma; Stage I Thyroid Gland Follicular Carcinoma; Stage I Thyroid Gland Papillary Carcinoma; Stage II Thyroid Gland Follicular Carcinoma; Stage II Thyroid Gland Papillary Carcinoma; Stage III Thyroid Gland Follicular Carcinoma; Stage III Thyroid Gland Papillary Carcinoma; Stage IVA Thyroid Gland Follicular Carcinoma; Stage IVA Thyroid Gland Papillary Carcinoma; Stage IVB Thyroid Gland Follicular Carcinoma; Stage IVB Thyroid Gland Papillary Carcinoma; Stage IVC Thyroid Gland Follicular Carcinoma; Stage IVC Thyroid Gland Papillary Carcinoma

  14. Risk of Thyroid Nodular Disease and Thyroid Cancer in Patients with Acromegaly – Meta-Analysis and Systematic Review

    PubMed Central

    Wolinski, Kosma; Czarnywojtek, Agata; Ruchala, Marek

    2014-01-01

    Introduction Acromegaly is a quite rare chronic disease caused by the increased secretion of growth hormone (GH) and subsequently insulin - like growth factor 1. Although cardiovascular diseases remains the most common cause of mortality among acromegalic patients, increased prevalence of malignant and benign neoplasms remains a matter of debate. The aim of this study is to evaluate the risk of thyroid nodular disease (TND) and thyroid cancer in patients with acromegaly. Materials and Methods PubMed, Cochrane Library, Scopus, Cinahl, Academic Search Complete, Web of Knowledge, PubMed Central, PubMed Central Canada and Clinical Key databases were searched to identify studies containing. Random–effects model was used to calculate pooled odds ratios and risk ratios of TND in acromegaly. Studies which not included control groups were systematically reviewed. Results TND was more frequent in acromegaly than in control groups (OR = 6.9, RR = 2.1). The pooled prevalence of TND was 59.2%. Also thyroid cancer (TC) proved to be more common in acromegalic patients (OR = 7.5, RR = 7.2), prevalence was 4.3%. The pooled rate of malignancy (calculated per patient) was equal to 8.7%. Conclusions This study confirms that both TND and TC occur significantly more often in acromegalic patients than in general population. These results indicate that periodic thyroid ultrasound examination and careful evaluation of eventual lesions should be an important part of follow-up of patients with acromegaly. PMID:24551163

  15. Differential Expression of Aquaporins and Its Diagnostic Utility in Thyroid Cancer

    PubMed Central

    Niu, Dongfeng; Kondo, Tetsuo; Nakazawa, Tadao; Kawasaki, Tomonori; Yamane, Tetsu; Mochizuki, Kunio; Kato, Yohichiro; Matsuzaki, Toshiyuki; Takata, Kuniaki; Katoh, Ryohei

    2012-01-01

    Background Aquaporin3 (AQP3) and Aquaporin4 (AQP4) play a major role in transcellular and transepithelial water movement as water channel membrane proteins. Little is known of their expression and significance in human thyroid tissues. Thus, we examined the expression of AQP3 and AQP4 in normal, hyperplastic and neoplastic thyroid tissues in conjunction with human thyroid cancer cell lines. Methods and Results Immunohistochemical analyses demonstrated AQP3 in the cytoplasmic membrane of normal C cells, but not in follicular cells. In contrast, AQP4 was not found in C cells but was identified in normal follicular cells. AQP4 was positive in 92% of Graves’ disease thyroids and 97% of multinodular goiters, and we failed to demonstrate AQP3 in these hyperplastic tissues. In neoplastic thyroid lesions, we observed AQP3 in 91% of medullary thyroid carcinomas but in no other follicular cell tumors. AQP4 was demonstrated in 100% of follicular adenomas, 90% of follicular carcinomas, and 85% of papillary carcinomas, while it was negative in all medullary carcinomas and undifferentiated carcinomas. Reverse transcriptase polymerase chain reaction (RT-PCR) analyses revealed AQP3 mRNA expression only in medullary carcinomas and AQP4 mRNA expression in follicular cell-derived tumors except for undifferentiated carcinomas. In thyroid cancer cell lines, using RT-PCR and western blotting, AQP3 mRNA and protein were only identified in the TT cell line (human medullary carcinoma cell line) and AQP4 in the other cell lines. In addition, AQP3 mRNA expression was up-regulated by FBS and calcium administration in both a dose and time dependent manner in TT cells. Conclusion The differential expressions of AQP3 and AQP4 may reflect the biological nature and/or function of normal, hyperplastic, and neoplastic thyroid cells and additionally may have value in determining differential diagnoses of thyroid tumors. PMID:22808259

  16. A new computational model for human thyroid cancer enhances the preoperative diagnostic efficacy

    PubMed Central

    Li, Tuo; Sheng, Jianguo; Li, Weiqin; Zhang, Xin; Yu, Hongyu; Chen, Xueyun; Zhang, Jianquan; Cai, Quancai; Shi, Yongquan; Liu, Zhimin

    2015-01-01

    Considering the high rate of missed diagnosis and delayed treatments for thyroid cancer, an effective systematic model for the differential diagnosis is highly needed. Thus we analyzed the data on the clinicopathological characteristics, routine laboratory tests and imaging examinations in a cohort of 13,980 patients with thyroid cancer to establish a new diagnostic model for differentiating thyroid cancer in clinical practice. Here, we randomly selected two-thirds of the population to develop the thyroid malignancy risk scoring system (TMRS) for preoperative differentiation between thyroid cancer and benignant thyroid diseases, and then validated its differential diagnostic power in the rest one-third population. The 18 predictors finally enrolled in the TMRS included male gender, clinical manifestations (fever, neck sore, neck lump, palpitations or sweating), laboratory findings (TSH>1.56mIU/L, FT3>5.85pmol/L, TPOAb>14.97IU/ml, TgAb>48.00IU/ml, Tg>34.59μg/L, Ct>64.00ng/L, and CEA>0.41μg/L), and ultrasound features (tumor number≤ 23mm, site, size, echo texture, margins, and shape of neck lymphnodes). The TMRS is validated to be well-calibrated (P = 0.437) and excellently discriminated (AUC = 0.93, 95% CI [0.92, 0.94]), with an accuracy of 83.2%, a sensitivity of 89.3%, a specificity of 81.5%, positive and negative predictive values of 56.8% and 96.6%, positive and negative likelihood ratios of 4.83 and 0.13 in the development cohort, respectively. The TMRS highlights that this differential diagnostic system could help provide accurate preoperative risk stratification for thyroid cancer, and avoid unnecessary over- and under-treatment for such patients. PMID:26325368

  17. Long-term trend of thyroid cancer risk among Japanese atomic-bomb survivors: 60 years after exposure

    PubMed Central

    Furukawa, Kyoji; Preston, Dale; Funamoto, Sachiyo; Yonehara, Shuji; Ito, Masahiro; Tokuoka, Shoji; Sugiyama, Hiromi; Soda, Midori; Ozasa, Kotaro; Mabuchi, Kiyohiko

    2014-01-01

    Thyroid cancer risk following exposure to ionizing radiation in childhood and adolescence is a topic of public concern. To characterize the long-term temporal trend and age-at-exposure variation in the radiation-induced risk of thyroid cancer, we analyzed thyroid cancer incidence data for the period from 1958 through 2005 among 105,401 members of the Life Span Study cohort of Japanese atomic-bomb survivors. During the follow-up period, 371 thyroid cancer cases (excluding those with microcarcinoma with a diameter <10 mm) were identified as a first primary among the eligible subjects. Using a linear dose–response model, the excess relative risk of thyroid cancer at 1 Gy of radiation exposure was estimated as 1.28 (95% confidence interval: 0.59–2.70) at age 60 after acute exposure at age 10. The risk decreased sharply with increasing age-at-exposure and there was little evidence of increased thyroid cancer rates for those exposed after age 20. About 36% of the thyroid cancer cases among those exposed before age 20 were estimated to be attributable to radiation exposure. While the magnitude of the excess risk has decreased with increasing attained age or time since exposure, the excess thyroid cancer risk associated with childhood exposure has persisted for >50 years after exposure PMID:22847218

  18. Long-term trend of thyroid cancer risk among Japanese atomic-bomb survivors: 60 years after exposure.

    PubMed

    Furukawa, Kyoji; Preston, Dale; Funamoto, Sachiyo; Yonehara, Shuji; Ito, Masahiro; Tokuoka, Shoji; Sugiyama, Hiromi; Soda, Midori; Ozasa, Kotaro; Mabuchi, Kiyohiko

    2013-03-01

    Thyroid cancer risk following exposure to ionizing radiation in childhood and adolescence is a topic of public concern. To characterize the long-term temporal trend and age-at-exposure variation in the radiation-induced risk of thyroid cancer, we analyzed thyroid cancer incidence data for the period from 1958 through 2005 among 105,401 members of the Life Span Study cohort of Japanese atomic-bomb survivors. During the follow-up period, 371 thyroid cancer cases (excluding those with microcarcinoma with a diameter <10 mm) were identified as a first primary among the eligible subjects. Using a linear dose-response model, the excess relative risk of thyroid cancer at 1 Gy of radiation exposure was estimated as 1.28 (95% confidence interval: 0.59-2.70) at age 60 after acute exposure at age 10. The risk decreased sharply with increasing age-at-exposure and there was little evidence of increased thyroid cancer rates for those exposed after age 20. About 36% of the thyroid cancer cases among those exposed before age 20 were estimated to be attributable to radiation exposure. While the magnitude of the excess risk has decreased with increasing attained age or time since exposure, the excess thyroid cancer risk associated with childhood exposure has persisted for >50 years after exposure. PMID:22847218

  19. A Screening Study of Thyroid Cancer and Other Thyroid Diseases among Individuals Exposed in Utero to Iodine-131 from Chernobyl Fallout

    PubMed Central

    Hatch, M.; Brenner, A.; Bogdanova, T.; Derevyanko, A.; Kuptsova, N.; Likhtarev, I.; Bouville, A.; Tereshchenko, V.; Kovgan, L.; Shpak, V.; Ostroumova, E.; Greenebaum, E.; Zablotska, L.; Ron, E.; Tronko, M.

    2009-01-01

    Background: Like stable iodine, radioiodines concentrate in the thyroid gland, increasing thyroid cancer risk in exposed children. Data on exposure to the embryonic/fetal thyroid are rare, raising questions about use of iodine 131 (I-131) in pregnant women. We present here estimated risks of thyroid disease from exposure in utero to I-131 fallout from the Chernobyl nuclear accident. Methods: We conducted a cross-sectional thyroid screening study (palpation, ultrasound, thyroid hormones, and, if indicated, fine needle aspiration) from 2003 to 2006. Participants were 2582 mother-child pairs from Ukraine in which the mother had been pregnant at the time of the accident on April 26, 1986, or 2 months after the time during which I-131 fallout was still present (1494 from contaminated areas, 1088 in the comparison group). Individual cumulative in utero thyroid dose estimates were derived from estimated I-131 activity in the mother’s thyroid (mean 72 mGy; range 0–3230 mGy). Results: There were seven cases of thyroid carcinoma and one case of Hurthle cell neoplasm identified as a result of the screening. Whereas the estimated excess odds ratio per gray for thyroid carcinoma was elevated (excess odds ratio per gray 11.66), it was not statistically significant (P = 0.12). No radiation risks were identified for other thyroid diseases. Conclusion: Our results suggest that in utero exposure to radioiodines may have increased the risk of thyroid carcinoma approximately 20 yr after the Chernobyl accident, supporting a conservative approach to medical uses of I-131 during pregnancy. PMID:19106267

  20. Recent Trends and Geographical Distribution of Thyroid Cancer in Iran from 2004 to 2009

    PubMed Central

    Safavi, Ali; Jafari, Rozita; Chaibakhsh, Samira; Ramezani-Daryasar, Rashid; Rezaei, Mansour; Safavi, Amir Ali

    2014-01-01

    Background To prevent and control the cancers in Iran, the Iranian Department of Health has released the cancer rates data of the country. As the report has suggested, the incidence rate of thyroid cancer would be the most rapidly increasing among all the cancers. The study has aimed to carry out a qualitative assessment of thyroid cancer in Iran, during the 2004 to 2009, in a cross-sectional setting. Methods The incidence rates, the trend of individual provinces, the mean age at which the disease occurred, the correlation between incidence rate and median urinary iodine concentration were the parameters evaluated in our study. Results The average annual incidence rate during these six years was 2.17 per 100000. Chaharmahal-o-bakhtiari, had the highest incidence rate, but the East Azerbaijan provinces had the lowest incidence rates respectively. The age of diagnosis was the lowest in Ardebil but the highest in West Azerbaijan. In our study, we have found the positive correlation between thyroid cancer incidences with low urinary iodine concentration among all provinces (p-value=0.025). Conclusion Presently, the only recognized measure procedure for reducing thyroid cancer risk would be perhaps the correction of median urinary iodine concentration. Further researches have seemed to be required for investigation the other factors, in order to introduce preventive measures in Iran. PMID:26396709

  1. Childhood thyroid cancers and radioactive iodine therapy: necessity of precautious radiation health risk management.

    PubMed

    Kumagai, Atsushi; Reiners, Christoph; Drozd, Valentina; Yamashita, Shunichi

    2007-12-01

    One of the lessons from Chernobyl's legacy on health impact beyond 20 years is not only how to detect and treat the patients with radiation-associated thyroid cancers but how to follow up those who received radioactive iodine treatment repetitively after surgery in order to monitor any recurrence/worsening and also how to predict the risk of secondary primary cancers for their lifetime period. To evaluate the possibility of second primary tumors after radioactive iodine treatment, we reviewed the reports on risks from both external and internal radiation exposure, especially at high doses during childhood through an internet service of the National Library of Medicine and the National Institutes of Health, PubMed by the end of June, 2007, together with our own experience of Chernobyl childhood thyroid cancers. Children who were internally exposed after Chernobyl accident have a long-term risk of well differentiated thyroid cancers. Once they have disease, ironically radioactive iodine ablation is one of the useful therapies after surgical treatment. Elevated risks of solid cancers and leukemia have been found in radioiodine-treated patients, however, so far precious few reports from Chernobyl thyroid cancer patient were published. To reduce the adverse effects of radioactive iodine therapy on non-target tissues, recombinant human TSH has been applied and proved effective. Period of latency of second primary cancers may be very long. Therefore patients treated with high activities of radioactive iodine, especially children cases, should be carefully followed up during their whole lifespan. PMID:17938505

  2. Targeted therapy for genetic cancer syndromes: Fanconi anemia, medullary thyroid cancer, tuberous sclerosis, and RASopathies.

    PubMed

    Agarwal, Rishi; Liebe, Sarah; Turski, Michelle L; Vidwans, Smruti J; Janku, Filip; Garrido-Laguna, Ignacio; Munoz, Javier; Schwab, Richard; Rodon, Jordi; Kurzrock, Razelle; Subbiah, Vivek

    2015-02-01

    With the advent of genomics-based treatment in recent years, the use of targeted therapies in the treatment of various malignancies has increased exponentially. Though much data is available regarding the efficacy of targeted therapies for common malignancies, genetic cancer syndromes remain a somewhat unexplored topic with comparatively less published literature. This review seeks to characterize targeted therapy options for the following genetic cancer syndromes: Fanconi anemia, inherited medullary thyroid cancer, tuberous sclerosis, and RASopathies. By understanding the pathophysiology of these conditions as well as available molecularly targeted therapies, oncologists, in collaboration with geneticists and genetic counsellors, can begin to develop effective clinical management options and therapy regimens for the patients with these genetic syndromes that they may encounter in their practice. PMID:25725224

  3. False-positive uptake on radioiodine whole-body scintigraphy: physiologic and pathologic variants unrelated to thyroid cancer

    PubMed Central

    Oh, Jong-Ryool; Ahn, Byeong-Cheol

    2012-01-01

    Radioiodine whole-body scintigraphy (WBS), which takes advantage of the high avidity of radioiodine in the functioning thyroid tissues, has been used for detection of differentiated thyroid cancer. Radioiodine is a sensitive marker for detection of thyroid cancer; however, radioiodine uptake is not specific for thyroid tissue. It can also be seen in healthy tissue, including thymus, breast, liver, and gastrointestinal tract, or in benign diseases, such as cysts and inflammation, or in a variety of benign and malignant non-thyroidal tumors, which could be mistaken for thyroid cancer. In order to accurately interpret radioiodine scintigraphy results, one must be familiar with the normal physiologic distribution of the tracer and frequently encountered physiologic and pathologic variants of radioiodine uptake. This article will provide a systematic overview of potential false-positive uptake of radioiodine in the whole body and illustrate how such unexpected findings can be appropriately evaluated. PMID:23133823

  4. A robust biomarker of differential correlations improves the diagnosis of cytologically indeterminate thyroid cancers.

    PubMed

    Gomez-Rueda, Hugo; Palacios-Corona, Rebeca; Gutiérrez-Hermosillo, Hugo; Trevino, Victor

    2016-05-01

    The fine-needle aspiration of thyroid nodules and subsequent cytological analysis is unable to determine the diagnosis in 15 to 30% of thyroid cancer cases; patients with indeterminate cytological results undergo diagnostic surgery which is potentially unnecessary. Current gene expression biomarkers based on well-determined cytology are complex and their accuracy is inconsistent across public datasets. In the present study, we identified a robust biomarker using the differences in gene expression values specifically from cytologically indeterminate thyroid tumors and a powerful multivariate search tool coupled with a nearest centroid classifier. The biomarker is based on differences in the expression of the following genes: CCND1, CLDN16, CPE, LRP1B, MAGI3, MAPK6, MATN2, MPPED2, PFKFB2, PTPRE, PYGL, SEMA3D, SERGEF, SLC4A4 and TIMP1. This 15-gene biomarker exhibited superior accuracy independently of the cytology in six datasets, including The Cancer Genome Atlas (TCGA) thyroid dataset. In addition, this biomarker exhibited differences in the correlation coefficients between benign and malignant samples that indicate its discriminatory power, and these 15 genes have been previously related to cancer in the literature. Thus, this 15-gene biomarker provides advantages in clinical practice for the effective diagnosis of thyroid cancer. PMID:27035928

  5. A novel mechanism of sodium iodide symporter repression in differentiated thyroid cancer.

    PubMed

    Smith, Vicki E; Read, Martin L; Turnell, Andrew S; Watkins, Rachel J; Watkinson, John C; Lewy, Greg D; Fong, Jim C W; James, Sally R; Eggo, Margaret C; Boelaert, Kristien; Franklyn, Jayne A; McCabe, Christopher J

    2009-09-15

    Differentiated thyroid cancers and their metastases frequently exhibit reduced iodide uptake, impacting on the efficacy of radioiodine ablation therapy. PTTG binding factor (PBF) is a proto-oncogene implicated in the pathogenesis of thyroid cancer. We recently reported that PBF inhibits iodide uptake, and have now elucidated a mechanism by which PBF directly modulates sodium iodide symporter (NIS) activity in vitro. In subcellular localisation studies, PBF overexpression resulted in the redistribution of NIS from the plasma membrane into intracellular vesicles, where it colocalised with the tetraspanin CD63. Cell-surface biotinylation assays confirmed a reduction in plasma membrane NIS expression following PBF transfection compared with vector-only treatment. Coimmunoprecipitation and GST-pull-down experiments demonstrated a direct interaction between NIS and PBF, the functional consequence of which was assessed using iodide-uptake studies in rat thyroid FRTL-5 cells. PBF repressed iodide uptake, whereas three deletion mutants, which did not localise within intracellular vesicles, lost the ability to inhibit NIS activity. In summary, we present an entirely novel mechanism by which the proto-oncogene PBF binds NIS and alters its subcellular localisation, thereby regulating its ability to uptake iodide. Given that PBF is overexpressed in thyroid cancer, these findings have profound implications for thyroid cancer ablation using radioiodine. PMID:19706688

  6. Sorafenib in radioactive iodine-refractory well-differentiated metastatic thyroid cancer

    PubMed Central

    McFarland, Daniel C; Misiukiewicz, Krzysztof J

    2014-01-01

    Recent Phase III data presented at the American Society of Clinical Oncology (ASCO) 2013 annual conference by Brose et al led to the US Food and Drug Administration (FDA) approval of sorafenib for the treatment of well-differentiated radioactive iodine-resistant metastatic thyroid cancer. This is the second drug in 40 years to be FDA approved for this indication. Recent reviews and a meta-analysis reveal a modest ability to induce a partial remission but substantial ability to halt disease progression. Given the significant activating mutations present in thyroid cancer, many of which are inhibited by sorafenib, the next logical approach may be to combine targeted rational therapies if permitted by collective toxicity profiles. This systematic review aims to summarize the recent Phase II/III data leading to the FDA approval of sorafenib for radioactive iodine therapy differentiated thyroid cancer and highlights recent novel combination therapy trials. PMID:25053887

  7. Evolutionary features of thyroid cancer in patients with thyroidectomies from 2008 to 2013 in China.

    PubMed

    Liu, Xiaoyun; Zhu, Lijun; Wang, Zhixiao; Cui, Dai; Chen, Huanhuan; Duan, Yu; Shen, Meiping; Lu, Hui; Zhang, Zhihong; Chen, Jiawei; Alexander, Erik K; Yang, Tao; Wang, Xiaodong

    2016-01-01

    To evaluate the characteristics of thyroid carcinoma over time, we carried out a retrospective study to illustrate the evolutionary features of thyroid carcinoma. All records of thyroidectomies from the First Affiliated Hospital of Nanjing Medical University from 2008 to 2013 were obtained focusing on pathological diagnosis, size, local lymph node metastasis (LNM) of the tumors. The thyroid cancer detection rate increased from 24.6% to 41.5% significantly (P < 0.05). Papillary thyroid carcinoma (PTC) remained to be the most common type counting 86.4% of all thyroid carcinomas. In all 1,704 PTCs, microPTC (mPTC) with maximum diameter less than or equal to 10 mm has become the dominant form taking up 56.5% of all PTCs in 2013 while only 43.1% in 2008. The mean maximum tumor size has decreased from 17.8 mm to 12.2 mm significantly (P < 0.05). However, the average age, female dominance, and local LNM remained similarly in the past six years. Logistic regression test showed that the determinants for local LNM were age, gender and tumor size. mPTC has become the most common form of thyroid carcinoma detected during thyroidectomies in China while other features of thyroid carcinoma remained similarly in the recent years. PMID:27328631

  8. Papillary Thyroid Cancer in a Child with Progressive Transformation of Germinal Centers.

    PubMed

    Mohan, Suresh; DeNardo, Bradley; Stachurski, Dariusz; Greene Welch, Jennifer; Groblewski, Jan C

    2016-01-01

    Objectives. To describe the presentation and management of a child with Progressive Transformation of Germinal Centers (PTGC), an uncommon condition characterized by significant persistent lymphadenopathy, who developed papillary thyroid carcinoma and to explore and review potential links between PTGC and neoplastic processes in the head and neck. Methods. Case presentation and literature review are used. Results. A 10-year-old female presented with a right parotid mass and cervical lymphadenopathy. Multiple biopsies revealed PTGC without malignancy. Two years later, she developed fatigue and weight gain, and a thyroid nodule was found. Fine needle aspiration was strongly suggestive of papillary thyroid carcinoma. The patient underwent total thyroidectomy and central neck dissection without surgical management of the longstanding right lateral neck lymphadenopathy. Final pathology confirmed papillary thyroid carcinoma. She was treated with radioactive iodine therapy postoperatively and remains free of disease at three years of follow-up. Conclusions. PTGC is considered a benign condition but has previously been associated with Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL). This is the first reported case of papillary thyroid cancer in a child with preexisting cervical PTGC and no defined risk factors for thyroid malignancy. No link has been established with thyroid carcinoma, but patients with PTGC may have a defect in immune surveillance that predisposes them to malignancy. PMID:27069706

  9. Papillary Thyroid Cancer in a Child with Progressive Transformation of Germinal Centers

    PubMed Central

    Mohan, Suresh; DeNardo, Bradley; Stachurski, Dariusz; Greene Welch, Jennifer; Groblewski, Jan C.

    2016-01-01

    Objectives. To describe the presentation and management of a child with Progressive Transformation of Germinal Centers (PTGC), an uncommon condition characterized by significant persistent lymphadenopathy, who developed papillary thyroid carcinoma and to explore and review potential links between PTGC and neoplastic processes in the head and neck. Methods. Case presentation and literature review are used. Results. A 10-year-old female presented with a right parotid mass and cervical lymphadenopathy. Multiple biopsies revealed PTGC without malignancy. Two years later, she developed fatigue and weight gain, and a thyroid nodule was found. Fine needle aspiration was strongly suggestive of papillary thyroid carcinoma. The patient underwent total thyroidectomy and central neck dissection without surgical management of the longstanding right lateral neck lymphadenopathy. Final pathology confirmed papillary thyroid carcinoma. She was treated with radioactive iodine therapy postoperatively and remains free of disease at three years of follow-up. Conclusions. PTGC is considered a benign condition but has previously been associated with Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL). This is the first reported case of papillary thyroid cancer in a child with preexisting cervical PTGC and no defined risk factors for thyroid malignancy. No link has been established with thyroid carcinoma, but patients with PTGC may have a defect in immune surveillance that predisposes them to malignancy. PMID:27069706

  10. Risk factors for thyroid abnormalities after neck irradiation for childhood cancer

    SciTech Connect

    Kaplan, M.M.; Garnick, M.B.; Gelber, R.; Li, F.P.; Cassady, J.R.; Sallan, S.E.; Fine, W.E.; Sack, M.J.

    1983-02-01

    Thyroid evaluations were performed in 95 patients who received radiotherapy to the neck region for childhood cancer five to 34 years earlier. Fifty-six patients (61 percent) had at least one abnormality of serum free thyroxine index, serum thyroid-stimulating hormone (thyrotropin), or thyroid palpation. Seven had subnormal free thyroxine index and 40 had elevated thyrotropin concentrations. Thyroidal radiation doses of 3,000 or more rads and lymphangiography independently increased the risk (p less than or equal to 0.01) of an elevated serum thyrotropin concentration (present in 11 percent of patients with neither risk factor, 50 percent of those who underwent lymphangiography and received less than 3,000 rads, 46 percent of those who had 3,000 or more rads and no lymphangiography, and 76 percent of those with both), but duration of follow-up did not. Twenty-six patients had thyroid nodules and six others had diffuse thyroid enlargement. The frequency of palpable abnormalities increased with the follow-up time after radiation (30 percent of patients followed up less than 10 years had abnormalities versus 43 percent of those followed up 10 or more years, p . 0.03), but was not related to the serum thyrotropin level, radiation dose, or lymphangiography. Among 10 patients who had surgery for nodules, three had localized papillary thyroid carcinomas.

  11. MRI findings of lumbosacral metastasis from occult follicular thyroid cancer: report of a case.

    PubMed

    Çoban, Gökçen; Yildirim, Erkan; Gemici, Kazim; Erinanç, Hilal

    2014-03-01

    A 63-year-old female was admitted to our hospital with bowel and bladder incontinence. Magnetic resonance imaging (MRI) showed a 13 × 12 × 12 cm mass invading the posterior regions of the L4, L5, S1 and S2 vertebrae with broad paravertebral soft tissue invasion. A Tru-cut biopsy of the mass was performed. The histopathological examination revealed metastatic follicular carcinoma of the thyroid. Thyroid functional tests were within the normal limits. Thyroid sonography revealed a heterogeneous, ill-defined, 14 × 9 mm hypoechoic solid nodule in the right lobe of the thyroid gland. On thyroid scintigraphy, an area of focal hyperactivity was detected in the right lobe at the nodule localization. Total thyroidectomy was performed, and the primary tumor pathology was determined to be follicular thyroid cancer. To our knowledge, only a few cases of lumbosacral cord compression as the initial manifestation of follicular thyroid carcinoma have been reported in the literature. We aimed to discuss the MRI findings of tumors in this age group with lumbosacral localization. PMID:23129029

  12. Evolutionary features of thyroid cancer in patients with thyroidectomies from 2008 to 2013 in China

    PubMed Central

    Liu, Xiaoyun; Zhu, Lijun; Wang, Zhixiao; Cui, Dai; Chen, Huanhuan; Duan, Yu; Shen, Meiping; Lu, Hui; Zhang, Zhihong; Chen, Jiawei; Alexander, Erik K.; Yang, Tao; Wang, Xiaodong

    2016-01-01

    To evaluate the characteristics of thyroid carcinoma over time, we carried out a retrospective study to illustrate the evolutionary features of thyroid carcinoma. All records of thyroidectomies from the First Affiliated Hospital of Nanjing Medical University from 2008 to 2013 were obtained focusing on pathological diagnosis, size, local lymph node metastasis (LNM) of the tumors. The thyroid cancer detection rate increased from 24.6% to 41.5% significantly (P < 0.05). Papillary thyroid carcinoma (PTC) remained to be the most common type counting 86.4% of all thyroid carcinomas. In all 1,704 PTCs, microPTC (mPTC) with maximum diameter less than or equal to 10 mm has become the dominant form taking up 56.5% of all PTCs in 2013 while only 43.1% in 2008. The mean maximum tumor size has decreased from 17.8 mm to 12.2 mm significantly (P < 0.05). However, the average age, female dominance, and local LNM remained similarly in the past six years. Logistic regression test showed that the determinants for local LNM were age, gender and tumor size. mPTC has become the most common form of thyroid carcinoma detected during thyroidectomies in China while other features of thyroid carcinoma remained similarly in the recent years. PMID:27328631

  13. Living near nuclear power plants and thyroid cancer risk: A systematic review and meta-analysis.

    PubMed

    Kim, Jaeyoung; Bang, Yejin; Lee, Won Jin

    2016-02-01

    There has been public concern regarding the safety of residing near nuclear power plants, and the extent of risk for thyroid cancer among adults living near nuclear power plants has not been fully explored. In the present study, a systematic review and meta-analysis of epidemiologic studies was conducted to investigate the association between living near nuclear power plants and the risk of thyroid cancer. A comprehensive literature search was performed on studies published up to March 2015 on the association between nuclear power plants and thyroid cancer risk. The summary standardized incidence ratio (SIR), standardized mortality ratio (SMR), and 95% confidence intervals (CIs) were calculated using a random-effect model of meta-analysis. Sensitivity analyses were performed by study quality. Thirteen studies were included in the meta-analysis, covering 36 nuclear power stations in 10 countries. Overall, summary estimates showed no significant increased thyroid cancer incidence or mortality among residents living near nuclear power plants (summary SIR=0.98; 95% CI 0.87-1.11, summary SMR=0.80; 95% CI 0.62-1.04). The pooled estimates did not reveal different patterns of risk by gender, exposure definition, or reference population. However, sensitivity analysis by exposure definition showed that living less than 20 km from nuclear power plants was associated with a significant increase in the risk of thyroid cancer in well-designed studies (summary OR=1.75; 95% CI 1.17-2.64). Our study does not support an association between living near nuclear power plants and risk of thyroid cancer but does support a need for well-designed future studies. PMID:26638017

  14. Genetically Engineered Immunotherapy for Advanced Cancer

    Cancer.gov

    In this trial, doctors will collect T lymphocytes from patients with advanced mesothelin-expressing cancer and genetically engineer them to recognize mesothelin. The gene-engineered cells will be multiplied and infused into the patient to fight the cancer

  15. Lymph Node Ratio Predicts Recurrence in Papillary Thyroid Cancer

    PubMed Central

    Mazeh, Haggi; Chen, Herbert; Sippel, Rebecca S.

    2013-01-01

    Background. Lymph node metastasis occurs in 20%–50% of patients presenting for initial treatment of papillary thyroid cancer (PTC). The significance of lymph node metastases remains controversial, and the aim of this study is to determine how the lymph node ratio (LNR) may predict the likelihood of disease recurrence. Methods. We conducted a retrospective review of patients undergoing total thyroidectomy for PTC at our institution from 2005 to 2010. A total LNR (positive nodes to total nodes) and central lymph node ratio (cLNR) was calculated. Regression was used to determine a threshold LNR that best predicted recurrence. Multivariate logistic regression then determined the influence of LNR on recurrence while accounting for other known predictors of recurrence. Kaplan-Meier analysis and the log-rank test were used to compare differences in disease-free survival. Results. Of the 217 patients undergoing total thyroidectomy for PTC, 69 patients had concomitant neck dissections. Sixteen (23.2%) patients developed disease recurrence. When disease-free survival functions were compared, we found that patients with a total LNR ≥0.7 (p < .01) or a cLNR ≥0.86 (p = .04) had significantly worse disease-free survival rates than patients with ratios below these threshold values. Considering other known predictors of recurrence, we found that LNR was significantly associated with recurrence (odds ratio: 19.5, 95% confidence interval: 4.1–22.9; p < .01). Conclusions. Elevated total LNR and cLNR are strongly associated with recurrence of PTC after initial operation. LNR in PTC is a tool that can be used to determine the likelihood of the patient developing recurrent disease and inform postoperative follow-up. PMID:23345543

  16. A review on ultrasound-based thyroid cancer tissue characterization and automated classification.

    PubMed

    Acharya, U R; Swapna, G; Sree, S V; Molinari, F; Gupta, S; Bardales, R H; Witkowska, A; Suri, J S

    2014-08-01

    In this paper, we review the different studies that developed Computer Aided Diagnostic (CAD) for automated classification of thyroid cancer into benign and malignant types. Specifically, we discuss the different types of features that are used to study and analyze the differences between benign and malignant thyroid nodules. These features can be broadly categorized into (a) the sonographic features from the ultrasound images, and (b) the non-clinical features extracted from the ultrasound images using statistical and data mining techniques. We also present a brief description of the commonly used classifiers in ultrasound based CAD systems. We then review the studies that used features based on the ultrasound images for thyroid nodule classification and highlight the limitations of such studies. We also discuss and review the techniques used in studies that used the non-clinical features for thyroid nodule classification and report the classification accuracies obtained in these studies. PMID:24206204

  17. Advances in cancer pain from bone metastasis

    PubMed Central

    Zhu, Xiao-Cui; Zhang, Jia-Li; Ge, Chen-Tao; Yu, Yuan-Yang; Wang, Pan; Yuan, Ti-Fei; Fu, Cai-Yun

    2015-01-01

    With the technological advances in cancer diagnosis and treatment, the survival rates for patients with cancer are prolonged. The issue of figuring out how to improve the life quality of patients with cancer has become increasingly prominent. Pain, especially bone pain, is the most common symptom in malignancy patients, which seriously affects the life quality of patients with cancer. The research of cancer pain has a breakthrough due to the development of the animal models of cancer pain in recent years, such as the animal models of mouse femur, humerus, calcaneus, and rat tibia. The establishment of several kinds of animal models related to cancer pain provides a new platform in vivo to investigate the molecular mechanisms of cancer pain. In this review, we focus on the advances of cancer pain from bone metastasis, the mechanisms involved in cancer pain, and the drug treatment of cancer pain in the animal models. PMID:26316696

  18. Thyroid disease

    SciTech Connect

    Falk, S.

    1990-01-01

    Presenting a multidisciplinary approach to the diagnosis and treatment of thyroid disease, this volume provides a comprehensive picture of current thyroid medicine and surgery. The book integrates the perspectives of the many disciplines that deal with the clinical manifestations of thyroid disorders. Adding to the clinical usefulness of the book is the state-of-the-art coverage of many recent developments in thyroidology, including the use of highly sensitive two-site TSH immunoradionetric measurements to diagnose thyroid activity; thyroglobulin assays in thyroid cancer and other diseases; new diagnostic applications of MRI and CT; treatment with radionuclides and chemotherapy; new developments in thyroid immunology, pathology, and management of hyperthyroidism; suppressive treatment with thyroid hormone; and management of Graves' ophthalmopathy. The book also covers all aspects of thyroid surgery, including surgical treatment of hyperthyroidism; papillary, follicular, and other carcinomas; thyroidectomy; and prevention and management of complications.

  19. Characterization of papillary thyroid microcarcinomas using sonographic features in malignant papillary thyroid cancer: a retrospective analysis.

    PubMed

    Gu, Wei-jun; Yan, Hui-xian; Luo, Yu-kun; Wang, Fu-lin; Yang, Guo-qing; Guo, Qing-hua; Jin, Nian; Zang, Li; Chen, Kang; Du, Jin; Wang, Xian-ling; Yang, Li-juan; Ba, Jian-ming; Dou, Jing-tao; Mu, Yi-ming; Pan, Chang-yu; Lv, Zhao-hui

    2015-05-01

    The diagnosis of malignant thyroid nodules is still a clinical challenge. This study aimed to determine the ultrasonographic characteristics of papillary thyroid carcinoma. The ultrasonographic and pathological data of 2453 thyroid nodules in a cohort of 1895 Chinese patients who underwent thyroidectomy from January 2010 to December 2012 were retrospectively reviewed. Anteroposterior and transversal (AP/TR) diameters ≥1, solid structure, infiltrative margins, hypoechoic appearance, and microcalcifications were more common in malignant nodules than in benign nodules (P < 0.01). These ultrasonographic features were independent risk factors of malignancy (P < 0.01) as determined by logistic regression analysis. Based on multivariate analysis, these characteristics were also present in large nodules (diameter >10 mm). However, in small nodules (diameter ≤10 mm), only AP/TR ≥1 and infiltrative margins were independent risk factors of malignancy (P < 0.01). Ultrasonography is of high diagnostic value for malignant thyroid nodules and may help to improve the differential diagnosis. Small and large nodules have distinct ultrasonographic features. PMID:26020388

  20. Thyroid cancer in a long-term nonprogressor HIV-1 infection

    PubMed Central

    Phatak, Uday A.; Chitale, P. V.; Jagdale, Rakhi V.

    2015-01-01

    Long-term non-progressor HIV infection (LTNP-HIV) is seen in <1 percent of HIV-afflicted population. There are definite criteria for the diagnosis of LTNP-HIV. Malignancies either solid tumors or haematological cancers have not been reported in such population. We report here a rare case of follicular thyroid carcinoma in LTNP-HIV infection. She never had any opportunistic infections. She did not receive anti-retroviral therapy in the entire course of illness and continued to have good quality of life. Treatment of follicular thyroid cancer was similar to other patients without HIV infection. This could be the first case study from India. PMID:26692617

  1. Geospatial and Temporal Analysis of Thyroid Cancer Incidence in a Rural Population

    PubMed Central

    Hanley, John P.; Jackson, Erin; Morrissey, Leslie A.; Rizzo, Donna M.; Sprague, Brian L.; Sarkar, Indra Neil

    2015-01-01

    Background: The increasing incidence of thyroid cancer has resulted in the rate tripling over the past 30 years. Reasons for this increase have not been established. Geostatistics and geographic information system (GIS) tools have emerged as powerful geospatial technologies to identify disease clusters, map patterns and trends, and assess the impact of ecological and socioeconomic factors (SES) on the spatial distribution of diseases. In this study, these tools were used to analyze thyroid cancer incidence in a rural population. Methods: Thyroid cancer incidence and socio-demographic factors in Vermont (VT), United States, between 1994 and 2007 were analyzed by logistic regression and geospatial and temporal analyses. Results: The thyroid cancer age-adjusted incidence in Vermont (8.0 per 100,000) was comparable to the national level (8.4 per 100,000), as were the ratio of the incidence of females to males (3.1:1) and the mortality rate (0.5 per 100,000). However, the estimated annual percentage change was higher (8.3 VT; 5.7 U.S.). Incidence among females peaked at 30–59 years of age, reflecting a significant rise from 1994 to 2007, while incidence trends for males did not vary significantly by age. For both females and males, the distribution of tumors by size did not vary over time; ≤1.0 cm, 1.1–2.0 cm, and >2.0 cm represented 38%, 22%, and 40%, respectively. In females, papillary thyroid cancer (PTC) accounted for 89% of cases, follicular (FTC) 8%, medullary (MTC) 2%, and anaplastic (ATC) 0.6%, while in males PTC accounted for 77% of cases, FTC 15%, MTC 1%, and ATC 3%. Geospatial analysis revealed locations and spatial patterns that, when combined with multivariate incidence analyses, indicated that factors other than increased surveillance and access to healthcare (physician density or insurance) contributed to the increased thyroid cancer incidence. Nine thyroid cancer incidence hot spots, areas with very high normalized incidence, were identified

  2. Differentiated thyroid cancer: determinants of disease progression in patients <21 years of age at diagnosis: a report from the Surgical Discipline Committee of the Children's Cancer Group.

    PubMed Central

    Newman, K D; Black, T; Heller, G; Azizkhan, R G; Holcomb, G W; Sklar, C; Vlamis, V; Haase, G M; La Quaglia, M P

    1998-01-01

    OBJECTIVE: This study was done to define the extent of disease and evaluate the effect of staging and treatment variables on progression-free survival in patients with differentiated thyroid carcinoma who were less than 21 years of age at diagnosis. SUMMARY BACKGROUND DATA: Differentiated thyroid cancer in young patients is associated with early regional lymph node involvement and distant parenchymal metastases. Despite this, the overall long-term survival rate is greater than 90%, which suggests that biologic rather than treatment factors have a greater effect on outcome. METHODS: Variables analyzed for their impact on progression-free survival in a multi-institutional cohort of 329 patients included age, antecedent thyroid irradiation, extrathyroidal tumor extension, size, nodal involvement, distant metastases, technique of thyroid surgery and lymphatic dissection, initial treatment with 131Iodine, residual cervical disease, and histopathologic subtype. Surgical complications were correlated with the specific procedures completed on the thyroid gland or cervical lymphatics. RESULTS: The overall progression-free survival rate was 67% (95%, CI: 61%-73%) at 10 years with 2 disease-related deaths. Regional lymph node and distant metastases were present in 74% and 25% of patients, respectively. Progression-free survival was less in younger patients (p = 0.009) and those with residual cervical disease after thyroid surgery (p = 0.001). Permanent hypocalcemia was more frequent after total or subtotal thyroidectomy (p = 0.001) while wound complications increased after radical neck dissections (p < 0.00001). CONCLUSIONS: The progression-free survival rate was better after a complete resection and in older patients. Progression-free survival rate was the same after lobectomy or more extensive thyroid procedures, but comparison was confounded by the increased use of total or subtotal thyroidectomy in patients with advanced disease. The risk of permanent hypocalcemia

  3. Cabozantinib-S-Malate in Treating Patients With Refractory Thyroid Cancer

    ClinicalTrials.gov

    2016-07-04

    Poorly Differentiated Thyroid Gland Carcinoma; Recurrent Thyroid Gland Carcinoma; Stage I Thyroid Gland Follicular Carcinoma; Stage I Thyroid Gland Papillary Carcinoma; Stage II Thyroid Gland Follicular Carcinoma; Stage II Thyroid Gland Papillary Carcinoma; Stage III Thyroid Gland Follicular Carcinoma; Stage III Thyroid Gland Papillary Carcinoma; Stage IVA Thyroid Gland Follicular Carcinoma; Stage IVA Thyroid Gland Papillary Carcinoma; Stage IVB Thyroid Gland Follicular Carcinoma; Stage IVB Thyroid Gland Papillary Carcinoma; Stage IVC Thyroid Gland Follicular Carcinoma; Stage IVC Thyroid Gland Papillary Carcinoma; Tall Cell Variant Thyroid Gland Papillary Carcinoma; Thyroid Gland Oncocytic Follicular Carcinoma

  4. On the cells of origin of radiogenic thyroid cancer: New studies based on an old idea

    SciTech Connect

    Clifton, K.H.; Domann, F.E.; Groch, K.M.

    1990-01-01

    We have presented evidence that the functional thyroid follicles (follicular units, FU) which are formed in grafts of monodispersed rat thyroid cells, and hence the thyroid tumors which later develop in such grafts, are clonal in origin. Recent studies have been designed to investigate: whether cell number-dependent inhibition of promotion-progression is mediated by remote hormonal feed-back, local cell-cell interactions, or both; the cell population kinetics of the clonogen subpopulation during goitrogenesis and goiter involution; and the effect of prolonged exposure to high levels of TSH (thyrotropin) on the capacity of the clonogens to give rise to functional FU. The results indicate that local cell-cell interactions play an important role in the cell number-dependent suppression of neoplastic promotion-progression. They also show that if sufficient thyroid cells are grafted, the thyroid-pituitary axis can be reestablished in thyroidectomized rats fed normal diets. In such animals given iodine deficient diets, the FU that develop in the thyroid grafts shift their secretory pattern to increase the ratio of T3 (triiodothyronine) to T4 (thyroxine), and thus conserve the available iodine. Finally, the clonogenic subpopulation is conserved during both goitrogenesis and goiter involution. When they are transplanted to thyroidectomized recipients, clonogens from two types of goiters form FU that are morphologically indistinguishable from those that develop in grafts of normal thyroid clonogens. Furthermore, the secretion of T3 and T4 by such grafts is dependent on the grafted clonogen number, and hence FU formation, and not on the total number of thyroid cells transplanted. We conclude that the thyroid clonogens, the presumptive cancer progenitor cells, have many of the characteristics of stem cells.

  5. On the cells of origin of radiogenic thyroid cancer: New studies based on an old idea

    SciTech Connect

    Clifton, K.H.; Domann, F.E.; Groch, K.M.

    1990-12-31

    We have presented evidence that the functional thyroid follicles (follicular units, FU) which are formed in grafts of monodispersed rat thyroid cells, and hence the thyroid tumors which later develop in such grafts, are clonal in origin. Recent studies have been designed to investigate: whether cell number-dependent inhibition of promotion-progression is mediated by remote hormonal feed-back, local cell-cell interactions, or both; the cell population kinetics of the clonogen subpopulation during goitrogenesis and goiter involution; and the effect of prolonged exposure to high levels of TSH (thyrotropin) on the capacity of the clonogens to give rise to functional FU. The results indicate that local cell-cell interactions play an important role in the cell number-dependent suppression of neoplastic promotion-progression. They also show that if sufficient thyroid cells are grafted, the thyroid-pituitary axis can be reestablished in thyroidectomized rats fed normal diets. In such animals given iodine deficient diets, the FU that develop in the thyroid grafts shift their secretory pattern to increase the ratio of T3 (triiodothyronine) to T4 (thyroxine), and thus conserve the available iodine. Finally, the clonogenic subpopulation is conserved during both goitrogenesis and goiter involution. When they are transplanted to thyroidectomized recipients, clonogens from two types of goiters form FU that are morphologically indistinguishable from those that develop in grafts of normal thyroid clonogens. Furthermore, the secretion of T3 and T4 by such grafts is dependent on the grafted clonogen number, and hence FU formation, and not on the total number of thyroid cells transplanted. We conclude that the thyroid clonogens, the presumptive cancer progenitor cells, have many of the characteristics of stem cells.

  6. Mitochondrial dynamics protein Drp1 is overexpressed in oncocytic thyroid tumors and regulates cancer cell migration.

    PubMed

    Ferreira-da-Silva, André; Valacca, Cristina; Rios, Elisabete; Pópulo, Helena; Soares, Paula; Sobrinho-Simões, Manuel; Scorrano, Luca; Máximo, Valdemar; Campello, Silvia

    2015-01-01

    Oncocytic cell tumors are characterized by the accumulation of morphologically abnormal mitochondria in their cells, suggesting a role for abnormal mitochondrial biogenesis in oncocytic cell transformation. Little is known about the reason for the dysmorphology of accumulated mitochondria. The proteins regulating the morphology of mitochondria, the "mitochondria-shaping" proteins, can modulate their size and number; however, nothing is known hitherto about a possible involvement of mitochondrial dynamics in oncocytic cell transformation in tumors. Our aim was to assess the status of the mitochondria morphology and its role in oncocytic cell transformation. We therefore evaluated the expression pattern of the main mitochondrial fusion and fission proteins in a series of thyroid cell tumor samples, as well as in thyroid tumor cell lines, with and without oncocytic cell features. The expression of mitochondrial fusion (Opa1, Mfn1 and Mfn2) and fission (Drp1 and Fis1) proteins were evaluated by immunohistochemistry (IHC) in a series of 88 human thyroid tumors. In vitro studies, for comparative purposes and to deepen the study, were performed using TPC1--a papillary thyroid carcinoma derived cell line--and XTC.UC1, an oncocytic follicular thyroid carcinoma-derived cell line. Both IHC and in vitro protein analyses showed an overall increase in the levels of "mitochondrial-shaping" proteins in oncocytic thyroid tumors. Furthermore, overexpression of the pro-fission protein Drp1 was found to be associated with malignant oncocytic thyroid tumors. Interestingly, genetic and pharmacological blockage of Drp1 activity was able to influence thyroid cancer cells' migration/invasion ability, a feature of tumor malignancy. In this study we show that unbalanced mitochondrial dynamics characterize the malignant features of thyroid oncocytic cell tumors, and participate in the acquisition of the migrating phenotype. PMID:25822260

  7. Mitochondrial Dynamics Protein Drp1 Is Overexpressed in Oncocytic Thyroid Tumors and Regulates Cancer Cell Migration

    PubMed Central

    Ferreira-da-Silva, André; Valacca, Cristina; Rios, Elisabete; Pópulo, Helena; Soares, Paula; Sobrinho-Simões, Manuel; Scorrano, Luca; Máximo, Valdemar; Campello, Silvia

    2015-01-01

    Oncocytic cell tumors are characterized by the accumulation of morphologically abnormal mitochondria in their cells, suggesting a role for abnormal mitochondrial biogenesis in oncocytic cell transformation. Little is known about the reason for the dysmorphology of accumulated mitochondria. The proteins regulating the morphology of mitochondria, the "mitochondria-shaping" proteins, can modulate their size and number; however, nothing is known hitherto about a possible involvement of mitochondrial dynamics in oncocytic cell transformation in tumors. Our aim was to assess the status of the mitochondria morphology and its role in oncocytic cell transformation. We therefore evaluated the expression pattern of the main mitochondrial fusion and fission proteins in a series of thyroid cell tumor samples, as well as in thyroid tumor cell lines, with and without oncocytic cell features. The expression of mitochondrial fusion (Opa1, Mfn1 and Mfn2) and fission (Drp1 and Fis1) proteins were evaluated by immunohistochemistry (IHC) in a series of 88 human thyroid tumors. In vitro studies, for comparative purposes and to deepen the study, were performed using TPC1 - a papillary thyroid carcinoma derived cell line—and XTC.UC1, an oncocytic follicular thyroid carcinoma-derived cell line. Both IHC and in vitro protein analyses showed an overall increase in the levels of "mitochondrial-shaping" proteins in oncocytic thyroid tumors. Furthermore, overexpression of the pro-fission protein Drp1 was found to be associated with malignant oncocytic thyroid tumors. Interestingly, genetic and pharmacological blockage of Drp1 activity was able to influence thyroid cancer cells’ migration/invasion ability, a feature of tumor malignancy. In this study we show that unbalanced mitochondrial dynamics characterize the malignant features of thyroid oncocytic cell tumors, and participate in the acquisition of the migrating phenotype. PMID:25822260

  8. Polybrominated Diphenyl Ethers and Thyroid Cancer Risk in the Prostate, Colorectal, Lung, and Ovarian Cancer Screening Trial Cohort

    PubMed Central

    Aschebrook-Kilfoy, Briseis; DellaValle, Curt T.; Purdue, Mark; Kim, Christopher; Zhang, Yawei; Sjodin, Andreas; Ward, Mary H.

    2015-01-01

    Polybrominated diphenyl ethers (PBDEs) alter thyroid hormone homeostasis, but their relationship with thyroid cancer is unknown. To investigate whether serum concentrations of PBDE were associated with thyroid cancer, we conducted a nested, case-control study in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, a large multicenter clinical trial in the United States. Cases with thyroid cancer (n = 104) were recruited from 1992 to 2001 and diagnosed through 2009, and controls (n = 208) were individually matched (2:1) to cases by race, sex, birth date (within 1 year), center, and blood collection date (within 15 days). We used gas chromatography isotope dilution high-resolution mass spectrometry to measure 10 tri- to heptabrominated diphenyl eithers in serum samples. Odds ratios and 95% confidence intervals were calculated using conditional logistic regression for lipid-adjusted PBDE levels detected in more than 50% of controls and for the sum of these BDEs (∑PBDEs). We observed no significant differences between cases and controls in lipid-adjusted concentrations of ∑PBDEs (for cases, median = 12.8 ng/g lipid (interquartile range, 6.2–42.1); for controls, median = 19.4 ng/g lipid (interquartile range, 7.6–50.2)) or for individual congeners. Increasing quartiles of ∑PBDEs and 4 BDE congeners were not associated with risk of thyroid cancer (for the fourth vs. first quartile of ∑PBDEs, adjusted odd ratio = 0.62, 95% confidence interval: 0.29, 1.30; P for trend = 0.56). Our study does not support an association between exposure to PBDEs and thyroid cancer. PMID:25939348

  9. Polybrominated diphenyl ethers and thyroid cancer risk in the Prostate, Colorectal, Lung, and Ovarian Cancer Screening Trial cohort.

    PubMed

    Aschebrook-Kilfoy, Briseis; DellaValle, Curt T; Purdue, Mark; Kim, Christopher; Zhang, Yawei; Sjodin, Andreas; Ward, Mary H

    2015-06-01

    Polybrominated diphenyl ethers (PBDEs) alter thyroid hormone homeostasis, but their relationship with thyroid cancer is unknown. To investigate whether serum concentrations of PBDE were associated with thyroid cancer, we conducted a nested, case-control study in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, a large multicenter clinical trial in the United States. Cases with thyroid cancer (n = 104) were recruited from 1992 to 2001 and diagnosed through 2009, and controls (n = 208) were individually matched (2:1) to cases by race, sex, birth date (within 1 year), center, and blood collection date (within 15 days). We used gas chromatography isotope dilution high-resolution mass spectrometry to measure 10 tri- to heptabrominated diphenyl eithers in serum samples. Odds ratios and 95% confidence intervals were calculated using conditional logistic regression for lipid-adjusted PBDE levels detected in more than 50% of controls and for the sum of these BDEs (∑PBDEs). We observed no significant differences between cases and controls in lipid-adjusted concentrations of ∑PBDEs (for cases, median = 12.8 ng/g lipid (interquartile range, 6.2-42.1); for controls, median = 19.4 ng/g lipid (interquartile range, 7.6-50.2)) or for individual congeners. Increasing quartiles of ∑PBDEs and 4 BDE congeners were not associated with risk of thyroid cancer (for the fourth vs. first quartile of ∑PBDEs, adjusted odd ratio = 0.62, 95% confidence interval: 0.29, 1.30; P for trend = 0.56). Our study does not support an association between exposure to PBDEs and thyroid cancer. PMID:25939348

  10. Autotaxin is an inflammatory mediator and therapeutic target in thyroid cancer.

    PubMed

    Benesch, Matthew G K; Ko, Yi M; Tang, Xiaoyun; Dewald, Jay; Lopez-Campistrous, Ana; Zhao, Yuan Y; Lai, Raymond; Curtis, Jonathan M; Brindley, David N; McMullen, Todd P W

    2015-08-01

    Autotaxin is a secreted enzyme that converts extracellular lysophosphatidylcholine to lysophosphatidate (LPA). In cancers, LPA increases tumour growth, metastasis and chemoresistance by activating six G-protein coupled receptors. We examined >200 human thyroid biopsies. Autotaxin expression in metastatic deposits and primary carcinomas was four- to tenfold higher than in benign neoplasms or normal thyroid tissue. Autotaxin immunohistochemical staining was also increased in benign neoplasms with leukocytic infiltrations. Malignant tumours were distinguished from benign tumours by high tumour autotaxin, LPA levels and inflammatory mediators including IL1β, IL6, IL8, GMCSF, TNFα, CCL2, CXCL10 and platelet-derived growth factor (PDGF)-AA. We determined the mechanistic explanation for these results and revealed a vicious regulatory cycle in which LPA increased the secretion of 16 inflammatory modulators in papillary thyroid cancer cultures. Conversely, treating cancer cells with ten inflammatory cytokines and chemokines or PDGF-AA and PDGF-BB increased autotaxin secretion. We confirmed that this autotaxin/inflammatory cycle occurs in two SCID mouse models of papillary thyroid cancer by blocking LPA signalling using the autotaxin inhibitor ONO-8430506. This decreased the levels of 16 inflammatory mediators in the tumours and was accompanied by a 50-60% decrease in tumour volume. This resulted from a decreased mitotic index for the cancer cells and decreased levels of vascular endothelial growth factor and angiogenesis in the tumours. Our results demonstrate that the autotaxin/inflammatory cycle is a focal point for driving malignant thyroid tumour progression and possibly treatment resistance. Inhibiting autotaxin activity provides an effective and novel strategy for decreasing the inflammatory phenotype in thyroid carcinomas, which should complement other treatment modalities. PMID:26037280

  11. Solitary thyroid metastasis from colon cancer: fine-needle aspiration cytology and molecular biology approach.

    PubMed

    Onorati, M; Uboldi, P; Bianchi, C L; Nicola, M; Corradini, G M; Veronese, S; Fascì, A I; Di Nuovo, F

    2015-01-01

    Thyroid gland is one of the most vascularized organs of the body, nevertheless clinical and surgical series report an incidence of secondary malignancies in this gland of only 3%. Colorectal carcinoma metastatic to the thyroid gland is not as uncommon as previously believed, infact the number of cases seems to be increased in recent years due to the more frequent use of fine-needle aspiration cytology (FNAC) guided by ultrasonography. Although kidney, breast and lung metastases to the thyroid are frequent, metastasis from colon cancer is clinically rare with 52 cases reported in the literature in the last 5 decades and three cases described as solitary thyroid metastasis from the colon cancer without any other visceral metastases. To the best of our knowledge, we report the fourth case of solitary, asymptomatic thyroid metastasis from colon cancer without involvement of other organs. We discuss the importance of FNAC to detect metastatazing process as a compulsory step of the diagnostic and therapeutic management algorithm, combined with a molecular biology approach. A review of the last 5 decades literature, to update the number of cases described to date, is also included. PMID:26946875

  12. Thyroid Cancer Imaging In Vivo by Targeting the Anti-Apoptotic Molecule Galectin-3

    PubMed Central

    Bartolazzi, Armando; Del Prete, Fabrizio; Lavra, Luca; Braesch-Andersen, Sten; Massari, Roberto; Trotta, Carlo; Soluri, Alessandro; Sciacchitano, Salvatore; Scopinaro, Francesco

    2008-01-01

    Background The prevalence of thyroid nodules increases with age, average 4–7% for the U.S.A. adult population, but it is much higher (19–67%) when sub-clinical nodules are considered. About 90% of these lesions are benign and a reliable approach to their preoperative characterization is necessary. Unfortunately conventional thyroid scintigraphy does not allow the distinction among benign and malignant thyroid proliferations but it provides only functional information (cold or hot nodules). The expression of the anti-apoptotic molecule galectin-3 is restricted to cancer cells and this feature has potential diagnostic and therapeutic implications. We show here the possibility to obtain thyroid cancer imaging in vivo by targeting galectin-3. Methods The galectin-3 based thyroid immuno-scintigraphy uses as radiotracer a specific 99mTc-radiolabeled mAb. A position-sensitive high-resolution mini-gamma camera was used as imaging capture device. Human galectin-3 positive thyroid cancer xenografts (ARO) and galectin-3 knockout tumors were used as targets in different experiments in vivo. 38 mice with tumor mass of about 1 gm were injected in the tail vein with 100 µCi of 99mTc-labeled mAb to galectin-3 (30 µg protein/in 100 µl saline solution). Tumor images were acquired at 1 hr, 3 hrs, 6 hrs, 9 hrs and 24 hrs post injection by using the mini-gamma camera. Findings Results from different consecutive experiments show an optimal visualization of thyroid cancer xenografts between 6 and 9 hours from injection of the radiotracer. Galectin-3 negative tumors were not detected at all. At 6 hrs post-injection galectin-3 expressing tumors were correctly visualized, while the whole-body activity had essentially cleared. Conclusions These results demonstrate the possibility to distinguish preoperatively benign from malignant thyroid nodules by using a specific galectin-3 radio-immunotargeting. In vivo imaging of thyroid cancer may allow a better selection of patients referred to

  13. An Occupational Study in Nurses: Prevalence of Thyroid Nodules and Cancer in Comparison to Health Check-up Female

    PubMed Central

    Kim, Kyung Hee; Woo, Seung Hoon

    2016-01-01

    Objectives. It is known that a great extent of radiation is emitted from the medical instruments used in hospitals and that radiation exposure can cause thyroid cancer. However, the correlation between occupational radiation exposure in hospitals and thyroid disease is not extensively recognized. Methods. The subjects of the study were female nurses, who worked at a single hospital and female, who had undergone a health examination at the same hospital during the same period. The 1,024 nurses and 2,631 healthy women were enrolled for the present study. All the participants were screened using thyroid ultrasonography, and fine-needle aspiration & cytology was performed on potentially malignant nodules. Results. Thyroid nodules were present in 315 nurses (30.8%) and 1,023 health check-up female (38.9%). Typically, 107 nurses (10.4%) and 201 health check-up female (7.6%) had suspicious nodule and were further tested with ultrasonography guided fine-needle aspiration & cytology. The 16 nurses (1.6%) and 38 health check-up female (1.4%) were diagnosed with thyroid cancer. The prevalence of thyroid nodules was enhanced in both the groups and a significant increase was noted in health check-up female group (P<0.05); however, no difference was seen in the incidence of thyroid cancer in both the groups (P>0.05). Conclusion. In our study, working in a hospital does not increase the prevalence of thyroid nodules or thyroid cancer. PMID:27334518

  14. Anthropometric Risk Factors for Differentiated Thyroid Cancer in Young Men and Women From Eastern France: A Case-Control Study.

    PubMed

    Xhaard, Constance; de Vathaire, Florent; Cléro, Enora; Maillard, Stéphane; Ren, Yan; Borson-Chazot, Françoise; Sassolas, Geneviève; Schvartz, Claire; Colonna, Marc; Lacour, Brigitte; Danzon, Arlette; Velten, Michel; Marrer, Emilie; Bailly, Laurent; Barjoan, Eugènia Mariné; Schlumberger, Martin; Orgiazzi, Jacques; Adjadj, Elisabeth; Rubino, Carole

    2015-08-01

    The incidence of thyroid cancer has risen over the past decade, along with a rise in obesity. We studied the role of anthropometric risk factors for differentiated thyroid cancer at the time of diagnosis and at age 20 years in a case-control study conducted in eastern France between 2005 and 2010. The study included 761 adults diagnosed with differentiated thyroid cancer before 35 years of age between 2002 and 2006. They were matched with 825 controls from the general population. Odds ratios were calculated using conditional logistic regression models and were reported for all participants, those with papillary cancer only, and women only. The risk of thyroid cancer was higher for participants with a high body surface area (BSA), great height, or excess weight and for women with a high body fat percentage. Conversely, no significant association was found between body mass index and the risk of thyroid cancer. In the present study, we provide further evidence of the role of BSA and excess weight in the risk of thyroid cancer. These epidemiologic observations should be confirmed by further exploration of the biological mechanisms responsible for the associations of obesity and BSA with thyroid cancer. PMID:26133374

  15. [Innovation in Surgery for Advanced Lung Cancer].

    PubMed

    Nakano, Tomoyuki; Yasunori, Sohara; Endo, Shunsuke

    2016-07-01

    Thoracoscopic surgery can be one of less invasive surgical interventions for early stage lung cancer. Locally advanced lung cancer, however, cannot avoid aggressive procedures including pneumonectomy and/or extended combined resection of chest wall, aorta, esophagus, etc. for complete resection. Surgical approach even for advanced lung cancer can be less invasive by benefit from new anti-cancer treatment, innovated manipulations of bronchoplasty and angioplasty, and bench surgery( lung autotransplantation technique). We herein reviewed the strategy to minimize invasive interventions for locally advanced lung cancer, introducing 2 successful cases with advanced lung cancer. The 1st patient is a 62-year old man with centrally advanced lung cancer invading to mediastinum. Right upper sleeve lobectomy with one-stoma carinoplasty following induction chemoradiation therapy was successful. The operation time was 241 minutes. The performance status is good with no recurrence for 60 months after surgery. The 2nd is a 79-year old man with advanced lung cancer invading to the distal aortic arch. Left upper segmentectomy following thoracic endovascular aortic repair with stentgraft was successful with no extracorporeal circulation. The operation time was 170 minutes. The performance status is good with no recurrence for 30 months after surgery. The invasiveness of surgical interventions for local advanced lung cancer can be minimized by innovated device and new anti-cancer drugs. PMID:27440037

  16. Robotic versus Open Thyroidectomy for Differentiated Thyroid Cancer: An Evidence-Based Review

    PubMed Central

    Liu, Shirley Yuk Wah; Ng, Enders Kwok Wai

    2016-01-01

    While open thyroidectomy (OT) is advocated as the gold standard treatment for differentiated thyroid cancer, the contemporary use of robotic thyroidectomy (RT) is often controversial. Although RT combines the unique benefits of the surgical robot and remote access thyroidectomy, its applicability on cancer patients is challenged by the questionable oncological benefits and safety. This review aims to analyze the current literature evidence in comparing RT to OT on thyroid cancers for their perioperative and oncological outcomes. To date, no randomized controlled trial is available in comparing RT to OT. All published studies are nonrandomized or retrospective comparisons. Current data suggests that RT compares less favorably than OT for longer operative time, higher cost, and possibly inferior oncological control with lower number of central lymph nodes retrieved. In terms of morbidity, quality of life outcomes, and short-term recurrence rates, RT and OT are comparable. While conventional OT continues to be appropriate for most thyroid cancers, RT should better be continued by expert surgeons on selected patients who have low-risk thyroid cancers and have high expectations on cosmetic outcomes. Future research should embark on prospective randomized studies for unbiased comparisons. Long-term follow-up studies are also needed to evaluate outcomes on recurrence and survival. PMID:27069476

  17. Quercetin-Induced Cell Death in Human Papillary Thyroid Cancer (B-CPAP) Cells

    PubMed Central

    Mutlu Altundağ, Ergül; Kasacı, Tolga; Yılmaz, Ayşe Mine; Karademir, Betül; Koçtürk, Semra; Taga, Yavuz; Yalçın, A. Süha

    2016-01-01

    In this study, we have investigated the antiproliferative effect of quercetin on human papillary thyroid cancer cells and determined the apoptotic mechanisms underlying its actions. We have used different concentrations of quercetin to induce apoptosis and measured cell viability. Apoptosis and cell cycle analysis was determined by flow cytometry using Annexin V and propidium iodide. Finally, we have measured changes in caspase-3 and cleaved poly(ADP-ribose) polymerase (PARP) protein expression levels as hallmarks of apoptosis and Hsp90 protein expression level as a marker of proteasome activity in treated and control cells. Quercetin treatment of human papillary thyroid cancer cells resulted in decreased cell proliferation and increased rate of apoptosis by caspase activation. Furthermore, it was demonstrated that quercetin induces cancer cell apoptosis by downregulating the levels of Hsp90. In conclusion, we have shown that quercetin induces downregulation of Hsp90 expression that may be involved in the decrease of chymotrypsin-like proteasome activity which, in order, induces inhibition of growth and causes cell death in thyroid cancer cells. Thus, quercetin appears to be a promising candidate drug for Hsp90 downregulation and apoptosis of thyroid cancer cells. PMID:27057371

  18. Trametinib with and without pazopanib has potent preclinical activity in thyroid cancer.

    PubMed

    Ball, Douglas W; Jin, Ning; Xue, Ping; Bhan, Sheetal; Ahmed, Shabina R; Rosen, D Marc; Schayowitz, Adam; Clark, Douglas P; Nelkin, Barry D

    2015-11-01

    Multikinase inhibitors (MKIs) targeting VEGF receptors and other receptor tyrosine kinases have shown considerable activity in clinical trials of thyroid cancer. Thyroid cancer frequently exhibits activation of the RAS/RAF/MEK/ERK pathway. In other types of cancer, paradoxical ERK activation has emerged as a potential resistance mechanism to RAF-inhibiting drugs including MKIs such as sorafenib and pazopanib. We therefore queried whether the MEK inhibitor trametinib, could augment the activity of pazopanib in thyroid cancer cell lines. Trametinib potently inhibited growth in vitro (GI50 1.1-4.8 nM), whereas pazopanib had more limited in vitro activity, as anticipated (GI50 1.4-7.1 µM). We observed progressive upregulation of ERK activity with pazopanib treatment, an effect abrogated by trametinib. For xenografts (bearing either KRASG12R or BRAFV600E mutations), the combination of trametinib and pazopanib led to sustained shrinkage in tumor volume by 50% or more, compared to pre-treatment baseline. Trametinib also was highly effective as a single agent, compared to pazopanib alone. These preclinical findings support the evaluation of trametinib, alone or in combination with pazopanib or other kinase inhibitors, in thyroid cancer clinical trials. We highlight the importance of pharmacodynamic assessment of the ERK pathway for patients enrolled in trials involving MKIs. PMID:26324075

  19. Trametinib with and without pazopanib has potent preclinical activity in thyroid cancer

    PubMed Central

    BALL, DOUGLAS W.; JIN, NING; XUE, PING; BHAN, SHEETAL; AHMED, SHABINA R.; ROSEN, D. MARC; SCHAYOWITZ, ADAM; CLARK, DOUGLAS P.; NELKIN, BARRY D.

    2015-01-01

    Multikinase inhibitors (MKIs) targeting VEGF receptors and other receptor tyrosine kinases have shown considerable activity in clinical trials of thyroid cancer. Thyroid cancer frequently exhibits activation of the RAS/RAF/MEK/ERK pathway. In other types of cancer, paradoxical ERK activation has emerged as a potential resistance mechanism to RAF-inhibiting drugs including MKIs such as sorafenib and pazopanib. We therefore queried whether the MEK inhibitor trametinib, could augment the activity of pazopanib in thyroid cancer cell lines. Trametinib potently inhibited growth in vitro (GI50 1.1–4.8 nM), whereas pazopanib had more limited in vitro activity, as anticipated (GI50 1.4–7.1 µM). We observed progressive upregulation of ERK activity with pazopanib treatment, an effect abrogated by trametinib. For xenografts (bearing either KRASG12R or BRAFV600E mutations), the combination of trametinib and pazopanib led to sustained shrinkage in tumor volume by 50% or more, compared to pre-treatment baseline. Trametinib also was highly effective as a single agent, compared to pazopanib alone. These preclinical findings support the evaluation of trametinib, alone or in combination with pazopanib or other kinase inhibitors, in thyroid cancer clinical trials. We highlight the importance of pharmacodynamic assessment of the ERK pathway for patients enrolled in trials involving MKIs. PMID:26324075

  20. Three-Gene Molecular Diagnostic Model for Thyroid Cancer

    PubMed Central

    Kowalski, Jeanne; Tsai, Hua-Ling; Talbot, Kristin; Somervell, Helina; Kouniavsky, Guennadi; Wang, Yongchun; Dackiw, Alan P.B.; Westra, William H.; Clark, Douglas P.; Libutti, Steven K.; Umbricht, Christopher B.

    2012-01-01

    Background The preoperative diagnosis of thyroid nodules primarily depends upon fine needle aspiration (FNA) cytology. However, up to 25% of FNA samples have associated “suspicious or indeterminate”, but not diagnostic cytologic reports, resulting in difficulty deciding appropriate clinical management for these patients. We hypothesize that the use of molecular markers as an adjunct to FNA cytology can improve the distinction of benign from malignant nodules that have associated suspicious or indeterminate cytology. Methods Using microarray analysis, we previously identified and reported on 75 genes useful in the distinction of benign versus malignant thyroid nodules. In the present study, we have further validated the expression of 14 of these markers in a large number of thyroid samples by immunohistochemistry (IHC) analysis of 154 thyroid tumors and quantitative real-time RT-PCR (QRT-PCR) analysis of 95 FNA samples. Of the 154 tumors analyzed by IHC, 44 samples (29%) had associated suspicious or indeterminate FNA cytology. Results Receiver operating characteristic using three-gene model, (HMGA2, MRC2, and SFN) analysis for the detection of malignant nodules resulted in areas under the curve (AUCs) of≥0.95 (80% sensitivity; 100% specificity) and≥0.84 (71% sensitivity; 84% specificity) for the IHC data in tumors, and QRT-PCR data in FNA samples, respectively. Conclusions Our results suggest that a three-gene model for the cytological diagnosis of indeterminate thyroid nodules is both feasible and promising. Implementation of this as an adjunct to thyroid cytology may significantly impact the clinical management of patients with suspicious or indeterminate thyroid FNA nodules. PMID:22280184

  1. Blood preoperative neutrophil-to-lymphocyte ratio is correlated with TNM stage in patients with papillary thyroid cancer

    PubMed Central

    Gong, Wenjie; Yang, Shenjiu; Yang, Xiumin; Guo, Fang

    2016-01-01

    OBJECTIVE: To predict the American Joint Cancer Committee tumor-node-metastasis stage in patients with papillary thyroid carcinoma by evaluating the relationship between the preoperative neutrophil-to-lymphocyte ratio and the tumor-node-metastasis stage. METHODS: We retrospectively examined 161 patients with a diagnosis of papillary thyroid carcinoma. The Neutrophil-to-Lymphocyte Ratio was calculated according to the absolute neutrophil counts and absolute lymphocyte counts on routine blood tests obtained prior to surgery and patients with a Neutrophil-to-Lymphocyte Ratio of 2.0 or more were classified as the high NLR group, while those with a Neutrophil-to-Lymphocyte Ratio less than 2.0 were classified as the low Neutrophil-to-Lymphocyte Ratio group. Clinicopathological variables, which were stratified by the Neutrophil-to-Lymphocyte Ratio, were analyzed. A multivariate analysis was performed to determine factors that affect the Neutrophil-to-Lymphocyte Ratio. The association between the Neutrophil-to-Lymphocyte Ratio and the TNM stage in patients ≥45 years of age was analyzed using the Spearman rank correlation. RESULTS: Various blood indices, including hemoglobin, platelet and thyroid-stimulating hormone levels in the two groups showed no significant differences. Lymph node metastasis, multifocality and tumor size exhibited significant differences in the two groups (p=0.000, p=0.000 and p=0.035, respectively). Correlation analysis indicated that a higher preoperative Neutrophil-to-Lymphocyte Ratio was observed in patients with lymph node metastasis, larger tumor size and multifocality (r=0.341, p=0.000; r=0.271, p=0.000; and r=0.182, p=0.010, respectively). For patients ≥45 years of age, the number of patients with an advanced TNM stage in the high NLR group was higher than that in the low Neutrophil-to-Lymphocyte Ratio group (p=0.013). A linear regression analysis showed that the preoperative Neutrophil-to-Lymphocyte Ratio was positively correlated with the

  2. Thyroid cancer epidemiology in England and Wales: time trends and geographical distribution.

    PubMed Central

    dos Santos Silva, I.; Swerdlow, A. J.

    1993-01-01

    Thyroid cancer incidence has been increasing in many countries, whereas mortality has been falling due to better survival. Radiation is the best-established risk factor and there has been concern that recent rises in incidence might be related to fallout radiation from atmospheric nuclear weapon tests. We examined thyroid cancer time trends and geographical distribution in England and Wales and possible interpretations of these. During 1962-84, there were significant increases in incidence (P < 0.001) in each sex at ages under 45. Cohort analysis by single year of birth showed an overall increase in incidence risks in women aged 0-44 born since 1920, with a sudden rise in risk for the birth years 1952-55 followed by a lower risk for the more recent cohorts. In men, there was an overall increase in risk at ages 0-44 in successive birth cohorts, but the pattern was irregular. In each sex, the risk in persons aged 45 and over decreased slightly in successive generations. Geographically, highest incidence risks were in countries in North and Mid Wales, in which the risk was almost twice that in the rest of the country. This pattern was present only at ages 45 and over and was most clear in rural areas. The peak of thyroid cancer risk in women born in 1952-55 is consistent with a carcinogenic effect of fallout radiation, since these women were children in the late 1950s and early 1960s when fallout radiation was greatest in England and Wales. The focus of high thyroid cancer risks in Wales was in areas with high levels of fallout radiation. However, thyroid cancer risks in Wales were not high for more recent cohorts (the ones who were exposed to fallout early in life), and a focus on high risk of benign thyroid diseases was present in Wales well before nuclear weapons existed. The distributions of these benign thyroid diseases, or of factors causing them, seem more likely than fallout to explain the high risk areas for thyroid cancer in the country. PMID:8431362

  3. Thyroid cancer epidemiology in England and Wales: time trends and geographical distribution.

    PubMed

    dos Santos Silva, I; Swerdlow, A J

    1993-02-01

    Thyroid cancer incidence has been increasing in many countries, whereas mortality has been falling due to better survival. Radiation is the best-established risk factor and there has been concern that recent rises in incidence might be related to fallout radiation from atmospheric nuclear weapon tests. We examined thyroid cancer time trends and geographical distribution in England and Wales and possible interpretations of these. During 1962-84, there were significant increases in incidence (P < 0.001) in each sex at ages under 45. Cohort analysis by single year of birth showed an overall increase in incidence risks in women aged 0-44 born since 1920, with a sudden rise in risk for the birth years 1952-55 followed by a lower risk for the more recent cohorts. In men, there was an overall increase in risk at ages 0-44 in successive birth cohorts, but the pattern was irregular. In each sex, the risk in persons aged 45 and over decreased slightly in successive generations. Geographically, highest incidence risks were in countries in North and Mid Wales, in which the risk was almost twice that in the rest of the country. This pattern was present only at ages 45 and over and was most clear in rural areas. The peak of thyroid cancer risk in women born in 1952-55 is consistent with a carcinogenic effect of fallout radiation, since these women were children in the late 1950s and early 1960s when fallout radiation was greatest in England and Wales. The focus of high thyroid cancer risks in Wales was in areas with high levels of fallout radiation. However, thyroid cancer risks in Wales were not high for more recent cohorts (the ones who were exposed to fallout early in life), and a focus on high risk of benign thyroid diseases was present in Wales well before nuclear weapons existed. The distributions of these benign thyroid diseases, or of factors causing them, seem more likely than fallout to explain the high risk areas for thyroid cancer in the country. PMID:8431362

  4. Feeding Artery of Laryngeal and Hypopharyngeal Cancers: Role of the Superior Thyroid Artery in Superselective Intraarterial Chemotherapy

    SciTech Connect

    Terayama, Noboru Sanada, Junichiro; Matsui, Osamu; Kobayashi, Satoshi; Kawashima, Hiroko; Yamashiro, Masashi; Takanaka, Tsuyoshi; Kumano, Tomoyasu; Yoshizaki, Tomokazu; Furukawa, Mitsuru

    2006-08-15

    The purpose of this study was to elucidate the role of the superior thyroid artery in intra-arterial infusion chemotherapy for laryngeal and hypopharyngeal cancers. Thirty-nine patients with laryngeal cancer and 29 patients with hypopharyngeal cancer underwent intra-arterial infusion chemotherapy. We performed a retrospective analysis of the feeding arteries confirmed by computed tomography during selective arteriography and compared the results with the extent of the tumors. In 14 of 39 laryngeal and 15 of 29 hypopharyngeal cancers, the tumor did not cross the midline (group 1). In the remaining 25 and 14 cancers, respectively, the tumor crossed the midline or located in the center (group 2). For 13 of 14 laryngeal and 7 of 15 hypopharyngeal cancers in group 1 and for 6 of 25 laryngeal cancers in group 2, the entire tumor was contrast enhanced by the ipsilateral superior thyroid and/or superior laryngeal artery. For 12 of 25 laryngeal and 1 of 14 hypopharyngeal cancers in group 2, the entire tumor was contrast enhanced by the bilateral superior thyroid artery. For the other patients, infusion via the other arterial branches such as the inferior thyroid and the lingual arteries were needed to achieve contrast enhancement of the entire tumor. Superselective intra-arterial chemotherapy for laryngeal cancer from the superior thyroid artery is appropriate, whereas that for hypopharyngeal cancer is less sufficient. To accomplish contrast enhancement of the entire tumor, additional intra-arterial infusion from other arteries such as the inferior thyroid artery is often necessary.

  5. SP600125 has a remarkable anticancer potential against undifferentiated thyroid cancer through selective action on ROCK and p53 pathways

    PubMed Central

    Grassi, Elisa Stellaria; Vezzoli, Valeria; Negri, Irene; Lábadi, Árpád; Fugazzola, Laura; Vitale, Giovanni; Persani, Luca

    2015-01-01

    Thyroid cancer is the most common endocrine malignancy with increasing incidence worldwide. The majority of thyroid cancer cases are well differentiated with favorable outcome. However, undifferentiated thyroid cancers are one of the most lethal human malignancies because of their invasiveness, metastatization and refractoriness even to the most recently developed therapies. In this study we show for the first time a significant hyperactivation of ROCK/HDAC6 pathway in thyroid cancer tissues, and its negative correlation with p53 DNA binding ability. We demonstrate that a small compound, SP600125 (SP), is able to induce cell death selectively in undifferentiated thyroid cancer cell lines by specifically acting on the pathogenic pathways of cancer development. In detail, SP acts on the ROCK/HDAC6 pathway involved in dedifferentiation and invasiveness of undifferentiated human cancers, by restoring its physiological activity level. As main consequence, cancer cell migration is inhibited and, at the same time, cell death is induced through the mitotic catastrophe. Moreover, SP exerts a preferential action on the mutant p53 by increasing its DNA binding ability. In TP53-mutant cells that survive mitotic catastrophe this process results in p21 induction and eventually lead to premature senescence. In conclusion, SP has been proved to be able to simultaneously block cell replication and migration, the two main processes involved in cancer development and dissemination, making it an ideal candidate for developing new drugs against anaplastic thyroid cancer. PMID:26415230

  6. A Novel Orthotopic Mouse Model of Human Anaplastic Thyroid Carcinoma

    PubMed Central

    Nucera, Carmelo; Nehs, Matthew A.; Mekel, Michal; Zhang, Xuefeng; Hodin, Richard; Lawler, Jack; Nose, Vânia

    2009-01-01

    Background Orthotopic mouse models of human cancer represent an important in vivo tool for drug testing and validation. Most of the human thyroid carcinoma cell lines used in orthotopic or subcutaneous models are likely of melanoma and colon cancer. Here, we report and characterize a novel orthotopic model of human thyroid carcinoma using a unique thyroid cancer cell line. Methods We used the cell line 8505c, originated from a thyroid tumor histologically characterized by anaplastic carcinoma cell features. We injected 8505c cells engineered using a green fluorescent protein–positive lentiviral vector orthotopically into the thyroid of severe combined immunodeficient mice. Results Orthotopic implantation with the 8505c cells produced thyroid tumors after 5 weeks, showing large neck masses, with histopathologic features of a high-grade neoplasm (anaplasia, necrosis, high mitotic and proliferative indexes, p53 positivity, extrathyroidal invasion, lymph node and distant metastases) and immunoprofile of follicular thyroid cell origin with positivity for thyroid transcription factor-1 and PAX8, and for cytokeratins. Conclusions Here we describe a novel orthotopic thyroid carcinoma model using 8505c cells. This model can prove to be a reliable and useful tool to investigate in vivo biological mechanisms determining thyroid cancer aggressiveness, and to test novel therapeutics for the treatment of refractory or advanced thyroid cancers. PMID:19772429

  7. Cancer

    MedlinePlus

    ... Leukemia Liver cancer Non-Hodgkin lymphoma Ovarian cancer Pancreatic cancer Testicular cancer Thyroid cancer Uterine cancer ... have any symptoms. In certain cancers, such as pancreatic cancer, symptoms often do not start until the disease ...

  8. Electric blanket (EB) use and risk of thyroid cancer in the Women’s Health Initiative (WHI) observational cohort

    PubMed Central

    Kato, Ikuko; Young, Alicia; Liu, Jingmin; Abrams, Judith; Bock, Cathryn; Simon, Michael

    2016-01-01

    Thyroid cancer disproportionally affects more women than men. The aim of this study was to assess whether exposure to extremely low frequency electric magnetic fields from electric blankets (EB) was associated with development of thyroid cancer. We analyzed data from 89,527 women who participated in the Women’s Health Initiative Observational Study and who responded to questions concerning prior use of EB. During a mean follow-up of 12.2 years, we identified 190 incident cases of thyroid cancer. We estimated the hazard ratio (HR) and 95% confidence interval (CI) of incident thyroid cancer associated with EB use by Cox’s proportional hazard model, adjusted for selected covariates. A majority, 57%, of the women in the cohort reported ever use of EB while sleeping and/or for warming the bed before sleep. We found no association between ever use of EB and subsequent risk of thyroid cancer (HR= 0.98, 95% CI: 0.72–1.32). Duration of EB use measured in years, months or hours had no effect on risk. These results did not change when the cases were limited to papillary thyroid cancer, the most frequently occurring histologic type. The results of this study do not support possible health hazards of EB in regards to thyroid cancer risk. PMID:25996298

  9. Risk Factors for Recurrence in Filipinos with Well-Differentiated Thyroid Cancer

    PubMed Central

    Canto, Abigail Uy; Maningat, Patricia Deanna D.

    2015-01-01

    Background The incidence of well-differentiated thyroid cancer (WDTC) has increased in recent years. Despite its excellent prognosis, increasing morbidity from recurrent diseases continues to affect long-term outcomes. Among at-risk populations, Filipinos have the highest incidence of thyroid cancer worldwide, characterized by a highly aggressive and recurrent form of disease. Here, we sought to identify risk factors associated with disease recurrence among Filipinos with WDTC. Methods This retrospective cohort study examined 723 patients diagnosed with WDTC seen at Philippine General Hospital. Affected individuals were classified based on the presence or absence of disease recurrence. Multivariate logistic regression analyses were used to determine significant predictors of recurrence. Results Multiple risk factors, including age >45 years (odds ratio [OR], 1.44), multifocality of cancer (OR, 1.43), nodal involvement (OR, 4.0), and distant metastases at presentation (OR, 2.78), were significantly associated with a recurrence of papillary thyroid cancer (PTC). In contrast, follicular variant histology (OR, 0.60) and postsurgical radioactive iodine therapy (OR, 0.31) were protective for PTC recurrence. Distant metastases at presentation (OR, 19.4) and postsurgical radioactive iodine therapy (OR, 0.41) were associated with follicular thyroid cancer (FTC) recurrence. Conclusion Lymph node metastases at presentation was the strongest predictor of recurrence in PTC, whereas distant metastases at presentation was the strongest for FTC recurrence. Among Filipinos, stratification of WDTC patients based on recurrence risk factors identified in this study will be helpful in guiding the intensity of treatment strategies and long-term thyroid cancer surveillance. PMID:26485470

  10. 8q24 rs6983267G variant is associated with increased thyroid cancer risk

    PubMed Central

    Sahasrabudhe, Ruta; Estrada, Ana; Lott, Paul; Martin, Lynn; Echeverry, Guadalupe Polanco; Velez, Alejandro; Neta, Gila; Takahasi, Meiko; Saenko, Vladimir; Mitsutake, Norisato; Jaeguer, Emma; Duque, Carlos Simon; Rios, Alejandro; Bohorquez, Mabel; Prieto, Rodrigo; Criollo, Angel; Echeverry, Magdalena; Tomlinson, Ian; Carvajal Carmona, Luis G.

    2015-01-01

    The G allele of the rs6983267 single nucleotide polymorphism, located on chromosome 8q24, has been associated with increased risk of several cancer types. The association between rs6983267G and thyroid cancer has been tested in different populations, mostly of European ancestry, and has led to inconclusive results. While significant associations have been reported in the British and Polish populations, no association has been detected in populations from Spain, Italy and the USA. To further investigate the role of rs6983267G in thyroid cancer susceptibility, we evaluated rs6983267 genotypes in three populations of different continental ancestry (British Isles, Colombia and Japan), providing a total of 3,067 cases and 8,575 controls. We detected significant associations between rs6983267G and thyroid cancer in the British Isles (Odds Ratio, OR= 1.19, 95% confidence interval, CI: 1.11–1.27, P= 4.03 × 10−7), Japan (OR= 1.20, 95% CI: 1.03–1.41, P= 0.022) and a borderline significant association of similar effect direction and size in Colombia (OR= 1.19, 95% CI: 0.99–1.44, P= 0.069). A meta-analysis of our multi-ethnic study and previously published non-overlapping datasets, which included a total of 5,484 cases and 12,594 controls, confirmed the association between rs6983267G and thyroid cancer (P= 1.23 × 10−7, OR= 1.13, 95% CI: 1.07–1.18). Our results therefore support the notion that rs6983267G is a bona fide thyroid cancer risk variant that increases the risk of disease by ~13%. PMID:26290501

  11. Germline PARP4 mutations in patients with primary thyroid and breast cancers.

    PubMed

    Ikeda, Yuji; Kiyotani, Kazuma; Yew, Poh Yin; Kato, Taigo; Tamura, Kenji; Yap, Kai Lee; Nielsen, Sarah M; Mester, Jessica L; Eng, Charis; Nakamura, Yusuke; Grogan, Raymon H

    2016-03-01

    Germline mutations in the PTEN gene, which cause Cowden syndrome, are known to be one of the genetic factors for primary thyroid and breast cancers; however, PTEN mutations are found in only a small subset of research participants with non-syndrome breast and thyroid cancers. In this study, we aimed to identify germline variants that may be related to genetic risk of primary thyroid and breast cancers. Genomic DNAs extracted from peripheral blood of 14 PTEN WT female research participants with primary thyroid and breast cancers were analyzed by whole-exome sequencing. Gene-based case-control association analysis using the information of 406 Europeans obtained from the 1000 Genomes Project database identified 34 genes possibly associated with the phenotype with P < 1.0 × 10(-3). Among them, rare variants in the PARP4 gene were detected at significant high frequency (odds ratio = 5.2; P = 1.0 × 10(-5)). The variants, G496V and T1170I, were found in six of the 14 study participants (43%) while their frequencies were only 0.5% in controls. Functional analysis using HCC1143 cell line showed that knockdown of PARP4 with siRNA significantly enhanced the cell proliferation, compared with the cells transfected with siControl (P = 0.02). Kaplan-Meier analysis using Gene Expression Omnibus (GEO), European Genome-phenome Archive (EGA) and The Cancer Genome Atlas (TCGA) datasets showed poor relapse-free survival (P < 0.001, Hazard ratio 1.27) and overall survival (P = 0.006, Hazard ratio 1.41) in a PARP4 low-expression group, suggesting that PARP4 may function as a tumor suppressor. In conclusion, we identified PARP4 as a possible susceptibility gene of primary thyroid and breast cancer. PMID:26699384

  12. Validation of the Korean version of the thyroid cancer-specific quality of life questionnaire

    PubMed Central

    Jeong, Youjin; Ahn, Ah-Leum; Oh, Eun-Jung; Oh, Hee-Kyung; Cho, Dong-Yung; Kweon, Hyuk-Jung; Park, Kyoung Sik

    2015-01-01

    Purpose The increasing incidence of thyroid cancer worldwide has drawn attention to the needs for assessing and managing health-related quality of life (HRQoL) of thyroid cancer survivors. We conducted this study to validate the Korean version of the thyroid cancer-specific quality of life (THYCA-QoL) questionnaire. Methods Data obtained from 227 thyroid cancer survivors were analyzed using standard validity and reliability analysis techniques. Reliability was assessed by measuring internal consistency via Cronbach α coefficient, and validity was assessed by determining the Pearson correlation coefficient between the THYCA-QoL questionnaire and the following relevant assessment tools: the European Organization for Research and Treatment of Cancer QLQ-C30 (EORTC QLQ-C30), the Korean version of Brief Fatigue Inventory (BFI-K), the Korean version of Brief Encounter Psychosocial Instrument (BEPSI-K), Goldberg Short Screening Scale for Anxiety and Depression, and a nine-item Patient Health Questionnaire (PHQ-9). A multitrait scaling analysis was performed to assess each item's convergent and discriminant validity. Results The reliability of the THYCA-QoL questionnaire was confirmed by Cronbach α coefficients for multiple-item scales which ranged from 0.54 (sensory) to 0.82 (psychological). Except for a single item (sexual interest), the questionnaire's validity was established by significant correlation observed between scales in the THYCA-QoL questionnaire and scales used in other assessment tools. A multitrait scaling analysis confirmed that all scales met the recommended psychometric standards. Conclusion The Korean version of the THYCA-QoL questionnaire is a reliable and valid assessment tool that can be used in combination with the EORTC QLQ-C30 to assess the HRQoL of thyroid cancer survivors in Korea. PMID:26665122

  13. microRNA-7 regulates cell growth, migration and invasion via direct targeting of PAK1 in thyroid cancer.

    PubMed

    Yue, Kai; Wang, Xudong; Wu, Yansheng; Zhou, Xuan; He, Qinghua; Duan, Yuansheng

    2016-09-01

    The expression and function of microRNA-7 (miR-7) has been studied in a variety of different cancer types. However, to date, no studies have investigated the expression of miR‑7 in human thyroid cancer. In the present study, the expression levels and biological function of miR‑7 were investigated in human thyroid cancer, with the aim of evaluating whether it may serve as a therapeutic biomarker. The expression levels of miR‑7 in human thyroid cancer tissues, matched, adjacent normal tissues, normal thyroid tissues and human thyroid cancer cell lines were determined using RT‑qPCR and western blot analysis. To explore the functional role of miR‑7 in human thyroid cancer cell lines, MTT assays, cell migration and invasion assays were employed. TargetScan software identified p21 activated kinase‑1 (PAK1) as a putative interacting partner of miR‑7. Therefore, functional assays were performed to explore the effects of endogenous PAK1 in thyroid cancer. In the present study, miR‑7 was significantly downregulated in thyroid cancer tissues and cells compared with normal thyroid tissue samples. A correlation between miR‑7 expression and thyroid tumor stage was also observed. Ectopic expression of miR‑7 was found to suppress the proliferation, migra-tion and invasion of thyroid cancer cells in vitro. Dual-luciferase reporter assays demonstrated that PAK1 was a direct target of miR-7 in vitro. RT-qPCR and western blot analysis demonstrated that miR‑7 negatively regulates PAK1 protein expression but has no effect on PAK1 mRNA expression. Knockdown of PAK1 expression markedly suppressed thyroid cancer cell proliferation, migration and invasion. These results suggest that miR‑7 functions as a tumor suppressor by targeting PAK1 directly and may therefore present a novel therapeutic target for the treatment of thyroid cancer. PMID:27430434

  14. Differentiated Thyroid Cancer: Focus on Emerging Treatments for Radioactive Iodine-Refractory Patients

    PubMed Central

    Gruber, Joshua J.

    2015-01-01

    Background. The treatment of differentiated thyroid cancer refractory to radioactive iodine (RAI) had been hampered by few effective therapies. Recently, tyrosine kinase inhibitors (TKIs) have shown activity in this disease. Clinical guidance on the use of these agents in RAI-refractory thyroid cancer is warranted. Materials and Methods. Molecular mutations found in RAI-refractory thyroid cancer are summarized. Recent phase II and III clinical trial data for TKIs axitinib, lenvatinib, motesanib, pazopanib, sorafenib, sunitinib, and vandetinib are reviewed including efficacy and side effect profiles. Molecular targets and potencies of these agents are compared. Inhibitors of BRAF, mammalian target of rapamycin, and MEK are considered. Results. Routine testing for molecular alterations prior to therapy is not yet recommended. TKIs produce progression-free survival of approximately 1 year (range: 7.7–19.6 months) and partial response rates of up to 50% by Response Evaluation Criteria in Solid Tumors. Pazopanib and lenvatinib are the most active agents. The majority of patients experienced tumor shrinkage with TKIs. Common adverse toxicities affect dermatologic, gastrointestinal, and cardiovascular systems. Conclusion. Multiple TKIs have activity in RAI-refractory differentiated thyroid cancer. Selection of a targeted agent should depend on disease trajectory, side effect profile, and goals of therapy. PMID:25616432

  15. Identification of kinase fusion oncogenes in post-Chernobyl radiation-induced thyroid cancers

    PubMed Central

    Ricarte-Filho, Julio C.; Li, Sheng; Garcia-Rendueles, Maria E.R.; Montero-Conde, Cristina; Voza, Francesca; Knauf, Jeffrey A.; Heguy, Adriana; Viale, Agnes; Bogdanova, Tetyana; Thomas, Geraldine A.; Mason, Christopher E.; Fagin, James A.

    2013-01-01

    Exposure to ionizing radiation during childhood markedly increases the risk of developing papillary thyroid cancer. We examined tissues from 26 Ukrainian patients with thyroid cancer who were younger than 10 years of age and living in contaminated areas during the time of the Chernobyl nuclear reactor accident. We identified nonoverlapping somatic driver mutations in all 26 cases through candidate gene assays and next-generation RNA sequencing. We found that 22 tumors harbored fusion oncogenes that arose primarily through intrachromosomal rearrangements. Altogether, 23 of the oncogenic drivers identified in this cohort aberrantly activate MAPK signaling, including the 2 somatic rearrangements resulting in fusion of transcription factor ETS variant 6 (ETV6) with neurotrophic tyrosine kinase receptor, type 3 (NTRK3) and fusion of acylglycerol kinase (AGK) with BRAF. Two other tumors harbored distinct fusions leading to overexpression of the nuclear receptor PPARγ. Fusion oncogenes were less prevalent in tumors from a cohort of children with pediatric thyroid cancers that had not been exposed to radiation but were from the same geographical regions. Radiation-induced thyroid cancers provide a paradigm of tumorigenesis driven by fusion oncogenes that activate MAPK signaling or, less frequently, a PPARγ-driven transcriptional program. PMID:24135138

  16. Identification of kinase fusion oncogenes in post-Chernobyl radiation-induced thyroid cancers.

    PubMed

    Ricarte-Filho, Julio C; Li, Sheng; Garcia-Rendueles, Maria E R; Montero-Conde, Cristina; Voza, Francesca; Knauf, Jeffrey A; Heguy, Adriana; Viale, Agnes; Bogdanova, Tetyana; Thomas, Geraldine A; Mason, Christopher E; Fagin, James A

    2013-11-01

    Exposure to ionizing radiation during childhood markedly increases the risk of developing papillary thyroid cancer. We examined tissues from 26 Ukrainian patients with thyroid cancer who were younger than 10 years of age and living in contaminated areas during the time of the Chernobyl nuclear reactor accident. We identified nonoverlapping somatic driver mutations in all 26 cases through candidate gene assays and next-generation RNA sequencing. We found that 22 tumors harbored fusion oncogenes that arose primarily through intrachromosomal rearrangements. Altogether, 23 of the oncogenic drivers identified in this cohort aberrantly activate MAPK signaling, including the 2 somatic rearrangements resulting in fusion of transcription factor ETS variant 6 (ETV6) with neurotrophic tyrosine kinase receptor, type 3 (NTRK3) and fusion of acylglycerol kinase (AGK) with BRAF. Two other tumors harbored distinct fusions leading to overexpression of the nuclear receptor PPARγ. Fusion oncogenes were less prevalent in tumors from a cohort of children with pediatric thyroid cancers that had not been exposed to radiation but were from the same geographical regions. Radiation-induced thyroid cancers provide a paradigm of tumorigenesis driven by fusion oncogenes that activate MAPK signaling or, less frequently, a PPARγ-driven transcriptional program. PMID:24135138

  17. Papillary and follicular thyroid cancer: impact of treatment in 1578 patients

    SciTech Connect

    Simpson, W.J.; Panzarella, T.; Carruthers, J.S.; Gospodarowicz, M.K.; Sutcliffe, S.B.

    1988-06-01

    We report the experience from 13 Canadian radiotherapy centers concerning the treatment and outcome for 1074 papillary and 504 follicular thyroid cancer patients followed for 4-24 years. Surgical resection was carried out in almost all patients; there was no correlation between the type of operation and recurrence or survival. Treatment with external irradiation (201 patients) radioiodine (214 patients), or both (107 patients) was used more often in poor prognosis patients than in those with good prognostic factors, and was effective in reducing local recurrences and improving survival, especially in patients with microscopic residual disease postoperatively. Treatment complications were common but rarely fatal. Thyroid cancer was the cause of death in over half of the papillary cancer deaths and in two-thirds of the follicular cancer deaths.

  18. Episodic pain in patients with advanced cancer.

    PubMed

    Zeppetella, Giovambattista; Ribeiro, Maria D C

    2002-01-01

    Episodic pain is a common problem for patients with advanced cancer and is often difficult to manage successfully. In this article, the daily variations in cancer-related episodic pain in a patient with metastatic lung cancer are described. The definition, etiology, prevalence, and pharmacological management of episodic pain are also reviewed PMID:12141792

  19. Iodine I-131 With or Without Selumetinib in Treating Patients With Recurrent or Metastatic Thyroid Cancer

    ClinicalTrials.gov

    2016-07-12

    Poorly Differentiated Thyroid Gland Carcinoma; Recurrent Thyroid Gland Carcinoma; Stage IVA Thyroid Gland Follicular Carcinoma; Stage IVA Thyroid Gland Papillary Carcinoma; Stage IVB Thyroid Gland Follicular Carcinoma; Stage IVB Thyroid Gland Papillary Carcinoma; Stage IVC Thyroid Gland Follicular Carcinoma; Stage IVC Thyroid Gland Papillary Carcinoma

  20. Trametinib in Increasing Tumoral Iodine Incorporation in Patients With Recurrent or Metastatic Thyroid Cancer

    ClinicalTrials.gov

    2016-06-30

    Poorly Differentiated Thyroid Gland Carcinoma; Recurrent Thyroid Gland Carcinoma; Stage IVA Thyroid Gland Follicular Carcinoma; Stage IVA Thyroid Gland Papillary Carcinoma; Stage IVB Thyroid Gland Follicular Carcinoma; Stage IVB Thyroid Gland Papillary Carcinoma; Stage IVC Thyroid Gland Follicular Carcinoma; Stage IVC Thyroid Gland Papillary Carcinoma

  1. Iodine-131 avid distant metastasis in differentiated thyroid cancer: An initial institutional experience from the northern part of India

    PubMed Central

    Khan, Shoukat Hussain; Hassan, Masood ul; Bhau, Rajesh Singh

    2015-01-01

    Objective: The aim of the study was to study the clinical profile in patients of differentiated thyroid cancer (DTC) with Iodine-131 avid distant metastasis at presentation. The study also attempted to evaluate factors influencing survival among these patients. Material and Methods: The cohort includes 35 patients (26 Female, 9 Male) studied retrospectively and prospectively over a period of 5 years at the Sher-I-Kashmir Institute of Medical Sciences, Srinagar, India. Results: The five years cause specific survival among patients of DTC with distant metastasis in the study group was 74.3%. The mean age at presentation was 41.4 years with female patients outnumbering the male patients in a ratio of 5:1. Papillary histopathology was the commonest in 65.7% followed by Follicular in 31.4% and poorly differentiated cancer in 2.9% of patients.31.4% 0f patients presented with relatively advanced AJC/UICC tumor stage of T3-T4. Bone was the commonest site of metastasis in 42.85% of patients followed by lung in 40% 0f patients. 82.9% of patients had only single organ metastasis. Therapeutic Radioiodine was administered in 31 (88.6%) patients. On univariate analysis of various factors that may be influencing the cause specific survival at 5 years, age ≥ 45 years, T3-T4 tumor stage, regional lymph node metastasis, follicular histopathology and non administration of radioiodine revealed significant (P<0.05) association with a poor 5 year survival. However multivariate analysis identified advanced tumor stage (T3-T4) and non administration of radioiodine to be the only independent factors associated with poor survival. Conclusion: Patients of differentiated thyroid cancer with distant metastasis having advanced tumor stage (T3-T4) and those in whom therapeutic radioiodine (I-131) is not administered seem to have an unfavorable prognosis in terms of a 5 years cause specific survival. PMID:26170565

  2. Laser-induced interstitial thermotherapy in treatment of recurrent nodular goiter and thyroid cancer

    NASA Astrophysics Data System (ADS)

    Seliverstov, Oleg V.; Privalov, Valeriy A.; Lappa, Alexander V.; Demidov, A. K.; Faizrakhmanov, Alexey B.; Yarovoy, Nicolay N.

    2001-10-01

    Laser-induced interstitial thermotherapy was performed in 29 patients with recurrent nodular and multinodular goiter, and in 3 patients with recurrent inoperable thyroid cancer. There were used transcutaneous puncture under ultrasonic control, diode lasers with wavelength 805, 980, and 1060 nm, quartz monofibers, special computerized thermometer with microthermocouples. Disappearance or significant reduction of nodes in the most goiter cases, and regress of tumor in the cancer cases were marked during observation period (0.5 - 2.5 years).

  3. [Value of scintigraphic explorations by radiomarkers others than iodine radioisotope in differentiated thyroid cancer].

    PubMed

    Sassolas, G; Houzard, C; Sigartau, C; Borson-Chazot, F

    1997-01-01

    Radioiodine scintigraphy is the gold standard exploration for imaging metastases of differentiated thyroid cancer and enables the decision of therapy with 131 radioactive iodine to be made. However, other approaches may be of use for diagnosis when there is no visible uptake after the administration of 131I, while elevated thyroblobulin levels suggest the presence of metastatic tissue in one third of metastatic patients. In order to detect recurrences or metastases, in conjunction with conventional imaging techniques (cervical and hepatic ultrasonography, lung CT scan..), other scintigraphic explorations with various radiopharmaceutics may be used, although none of them has any specificity towards thyroid cancer. Tl201 and MIBI which are used as perfusion tracers for myocardial explorations, are also used for detection of various tumors and for metastatic thyroid cancer. The performances of both radiopharmaceutics in imaging metastases are differently evaluated between investigators with a sensitivity ranging from 45 to 94% while the specificity varies less (82-97%). 18-Fluoro-deoxyglucose is retained in malignant tissue depending on the grade of malignancy. It has been shown to accumulate in thyroid cancer and metastases. Its detection by whole body PETscan represents a limitation for use which will be modified by new techniques. 111In-octreotide which binds to somatostatin receptors located on tumor cell membranes is able to show thyroid cancer metastases in some instances. We report on the very preliminary results of these combined scintigraphic approaches, performed in a limited number of patients who had no radioiodine uptake and elevated Tg levels, in order to determine the most appropriate exploration in terms of performance and cost. PMID:9207967

  4. Utility of a Histone Deacetylase Inhibitor (PXD101) for Thyroid Cancer Treatment

    PubMed Central

    Lin, Shu-Fu; Lin, Jen-Der; Chou, Ting-Chao; Huang, Yu-Yao; Wong, Richard J.

    2013-01-01

    Background We evaluated the therapeutic effects of the histone deacetylase inhibitor PXD101 alone and in combination with conventional chemotherapy in treating thyroid cancer. Methodology/Principal Findings We studied eight cell lines from four types of thyroid cancer (papillary, follicular, anaplastic and medullary). The cytotoxicity of PXD101 alone and in combination with three conventional chemotherapeutic agents (doxorubicin, paclitaxel and docetaxel) was measured using LDH assay. Western blot assessed expression of acetylation of histone H3, histone H4 and tubulin, proteins associated with apoptosis, RAS/RAF/ERK and PI3K/AKT/mTOR signaling pathways, DNA damage and repair. Apoptosis and intracellular reactive oxygen species (ROS) were measured by flow cytometry. Mice bearing flank anaplastic thyroid cancers (ATC) were daily treated with intraperitoneal injection of PXD101 for 5 days per week. PXD101 effectively inhibited thyroid cancer cell proliferation in a dose-dependent manner. PXD101 induced ROS accumulation and inhibited RAS/RAF/ERK and PI3K/mTOR pathways in sensitive cells. Double-stranded DNA damage and apoptosis were induced by PXD101 in both sensitive and resistant cell lines. PXD101 retarded growth of 8505C ATC xenograft tumors with promising safety. Combination therapy of PXD101with doxorubicin and paclitaxel demonstrated synergistic effects against four ATC lines in vitro. Conclusions PXD101 represses thyroid cancer proliferation and has synergistic effects in combination with doxorubicin and paclitaxel in treating ATC. These findings support clinical trials using PXD101 for patients with this dismal disease. PMID:24155971

  5. Quantification of the increase in thyroid cancer prevalence in Fukushima after the nuclear disaster in 2011--a potential overdiagnosis?

    PubMed

    Katanoda, Kota; Kamo, Ken-Ichi; Tsugane, Shoichiro

    2016-03-01

    A thyroid ultrasound examination programme has been conducted in Fukushima Prefecture, Japan, after the nuclear disaster in 2011. Although remarkably high prevalence of thyroid cancer was observed, no relevant quantitative evaluation was conducted. We calculated the observed/expected (O/E) ratio of thyroid cancer prevalence for the residents aged ≤20 years. Observed prevalence was the number of thyroid cancer cases detected by the programme through the end of April 2015. Expected prevalence was calculated as cumulative incidence by a life-table method using the national estimates of thyroid cancer incidence rate in 2001-10 (prior to the disaster) and the population of Fukushima Prefecture. The underlying assumption was that there was neither nuclear accident nor screening intervention. The observed and estimated prevalence of thyroid cancer among residents aged ≤20 years was 160.1 and 5.2, respectively, giving an O/E ratio of 30.8 [95% confidence interval (CI): 26.2, 35.9]. When the recent increasing trend in thyroid cancer was considered, the overall O/E ratio was 22.2 (95% CI: 18.9, 25.9). The cumulative number of thyroid cancer deaths in Fukushima Prefecture, estimated with the same method (annual average in 2009-13), was 0.6 under age 40. Combined with the existing knowledge about radiation effect on thyroid cancer, our descriptive analysis suggests the possibility of overdiagnosis. Evaluation including individual-level analysis is required to further clarify the contribution of underlying factors. PMID:26755830

  6. Thyroid, Renal, and Breast Carcinomas, Chondrosarcoma, Colon Adenomas, and Ganglioneuroma: A New Cancer Syndrome, FAP, or Just Coincidence

    PubMed Central

    Atta, Ihab Shafek; AlQahtani, Fahd Nasser

    2016-01-01

    We are presenting a case associated with papillary thyroid carcinoma, renal cell carcinoma, invasive mammary carcinoma, chondrosarcoma, benign ganglioneuroma, and numerous colon adenomas. The patient had a family history of colon cancer, kidney and bladder cancers, lung cancer, thyroid cancer, leukemia, and throat and mouth cancers. She was diagnosed with colonic villous adenoma at the age of 41 followed by thyroid, renal, and breast cancers and chondrosarcoma at the ages of 48, 64, 71, and 74, respectively. Additionally, we included a table with the most common familial cancer syndromes with one or more benign or malignant tumors diagnosed in our case, namely, FAP, HNPCC, Cowden, Peutz-Jeghers, renal cancer, tuberous sclerosis, VHL, breast/other, breast/ovarian, Carney, Werner's, Bloom, Li-Fraumeni, xeroderma pigmentosum, ataxia-telangiectasia, osteochondromatosis, retinoblastoma, and MEN2A. PMID:27087812

  7. Thyroid, Renal, and Breast Carcinomas, Chondrosarcoma, Colon Adenomas, and Ganglioneuroma: A New Cancer Syndrome, FAP, or Just Coincidence.

    PubMed

    Atta, Ihab Shafek; AlQahtani, Fahd Nasser

    2016-01-01

    We are presenting a case associated with papillary thyroid carcinoma, renal cell carcinoma, invasive mammary carcinoma, chondrosarcoma, benign ganglioneuroma, and numerous colon adenomas. The patient had a family history of colon cancer, kidney and bladder cancers, lung cancer, thyroid cancer, leukemia, and throat and mouth cancers. She was diagnosed with colonic villous adenoma at the age of 41 followed by thyroid, renal, and breast cancers and chondrosarcoma at the ages of 48, 64, 71, and 74, respectively. Additionally, we included a table with the most common familial cancer syndromes with one or more benign or malignant tumors diagnosed in our case, namely, FAP, HNPCC, Cowden, Peutz-Jeghers, renal cancer, tuberous sclerosis, VHL, breast/other, breast/ovarian, Carney, Werner's, Bloom, Li-Fraumeni, xeroderma pigmentosum, ataxia-telangiectasia, osteochondromatosis, retinoblastoma, and MEN2A. PMID:27087812

  8. [Procedure guidelines for radioiodine therapy of differentiated thyroid cancer. Version 4].

    PubMed

    Dietlein, Markus; Eschner, Wolfgang; Grünwald, Frank; Lassmann, Michael; Verburg, Frederik A; Luster, Markus

    2016-06-28

    The procedure guideline for radioiodine therapy of differentiated thyroid cancer (version 4) was developed in the consensus of a representative expert group. This fulfils the level S1 (first step) within the AWMF classification of Clinical Practice Guidelines (AWMF, Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, Germany). This procedure guideline completed the guideline for surgical management of thyroid cancer (level S2) with the aspects from nuclear medicine. Controversies over ablative radioiodine therapy in small papillary thyroid cancers and in minimally invasive follicular cancer without angioinvasion, over empirical standard doses for ablative radioiodine therapy, and over the kind of TSH-stimulation were described and the guideline formulated a corridor of good clinical practice. The text has included the recent results from the National Cancer database and the SEER database (both from the USA), indicating that the ablative radioiodine therapy has improved the survival rate even in low risk patients. Such a statistically significant benefit can be detected only by a national cancer registry with long-term follow-up data. PMID:27350004

  9. Challenges of thyroid cancer management in amiodarone-treated patients: a case report

    PubMed Central

    PETRULEA, MIRELA SANDA; LENCU, CODRUTA; PICIU, DOINA; LISENCU, COSMIN IOAN; GEORGESCU, CARMEN EMANUELA

    2015-01-01

    Thyroid carcinoma (TC) is the most common endocrine malignancy. Although the overall prognosis for patients with TC is good, up to 20–30% of patients have recurrent or persistent disease after conventional therapy by surgical resection and radioactive iodine (RAI). Amiodarone is a highly efficient anti-arrhythmic drug with a very long half-life, so it may interfere with RAI many months after the drug withdrawal. This case report mirrors the challenges of thyroid cancer management in an amiodarone-treated patient. PMID:26733755

  10. Challenges of thyroid cancer management in amiodarone-treated patients: a case report.

    PubMed

    Petrulea, Mirela Sanda; Lencu, Codruta; Piciu, Doina; Lisencu, Cosmin Ioan; Georgescu, Carmen Emanuela

    2015-01-01

    Thyroid carcinoma (TC) is the most common endocrine malignancy. Although the overall prognosis for patients with TC is good, up to 20-30% of patients have recurrent or persistent disease after conventional therapy by surgical resection and radioactive iodine (RAI). Amiodarone is a highly efficient anti-arrhythmic drug with a very long half-life, so it may interfere with RAI many months after the drug withdrawal. This case report mirrors the challenges of thyroid cancer management in an amiodarone-treated patient. PMID:26733755

  11. Predictors of Regional Lymph Node Recurrence after Initial Thyroidectomy in Patients with Thyroid Cancer

    PubMed Central

    Sharifi, Amirsina; Shojaeifard, Abolfazl; Soroush, Ahmadreza; Jafari, Mehdi; Abdehgah, Ali Ghorbani; Mahmoudzade, Hossein

    2016-01-01

    Background. Regional lymph node recurrence (RLNR) is common in patients with thyroid cancer but clinicopathological predictors are unclear. We aimed to clarify these predictors and identify patients who would benefit from prophylactic lymph node dissection the most. Method. 343 patients with different types of thyroid cancer were analyzed retrospectively. All patients underwent total thyroidectomy between 2007 and 2013. Results. The median ± interquartile range of patients' age was 40 ± 25 years. 245 (71.4%) patients were female. Regarding the risk of regional lymph node recurrence, we found that male gender, age ≥45 years, non-PTC (i.e., medullary, follicular, and anaplastic types) histopathology, T3 (i.e., tumor size >4 cm in the greatest dimension limited to the thyroid or any tumor with minimal extrathyroid extension), stage IVa, and isolated cervical lymphadenopathy as initial manifestation (ICL) are significant risk factors. T3 (p < 0.001; odds ratio = 156.41, 95% CI [55.72–439.1]) and ICL (p < 0.001; odds ratio = 77.79, 95% CI [31.55–191.81]) were the strongest predictors of regional lymph node recurrence. Conclusion. We found easily achievable risk factors for RLNR in thyroid cancers patients. We suggested that patients with specific clinicopathological features like male gender, age ≥45 years, larger tumor size, and extrathyroidal extension be considered as prophylactic lymphadenectomy candidates. PMID:27403370

  12. A Rare Presentation of Autonomously Functioning Papillary Thyroid Cancer: Malignancy in Marine-Lenhart Syndrome Nodule

    PubMed Central

    Uludag, Mehmet; Aygun, Nurcihan; Ozel, Alper; Yener Ozturk, Feyza; Karasu, Rabia; Ozguven, Banu Yilmaz; Citgez, Bulent; Mihmanli, Mehmet; Isgor, Adnan

    2016-01-01

    Objective. Marine-Lenhart Syndrome (MLS) is defined as concomitant occurrence of autonomously functioning thyroid nodule (AFTN) with Graves' disease (GD). Malignancy in a functional nodule is rare. We aimed to present an extremely rare case of papillary thyroid cancer in a MLS nodule with lateral lymph node metastases. Case. A 43-year-old male presented with hyperthyroidism and Graves' ophthalmopathy. On Tc99m pertechnetate scintigraphy, a hyperactive nodule in the left upper thyroid pole was detected and the remaining tissue showed a mildly increased uptake. The ultrasonography demonstrated 15.5 × 13.5 × 12 mm sized hypoechoic nodule in the left upper pole of the thyroid and round lymph nodes on the left side of the neck. Fine needle aspiration biopsy (FNAB) of the nodule and lymph node revealed cytological findings consistent with papillary cancer. Total thyroidectomy with central and left modified radical neck dissection was performed. On pathologic examination, two foci of micropapillary cancer were detected. The skip metastases were present in three lymph nodes on the neck. Conclusion. AFTN can be seen rarely in association with GD. It is not possible to exclude malignancy due to the clinical and imaging findings. In the presence of suspicious clinical and sonographic features, FNAB should be performed. PMID:27110424

  13. Thyroid hormones in conditions of chronic malnutrition. A study with special reference to cancer cachexia.

    PubMed Central

    Persson, H; Bennegård, K; Lundberg, P A; Svaninger, G; Lundholm, K

    1985-01-01

    Circulating levels of thyroid hormones (T4, free T4, T3) and reverse tri-iodo thyronine (rT3) and thyroid-hormone binding globulin were related to the nutritional state of patients with cancer cachexia, patients with malnutrition due to other reasons and to well-nourished patients with acute illness. Hospitalized weight-stable and well-nourished patients served as controls. Malnourished patients with or without cancer and acutely ill patients had a low T3 syndrome involving both peripheral metabolism of thyroid hormones and the hypothalamus-pituitary-thyroid gland axis. T3 levels were correlated to altered protein metabolism and protein nutritional state. There were pronounced elevations of circulating rT3 concentrations in patients with serum albumin concentration less than 35 g/l irrespective of diagnosis. The results indicate that the low T3 syndrome in our patients is secondary to insufficient caloric intake. It seems to be maintained by the abnormal nutritional state and is related closely to protein metabolism. The authors found no differences between the low T3 syndrome in cancer patients suffering from cachexia compared with that of patients with malnutrition caused by other factors. PMID:3917657

  14. Targeting mTOR in RET mutant medullary and differentiated thyroid cancer cells

    PubMed Central

    Gild, Matti L; Landa, Iñigo; Ryder, Mabel; Ghossein, Ronald A; Knauf, Jeffrey A; Fagin, James A

    2015-01-01

    Inhibitors of RET, a tyrosine kinase receptor encoded by a gene that is frequently mutated in medullary thyroid cancer, have emerged as promising novel therapies for the disease. Rapalogs and other mammalian target of rapamycin (mTOR) inhibitors are effective agents in patients with gastroenteropancreatic neuroendocrine tumors, which share lineage properties with medullary thyroid carcinomas. The objective of this study was to investigate the contribution of mTOR activity to RET-induced signaling and cell growth and to establish whether growth suppression is enhanced by co-targeting RET and mTOR kinase activities. Treatment of the RET mutant cell lines TT, TPC-1, and MZ-CRC-1 with AST487, a RET kinase inhibitor, suppressed growth and showed profound and sustained inhibition of mTOR signaling, which was recapitulated by siRNA-mediated RET knockdown. Inhibition of mTOR with INK128, a dual mTORC1 and mTORC2 kinase inhibitor, also resulted in marked growth suppression to levels similar to those seen with RET blockade. Moreover, combined treatment with AST487 and INK128 at low concentrations suppressed growth and induced apoptosis. These data establish mTOR as a key mediator of RET-mediated cell growth in thyroid cancer cells and provide a rationale for combinatorial treatments in thyroid cancers with oncogenic RET mutations. PMID:23828865

  15. Late Intervention with anti-BRAFV600E Therapy Induces Tumor Regression in an Orthotopic Mouse Model of Human Anaplastic Thyroid Cancer

    PubMed Central

    Nehs, Matthew A.; Nucera, Carmelo; Nagarkatti, Sushruta S.; Sadow, Peter M.; Morales-Garcia, Dieter; Hodin, Richard A.

    2012-01-01

    Human anaplastic thyroid cancer (ATC) is a lethal disease with an advanced clinical presentation and median survival of 3 months. The BRAFV600E oncoprotein is a potent transforming factor that causes human thyroid cancer cell progression in vitro and in vivo; therefore, we sought to target this oncoprotein in a late intervention model of ATC in vivo. We used the human ATC cell line 8505c, which harbors the BRAFV600E and TP53R248G mutations. Immunocompromised mice were randomized to receive the selective anti-BRAFV600E inhibitor, PLX4720, or vehicle by oral gavage 28 d after tumor implantation, 1 wk before all animals typically die due to widespread metastatic lung disease and neck compressive symptoms in this model. Mice were euthanized weekly to evaluate tumor volume and metastases. Control mice showed progressive tumor growth and lung metastases by 35 d after tumor implantation. At that time, all control mice had large tumors, were cachectic, and were euthanized due to their tumor-related weight loss. PLX4720-treated mice, however, showed a significant decrease in tumor volume and lung metastases in addition to a reversal of tumor-related weight loss. Mouse survival was extended to 49 d in PLX4720-treated animals. PLX4720 treatment inhibited cell cycle progression from 28 d to 49 d in vivo. PLX4720 induces striking tumor regression and reversal of cachexia in an in vivo model of advanced thyroid cancer that harbors the BRAFV600E mutation. PMID:22202162

  16. Overview and Management of Dermatologic Events Associated with Targeted Therapies for Medullary Thyroid Cancer

    PubMed Central

    Ciccolini, Kathryn; Kloos, Richard T.; Agulnik, Mark

    2014-01-01

    Background: Treatment options for patients with advanced or metastatic medullary thyroid cancer (MTC) have, in recent years, expanded with the approval of two tyrosine kinase inhibitors (TKIs): vandetanib and cabozantinib. Other agents, including TKIs, are under clinical investigation for MTC. Although patients treated with TKIs are at risk of developing dermatologic adverse events (AE), these untoward events may be mitigated through AE-driven algorithms. Summary: AE-driven algorithms combine effective nonpharmaceutical and pharmaceutical treatment modalities implemented by a multidisciplinary effort that incorporates nursing interventions, patient education, and referrals to pain-management specialists, podiatrists, and dermatologists, as appropriate. Effective AE prevention and management reduce the need for dose interruptions and modifications, allowing patients the opportunity to derive the maximal benefit from TKI therapy, while maintaining quality of life. Conclusions: Optimal use of targeted therapies in the treatment of MTC depends on careful patient selection, interdisciplinary communication, and patient education and encouragement to enhance compliance and safety, optimize consistent dosing, and maximize the use of effective therapies. PMID:24902006

  17. The effect of raw vegetable and fruit intake on thyroid cancer risk among women: a case-control study in South Korea.

    PubMed

    Jung, Su Kyoung; Kim, Kirang; Tae, Kyung; Kong, Gu; Kim, Mi Kyung

    2013-01-14

    Thyroid cancer is the most common cancer among Korean women. However, there are few data on dietary factors related to thyroid cancer risk. The objective of the present study was to evaluate the association between raw vegetables and fruits intake and thyroid cancer in a case-control study. We included 111 histologically confirmed malignant thyroid cancer cases and 115 benign cases. Controls who did not have nodules in thyroid ultrasonography were matched to cases by age (± 2 years). Food and nutrient intakes were estimated using a quantitative FFQ with 121 items. Conditional logistic regression analysis was used to obtain OR and corresponding 95 % CI. The intake of total vegetables was not associated with malignant thyroid cancer, but inversely associated with benign cases. High raw vegetable intake was inversely associated with thyroid cancer risk both in malignant and benign cases (P for trend = 0·01 in both malignant and benign cases). Among fruits, persimmon intake had an inverse association with thyroid cancer risk in both malignant and benign cases (P for trend = 0·06 in malignant cases; P for trend = 0·01 in benign cases) and tangerine intake had an inverse association in malignant cases (P for trend = 0·03). The frequency of consumption of raw vegetables and persimmon also had a consistent inverse association in both malignant and benign cases. These results suggest that high consumption of raw vegetables, persimmons and tangerines may decrease thyroid cancer risk and help prevent early-stage thyroid cancer. PMID:22455656

  18. The Association between Selenium and Other Micronutrients and Thyroid Cancer Incidence in the NIH-AARP Diet and Health Study

    PubMed Central

    O’Grady, Thomas J.; Kitahara, Cari M.; DiRienzo, A. Gregory; Gates, Margaret A.

    2014-01-01

    Background Selenium is an essential trace element that is important for thyroid hormone metabolism and has antioxidant properties which protect the thyroid gland from oxidative stress. The association of selenium, as well as intake of other micronutrients, with thyroid cancer is unclear. Methods We evaluated associations of dietary selenium, beta-carotene, calcium, vitamin D, vitamin C, vitamin E, folate, magnesium, and zinc intake with thyroid cancer risk in the National Institutes of Health – American Association of Retired Persons Diet and Health Study, a large prospective cohort of 566,398 men and women aged 50–71 years in 1995–1996. Multivariable-adjusted Cox proportional hazards regression was used to examine associations between dietary intake of micronutrients, assessed using a food frequency questionnaire, and thyroid cancer cases, ascertained by linkage to state cancer registries and the National Death Index. Results With the exception of vitamin C, which was associated with an increased risk of thyroid cancer (HRQ5 vs Q1, 1.34; 95% CI, 1.02–1.76; Ptrend, <0.01), we observed no evidence of an association between quintile of selenium (HRQ5 vs Q1, 1.23; 95% CI, 0.92–1.65; Ptrend, 0.26) or other micronutrient intake and thyroid cancer. Conclusion Our study does not suggest strong evidence for an association between dietary intake of selenium or other micronutrients and thyroid cancer risk. More studies are needed to clarify the role of selenium and other micronutrients in thyroid carcinogenesis. PMID:25329812

  19. LGR5 is associated with tumor aggressiveness in papillary thyroid cancer

    PubMed Central

    Michelotti, Gregory; Jiang, Xiaoyin; Sosa, Julie Ann; Diehl, Anna Mae; Henderson, Brittany Bohinc

    2015-01-01

    PURPOSE Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) is a cancer stem cell marker and a down-stream target in Wnt/β-catenin signaling. In human papillary thyroid cancer (PTC), over activation of Wnt/β-catenin has been associated with tumor aggressiveness. PATIENTS AND METHODS Using established human cell lines (TPC-1, KTC-1, Nthy-ori-3–1), we report LGR5 and R-spondin (RSPO1–3) overexpression in PTC and manipulate LGR5 and Wnt/β-catenin signaling via both pharmacologic and genetic interventions. We test the association of LGR5 tumor expression with markers of PTC aggressiveness using a Discovery Cohort (n = 26 patients) and a Validation Cohort (n = 157 patients). Lastly, we explore the association between LGR5 and the BRAFV600E mutation (n = 33 patients). RESULTS Our results reveal that LGR5 and its ligand, RSPO, are overexpressed in human PTC, whereby Wnt/β-catenin signaling regulates LGR5 expression and promotes cellular migration. In two separate cohorts of patients, LGR5 and RSPO2 were associated with markers of tumor aggressiveness including: lymph node metastases, vascular invasion, increased tumor size, aggressive histology, advanced AJCC TNM stage, microscopic extra thyroidal extension, capsular invasion, and macroscopic invasion. As a biomarker, LGR5 positivity predicts lymph node metastasis with 95.5% sensitivity (95% CI 88.8%-98.7%) and 61% specificity (95% CI: 48.4%–72.4%) and has a negative predictive value (NPV) of 91.3% (95% CI 79.2%–97.5%) for lymph node metastatic disease. In human PTC, LGR5 is also strongly associated with the BRAFV600E mutation (p = 0.005). CONCLUSION We conclude that overexpression of LGR5 is associated with markers of tumor aggressiveness in human PTC. LGR5 may serve as a future potential biomarker for patient risk stratification and loco regional metastases in PTC. PMID:26416247

  20. Sorafenib in the treatment of radioiodine-refractory differentiated thyroid cancer: a meta-analysis.

    PubMed

    Shen, Chen-Tian; Qiu, Zhong-Ling; Luo, Quan-Yong

    2014-04-01

    The advent of biologically targeted agents and increased understanding of thyroid carcinogenesis have generated much interest in the development of biologically targeted therapeutic agents for thyroid cancer. Among them, sorafenib is the most commonly studied drug. The current meta-analysis was carried out to estimate the efficacy and safety of sorafenib administered in radioiodine-refractory differentiated thyroid cancer patients. An electronic search was conducted using PubMed/MEDLINE and EMBASE. Statistical analyses were carried out using either random-effects or fixed-effects models according to heterogeneity. All the statistical analyses were carried out using the Stata version 12.0 software. Seven eligible studies were identified. The final results indicated that 22% of the patients (95% CI: 15-28) achieved a partial response. Hand-foot syndrome, diarrhea, fatigue, rash, weight loss, and hypertension were the most frequently observed adverse effects (AEs) associated with sorafenib use and the incidence of these AEs (all grades) was 80% (95% CI: 68-91), 68% (95% CI: 59-77), 67% (95% CI: 57-78), 66% (95% CI: 50-82), 52%(95% CI: 33-72), and 31% (95% CI: 21-42) respectively. Sixty-two percent (95% CI: 36-89) patients required dose reductions due to toxicity of sorafenib. As far as PR and AEs are concerned, the results of this meta-analysis indicate that sorafenib has a modest effect in patients with radioiodine-refractory differentiated thyroid cancer and the high incidence of AEs associated with this agent may affect the quality of patients' lives. Though the use of sorafenib in the treatment of radioiodine-refractory differentiated thyroid cancer is considered promising by most physicians working in this field, more effective agents with less toxicity and cost are still needed. PMID:24302666

  1. The relevance of preoperative ultrasound cervical mapping in patients with thyroid cancer

    PubMed Central

    Kocharyan, Davit; Schwenter, Frank; Bélair, Manon; Nassif, Edgard

    2016-01-01

    Background Cervical lymph node involvement in thyroid cancer is associated with locoregional recurrence and decreased disease-free survival. Preoperative lymph node mapping helps in planning surgery for neck dissection and improves patient outcomes. We sought to perform a qualitative and quantitative analysis of ultrasound mapping for thyroid cancer and evaluate the clinical importance of this exam in terms of identifying the group of patients who would benefit most from subsequent surgical dissection. Methods We retrospectively reviewed the cases of 263 patients who underwent thyroid surgery between 2009 and 2013. We calculated the positive predictive values (PPVs) of ultrasound mapping of both the lateral and central compartments together and the lateral or central compartment individually. A quantitative analysis was performed by comparing the number of positive lymph nodes at ultrasound imaging with histopathologic evaluation. Results A total of 136 cases of thyroid cancer in 120 patients met the inclusion criteria for ultrasound mapping analysis. The PPVs (and 95% confidence intervals) were 83.82 (0.76–0.89) for the lateral and central compartments, 85.39% (0.76–0.91) for the lateral compartment, and 80.48% (0.7–0.87) for the central compartment. When comparing the positive lymph nodes at ultrasound imaging with histopathologic evaluation, the result was χ2 = 10.33 (p = 0.006). Conclusion This single-institution study indicated that preoperative ultrasound mapping is an accurate imaging procedure for predicting lymphatic spread in differentiated and medullary thyroid cancer. Ultrasound mapping can be used as an efficient tool for surgical planning and prognosis determination, as well as for identifying the group of patients who would benefit most from subsequent surgical intervention. PMID:27007092

  2. Treatment of rectal cancer metastases to the thyroid gland: report of two cases.

    PubMed

    Cheung, Winson Y; Brierley, James; Mackay, Helen J

    2008-07-01

    Rectal cancer rarely metastasizes to the thyroid gland. When it does, however, it poses particular problems with regard to diagnosis and management. Case reports to date support a first-line surgical approach alone or in combination with radiation therapy. Despite the use of these treatment modalities, the presence of thyroid metastasis is associated with a very poor prognosis and significant morbidity. Herein, we review the literature and report on 2 cases of rectal carcinoma metastatic to the thyroid gland that were treated with oxaliplatin-containing chemotherapy regimens. In both cases, the patients responded well to combination chemotherapy up front or after previous surgery and chemoradiation. The favorable survival and symptom benefits observed in these patients suggest that combination chemotherapy should be considered in the management of these very rare cases. PMID:18650197

  3. Analysis of the uncertainties associated with the age-dependent thyroid doses and risk of thyroid cancer due to exposure to {sup 131}I

    SciTech Connect

    Hoffman, F.O.; Apostoaei, A.I.; Nair, S.K.

    1996-06-01

    Effects on the thyroid gland due to exposure to {sup 131}I are currently of interest for ongoing retrospective studies of historical releases in Oak Ridge, Tennessee, and Hanford, Washington. Most of the work to date has been limited to dose estimation. This work focuses on estimating both dose and risk of thyroid cancer to an exposed individual. The age-dependent thyroid dose is calculated using a standard metabolic model for iodine. Updated information on thyroid mass from measurements using modem ultrasound techniques was used. The age-dependent risk is calculated using a linear excess relative risk model. An analysis of uncertainties in dose and risk estimates was performed for an individual in a population characterized by the mass of thyroid, by the iodine metabolic parameters, by the background incidence of thyroid cancer and by the excess relative risk per Gy of absorbed dose. The uncertainty analysis was performed using Monte-Carlo simulation, by considering the age-dependent parameters as random functions. The correlation between the metabolic age-dependent parameters was considered explicitly. Special attention is given to a modifying factor that accounts for the effectiveness of {sup 131}I in inducing thyroid cancer as compared to gamma irradiation, for which most of the excess risk factors are derived. This factor is based on review of recent literature and on informal interviews with outside experts, and thus, the expressed uncertainty is subjective in nature. The paper summarizes the age-dependent dose conversion factors (Sv Bq{sup -1}) and slope factors (risk Bq{sup -1}) as well as the uncertainty associated with them. An analysis that identifies the parameters of dominant importance by their contributions to the overall uncertainty is also included.

  4. The thyroid hormone receptor gene (c-erbA alpha) is expressed in advance of thyroid gland maturation during the early embryonic development of Xenopus laevis.

    PubMed Central

    Banker, D E; Bigler, J; Eisenman, R N

    1991-01-01

    The c-erbA proto-oncogene encodes the thyroid hormone receptor, a ligand-dependent transcription factor which plays an important role in vertebrate growth and development. To define the role of the thyroid hormone receptor in developmental processes, we have begun studying c-erbA gene expression during the ontogeny of Xenopus laevis, an organism in which thyroid hormone has well-documented effects on morphogenesis. Using polymerase chain reactions (PCR) as a sensitive assay of specific gene expression, we found that polyadenylated erbA alpha RNA is present in Xenopus cells at early developmental stages, including the fertilized egg, blastula, gastrula, and neurula. By performing erbA alpha-specific PCR on reverse-transcribed RNAs from high-density sucrose gradient fractions prepared from early-stage embryos, we have demonstrated that these erbA transcripts are recruited to polysomes. Therefore, erbA is expressed in Xenopus development prior to the appearance of the thyroid gland anlage in tailbud-stage embryos. This implies that erbA alpha/thyroid hormone receptors may play ligand-independent roles during the early development of X. laevis. Quantitative PCR revealed a greater than 25-fold range in the steady-state levels of polyadenylated erbA alpha RNA across early stages of development, as expressed relative to equimolar amounts of total embryonic RNA. Substantial increases in the levels of erbA alpha RNA were noted at stages well after the onset of zygotic transcription at the mid-blastula transition, with accumulation of erbA alpha transcripts reaching a relative maximum in advance of metamorphosis. We also show that erbA alpha RNAs are expressed unequally across Xenopus neural tube embryos. This differential expression continues through later stages of development, including metamorphosis. This finding suggests that erbA alpha/thyroid hormone receptors may play roles in tissue-specific processes across all of Xenopus development. Images PMID:1656222

  5. Radiation signatures in childhood thyroid cancers after the Chernobyl accident: possible roles of radiation in carcinogenesis.

    PubMed

    Suzuki, Keiji; Mitsutake, Norisato; Saenko, Vladimir; Yamashita, Shunichi

    2015-02-01

    After the Tokyo Electric Power Company Fukushima Daiichi nuclear power plant accident, cancer risk from low-dose radiation exposure has been deeply concerning. The linear no-threshold model is applied for the purpose of radiation protection, but it is a model based on the concept that ionizing radiation induces stochastic oncogenic alterations in the target cells. As the elucidation of the mechanism of radiation-induced carcinogenesis is indispensable to justify the concept, studies aimed at the determination of molecular changes associated with thyroid cancers among children who suffered effects from the Chernobyl nuclear accident will be overviewed. We intend to discuss whether any radiation signatures are associated with radiation-induced childhood thyroid cancers. PMID:25483826

  6. Impact of sex on the clinicopathological characteristics and prognosis of papillary thyroid cancer

    PubMed Central

    Yorke, Ekua; Melck, Adrienne; Wiseman, Sam M.

    2016-01-01

    Summary Papillary thyroid cancer (PTC) is the most common endocrine malignancy. Observed clinical and pathological differences between the sexes of PTC patients have been reported. There is currently no consensus regarding the impact of sex on PTC prognostication. We studied 566 PTC patients and observed that there was a higher PTC incidence in women, that PTC diagnosis was more challenging in women, and that men tended to present with larger cancers. However, once PTC is diagnosed, both sexes have a similar cancer prognosis, as evaluated using the MACIS (Metastasis, Age, Completeness of Resection, Invasion, Size) score. Our observations suggest that research efforts should be especially directed at improving the diagnostic yield of preoperative fine needle aspiration biopsy in women who present with nodular thyroid disease. PMID:27454841

  7. Radiation signatures in childhood thyroid cancers after the Chernobyl accident: Possible roles of radiation in carcinogenesis

    PubMed Central

    Suzuki, Keiji; Mitsutake, Norisato; Saenko, Vladimir; Yamashita, Shunichi

    2015-01-01

    After the Tokyo Electric Power Company Fukushima Daiichi nuclear power plant accident, cancer risk from low-dose radiation exposure has been deeply concerning. The linear no-threshold model is applied for the purpose of radiation protection, but it is a model based on the concept that ionizing radiation induces stochastic oncogenic alterations in the target cells. As the elucidation of the mechanism of radiation-induced carcinogenesis is indispensable to justify the concept, studies aimed at the determination of molecular changes associated with thyroid cancers among children who suffered effects from the Chernobyl nuclear accident will be overviewed. We intend to discuss whether any radiation signatures are associated with radiation-induced childhood thyroid cancers. PMID:25483826

  8. Global controversies and advances in skin cancer.

    PubMed

    Baldwin, Louise; Dunn, Jeff

    2013-01-01

    Advances and controversies of skin cancer prevention in the Asian-Pacific region are to be examined the world's first Global Controversies and Advances in Skin Cancer Conference to be held in Brisbane, Australia this November. APOCP Members are cordially invited to register early for the opportunity to contribute to the debate on a cancer which continues to be a prominent issue in the Asia Pacific and indeed worldwide. We need answers to the questions of why a cancer that is so preventable and easily detectable is still shrouded in controversy. Primary focuses will be on issues like viral involvement, vaccines and novel clinical approaches. PMID:23725105

  9. Role of MTHFR C677T and MTR A2756G polymorphisms in thyroid and breast cancer development.

    PubMed

    Zara-Lopes, T; Gimenez-Martins, A P A; Nascimento-Filho, C H V; Castanhole-Nunes, M M U; Galbiatti-Dias, A L S; Padovani-Júnior, J A; Maniglia, J V; Francisco, J L E; Pavarino, E C; Goloni-Bertollo, E M

    2016-01-01

    Folate metabolism is essential for DNA synthesis and repair. Alterations in genes that participate in folate metabolism can be associated with several types of malignant neoplasms, including thyroid and breast cancer. In the present case-control study, we examined the association between methylenetetrahydrofolate reductase (MTHFR C677T, rs1801133) and methionine synthase (MTR A2756G, rs1805087) polymorphisms and risk for thyroid and breast cancer. Polymerase chain reaction-restriction fragment length technique was used to determine the specific genotypes in the genes of interest. Statistical analysis was performed by multiple logistic regression test. We found an association between MTHFR C677T polymorphism and risks to both thyroid (OR = 2.50; 95%CI = 1.15-5.46; P = 0.02) and breast cancer (OR = 2.53; 95%CI = 1.08-5.93; P = 0.03). Tobacco consumption and high body mass index were also associated with thyroid cancer. In addition, increased age (≥50 years) and alcohol consumption were found to be associated with breast cancer. Our results indicated that MTHFR C677T is significantly associated with thyroid and breast cancer risks. Thus, these factors may be used as potential prognostic markers for thyroid and breast cancers. PMID:27173331

  10. Assessing risk of thyroid cancer using resonance-frequency based electrical impedance measurements

    NASA Astrophysics Data System (ADS)

    Zheng, Bin; Tublin, Mitchell E.; Lederman, Dror; Klym, Amy H.; Brown, Erica D.; Gur, David

    2011-03-01

    The incidence of thyroid cancer has risen faster than many malignancies and has nearly doubled in the USA over the past 30 years. Palpable nodules and subclinical nodules detected by imaging are found in a large percentage of the USA population. Most of these (.>95%) are fortunately benign. This vast reservoir of nodules makes the detection and diagnosis of thyroid cancer a diagnostic dilemma. Ultrasound guided Fine Needle Aspiration Biopsy (FNAB) is excellent for triaging patients but up to 25% of FNABs are inconclusive. As a result, definitive diagnosis is often only possible with a diagnostic lobectomy; many thousands of these are performed in the USA annually for ultimately benign disease. It would be extremely beneficial if we could develop a non-invasive procedure that could assist the diagnostician in reliably predicting the likelihood of malignancy of otherwise indeterminate thyroid nodules, thereby reducing the number of these "exploratory/diagnostic" lobectomies performed under general anesthesia. Electrical Impedance Spectroscopy (EIS) was considered as a possible approach to address this problem. However, the diagnostic accuracy of EIS is too low for routine clinical use to date. In our group, we developed a substantially modified technology termed Resonance-frequency Electrical Impedance Spectroscopy (REIS), which yields usable information for classifying risk of having breast abnormalities. We preliminarily applied REIS to measure signals on participants having thyroid nodules aiming to assess whether we can assist in improving diagnosis of indeterminate thyroid nodules. In this study we present a new multi-probe based REIS device specifically designed for the assessment of indeterminate thyroid nodules. Our preliminary assessment presented here demonstrates the feasibility of using this proposed REIS device in a busy tertiary care center.

  11. Fibronectin-1 expression is increased in aggressive thyroid cancer and favors the migration and invasion of cancer cells.

    PubMed

    Sponziello, Marialuisa; Rosignolo, Francesca; Celano, Marilena; Maggisano, Valentina; Pecce, Valeria; De Rose, Roberta Francesca; Lombardo, Giovanni Enrico; Durante, Cosimo; Filetti, Sebastiano; Damante, Giuseppe; Russo, Diego; Bulotta, Stefania

    2016-08-15

    In this study we analyzed the expression levels of markers of epithelial-to-mesenchymal transition (EMT) in several papillary thyroid carcinomas (PTCs) and the relation with tumor genotypes and clinicopathological characteristics. The role of fibronectin-1 (FN1) was investigated by analyzing the effects of FN1 silencing in two human thyroid cancer cell lines. Most of EMT markers were significantly over-expressed in a group of 36 PTCs. In particular, FN1 mRNA levels were higher in tumor vs non-tumor tissue (117.3, p < 0.001) and also in aggressive and BRAF(V600E) samples. Similar results were observed (and confirmed at the protein level) when FN1 expression was analyzed in a validation group of 50 PTCs and six lymph node (LN) metastases. Silencing of FN1 in TPC-1 and BCPAP thyroid cancer cells significantly reduced proliferation, adhesion, migration, and invasion in both cell lines. Collectively, our data indicate that FN1 overexpression is an important determinant of thyroid cancer aggressiveness. PMID:27173027

  12. Respective roles of thyroglobulin, radioiodine imaging, and positron emission tomography in the assessment of thyroid cancer.

    PubMed

    Lind, Peter; Kohlfürst, Susanne

    2006-07-01

    Depending on the iodine supply of an area, the incidence of thyroid cancer ranges between 4 and 12/100,000 per year. To detect thyroid cancer in an early stage, the assessment of thyroid nodules includes ultrasonography, ultrasonography-guided fine-needle aspiration biopsy, and conventional scintigraphic methods using (99m)Tc-pertechnetate, (99m)Tc-sestamibi or -tetrofosmin, and (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) in selected cases. After treatment of thyroid cancer, a consequent follow-up is necessary over a period of several years. For following up low-risk patients, recombinant thyroid-stimulating hormone-stimulated thyroglobulin and ultrasonography is sufficient in most cases. After total thyroidectomy and radioiodine ablation therapy, thyroid-stimulating hormone-stimulated thyroglobulin should be below the detection limit (eg, <0.5 ng/mL, R: 70-130). An increase of thyroglobulin over time is suspicious for recurrent or metastatic disease. Especially in high-risk patients, aside from the use of ultrasonography for the detection of local recurrence and cervial lymph node metastases, nuclear medicine methods such as radioiodine imaging and FDG-PET are the methods of choice for localizing metastatic disease. Radioiodine imaging detects well-differentiated recurrences and metastases with a high specificity but only moderate sensitivity. The sensitivity of radioiodine imaging depends on the activity administered. Therefore a low activity diagnostic (131)I whole-body scan (74-185 MBq) has a lower detection rate than a high activity post-therapy scan (3700-7400 MBq). In patients with low or dedifferentiated thyroid cancer and after several courses of radioiodine therapy caused by metastatic disease, iodine negative metastases may develop. In these cases, despite clearly elevated levels of thyroglobulin, radioiodine imaging is negative or demonstrates only faint iodine uptake. The method of choice to image these iodine negative metastases is

  13. Integrated Molecular Profiling in Advanced Cancers Trial

    ClinicalTrials.gov

    2016-08-19

    Breast Cancer; Non-small Cell Lung Cancer; Colorectal Cancer; Genitourinary Cancer; Pancreatobiliary Gastrointestinal Cancer; Upper Aerodigestive Tract Cancer; Gynecological Cancers; Melanoma Cancers; Rare Cancers; Unknown Primary Cancers

  14. Precision medicine for advanced prostate cancer

    PubMed Central

    Mullane, Stephanie A.; Van Allen, Eliezer M.

    2016-01-01

    Purpose of review Precision cancer medicine, the use of genomic profiling of patient tumors at the point-of-care to inform treatment decisions, is rapidly changing treatment strategies across cancer types. Precision medicine for advanced prostate cancer may identify new treatment strategies and change clinical practice. In this review, we discuss the potential and challenges of precision medicine in advanced prostate cancer. Recent findings Although primary prostate cancers do not harbor highly recurrent targetable genomic alterations, recent reports on the genomics of metastatic castration-resistant prostate cancer has shown multiple targetable alterations in castration-resistant prostate cancer metastatic biopsies. Therapeutic implications include targeting prevalent DNA repair pathway alterations with PARP-1 inhibition in genomically defined subsets of patients, among other genomically stratified targets. In addition, multiple recent efforts have demonstrated the promise of liquid tumor profiling (e.g., profiling circulating tumor cells or cell-free tumor DNA) and highlighted the necessary steps to scale these approaches in prostate cancer. Summary Although still in the initial phase of precision medicine for prostate cancer, there is extraordinary potential for clinical impact. Efforts to overcome current scientific and clinical barriers will enable widespread use of precision medicine approaches for advanced prostate cancer patients. PMID:26909474

  15. Identification of the transforming STRN-ALK fusion as a potential therapeutic target in the aggressive forms of thyroid cancer

    PubMed Central

    Kelly, Lindsey M.; Barila, Guillermo; Liu, Pengyuan; Evdokimova, Viktoria N.; Trivedi, Sumita; Panebianco, Federica; Gandhi, Manoj; Carty, Sally E.; Hodak, Steven P.; Luo, Jianhua; Dacic, Sanja; Yu, Yan P.; Nikiforova, Marina N.; Ferris, Robert L.; Altschuler, Daniel L.; Nikiforov, Yuri E.

    2014-01-01

    Thyroid cancer is a common endocrine malignancy that encompasses well-differentiated as well as dedifferentiated cancer types. The latter tumors have high mortality and lack effective therapies. Using a paired-end RNA-sequencing approach, we report the discovery of rearrangements involving the anaplastic lymphoma kinase (ALK) gene in thyroid cancer. The most common of these involves a fusion between ALK and the striatin (STRN) gene, which is the result of a complex rearrangement involving the short arm of chromosome 2. STRN-ALK leads to constitutive activation of ALK kinase via dimerization mediated by the coiled-coil domain of STRN and to a kinase-dependent, thyroid-stimulating hormone–independent proliferation of thyroid cells. Moreover, expression of STRN-ALK transforms cells in vitro and induces tumor formation in nude mice. The kinase activity of STRN-ALK and the ALK-induced cell growth can be blocked by the ALK inhibitors crizotinib and TAE684. In addition to well-differentiated papillary cancer, STRN-ALK was found with a higher prevalence in poorly differentiated and anaplastic thyroid cancers, and it did not overlap with other known driver mutations in these tumors. Our data demonstrate that STRN-ALK fusion occurs in a subset of patients with highly aggressive types of thyroid cancer and provide initial evidence suggesting that it may represent a therapeutic target for these patients. PMID:24613930

  16. Novel agents for advanced pancreatic cancer

    PubMed Central

    Akinleye, Akintunde; Iragavarapu, Chaitanya; Furqan, Muhammad; Cang, Shundong; Liu, Delong

    2015-01-01

    Pancreatic cancer is relatively insensitive to conventional chemotherapy. Therefore, novel agents targeting dysregulated pathways (MAPK/ERK, EGFR, TGF-β, HEDGEHOG, NOTCH, IGF, PARP, PI3K/AKT, RAS, and Src) are being explored in clinical trials as monotherapy or in combination with cytotoxic chemotherapy. This review summarizes the most recent advances with the targeted therapies in the treatment of patients with advanced pancreatic cancer. PMID:26369833

  17. Advances in bronchoscopy for lung cancer

    PubMed Central

    Dhillon, Samjot Singh; Dexter, Elisabeth U.

    2012-01-01

    Bronchoscopic techniques have seen significant advances in the last decade. The development and refinement of different types of endobronchial ultrasound and navigation systems have led to improved diagnostic yield and lung cancer staging capabilities. The complication rate of these minimally invasive procedures is extremely low as compared to traditional transthoracic needle biopsy and surgical sampling. These advances augment the safe array of methods utilized in the work up and management algorithms of lung cancer. PMID:23346012

  18. Prostate Cancer Stem Cells: Research Advances

    PubMed Central

    Jaworska, Dagmara; Król, Wojciech; Szliszka, Ewelina

    2015-01-01

    Cancer stem cells have been defined as cells within a tumor that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor. Experimental evidence showed that these highly tumorigenic cells might be responsible for initiation and progression of cancer into invasive and metastatic disease. Eradicating prostate cancer stem cells, the root of the problem, has been considered as a promising target in prostate cancer treatment to improve the prognosis for patients with advanced stages of the disease. PMID:26593898

  19. Combinatorial Antitumor Effect of Rapamycin and β-Elemene in Follicular Thyroid Cancer Cells

    PubMed Central

    Zhou, Jun; He, Li-Li; Ding, Xiao-Fei; Yuan, Qiu-Qi; Zhang, Jian-Xin; Liu, Shuang-Chun; Chen, Guang

    2016-01-01

    Background. mTOR signaling would be a promising target for thyroid cancer therapy. However, in clinical trials, objective response rate with mTOR inhibitor monotherapy in most cancer types was modest. A new focus on development of combinatorial strategies with rapalogs is increasing. Objective. Investigating the combinatorial antitumor effect of rapamycin and β-elemene in follicular thyroid cancer cells. Methods. MTT assay was used to determine the FTC-133 cell proliferation after culturing with rapamycin and/or β-elemene. To analyze their combinatorial effect, immunoblotting was performed to analyze the activation status of AKT. Moreover, β-elemene attenuated rapamycin-induced immunosuppression was tested in mice. Results. Combination of rapamycin and β-elemene exerted significant synergistic antiproliferative effects in FTC-133 cell lines in vitro, based on inhibiting the AKT feedback activation induced by rapamycin. In vivo, the β-elemene could attenuate rapamycin-induced immunosuppression via reversing imbalance of Treg/Th17, with the underlying mechanism needed to be declared. Conclusions. We demonstrate that the novel combination of mTOR inhibitor with β-elemene synergistically attenuates tumor cell growth in follicular thyroid cancer, which requires additional preclinical validation. PMID:27274989

  20. Association of rs6983267 Polymorphism and Thyroid Cancer Susceptibility: A Systematic Review and Meta-Analysis.

    PubMed

    Li, Jingdong; Wang, Xiaofei; Dong, Jiahong

    2016-01-01

    BACKGROUND Recent genome-wide association studies have identified rs6983267 polymorphism as a key locus in the 8q24 region associated with multisite cancers. However, the information on its association with thyroid cancer is inconclusive. The aim of this study was to determine whether this locus is a risk factor for susceptibility to thyroid cancer by conducting a meta-analysis. MATERIAL AND METHODS Relevant studies were identified by searching PubMed and Embase databases. The pooled odds ratio (OR) and corresponding 95% confidence interval (95% CI) were calculated. RESULTS A total of 4 studies including 2825 cases and 9684 controls were enrolled to this meta-analysis. The pooled data showed the G allele of the rs6983267 polymorphism is a risk factor for susceptibility to thyroid cancer (OR=1.08, 95%CI: 1.02-1.16, P=0.01). Significant associations were also found in homozygote comparison (GG vs. TT: OR=1.17, 95%CI: 1.03-1.33, P=0.02) and dominant model (GG+GT vs. TT: OR=1.13, 95%CI: 1.01-1.26, P=0.03). Borderline significant associations in similar directions were found in the recessive model (GG vs. GT+TT: OR=1.10, 95%CI: 0.99-1.22, P=0.07) and heterozygote comparison (GT vs. TT: OR=1.10, 95%CI: 0.99-1.24, P=0.09). CONCLUSIONS Our meta-analysis shows that the rs6983267 G>T polymorphism might be associated with higher risk of thyroid cancer. Further research with larger sample sizes and full investigation of confounding risk factors is needed to confirm or revise our conclusions. PMID:27251952

  1. Association of rs6983267 Polymorphism and Thyroid Cancer Susceptibility: A Systematic Review and Meta-Analysis

    PubMed Central

    Li, Jingdong; Wang, Xiaofei; Dong, Jiahong

    2016-01-01

    Background Recent genome-wide association studies have identified rs6983267 polymorphism as a key locus in the 8q24 region associated with multisite cancers. However, the information on its association with thyroid cancer is inconclusive. The aim of this study was to determine whether this locus is a risk factor for susceptibility to thyroid cancer by conducting a meta-analysis. Material/Methods Relevant studies were identified by searching PubMed and Embase databases. The pooled odds ratio (OR) and corresponding 95% confidence interval (95% CI) were calculated. Results A total of 4 studies including 2825 cases and 9684 controls were enrolled to this meta-analysis. The pooled data showed the G allele of the rs6983267 polymorphism is a risk factor for susceptibility to thyroid cancer (OR=1.08, 95%CI: 1.02–1.16, P=0.01). Significant associations were also found in homozygote comparison (GG vs. TT: OR=1.17, 95%CI: 1.03–1.33, P=0.02) and dominant model (GG+GT vs. TT: OR=1.13, 95%CI: 1.01–1.26, P=0.03). Borderline significant associations in similar directions were found in the recessive model (GG vs. GT+TT: OR=1.10, 95%CI: 0.99–1.22, P=0.07) and heterozygote comparison (GT vs. TT: OR=1.10, 95%CI: 0.99–1.24, P=0.09). Conclusions Our meta-analysis shows that the rs6983267 G>T polymorphism might be associated with higher risk of thyroid cancer. Further research with larger sample sizes and full investigation of confounding risk factors is needed to confirm or revise our conclusions. PMID:27251952

  2. AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY DISEASE STATE CLINICAL REVIEW: THE INCREASING INCIDENCE OF THYROID CANCER

    PubMed Central

    Davies, Louise; Morris, Luc G.T.; Haymart, Megan; Chen, Amy Y.; Goldenberg, David; Morris, John; Ogilvie, Jennifer B.; Terris, David J.; Netterville, James; Wong, Richard J.; Randolph, Gregory

    2016-01-01

    Objective (1) Describe current epidemiology of thyroid cancer in the United States; (2) evaluate hypothesized causes of the increased incidence of thyroid cancer; and (3) suggest next steps in research and clinical action. Methods Analysis of data from Surveillance, Epidemiology and End Results System and the National Center for Vital Statistics. Literature review of published English-language articles through December 31, 2013. Results The incidence of thyroid cancer has tripled over the past 30 years, whereas mortality is stable. The increase is mainly comprised of smaller tumors. These facts together suggest the major reason for the increased incidence is detection of subclinical, nonlethal disease. This has likely occurred through: health care system access, incidental detection on imaging, more frequent biopsy, greater volumes of and extent of surgery, and changes in pathology practices. Because larger-size tumors have increased in incidence also, it is possible that there is a concomitant true rise in thyroid cancer incidence. The only clearly identifiable contributor is radiation exposure, which has likely resulted in a few additional cases annually. The contribution of the following causes to the increasing incidence is unclear: iodine excess or insufficiency, diabetes and obesity, and molecular disruptions. The following mechanisms do not currently have strong evidence to support a link with the development of thyroid cancer: estrogen, dietary nitrate, and autoimmune thyroid disease. Conclusion Research should focus on illuminating which thyroid cancers need treatment. Patients should be advised of the benefits as well as harms that can occur with treatment of incidentally identified, small, asymptomatic thyroid cancers. PMID:26135963

  3. Diversity of mutations in the RET proto-oncogene and its oncogenic mechanism in medullary thyroid cancer.

    PubMed

    Hedayati, Mehdi; Zarif Yeganeh, Marjan; Sheikholeslami, Sara; Afsari, Farinaz

    2016-08-01

    Thyroid cancer is the most common endocrine malignancy and accounts for nearly 1% of all of human cancer. Thyroid cancer has four main histological types: papillary, follicular, medullary, and anaplastic. Papillary, follicular, and anaplastic thyroid carcinomas are derived from follicular thyroid cells, whereas medullary thyroid carcinoma (MTC) originates from the neural crest parafollicular cells or C-cells of the thyroid gland. MTC represents a neuroendocrine tumor and differs considerably from differentiated thyroid carcinoma. MTC is one of the aggressive types of thyroid cancer, which represents 3-10% of all thyroid cancers. It occurs in hereditary (25%) and sporadic (75%) forms. The hereditary form of MTC has an autosomal dominant mode of inheritance. According to the present classification, hereditary MTC is classified as a multiple endocrine neoplasi type 2 A & B (MEN2A & MEN2B) and familial MTC (FMTC). The RET proto-oncogene is located on chromosome 10q11.21. It is composed of 21 exons and encodes a transmembrane receptor tyrosine kinase. RET regulates a complex network of signal transduction pathways during development, survival, proliferation, differentiation, and migration of the enteric nervous system progenitor cells. Gain of function mutations in RET have been well demonstrated in MTC development. Variants of MTC result from different RET mutations, and they have a good genotype-phenotype correlation. Various MTC related mutations have been reported in different exons of the RET gene. We proposed that RET genetic mutations may be different in distinct populations. Therefore, the aim of this study was to find a geographical pattern of RET mutations in different populations. PMID:26678667

  4. A case of synchronous isolated thyroid metastasis from a primary lung cancer presenting as thyroid primary: Diagnostic challenge!

    PubMed Central

    Hulikal, Narendra; Naru, Ramana Reddy; Gangasani, Revanth; Nandyala, Rukmangadha; Pai, Ananth; Meenakshisundaram, Manickavasgam

    2016-01-01

    The thyroid metastasis from any primary is rare, and usually is a late event and presents as a thyroid swelling. Further, the diagnosis of a metastatic lesion in a patient with no antecedent history of any malignancy can be very challenging. Recently, a patient presented to us with a history of diagnostic evaluation suggesting a primary thyroid malignancy with a synchronous lung primary. After surgery for the thyroid swelling, final histopathology revealed a metastatic lesion from a lung primary. Here, we discuss this rare case of isolated synchronous thyroid metastasis from a lung primary and review the relevant literature. PMID:27186001

  5. Response and Acquired Resistance to Everolimus in Anaplastic Thyroid Cancer

    PubMed Central

    Wagle, Nikhil; Grabiner, Brian C.; Van Allen, Eliezer M.; Amin-Mansour, Ali; Taylor-Weiner, Amaro; Rosenberg, Mara; Gray, Nathanael; Barletta, Justine A.; Guo, Yanan; Swanson, Scott J.; Ruan, Daniel T.; Hanna, Glenn J.; Haddad, Robert I.; Getz, Gad; Kwiatkowski, David J.; Carter, Scott L.; Sabatini, David M.; Jänne, Pasi A.; Garraway, Levi A.; Lorch, Jochen H.

    2015-01-01

    SUMMARY Everolimus, an inhibitor of the mammalian target of rapamycin (mTOR), is effective in treating tumors harboring alterations in the mTOR pathway. Mechanisms of resistance to everolimus remain undefined. Resistance developed in a patient with metastatic anaplastic thyroid carcinoma after an extraordinary 18-month response. Whole-exome sequencing of pretreatment and drug-resistant tumors revealed a nonsense mutation in TSC2, a negative regulator of mTOR, suggesting a mechanism for exquisite sensitivity to everolimus. The resistant tumor also harbored a mutation in MTOR that confers resistance to allosteric mTOR inhibition. The mutation remains sensitive to mTOR kinase inhibitors. PMID:25295501

  6. Activated Thyroid Hormone Promotes Differentiation and Chemotherapeutic Sensitization of Colorectal Cancer Stem Cells by Regulating Wnt and BMP4 Signaling.

    PubMed

    Catalano, Veronica; Dentice, Monica; Ambrosio, Raffaele; Luongo, Cristina; Carollo, Rosachiara; Benfante, Antonina; Todaro, Matilde; Stassi, Giorgio; Salvatore, Domenico

    2016-03-01

    Thyroid hormone is a pleiotropic factor that controls many cellular processes in multiple cell types such as cancer stem cells (CSC). Thyroid hormone concentrations in the blood are stable, but the action of the deiodinases (D2-D3) provides cell-specific regulation of thyroid hormone activity. Deregulation of deiodinase function and thyroid hormone status has been implicated in tumorigenesis. Therefore, we investigated the role of thyroid hormone metabolism and signaling in colorectal CSCs (CR-CSC), where deiodinases control cell division and chemosensitivity. We found that increased intracellular thyroid hormone concentration through D3 depletion induced cell differentiation and sharply mitigated tumor formation. Upregulated BMP4 expression and concomitantly attenuated Wnt signaling accompanied these effects. Furthermore, we demonstrate that BMP4 is a direct thyroid hormone target and is involved in a positive autoregulatory feedback loop that modulates thyroid hormone signaling. Collectively, our findings highlight a cell-autonomous metabolic mechanism by which CR-CSCs exploit thyroid hormone signaling to facilitate their self-renewal potential and suggest that drug-induced cell differentiation may represent a promising therapy for preventing CSC expansion and tumor progression. PMID:26676745

  7. Effect of 131I ‘clear residual thyroid tissue’ after surgery on the function of parathyroid gland in differentiated thyroid cancer

    PubMed Central

    ZHAO, ZHI-HUA; LI, FENG-QI; HAN, JIAN-KUI; LI, XIAN-JUN

    2015-01-01

    Thyroid cancer is a common malignant tumor of the endocrine glands. Although surgery is the optimal treatment utilized, the disease is characterized by recurrence and metastasis. The aim of the present study was to determine the effect of iodine-131 (131I) ‘clear residual thyroid tissue’ following surgery on the treatment of differentiated thyroid cancer (DTC) and its effect on the function of the parathyroid gland. A total of 160 patients diagnosed with DTC, who were consecutively admitted to our Hospital between June 2012 and June 2014 and underwent total thyroidectomy or subtotal resection, were included in the present study. After three months, the patients were administered 131I ‘clear residual thyroid tissue’ treatment and underwent a whole body scan after 1 week to determine whether ‘clear residual thyroid tissue’ treatment was successful or not. The treatment was repeated within 3 months if not successful. Of the 160 patients, 24 patients had cancer metastasis (15.0%). The average dose of 131I used for the first time was 6.4+1.2 GBq and the treatment was successful in 66 cases (41.3%). The average treatment time was 2.8±0.6 therapy sessions. The results showed that, prior to and following the first treatment and at the end of the follow up, levels of the parathyroid hormone, serum calcium and phosphorus were compared, and no statistically significant difference (P>0.05) was observed. There were 5 patients with persistent hypothyroidism and 8 patients with transient hypothyroidism. The levels of thyroglobulin were significantly decreased, and the difference was statistically significant (P<0.05). A total of 48 patients (30%) with hypothyroidism were identified. In conclusion, the results have shown that DTC resection and 131I ‘clear residual thyroid tissue’ treatment did not significantly impair the parathyroid function, thereby improving the treatment effect. PMID:26668598

  8. Troglitazone, the peroxisome proliferator-activated receptor-gamma agonist, induces antiproliferation and redifferentiation in human thyroid cancer cell lines.

    PubMed

    Park, Jin-Woo; Zarnegar, Rasa; Kanauchi, Hajime; Wong, Mariwil G; Hyun, William C; Ginzinger, David G; Lobo, Margaret; Cotter, Philip; Duh, Quan-Yang; Clark, Orlo H

    2005-03-01

    Troglitazone is a potent agonist for the peroxisome proliferator-activated receptor-gamma (PPARgamma) that is a ligand-activated transcription factor regulating cell differentiation and growth. PPARgamma may play a role in thyroid carcinogenesis since PAX8-PPARgamma1 chromosomal translocations are commonly found in follicular thyroid cancers. We investigated the antiproliferative and redifferentiation effects of troglitazone in 6 human thyroid cancer cell lines: TPC-1 (papillary), FTC-133, FTC-236, FTC-238 (follicular), XTC-1 (Hürthle cell), and ARO82-1 (anaplastic) cell lines. PPARgamma was expressed variably in these cell lines. FTC-236 and FTC-238 had a rearranged chromosome at 3p25, possibly implicating the involvement of the PPARgamma encoding gene whereas the other cell lines did not. Troglitazone significantly inhibited cell growth by cell cycle arrest and apoptotic cell death. PPARgamma overexpression did not appear to be a prerequisite for a response to treatment with troglitazone. Troglitazone also downregulated surface expression of CD97, a novel dedifferentiation marker, in FTC-133 cells and upregulated sodium iodide symporter (NIS) mRNA in TPC-1 and FTC-133 cells. Our investigations document that human thyroid cancer cell lines commonly express PPARgamma, but chromosomal translocations involving PPARgamma are uncommon. Troglitazone, a PPARgamma agonist, induced antiproliferation and redifferentiation in thyroid cancer cell lines. PPARgamma agonists may therefore be effective therapeutic agents for the treatment of patients with thyroid cancer that fails to respond to traditional treatments. PMID:15785241

  9. Delineating Chromosomal Breakpoints in Radiation-Induced Papillary Thyroid Cancer

    PubMed Central

    Weier, Heinz-Ulrich G.; Ito, Yuko; Kwan, Johnson; Smida, Jan; Weier, Jingly F.; Hieber, Ludwig; Lu, Chun-Mei; Lehmann, Lars; Wang, Mei; Kassabian, Haig J.; Zeng, Hui; O'Brien, Benjamin

    2011-01-01

    Recurrent translocations are well known hallmarks of many human solid tumors and hematological disorders, where patient- and breakpoint-specific information may facilitate prognostication and individualized therapy. In thyroid carcinomas, the proto-oncogenes RET and NTRK1 are often found to be activated through chromosomal rearrangements. However, many sporadic tumors and papillary thyroid carcinomas (PTCs) arising in patients with a history of exposure to elevated levels of ionizing irradiation do not carry these known abnormalities. We developed a rapid scheme to screen tumor cell metaphase spreads and identify candidate genes of tumorigenesis and neoplastic progression for subsequent functional studies. Using a series of overnight fluorescence in situ hybridization (FISH) experiments with pools comprised of bacterial artificial chromosome (BAC) clones, it now becomes possible to rapidly refine breakpoint maps and, within one week, progress from the low resolution Spectral Karyotyping (SKY) maps or Giemsa-banding (G-banding) karyotypes to fully integrated, high resolution physical maps including a list of candiate genes in the critical regions. PMID:22096618

  10. Treatment of distant metastases from follicular cell-derived thyroid cancer.