Imaging oxygenation of human tumours

International Nuclear Information System (INIS)

Padhani, Anwar R.; Krohn, Kenneth A.; Lewis, Jason S.; Alber, Markus

2007-01-01

Tumour hypoxia represents a significant challenge to the curability of human tumours leading to treatment resistance and enhanced tumour progression. Tumour hypoxia can be detected by non-invasive and invasive techniques but the inter-relationships between these remains largely undefined. 18 F-MISO and Cu-ATSM-PET, and BOLD-MRI are the lead contenders for human application based on their non-invasive nature, ease of use and robustness, measurement of hypoxia status, validity, ability to demonstrate heterogeneity and general availability, these techniques are the primary focus of this review. We discuss where developments are required for hypoxia imaging to become clinically useful and explore potential new uses for hypoxia imaging techniques including biological conformal radiotherapy. (orig.)

Molecular mechanisms of thyroid tumorigenesis

International Nuclear Information System (INIS)

Krause, K.; Fuehrer, D.

2008-01-01

Thyroid nodules are the most frequent endocrine disorder and occur in approximately 30% of the German population. Thyroid nodular disease constitutes a very heterogeneous entity. A striking diversity of possible functional and morphological features of a thyroid tumour derived from the same thyroid ancestor cell, is a hallmark of thyroid tumorigenesis and is due to specific genetic alterations. Defects in known candidate genes can be found in up to 70% of differentiated thyroid carcinomas and determine the respective cancer phenotype. Papillary thyroid cancers (PTC) harbour BRAF (or much less frequently RAS) mutations in sporadically occurring tumours, while radiation-induced PTC display chromosomal rearrangements such as RET, TRK, APR9 / BRAF. These genetic events results in constitutive MAPKinase activation. Follicular thyroid cancers (FTC) harbour RAS mutations or PAX8/ PPARγ rearrangements, both of which, however have also been identified in follicular adenoma. In addition, recent studies show, that activation of PI3K/AKT signalling occurs with high frequency in follicular thyroid tumours. Undifferentiated (anaplastic) thyroid cancers (ATC) display genetic features of FTC or PTC, in addition to aberant activation of multiple tyrosinkinase pathways (overexpression or mutations in PI3K and MAPK pathways). This underscores the concept of a sequential evolution of ATC from differentiated thyroid cancer, a process widely conceived to be triggered by p53 inactivation. In contrast, the molecular pathogenesis of benign thyroid tumours, in particular cold thyroid nodules is less known, except for toxic thyroid nodules, which arise from constitutive activation of cAMP signalling, predominantly through TSHR mutations. (orig.)

Cyclin D1 in well differentiated thyroid tumour of uncertain malignant potential.

Science.gov (United States)

Lamba Saini, Monika; Weynand, Birgit; Rahier, Jacques; Mourad, Michel; Hamoir, Marc; Marbaix, Etienne

2015-04-18

Encapsulated follicular tumours with equivocal papillary thyroid carcinoma (PTC) type nuclear features continue to remain a challenge despite the recent attempts to classify these borderline lesions. The term 'well differentiated tumour of uncertain malignant potential (WDT-UMP)' was introduced to classify these tumours. The present study aimed to evaluate the role of a cell cycle regulator like cyclin D1 in these tumours along with assessment of other well established PTC markers like galectin-3, HBME-1, CK19. Thirteen cases of metastatic PTC, papillary microcarcinoma and follicular variant of PTC (FVPTC) were identified from a histological review of 510 cases. In addition, 13 cases of a subset of follicular adenomatoid nodules with focal areas showing nuclear features characteristic of PTC, identified as WDT-UMP, were also analyzed. Immunohistochemical analysis of galectin-3, HBME-1, CK19 and the proliferation markers Ki67 and cyclin D1 was performed. Lesions were analyzed for cyclin D1 gene amplification by fluorescent in-situ hybridization. All WDT-UMP lesions showed immunolabelling of cyclin D1, Ki67; 11/ 13 cases showed immunolabelling of CK19; 10/13 cases showed immunolabelling of HBME-1 and 4/13 cases showed immunolabelling of galectin-3. Surrounding benign adenomatoid areas showed no to faint focal staining in all thirteen cases of cyclin D1, HBME-1 and galectin-3. A low rate of cyclin D1 gene amplification was identified in a significant proportion of cells in the WDT-UMP lesions as compared to surrounding benign adenomatoid areas. Increased expression of cyclin D1 and amplification of its gene along with immunolabelling of HBME-1 in WDT-UMP lesions showing cytological features of papillary thyroid carcinoma within follicular adenomatoid nodules suggest that these areas could correspond to a precursor lesion of follicular variant of PTC. Overexpression of cyclin D1, associated with the amplification of the gene suggests that these WDT-UMP lesions are an

Cytological Diagnosis of an Uncommon High Grade Malignant Thyroid Tumour: A Case Report.

Science.gov (United States)

Nagpal, Ruchi; Kaushal, Manju; Kumar, Sawan

2017-07-01

Anaplastic Thyroid Carcinoma (ATC) is a relatively uncommon highly malignant tumour originating from the follicular cells of thyroid gland having poor prognosis. It accounts for 2% to 5% of all thyroid carcinomas and patients typically present with a rapidly growing anterior neck mass with aggressive symptoms. A 53-year-old male presented with diffuse neck swelling measuring 8x6 cm and right cervical lymph node measuring 2x2 cm since one month which was associated with dyspepsia and dyspnoea. Ultrasound and Contrast Enhanced Computed Tomography (CECT) neck revealed enlarged right lobe of thyroid and multiple enlarged cervical lymph nodes with soft tissue density nodules in bilateral lungs. Fine Needle Aspiration (FNA) from the swelling revealed giant cell, spindle cell and squamoid pattern. Focal areas showed follicular epithelial cells arranged in repeated microfollicular pattern suggesting an underlying follicular neoplasm. FNAC smears from the lymph node also revealed similar findings. Based on the cytomorphological and radiological findings, final diagnosis of ATC probably arising from underlying follicular carcinoma with cervical lymph node and lung metastasis was given. FNAC leads to prompt and definitive diagnosis, so that therapy can be initiated as soon as possible for better outcome. Multimodality therapy (surgery, external beam radiation, and chemotherapy) is the mainstay of treatment.

Thyroid carcinomas of Belarussian children

International Nuclear Information System (INIS)

Bauchinger, M.

1999-01-01

The incidence of thyroid carcinoma increases significantly following exposure to ionizing irradiation. However, the mechanisms of radiation-induced tumorigenesis at the molecular and chromosomal levels have not been identified. In order to gain some indication of the processes affecting the thyroid epithelium, cytogenetic and molecular genetic investigations were performed on childhood thyroid carcinomas that developed after the Chernobyl nuclear accident in Belarussia, and on secondary thyroid tumours that developed after radiotherapy. At the cytogenetic level, the radiation-induced tumours were shown to have an increased frequency of translocations, multiple and complex chromosome aberrations, and novel breakpoints for structural chromosome aberrations. At the molecular level, different alterations of the RET protooncogene were detected in 65% of the Belarussian tumours. (orig.) [de

The Effect of Tamoxifen Administration and γ-Irradiation on Thyroid Hormones Levels in Rats Bearing Mammary Tumours

International Nuclear Information System (INIS)

Abdelgawad, M.R.

2013-01-01

Breast Cancer is the most common malignancy among women in most developed and developing regions of the world, in female, tamoxifen acting as an oestrogen antagonist on the breast. Thyroid hormones can stimulate the proliferation in vitro of certain tumor cell lines. The aim of the present study is to evaluate the effect of tamoxifen and/ or irradiation treatment on thyroid hormones in rats' mammary tumours. Forty-two female Sprague-Dawely rats randomly divided into seven groups' proliferation (6 rats each). Control group, normal rats supplemented with tamoxifen for 3 weeks, normal rats exposed to a single dose 3Gy γ-rays, rats treated with Dimethylbenz (a) anthracene (DMBA) dissolved in corn oil (30ppm) sc and followed for 6 months until breast cancer occurrence, breast cancer bearing rats supplemented with tamoxifen for 3 weeks twice a day, breast cancer bearing rats exposed to a single dose 3Gy γ-rays, breast cancer bearing rats exposed to a single dose 3Gy γ-rays and supplemented with tamoxifen for 3 weeks twice a day. At the end of the experiment, mammary tumours and control rats were sacrificed after 3 weeks from different treatments and serum thyroid hormones and estradiol (E2) levels were assayed using commercial kits. Results show T4 and E2 levels not triiodothyronine (T3) were altered in different experimental groups. It could be concluded that γ-irradiation promote the expression of neoplastic potential by affecting both E2 and thyroid hormones and tamoxifen may alter the thyroid hormones. Tamoxifen administration and γ-irradiation may have worth effects on thyroxin (T4) and E2 levels. It is recommended to further studies towards the bystander effect of γ-rays exposure and tamoxifen treatment on the tissue culture and molecular biology scale.

WOMEN IN CANCER THEMATIC REVIEW: Thyroid-stimulating hormone in thyroid cancer: does it matter?

Science.gov (United States)

Nieto, Hannah; Boelaert, Kristien

2016-11-01

Differentiated thyroid cancer is the most common endocrine malignancy and the incidence is increasing rapidly worldwide. Appropriate diagnosis and post-treatment monitoring of patients with thyroid tumours are critical. Fine needle aspiration cytology remains the gold standard for diagnosing thyroid cancer, and although there have been significant refinements to this technique, diagnostic surgery is often required for patients suspected to have malignancy. Serum thyroid-stimulating hormone (TSH) is higher in patients with malignant thyroid nodules than in those with benign disease, and TSH is proportionally increased in more aggressive tumours. Importantly, we have shown that the pre-operative serum TSH concentration independently predicts the presence of malignancy in subjects presenting with thyroid nodules. Establishing the use of TSH measurements in algorithms identifying high-risk thyroid nodules in routine clinical practice represents an exciting, cost-efficient and non-invasive approach to optimise thyroid cancer diagnosis. Binding of TSH to receptors on thyrocytes stimulates a number of growth promoting pathways both in normal and malignant thyroid cells, and TSH suppression with high doses of levothyroxine is routinely used after thyroidectomy to prevent cancer recurrence, especially in high-risk tumours. This review examines the relationship between serum TSH and thyroid cancer and reflects on the clinical potential of TSH measurements in diagnosis and disease monitoring. © 2016 Society for Endocrinology.

Humanized medium (h7H) allows long-term primary follicular thyroid cultures from human normal thyroid, benign neoplasm, and cancer.

Science.gov (United States)

Bravo, Susana B; Garcia-Rendueles, Maria E R; Garcia-Rendueles, Angela R; Rodrigues, Joana S; Perez-Romero, Sihara; Garcia-Lavandeira, Montserrat; Suarez-Fariña, Maria; Barreiro, Francisco; Czarnocka, Barbara; Senra, Ana; Lareu, Maria V; Rodriguez-Garcia, Javier; Cameselle-Teijeiro, Jose; Alvarez, Clara V

2013-06-01

Mechanisms of thyroid physiology and cancer are principally studied in follicular cell lines. However, human thyroid cancer lines were found to be heavily contaminated by other sources, and only one supposedly normal-thyroid cell line, immortalized with SV40 antigen, is available. In primary culture, human follicular cultures lose their phenotype after passage. We hypothesized that the loss of the thyroid phenotype could be related to culture conditions in which human cells are grown in medium optimized for rodent culture, including hormones with marked differences in its affinity for the relevant rodent/human receptor. The objective of the study was to define conditions that allow the proliferation of primary human follicular thyrocytes for many passages without losing phenotype. Concentrations of hormones, transferrin, iodine, oligoelements, antioxidants, metabolites, and ethanol were adjusted within normal homeostatic human serum ranges. Single cultures were identified by short tandem repeats. Human-rodent interspecies contamination was assessed. We defined an humanized 7 homeostatic additives medium enabling growth of human thyroid cultures for more than 20 passages maintaining thyrocyte phenotype. Thyrocytes proliferated and were grouped as follicle-like structures; expressed Na+/I- symporter, pendrin, cytokeratins, thyroglobulin, and thyroperoxidase showed iodine-uptake and secreted thyroglobulin and free T3. Using these conditions, we generated a bank of thyroid tumors in culture from normal thyroids, Grave's hyperplasias, benign neoplasms (goiter, adenomas), and carcinomas. Using appropriate culture conditions is essential for phenotype maintenance in human thyrocytes. The bank of thyroid tumors in culture generated under humanized humanized 7 homeostatic additives culture conditions will provide a much-needed tool to compare similarly growing cells from normal vs pathological origins and thus to elucidate the molecular basis of thyroid disease.

The role of oestrogen receptor {alpha} in human thyroid cancer: contributions from coregulatory proteins and the tyrosine kinase receptor HER2.

LENUS (Irish Health Repository)

Kavanagh, Dara O

2012-02-01

Epidemiological, clinical, and molecular studies suggest a role for oestrogen in thyroid cancer. How oestrogen mediates its effects and the consequence of it on clinical outcome has not been fully elucidated. The participation of coregulatory proteins in modulating oestrogen receptor (ER) function and input of crosstalk with the tyrosine kinase receptor HER2 was investigated. Oestrogen induced cell proliferation in the follicular thyroid cancer (FTC)-133 cells, but not in the anaplastic 8305C cell line. Knockdown of the coactivator steroid receptor coactivator (SRC)-1 inhibited FTC-133 basal, but not oestrogen induced, cell proliferation. Oestrogen also increased protein expression of SRC-1 and the ER target gene cyclin D1 in the FTC-133 cell line. ERalpha, ERbeta, the coregulatory proteins SRC-1 and nuclear corepressor (NCoR), and the tyrosine kinase receptor HER2 were localised by immunohistochemistry and immnofluorescence in paraffin-embedded tissue from thyroid tumour patients (n=111). ERalpha was colocalised with both SRC-1 and NCoR to the nuclei of the tumour epithelial cells. Expression of ERalpha and NCoR was found predominantly in non-anaplastic tumours and was significantly associated with well-differentiated tumours and reduced incidence of disease recurrence. In non-anaplastic tumours, HER2 was significantly associated with SRC-1, and these proteins were associated with poorly differentiated tumours, capsular invasion and disease recurrence. Totally, 87% of anaplastic tumours were positive for SRC-1. Kaplan-Meier estimates of disease-free survival indicated that in thyroid cancer, SRC-1 strongly correlates with reduced disease-free survival (P<0.001), whereas NCoR predicted increased survival (P<0.001). These data suggest opposing roles for the coregulators SRC-1 and NCoR in thyroid tumour progression.

Ras mutations are rare in solitary cold and toxic thyroid nodules.

Science.gov (United States)

Krohn, K; Reske, A; Ackermann, F; Müller, A; Paschke, R

2001-08-01

Activation of ras proto-oncogenes as a result of point mutations is detectable in a significant percentage of most types of tumour. Similar to neoplasms of other organs, mutations of all three ras genes can be found in thyroid tumours. H-, K- and N-ras mutations have been detected in up to 20% of follicular adenomas and adenomatous nodules which were not functionally characterized. This raises the question as to whether ras mutations are specific for hypofunctional nodules and TSH receptor mutations for hyperfunctioning nodules. To investigate ras and TSH receptor mutations with respect to functional differentiation we studied 41 scintigraphically cold nodules and 47 toxic thyroid nodules. To address the likelihood of a somatic mutation we also studied the clonal origin of these tumours. Genomic DNA was extracted from nodular and surrounding tissue. Mutational hot spots in exons 1 and 2 of the H- and K-ras gene were PCR amplified and sequenced using big dye terminator chemistry. Denaturing gradient gel electrophoresis (DGGE) was used to verify sequencing results for the H-ras gene and to analyse the N-ras gene because its greater sensitivity in detecting somatic mutations. Clonality of nodular thyroid tissue was evaluated using X-Chromosome inactivation based on PCR amplification of the human androgen receptor locus. Monoclonal origin was detectable in 14 of 23 informative samples from cold thyroid nodules. In toxic thyroid nodules the frequency of clonal tissue was 20 in 30 informative cases. Only one point mutation could be found in the N-ras gene codon 61 (Gly to Arg) in a cold adenomatous nodule which was monoclonal. In toxic thyroid nodules no ras mutation was detectable. Our study suggests that ras mutations are rare in solitary cold and toxic thyroid nodules and that the frequent monoclonal origin of these tumours implies somatic mutations in genes other than H-, K- and N-ras.

Molecular mechanisms of thyroid tumorigenesis; Molekulare Mechanismen der Schilddruesentumorgenese

Energy Technology Data Exchange (ETDEWEB)

Krause, K.; Fuehrer, D. [Universitaetsklinikum Leipzig (Germany). Abt. fuer Endokrinolgoie, Diabetologie und Nephrologie

2008-09-15

Thyroid nodules are the most frequent endocrine disorder and occur in approximately 30% of the German population. Thyroid nodular disease constitutes a very heterogeneous entity. A striking diversity of possible functional and morphological features of a thyroid tumour derived from the same thyroid ancestor cell, is a hallmark of thyroid tumorigenesis and is due to specific genetic alterations. Defects in known candidate genes can be found in up to 70% of differentiated thyroid carcinomas and determine the respective cancer phenotype. Papillary thyroid cancers (PTC) harbour BRAF (or much less frequently RAS) mutations in sporadically occurring tumours, while radiation-induced PTC display chromosomal rearrangements such as RET, TRK, APR9 / BRAF. These genetic events results in constitutive MAPKinase activation. Follicular thyroid cancers (FTC) harbour RAS mutations or PAX8/ PPAR{gamma} rearrangements, both of which, however have also been identified in follicular adenoma. In addition, recent studies show, that activation of PI3K/AKT signalling occurs with high frequency in follicular thyroid tumours. Undifferentiated (anaplastic) thyroid cancers (ATC) display genetic features of FTC or PTC, in addition to aberant activation of multiple tyrosinkinase pathways (overexpression or mutations in PI3K and MAPK pathways). This underscores the concept of a sequential evolution of ATC from differentiated thyroid cancer, a process widely conceived to be triggered by p53 inactivation. In contrast, the molecular pathogenesis of benign thyroid tumours, in particular cold thyroid nodules is less known, except for toxic thyroid nodules, which arise from constitutive activation of cAMP signalling, predominantly through TSHR mutations. (orig.)

Multiparametric PET imaging in thyroid malignancy characterizing tumour heterogeneity: somatostatin receptors and glucose metabolism

Energy Technology Data Exchange (ETDEWEB)

Traub-Weidinger, Tatjana [Medical University of Vienna, Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Medical University of Innsbruck, Department of Nuclear Medicine, Innsbruck (Austria); Putzer, Daniel; Bale, Reto [Medical University of Innsbruck, Department of Radiology, Innsbruck (Austria); Guggenberg, Elisabeth von; Dobrozemsky, Georg; Nilica, Bernhard; Kendler, Dorota; Virgolini, Irene Johanna [Medical University of Innsbruck, Department of Nuclear Medicine, Innsbruck (Austria)

2015-12-15

Radiolabelled somatostatin (SST) analogues have proven useful in diagnosing tumours positive for SST receptor (SSTR). As different subtypes of SSTR are expressed on the tumour cell surface, the choice of appropriate therapeutic SST analogue is crucial. We evaluated the SSTR status of thyroid cancer patients who had signs of progressive disease comparing different SSTR ligands for PET imaging to evaluate possible further therapeutic options. PET with {sup 68}Ga-radiolabelled SSTR ligands DOTA lanreotide (DOTA-LAN), DOTA-Tyr{sup 3} octreotide (DOTA-TOC) and {sup 18}F-FDG was performed in 31 patients with thyroid cancer (TC). These 31 patients comprised 18 with radioiodine non-avid differentiated TC (DTC) including 6 papillary TC (PTC), 8 follicular TC (FTC) and 4 oxyphilic TC (oxyTC), 5 with anaplastic TC (ATC), and 8 with medullary TC (MTC). The PET results were compared in a region-based evaluation. All patients underwent a PET study with {sup 68}Ga-DOTA-LAN, 28 patients with {sup 68}Ga-DOTA-TOC and 28 patients with {sup 18}F-FDG. A lack of SSTR expression was found in 13 of the 31 patients (42 %) with negative results with both SSTR tracers in 12 patients. Ambiguous results with both SSTR tracers were observed in one patient. High tracer uptake in SSTR PET images was seen in seven DTC patients (39 %; two PTC, three FTC, two oxyTC), in four ATC patients (80 %) and in six MTC patients (75 %). Lesions showing aerobic glycolysis on {sup 18}F-FDG PET were found in 24 of 28 patients (86 %) with corresponding positive results with {sup 68}Ga-DOTA-LAN in 35 % and with {sup 68}Ga-DOTA-TOC in 29 %. The heterogeneous SSTR profile of TC tumour lesions needs to be evaluated using different SSTR PET tracers to characterize more closely the SSTR subtype affinities in patients with progressive TC in order to further stratify therapy with SSTR therapeutics. (orig.)

MIBI-SPECT in hypofunctioning thyroid nodules for detection of thyroid carcinoma; MIBI-SPECT bei kalten Knoten zur Schilddruesenkarzinomdetektion

Energy Technology Data Exchange (ETDEWEB)

Schmidt, M.; Schicha, H. [Universitaetsklinikum Koeln (Germany). Klinik und Poliklinik fuer Nuklearmedizin

2010-12-15

The clinical usefulness of Tc-99m-MIBI in hypofunctioning thyroid nodules for detection of thyroid carcinoma is presented. Tc-99m-MIBI is a lipophilic cation and a non-specific radiopharmaceutical for tumour imaging. It has become an important imaging technique for the assessment of hypofunctioning thyroid nodules because of its high negative predictive value excluding malignant thyroid tumours. After injection of Tc-99m-MIBI either a single-phase protocol with late planar and SPECT images about 1-2 h post injection or a double-phase protocol with early (about 15-30 min p.i.) and late images (about 2 h p.i.) were reported. Findings include a reduced, an isointense or an increased Tc-99m-MIBI accumulation in the thyroid nodule in comparison to the paranodular thyroid tissue and in comparison to pertechnetate thyroid scintigraphy. A 'Match' between pertechnetate and Tc-99m-MIBI scintigraphy is a concordantly decreased uptake in the thyroid nodule in comparison to the normal thyroid gland. This finding has a negative predictive value of >97% to exclude differentiated thyroid cancer. A definite 'Mismatch' means a cold thyroid nodule on pertechnetate scintigraphy and an increased uptake of Tc-99m-MIBI in comparison to the MIBI-uptake of the paranodular thyroid tissue. The positive predictive value of this finding for malignancy varies between studies and is in the range of <10-65% (Cologne data: 19%) depending on the prevalence of malignant thyroid tumours in the patient population studied. An isointense uptake was not associated with thyroid malignancy according to 'Cologne' data. Further studies are desirable for better characterization of the method. (orig.)

Molecular pathology and thyroid FNA.

Science.gov (United States)

Poller, D N; Glaysher, S

2017-12-01

This review summarises molecular pathological techniques applicable to thyroid FNA. The molecular pathology of thyroid tumours is now fairly well understood. Molecular methods may be used as a rule-in test for diagnosis of malignancy in thyroid nodules, eg BRAF V600E point mutation, use of a seven-gene mutational panel (BRAF V600E, RAS genes, RET/PTC or PAX8/PPARG rearrangement), or as a comprehensive multigene next-generation sequencing panel, eg ThyroSeq v2. Molecular methods can also be applied as rule-out tests for malignancy in thyroid nodules, eg Afirma or ThyroSeq v2 or as markers of prognosis, eg TERT promoter mutation or other gene mutations including BRAF V600E, TP53 and AKT1, and as tests for newly defined tumour entities such as non-invasive follicular thyroid neoplasm with papillary like nuclei, or as a molecular marker(s) for targeted therapies. This review describes practical examples of molecular techniques as applied to thyroid FNA in routine clinical practice and the value of molecular diagnostics in thyroid FNA. It describes the range of molecular abnormalities identified in thyroid nodules and thyroid cancers with some practical applications of molecular methods to diagnosis and prognosis of thyroid nodules and thyroid cancer. © 2017 John Wiley & Sons Ltd.

Somatostatin receptor scintigraphy on thyroid carcinoma

International Nuclear Information System (INIS)

Pan Weimin; Tan Tianzhi

2004-01-01

Purpose: To study the diagnostic value and clinical method of somatostatin receptor scintigraphy on thyroid carcinoma using 99 Tc m -RC-160 labeled with direct method as scintigraphy reagent; Methods: Somatostatin receptor scintigraphy (SRS) were performed on 25 patients with thyroid carcinoma, using 99 Tc m -RC-160 labeled with direct method as scintigraphy reagent, controlling with 131 I- whole- body- imaging(1312 -WBI). Results: Of 4 patients with MTC (medullary thyroid carcinoma), positive metastasis and primary tumour were detected on 3 patients by SRS, negative results were obtained by 131 I-WBI, the positive detective rate by SRS is 3/4; of 12 patients with PTC (papillary thyroid carcinoma), positive metastasis and primary tumour were detected on 2 patients by SRS or 131 I-WBI,1 of which only by SRS, while negative results were obtained by 131 I- WBI, the positive detective rate by SRS is 3/12; of 8 patients with FTC(follicular thyroid carcinoma), positive metastasis and primary tumour were detected on 1 patients by SRS or 131 I-WBI, and 2 positive results were obtained only by SRS, while negative by 131 I-WBI, the positive detective rate by SRS is 3/8; of 1 patients with HCC (hurthle cell carcinoma ), positive metastasis and primary tumour were detected by SRS, while negative by 131 I-WBI; Conclusions: SRS using 99 Tc m -RC-160 labeled with direct method as scintigraphy reagent has high diagnostic value on thyroid carcinoma, especially on MTC and HCC. (authors)

Metastatic behaviour of primary human tumours in a zebrafish xenotransplantation model

International Nuclear Information System (INIS)

Marques, Ines J; Bagowski, Christoph P; Weiss, Frank Ulrich; Vlecken, Danielle H; Nitsche, Claudia; Bakkers, Jeroen; Lagendijk, Anne K; Partecke, Lars Ivo; Heidecke, Claus-Dieter; Lerch, Markus M

2009-01-01

Aberrant regulation of cell migration drives progression of many diseases, including cancer cell invasion and metastasis formation. Analysis of tumour invasion and metastasis in living organisms to date is cumbersome and involves difficult and time consuming investigative techniques. For primary human tumours we establish here a simple, fast, sensitive and cost-effective in vivo model to analyse tumour invasion and metastatic behaviour. We fluorescently labelled small explants from gastrointestinal human tumours and investigated their metastatic behaviour after transplantation into zebrafish embryos and larvae. The transparency of the zebrafish embryos allows to follow invasion, migration and micrometastasis formation in real-time. High resolution imaging was achieved through laser scanning confocal microscopy of live zebrafish. In the transparent zebrafish embryos invasion, circulation of tumour cells in blood vessels, migration and micrometastasis formation can be followed in real-time. Xenografts of primary human tumours showed invasiveness and micrometastasis formation within 24 hours after transplantation, which was absent when non-tumour tissue was implanted. Furthermore, primary human tumour cells, when organotopically implanted in the zebrafish liver, demonstrated invasiveness and metastatic behaviour, whereas primary control cells remained in the liver. Pancreatic tumour cells showed no metastatic behaviour when injected into cloche mutant embryos, which lack a functional vasculature. Our results show that the zebrafish is a useful in vivo animal model for rapid analysis of invasion and metastatic behaviour of primary human tumour specimen

Computed tomography, conventional X-ray examination, scintigraphy and tumour markers in thyroid carcinomas and suspected metastisation into the thoracic region

International Nuclear Information System (INIS)

Heintz, P.

1986-01-01

In 43 patients suffering from differentiated carcinomas of thyroid, who had previously been subjected to thyroidectomy and curative radioiodine treatment, CT scans of the thorax were used in addition to the usual X-ray examinations in order to exclude the formation of pulmonary metastases. Separate analyses of 45 records on the basis of the stage of the tumour when it was diagnosed and the behaviour of tumour marker hTg under suppression with L-thyroxin and endogenous stimulation during the follow-up permitted patient groups to be defined that are most at risk of metastisation. The results of the three methods of medical imaging were compared to those obtained using tumour marker hTg. The rate of findings revealed by CT, scintigraphy and X-ray examination was calculated with reference to the total number of results suggesting pulmonary metastisation and amounted to 89%, 48% and 44%, respectively. (orig./MG) [de

Less aggressive disease in patients with primary squamous cell carcinomas of the thyroid gland and coexisting lymphocytic thyroiditis.

Science.gov (United States)

Asik, Mehmet; Binnetoglu, Emine; Sen, Hacer; Gunes, Fahri; Muratli, Asli; Kankaya, Duygu; Uysal, Fatma; Sahin, Mustafa; Ukinc, Kubilay

2015-01-01

Primary squamous cell carcinoma (SCC) of the thyroid gland is extremely rare. Infrequently, primary SCC of the thyroid gland is accompanied by other thyroid diseases such as Hashimoto's thyroiditis (HT). Recently, studies have demonstrated that differentiated thyroid cancer with coexisting HT has a better prognosis. However, the prognosis of patients with primary SCC of the thyroid gland and coexistent HT has not been clearly identified. We compared the clinical characteristics and disease stages of patients with primary SCC with and without lymphocytic thyroiditis (LT). We reviewed reports of primary SCC of the thyroid gland published in the English literature. We identified 46 papers that included 17 cases of primary SCC of the thyroid gland with LT and 77 cases of primary SCC of the thyroid gland without LT. Lymph node metastasis and local invasion rates did not differ between these two groups. Distant metastases were absent in patients with LT, and were observed in 13 (16.9%) patients without LT. A greater proportion of patients without LT had advanced stage disease (stage IV A-B-C) than patients with LT (p thyroid gland and coexisting LT had lower tumour-node-metastasis stage and frequency of distant metastasis than those without LT. Lymphocytic infiltration in patients with SCC appears to limit tumour growth and distant metastases.

Deposition in the human thyroid gland

International Nuclear Information System (INIS)

Tanaka, Giichiro

1979-01-01

Deposition of radioiodine in the thyroid gland of the Japanese has been described, especially on the following aspects of metabolic and radiological importance. 1) The measurements of radioiodine, essentially 131 I, in milk, thyroid glands of humans and cattles, and human urine are presented which were obtained at times following major Chinese nuclear tests. Highest observed 131 I concentration in cattle milk was 437 pCi per liter, and the transfer of 131 I in the environment to the thyroid gland was demonstrated. 2) Thyroidal uptake rate of radioiodine in the Japanese was estimated to be in a range 0.15 - 0.20 for f sub(w), lower than the reference value of 0.30 for the European and North Americans. The effect of stable isotope intake in the Japanese diet, estimated as 1.5 - 2.0 mg per day, which is one order of magnitude higher than the level in the latter populations, 0.2 mg per day, is demonstrated. This is based on uptake study data, obtained by the author et al. and also reported in the field of nuclear medicine. 3) Mass and dimensions of the thyroid gland in the Japanese male and female are described as a function of age and total body weight. The data reasonably assumed to be valid as reference values for the Japanese as of 1980s. 4) In vivo measurement of radioiodine in the human thyroid gland in case of any unplanned or accidental release of gaseous radionuclides from nuclear facilities is described using a Ge(Li) gamma spectrometry and also a scintillation surveymeter. The high-resolution gamma energy spectroscopy does not seem to be employed before for the present purpose. (author)

The mechanism of 67Ga uptake in animal and human tumours

International Nuclear Information System (INIS)

Hammersley, P.A.G.; Cronshaw, S.; Taylor, D.M.; Kernforschungszentrum Karlsruhe G.m.b.H.

1980-01-01

The subcellular distribution of 67 Ga has been studied by differential centrifugation in 3 transplantable mouse tumours, 3 transplantable rat tumours, 1 dog tumour, 3 human tumour xenografts and 2 human tumours in situ at various times after injection of the citrate complex. From 24 h post injection the nuclide was located predominantly in lysosomal structures in all the tumours studied. Studies in two murine tumours showed marked differences in the rate of lysosomal accumulation of 67 Ga. In the ADJ/PC6 plasmacytoma lysosomal uptake of 67 Ga had reached a plateau within 15 min while in the S180 tumour lysosomal accumulation of the nuclide occurred over the first 24 h. Normal mouse liver showed a similar pattern to this latter tumour. It is postulated that these variations in the rate of lysosomal accumulation of 67 Ga reflect differences in the permeability of the lysosomal membrane. While large amounts of 67 Ga were found in the crude nuclear fraction of some tumours this was attributed to unbroken cells as studies with purified nuclei from 7 different tumours indicated that between 2 and 14% of the total tumour 67 Ga was associated with the nuclei. (orig.)

The measurement of intrinsic cellular radiosensitivity in human tumours and normal tissues

International Nuclear Information System (INIS)

Lawton, P.A.

1995-01-01

Human tumour and normal cell radiosensitivity are thought to be important factors determining the response of tumour and normal tissues to radiotherapy, respectively. Clonogenic assays are the standard method for measuring radiosensitivity but they are of limited applicability for clinical use with fresh human tumours. The main aim of this work was to evaluate the Adhesive Tumour Cell Culture System (ATCCS), as a method for measuring the radiosensitivity of human tumours. A soft agar clonogenic assay, the modified Courtenay-Mills assay, was used as a standard to compare with the ATCCS. The demonstration that fibroblast contamination could occur with both assay methods led to the investigation of a new technique for removing unwanted fibroblasts from tumour cell suspensions and to the use of a multiwell assay for measuring fibroblast radiosensitivity. (author)

The measurement of intrinsic cellular radiosensitivity in human tumours and normal tissues

Energy Technology Data Exchange (ETDEWEB)

Lawton, P.A.

1995-12-31

Human tumour and normal cell radiosensitivity are thought to be important factors determining the response of tumour and normal tissues to radiotherapy, respectively. Clonogenic assays are the standard method for measuring radiosensitivity but they are of limited applicability for clinical use with fresh human tumours. The main aim of this work was to evaluate the Adhesive Tumour Cell Culture System (ATCCS), as a method for measuring the radiosensitivity of human tumours. A soft agar clonogenic assay, the modified Courtenay-Mills assay, was used as a standard to compare with the ATCCS. The demonstration that fibroblast contamination could occur with both assay methods led to the investigation of a new technique for removing unwanted fibroblasts from tumour cell suspensions and to the use of a multiwell assay for measuring fibroblast radiosensitivity. (author).

Vitamin D in thyroid tumorigenesis and development.

Science.gov (United States)

Clinckspoor, Isabelle; Verlinden, Lieve; Mathieu, Chantal; Bouillon, Roger; Verstuyf, Annemieke; Decallonne, Brigitte

2013-08-01

Besides its classical role in bone and calcium homeostasis, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), the active form of vitamin D, has many non-classical effects; antiproliferative, anti-apoptotic and prodifferentiating effects of 1,25(OH)2D3 have been described in several tumour types in preclinical models. This review focuses on the insights gained in the elucidation of the role of 1,25(OH)2D3 in the normal thyroid and in the pathogenesis, progression and treatment of thyroid cancer, the most common endocrine malignancy. An increasing amount of observations points towards a role for impaired 1,25(OH)2D3-VDR signalling in the occurrence and progression of thyroid cancer, and a potential for structural analogues in the multimodal treatment of dedifferentiated iodine-resistant thyroid cancer. A role for vitamin D in thyroid-related autoimmunity is less convincing and needs further study. Altered 1,25(OH)2D3-VDR signalling does not influence normal thyroid development nor thyrocyte function, but does affect C-cell function, at least in rodents. If these findings also apply to humans deserves further study. Copyright © 2013 Elsevier GmbH. All rights reserved.

Tumour reduction with a Cavitron Ultrasonic Surgical Aspirator® in ...

African Journals Online (AJOL)

of a scarf made the patient appear natural and presentable. Figure 1: The fungating tumour before tumour reduction with a Cavitron Ultrasonic Surgical Aspirator®. Tumour reduction with a Cavitron Ultrasonic. Surgical Aspirator® in the palliative care of anaplastic thyroid cancer. CASE REPORT. JHR Becker,1,2 F Ghoor1,2.

Demonstration of vascular endothelium in thyroid carcinomas using Ulex europaeus I agglutinin.

Science.gov (United States)

González-Cámpora, R; Montero, C; Martin-Lacave, I; Galera, H

1986-03-01

The usefulness of using peroxidase-labelled Ulex europaeus agglutinin I for the staining of small vessels and capillaries in the capsule of thyroid tumours is demonstrated. With this procedure the scanning for small tumour deposits in those vessels and, consequently, the diagnosis of follicular carcinoma of the thyroid is facilitated.

Statins as a new therapeutic approach in dedifferentiated thyroid cancer?

International Nuclear Information System (INIS)

Hofmann, A.; John, P.; Sinzinger, H.; Staudenherz, A.; Schaffarich, M.P.

2006-01-01

Generally, primary differentiated tumours are removed surgically followed by adjuvant radioiodine treatment. The effect and outcome of radioiodine ablation depends on the uptake in the thyroid carcinoma cells. But, about one third of patients with local recurrent thyroid carcinomas or distant metastases do not respond to iodine treatment due to loss of differentiation. Prognosis was impaired if tumour cells are losing the capability for radioiodine uptake due to dedifferentiation. However, several trials have been attempted to induce re-differentiation of tumour cells in order to regain their potential for radioiodine uptake. (orig.)

A comparative study between mixed-type tumours from human salivary and canine mammary glands

International Nuclear Information System (INIS)

Genelhu, Marisa CLS; Cardoso, Sérgio V; Gobbi, Helenice; Cassali, Geovanni D

2007-01-01

In comparative pathology, canine mammary tumours have special interest because of their similarities with human breast cancer. Mixed tumours are uncommon lesions in the human breast, but they are found most frequently in the mammary gland of the female dogs and in the human salivary glands. The aim of the study was to compare clinical, morphological and immunohistochemical features of human salivary and canine mammary gland mixed tumours, in order to evaluate the latter as an experimental model for salivary gland tumours. Ten examples of each mixed tumour type (human pleomorphic adenoma and carcinomas ex-pleomorphic adenomas and canine mixed tumour and metaplastic carcinoma) were evaluated. First, clinical and morphologic aspects of benign and malignant variants were compared between the species. Then, streptavidin-biotin-peroxidase immunohistochemistry was performed to detect the expression of cytokeratins, vimentin, p63 protein, estrogen receptor, β-catenin, and E-cadherin. After standardization, similar age and site distributions were observed in human and canine tumours. Histological similarities were identified in the comparison of the benign lesions as well. Metaplastic carcinomas also resembled general aspects of carcinomas ex-pleomorphic adenomas in morphological evaluation. Additionally, immunohistochemical staining further presented similar antigenic expression between lesions. There are many similar features between human salivary and canine mammary gland mixed tumours. This observation is of great relevance for those interested in the study and management of salivary gland tumours, since canine lesions may constitute useful comparative models for their investigations

Intracapillary HbO2 saturations in murine tumours and human tumour xenografts measured by cryospectrophotometry: relationship to tumour volume, tumour pH and fraction of radiobiologically hypoxic cells.

Science.gov (United States)

Rofstad, E K; Fenton, B M; Sutherland, R M

1988-05-01

Frequency distributions for intracapillary HbO2 saturation were determined for two murine tumour lines (KHT, RIF-1) and two human ovarian carcinoma xenograft lines (MLS, OWI) using a cryospectrophotometric method. The aim was to search for possible relationships between HbO2 saturation status and tumour volume, tumour pH and fraction of radiobiologically hypoxic cells. Tumour pH was measured by 31P NMR spectroscopy. Hypoxic fractions were determined from cell survival curves for tumours irradiated in vivo and assayed in vitro. Tumours in the volume range 100-4000 mm3 were studied and the majority of the vessels were found to have HbO2 saturations below 10%. The volume-dependence of the HbO2 frequency distributions differed significantly among the four tumour lines; HbO2 saturation status decreased with increasing tumour volume for the KHT, RIF-1 and MLS lines and was independent of tumour volume for the OWI line. The data indicated that the rate of decrease in HbO2 saturation status during tumour growth was related to the rate of development of necrosis. The volume-dependence of tumour pH was very similar to that of the HbO2 saturation status for all tumour lines. Significant correlations were therefore found between HbO2 saturation status and tumour pH, both within tumour lines and across the four tumour lines, reflecting that the volume-dependence of both parameters probably was a compulsory consequence of reduced oxygen supply conditions during tumour growth. Hypoxic fraction increased during tumour growth for the KHT, RIF-1 and MLS lines and was volume-independent for the OWI line, suggesting a relationship between HbO2 saturation status and hypoxic fraction within tumour lines. However, there was no correlation between these two parameters across the four tumour lines, indicating that the hypoxic fraction of a tumour is not determined only by the oxygen supply conditions; other parameters may also be important, e.g. oxygen diffusivity, rate of oxygen

Hashimoto's thyroiditis predicts outcome in intrathyroidal papillary thyroid cancer.

Science.gov (United States)

Marotta, Vincenzo; Sciammarella, Concetta; Chiofalo, Maria Grazia; Gambardella, Claudio; Bellevicine, Claudio; Grasso, Marica; Conzo, Giovanni; Docimo, Giovanni; Botti, Gerardo; Losito, Simona; Troncone, Giancarlo; De Palma, Maurizio; Giacomelli, Laura; Pezzullo, Luciano; Colao, Annamaria; Faggiano, Antongiulio

2017-09-01

Hashimoto's thyroiditis (HT) seems to have favourable prognostic impact on papillary thyroid cancer (PTC), but data were obtained analysing all disease stages. Given that HT-related microenvironment involves solely the thyroid, we aimed to assess the relationship between HT, as detected through pathological assessment, and outcome in intrathyroidal PTC. This was a multicentre, retrospective, observational study including 301 PTC with no evidence of extrathyroidal disease. Primary study endpoint was the rate of clinical remission. Auxiliary endpoint was recurrence-free survival (RFS). HT was detected in 42.5% of the cohort and was associated to female gender, smaller tumour size, lower rate of aggressive PTC variants and less frequent post-surgery radio-iodine administration. HT showed relationship with significantly higher rate of clinical remission ( P  < 0.001, OR 4, 95% CI 1.78-8.94). PTCs with concomitant HT had significantly longer RFS, as compared with non-HT tumours ( P  = 0.004). After adjustment for other parameters affecting disease outcome at univariate analysis (age at diagnosis, histology, tumour size and multifocality), prognostic effect of HT remained significant ( P  = 0.006, OR 3.28, 95% CI 1.39-7.72). To verify whether HT could optimise the identification of PTCs with unfavourable outcome, we assessed the accuracy of 'non-HT status' as negative prognostic marker, demonstrating poor capability of identifying patients not maintaining clinical remission until final follow-up (probability of no clinical remission in PTCs without HT: 21.05%, 95% CI 15.20-27.93). In conclusion, our data show that HT represents an independent prognostic parameter in intrathyroidal PTC, but cannot improve prognostic specificity. © 2017 Society for Endocrinology.

Adaptation to statins restricts human tumour growth in Nude mice

International Nuclear Information System (INIS)

Follet, Julie; Rémy, Lionel; Hesry, Vincent; Simon, Brigitte; Gillet, Danièle; Auvray, Pierrick; Corcos, Laurent; Le Jossic-Corcos, Catherine

2011-01-01

Statins have long been used as anti-hypercholesterolemia drugs, but numerous lines of evidence suggest that they may also bear anti-tumour potential. We have recently demonstrated that it was possible to isolate cancer cells adapted to growth in the continuous presence of lovastatin. These cells grew more slowly than the statin-sensitive cells of origin. In the present study, we compared the ability of both statin-sensitive and statin-resistant cells to give rise to tumours in Nude mice. HGT-1 human gastric cancer cells and L50 statin-resistant derivatives were injected subcutaneously into Nude mice and tumour growth was recorded. At the end of the experiment, tumours were recovered and marker proteins were analyzed by western blotting, RT-PCR and immunohistochemistry. L50 tumours grew more slowly, showed a strong decrease in cyclin B1, over-expressed collagen IV, and had reduced laminin 332, VEGF and CD34 levels, which, collectively, may have restricted cell division, cell adhesion and neoangiogenesis. Taken together, these results showed that statin-resistant cells developed into smaller tumours than statin-sensitive cells. This may be reflective of the cancer restricting activity of statins in humans, as suggested from several retrospective studies with subjects undergoing statin therapy for several years

Natural Radium-226 accumulation in the human thyroid gland

International Nuclear Information System (INIS)

Simon, Steven L.; Ibrahim, Shawki A.; Barden, Adam O.; VanMiddlesworth, Lester

2008-01-01

Full text: Small amounts of Ra-226 and other radium isotopes routinely enter the human body through normal dietary intake and, in some cases, through occupational exposure. Currently accepted biokinetic models for radium in the human body assume a uniform distribution among all soft tissues and a short retention time in those tissues. These assumptions persist despite publications in the mid-1980s indicating that radium concentrations in tissue are related to calcium levels in each organ, implying that the thyroid gland could accumulate greater concentrations of radium isotopes than any other tissue. Moreover, the natural intake or production of sulfate or barium compounds in the body could serve to precipitate radium in the thyroid gland, thereby immobilizing it, with the result that the radionuclide stays resident for many years. Evidence of both accumulation and immobilization of Ra-226 in thyroids of grazing animals has been documented since the 1960s by one of us (LVM). Little is known, however, about the concentration and retention of radium in the human thyroid. Reported here, for the first time, are Ra-226 measurement data from about 100 human thyroids collected from over 95 persons with no known occupational exposure to radium with lifetime residences in the US and other countries, one person who routinely ingested a homeopathic preparation containing Ra-226, and three uranium miners. Sensitive measurements were made using the radon emanation technique. Regardless of the origin of the thyroid sample, Ra-226 activity was almost always detected above the detection limit of 0.65 mBq when at least 10 g of thyroid tissue were available. Our analyses to-date suggests a background concentration in human thyroids of about 0.1 ±0.01 Bq/kg, considerably greater than the commonly reported literature value of 0.003 Bq/kg in soft tissues. In addition, our measurements indicate concentrations of Ra-226 in the three uranium miners (whose exact job description was

Assessment of absorbed dose to thyroid, parotid and ovaries in patients undergoing Gamma Knife radiosurgery

International Nuclear Information System (INIS)

Hasanzadeh, H; Sharafi, A; Verdi, M Allah; Nikoofar, A

2006-01-01

Stereotactic radiosurgery was originally introduced by Lars Leksell in 1951. This treatment refers to the noninvasive destruction of an intracranial target localized stereotactically. The purpose of this study was to identify the dose delivered to the parotid, ovaries, testis and thyroid glands during the Gamma Knife radiosurgery procedure. A three-dimensional, anthropomorphic phantom was developed using natural human bone, paraffin and sodium chloride as the equivalent tissue. The phantom consisted of a thorax, head and neck and hip. In the natural places of the thyroid, parotid (bilateral sides) and ovaries (midline), some cavities were made to place TLDs. Three TLDs were inserted in a batch with 1 cm space between the TLDs and each batch was inserted into a single cavity. The final depth of TLDs was 3 cm from the surface for parotid and thyroid and was 15 cm for the ovaries. Similar batches were placed superficially on the phantom. The phantom was gamma irradiated using a Leksell model C Gamma Knife unit. Subsequently, the same batches were placed superficially over the thyroid, parotid, testis and ovaries in 30 patients (15 men and 15 women) who were undergoing radiosurgery treatment for brain tumours. The mean dosage for treating these patients was 14.48 ± 3.06 Gy (10.5-24 Gy) to a mean tumour volume of 12.30 ± 9.66 cc (0.27-42.4 cc) in the 50% isodose curve. There was no significant difference between the superficial and deep batches in the phantom studies (P-value < 0.05). The mean delivered doses to the parotid, thyroid, ovaries and testis in human subjects were 21.6 ± 15.1 cGy, 9.15 ± 3.89 cGy, 0.47 ± 0.3 cGy and 0.53 ± 0.31 cGy, respectively. The data can be used in making decisions for special clinical situations such as treating pregnant patients or young patients with benign lesions who need radiosurgery for eradication of brain tumours

BCNT studies for application to the undifferentiated thyroid carcinoma

International Nuclear Information System (INIS)

Dagrosa, Maria A.; Viaggi, Mabel E.; Cabrini, Romulo L.; Juvenal, Guillermo J.; Pisarev, Mario A.; Garavaglia, Ricardo N.; Farias, Silvia S.; Belli, Carolina; Larripa, Irene; Gangitano, David

2000-01-01

Undifferentiated thyroid carcinoma (UTC) lacks an effective treatment. Boron neutron capture therapy (BNCT) is based on the selective uptake of 10 B-boronated compounds by some tumours, followed by irradiation with an appropriate neutron beam. The radioactive boron originated ( 11 B) decays releasing 7 Li, gamma rays and alpha particles, and these latter will destroy the tumour. In order to explore the possibility of applying BNCT to UTC we have studied the biodistribution of BPA. Animal Model: To develop an animal model of undifferentiated thyroid carcinoma (UTC), which may be useful to study of BNCT. The UTC human cell line ARO was implanted into the back of the nude mice. We performed successive passages in mouse after tumor culturing in order to obtain an animal model similar to the human tumor. We studied the kinetics and the tumoral histology, the capability to induce metastasis, the biokinetics of in vitro growth, as well as cytogenetic and molecular aspects. Histological specimens of tumor showed extensive viability with high mitotic activity. At 117 days, the tumors reached a size of 1700 mm 3 and showed a central necrotic portion with a thin layer of viable cells presence of micro metastasis could be observed in the lung. The kinetics of growth both in vivo and in vitro showed that when the number of passages in mouse increases the growth rate decreases. The cytogenetic and molecular studies did not show differences between the original line and the sublines that could explain this phenotypic change. Moreover, the cytogenetic studies proved that the ARO cell line and its sublines showed a complex clonal karyotype including structural alterations with deletions and translocations involving chromosomes 5, 7, 8, 9p, 11p, 17q 19p, and 20q that were consistent with earlier reported data in UTC. In vivo BNCT studies: ARO cells were transplanted into the scapular region of NIH nude mice, and after 2 weeks BPA (350 or 600 mg/kg bw) was injected via i.p. The

Acute paraparesis as presentation of an occult follicular thyroid carcinoma: A case report

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José Miguel Baião

Full Text Available Introduction: Follicular thyroid carcinoma is the second most frequent type of well differentiated thyroid tumours. It is usually confined to the thyroid gland, however it can metastasize in a later stage of the disease. Signs and symptoms associated with bone metastasis are rare as first clinical manifestations. Case report: An 84-year-old female complained with acute paraparesis. Magnetic resonance imaging revealed an extensive intraosseous infiltrating lesion compatible with a bone metastasis from an occult tumour. Biopsy samples were compatible with bone metastasis from a follicular thyroid carcinoma. The patient was submitted to total thyroidectomy followed by iodine ablative therapy. Discussion: Follicular thyroid carcinoma presentation with symptoms related to bone metastasis is rare. Patients with bone lesions, such as pathological fractures or compressive symptoms should be studied since they may have clinically unapparent lesions from an unknown tumour. Patients with FTC should be submitted to total thyroidectomy. Bone lesions may be addressed to improve quality of life however this decision depends on disease extent. Conclusion: Acute paraparesis is a rare form of presentation of thyroid carcinoma. These neoplasms must be taken into account when investigating metastasis to the bone from unknown neoplasms. Keywords: Acute paraparesis, Follicular thyroid carcinoma, Bone metastasis, Case report

Tumour localization and pharmacokinetics of iodine-125 human monoclonal IgM antibody (COU-1) and its monomeric and half-monomeric fragments analysed in nude mice grafted with human tumour

International Nuclear Information System (INIS)

Ditzel, H.; Erb, K.; Rasmussen, J.W.; Jensenius, J.C.

1992-01-01

Human monoclonal IgM antibodies reactive with cancer-associated antigens may not have the optimal imaging capability due to their large size. Fragmentation of human IgM is less than straight-forward due to the loss of immunoreactivity. From the human monoclonal IgM antibody COU-1 we have prepared monomeric and half-monomeric fragments, which retain the ability to bind to colon cancer cells in vitro. The pharmacokinetics and tumour localization were evaluated in nude mice bearing human colon adenocarcinoma and human melanoma grafts. Faster clearance from the circulation was seen for the smaller half-monomeric fragment with a half-life (rapid phase/slow phase) of 2 h/16 h compared with the intact antibody, 4 h/25 h, and the monomeric fragment, 3 h/27 h. Intact COU-1 as well as the fragments accumulated in the colon tumour graft. Higher amounts of radioactivity were found in the colon tumour as compared to normal organs for intact COU-1 at days 4 and 6, for the monomeric fragment at day 4, and for the half-monomeric fragment at day 2 after injection. This investigation demonstrates the favourable biodistribution of the half monomeric COU-1 fragment. The fast clearance of this fragment resulted in a tumour-to-muscle ratio as high as 22 on day 2 after injection. Also, only this fragment gave a positive tumour-to-blood ratio. Normal IgM and its fragments were used as controls. Radioimmunoscintigraphy demonstrated the colon tumour discriminatory properties of each of the three iodine-labelled antibody preparations. The results compare favourably with previously reported investigations of the localization of human monoclonal antibodies and suggest that fragments of human monoclonal IgM antibodies may be useful tools for the immunodetection of cancer in patients. (orig.)

Alpha-amidated peptides derived from pro-opiomelanocortin in human pituitary tumours

DEFF Research Database (Denmark)

Fenger, M; Johnsen, A H

1988-01-01

Human pituitary tumours, obtained at surgery for Cushing's disease and Nelson's syndrome, were extracted and the content and molecular forms of pro-opiomelanocortin (POMC)-derived peptides determined by radioimmunoassay, gel chromatography, reversed-phase high-performance liquid chromatography....... In conclusion, all the molecular forms of the amidated peptides detected in tumours from patients with Cushing's disease and Nelson's syndrome were similar to the molecular forms found in the normal human pituitary. The main difference between the tumours and the normal pituitary was the greater amount...... (HPLC) and sequence analysis. In the tumours from patients with Cushing's disease the mean concentrations of amidated peptides relative to the total amount of POMC were as follows: alpha-MSH, 1.7%; amidated gamma-MSH (gamma 1-MSH), 8.5% and the peptide linking gamma-MSH and ACTH in the precursor (hinge...

Ultrasound surveillance for radiation-induced thyroid carcinoma in adult survivors of childhood cancer.

Science.gov (United States)

Brignardello, Enrico; Felicetti, Francesco; Castiglione, Anna; Gallo, Marco; Maletta, Francesca; Isolato, Giuseppe; Biasin, Eleonora; Fagioli, Franca; Corrias, Andrea; Palestini, Nicola

2016-03-01

The optimal surveillance strategy to screen for thyroid carcinoma childhood cancer survivors (CCS) at increased risk is still debated. In our clinical practice, beside neck palpation we routinely perform thyroid ultrasound (US). Here we describe the results obtained using this approach. We considered all CCS referred to our long term clinic from November 2001 to September 2014. One hundred and ninety-seven patients who had received radiation therapy involving the thyroid gland underwent US surveillance. Thyroid US started 5 years after radiotherapy and repeated every 3 years, if negative. Among 197 CCS previously irradiated to the thyroid gland, 74 patients (37.5%) developed thyroid nodules, and fine-needle aspiration was performed in 35. In 11 patients the cytological examination was suspicious or diagnostic for malignancy (TIR 4/5), whereas a follicular lesion was diagnosed in nine. Patients with TIR 4/5 cytology were operated and in all cases thyroid cancer diagnosis was confirmed. The nine patients with TIR 3 cytology also underwent surgery and a carcinoma was diagnosed in three of them. Prevalence of thyroid cancer was 7.1%. Tumour size ranged between 4 and 25 mm, but six (43%) were classified T3 because of extra-thyroidal extension. Six patients had nodal metastases; in eight patients the tumour was multifocal. At the time of the study all patients are disease free, without evidence of surgery complications. Applying our US surveillance protocol, the prevalence of radiation-induced thyroid cancer is high. Histological features of the thyroid cancers diagnosed in our cohort suggest that most of them were clinically relevant tumours. Copyright © 2015 Elsevier Ltd. All rights reserved.

Perfluoroalkyl substances exposure and thyroid hormones in humans: epidemiological observations and implications

Directory of Open Access Journals (Sweden)

Jung Eun Lee

2017-03-01

Full Text Available Thyroid hormones play crucial roles in normal neurodevelopment of fetus and child. Many chemicals can affect control and homeostasis of thyroid hormones, and eventually lead to various adverse health effects including neurodevelopmental disorders. Perfluoroalkyl substances (PFASs are among the thyroid disrupting chemicals that can be encountered among general human population. Due to their unique physicochemical characteristics, PFASs have been used as surfactants and surface coating materials in many applications. Therefore, PFASs have been frequently detected in humans and environment worldwide. In cross-sectional studies using nationally representative general human populations of United States, several PFASs have shown significant associations with thyroid hormones. Moreover, among pregnant women and their infants, not only major PFASs such as perfluorooctane sulfonic acid and perfluorooctanoic acid, but also those with shorter or longer carbon chains showed significant associations with thyroid hormones. Often demographic characteristics such as sex, age, and disease status appear to influence the associations between PFASs exposure and thyroid hormones. In general, major PFASs showed hypothyroidism effects among pregnant women and infants. As 8 carbon based PFASs have been phased out, those with shorter or longer carbon chains have been used in growing amount as replacement. However, only limited information is available for their occurrences and toxicity among humans. Further investigations on these substituting PFASs are required. In addition, efforts are warranted to identify sources of and mitigate exposure to these thyroid disrupting chemicals especially during pregnancy and early stages of life.

Human T-Cell Clones from Autoimmune Thyroid Glands: Specific Recognition of Autologous Thyroid Cells

Science.gov (United States)

Londei, Marco; Bottazzo, G. Franco; Feldmann, Marc

1985-04-01

The thyroid glands of patients with autoimmune diseases such as Graves' disease and certain forms of goiter contain infiltrating activated T lymphocytes and, unlike cells of normal glands, the epithelial follicular cells strongly express histocompatability antigens of the HLA-DR type. In a study of such autoimmune disorders, the infiltrating T cells from the thyroid glands of two patients with Graves' disease were cloned in mitogen-free interleukin-2 (T-cell growth factor). The clones were expanded and their specificity was tested. Three types of clones were found. One group, of T4 phenotype, specifically recognized autologous thyroid cells. Another, also of T4 phenotype, recognized autologous thyroid or blood cells and thus responded positively in the autologous mixed lymphocyte reaction. Other clones derived from cells that were activated in vivo were of no known specificity. These clones provide a model of a human autoimmune disease and their analysis should clarify mechanisms of pathogenesis and provide clues to abrogating these undesirable immune responses.

Selenoproteins in human body: focus on thyroid pathophysiology.

Science.gov (United States)

Valea, Ana; Georgescu, Carmen Emanuela

2018-06-05

Selenium (Se) has a multilevel, complex and dynamic effect on the human body as a major component of selenocysteine, incorporated into selenoproteins, which include the selenocysteine-containing enzymes iodothyronine deiodinases. At the thyroid level, these proteins play an essential role in antioxidant protection and hormone metabolism. This is a narrative review based on PubMed/Medline database research regarding thyroid physiology and conditions with Se and Se-protein interferences. In humans, Se-dependent enzyme functions are best expressed through optimal Se intake, although there is gap in our knowledge concerning the precise mechanisms underlying the interrelation. There is a good level of evidence linking low serum Se to autoimmune thyroid diseases and, to a lesser extent, differentiated thyroid cancer. However, when it comes to routine supplementation, the results are heterogeneous, except in the case of mild Graves' orbitopathy. Autoimmune hypothyroidism is associated with a state of higher oxidative stress, but not all studies found an improvement of thyroid function after Se was introduced as antioxidant support. Meanwhile, no routine supplementation is recommended. Low Se intake is correlated with an increased risk of developing antithyroid antibodies, its supplementation decreasing their titres; there is also a potential reduction in levothyroxine replacement dose required for hypothyroidism and/or the possibility that it prevents progression of subclinical hypothyroidism, although not all studies agree. In thyroid-associated orbitopathy, euthyroidism is more rapidly achieved if the micronutrient is added to traditional drugs, while controls appear to benefit from the microelement only if they are deficient; thus, a basal assay of Se appears advisable to better select patients who need substitution. Clearly, further Se status biomarkers are required. Future introduction of individual supplementation algorithms based on baseline micronutrient levels

Hyperfunctioning parathyroid tumours in patients with thyroid nodules. Sensitivity and positive predictive value of high-resolution ultrasonography and 99mTc-sestamibi scintigraphy.

Science.gov (United States)

Lumachi, F; Marzola, M C; Zucchetta, P; Tregnaghi, A; Cecchin, D; Bui, F

2003-09-01

A series of 112 consecutive patients with primary hyperparathyroidism who underwent both high-resolution neck ultrasonography (US) and 99mTc-sestamibi/99mTc-pertechnetate subtraction scintigraphy (SS) prior to successful parathyroidectomy was reviewed. There were 29 (25.9%) men and 83 (74.1%) women, with a median age of 58 years (range 13-78 years). Patients were divided into two groups, according to the preoperative US findings: group A (87 patients, 77.7%) without thyroid diseases, and group B (25 patients, 22.3%) with either multinodular goitre or a solitary nontoxic thyroid nodule. In group B patients partial or total thyroidectomy was also performed, according to the intraoperative findings and frozen-section examination results. Final histopathology showed 99 (88.4%) solitary parathyroid (PT) adenomas and 3 (2.7%) PT carcinomas, while 10 (8.9%) patients had a multiglandular disease. The sensitivity and positive predictive value (PPV) were (group A vs group B) 79.8% vs 70.8% (P=0.25) and 95.7% vs 94.4% (P=0.58) for US, and 83.3% vs 87.0% (P=0.47) and 95.9% vs 90.9% (P=0.32) for SS respectively. Better but similar (P=not significant) results were obtained in patients with solitary PT tumours: 81.5% vs 77.8% (US) and 85.0 vs 94.1% (SS) sensitivity; 97.1% vs 93.3% (US) and 95.8% vs 88.9% (SS) PPV. Overall, the combination of US and SS was 92.9% sensitive (group A=93.1%, group B=92.0%; P=0.55), and the PPV reached 100% in each group. In conclusion, in patients with primary hyperparathyroidism the results of both US and SS are independent of coexistent thyroid disease, especially in patients with solitary PT tumours.

Tumours of the head and neck induced by ionizing radiation

International Nuclear Information System (INIS)

Daal, W.A.J. van.

1979-01-01

Reference is made to the cases of two patients who between 20 and 45 years after irradiation for tuberculous lymphomas in the neck developed malignant and benign tumours in the skin, the thyroid and the larynx-hypopharynx. The literature on induction of tumours by ionizing radiation is reviewed. So far, only one patient has been described in whome tumours in three organs may have been induced by irradiation. In the course of the examination of patients who have been irradiated for benign conditions, the possibility of tumours developing in several organs should be kept in mind. (Auth.)

A reproducible brain tumour model established from human glioblastoma biopsies

International Nuclear Information System (INIS)

Wang, Jian; Chekenya, Martha; Bjerkvig, Rolf; Enger, Per Ø; Miletic, Hrvoje; Sakariassen, Per Ø; Huszthy, Peter C; Jacobsen, Hege; Brekkå, Narve; Li, Xingang; Zhao, Peng; Mørk, Sverre

2009-01-01

Establishing clinically relevant animal models of glioblastoma multiforme (GBM) remains a challenge, and many commonly used cell line-based models do not recapitulate the invasive growth patterns of patient GBMs. Previously, we have reported the formation of highly invasive tumour xenografts in nude rats from human GBMs. However, implementing tumour models based on primary tissue requires that these models can be sufficiently standardised with consistently high take rates. In this work, we collected data on growth kinetics from a material of 29 biopsies xenografted in nude rats, and characterised this model with an emphasis on neuropathological and radiological features. The tumour take rate for xenografted GBM biopsies were 96% and remained close to 100% at subsequent passages in vivo, whereas only one of four lower grade tumours engrafted. Average time from transplantation to the onset of symptoms was 125 days ± 11.5 SEM. Histologically, the primary xenografts recapitulated the invasive features of the parent tumours while endothelial cell proliferations and necrosis were mostly absent. After 4-5 in vivo passages, the tumours became more vascular with necrotic areas, but also appeared more circumscribed. MRI typically revealed changes related to tumour growth, several months prior to the onset of symptoms. In vivo passaging of patient GBM biopsies produced tumours representative of the patient tumours, with high take rates and a reproducible disease course. The model provides combinations of angiogenic and invasive phenotypes and represents a good alternative to in vitro propagated cell lines for dissecting mechanisms of brain tumour progression

A reproducible brain tumour model established from human glioblastoma biopsies

Directory of Open Access Journals (Sweden)

Li Xingang

2009-12-01

Full Text Available Abstract Background Establishing clinically relevant animal models of glioblastoma multiforme (GBM remains a challenge, and many commonly used cell line-based models do not recapitulate the invasive growth patterns of patient GBMs. Previously, we have reported the formation of highly invasive tumour xenografts in nude rats from human GBMs. However, implementing tumour models based on primary tissue requires that these models can be sufficiently standardised with consistently high take rates. Methods In this work, we collected data on growth kinetics from a material of 29 biopsies xenografted in nude rats, and characterised this model with an emphasis on neuropathological and radiological features. Results The tumour take rate for xenografted GBM biopsies were 96% and remained close to 100% at subsequent passages in vivo, whereas only one of four lower grade tumours engrafted. Average time from transplantation to the onset of symptoms was 125 days ± 11.5 SEM. Histologically, the primary xenografts recapitulated the invasive features of the parent tumours while endothelial cell proliferations and necrosis were mostly absent. After 4-5 in vivo passages, the tumours became more vascular with necrotic areas, but also appeared more circumscribed. MRI typically revealed changes related to tumour growth, several months prior to the onset of symptoms. Conclusions In vivo passaging of patient GBM biopsies produced tumours representative of the patient tumours, with high take rates and a reproducible disease course. The model provides combinations of angiogenic and invasive phenotypes and represents a good alternative to in vitro propagated cell lines for dissecting mechanisms of brain tumour progression.

Nuclear medicine in childhood tumours

International Nuclear Information System (INIS)

Hoefnagel, C.A.

2004-01-01

Full text: In recent years the contribution of nuclear medicine has been of increasing interest to paediatric oncology, in particular in imaging for diagnosis, staging and follow-up, in quantitative function analysis of organs at risk during oncological therapy, as well as in radionuclide therapy. For tumour imaging a great number of tumour-seeking radiopharmaceuticals are available, exploiting various metabolic and biological properties of individual tumours; several of these agents can also be applied for radionuclide therapy. More recent tracers allow the characterization of tumours, highlighting features like hormone receptors, hypoxia, MDR and apoptosis. New techniques in paediatric oncology include PET and probe-guided surgery. As a functional modality, nuclear medicine is well suited to monitor the function of organs at risk during treatment in paediatric oncology, in particular cardiac, pulmonary, renal and salivary gland function. A summary of applications and major Indications will be presented. Osteosarcoma: In differentiated osteosarcoma bone scintigraphy/SPECT using 99m Tc-diphosphonate may, as a result of Its targeting the tumour-produced osteoid, visualize not only the primary bone tumour and skeletal metastases, but also the extraosseous metastases. For preoperative therapy nd palliation of metastases beta-emitting bone-seeking agents, such as 89 Sr-chloride, 186 Re-HEDP and 153 Sm-EDTMP, are available. Lymphoma: 67 Ga-citrate has been used for decades in the detection, staging and follow up of lymphoma, as well as for early recognition of response to therapy. 201 TI-chloride scintigraphy/SPECT and PET using 18 F-deoxyglucose can also be used for this purpose. 99m Tc- sestamibi and 99m Tc-tetrofosmin are associated with p-glycoprotein, playing a role in multidrug resistance. In adults with recurrent non Hodgkin lymphoma treatment with 131 l- or 90 Y labelled anti-CD20 antibodies is highly effective. Thyroid carcinoma. 201 TI-chloride scintigraphy

Radiosensitivity of drug-resistant human tumour xenografts

International Nuclear Information System (INIS)

Mattern, J.; Bak, M. Jr.; Volm, M.; Hoever, K.H.

1989-01-01

The radiosensitivity of three drug-resistant sublines of a human epidermoid lung carcinoma growing as xenografts in nude mice was investigated. Drug resistance to vincristine, actinomycin D and cisplatin was developed in vivo by repeated drug treatment. It was found that all three drug-resistant tumour lines were not cross-resistant to irradiation. (orig.) [de

The potential value of somatostatin receptor scintigraphy in medullary thyroid carcinoma

Energy Technology Data Exchange (ETDEWEB)

Doerr, U.; Bihl, H. (Katharinenhospital, Stuttgart (Germany). Dept. of Nuclear Medicine); Frank-Raue, K.; Raue, F. (Heidelberg Univ. (Germany). Dept. of Internal Medicine); Sautter-Bihl, M.L.; Buhr, H.J. (Staedt. Klinikum, Karlsruhe (Germany). Dept. of Radiooncology and Nuclear Medicine); Guzman, G. (Katherinenhospital, Stuttgart (Germany). Dept. of Nuclear Medicine Inst. de Neurocirugia, Investigationes Cerebrales ' Dr Asenjo' Santiago (Chile). Dept. de Medicina Nuclear)

1993-06-01

In a prospective study, ten patients with recurrent medullary thyroid carcinoma (markedly elevated calcitonin levels) were investigated by means of somatostatin receptor scintigraphy (SRS) with [sup 111]In-pentetreotide. Scintigraphically, 30 sites of pathological uptake were found, mostly located in the neck and upper mediastinum. So far, 18 suspected tumour sites underwent histological examination and 14 of them could be verified as metastases of medullary thyroid carcinoma (MTC). The remaining four putative tumour lesions turned out to be false positive scintigraphic findings caused by chronic inflammation and somatostatin receptor positive tumours other than MTC. We conclude that SRS is a promising imaging modality for localization of MTC recurrence and may thus make a contribution to better management of this patient group. (Author).

The potential value of somatostatin receptor scintigraphy in medullary thyroid carcinoma

International Nuclear Information System (INIS)

Doerr, U.; Bihl, H.; Frank-Raue, K.; Raue, F.; Sautter-Bihl, M.L.; Buhr, H.J.; Guzman, G.; Inst. de Neurocirugia, Investigationes Cerebrales 'Dr Asenjo' Santiago

1993-01-01

In a prospective study, ten patients with recurrent medullary thyroid carcinoma (markedly elevated calcitonin levels) were investigated by means of somatostatin receptor scintigraphy (SRS) with 111 In-pentetreotide. Scintigraphically, 30 sites of pathological uptake were found, mostly located in the neck and upper mediastinum. So far, 18 suspected tumour sites underwent histological examination and 14 of them could be verified as metastases of medullary thyroid carcinoma (MTC). The remaining four putative tumour lesions turned out to be false positive scintigraphic findings caused by chronic inflammation and somatostatin receptor positive tumours other than MTC. We conclude that SRS is a promising imaging modality for localization of MTC recurrence and may thus make a contribution to better management of this patient group. (Author)

Generalized resistance to thyroid hormone associated with a mutation in the ligand-binding domain of the human thyroid hormone receptor β

International Nuclear Information System (INIS)

Sakurai, A.; Takeda, K.; Ain, K.; Ceccarelli, P.; Nakai, A.; Seino, S.; Bell, G.I.; Refetoff, S.; DeGroot, L.J.

1989-01-01

The syndrome of generalized resistance to thyroid hormone is characterized by elevated circulating levels of thyroid hormone in the presence of an overall eumetabolic state and failure to respond normally to triiodothyronine. The authors have evaluated a family with inherited generalized resistance to thyroid hormone for abnormalities in the thyroid hormone nuclear receptors. A single guanine → cytosine replacement in the codon for amino acid 340 resulted in a glycine → arginine substitution in the hormone-binding domain of one of two alleles of the patient's thyroid hormone nuclear receptor β gene. In vitro translation products of this mutant human thyroid hormone nuclear receptor β gene did not bind triiodothyronine. Thus, generalized resistance to thyroid hormone can result from expression of an abnormal thyroid hormone nuclear receptor molecule

Neutron autoradiography imaging of selective boron uptake in human metastatic tumours

Energy Technology Data Exchange (ETDEWEB)

Altieri, S. [Department of Nuclear and Theoretical Physics, University of Pavia, Via Bassi 6, Pavia (Italy); National Institute of Nuclear Physics (INFN), Section of Pavia, Via Bassi 6, Pavia (Italy)], E-mail: saverio.altieri@pv.infn.it; Bortolussi, S. [Department of Nuclear and Theoretical Physics, University of Pavia, Via Bassi 6, Pavia (Italy); National Institute of Nuclear Physics (INFN), Section of Pavia, Via Bassi 6, Pavia (Italy); Bruschi, P.; Chiari, P.; Fossati, F.; Stella, S. [Department of Nuclear and Theoretical Physics, University of Pavia, Via Bassi 6, Pavia (Italy); Prati, U.; Roveda, L. [Unit of cancer surgery, Cancer Center of Excellence, Foundation T. Campanella, Catanzaro (Italy); Zonta, A.; Zonta, C.; Ferrari, C.; Clerici, A. [Department of Surgery, University of Pavia, Piazza Botta, Pavia (Italy); Nano, R. [Department of Animal Biology, University of Pavia, Piazza Botta, Pavia (Italy); Pinelli, T. [Department of Nuclear and Theoretical Physics, University of Pavia, Via Bassi 6, Pavia (Italy); National Institute of Nuclear Physics (INFN), Section of Pavia, Via Bassi 6, Pavia (Italy)

2008-12-15

The ability to selectively hit the tumour cells is an essential characteristic of an anti-tumour therapy. In boron neutron capture therapy (BNCT) this characteristic is based on the selective uptake of {sup 10}B in the tumour cells with respect to normal tissues. An important step in the BNCT planning is the measurement of the boron concentration in the tissue samples, both tumour and healthy. When the tumour is spread through the healthy tissue, as in the case of metastases, the knowledge of the different kinds of tissues in the sample being analysed is crucial. If the percentage of tumour and normal tissues cannot be evaluated, the obtained concentration is a mean value depending on the composition of the different samples being measured. In this case an imaging method that could give information both on the morphology and on the spatial distribution of boron concentration in the sample would be a fundamental support. In this paper, the results of the boron uptake analysis in the tumour and in the healthy samples taken from human livers after boron phenylalanine (BPA) infusion are shown; boron imaging was performed using neutron autoradiography.

Carcinoma of the Thyroid. Preoperative diagnostic and prognostic factors

International Nuclear Information System (INIS)

Tennvall, J.

1984-01-01

By improving preoperative diagnosis and identification of important prognostic factors of thyroid carcinoma (TC) it might be possible to decrease the number of diagnostic surgical intervantions and to give patients with a confirmed TC a more adequate treatment. Preoperative diagnosis: consecutive series of 83 patients with scintigrams and of 203 patients with fine-needle aspiration (AC) with subsequently histologically confirmed TC were evaluated as well as 217 patients with confirmed benign thyroid disorders. The most common scintigraphic appearance was a solitary reduced uptake (70%). The sensitivity of AC for medullary and undifferentiated TC was 0.82-0.84, but it was for papillary (occult TC excluded) 0.58 and for follicular TC 0.42. A 'cold' nodule with also a decreased thallium-uptake is mostly a benign disorder, but with an increased uptake it might be a well-differentiated TC or a follicular adenoma. These could, however, be significantly separated by the thallium-elimination rate (p=0.0001). Prognostic factors: During 1955-1972, 262 patients with histologically verified TC were referred to the Department and 226 of these (86%) with a median follow-up of 11 years form the basis for prognostic multivariate analyses. According to these analyses, and when deaths in intercurrent disease were estimated, neither age at diagnosis nor sex were found to be important predictors of survival of TC. The following predictors were identified: for papillary TC: tumour extension beyond the thyroid capsule and marked cellular atypia; for follicular TC: tumour extension beyond the thyroid capsule, marked cellular atypia and distant metastases; for medullary TC: tumour extension beyond the thyroid capsule. (Author)

Detection of human cancer in an animal model using radio-labelled tumour-associated monoclonal antibodies

International Nuclear Information System (INIS)

Epenetos, A.A.; Arklie, J.; Knowles, R.W.; Bodmer, W.F.

1982-01-01

Monoclonal antibodies to epithelial-cell antigenic determinants, labelled with 123 I and 125 I, were administered parenterally to immunodeficient mice bearing human tumours derived from a human cancer cell line. Anterior, posterior and lateral radioscans of the body were taken with a gamma scintillation camera at various times from immediately to 65 days after injection. Visual displays of the images were processed by standard computer techniques. The model used a human colon-cancer cell line, HT29, and the monoclonal antibody, AUAl, which is specific to an epithelial proliferating antigen. Tumour detection was achieved in all the mice. The smallest tumour detectable appeared to be about 1 mm in diameter. The degree of antibody uptake in a tumour depended on its size and the blood supply of its surrounding tissues. (author)

Iodine-129 in human thyroids and seaweed in China

DEFF Research Database (Denmark)

Hou, Xiaolin; Dahlgaard, H.; Nielsen, S.P.

2000-01-01

The concentrations of I-129 and the ratios of I-129/I-127 in normal human thyroids collected in Tianjin, China, and some seaweed samples from the Chinese coast were determined by neutron activation analysis. The mean I-129/I-127 ratio in these thyroids was found to be 1.13 x 10(-9), which is two...... orders of magnitude higher than the level of the pre-nuclear era, but one order of magnitude lower than the level in Europe in the post-nuclear era. There is no significant difference between the ratio of I-129/I-127 in the thyroids for the post-nuclear era from China and other areas, which...

lmmunohistochemical study of effect of ionizing radiation on human malignant tumours

International Nuclear Information System (INIS)

Adomaitiene, D. I.; Aleknavicius, E.; Valuckas, K. and others

2000-01-01

Cell proliferation-associated tumour markers are considered to have a valuable clinical significance. The current study was designed to investigate changes in immunohistochemical (IH) expression of proliferating cell nuclear antigen PCNA in human malignant tumour tissue samples obtained before and after preoperative radiotherapy. Tumour tissue samples were obtained from 26 patients with rectal carcinoma, from 22 patients with carcinoma corporis uteri and from 82 patients with breast cancer. Tumour samples were processed for IH examination by using monoclonal antibodies (MoAbs) PC10 against PCNA. IH analysis of histological specimens of carcinoma corporis uteri and rectal carcinoma obtained before and after preoperative radiotherapy has revealed heterogeneity of biological response to irradiation. The great majority of tumour specimens after irradiation showed a high PCNA expression level in cell population. Only minority of tumour specimens (15-20%) exhibited reduced immunoreactivity with MoAbs PC10. PCNA positivity rate in breast cancer specimens obtained during surgery from 55 patients after preoperative radiotherapy in comparison to biomarker expression pattern in tumour specimens from 27 unirradiated patients (control group) was found to be tended to decrease. These in vivo findings are discussed in terms of radiation-induced cell death, followed after proliferation, and PCNA role in DNA repair. (author)

Progesterone Upregulates Gene Expression in Normal Human Thyroid Follicular Cells

Directory of Open Access Journals (Sweden)

Ana Paula Santin Bertoni

2015-01-01

Full Text Available Thyroid cancer and thyroid nodules are more prevalent in women than men, so female sex hormones may have an etiological role in these conditions. There are no data about direct effects of progesterone on thyroid cells, so the aim of the present study was to evaluate progesterone effects in the sodium-iodide symporter NIS, thyroglobulin TG, thyroperoxidase TPO, and KI-67 genes expression, in normal thyroid follicular cells, derived from human tissue. NIS, TG, TPO, and KI-67 mRNA expression increased significantly after TSH 20 μUI/mL, respectively: 2.08 times, P<0.0001; 2.39 times, P=0.01; 1.58 times, P=0.0003; and 1.87 times, P<0.0001. In thyroid cells treated with 20 μUI/mL TSH plus 10 nM progesterone, RNA expression of NIS, TG, and KI-67 genes increased, respectively: 1.78 times, P<0.0001; 1.75 times, P=0.037; and 1.95 times, P<0.0001, and TPO mRNA expression also increased, though not significantly (1.77 times, P=0.069. These effects were abolished by mifepristone, an antagonist of progesterone receptor, suggesting that genes involved in thyroid cell function and proliferation are upregulated by progesterone. This work provides evidence that progesterone has a direct effect on thyroid cells, upregulating genes involved in thyroid function and growth.

Familial occurrence of subacute thyroiditis associated with human leukocyte antigen-B35

NARCIS (Netherlands)

Kramer, AB; Roozendaal, C; Dullaart, RPF

Subacute thyroiditis (SAT) is a spontaneously remitting inflammatory disorder of the thyroid, associated with human leukocyte antigen (HLA)-B35, and may be virally induced in genetically predisposed individuals. A 57-year-old Caucasian man presented with symptoms of hyperthyroidism as well as

Alterations in tumour suppressor gene p53 in human gliomas from ...

Indian Academy of Sciences (India)

Unknown

Alterations in the tumour suppressor p53 gene are among the most common defects seen in a variety of human cancers. ..... rangement of the EGF receptor gene in primary human brain tumors ... the INK4A gene in superficial bladder tumors.

Correlation of MLH1 and MGMT expression and promoter methylation with genomic instability in patients with thyroid carcinoma

International Nuclear Information System (INIS)

Santos, Juliana Carvalho; Bastos, André Uchimura; Cerutti, Janete Maria; Ribeiro, Marcelo Lima

2013-01-01

Gene silencing of the repair genes MLH1 and MGMT was shown to be a mechanism underlying the development of microsatellite instability (MSI), a phenotype frequently associated with various human malignancies. Recently, aberrant methylation of MLH1, MGMT and MSI were shown to be associated with mutations in genes such as BRAF, RAS and IDH1 in colon and brain tumours. Little is known about the methylation status of MLH1 and MGMT in thyroid tumours and its association with MSI and mutational status. In a series of 96 thyroid tumours whose mutational profiles of BRAF, IDH1 and NRAS mutations and RET/PTC were previously determined, we investigated MLH1 and MGMT expression and methylation status by qPCR and methylation-specific PCR after bisulphite treatment, respectively. MSI was determined by PCR using seven standard microsatellite markers. Samples with point mutations (BRAF, IDH1 and NRAS) show a decrease in MLH1 expression when compared to negative samples. Additionally, malignant lesions show a higher MSI pattern than benign lesions. The MSI phenotype was also associated with down-regulation of MLH1. The results of this study allow us to conclude that low expression of MLH1 is associated with BRAF V600E mutations, RET/PTC rearrangements and transitions (IDH1 and NRAS) in patients with thyroid carcinoma. In addition, a significant relationship between MSI status and histological subtypes was found

Sperm protein 17 is expressed in human nervous system tumours

International Nuclear Information System (INIS)

Grizzi, Fabio; Baena, Riccardo Rodriguez y; Dioguardi, Nicola; Chiriva-Internati, Maurizio; Gaetani, Paolo; Franceschini, Barbara; Di Ieva, Antonio; Colombo, Piergiuseppe; Ceva-Grimaldi, Giorgia; Bollati, Angelo; Frezza, Eldo E; Cobos, E

2006-01-01

Human sperm protein 17 (Sp17) is a highly conserved protein that was originally isolated from a rabbit epididymal sperm membrane and testis membrane pellet. It has recently been included in the cancer/testis (CT) antigen family, and shown to be expressed in multiple myeloma and ovarian cancer. We investigated its immunolocalisation in specimens of nervous system (NS) malignancies, in order to establish its usefulness as a target for tumour-vaccine strategies. The expression of Sp17 was assessed by means of a standardised immunohistochemical procedure [(mAb/antigen) MF1/Sp17] in formalin-fixed and paraffin embedded surgical specimens of NS malignancies, including 28 neuroectodermal primary tumours (6 astrocytomas, 16 glioblastoma multiforme, 5 oligodendrogliomas, and 1 ependymoma), 25 meningeal tumours, and five peripheral nerve sheath tumours (4 schwannomas, and 1 neurofibroma),. A number of neuroectodermal (21%) and meningeal tumours (4%) were found heterogeneously immunopositive for Sp17. None of the peripheral nerve sheath tumours was immunopositive for Sp17. The expression pattern was heterogeneous in all of the positive samples, and did not correlate with the degree of malignancy. The frequency of expression and non-uniform cell distribution of Sp17 suggest that it cannot be used as a unique immunotherapeutic target in NS cancer. However, our results do show the immunolocalisation of Sp17 in a proportion of NS tumour cells, but not in their non-pathological counterparts. The emerging complex function of Sp17 makes further studies necessary to clarify the link between it and immunopositive cells

Effect of cell phone-like electromagnetic radiation on primary human thyroid cells.

Science.gov (United States)

Silva, Veronica; Hilly, Ohad; Strenov, Yulia; Tzabari, Cochava; Hauptman, Yirmi; Feinmesser, Raphael

2016-01-01

To evaluate the potential carcinogenic effects of radiofrequency energy (RFE) emitted by cell phones on human thyroid primary cells. Primary thyroid cell culture was prepared from normal thyroid tissue obtained from patients who underwent surgery at our department. Subconfluent thyroid cells were irradiated under different conditions inside a cell incubator using a device that simulates cell phone-RFE. Proliferation of control and irradiated cells was assessed by the immunohistochemical staining of antigen Kiel clone-67 (Ki-67) and tumor suppressor p53 (p53) expression. DNA ploidy and the stress biomarkers heat shock protein 70 (HSP70) and reactive oxygen species (ROS) was evaluated by fluorescence-activated cell sorting (FACS). Our cells highly expressed thyroglobulin (Tg) and sodium-iodide symporter (NIS) confirming the origin of the tissue. None of the irradiation conditions evaluated here had an effect neither on the proliferation marker Ki-67 nor on p53 expression. DNA ploidy was also not affected by RFE, as well as the expression of the biomarkers HSP70 and ROS. Our conditions of RFE exposure seem to have no potential carcinogenic effect on human thyroid cells. Moreover, common biomarkers usually associated to environmental stress also remained unchanged. We failed to find an association between cell phone-RFE and thyroid cancer. Additional studies are recommended.

Classification of follicular cell-derived thyroid cancer by global RNA profiling

DEFF Research Database (Denmark)

Rossing, Maria

2013-01-01

The incidence of thyroid cancer is increasing worldwide and thyroid nodules are a frequent clinical finding. Diagnosing follicular cell-derived cancers is, however, challenging both histopathologically and especially cytopathologically. The advent of high-throughput molecular technologies has...... profiling of follicular cell-derived thyroid cancers....... prompted many researchers to explore the transcriptome and, in recent years, also the miRNome in order to generate new molecular classifiers capable of classifying thyroid tumours more accurately than by conventional cytopathological and histopathological methods. This has led to a number of molecular...

Quantitation of glial fibrillary acidic protein in human brain tumours

DEFF Research Database (Denmark)

Rasmussen, S; Bock, E; Warecka, K

1980-01-01

The glial fibrillary acidic protein (GFA) content of 58 human brain tumours was determined by quantitative immunoelectrophoresis, using monospecific antibody against GFA. Astrocytomas, glioblastomas, oligodendrogliomas, spongioblastomas, ependymomas and medulloblastomas contained relatively high...

Enhanced casein kinase II activity in human tumour cell cultures

DEFF Research Database (Denmark)

Prowald, K; Fischer, H; Issinger, O G

1984-01-01

Casein kinase II (CKII) activity is enhanced as much as 2-3 fold in established and 4-5-fold in transformed human cell lines when compared to that of fibroblasts and primary human tumour cell cultures where CKII activity never exceeded a basic level. The high activity of CKII in transformed cells...

Solitary Cystic Metastasis Of Thyroid Papillary Carcinoma: Two Cases Reports

Directory of Open Access Journals (Sweden)

Ozgur Tarkan

2011-02-01

Full Text Available The appearance of a solitary lateral cervical cystic mass as the only initial presenting symptom of occult thyroid carcinoma is uncommon. Its presence is often related with the more frequently branchial cyst in young adults, but also rarely related with thyroid carcinomas. In most of these cases all such lesions may initially be considered as metastatic foci from a primary thyroid lesion. However, an alternative explanation by means of which ectopic thyroid tissue is associated with a branchial cyst has to be considered, especially if no primary tumour is observed in the histological examination of the thyroid gland. We present two case of solitary cystic lymph node metastasis of occult papillary carcinoma of the thyroid. [Cukurova Med J 2011; 36(1.000: 29-33

Solitary Cystic Metastasis Of Thyroid Papillary Carcinoma: Two Cases Reports

Directory of Open Access Journals (Sweden)

Ozgur Tarkan

2011-03-01

Full Text Available The appearance of a solitary lateral cervical cystic mass as the only initial presenting symptom of occult thyroid carcinoma is uncommon. Its presence is often related with the more frequently branchial cyst in young adults, but also rarely related with thyroid carcinomas. In most of these cases all such lesions may initially be considered as metastatic foci from a primary thyroid lesion. However, an alternative explanation by means of which ectopic thyroid tissue is associated with a branchial cyst has to be considered, especially if no primary tumour is observed in the histological examination of the thyroid gland. We present two case of solitary cystic lymph node metastasis of occult papillary carcinoma of the thyroid. [Cukurova Med J 2011; 36(1: 29-33

Improvement of Radiation-Mediated Immunosuppression of Human NSCLC Tumour Xenografts in a Nude Rat Model

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Sergey V. Tokalov

2010-01-01

Full Text Available Human tumour xenografts in a nude rat model have consistently been used as an essential part of preclinical studies for anticancer drugs activity in human. Commonly, these animals receive whole body irradiation to assure immunosuppression. But whole body dose delivery might be inhomogeneous and the resulting incomplete bone marrow depletion may modify tumour behaviour. To improve irradiation-mediated immunosuppression of human non-small cell lung cancer (NSCLC xenografts in a nude rat model irradiation (2 + 2 Gy from opposite sides of animals has been performed using a conventional X-ray tube. The described modification of whole body irradiation improves growth properties of human NSCLC xenografts in a nude rat model. The design of the whole body irradiation mediated immunosuppression described here for NSCLC xenografts may be useful for research applications involving other types of human tumours.

The value of ultrasound in the follow-up of thyroid cancer

DEFF Research Database (Denmark)

Bennedbæk, Finn Noe; Hegedüs, Laszlo

2014-01-01

The value of ultrasound in the follow-up of thyroid cancer The commonly used tumour-node-metastasis (TNM) staging system is designed to predict death and not recurrence. Based on this, patients with thyroid cancer are grouped into risk categories at the time of initial treatment. However, recent......-up is measurement of plasma-thyroglobulin concentration and ultrasound of the neck focusing on the thyroid bed and classification of lymph nodes according to their location and high risk signs....

Chemosensitivity and radiosensitivity testing of freshly explanted human tumour cells in vitro

International Nuclear Information System (INIS)

Wells, J.

1977-10-01

In this thesis, in vitro testing for the chemosensitivity and radiosensitivity of freshly explanted human tumour cells is described. The cells were incubated with anti-tumour drugs and either a 6-day growth test performed or a clonal growth test as a measure of survival of cell reproductive capacity. It was shown that if one aims to develop a suitable in vitro method for predicting the subsequent response of human tumour cells in situ to cytotoxic chemotherapy, the test procedure must be initiated before the explanted cells have undergone significant growth in vitro. The survival of the reproductive capacity of tumour cell explants following X-radiation was also studied. Using a 'feeder' layer technique, values for the survival curve parameter Dsub(q) were in the range 400-610 rad and the values for D 0 were in the range 120-160 rad. The shape of the X-ray survival curves did not change when cells were retested after repeated subculturing in vitro. Therefore, unlike chemosensitivity measured by the same biological end-point, radiosensitivity apparently does not change once cells have reached their maximum growth potential. (UK)

Microdosimetry of 129I in the human thyroid

International Nuclear Information System (INIS)

Feige, Y.

1977-01-01

A microdosimetric evaluation of the dose distribution from I-129 in the human thyroid gland, taking into account the various physical, geometrical and physiological parameters suggested by the ICRP Pub. 23 (1975) will be presented, and compared to the dose distribution of other radioisotopes of iodine. Using Dillman's decay scheme data, (NM/MIRD No. 10, p. 73, 1975), and the methods applied by Feige et al. for the microdosimetry of I-125, it is found that the dose to the cell nucleus is about 60% of the 'average' calculated dose for the whole thyroid gland. This follows from the assumptions that typical thyroid follicles are 150 to 300μm in diameter, and that all the iodine is contained in the colloid fraction of the gland. Thus a significant part of the decay energy of I-129, which is due mainly to the beta particles whose average range in tissue is only about 30 μm, is deposited within the colloid itself, and fails to reach the cell nucleus, 3 μm away from the colloid/cell interface. Uncertainties and variations in the parameters of the thyroid model will also be discussed. When thyroid doses due to I-129 releases are assessed, by either the specific activity or the critical pathway models, the conservative environmental and biological assumptions usually made lead to a large margin of safety. If 'average' doses are used instead of the microdosimetric dose distribution an additional safety factor of about 2 is obtained

Differential regulation of monocarboxylate transporter 8 expression in thyroid cancer and hyperthyroidism.

Science.gov (United States)

Badziong, Julia; Ting, Saskia; Synoracki, Sarah; Tiedje, Vera; Brix, Klaudia; Brabant, Georg; Moeller, Lars Christian; Schmid, Kurt Werner; Fuhrer, Dagmar; Zwanziger, Denise

2017-09-01

Thyroid hormone (TH) transporters are expressed in thyrocytes and most play a role in TH release. We asked whether expression of the monocarboxylate transporter 8 (MCT8) and the L-type amino acid transporters LAT2 and LAT4 is changed with thyrocyte dedifferentiation and in hyperfunctioning thyroid tissues. Protein expression and localization of transporters was determined by immunohistochemistry in human thyroid specimen including normal thyroid tissue (NT, n  = 19), follicular adenoma (FA, n  = 44), follicular thyroid carcinoma (FTC, n  = 45), papillary thyroid carcinoma (PTC, n  = 40), anaplastic thyroid carcinoma (ATC, n  = 40) and Graves' disease (GD, n  = 50) by calculating the 'hybrid' (H) score. Regulation of transporter expression was investigated in the rat follicular thyroid cell line PCCL3 under basal and thyroid stimulating hormone (TSH) conditions. MCT8 and LAT4 were localized at the plasma membrane, while LAT2 transporter showed cytoplasmic localization. MCT8 expression was downregulated in benign and malignant thyroid tumours as compared to NT. In contrast, significant upregulation of MCT8, LAT2 and LAT4 was found in GD. Furthermore, a stronger expression of MCT8 was demonstrated in PCCL3 cells after TSH stimulation. Downregulation of MCT8 in thyroid cancers qualifies MCT8 as a marker of thyroid differentiation. The more variable expression of LATs in distinct thyroid malignancies may be linked with other transporter properties relevant to altered metabolism in cancer cells, i.e. amino acid transport. Consistent upregulation of MCT8 in GD is in line with increased TH release in hyperthyroidism, an assumption supported by our in vitro results showing TSH-dependent upregulation of MCT8. © 2017 European Society of Endocrinology.

Cyclooxygenase-2 expression in the normal human eye and its expression pattern in selected eye tumours

DEFF Research Database (Denmark)

Wang, Jinmei; Wu, Yazhen; Heegaard, Steffen

2011-01-01

Purpose: Cyclooxygenase-2 (COX-2) is an enzyme involved in neoplastic processes. The purpose of the present study is to investigate COX-2 expression in the normal human eye and the expression pattern in selected eye tumours involving COX-2 expressing cells. Methods: Immunohistochemical staining...... using antibodies against COX-2 was performed on paraffin sections of normal human eyes and selected eye tumours arising from cells expressing COX-2. Results: Cyclooxygenase-2 expression was found in various structures of the normal eye. Abundant expression was seen in the cornea, iris, ciliary body...... and retina. The COX-2 expression was less in tumours deriving from the ciliary epithelium and also in retinoblastoma. Conclusion: Cyclooxygenase-2 is constitutively expressed in normal human eyes. The expression of COX-2 is much lower in selected eye tumours involving COX-2 expressing cells....

An enhanced heterologous virus-like particle for human papillomavirus type 16 tumour immunotherapy.

Directory of Open Access Journals (Sweden)

Khairunadwa Jemon

Full Text Available Cervical cancer is caused by high-risk, cancer-causing human papillomaviruses (HPV and is the second highest cause of cancer deaths in women globally. The majority of cervical cancers express well-characterized HPV oncogenes, which are potential targets for immunotherapeutic vaccination. Here we develop a rabbit haemorrhagic disease virus (RHDV virus-like particle (VLP-based vaccine designed for immunotherapy against HPV16 positive tumours. An RHDV-VLP, modified to contain the universal helper T cell epitope PADRE and decorated with an MHC I-restricted peptide (aa 48-57 from the HPV16 E6, was tested for its immunotherapeutic efficacy against the TC-1 HPV16 E6 and E7-expressing tumour in mice. The E6-RHDV-VLP-PADRE was administered therapeutically for the treatment of a pre-existing TC-1 tumour and was delivered with antibodies either to deplete regulatory T cells (anti-CD25 or to block T cell suppression mediated through CTLA-4. As a result, the tumour burden was reduced by around 50% and the median survival time of mice to the humane endpoint was almost doubled the compared to controls. The incorporation of PADRE into the RHDV-VLP was necessary for an E6-specific enhancement of the anti-tumour response and the co-administration of the immune modifying antibodies contributed to the overall efficacy of the immunotherapy. The E6-RHDV-VLP-PADRE shows immunotherapeutic efficacy, prolonging survival for HPV tumour-bearing mice. This was enhanced by the systemic administration of immune-modifying antibodies that are commercially available for use in humans. There is potential to further modify these particles for even greater efficacy in the path to development of an immunotherapeutic treatment for HPV precancerous and cancer stages.

Anaplastic lymphoma kinase (ALK) gene rearrangements in radiation-related human papillary thyroid carcinoma after the Chernobyl accident.

Science.gov (United States)

Arndt, Annette; Steinestel, Konrad; Rump, Alexis; Sroya, Manveer; Bogdanova, Tetiana; Kovgan, Leonila; Port, Matthias; Abend, Michael; Eder, Stefan

2018-04-06

Childhood radiation exposure has been associated with increased papillary thyroid carcinoma (PTC) risk. The role of anaplastic lymphoma kinase (ALK) gene rearrangements in radiation-related PTC remains unclear, but STRN-ALK fusions have recently been detected in PTCs from radiation exposed persons after Chernobyl using targeted next-generation sequencing and RNA-seq. We investigated ALK and RET gene rearrangements as well as known driver point mutations in PTC tumours from 77 radiation-exposed patients (mean age at surgery 22.4 years) and PTC tumours from 19 non-exposed individuals after the Chernobyl accident. ALK rearrangements were detected by fluorescence in situ hybridisation (FISH) and confirmed with immunohistochemistry (IHC); point mutations in the BRAF and RAS genes were detected by DNA pyrosequencing. Among the 77 tumours from exposed persons, we identified 7 ALK rearrangements and none in the unexposed group. When combining ALK and RET rearrangements, we found 24 in the exposed (31.2%) compared to two (10.5%) in the unexposed group. Odds ratios increased significantly in a dose-dependent manner up to 6.2 (95%CI: 1.1, 34.7; p = 0.039) at Iodine-131 thyroid doses >500 mGy. In total, 27 cases carried point mutations of BRAF or RAS genes, yet logistic regression analysis failed to identify significant dose association. To our knowledge we are the first to describe ALK rearrangements in post-Chernobyl PTC samples using routine methods such as FISH and IHC. Our findings further support the hypothesis that gene rearrangements, but not oncogenic driver mutations, are associated with ionizing radiation-related tumour risk. IHC may represent an effective method for ALK-screening in PTCs with known radiation aetiology, which is of clinical value since oncogenic ALK activation might represent a valuable target for small molecule inhibitors. © 2018 The Authors The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and

The association between thyroid malignancy and chronic lymphocytic thyroiditis: should it alter the surgical approach?

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Büyükaşık, Oktay; Hasdemir, Ahmet Oğuz; Yalçın, Erol; Celep, Bahadır; Sengül, Serkan; Yandakçı, Kemal; Tunç, Gündüz; Küçükpınar, Tevfik; Alkoy, Seval; Cöl, Cavit

2011-01-01

The relation between thyroid neoplasms and chronic lymphocytic thyroiditis (CLT) is controversial. While it is accepted that focal lymphocytic thyroiditis develops secondarily to malignancy, it is not clear whether diffuse lymphocytic thyroiditis has a tendency to develop into thyroid cancer. The aim of this study was to investigate the relation between CLT and malignant tumours of the thyroid and evaluate the surgical approach to CLT cases. In this study, 917 patients operated on for thyroid diseases were investigated retrospectively. Seventy-seven (8.4%) patients histopathologically diagnosed as having CLT (either non-specific or Hashimoto's thyroiditis) were investigated for any concurrent malignant neoplasm. Fifteen patients in whom CLT and thyroid malignancy were coexisting were included in the study. In the pathological evaluation of 917 cases, malignancy in the thyroid was found in 97 (10.6%) cases. Seventy-seven cases were categorised as CLT. Of these 77, 16 (20.8%) were Hashimoto's thyroiditis (specific CLT) and the other 61 (79.2%) were non-specific CLT. In 15 cases, thyroid malignancy was found to be concurrent with CLT. Of the malignities, nine (60%) were papillary carcinoma, three (20%) medullar carcinoma, one (6.6%) follicular carcinoma, one (6.6%) Hurthle cell carcinoma, and one (6.6%) lymphoma. In our series, the rate of the development of malignancy against the background of CLT was 19.48%, while the rate in the groups without CLT was 9.76%, with a statistically significant difference between the groups (p = 0.008). CLT cases should be evaluated more carefully in terms of malignancy. If a nodule is detected on thyroiditis, the minimal surgical intervention should be lobectomy. Total thyroidectomy should be considered as preferable to subtotal thyroidectomy because of its many advantages such as controlling thyroiditis, removing the probability of reoperation, and hormonal stability.

Thyroid effects

International Nuclear Information System (INIS)

Maxon, H.; Thomas, S.; Buncher, C.; Book, S.; Hertzberg, V.

1985-01-01

Risk coefficients for thyroid disorders have been developed for both 131 I and external x or gamma low-LET radiation. A linear, no-threshold model has been used for thyroid neoplasms. A linear, threshold model has been used for other thyroid disorders. Improvements since the Reactor Safety Study were made possible by relevant new animal and human data. Major changes are as follows. Animal data are used to supplement the human experience where necessary. A specific risk estimate model is used for thyroid neoplasms, which accounts for observed effects of gender and age at exposure on risk. For thyroid cancer, the basis of the risk coefficients is the experience of North Americans following x-irradiation for benign disease in childhood. This recognizes possible differences in susceptibility in people of different heritage. A minimum induction period for thyroid neoplasms following irradiation is used to define periods at risk. An upper bound risk coefficient for cancer induction following exposure to 131 I is based on human experience at relatively low dose exposures. While the overall lifetime risks of death due to thyroid cancer are consistent with projections by the ICRP, BEIR III, and UNSCEAR Reports, the current model permits greater flexibility in determining risk for population subgroups. 88 references, 8 tables

Plasma Bile Acids Are Associated with Energy Expenditure and Thyroid Function in Humans

NARCIS (Netherlands)

Ockenga, Johann; Valentini, Luzia; Schuetz, Tatjana; Wohlgemuth, Franziska; Glaeser, Silja; Omar, Ajmal; Kasim, Esmatollah; duPlessis, Daniel; Featherstone, Karen; Davis, Julian R.; Tietge, Uwe J. F.; Kroencke, Thomas; Biebermann, Heike; Koehrle, Josef; Brabant, Georg

Background/Aims: Animal studies implicate a role of bile acids (BA) in thyroid-regulated energy expenditure (EE) via activation of the TGR-5/adenylate cyclase/deiodinase type 2 pathway. Here we investigated these possible associations in humans. Methods: EE, BA, and thyroid hormone status were

Expression of Selected Markers in Immunohistochemical Diagnosis of Canine and Human Testicular Tumours

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Ciaputa Rafał

2015-04-01

Full Text Available Immunohistochemical profiles of the most common canine testicular tumours, including the Leydig cell tumours, seminomas, and Sertoli cell tumours were analysed, and the results were compared with those obtained in the corresponding types of human testicular neoplasms. The expressions of vimentin, von Willebrand factor (FVIII, chromogranin A, synaptophysin, and MCM3 were quantified. In the case of Sertoli cell tumours, only canine ones were analysed, since this type of tumour is very rarely diagnosed in men. The expression of the analysed proteins in the testicular tumours was similar. The von Willebrand factor exhibited the strongest expression in Leydig cell tumours in dogs and men, while vimentin was expressed more strongly in dogs (96.7% had an intensity at +++ than in men (62.5% had +++ in the Leydigioma. The immunoexpression of MCM3 in seminomas was high in both men and dogs – 90% +++ and 100% +++ respectively. The lack of chromogranin A and synaptophysin was observed in almost 100% of seminomas in men and dogs. This differed from the results obtained for Leydigioma, where chromogranin A was expressed in 70% of dogs at +++ and in 100% of men at ++++. The results may indicate that the antibodies were selected correctly. Their analysis and interpretation provides valuable information concerning the nature of the studied tumours.

Papillary microcarcinoma of the thyroid gland

DEFF Research Database (Denmark)

Londero, Stefano Christian; Godballe, Christian; Krogdahl, Annelise

2008-01-01

at the time of diagnosis. Material and methods. From the 1(st) of January 1996 to 31(st) of December 2002 a total of 169 PMC patients were diagnosed and registered in the national Danish thyroid cancer database DATHYRCA and 131 of these were eligible for the study. Forty-three (33%) had histologically......Introduction. Papillary microcarcinomas (PMC) of the thyroid gland are defined according to The WHO Committee as papillary carcinomas measuring 10 mm or less in diameter. A large proportion of these tumours are found coincidentally in the treatment of symptomatic goitre and most cases follow...

Chronic lymphocytic thyroiditis is associated with invasive characteristics of differentiated thyroid carcinoma in children and adolescents.

Science.gov (United States)

Iliadou, Paschalia K; Effraimidis, Grigoris; Konstantinos, Michalakis; Grigorios, Panagiotou; Mitsakis, Periklis; Patakiouta, Frideriki; Pazaitou-Panayiotou, Kalliopi

2015-12-01

The association between chronic lymphocytic thyroiditis (CLT) and thyroid cancer is an interesting topic. The aim of the present study was to evaluate if demographic and histological characteristics as well as the long-term outcome of thyroid cancer was different in children and adolescents with and without CLT. The medical records of children and adolescents (≤21 years old) were reviewed. The following data were recorded: gender, year and age at diagnosis, family history of thyroid cancer, history of external radiation therapy, histological type (papillary and variants, follicular and variants), tumour size, multifocality, infiltration of thyroid parenchyma or surrounding soft tissues, vascular invasion, presence of lymph node and distant metastases. Information about the presence of TgAb and TPOAb was also collected. One hundred eight children and adolescents (median age 19.0, interquartile range 4.0 years) were diagnosed with differentiated thyroid carcinoma (DTC); 31 patients (28.7%) presented histological characteristics compatible with CLT. Infiltration of thyroid parenchyma was more frequent in patients with CLT compared to patients without (74.2% vs 48.1% respectively, P=0.024). Familial papillary thyroid carcinoma (PTC) was more frequent in patients with CLT compared to those without CLT (20.7% vs 2.8% respectively, P=0.009). There was no better outcome with respect to the presence of CLT or not. Children and adolescents with CLT present more frequently familial PTC as well as thyroid cancer with invasive characteristics. © 2015 European Society of Endocrinology.

Tumour suppressive function of HUWE1 in thyroid cancer

Indian Academy of Sciences (India)

It has been found to be dysregulated in various cancer typeand its functions in ... investigated by knocking down HUWE1 in three authentic thyroid cancer cell lines, ... overexpression of HUWE1 significantly inhibited tumourgrowth in vivo using ...

Spect-CT and PET: CT in the management of differentiated thyroid cancer

International Nuclear Information System (INIS)

Khan, Shoukat H.

2007-01-01

Full text: With the advancement and evolution in medical technology notably imaging there has been a sea change in the overall management strategy of most of the cancers of human body. The present day functional, imaging with PET and MRI enables us to pick up a tumour at its cellular stage. Molecular imaging and nanotechnology have further added to this expanding armamentarium of cancer imaging and treatment. Thyroid cancer is one such cancer where the cutting edge biotechnology has dramatically changed the management profile of a disease. Thyroid cancer can safely be classified as one of the cancers which if optimally managed is curable. Hybrid and fusion imaging like SPECT-CT and PET-CT with their superior sensitivity and specificity have greatly improved the accuracy of disease detection and reduced drastically the false positive disease sites. Disease not detected by conventional planar imaging can now be detected and also anatomically localized using hybrid imaging modalities of SPECT-CT and PET-CT. An accurate detection and precise localization improves image interpretation and a treatment optimization in the curable cancer of thyroid

CD133-expressing thyroid cancer cells are undifferentiated, radioresistant and survive radioiodide therapy

International Nuclear Information System (INIS)

Ke, Chien-Chih; Liu, Ren-Shyan; Yang, An-Hang; Liu, Ching-Sheng; Chi, Chin-Wen; Tseng, Ling-Ming; Tsai, Yi-Fan; Ho, Jennifer H.; Lee, Chen-Hsen; Lee, Oscar K.

2013-01-01

131 I therapy is regularly used following surgery as a part of thyroid cancer management. Despite an overall relatively good prognosis, recurrent or metastatic thyroid cancer is not rare. CD133-expressing cells have been shown to mark thyroid cancer stem cells that possess the characteristics of stem cells and have the ability to initiate tumours. However, no studies have addressed the influence of CD133-expressing cells on radioiodide therapy of the thyroid cancer. The aim of this study was to investigate whether CD133 + cells contribute to the radioresistance of thyroid cancer and thus potentiate future recurrence and metastasis. Thyroid cancer cell lines were analysed for CD133 expression, radiosensitivity and gene expression. The anaplastic thyroid cancer cell line ARO showed a higher percentage of CD133 + cells and higher radioresistance. After γ-irradiation of the cells, the CD133 + population was enriched due to the higher apoptotic rate of CD133 - cells. In vivo 131 I treatment of ARO tumour resulted in an elevated expression of CD133, Oct4, Nanog, Lin28 and Glut1 genes. After isolation, CD133 + cells exhibited higher radioresistance and higher expression of Oct4, Nanog, Sox2, Lin28 and Glut1 in the cell line or primarily cultured papillary thyroid cancer cells, and lower expression of various thyroid-specific genes, namely NIS, Tg, TPO, TSHR, TTF1 and Pax8. This study demonstrates the existence of CD133-expressing thyroid cancer cells which show a higher radioresistance and are in an undifferentiated status. These cells possess a greater potential to survive radiotherapy and may contribute to the recurrence of thyroid cancer. A future therapeutic approach for radioresistant thyroid cancer may focus on the selective eradication of CD133 + cells. (orig.)

Reduced expression of N-Myc downstream-regulated gene 2 in human thyroid cancer

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Ma Jianjun

2008-10-01

Full Text Available Abstract Background NDRG2 (N-Myc downstream-regulated gene 2 was initially cloned in our laboratory. Previous results have shown that NDRG2 expressed differentially in normal and cancer tissues. Specifically, NDRG2 mRNA was down-regulated or undetectable in several human cancers, and over-expression of NDRG2 inhibited the proliferation of cancer cells. NDRG2 also exerts important functions in cell differentiation and tumor suppression. However, it remains unclear whether NDRG2 participates in carcinogenesis of the thyroid. Methods In this study, we investigated the expression profile of human NDRG2 in thyroid adenomas and carcinomas, by examining tissues from individuals with thyroid adenomas (n = 40 and carcinomas (n = 35, along with corresponding normal tissues. Immunohistochemistry, quantitative RT-PCR and western blot methods were utilized to determine both the protein and mRNA expression status of Ndrg2 and c-Myc. Results The immunostaining analysis revealed a decrease of Ndrg2 expression in thyroid carcinomas. When comparing adenomas or carcinomas with adjacent normal tissue from the same individual, the mRNA expression level of NDRG2 was significantly decreased in thyroid carcinoma tissues, while there was little difference in adenoma tissues. This differential expression was confirmed at the protein level by western blotting. However, there were no significant correlations of NDRG2 expression with gender, age, different histotypes of thyroid cancers or distant metastases. Conclusion Our data indicates that NDRG2 may participate in thyroid carcinogenesis. This finding provides novel insight into the important role of NDRG2 in the development of thyroid carcinomas. Future studies are needed to address whether the down-regulation of NDRG2 is a cause or a consequence of the progression from a normal thyroid to a carcinoma.

Reduced expression of N-Myc downstream-regulated gene 2 in human thyroid cancer

International Nuclear Information System (INIS)

Zhao, Huadong; Chen, Suning; Lin, Wei; Shi, Hai; Ma, Jianjun; Liu, Xinping; Ma, Qingjiu; Yao, Libo; Zhang, Jian; Lu, Jianguo; He, Xianli; Chen, Changsheng; Li, Xiaojun; Gong, Li; Bao, Guoqiang; Fu, Qiang

2008-01-01

NDRG2 (N-Myc downstream-regulated gene 2) was initially cloned in our laboratory. Previous results have shown that NDRG2 expressed differentially in normal and cancer tissues. Specifically, NDRG2 mRNA was down-regulated or undetectable in several human cancers, and over-expression of NDRG2 inhibited the proliferation of cancer cells. NDRG2 also exerts important functions in cell differentiation and tumor suppression. However, it remains unclear whether NDRG2 participates in carcinogenesis of the thyroid. In this study, we investigated the expression profile of human NDRG2 in thyroid adenomas and carcinomas, by examining tissues from individuals with thyroid adenomas (n = 40) and carcinomas (n = 35), along with corresponding normal tissues. Immunohistochemistry, quantitative RT-PCR and western blot methods were utilized to determine both the protein and mRNA expression status of Ndrg2 and c-Myc. The immunostaining analysis revealed a decrease of Ndrg2 expression in thyroid carcinomas. When comparing adenomas or carcinomas with adjacent normal tissue from the same individual, the mRNA expression level of NDRG2 was significantly decreased in thyroid carcinoma tissues, while there was little difference in adenoma tissues. This differential expression was confirmed at the protein level by western blotting. However, there were no significant correlations of NDRG2 expression with gender, age, different histotypes of thyroid cancers or distant metastases. Our data indicates that NDRG2 may participate in thyroid carcinogenesis. This finding provides novel insight into the important role of NDRG2 in the development of thyroid carcinomas. Future studies are needed to address whether the down-regulation of NDRG2 is a cause or a consequence of the progression from a normal thyroid to a carcinoma

Expression of p16(INK4A) gene in human pituitary tumours.

Science.gov (United States)

Machiavelli, Gloria; Cotignola, Javier; Danilowicz, Karina; Carbonara, Carolina; Paes de Lima, Andrea; Basso, Armando; Bruno, Oscar Domingo; Szijan, Irene

2008-01-01

Pituitary adenomas comprise 10-15% of primary intracranial tumours but the mechanisms leading to tumour development are yet to be clearly established. The retinoblastoma pathway, which regulates the progression through the cell cycle, is often deregulated in different types of tumours. We studied the cyclin-dependent kinase inhibitor p16(INK4A) gene expression at mRNA level in human pituitary adenomas. Forty-six tumour specimens of different subtypes, 21 clinically non-functioning, 12 growth hormone-secreting, 6 prolactin-secreting, 6 adrenocorticotropin-secreting, and 1 thyrotropin-secreting tumours were studied. All clinically non-functioning and most of the hormone-secreting tumours were macroadenomas (38/46). The RT-PCR assay and electrophoresis of the PCR-products showed that p16(INK4A) mRNA was undetectable in: 62% of non-functioning, 8% of growth hormone-secreting, 17% of prolactin-secreting and 17% of adrenocorticotropin-secreting adenomas. Forty percent of all macroadenomas and 25% of microadenomas had negative p16(INK4A) mRNA, the latter results suggest that the absence of p16(INK4A) product might be an early event in tumours with no expression of this suppressor gene. Within the non-functioning adenomas 63% were "null cell" and 37% were positive for some hormone, both subgroups showed similar percentage of cases with absence of p16(INK4A) mRNA. Our results show that clinically non-functioning macroadenomas have impaired p16(INK4A) expression in a clearly higher proportion than any other pituitary tumour subtype investigated. Other regulatory pathways may be implicated in the development of tumours with positive p16(INK4A) expression.

Three cases of thyroid cancer following the diagnosis of testicular cancer: treatment-related complication or genetics?

Science.gov (United States)

Spiliopoulou, Pavlina; Bowers, Sarah Pauline; Gibson, Sarah; White, Jeff; Reed, Nick

2016-05-01

Large-scale epidemiological studies have shown that the incidence of second primary thyroid cancer in subjects diagnosed and treated for testicular cancer is raised. This finding is strongly associated to treatment with radiotherapy and/or chemotherapy and it is explained by their mutagenic effect. On the other hand, inherited cancer susceptibility syndromes inducing both testicular and thyroid cancers denote that these tumours might share common genomic aberrations. We herein present our experience with three cases of metachronous development of thyroid cancer after diagnosis and treatment of testicular cancer in our tertiary cancer centre. Our case report contributes to the limited available literature on such findings and aims to raise awareness of the cancer physicians treating these particular tumour types. © The Author(s) 2016.

Recovery of NIS expression in thyroid cancer cells by overexpression of Pax8 gene

International Nuclear Information System (INIS)

Presta, Ivan; Filetti, Sebastiano; Russo, Diego; Arturi, Franco; Ferretti, Elisabetta; Mattei, Tiziana; Scarpelli, Daniela; Tosi, Emanuele; Scipioni, Angela; Celano, Marilena; Gulino, Alberto

2005-01-01

Recovery of iodide uptake in thyroid cancer cells by means of obtaining the functional expression of the sodium/iodide symporter (NIS) represents an innovative strategy for the treatment of poorly differentiated thyroid cancer. However, the NIS gene expression alone is not always sufficient to restore radioiodine concentration ability in these tumour cells. In this study, the anaplastic thyroid carcinoma ARO cells were stably transfected with a Pax8 gene expression vector. A quantitative RT-PCR was performed to assess the thyroid specific gene expression in selected clones. The presence of NIS protein was detected by Western blot and localized by immunofluorescence. A iodide uptake assay was also performed to verify the functional effect of NIS induction and differentiation switch. The clones overexpressing Pax8 showed the re-activation of several thyroid specific genes including NIS, Pendrin, Thyroglobulin, TPO and TTF1. In ARO-Pax8 clones NIS protein was also localized both in cell cytoplasm and membrane. Thus, the ability to uptake the radioiodine was partially restored, associated to a high rate of efflux. In addition, ARO cells expressing Pax8 presented a lower rate of cell growth. These finding demonstrate that induction of Pax8 expression may determine a re-differentiation of thyroid cancer cells, including a partial recovery of iodide uptake, fundamental requisite for a radioiodine-based therapeutic approach for thyroid tumours

Treatment room length-of-stay and patient throughput with radioiodine thyroid remnant ablation in differentiated thyroid cancer: comparison of thyroid-stimulating hormone stimulation methods.

Science.gov (United States)

Vallejo Casas, Juan Antonio; Mena Bares, Luisa M; Gálvez, María Angeles; Marlowe, Robert J; Latre Romero, José M; Martínez-Paredes, María

2011-09-01

We sought to empirically compare treatment room length-of-stay and patient throughput for recombinant human thyroid-stimulating hormone (rhTSH)-aided thyroid remnant ablation with thyroid hormone withdrawal (THW)-aided ablation in patients with differentiated thyroid carcinoma (DTC). We retrospectively reviewed charts of all eligible (near) totally thyroidectomized patients with DTC undergoing ablation and 1-year ablation success evaluation at our tertiary referral centre from January 2003 to February 2009 (N=274). M1 disease caused exclusion unless discovered by a postablation scan or present when rhTSH was the only tolerable stimulation method. We extracted data on the length-of-stay, defined as the time between treatment room admission and discharge, and patient throughput, defined as patients ablated per treatment room per week. The treatment room discharge criterion was a whole-body dose rate of less than 60 μSv/h at 50 cm. The treatment groups (rhTSH, n=187; THW, n=87) had mostly statistically similar characteristics, but differed in primary tumour status distribution. In addition, at ablation, the rhTSH patients had a greater prevalence of prior diagnostic scintigraphy, higher mean serum TSH, and shorter interval since surgery, and received a 5.6% larger mean ablation activity. On average, rhTSH patients had a significantly lower peak whole-body dose rate (57.1 vs. 83.4 μSv/h at 50 cm; P<0.0001) and a significantly shorter treatment room stay than did the THW patients (1.41 vs. 2.02 days; P<0.001). rhTSH use allowed significantly more patients to be ablated per room per week (2.7 vs. 1.2; P<0.001). Relative to THW, rhTSH use to aid ablation reduced mean treatment room length-of-stay by almost one-third and more than doubled the average weekly patient throughput, both of which were significant differences.

The effects of thyroid hormones on brown adipose tissue in humans: a PET-CT study.

Science.gov (United States)

Zhang, Qiongyue; Miao, Qing; Ye, Hongying; Zhang, Zhaoyun; Zuo, Chuantao; Hua, Fengchun; Guan, Yihui; Li, Yiming

2014-09-01

Brown adipose tissue (BAT) is important for energy expenditure through thermogenesis, although its regulatory factors are not well known in humans. There is evidence suggesting that thyroid hormones affect BAT functions in some mammals, but the effects of thyroid hormones on BAT activity in humans are still unclear. The aim of this study was to investigate the effects of thyroid hormones on glucose metabolism of BAT and other organs in humans. Nine Graves' disease-caused hyperthyroid patients who were newly diagnosed and untreated were studied. Putative brown adipose tissue activity was determined by the integrated ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron-emission tomography and computed tomography (PET-CT). All hyperthyroid patients were treated with methimazole and had been monitored until their symptoms disappeared and thyroid hormone levels returned to normal. At the end, a second PET-CT scan was performed. The average follow-up period was 77 days. Meanwhile, compared with a group of seventy-five brown adipose tissue-negative controls, thyroid hormones of seventy-five BAT-positive healthy subjects were measured. Active brown adipose tissue was not present in any of the hyperthyroid patients. However, one patient with normalized thyroid function showed active BAT after therapy. The free T3 levels and free T4 levels were significantly lower in the 75 BAT-positive subjects than in the BAT-negative subjects. All hyperthyroid patients showed symmetrically increased uptake of fluorodeoxyglucose in skeletal muscles before treatment, whereas, the standardized uptake value was substantially decreased after treatment. Abnormally high circulating thyroid hormone levels may not increase brown adipose tissue activity, which may be limited by the increased obligatory thermogenesis of muscle in adult humans. Copyright © 2014 John Wiley & Sons, Ltd.

Diffuse Optical Characterization of the Healthy Human Thyroid Tissue and Two Pathological Case Studies.

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Claus Lindner

Full Text Available The in vivo optical and hemodynamic properties of the healthy (n = 22 and pathological (n = 2 human thyroid tissue were measured non-invasively using a custom time-resolved spectroscopy (TRS and diffuse correlation spectroscopy (DCS system. Medical ultrasound was used to guide the placement of the hand-held hybrid optical probe. TRS measured the absorption and reduced scattering coefficients (μa, μs' at three wavelengths (690, 785 and 830 nm to derive total hemoglobin concentration (THC and oxygen saturation (StO2. DCS measured the microvascular blood flow index (BFI. Their dependencies on physiological and clinical parameters and positions along the thyroid were investigated and compared to the surrounding sternocleidomastoid muscle. The THC in the thyroid ranged from 131.9 μM to 144.8 μM, showing a 25-44% increase compared to the surrounding sternocleidomastoid muscle tissue. The blood flow was significantly higher in the thyroid (BFIthyroid = 16.0 × 10-9 cm2/s compared to the muscle (BFImuscle = 7.8 × 10-9 cm2/s, while StO2 showed a small (StO2, muscle = 63.8% to StO2, thyroid = 68.4%, yet significant difference. Two case studies with thyroid nodules underwent the same measurement protocol prior to thyroidectomy. Their THC and BFI reached values around 226.5 μM and 62.8 × 10-9 cm2/s respectively showing a clear contrast to the nodule-free thyroid tissue as well as the general population. The initial characterization of the healthy and pathologic human thyroid tissue lays the ground work for the future investigation on the use of diffuse optics in thyroid cancer screening.

Radioiodine Thyroid Remnant Ablation after Recombinant Human Thyrotropin or Thyroid Hormone Withdrawal in Patients with High-Risk Differentiated Thyroid Cancer

Directory of Open Access Journals (Sweden)

Fabián Pitoia

2012-01-01

Full Text Available To supplement limited relevant literature, we retrospectively compared ablation and disease outcomes in high-risk differentiated thyroid carcinoma (DTC patients undergoing radioiodine thyroid remnant ablation aided by recombinant human thyrotropin (rhTSH versus thyroid hormone withdrawal/withholding (THW. Our cohort was 45 consecutive antithyroglobulin antibody- (TgAb- negative, T3-T4/N0-N1-Nx/M0 adults ablated with high activities at three referral centers. Ablation success comprised negative (<1 μg/L stimulated serum thyroglobulin (Tg and TgAb, with absent or <0.1% scintigraphic thyroid bed uptake. “No evidence of disease” (NED comprised negative unstimulated/stimulated Tg and no suspicious neck ultrasonography or pathological imaging or biopsy. “Persistent disease” was failure to achieve NED, “recurrence,” loss of NED status. rhTSH patients (n=18 were oftener ≥45 years old and higher stage (P=0.01, but otherwise not different than THW patients (n=27 at baseline. rhTSH patients were significantly oftener successfully ablated compared to THW patients (83% versus 67%, P<0.02. After respective 3.3 yr and 4.5 yr mean follow-ups (P=0.02, NED was achieved oftener (72% versus 59% and persistent disease was less frequent in rhTSH patients (22% versus 33% (both comparisons P=0.03. rhTSH stimulation is associated with at least as good outcomes as is THW in ablation of high-risk DTC patients.

Radioiodine thyroid remnant ablation after recombinant human thyrotropin or thyroid hormone withdrawal in patients with high-risk differentiated thyroid cancer.

Science.gov (United States)

Pitoia, Fabián; Marlowe, Robert J; Abelleira, Erika; Faure, Eduardo N; Bueno, Fernanda; Schwarzstein, Diego; Lutfi, Rubén Julio; Niepomniszcze, Hugo

2012-01-01

To supplement limited relevant literature, we retrospectively compared ablation and disease outcomes in high-risk differentiated thyroid carcinoma (DTC) patients undergoing radioiodine thyroid remnant ablation aided by recombinant human thyrotropin (rhTSH) versus thyroid hormone withdrawal/withholding (THW). Our cohort was 45 consecutive antithyroglobulin antibody- (TgAb-) negative, T3-T4/N0-N1-Nx/M0 adults ablated with high activities at three referral centers. Ablation success comprised negative (<1 μg/L) stimulated serum thyroglobulin (Tg) and TgAb, with absent or <0.1% scintigraphic thyroid bed uptake. "No evidence of disease" (NED) comprised negative unstimulated/stimulated Tg and no suspicious neck ultrasonography or pathological imaging or biopsy. "Persistent disease" was failure to achieve NED, "recurrence," loss of NED status. rhTSH patients (n = 18) were oftener ≥45 years old and higher stage (P = 0.01), but otherwise not different than THW patients (n = 27) at baseline. rhTSH patients were significantly oftener successfully ablated compared to THW patients (83% versus 67%, P < 0.02). After respective 3.3 yr and 4.5 yr mean follow-ups (P = 0.02), NED was achieved oftener (72% versus 59%) and persistent disease was less frequent in rhTSH patients (22% versus 33%) (both comparisons P = 0.03). rhTSH stimulation is associated with at least as good outcomes as is THW in ablation of high-risk DTC patients.

Immunity to tumour antigens.

Science.gov (United States)

Li, Geng; Ali, Selman A; McArdle, Stephanie E B; Mian, Shahid; Ahmad, Murrium; Miles, Amanda; Rees, Robert C

2005-01-01

During the last decade, a large number of human tumour antigens have been identified. These antigens are classified as tumour-specific shared antigens, tissue-specific differentiation antigens, overexpressed antigens, tumour antigens resulting from mutations, viral antigens and fusion proteins. Antigens recognised by effectors of immune system are potential targets for antigen-specific cancer immunotherapy. However, most tumour antigens are self-proteins and are generally of low immunogenicity and the immune response elicited towards these tumour antigens is not always effective. Strategies to induce and enhance the tumour antigen-specific response are needed. This review will summarise the approaches to discovery of tumour antigens, the current status of tumour antigens, and their potential application to cancer treatment.

Thyroid carcinoma: The experience at the Oncology Centre in Nicosia, Cyprus

International Nuclear Information System (INIS)

Frangos, S.; Petrou, M.; Katodritis, N.

2004-01-01

Full text: Carcinoma of the thyroid is usually of follicular cell origin. Four distinct histologic types of follicular cell-derived cancers (FCDC) are recognized. The majority of cases are papillary, with its major sub-type being the follicular variant (FVPTC). The other histological types are follicular, oxyphilic or Hurthle cell, and anaplastic. Each tumour type differs substantially in its initial mode of spread and subsequent pattern of recurrence and metastatic involvement. Although thyroid nodules are extremely common but clinically recognized thyroid carcinomas constitute less than 1% of all human malignant tumours. The annual incidence of thyroid cancer varies worldwide from 0.5 to 10 per 100000 population. In Cyprus, in the year 2000, there were 41 registered cases of newly diagnosed thyroid carcinoma (medullary excluded) in the Cancer Archive. This is an incidence of 5.6 per 100000. A Bank of Cyprus Oncology Center (BOCOC) was established in 1998 and very soon became the referral hospital for oncological patients in Cyprus. The thyroid clinic of the center was also established in that year which in collaboration with the NM department of the Nicosia General Hospital provided follow-up services to thyroid cancer patients. The Nuclear Medicine Department of the BOCOC was established on 1 July 2001 and since then the radioiodine therapy and follow-up thyroid carcinoma patients is done in this center. The patients are referred to the clinic after surgery and confirmed diagnosis of Thyroid Cancer. A total of 34 patients (5 males 29 females, age range 20-79 years) of thyroid carcinoma (medullary excluded) visited the clinic between July 2001 and July 2003. The histopathological form was 32 papillary and 2 follicular thyroid carcinoma. Of the 32 papillary 2 were metastatic, 4 papillary with follicular elements, 1 with papillary at the isthmus and follicular in right lobe and 1 papillary in the thyroglossal cyst. Preoperative diagnosis in most of the patients was

Stereology of the thyroid gland in Indo-Pacific bottlenose dolphin (Tursiops aduncus in comparison with human (Homo sapiens: quantitative and functional implications.

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Brian Chin Wing Kot

Full Text Available The mammalian thyroid gland maintains basal metabolism in tissues for optimal function. Determining thyroid volume is important in assessing growth and involution. Volume estimation is also important in stereological studies. Direct measurements of colloid volume and nuclear-to-cytoplasmic ratio of the follicular cells may provide important information about thyroid gland function such as hormone storage and secretion, which helps understand the changes at morphological and functional levels. The present study determined the colloid volume using simple stereological principle and the nuclear-to-cytoplasmic ratio of 4 Indo-Pacific bottlenose dolphins and 2 human thyroid glands. In both dolphin and human thyroid glands, the size of the follicles tended to be quite variable. The distribution of large and small follicles within the thyroid gland was also found to be random in both the dolphin and human thyroid gland; however, the size of follicles appeared to decrease as a function of increasing age in the dolphin thyroid gland. The mean colloid volume of the dolphin thyroid gland and human thyroid gland was 1.22×10(5 µm(3 and 7.02×10(5 µm(3 respectively. The dolphin and human subjects had a significant difference in the mean colloid volume. The mean N/C ratio of the dolphin thyroid follicular epithelia and human follicular epithelia was 0.50 and 0.64 respectively. The dolphin and human subjects had a significant difference in the mean N/C ratio. This information contributes to understanding dolphin thyroid physiology and its structural adaptations to meet the physical demands of the aquatic environment, and aids with ultrasonography and corrective therapy in live subjects.

(−) Arctigenin and (+) Pinoresinol Are Antagonists of the Human Thyroid Hormone Receptor β

Science.gov (United States)

2015-01-01

Lignans are important biologically active dietary polyphenolic compounds. Consumption of foods that are rich in lignans is associated with positive health effects. Using modeling tools to probe the ligand-binding pockets of molecular receptors, we found that lignans have high docking affinity for the human thyroid hormone receptor β. Follow-up experimental results show that lignans (−) arctigenin and (+) pinoresinol are antagonists of the human thyroid hormone receptor β. The modeled complexes show key plausible interactions between the two ligands and important amino acid residues of the receptor. PMID:25383984

Neutrophil-induced transmigration of tumour cells treated with tumour-conditioned medium is facilitated by granulocyte-macrophage colony-stimulating factor.

LENUS (Irish Health Repository)

Wu, Q D

2012-02-03

OBJECTIVE: To investigate the effect of different cytokines that are present in tumour-conditioned medium on human neutrophil (PMN)-induced tumour cell transmigration. DESIGN: Laboratory study. SETTING: University hospital, Ireland. MATERIAL: Isolated human PMN and cultured human breast tumour cell line, MDA-MB-231. Interventions: Human PMN treated with either tumour-conditioned medium or different media neutralised with monoclonal antibodies (MoAb), and MDA-MB-231 cells were plated on macrovascular and microvascular endothelial monolayers in collagen-coated transwells to assess migration of tumour cells. MAIN OUTCOME MEASURES: Cytokines present in tumour-conditioned medium, PMN cytocidal function and receptor expression, and tumour cell transmigration. RESULTS: tumour-conditioned medium contained high concentrations of granulocyte-macrophage colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF), and interleukin 8 (IL-8), but not granulocyte colony-stimulating factor (G-CSF) and interleukin 3 (IL-3). Anti-GM-CSF MoAb significantly reduced PMN-induced transmigration of tumour cells treated with tumour-conditioned medium (p < 0.05), whereas anti-VEGF and anti-IL-8 MoAbs did not affect their migration. In addition, anti-GM-CSF MoAb, but not anti-VEGF or anti-IL-8 MoAb, reduced PMN CD11b and CD18 overexpression induced by tumour-conditioned medium (p < 0.05). CONCLUSION: These results indicate that the GM-CSF that is present in tumour-conditioned medium may be involved, at least in part, in alterations in PMN function mediated by the medium and subsequently PMN-induced transmigration of tumour cells.

Human cytomegalovirus tegument protein pp65 is detected in all intra- and extra-axial brain tumours independent of the tumour type or grade.

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Sylwia Libard

Full Text Available Human cytomegalovirus (HCMV has been indicated being a significant oncomodulator. Recent reports have suggested that an antiviral treatment alters the outcome of a glioblastoma. We analysed the performance of commercial HCMV-antibodies applying the immunohistochemical (IHC methods on brain sample obtained from a subject with a verified HCMV infection, on samples obtained from 14 control subjects, and on a tissue microarray block containing cores of various brain tumours. Based on these trials, we selected the best performing antibody and analysed a cohort of 417 extra- and intra-axial brain tumours such as gliomas, medulloblastomas, primary diffuse large B-cell lymphomas, and meningiomas. HCMV protein pp65 immunoreactivity was observed in all types of tumours analysed, and the IHC expression did not depend on the patient's age, gender, tumour type, or grade. The labelling pattern observed in the tumours differed from the labelling pattern observed in the tissue with an active HCMV infection. The HCMV protein was expressed in up to 90% of all the tumours investigated. Our results are in accordance with previous reports regarding the HCMV protein expression in glioblastomas and medulloblastomas. In addition, the HCMV protein expression was seen in primary brain lymphomas, low-grade gliomas, and in meningiomas. Our results indicate that the HCMV protein pp65 expression is common in intra- and extra-axial brain tumours. Thus, the assessment of the HCMV expression in tumours of various origins and pathologically altered tissue in conditions such as inflammation, infection, and even degeneration should certainly be facilitated.

Skeletal muscle metastases: primary tumours, prevalence, and radiological features

International Nuclear Information System (INIS)

Surov, Alexey; Spielmann, Rolf Peter; Behrmann, Curd; Hainz, Michael; Holzhausen, Hans-Juergen; Arnold, Dirk; Katzer, Michaela; Schmidt, Joerg

2010-01-01

Although skeletal muscles comprise nearly 50% of the total human body mass and are well vascularised, metastases in the musculature are rare. The reported prevalence of skeletal muscle metastases from post-mortem studies of patients with cancer is inconstant and ranges from 0.03 to 17.5%. Of 5,170 patients with metastasised cancer examined and treated at our institution during the period from January 2000 to December 2007, 61 patients with muscle metastases (80 lesions) were identified on computed tomography (CT). Genital tumours (24.6%) were the most frequent malignancies metastasising into the skeletal musculature, followed by gastrointestinal tumours (21.3%), urological tumours (16.4%), and malignant melanoma (13.1%). Other primary malignancies were rarer, including bronchial carcinoma (8.2%), thyroid gland carcinoma (4.9%), and breast carcinoma (3.3%). In 8.2%, carcinoma of unknown primary was diagnosed. Skeletal muscle metastases (SMM) were located in the iliopsoas muscle (27.5%), paravertebral muscles (25%), gluteal muscles (16.3%), lower extremity muscles (12.5%), abdominal wall muscles (10%), thoracic wall muscles (5%), and upper extremity muscles (3.8%). Most (76.3%) of the 80 SMM were diagnosed incidentally during routine staging CT examinations, while 23.7% were symptomatic. Radiologically, SMM presented with five different types of lesions: focal intramuscular masses (type I, 52.5% of SMM), abscess-like intramuscular lesions (type II, 32.5%), diffuse metastatic muscle infiltration (type III, 8.8%), multifocal intramuscular calcification (type IV, 3.7%) and intramuscular bleeding (type V, 2.5%). (orig.)

Skeletal muscle metastases: primary tumours, prevalence, and radiological features

Energy Technology Data Exchange (ETDEWEB)

Surov, Alexey; Spielmann, Rolf Peter; Behrmann, Curd [Martin-Luther-University Halle-Wittenberg, Department of Radiology, Halle (Germany); Hainz, Michael; Holzhausen, Hans-Juergen [Martin-Luther-University Halle-Wittenberg, Department of Pathology, Halle (Germany); Arnold, Dirk [Martin-Luther-University Halle-Wittenberg, Department of Haematology/Oncology, Halle (Germany); Katzer, Michaela [Martin-Luther-University Halle-Wittenberg, Department of Urology, Halle (Germany); Schmidt, Joerg [Martin-Luther-University Halle-Wittenberg, Department of Medical Statistics and Controlling, Halle (Germany)

2010-03-15

Although skeletal muscles comprise nearly 50% of the total human body mass and are well vascularised, metastases in the musculature are rare. The reported prevalence of skeletal muscle metastases from post-mortem studies of patients with cancer is inconstant and ranges from 0.03 to 17.5%. Of 5,170 patients with metastasised cancer examined and treated at our institution during the period from January 2000 to December 2007, 61 patients with muscle metastases (80 lesions) were identified on computed tomography (CT). Genital tumours (24.6%) were the most frequent malignancies metastasising into the skeletal musculature, followed by gastrointestinal tumours (21.3%), urological tumours (16.4%), and malignant melanoma (13.1%). Other primary malignancies were rarer, including bronchial carcinoma (8.2%), thyroid gland carcinoma (4.9%), and breast carcinoma (3.3%). In 8.2%, carcinoma of unknown primary was diagnosed. Skeletal muscle metastases (SMM) were located in the iliopsoas muscle (27.5%), paravertebral muscles (25%), gluteal muscles (16.3%), lower extremity muscles (12.5%), abdominal wall muscles (10%), thoracic wall muscles (5%), and upper extremity muscles (3.8%). Most (76.3%) of the 80 SMM were diagnosed incidentally during routine staging CT examinations, while 23.7% were symptomatic. Radiologically, SMM presented with five different types of lesions: focal intramuscular masses (type I, 52.5% of SMM), abscess-like intramuscular lesions (type II, 32.5%), diffuse metastatic muscle infiltration (type III, 8.8%), multifocal intramuscular calcification (type IV, 3.7%) and intramuscular bleeding (type V, 2.5%). (orig.)

Triiodothyronine and reverse triiodothyronine contents in human and pig thyroids at different periods of development

International Nuclear Information System (INIS)

Etling, Nicole; Gehin-Fouque, Francoise

1978-01-01

3,5,3'-triiodothyronine (T 3 ), and 3,3',5'-triiodothyronine (rT 3 ) were measured by radioimmunoassay in saline extracts of neonates and human adult thyroid tissues and of fetuses, Piglets and adult Swine thyroid tissues. In all these extracts, T 3 content was higher than rT 3 content whatever the period of development. Both triiodoamino acids represent a small percentage of the iodinated protein in thyroid tissues [fr

Relative quantification of PIK3CA gene expression level in fine-needle aspiration biopsy thyroid specimens collected from patients with papillary thyroid carcinoma and non-toxic goitre by real-time RT-PCR

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Wojciechowska-Durczyńska Katarzyna

2010-08-01

Full Text Available Abstract Background Recent studies have shown that the phosphatidylinositol 3-kinase (PI3K signaling pathway is important regulator of many cellular events, including apoptosis, proliferation and motility. PI3K pathway alterations (PIK3CA gene mutations and/or amplification have been observed in various human tumours. In the majority of diagnosed cases, mutations are localized in one of the three "hot spots" in the gene, responsible for coding catalytic subunit α of class I PI3K (PIK3CA. Mutations and amplification of PIK3CA gene are characteristic for thyroid cancer, as well. Methods The aim of our study was to examine a gene expression level of PIK3CA in fine-needle aspiration biopsy (FNAB thyroid specimens in two types of thyroid lesions, papillary thyroid carcinoma (PTC and non-toxic goitre (NTG. Following conventional cytological examination, 42 thyroid FNAB specimens, received from patients with PTC (n = 20 and NTG (n = 22, were quantitatively evaluated regarding PIK3CA expression level by real-time PCR in the ABI PRISM® 7500 Sequence Detection System. Results Significantly higher expression level (RQ of PIK3CA in PTC group has been noted in comparison with NTG group (p Conclusion These observations may suggest role of PIK3CA alterations in PTC carcinogenesis.

Thyroid remnant ablation success and disease outcome in stage III or IV differentiated thyroid carcinoma: recombinant human thyrotropin versus thyroid hormone withdrawal.

Science.gov (United States)

Vallejo Casas, Juan A; Mena Bares, Luisa M; Gálvez Moreno, Maria A; Moreno Ortega, Estefanía; Marlowe, Robert J; Maza Muret, Francisco R; Albalá González, María D

2016-06-01

Most publications to date compare outcomes after post-surgical thyroid remnant ablation stimulated by recombinant human thyrotropin (rhTSH) versus thyroid hormone withholding/withdrawal (THW) in low-recurrence risk differentiated thyroid carcinoma (DTC) patients. We sought to perform this comparison in high-risk patients. We retrospectively analyzed ~9-year single-center experience in 70 consecutive adults with initial UICC (Union for International Cancer Control) stage III/IV, M0 DTC undergoing rhTSH-aided (N.=54) or THW-aided (N.=16) high-activity ablation. Endpoints included ablation success and DTC outcome. Assessed ≥1 year post-ablation, ablation success comprised a) no visible scintigraphic thyroid bed uptake or pathological extra-thyroidal uptake; b) undetectable stimulated serum thyroglobulin (Tg) without interfering autoantibodies; c) both criteria. DTC outcome, determined at the latest visit, comprised either 1) "no evidence of disease" (NED): undetectable Tg, negative Tg autoantibodies, negative most recent whole-body scan, no suspicious findings clinically, on neck ultrasonography, or on other imaging; 2) persistent disease: failure to attain NED; or 3) recurrence: loss of NED. After the first ablative activity, ablation success by scintigraphic plus biochemical criteria was 64.8% in rhTSH patients, 56.3% in THW patients (P=NS). After 3.5-year versus 6.2-year median follow-up (P<0.05), DTC outcomes were NED, 85.2%, persistent disease, 13.0%, recurrence, 1.9%, in the rhTSH group and NED, 87.5%, persistent or recurrent disease, 6.3% each, in the THW group (P=NS). In patients with initial stage III/IV, M0 DTC, rhTSH-aided and THW-assisted ablation were associated with comparable remnant eradication or DTC cure rates.

Electrical conductivity measurement of excised human metastatic liver tumours before and after thermal ablation.

Science.gov (United States)

Haemmerich, Dieter; Schutt, David J; Wright, Andrew W; Webster, John G; Mahvi, David M

2009-05-01

We measured the ex vivo electrical conductivity of eight human metastatic liver tumours and six normal liver tissue samples from six patients using the four electrode method over the frequency range 10 Hz to 1 MHz. In addition, in a single patient we measured the electrical conductivity before and after the thermal ablation of normal and tumour tissue. The average conductivity of tumour tissue was significantly higher than normal tissue over the entire frequency range (from 4.11 versus 0.75 mS cm(-1) at 10 Hz, to 5.33 versus 2.88 mS cm(-1) at 1 MHz). We found no significant correlation between tumour size and measured electrical conductivity. While before ablation tumour tissue had considerably higher conductivity than normal tissue, the two had similar conductivity throughout the frequency range after ablation. Tumour tissue conductivity changed by +25% and -7% at 10 Hz and 1 MHz after ablation (0.23-0.29 at 10 Hz, and 0.43-0.40 at 1 MHz), while normal tissue conductivity increased by +270% and +10% at 10 Hz and 1 MHz (0.09-0.32 at 10 Hz and 0.37-0.41 at 1 MHz). These data can potentially be used to differentiate tumour from normal tissue diagnostically.

Ribosomal protein S6 phosphorylation and morphological changes in response to the tumour promoter 12-O-tetradecanoylphorbol 13-acetate in primary human tumour cells, established and transformed cell lines

DEFF Research Database (Denmark)

Rance, A J; Thönnes, M; Issinger, O G

1985-01-01

lifespan (fibroblasts, primary human tumour cells) can be mimicked by unknown steps also associated with immortalization (establishment function) and the transformed state of the tumour cells. Another interesting observation were morphological changes of the established and SV40-transformed cells which...

The value of ultrasound in the follow-up of thyroid cancer

DEFF Research Database (Denmark)

Bennedbæk, Finn Noe; Hegedüs, Laszlo

2014-01-01

The value of ultrasound in the follow-up of thyroid cancer The commonly used tumour-node-metastasis (TNM) staging system is designed to predict death and not recurrence. Based on this, patients with thyroid cancer are grouped into risk categories at the time of initial treatment. However, recent...... guidelines proposed a novel staging system focusing on microscopic invasion into the perithyroidal tissues, neck lymph node involvement and 131I uptake outside the thyroid bed following treatment. This risk re-assessment improves the prediction of recurrent/persistent disease. The cornerstone in the follow......-up is measurement of plasma-thyroglobulin concentration and ultrasound of the neck focusing on the thyroid bed and classification of lymph nodes according to their location and high risk signs....

History of thyroid disease and survival of ovarian cancer patients

DEFF Research Database (Denmark)

Minlikeeva, Albina N; Freudenheim, Jo L; Cannioto, Rikki A

2017-01-01

BACKGROUND: Findings from in vitro studies suggest that increased exposure to thyroid hormones can influence progression of ovarian tumours. However, epidemiologic evidence on this topic is limited. METHODS: We pooled data from 11 studies from the Ovarian Cancer Association Consortium. Using mult...

Acetyltransferases and tumour suppression

International Nuclear Information System (INIS)

Phillips, A C; Vousden, Karen H

2000-01-01

The acetyltransferase p300 was first identified associated with the adenoviral transforming protein E1A, suggesting a potential role for p300 in the regulation of cell proliferation. Direct evidence demonstrating a role for p300 in human tumours was lacking until the recentl publication by Gayther et al, which strongly supports a role for p300 as a tumour suppressor. The authors identify truncating mutations associated with the loss or mutation of the second allele in both tumour samples and cell lines, suggesting that loss of p300 may play a role in the development of a subset of human cancers

Altered Peptidase Activities in Thyroid Neoplasia and Hyperplasia

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Gorka Larrinaga

2013-01-01

Full Text Available Background. Papillary thyroid carcinoma (PTC, follicular thyroid adenoma (FTA, and thyroid nodular hyperplasia (TNH are the most frequent diseases of the thyroid gland. Previous studies described the involvement of dipeptidyl-peptidase IV (DPPIV/CD26 in the development of thyroid neoplasia and proposed it as an additional tool in the diagnosis/prognosis of these diseases. However, very little is known about the involvement of other peptidases in neoplastic and hyperplastic processes of this gland. Methods. The catalytic activity of 10 peptidases in a series of 30 PTC, 10 FTA, and 14 TNH was measured fluorimetrically in tumour and nontumour adjacent tissues. Results. The activity of DPPIV/CD26 was markedly higher in PTC than in FTA, TNH, and nontumour tissues. Aspartyl aminopeptidase (AspAP, alanyl aminopeptidase (AlaAP, prolyl endopeptidase, pyroglutamyl peptidase I, and aminopeptidase B activities were significantly increased in thyroid neoplasms when compared to nontumour tissues. AspAP and AlaAP activities were also significantly higher in PTC than in FTA and TNH. Conclusions. These data suggest the involvement of DPPIV/CD26 and some cytosolic peptidases in the neoplastic development of PTC and FTA. Further studies will help to define the possible clinical usefulness of AlaAP and AspAP in the diagnosis/prognosis of thyroid neoplasms.

Altered peptidase activities in thyroid neoplasia and hyperplasia.

Science.gov (United States)

Larrinaga, Gorka; Blanco, Lorena; Errarte, Peio; Beitia, Maider; Sanz, Begoña; Perez, Itxaro; Irazusta, Amaia; Sánchez, Clara E; Santaolalla, Francisco; Andrés, Leire; López, José I

2013-01-01

Papillary thyroid carcinoma (PTC), follicular thyroid adenoma (FTA), and thyroid nodular hyperplasia (TNH) are the most frequent diseases of the thyroid gland. Previous studies described the involvement of dipeptidyl-peptidase IV (DPPIV/CD26) in the development of thyroid neoplasia and proposed it as an additional tool in the diagnosis/prognosis of these diseases. However, very little is known about the involvement of other peptidases in neoplastic and hyperplastic processes of this gland. The catalytic activity of 10 peptidases in a series of 30 PTC, 10 FTA, and 14 TNH was measured fluorimetrically in tumour and nontumour adjacent tissues. The activity of DPPIV/CD26 was markedly higher in PTC than in FTA, TNH, and nontumour tissues. Aspartyl aminopeptidase (AspAP), alanyl aminopeptidase (AlaAP), prolyl endopeptidase, pyroglutamyl peptidase I, and aminopeptidase B activities were significantly increased in thyroid neoplasms when compared to nontumour tissues. AspAP and AlaAP activities were also significantly higher in PTC than in FTA and TNH. These data suggest the involvement of DPPIV/CD26 and some cytosolic peptidases in the neoplastic development of PTC and FTA. Further studies will help to define the possible clinical usefulness of AlaAP and AspAP in the diagnosis/prognosis of thyroid neoplasms.

Near-lethal respiratory failure after recombinant human thyroid-stimulating hormone use in a patient with metastatic thyroid carcinoma.

Science.gov (United States)

Goffman, Thomas; Ioffe, Vladimir; Tuttle, Michael; Bowers, John T; Mason, M Elizabeth

2003-08-01

A patient with widely metastatic differentiated thyroid cancer who had been heavily pretreated with (131)I was given recombinant human thyroid stimulating hormone (rhTSH) prior to (131)I treatment. Clinical and physical data from both this case and the literature suggest that the recombinant hormone, not the (131)I, may have caused a significant portion of the tumor swelling, which in turn was the most likely cause of the patient's symptoms. The potential effect of (131)I-induced tumor swelling and direct radiation effect on the lung is also analyzed. We review the potential hazards associated with rhTSH in patients with metastasis and propose means of minimizing this risk.

Hyperactivity and Learning Deficits in Transgenic Mice Bearing a Human Mutant Thyroid Hormone β1 Receptor Gene

OpenAIRE

McDonald, Michael P.; Wong, Rosemary; Goldstein, Gregory; Weintraub, Bruce; Cheng, Sheue-yann; Crawley, Jacqueline N.

1998-01-01

Resistance to thyroid hormone (RTH) is a human syndrome mapped to the thyroid receptor β (TRβ) gene on chromosome 3, representing a mutation of the ligandbinding domain of the TRβ gene. The syndrome is characterized by reduced tissue responsiveness to thyroid hormone and elevated serum levels of thyroid hormones. A common behavioral phenotype associated with RTH is attention deficit hyperactivity disorder (ADHD). To test the hypothesis that RTH produces attention deficits and/or hyperactivity...

Neuroanatomical pathways for thyroid hormone feedback in the human hypothalamus

NARCIS (Netherlands)

Alkemade, Anneke; Friesema, Edith C.; Unmehopa, Unga A.; Fabriek, Babs O.; Kuiper, George G.; Leonard, Jack L.; Wiersinga, Wilmar M.; Swaab, Dick F.; Visser, Theo J.; Fliers, Eric

2005-01-01

Context: Recent findings point to an increasing number of hypothalamic proteins involved in the central regulation of thyroid hormone feedback. The functional neuroanatomy of these proteins in the human hypothalamus is largely unknown at present. Objective: The aim of this study was to report the

Oxygen tension in human tumours measured with polarographic needle electrodes and its relationship to vascular density, necrosis and hypoxia

International Nuclear Information System (INIS)

Lyng, Heidi; Sundfoer, Kolbein; Rofstad, Einar K.

1997-01-01

Background and purpose: The use of polarographic needle electrodes for measurement of oxygen tension (pO 2 ) in tumours requires documentation of the validity of the method. In the present work the pO 2 values measured polarographically with the Eppendorf pO 2 histograph in human tumours were compared with the histological appearance of the tumour tissue, i.e. vascular density, fraction of necrosis and fraction of hypoxic tissue, to investigate whether the measurements reflected the expected pO 2 . Materials and methods: The pO 2 was measured in cervix tumours in patients and in human melanoma xenografted tumours in athymic mice. Vascular density was determined in the cervix tumours by histological analysis of biopsies from the pO 2 measurement tracks. Fraction of necrosis and fraction of hypoxic tissue, i.e. tissue binding the hypoxia marker pimonidazole, were determined in the melanomas by analysis of histological sections from the tumour planes in which the pO 2 measurements were performed. Results: The pO 2 distributions showed large intratumour heterogeneity. In cervix tumours, tumour regions with vascular density (vascular length per unit tissue volume) in the range of 47-77 mm/mm 3 showed higher pO 2 than tumour regions with vascular density in the range of 20-47 mm/mm 3 , which in turn showed higher pO 2 than tumour regions with vascular density in the range of 0-20 mm/mm 3 . In melanomas, tumour regions in which necrosis and hypoxia constituted more than 50% of the tissue showed lower pO 2 than other tumour regions. Conclusions: The pO 2 measured in the tumours was consistent with the histological appearance of the tissue in which the measurements were performed, suggesting that reliable pO 2 distributions of tumours can be obtained with polarographic needle electrodes

Deregulation of the RB pathway in human testicular germ cell tumours

DEFF Research Database (Denmark)

Bartkova, Jirina; Lukas, Claudia; Sørensen, Claus S

2003-01-01

Deregulation of the RB pathway is shared by most human malignancies. Components upstream of the retinoblastoma tumour suppressor (pRB), namely the INK4 family of cyclin-dependent kinase (CDK) inhibitors, the D-type cyclins, their partner kinases CDK4/CDK6, and pRB as their critical substrate...

[Autonomy and malignancy of thyroid glad tumors. A critical analysis of the literature on the existence of hyperfunctioning follicular and papillary thyroid gland carcinomas].

Science.gov (United States)

Schröder, S; Marthaler, B

1996-09-01

Data in the literature communicated in 63 publications were evaluated in which scintigraphically warm or hot nodules were described as identical to a follicular or papillary carcinoma diagnosed based on histology of the resection specimen, thus suggesting autonomous hyperfunction of a malignant thyroid neoplasia. In the majority of cases, this assumption could not be accepted, or only within strict limits. In these patients, it appeared more likely that the carcinoma was located adjacent to or within a benign hyperfunctioning thyroid area or that large masses of a thyroid carcinoma had only simulated the picture of a hyperfunctioning nodule by suppression of endogenous TSH and thus of the residual parenchyma's function. In other cases, the diagnosis of a hyperfunctioning thyroid carcinoma had to be doubted or rejected owing to the lack of plausibility of the documented morphological findings. At the end of the literature survey, only 10 case descriptions unequivocally verified that, though very rarely, a papillary or follicular thyroid carcinoma may manifest itself as a solitary warm or hot thyroid nodule. Such a scintigraphical finding thus cannot be regarded as proof of benignancy of a given thyroid tumour.

Peripheral blood and intrathyroidal T cell clones from patients with thyroid autoimmune diseases.

Science.gov (United States)

Massart, C; Caroff, G; Maugendre, D; Genetet, N; Gibassier, J

1999-01-01

For a better understanding of the pathogenesis of thyroid autoimmune diseases, we have studied morphological and functional properties of T clones from peripheral blood lymphocytes (PBL) and from intrathyroidal lymphocytes (ITL) obtained from 3 patients with Graves' disease or 1 Hashimoto's thyroiditis. Investigations were carried out on clones cultured alone or cocultured with autologous thyrocytes. Clonage efficiency ranged from 30% to 33% for PBL and 10% to 36% for ITL. A predominance of CD4-positive clones was observed whatever the origin of the lymphocytes or the autoimmune pathology. Gamma interferon (IFN-gamma) was detected in the majority (17/19) of the clones tested. Intracytoplasmic interleukin (IL-4) was secreted in 7/19 clones and both cytokines were produced in 5/19 clones. In coculture a proliferative response and tumour necrosis factor (TNF-alpha) production were observed with 6 clones (4 from Graves thyrocytes and 2 from thyroiditis). No cytotoxic clone was derived from Graves or thyroiditis tissues. These data demonstrate that the large majority of T clones are principally CD4-T cells; all the clones secreted TNF-alpha and a large majority produced IFN-gamma. Only a few clones produced IL-4 alone or associated with IFN-gamma. Six T clones induced proliferative response and of TNF-alpha secretion in coculture. Further investigations must be performed on these antigen-reactive T clones to analyse their role in the pathogenesis of the human thyroid autoimmune diseases.

When should genetic testing be performed in patients with neuroendocrine tumours?

Science.gov (United States)

O'Shea, Triona; Druce, Maralyn

2017-12-01

Neuroendocrine tumours (NETs) are a heterogenous group of tumours arising from neuroendocrine cells in several sites around the body. They include tumours of the gastroenteropancreatic system, phaeochromocytoma and paraganglioma and medullary thyroid cancer. In recent years, it has become increasingly apparent that a number of these tumours arise as a result of germline genetic mutations and are inherited in an autosomal dominant pattern. The number of genes implicated is increasing rapidly. Identifying which patients are likely to have a germline mutation enables clinicians to counsel patients adequately about their future disease risk, and allows for earlier detection of at-risk patients through family screening. The institution of screening and surveillance programmes may in turn lead to a major shift in presentation patterns for some of these tumours. In this review, we examine the features which may lead a clinician to suspect that a patient may have an inherited cause of a NET and we outline which underlying conditions should be suspected. We also discuss what type of screening may be appropriate in a variety of situations.

Modification of nucleotide metabolism in relationship with differentiation and in response to irradiation in human tumour cells

International Nuclear Information System (INIS)

Wei, Shuang

1998-01-01

This research thesis reports the study of the metabolism of nucleotides in human tumour cells. The first part addresses the modifications of nucleotide (more specifically purine) metabolism in relationship with human melanoma cell proliferation and differentiation. The second part addresses the modifications of this metabolism in response to an irradiation in human colon tumour cells. For each part, the author proposes a bibliographic synthesis, and a presentation of studied cells and of methods used to grow cells, and respectively to proliferate and differentiate them or to irradiate them, and then discusses the obtained results [fr

Electrochemotherapy of tumours

International Nuclear Information System (INIS)

Sersa, G.; Cemazar, M.; Rudolf, Z.; Miklavcic, D.

2006-01-01

Electrochemotherapy consists of chemotherapy followed by local application of electric pulses to the tumour to increase drug delivery into cells. Drug uptake can be increased by electroporation for only those drugs whose transport through the plasma membrane is impeded. Among many drugs that have been tested so far, only bleomycin and cisplatin found their way from preclinical testing to clinical trials. In vitro studies demonstrated several fold increase of their cytotoxicity after electroporation of cells. In vivo, electroporation of tumours after local or systemic administration of either of the drugs, i.e. electrochemotherapy, proved to be an effective antitumour treatment. In preclinical studies on several tumour models, electrochemotherapy either with bleomycin or cisplatin was elaborated and parameters for effective local tumour control were determined. In veterinary medicine, electrochemotherapy also proved to be effective in the treatment of primary tumours in cats, dogs and horses. In human clinical studies, electrochemotherapy was performed on the patients with progressive disease and accessible tumour nodules of different malignancies. All clinical studies demonstrated that electrochemotherapy is an effective treatment for local tumour control in cancer patients. (author)

Dual prognostic significance of tumour-associated macrophages in human pancreatic adenocarcinoma treated or untreated with chemotherapy.

Science.gov (United States)

Di Caro, Giuseppe; Cortese, Nina; Castino, Giovanni Francesco; Grizzi, Fabio; Gavazzi, Francesca; Ridolfi, Cristina; Capretti, Giovanni; Mineri, Rossana; Todoric, Jelena; Zerbi, Alessandro; Allavena, Paola; Mantovani, Alberto; Marchesi, Federica

2016-10-01

Tumour-associated macrophages (TAMs) play key roles in tumour progression. Recent evidence suggests that TAMs critically modulate the efficacy of anticancer therapies, raising the prospect of their targeting in human cancer. In a large retrospective cohort study involving 110 patients with pancreatic ductal adenocarcinoma (PDAC), we assessed the density of CD68-TAM immune reactive area (%IRA) at the tumour-stroma interface and addressed their prognostic relevance in relation to postsurgical adjuvant chemotherapy (CTX). In vitro, we dissected the synergism of CTX and TAMs. In human PDAC, TAMs predominantly exhibited an immunoregulatory profile, characterised by expression of scavenger receptors (CD206, CD163) and production of interleukin 10 (IL-10). Surprisingly, while the density of TAMs associated to worse prognosis and distant metastasis, CTX restrained their protumour prognostic significance. High density of TAMs at the tumour-stroma interface positively dictated prognostic responsiveness to CTX independently of T-cell density. Accordingly, in vitro, gemcitabine-treated macrophages became tumoricidal, activating a cytotoxic gene expression programme, inhibiting their protumoural effect and switching to an antitumour phenotype. In patients with human PDAC, neoadjuvant CTX was associated to a decreased density of CD206(+) and IL-10(+) TAMs at the tumour-stroma interface. Overall, our data highlight TAMs as critical determinants of prognostic responsiveness to CTX and provide clinical and in vitro evidence that CTX overall directly re-educates TAMs to restrain tumour progression. These results suggest that the quantification of TAMs could be exploited to select patients more likely to respond to CTX and provide the basis for novel strategies aimed at re-educating macrophages in the context of CTX. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

ULTRASOUND EVALUATION OF THYROID DISEASES

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Battula

2016-04-01

Full Text Available AIMS & OBJECTIVES: 1. To differentiate cystic lesions from solid lesions. 2. The possibility to differentiate the intrinsic thyroid lesions from those arising from adjoining structures. 3. To evaluate the neoplasms and to differentiate benign from malignant lesions by USG characteristics and to correlate with FNAC reports. 4. Role of USG in rapidly growing thyroid lesions: To differentiate haemorrhage into the cystic lesions and rapidly growing malignant tumours. 5. Compare the results of our study with similar studies available in the present literature. MATERIALS & METHODS This study included 75 patients who attended outpatient departments of the Endocrinology, Medical and Surgical Units and also those who were inpatients. RESULTS Broadly pathological conditions of thyroid glands can be divided into nodular and diffuse thyroid diseases. Among Nodular Diseases Majority are benign, only few are malignant. Characteristics of benign lesions are: 1. Well-differentiated margins. 2. Thin complete peripheral sonolucent halo. 3. Coarse peripheral calcifications. Characteristics of malignant nodules are: 1. Ill-defined margins. 2. Thick incomplete peripheral halo. 3. Fine punctuate calcifications. Diffuse Thyroid Diseases 1. Hashimoto’s thyroiditis: Painless diffuse enlargement of thyroid gland usually in women with coarse echotexture and no normal gland tissue. There may be discrete hypoechoic nodules within it with cervical lymphadenopathy. 2. Goitres: a Simple diffuse goitre: Symmetrical enlargement of gland without tenderness or bruit or lymphadenopathy, T3, T4 and TSH are within normal limits and no thyroid autoantibodies in the serum. a Diffuse Toxic goitre: Diffuse enlargement of gland with increased vascularity on colour Doppler study. b Multinodular goitre: Multiple hypoechoic nodule within normal thyroid parenchyma. c Colloid goitre: Present as single or multiple swellings in the thyroid gland. CONCLUSION USG is the fast and cost effective

[F18]-FDG imaging of experimental animal tumours using a hybrid gamma-camera

International Nuclear Information System (INIS)

Lausson, S.; Maurel, G.; Kerrou, K.; Montravers, F.; Petegnief, Y.; Talbot, J.N.; Fredelizi, D.

2001-01-01

Positron emission tomography (PET) has been widely used in clinical studies. This technology permits detection of compounds labelled with positron emitting radionuclides and in particular, [F18]-fluorodeoxyglucose ([F18]-FDG).[F18]-FDG uptake and accumulation is generally related to malignancy; some recent works have suggested the usefulness of PET camera dedicated to small laboratory animals (micro-PET). Our study dealt with the feasibility of [F18]-FDG imaging of malignant tumours in animal models by means of an hybrid camera dedicated for human scintigraphy. We evaluated the ability of coincidence detection emission tomography (CDET) using this hybrid camera to visualize in vivo subcutaneous tumours grafted to mice or rats. P815 murine mastocytoma grafted in syngeneic DBA/2 mice resulted with foci of very high FDG uptake. Tumours with a diameter of only 3 mm were clearly visualized. Medullary thyroid cancer provoked by rMTC 6/23 and CA77 lines in syngeneic Wag/Rij rat was also detected. The differentiated CA77 tumours exhibited avidity for [F18]-FDG and a tumour, which was just palpable (diameter lower than 2 mm), was identified. In conclusion, CDET-FDG is a non-invasive imaging tool which can be used to follow grafted tumours in the small laboratory animal, even when their size is smaller than 1 cm. It has the potential to evaluate experimental anticancer treatments in small series of animals by individual follow-up. It offers the opportunity to develop experimental PET research within a nuclear medicine or biophysics department, the shift to a dedicated micro-PET device being subsequently necessary. It is indeed compulsory to strictly follow the rules for non contamination and disinfection of the hybrid camera. (authors)

Breaking Tolerance to Thyroid Antigens: Changing Concepts in Thyroid Autoimmunity

Science.gov (United States)

Rapoport, Basil

2014-01-01

Thyroid autoimmunity involves loss of tolerance to thyroid proteins in genetically susceptible individuals in association with environmental factors. In central tolerance, intrathymic autoantigen presentation deletes immature T cells with high affinity for autoantigen-derived peptides. Regulatory T cells provide an alternative mechanism to silence autoimmune T cells in the periphery. The TSH receptor (TSHR), thyroid peroxidase (TPO), and thyroglobulin (Tg) have unusual properties (“immunogenicity”) that contribute to breaking tolerance, including size, abundance, membrane association, glycosylation, and polymorphisms. Insight into loss of tolerance to thyroid proteins comes from spontaneous and induced animal models: 1) intrathymic expression controls self-tolerance to the TSHR, not TPO or Tg; 2) regulatory T cells are not involved in TSHR self-tolerance and instead control the balance between Graves' disease and thyroiditis; 3) breaking TSHR tolerance involves contributions from major histocompatibility complex molecules (humans and induced mouse models), TSHR polymorphism(s) (humans), and alternative splicing (mice); 4) loss of tolerance to Tg before TPO indicates that greater Tg immunogenicity vs TPO dominates central tolerance expectations; 5) tolerance is induced by thyroid autoantigen administration before autoimmunity is established; 6) interferon-α therapy for hepatitis C infection enhances thyroid autoimmunity in patients with intact immunity; Graves' disease developing after T-cell depletion reflects reconstitution autoimmunity; and 7) most environmental factors (including excess iodine) “reveal,” but do not induce, thyroid autoimmunity. Micro-organisms likely exert their effects via bystander stimulation. Finally, no single mechanism explains the loss of tolerance to thyroid proteins. The goal of inducing self-tolerance to prevent autoimmune thyroid disease will require accurate prediction of at-risk individuals together with an antigen

Thyrotropin receptor mutations and thyroid hyperfunctioning adenomas ten years after their first discovery: unresolved questions.

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Arturi, F; Scarpelli, D; Coco, A; Sacco, R; Bruno, R; Filetti, S; Russo, D

2003-04-01

Ten years after the first description of activating mutations in the thyroid stimulating hormone receptor (TSHR) gene in sporadic autonomous hyperfunctioning thyroid adenomas, there is general agreement in assigning a major pathogenic role of this genetic abnormality, acting via the constitutive activation of the cAMP pathway, in both the growth and functional characteristic of these tumours. From the beginning, however, the pathophysiological and clinical relevance of somatic TSHR mutations has been debated and some arguments still exist against a fully causative role of these mutations and the practical value of detecting these mutations for the diagnosis, treatment and prognosis of thyroid hot nodules. Some major issues will be examined herein, including (a) the frequency of TSHR alterations in various reports showing that the genetic abnormality underlying the pathogenesis of a substantial subset of thyroid tumours has yet to be identified; (b) the limitations of the present experimental models, which suggest greater caution in the interpretation of in vitro results; (c) the still unresolved question of absence of genotype-phenotype correlation. Clarification of these issues may hopefully provide new and useful tools for improving the clinical management of this disease.

Environmental chemicals and thyroid function

DEFF Research Database (Denmark)

Boas, Malene; Feldt-Rasmussen, Ulla; Skakkebaek, Niels E

2006-01-01

. There is substantial evidence that polychlorinated biphenyls, dioxins and furans cause hypothyroidism in exposed animals and that environmentally occurring doses affect human thyroid homeostasis. Similarly, flame retardants reduce peripheral thyroid hormone (TH) levels in rodents, but human studies are scarce. Studies...... also indicate thyroid-disruptive properties of phthalates, but the effect of certain phthalates seems to be stimulative on TH production, contrary to most other groups of chemicals. Thyroid disruption may be caused by a variety of mechanisms, as different chemicals interfere with the hypothalamic...

In vivo 1H MR spectroscopy of thyroid carcinoma

International Nuclear Information System (INIS)

King, Ann D.; Yeung, David K.W.; Ahuja, Anil T.; Tse, Gary M.K.; Chan, Amy B.W.; Lam, Sherlock S.L.; Hasselt, Andrew C. van

2005-01-01

To determine if proton magnetic resonance spectroscopy ( 1 H MRS) of thyroid carcinoma is feasible and to determine if 1 H MRS spectra of malignant tumors differ from that of normal thyroid tissue. We performed 1 H MRS at 1.5 T at echo-times (TE) 136 and 272 ms to examine eight patients with thyroid cancer (primary tumour or nodal metastasis) larger than 1 cm 3 in size and five volunteers with normal thyroids. Spectra acquired from six primary tumors (three anaplastic carcinomas, two papillary carcinomas and one follicular carcinoma) and two nodes (two papillary carcinoma metastases) were analyzed in the time-domain using a non-linear least squares fitting algorithm with incorporation of prior knowledge. Choline (3.2 ppm) was identified in all solid carcinomas with a mean choline/creatine of 4.3 at TE 136 ms and 5.4 at TE 272 ms. Ratios for malignant tumors at TE 136 ms ranged from 1.6 in well differentiated follicular carcinoma to 9.4 in anaplastic carcinoma. No choline was detected in normal thyroid tissues. Our results showed that 1 H MRS is a feasible technique for the evaluation of malignant thyroid tumors larger than 1 cm 3 and that proton spectra of malignant tumors differ from that of normal thyroid tissue

RIA for calcitonin detection in human serum

International Nuclear Information System (INIS)

Mander, M.

1977-01-01

A RIA for human calcitonin (HCT) was adapted to the microtiter system. The method had a sensitivity of 60 pmol/l which is, however, not sufficient for measurements of the HCT level in healthy persons. Oral and i.v. administration of calcium, oral administration of vitamin D, and glucose tolerance tests did not result in a calcitonin increase over the detection limit. In two patients with histologically confirmed medullary thyroid carcinoma, there are extremely increased calcitonin levels: 16,000 and 120,000 pmol/l. In two other patients with medullary thyroid carcinoma after total resection of the thyroid, HCT levels were below the detection limit. In patients with hypercalcaemia (tumor hypercalcaemia), increased HCT levels were not observed. On the other hand, a HCT value of 150 pmol/l was found in a patient with vitamin D intoxication. As is normal in tumour cases of this kind, the two patients with medullar thyroid carcinoma examined during the study suffered from severe diarrhoea. In both cases, the family anamnesis showed that the mothers of the two patients had also suffered from thyroid cancer. (orig.) [de

Decreased staging of differentiated thyroid cancer in patients with chronic lymphocytic thyroiditis.

Science.gov (United States)

Borowczyk, M; Janicki, A; Dworacki, G; Szczepanek-Parulska, E; Danieluk, M; Barnett, J; Antonik, M; Kałużna, M; Bromińska, B; Czepczyński, R; Bączyk, M; Ziemnicka, K; Ruchała, M

2018-04-04

The biological association between chronic lymphocytic thyroiditis (CLT) and differentiated thyroid cancer (DTC) has not been elucidated yet. The aim of the study was to assess whether the presence of CLT exerts any influence on clinical or histological presentation of DTC. Nine hundred and seven consecutive patients with DTC treated in the years 1998-2016 were divided into two groups according to the presence or absence of concomitant CLT. The statistical differences were analysed. Out of 907 patients included in the study, 331 were diagnosed with DTC and CLT (studied group), while 576 patients with DTC but without CLT constituted a control group. The distribution of papillary and follicular thyroid cancer did not differ. In CLT group, the prevalence of pT1 was greater than for pT2-pT4 DTC (P = 0.0003; OR = 1.69, 95% CI 1.27-2.24) compared to controls (68.3 vs. 56.1%, respectively). The presence of multifocal lesions was similar. The thyroid capsule infiltration without extrathyroidal invasion (P CLT (P = 0.004; OR = 1.66; 95% CI 1.17-2.34) as well as nodal involvement (P = 0.048; OR = 0.65, 95% CI 0.42-0.99). The collected data indicate a protective role of CLT in preventing the spread of the DTC. The presence of CLT might limit tumour growth to the primary site.

Correlation between serum lead and thyroid diseases: papillary thyroid carcinoma, nodular goiter, and thyroid adenoma.

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Li, Hui; Li, Xiang; Liu, Jie; Jin, Langping; Yang, Fan; Wang, Junbo; Wang, Ouchen; Gao, Ying

2017-10-01

Studies have showed that lead was associated with human health. However, the effects of lead on thyroid functions are inconsistent, and studies based on Chinese population are fragmentary. To evaluate the correlation between lead and thyroid functions of Chinese with different thyroid diseases, we conducted a hospital-based study. Ninety-six papillary thyroid carcinoma (PTC), 10 nodular goiter (NG), and 7 thyroid adenoma (TA) patients were recruited from the First Affiliated Hospital of Wenzhou Medical University, China. Serum triiodothyronine (T3), free triiodothyronine (FT3), free thyroxin (FT4), and thyroid stimulating hormone (TSH) were evaluated with chemiluminescent microparticle immunoassay. Serum lead was assessed with ICP-MASS. Partial correlation was used to explore the correlations of serum lead and thyroid diseases. Compared to PTC, the level of lead was significantly higher in TA, and lower in NG (p lead was negatively correlated with TSH (r s  =  - 0.27, p lead at quartile4 (r s  = 0.61, p lead and FT3 or FT4 in any group. The results suggested that lead might have different etiological roles in these three thyroid diseases.

Prevention and treatment of colon cancer by peroral administration of HAMLET (human α-lactalbumin made lethal to tumour cells).

Science.gov (United States)

Puthia, Manoj; Storm, Petter; Nadeem, Aftab; Hsiung, Sabrina; Svanborg, Catharina

2014-01-01

Most colon cancers start with dysregulated Wnt/β-catenin signalling and remain a major therapeutic challenge. Examining whether HAMLET (human α-lactalbumin made lethal to tumour cells) may be used for colon cancer treatment is logical, based on the properties of the complex and its biological context. To investigate if HAMLET can be used for colon cancer treatment and prevention. Apc(Min)(/+) mice, which carry mutations relevant to hereditary and sporadic human colorectal tumours, were used as a model for human disease. HAMLET was given perorally in therapeutic and prophylactic regimens. Tumour burden and animal survival of HAMLET-treated and sham-fed mice were compared. Tissue analysis focused on Wnt/β-catenin signalling, proliferation markers and gene expression, using microarrays, immunoblotting, immunohistochemistry and ELISA. Confocal microscopy, reporter assay, immunoprecipitation, immunoblotting, ion flux assays and holographic imaging were used to determine effects on colon cancer cells. Peroral HAMLET administration reduced tumour progression and mortality in Apc(Min)(/+) mice. HAMLET accumulated specifically in tumour tissue, reduced β-catenin and related tumour markers. Gene expression analysis detected inhibition of Wnt signalling and a shift to a more differentiated phenotype. In colon cancer cells with APC mutations, HAMLET altered β-catenin integrity and localisation through an ion channel-dependent pathway, defining a new mechanism for controlling β-catenin signalling. Remarkably, supplying HAMLET to the drinking water from the time of weaning also significantly prevented tumour development. These data identify HAMLET as a new, peroral agent for colon cancer prevention and treatment, especially needed in people carrying APC mutations, where colon cancer remains a leading cause of death.

Expression of stanniocalcin 1 in thyroid side population cells and thyroid cancer cells.

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Hayase, Suguru; Sasaki, Yoshihito; Matsubara, Tsutomu; Seo, Daekwan; Miyakoshi, Masaaki; Murata, Tsubasa; Ozaki, Takashi; Kakudo, Kennichi; Kumamoto, Kensuke; Ylaya, Kris; Cheng, Sheue-yann; Thorgeirsson, Snorri S; Hewitt, Stephen M; Ward, Jerrold M; Kimura, Shioko

2015-04-01

Mouse thyroid side population (SP) cells consist of a minor population of mouse thyroid cells that may have multipotent thyroid stem cell characteristics. However the nature of thyroid SP cells remains elusive, particularly in relation to thyroid cancer. Stanniocalcin (STC) 1 and 2 are secreted glycoproteins known to regulate serum calcium and phosphate homeostasis. In recent years, the relationship of STC1/2 expression to cancer has been described in various tissues. Microarray analysis was carried out to determine genes up- and down-regulated in thyroid SP cells as compared with non-SP cells. Among genes up-regulated, stanniocalcin 1 (STC1) was chosen for study because of its expression in various thyroid cells by Western blotting and immunohistochemistry. Gene expression analysis revealed that genes known to be highly expressed in cancer cells and/or involved in cancer invasion/metastasis were markedly up-regulated in SP cells from both intact as well as partial thyroidectomized thyroids. Among these genes, expression of STC1 was found in five human thyroid carcinoma-derived cell lines as revealed by analysis of mRNA and protein, and its expression was inversely correlated with the differentiation status of the cells. Immunohistochemical analysis demonstrated higher expression of STC1 in the thyroid tumor cell line and thyroid tumor tissues from humans and mice. These results suggest that SP cells contain a population of cells that express genes also highly expressed in cancer cells including Stc1, which warrants further study on the role of SP cells and/or STC1 expression in thyroid cancer.

Follicular thyroid carcinoma mimicking meningioma: A case report

Directory of Open Access Journals (Sweden)

Krishnalatha Buandasan

2012-02-01

Full Text Available Follicular thyroid carcinoma (FTC is a well-differentiated tumor which resembles the normal microscopic pattern of the thyroid. Although intracranial metastasis to the brain is frequent in adults, metastasis from FTC is very rare. Dural metastases mimicking meningioma have been documented in the literature now and then. However, cases arising from a FTC are again very rare. We report the case of a middle-aged lady who presented with progressive, painless left eye proptosis. She was noted to have a non-axial proptosis with dystopia, compressive optic neuropathy and exposure keratitis. She also had a painless swelling over the occipital region. She was initially misdiagnosed to have multiple foci of meningioma based on magnetic resonance imaging findings. Subsequent histopathological examination revealed presence of FTC. She was euthyroid but was found to have multiple small thyroid nodules by ultrasonography. Hence, the definite diagnosis of all dural masses must be histological wherever possible and thyroid carcinoma should be considered as a potential primary tumour in such presentations.

Thyroid effects of endocrine disrupting chemicals.

Science.gov (United States)

Boas, Malene; Feldt-Rasmussen, Ulla; Main, Katharina M

2012-05-22

In recent years, many studies of thyroid-disrupting effects of environmental chemicals have been published. Of special concern is the exposure of pregnant women and infants, as thyroid disruption of the developing organism may have deleterious effects on neurological outcome. Chemicals may exert thyroid effects through a variety of mechanisms of action, and some animal experiments and in vitro studies have focused on elucidating the mode of action of specific chemical compounds. Long-term human studies on effects of environmental chemicals on thyroid related outcomes such as growth and development are still lacking. The human exposure scenario with life long exposure to a vast mixture of chemicals in low doses and the large physiological variation in thyroid hormone levels between individuals render human studies very difficult. However, there is now reasonably firm evidence that PCBs have thyroid-disrupting effects, and there is emerging evidence that also phthalates, bisphenol A, brominated flame retardants and perfluorinated chemicals may have thyroid disrupting properties. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Human tumour xenografts established and serially transplanted in mice immunologically deprived by thymectomy, cytosine arabinoside and whole-body irradiation

International Nuclear Information System (INIS)

Selby, P.J.; Thomas, J.M.; Peckham, M.J.

1980-01-01

Mice immunologically deprived by thymectomy, cytosine arabinoside treatment and whole-body irradiation were used to study the growth of human tumours as xenografts. 10/16 melanoma biopsies, 4/13 ovarian carcinoma biopsies and 3/6 uterine cancer biopsies grew as serially transplantable xenograft lines. The tumour lines were studied through serial passages by histology, histo-chemistry, electron microscopy, chromosome analysis, immune fluorescence, growth rate measurement and mitotic counts. They retained the characteristics of the tumours of origin, with the exception of loss of pigmentation in two melanomas, histological dedifferentiation in the uterine carcinomas, and increased mitotic frequency and growth rate in some melanomas. It was concluded that this type of animal preparation is as useful as alternative methods of immunological deprivation, or as athymic nude mice, for the growth of human tumour xenografts, at least for some experimental purposes. (author)

IL-1β a potential factor for discriminating between thyroid carcinoma and atrophic thyroiditis.

Science.gov (United States)

Kammoun-Krichen, Maha; Bougacha-Elleuch, Noura; Mnif, Mouna; Bougacha, Fadia; Charffedine, Ilhem; Rebuffat, Sandra; Rebai, Ahmed; Glasson, Emilie; Abid, Mohamed; Ayadi, Fatma; Péraldi-Roux, Sylvie; Ayadi, Hammadi

2012-01-01

Interactions between cytokines and others soluble factors (hormones, antibodies...) can play an important role in the development of thyroid pathogenesis. The purpose of the present study was to examine the possible correlation between serum cytokine concentrations, thyroid hormones (FT4 and TSH) and auto-antibodies (Tg and TPO), and their usefulness in discriminating between different thyroid conditions. In this study, we investigated serum from 115 patients affected with a variety of thyroid conditions (44 Graves' disease, 17 Hashimoto's thyroiditis, 11 atrophic thyroiditis, 28 thyroid nodular goitre and 15 papillary thyroid cancer), and 30 controls. Levels of 17 cytokines in serum samples were measured simultaneously using a multiplexed human cytokine assay. Thyroid hormones and auto-antibodies were measured using ELISA. Our study showed that IL-1β serum concentrations allow the discrimination between atrophic thyroiditis and papillary thyroid cancer groups (p = 0.027).

Quantifying heterogeneity in human tumours using MRI and PET.

Science.gov (United States)

Asselin, Marie-Claude; O'Connor, James P B; Boellaard, Ronald; Thacker, Neil A; Jackson, Alan

2012-03-01

Most tumours, even those of the same histological type and grade, demonstrate considerable biological heterogeneity. Variations in genomic subtype, growth factor expression and local microenvironmental factors can result in regional variations within individual tumours. For example, localised variations in tumour cell proliferation, cell death, metabolic activity and vascular structure will be accompanied by variations in oxygenation status, pH and drug delivery that may directly affect therapeutic response. Documenting and quantifying regional heterogeneity within the tumour requires histological or imaging techniques. There is increasing evidence that quantitative imaging biomarkers can be used in vivo to provide important, reproducible and repeatable estimates of tumoural heterogeneity. In this article we review the imaging methods available to provide appropriate biomarkers of tumour structure and function. We also discuss the significant technical issues involved in the quantitative estimation of heterogeneity and the range of descriptive metrics that can be derived. Finally, we have reviewed the existing clinical evidence that heterogeneity metrics provide additional useful information in drug discovery and development and in clinical practice. Copyright © 2012 Elsevier Ltd. All rights reserved.

The thyroid: medical surveillance of exposed workers

Energy Technology Data Exchange (ETDEWEB)

Virgili, M. [Radiation Protection ASL Frosinone (Italy); Strambi, E. [Board for the new Technologies, the Energy and the Environment (ENEA), Rome (Italy); Trenta, G. [National Institute of Nuclear Physics (INFN) Frascati, Roma (Italy)

2000-05-01

In this paper the authors, on the basis of a prevalence study of thyroid diseases on a group of 234 radiation workers observed over a ten-years (1989-1999): discuss the issues and suggest an up-to-date approach to diagnosis and management of nodular thyroid diseases in the medical surveillance of radiation protection; identify and discuss, specific clinical situations, which, representing special problems, deserve a more restrictive judgement of fitness; intend to demonstrate that the diagnostic protocol used conciliates with due economy but with the right balance, the real requirements of medical surveillance reducing as far as possible undesirable effects such as damage from excessive protection and patient/physician delay, which is extremely dangerous in the early diagnosis of tumours. (author)

Studies on binding of radiolabeled thyrotropin to cultured human thyroid cells

International Nuclear Information System (INIS)

Yamamoto, M.; Rapoport, B.

1978-01-01

A line of cultured human thyroid adenoma cells was used in a study designed to compare the stimulatory effect of TSH on cellular cAMP generation with the binding of radiolabeled TSH to the cells. At 37 C, specific binding of [ 125 I]TSH to suspensions of thyroid cells was maximal at 20 min and was reversed by the addition of excess TSH. Unlike the generation of cellular cAMP in response to TSH stimulation, which was maximal at pH 7.5, the binding of [ 125 ]TSH to the cells was maximal at pH 5.5 and progressively declined up to pH 8.5. Increasing NaCl concentrations progressively inhibited cellular binding of TSH; at physiological salt concentrations, almost no TSH binding was detectable. Competitive inhibition studies of [ 125 I]TSH binding to cells revealed a binding site with a dissociation constant of 5.5 x 10 -8 M at pH 7.4. GH, PRL, hCG, FSH, insulin, and glucagon did not compete with [ 125 I)TSH binding. ACTH, however, was a potent inhibitor of [ 125 I]TSH binding. Despite this inhibitory effect on TSH binding, ACTH had little or no effect on cellular cAMP generation. High concentrations of ACTH did not inhibit the biological effect of TSH on cAMP generation. Specific binding of [ 125 I]TSH to empty plastic culture dishes was time dependent, reversible, and displayed a hormonal specificity identical to binding to thyroid cells. The effects of pH and NaCl concentrations on TSH binding to dishes were similarbut not identical to those on cellular binding. This study raises serious questions as to the biological significance of [ 125 I]TSH binding to cultured human thyroid cells

In vivo magnetic resonance imaging and 31P spectroscopy of large human brain tumours at 1.5 tesla

DEFF Research Database (Denmark)

Thomsen, C; Jensen, K E; Achten, E

1988-01-01

31P MR spectroscopy of human brain tumours is one feature of magnetic resonance imaging. Eight patients with large superficial brain tumours and eight healthy volunteers were examined with 31P spectroscopy using an 8 cm surface coil for volume selection. Seven frequencies were resolved in our spe...

Thyroid Stimulating Immunoglobulin Bioassay Using Cultured Human Thyroid Cells; A Simplified Micromethod

International Nuclear Information System (INIS)

Lee, Myung Chul; Chung, June Key; Cho, Bo Youn; Koh, Chang Soon; Lee, Moon Ho; Ahn, Il Min; Ahn, Hee Kwon

1985-01-01

The activation of adenylate cyclase of human thymocytes in primary cell culture and the release of c-AMP into the medium are used to detect b-TSH and TSAb in sera of patients with autoimmune thyroid disease. Sera of patients are used directly as a part of cell culture without immunoglobulin precipitation. In the above TSI bioassay, TSAb pooled serum show c-AMP concentration between that of 1 mU/ml and 10 mU/ml b-TSH but normal control pooled serum doesn't show any detectable c-AMP response. Ninety five percent of untreated Graves' patients shows TSAb activity above normal range, 20% of Hashimoto's and 363/0 of euthyroid Graves' patients show detectable TSAb activity.

Influence of TSH on uptake of [18F]fluorodeoxyglucose in human thyroid cells in vitro

International Nuclear Information System (INIS)

Deichen, J.T.; Schmidt, C.; Prante, O.; Maschauer, S.; Kuwert, T.; Papadopoulos, T.

2004-01-01

Recent clinical evidence suggests that positron emission tomography with fluorine-18 fluorodeoxyglucose (FDG-PET) is more accurate in detecting thyroid carcinomatous tissue at high than at low TSH levels. The aim of this study was to determine the influence of TSH on FDG uptake in human thyroid cells in vitro. Monolayers of human thyroid tissue were cultured after mechanical disintegration and enzymatic digestion of samples from patients undergoing surgery for nodular goitre. The purity of thyroid cell preparations was ascertained by immunohistochemical staining for the epithelial antigen KL-1, and their viability by measuring the synthesis of thyroglobulin in vitro. The cells were incubated with 0.8-1.5 MBq FDG/ml uptake medium for 1 h. FDG uptake in thyroid cells was quantified as percent of whole FDG activity per well (% ID) or as % ID in relation to total protein mass. This experimental protocol was subsequently varied to study the effect of incubation time, glucose dependency and TSH. Furthermore, radio-thin layer chromatography was used to identify intracellular FDG metabolites. FDG accumulated in the thyroid cells linearly with time, doubling roughly every 20 min. Uptake was competitively inhibited by unlabelled glucose and decreased to approximately 70% at 100 mg/dl glucose compared to the value measured in glucose-free medium. FDG was intracellularly trapped as FDG-6 phosphate and FDG-1,6-diphosphate. TSH significantly increased FDG uptake in vitro in a time- and concentration-dependent manner: Cells cultured at a TSH concentration of 50 μU/ ml doubled FDG uptake compared to TSH-free conditions, and uptake after 72 h of TSH pre-incubation was approximately 300% of that without TSH pre-incubation. TSH stimulates FDG uptake by benign thyroid cells in a time- and concentration-dependent manner. This supports the clinical evidence that in well-differentiated thyroid carcinomas, most of which are still TSH-sensitive, FDG-PET is more accurate at high levels of

Immunohistochemical Expression of TGF-Β1, SMAD4, SMAD7, TGFβRII and CD68-Positive TAM Densities in Papillary Thyroid Cancer

Directory of Open Access Journals (Sweden)

Koni Ivanova

2018-03-01

Full Text Available BACKGROUND: Papillary thyroid carcinoma (PTC accounts for 80% of the thyroid malignancies that are characterised by slow growth and an excellent prognosis. Over-expression of SMAD4 protein restores TGF-β signalling, determines a strong increase in anti-proliferative effect and reduces invasive potential of tumour cells expressing it. AIM: The study aimed to analyse the immunohistochemical expression of TGF-β1 and its downstream phosphorylated SMAD4, element and of the inhibitory SMAD7 PTC variants and their association with the localisation of TAMs within the tumour microenvironment. METHODS: For this retrospective study we investigated 69 patients immunohistochemistry with antibodies against TGF-β, TGF – β-RII, SMAD4, SMAD7, CD68+ macrophages. RESULTS: Patients with low infiltration with CD68+ cells in tumour stroma has significantly shorter survival (median of 129.267 months compared to those with high CD68+ cells infiltration (p = 0.034. From the analysis of CD68+ cells in tumour border and tumour stroma correlated with expression of TGF-β1 / SMAD proteins, we observed that the positive expression of TGF-β1 in tumour cytoplasm, significantly correlated with increased number of CD68+ cells in tumour border (X2 = 5,945; р = 0.015. CONCLUSION: TGF-β enhances motility and stimulates recruitment of monocytes, macrophages and other immune cells while directly inhibiting their anti-tumour effector functions.

Cytotoxic effects of radiation and docetaxel in human tumour cells

International Nuclear Information System (INIS)

Dunne, A.L.

2000-12-01

Data from both single institutions and from randomised multicentre trials have demonstrated that the combination of chemotherapy with radiotherapy can increase the survival of cancer patients. Treatment regimens consisting of taxanes (paclitaxel and docetaxel), a potent class of new chemotherapeutic agents, combined with radiotherapy have recently undergone preclincal investigation. Overall, these studies show that taxanes can enhance the radiation sensitivity of tumour cells. However, data on docetaxel is very limited and the mechanism of radiosensitisation by docetaxel remains largely unknown. The chief purpose of this thesis was to investigate the ability of docetaxel to radiosensitise human tumour cells and investigate potential mechanisms for radiosensitisation. The results reported here for docetaxel indicate that for the cell fines examined this drug does have a synergistic effect and is thus a radiosensitising agent. The degree of radiosensitisation seen seems to be largely dependent on drug concentration. A mechanism involving docetaxel potentiation of radiation-induced apoptosis is also suggested. The second purpose of this thesis is to investigate the potential usefulness of an apoptosis assay and the comet assay as biological indicators for cellular radiosensitivity. Many scientists and clinicans have highlighted the need for development of new rapid, predictive assays of radiation responses. If the radiosensitivity of tumours could be predicted, it may eventually allow the individualisation of patient treatment by radiotherapy. In summary, initial DNA damage measured using the comet assay was successful in predicting the radiosensitivity of colorectal tumour cells. The results suggest that the comet assay appears more suitable than the detection of apoptosis for the prediction of radiosensitivity. We conclude that the results obtained from this thesis will contribute to the current attempts to improve the radiotherapeutic management of cancer. (author)

Circulating leptin and thyroid dysfunction

DEFF Research Database (Denmark)

Zimmermann-Belsing, Tina; Brabant, Georg; Holst, Jens Juul

2003-01-01

and triiodothyronine are involved in the starvation-induced decrease in thermogenesis. Both rodent and human studies of leptin have failed to show any consistent relationship between thyroid function and serum leptin concentrations. However, leptin might have an important role in thyroid pathophysiology due to thyroid...

Analysis of clonogenic human brain tumour cells: preliminary results of tumour sensitivity testing with BCNU

Energy Technology Data Exchange (ETDEWEB)

Rosenblum, M L; Dougherty, D A; Deen, D F; Hoshino, T; Wilson, C B [California Univ., San Francisco (USA). Dept. of Neurology

1980-04-01

Biopsies from 6 patients with glioblastoma multiforme were disaggregated and single cells were treated in vitro with various concentrations of 1,3-bis(2-chloroethyl)-1-nitroso urea (BCNU) and plated for cell survival. One patient's cells were sensitive to BCNU in vitro; after a single dose of BCNU her brain scan reverted to normal and she was clinically well. Five tumours demonstrated resistance in vitro. Three of these tumours progressed during the first course of chemotherapy with a nitrosourea and the patients died at 21/2, 4 and 81/2 months after operation. Two patients who showed dramatic responses to radiation therapy were considered unchanged after the first course of nitrosourea therapy (although one demonstrated tumour enlargement on brain scan). The correlation of in vitro testing of tumour cell sensitivity with actual patient response is encouraging enough to warrant further work to determine whether such tests should weigh in decisions on patient therapy.

In vivo imaging of chromogranin A-positive endocrine tumours by three-step monoclonal antibody targeting

International Nuclear Information System (INIS)

Siccardi, A.G.; Paganelli, G.; Pontiroli, A.E.; Pelagi, M.; Magnani, P.; Viale, G.; Faglia, G.; Fazio, F.

1996-01-01

The detection of chromogranins (Cg) by immunohistochemistry and serology represents a new in vitro diagnostic tool for endocrine tumours. We have recently reported on the feasibility of targeting chromogranin A (CgA) for in vivo detection of pituitary adenomas by immunoscintigraphy (ISG). The scintigraphic procedure, based on an anti-CgA monoclonal antibody and on the avidin-biotin three-step method (Cg-3S-ISG), was evaluated on a group of 29 consecutive patients with known or suspected endocrine tumours other than pituitary adenomas, i.e. medullary thyroid carcinoma, carcinoid, insulinoma and parathormone- or ACTH-producing tumours. Primary tumours (10) and recurrences (16) were visualised in 26 patients, whereas conventional imaging techniques (planar radiography, computerised tomography, magnetic resonance imaging and ultrasonography) failed to detect the tumour sites in ten of the same (Cg-3S-ISG-positive) patients. Therefore, these preliminary results indicate that Cg-3S-ISG, the first immunological method able to detect endocrine tumours in vivo, has a higher diagnostic accuracy than conventional imaging techniques (93.1% compared with 65.5%). (orig.). With 3 figs., 1 tab

Hepatitis C Virus E2 Protein Induces Upregulation of IL-8 Pathways and Production of Heat Shock Proteins in Human Thyroid Cells.

Science.gov (United States)

Hammerstad, Sara Salehi; Stefan, Mihaela; Blackard, Jason; Owen, Randall P; Lee, Hanna J; Concepcion, Erlinda; Yi, Zhengzi; Zhang, Weijia; Tomer, Yaron

2017-02-01

Thyroiditis is one of the most common extrahepatic manifestations of hepatitis C virus (HCV) infection. By binding to surface cell receptor CD81, HCV envelope glycoprotein E2 mediates entry of HCV into cells. Studies have shown that different viral proteins may individually induce host responses to infection. We hypothesized that HCV E2 protein binding to CD81 expressed on thyroid cells activates a cascade of inflammatory responses that can trigger autoimmune thyroiditis in susceptible individuals. Human thyroid cell lines ML-1 and human thyrocytes in primary cell culture were treated with HCV recombinant E2 protein. The expression of major proinflammatory cytokines was measured at the messenger RNA and protein levels. Next-generation transcriptome analysis was used to identify early changes in gene expression in thyroid cells induced by E2. HCV envelope protein E2 induced strong inflammatory responses in human thyrocytes, resulting in production of interleukin (IL)-8, IL-6, and tumor necrosis factor-α. Furthermore, the E2 protein induced production of several heat shock proteins including HSP60, HSP70p12A, and HSP10, in human primary thyrocytes. In thyroid cell line ML-1, RNA sequencing identified upregulation of molecules involved in innate immune pathways with high levels of proinflammatory cytokines and chemokines and increased expression of costimulatory molecules, specifically CD40, known to be a major thyroid autoimmunity gene. Our data support a key role for HCV envelope protein E2 in triggering thyroid autoimmunity through activation of cytokine pathways by bystander mechanisms. Copyright © 2017 by the Endocrine Society

Human thyroid specimen imaging by fluorescent x-ray computed tomography with synchrotron radiation

Science.gov (United States)

Takeda, Tohoru; Yu, Quanwen; Yashiro, Toru; Yuasa, Tetsuya; Hasegawa, Yasuo; Itai, Yuji; Akatsuka, Takao

1999-09-01

Fluorescent x-ray computed tomography (FXCT) is being developed to detect non-radioactive contrast materials in living specimens. The FXCT system consists of a silicon (111) channel cut monochromator, an x-ray slit and a collimator for fluorescent x ray detection, a scanning table for the target organ and an x-ray detector for fluorescent x-ray and transmission x-ray. To reduce Compton scattering overlapped on the fluorescent K(alpha) line, incident monochromatic x-ray was set at 37 keV. The FXCT clearly imaged a human thyroid gland and iodine content was estimated quantitatively. In a case of hyperthyroidism, the two-dimensional distribution of iodine content was not uniform, and thyroid cancer had a small amount of iodine. FXCT can be used to detect iodine within thyroid gland quantitatively and to delineate its distribution.

Overexpression of BID in thyroids of transgenic mice increases sensitivity to iodine-induced autoimmune thyroiditis

Science.gov (United States)

2014-01-01

Background BID functions as a bridge molecule between death-receptor and mitochondrial related apoptotic pathways to amplify apoptotic signaling. Our previous studies have demonstrated a substantial increase in BID expression in primary normal thyroid epithelia cells treated with inflammatory cytokines, including the combination of IFNγ and IL-1β or IFNγ and TNFα. The aim of this study was to determine whether an increase in BID expression in thyroid can induce autoimmune thyroiditis. Methods A transgenic mouse line that expresses human BID in thyroid cells was established by fusing a mouse thyroglobulin (Tg) promoter upstream of human BID (Tg-BID). We tested whether the increased expression of pro-apoptotic BID in thyroid would induce autoimmune thyroiditis, both in the presence and absence of 0.3% iodine water. Results Our data show that Tg-BID mice in a CBA/J (H-2 k) background do not spontaneously develop autoimmune thyroiditis for over a year. However, upon ingestion of iodine in the drinking water, autoimmune thyroiditis does develop in Tg-BID transgenic mice, as shown by a significant increase in anti-Tg antibody and mononuclear cell infiltration in the thyroid glands in 30% of mice tested. Serum T4 levels, however, were similar between iodine-treated Tg-BID transgenic mice and the wild type mice. Conclusions Our data demonstrate that increased thyroid expression of BID facilitates the development of autoimmune thyroiditis induced by iodine uptake. However, the overexpression of BID itself is not sufficient to initiate thyroiditis in CBA/J (H-2 k) mice. PMID:24957380

BCNT studies for application to the undifferentiated thyroid carcinoma; Estudios de terapia por captura neutronica en boro para su aplicacion al tratamiento del cancer indiferenciado de tiroides

Energy Technology Data Exchange (ETDEWEB)

Dagrosa, Maria A; Viaggi, Mabel E; Cabrini, Romulo L; Juvenal, Guillermo J; Pisarev, Mario A [Comision Nacional de Energia Atomica, General San Martin (Argentina). Dept. de Radiobiologia; Garavaglia, Ricardo N; Farias, Silvia S [Comision Nacional de Energia Atomica, General San Martin (Argentina). Dept. de Quimica; Belli, Carolina; Larripa, Irene [Academia Nacional de Medicina, Buenos Aires (Argentina). Dept. de Genetica; Gangitano, David [Policia Federal Argentina, Buenos Aires (Argentina). Lab. de Quimica

2000-07-01

Undifferentiated thyroid carcinoma (UTC) lacks an effective treatment. Boron neutron capture therapy (BNCT) is based on the selective uptake of {sup 10}B-boronated compounds by some tumours, followed by irradiation with an appropriate neutron beam. The radioactive boron originated ({sup 11}B) decays releasing {sup 7}Li, gamma rays and alpha particles, and these latter will destroy the tumour. In order to explore the possibility of applying BNCT to UTC we have studied the biodistribution of BPA. Animal Model: To develop an animal model of undifferentiated thyroid carcinoma (UTC), which may be useful to study of BNCT. The UTC human cell line ARO was implanted into the back of the nude mice. We performed successive passages in mouse after tumor culturing in order to obtain an animal model similar to the human tumor. We studied the kinetics and the tumoral histology, the capability to induce metastasis, the biokinetics of in vitro growth, as well as cytogenetic and molecular aspects. Histological specimens of tumor showed extensive viability with high mitotic activity. At 117 days, the tumors reached a size of 1700 mm{sup 3} and showed a central necrotic portion with a thin layer of viable cells presence of micro metastasis could be observed in the lung. The kinetics of growth both in vivo and in vitro showed that when the number of passages in mouse increases the growth rate decreases. The cytogenetic and molecular studies did not show differences between the original line and the sublines that could explain this phenotypic change. Moreover, the cytogenetic studies proved that the ARO cell line and its sublines showed a complex clonal karyotype including structural alterations with deletions and translocations involving chromosomes 5, 7, 8, 9p, 11p, 17q 19p, and 20q that were consistent with earlier reported data in UTC. In vivo BNCT studies: ARO cells were transplanted into the scapular region of NIH nude mice, and after 2 weeks BPA (350 or 600 mg/kg bw) was injected

Hypothalamus-pituitary-thyroid axis disruption in rats with breast cancer is related to an altered endogenous oxytocin/insulin-regulated aminopeptidase (IRAP) system.

Science.gov (United States)

Carrera-González, María Pilar; Ramírez-Expósito, María Jesús; de Saavedra, Jose Manuel Arias; Sánchez-Agesta, Rafael; Mayas, María Dolores; Martínez-Martos, Jose Manuel

2011-06-01

Associations of breast cancer with diseases of the thyroid have been repeatedly reported, but the mechanism underlying this association remains to be elucidated. It has been reported that oxytocin (OXT) attenuates the thyroid-stimulating hormone (TSH) release in response to thyrotrophin-releasing hormone (TRH) and decreased plasma levels of TSH as well as the thyroid hormones by an effect mediated by the central nervous system. Oxytocinase (IRAP) is the regulatory proteolytic enzyme reported to hydrolyze OXT. Changes in IRAP activity have been reported in both human breast cancer and N-methyl-nitrosourea (NMU)-induced rat mammary tumours. Here, we measure IRAP activity fluorometrically using cystyl-β-naphthylamide as the substrate, in the hypothalamus-pituitary-thyroid axis together with the circulating levels of OXT, and its relationship with circulating levels of TSH and free thyroxine (fT4), as markers of thyroid function in control rats and rats with breast cancer induced by NMU. We found decreased thyroid function in rats with breast cancer induced by NMU, supported by the existence of lower serum circulating levels of both TSH and fT4 than their corresponding controls. Concomitantly, we found a decrease of hypothalamic IRAP activity and an increase in circulating levels of OXT. We propose that breast cancer increases OXT pituitary release by decreasing its hypothalamic catabolism through IRAP activity, probably due to the alteration of the estrogenic endocrine status. Thus, high circulating levels of OXT decreased TSH release from the pituitary, and therefore, of thyroid hormones from the thyroid, supporting the association between breast cancer and thyroid function disruption.

Recombinant TSH in follow-up and therapy of differentiated thyroid carcinoma

International Nuclear Information System (INIS)

Luster, M.; Reiners, C.

2000-01-01

I-131-scintigraphy and serum thyroglobulin testing - if possible under stimulation of thyrotropin - are besides physical examination and ultrasonography crucial for the optimal follow-up of patients with well-differentiated thyroid carcinoma. This required physicians to withdraw patients from thyroid hormone suppression therapy (THST) for several weeks in order to raise endogenous TSH-levels. Clinical hypothyroidism often results in substantial patient discomfort, with sometimes major psychic alterations; the subsequent disability to work is occasionally an unpleasant consequence from an economical point of view. The temporary use of bovine, and for a short period of time human TSH is obsolete today because of a high risk of allergic reactions or the potential transmission of the Creutzfeldt-Jakob disease, respectively. Lately recombinant human TSH (rhTSH, Thyrogen trademark ), a hormone that was developed with the help of genetic engineering techniques, is available; its pharmacological safety has been demonstrated in previous phase-I/II-studies. The results of a phase-III-study showed in the majority of patients a marked rise in thyroglobulin levels after rhTSH. In all cases an adequate TSH level (>100 mU/l) was achieved after i.m. injection of recombinant TSH. Wholebody-scans showed a high level of accordance (>90%) in addition to a substantially lower background-activity. A tumour-background-ratio corresponding to conventional imaging could be demonstrated. (orig.) [de

Selenomethionine scintigraphy in the diagnosis of cold thyroid nodules

International Nuclear Information System (INIS)

Rinaldi, Chantal.

1976-01-01

This work attempts to establish the value of a tumoral radiotracer for thyroid exploration: 75 Se-labelled methionine. The purpose of such a radioelement for US in scintigraphy is to allow the cold thyroid nodule diagnosis to be established before surgery, the extent of which depends on whether the nodule is benign or malignant. After a survey of present thyroid cancer diagnosis methods the different tumoral radiotracers are reviewed especially those used to diagnose thyroid neoformations. Selenomethionine appears as one of the most universal of these radiotracers since methionine is an essential amino acid involved in protein synthesis, which is accelerated inside tumour cells, while selenium itself in the form of certain salts possesses a known tropism for neoplastic tissues. The original feature of our study is the use of a method attempting to optimise the results by a more objective reading of the images. To this end we employed a scintillation camera for image acquisition and a data processing system to perform an electronic subtraction, on the thyroid image obtained with selenomethionine, of the thyroid image supplied by radioiodine. The method is nevertheless limited by the properties of the radiotracer used: its long physical and biological half-life is a contra-indication in patients under forty, the dose received by the gonads being relatively large [fr

The flame retardant DE-71 (a mixture of polybrominated diphenyl ethers) inhibits human differentiated thyroid cell function in vitro

DEFF Research Database (Denmark)

Kronborg, Thit Mynster; Hansen, Juliana Frohnert; Rasmussen, Åse Krogh

2017-01-01

Normal thyroid function is essential for general growth and metabolism, but can be affected by endocrine disrupting chemicals (EDCs). Polybrominated diphenyl ethers (PBDEs) have been used worldwide to reduce flammability in different materials and are suspected to be EDCs. The production...... of the commercial Penta- and OctaBDE mixtures is banned, but DecaBDEs and existing products may leak PBDEs into the environment. Our aim was to investigate the effect of the PentaBDE mixture DE-71 on human thyroid cells in vitro. Primary human thyroid cells were obtained as paraadenomatous tissue and cultured...... in monolayers. The influence of DE-71 on cyclic adenosine monophosphate (cAMP) and thyroglobulin (Tg) production was examined in the culture medium by competitive radioimmunoassay and enzyme-linked immunosorbent assay, respectively. Real-time quantitative PCR analysis of thyroid-specific genes was performed...

Thyroid and radiation

Energy Technology Data Exchange (ETDEWEB)

Yamashita, Shunichi; Namba, Hiroyuki; Nagataki, Shigenobu (Nagasaki Univ. (Japan). School of Medicine)

1993-11-01

The topic 'Thyroid and Radiation' is both an old and new area to be solved by human beings. The thyroid is an organ that is usually susceptible to exposure to ionizing radiation, both by virtue of its ability to concentrate radioiodine (internal radiation) and by routine medical examination: Chest X-ray, Dental X-ray, X-irradiation of cervical lymph nodes etc. (external radiation). Iodine-131 is widely used for the therapy of Graves' disease and thyroid cancers, of which the disadvantage is radiation-induced hypothyroidism but not complications of thyroid tumor. The thyroid gland is comparatively radioresistant, however, the data obtained from Hiroshima, Nagasaki and Marshall islands indicates a high incidence of external radiation-induced thyroid tumors as well as hypothyroidism. The different biological effects of internal and external radiation remains to be further clarified. Interestingly, recent reports demonstrate the increased number of thyroid cancer in children around Chernobyl in Belarus. In this review, we would like to introduce the effect of radiation on the thyroid gland at the molecular, cellular and tissue levels. Furthermore the clinical usefulness of iodine-131, including the safety-control for radiation exposure will be discussed. (author) 50 refs.

Induction of human airway hyperresponsiveness by tumour necrosis factor-alpha.

Science.gov (United States)

Anticevich, S Z; Hughes, J M; Black, J L; Armour, C L

1995-09-15

Tumour necrosis factor-alpha (TNF alpha) is implicated in the pathogenesis of asthma; however, little is known of its direct effect on smooth muscle reactivity. We investigated the effect of TNF alpha on the responsiveness of human bronchial tissue to electrical field stimulation in vitro. Incubation of non-sensitized tissue with 1 nM, 3 nM and 10 nM TNF alpha significantly increased responsiveness to electrical field stimulation (113 +/- 8, 110 +/- 4 and 112 +/- 2% respectively) compared to control (99 +/- 2%) (P 0.05) nor were responses to exogenous acetylcholine (93 +/- 4% versus 73 +/- 7%, n = 3, P = 0.38). These results show that TNF alpha causes an increase in responsiveness of human bronchial tissue and that this occurs prejunctionally on the parasympathetic nerve pathway. This is the first report of a cytokine increasing human airway tissue responsiveness.

Thyroid carcinoma. A descriptive retrospective study

International Nuclear Information System (INIS)

Gonzalez, Carolina C.; Yaniskowski, Maria L.; Wyse, Eduardo P.; Giovannini, Andrea A.; Lopez, Monica B.; Wior, Myrian E.

2006-01-01

The thyroid carcinoma (TC) is not very frequent among all cancer. Its course is slow and is high potentially curable. Our aim was to analyse the characteristics in patients with TC. A retrospective analysis on 171 patients, with an average age of 41.1. (± 14.6), who asked for TC to our service between the years 2000-2004, was performed. From case histories it was evaluated: anamnesis, diagnostic image, histopathology and evolution. Tumours were grouped for size and TNM (tumor-nodule-metastasis) in stage (S). A simulated serum thyroglobulin level >2 ng/ml and positive image with 131 I or another nuclear marker were considered as positive for residual TC. In the totality of the analyzed patients 88% were female, 62% below 45 years old, and in 77% the thyroid function was normal. The fine needle aspiration (FNA) was diagnostic in 78%. Papillary thyroid carcinoma (PTC) in 96%. The 63% was SI; 14% SII; 19% SIII and 4% SIV. During follow-up, we observed that 90% of patients with Tg between 2 and 10 had evidence of residual TC, and 100% with Tg > 10 ng/ml, whereas 18% of those whose simulated Tg [es

Kinetics of the human thyroid trap: experience in normal subjects and in thyroid disease

Energy Technology Data Exchange (ETDEWEB)

Hays, M.T.

1979-03-01

Kinetics of the thyroid pertechnetate trap were assessed in 39 normal subjects, five untreated patients with Graves' disease (two before and after treatment), two hypothyroid patients, and in one patient each with Hashimoto's thyroiditis of recent onset, subacute thyroiditis, and massive anaplastic carcinoma. In normal subjects, the effects of sex, time of day, and order of experimental sessions were studied. A three-compartment model was assumed for all studies. Data on thyroidal and neck-background pertechnetate were collected with a multicrystal camera during 40 min after iv injection. The two thyroidal compartments in the model - the follicular cell, v/sub 2/, and the colloidal plasma-equivalent space, V/sub 3/ - is a multi-exponential function of plasma radioactivity, V/sub 1/. None of the model parameters was systematically affected by sex and order of session did not consistently alter any parameter, except for V/sub 3/, which was greater in session 2 than in session 1. That increase was not consistent and is believed to be spurious. Time of day affected only the exit rate constant from the colloid ..lambda../sub 23/, which was increased later in the day (P < 0.02). Distribution of the normal parameters was more log-normal than normal. After 5% were excluded at the high end and at the low end, the range for a parameter, p, was found empirically to be: antiln (mean ln p - 1.7 s.d. ln p), and antiln (mean ln p + 1.5 s.d. ln p). In Graves' disease, V/sub 2/ is increased (P < 0.02), but the increases in V/sub 3/ and in ..lambda../sub 21/ (the clearance into the thyroid from serum) are more dramatic (P < 10/sup -8/). After treatment, V/sub 3/ and ..lambda../sub 21/ fell toward normal. The hypothyroid patients showed no trap activity, and the trap was normal in the patient with early Hashimoto's thyroiditis. The patients with subacute thyroiditis and anaplastic carcinoma had increases in V/sub 2/, V/sub 3/, and ..lambda../sub 21/, but the

Scintigraphic assessment of vascularity and blood-tissue barrier of human brain tumours

International Nuclear Information System (INIS)

Front, D.

1978-01-01

Assessment of vascularity and blood-tissue barrier was performed by sequential scintigraphy in 43 patients with brain tumours. The blood-tumour barrier was evaluated by use of sup(99m)Tc-pertechnetate, and vascularity using sup(99m)Tc-labelled red blood cells. Three groups of tumours were found: tumours with low vascularity and permeable barrier, tumours with high vascularity and permeable barrier, and tumours with low vascularity and relatively impermeable barrier. The first group indicates that when vessels are permeable, there may be a rapid penetration of large amounts of pertechnetate into the tumour even when vascularity is not increased. In the other two groups penetration of pertechnetate into the tumour is affected by vascularity, as it determines the total area where passage of the radiopharmaceutical takes place. It is suggested that the permeability of the blood-tumour barrier and the amount of vascularity may have an effect on the success of chemotherapy in brain tumours. (author)

Aberrantly methylated genes in human papillary thyroid cancer and their association with BRAF/RAS mutation.

Directory of Open Access Journals (Sweden)

Yasuko eKikuchi

2013-12-01

Full Text Available Cancer arises through accumulation of epigenetic and genetic alteration. Aberrant promoter methylation is a common epigenetic mechanism of gene silencing in cancer cells. We here performed genome-wide analysis of DNA methylation of promoter regions by Infinium HumanMethylation27 BeadChip, using 14 clinical papillary thyroid cancer samples and 10 normal thyroid samples. Among the 14 papillary cancer cases, 11 showed frequent aberrant methylation, but the other three cases showed no aberrant methylation at all. Distribution of the hypermethylation among cancer samples was non-random, which implied existence of a subset of preferentially methylated papillary thyroid cancer. Among 25 frequently methylated genes, methylation status of six genes (HIST1H3J, POU4F2, SHOX2, PHKG2, TLX3, HOXA7 was validated quantitatively by pyrosequencing. Epigenetic silencing of these genes in methylated papillary thyroid cancer cell lines was confirmed by gene re-expression following treatment with 5-aza-2'-deoxycytidine and trichostatin A, and detected by real-time RT-PCR. Methylation of these six genes was validated by analysis of additional 20 papillary thyroid cancer and 10 normal samples. Among the 34 cancer samples in total, 26 cancer samples with preferential methylation were significantly associated with mutation of BRAF/RAS oncogene (P=0.04, Fisher’s exact test. Thus we identified new genes with frequent epigenetic hypermethylation in papillary thyroid cancer, two subsets of either preferentially methylated or hardly methylated papillary thyroid cancer, with a concomitant occurrence of oncogene mutation and gene methylation. These hypermethylated genes may constitute potential biomarkers for papillary thyroid cancer.

Congenital leptin deficiency and thyroid function

Directory of Open Access Journals (Sweden)

Paz-Filho Gilberto

2009-11-01

Full Text Available Abstract Thyroid function is closely related to leptin's secretion by the adipose tissue. In states of leptin-deficiency, the circadian rhythm of TSH is altered, leading to central hypothyroidism in animal models. In humans, central hypothyroidism has also been described in rare cases of congenital leptin deficiency. However, the thyroid phenotype in these cases is heterogeneous, with the occurrence of central hypothyroidism in a minority of cases. Here we describe thyroid function in four leptin-deficient humans (2 males aged 5 and 27, and 2 females aged 35 and 40, before and during leptin replacement with recombinant human methionyl leptin (r-metHuLeptin. The child was evaluated for four years, and the adults, for eight years. In addition, the adults were submitted to a brief withdrawal of leptin during six weeks in the sixth year. Our results show that, regardless of leptin replacement, our leptin-deficient patients have normal thyroid function. In spite of having an important role in regulating the hypothalamic-pituitary-thyroidal axis, leptin is not required for normal thyroid function. Trial Registration ClinicalTrials.gov Identifiers: NCT00659828 and NCT00657605

Recombinant human TSH in differentiated thyroid cancer: a nuclear medicine perspective

Energy Technology Data Exchange (ETDEWEB)

Zanotti-Fregonara, P. [CEA, DSV, I2BM, SHFJ, LMNRB, Orsay (France); Rubello, D. [Osped S Maria Misericordia, IRCCS, IOV, Dept Nucl Med, PET Ctr, I-45100 Rovigo (Italy); Hindie, E. [Hop St Louis, Dept Nucl Med, Paris (France)

2008-07-01

The use of recombinant human thyroid-stimulating hormone (rhTSH) in differentiated thyroid cancer (DTC) is widely discussed in the literature with regard to the diagnostic and therapeutic aspects of the management of DTC patients. However, some controversy about the appropriate indications, advantages and potential disadvantages of the use of rhTSH may still exist within the community of nuclear medicine physicians. In our opinion, the clinical benefits of rhTSH in avoiding hypothyroidism outweigh its somewhat lesser diagnostic accuracy. However, we disagree on designating rhTSH as the 'golden standard' to obtain TSH stimulation, as suggested by some authors. Thus, the first follow-up examination after ablation, which is determinant for patients' prognostic classification, can be either done under rhTSH stimulation or after hormone withdrawal. In our practice, and for higher risk patients, we still favour performing the initial follow-up after thyroid hormone withdrawal. rhTSH also shows the ability to enhance radioiodine concentration into thyroid cells. This characteristic is obviously of great interest among the nuclear medicine community. In clinical practice, it seems preferable to perform {sup 131}I treatment for metastatic disease during hypothyroidism. rhTSH may find its utility for the treatment of specific populations of patients, i.e. those in whom hormone withdrawal is medically contraindicated or in whom adequate endogenous TSH levels cannot be obtained due to reduced pituitary reserve or continued thyroxine production by metastatic tissue. In conclusion, rhTSH has demonstrated to be a reliable alternative to hypothyroidism for the stimulation of Tg in the follow-up of thyroid cancer patients. However, its use must be more carefully chosen in the therapeutic setting. Our feeling is that rhTSH should no tbe used for remnant ablation in high-risk patients and for the treatment of metastatic disease, except for specific populations of

Recombinant human TSH in differentiated thyroid cancer: a nuclear medicine perspective

International Nuclear Information System (INIS)

Zanotti-Fregonara, P.; Rubello, D.; Hindie, E.

2008-01-01

The use of recombinant human thyroid-stimulating hormone (rhTSH) in differentiated thyroid cancer (DTC) is widely discussed in the literature with regard to the diagnostic and therapeutic aspects of the management of DTC patients. However, some controversy about the appropriate indications, advantages and potential disadvantages of the use of rhTSH may still exist within the community of nuclear medicine physicians. In our opinion, the clinical benefits of rhTSH in avoiding hypothyroidism outweigh its somewhat lesser diagnostic accuracy. However, we disagree on designating rhTSH as the 'golden standard' to obtain TSH stimulation, as suggested by some authors. Thus, the first follow-up examination after ablation, which is determinant for patients' prognostic classification, can be either done under rhTSH stimulation or after hormone withdrawal. In our practice, and for higher risk patients, we still favour performing the initial follow-up after thyroid hormone withdrawal. rhTSH also shows the ability to enhance radioiodine concentration into thyroid cells. This characteristic is obviously of great interest among the nuclear medicine community. In clinical practice, it seems preferable to perform 131 I treatment for metastatic disease during hypothyroidism. rhTSH may find its utility for the treatment of specific populations of patients, i.e. those in whom hormone withdrawal is medically contraindicated or in whom adequate endogenous TSH levels cannot be obtained due to reduced pituitary reserve or continued thyroxine production by metastatic tissue. In conclusion, rhTSH has demonstrated to be a reliable alternative to hypothyroidism for the stimulation of Tg in the follow-up of thyroid cancer patients. However, its use must be more carefully chosen in the therapeutic setting. Our feeling is that rhTSH should no tbe used for remnant ablation in high-risk patients and for the treatment of metastatic disease, except for specific populations of patients. (O.M.)

Thyroid dosimetry after the Chernobyl accident and thyroid cancer in iodine deficient areas

Energy Technology Data Exchange (ETDEWEB)

Szybinski, Z [Jagiellonian Univ., Cracow (Poland). Dept. of Endocrinology

1996-08-01

Of the radionuclides generated from 235-U and 239-Pu in a core of the nuclear reactor, radioiodines particularly 131-I, is the most significant in view of its huge quantities, easy dispersion and cumulation in the human thyroid in case of a nuclear accident. After nuclear accident in Chernobyl 20-50 million Ci of 131-I was released. Depending on the dose absorbed to the thyroid, 131-I can cause a late appearance of a thyroid nodule or cancer and/or thyroid destruction leading to hypothyroidism. Thyroid irradiation may origin from two sources: external cumulative radiation mainly of gamma type and internal related to 131-I cumulation. So far most information on the risk factors of the thyroid cancer due to is related to from external radiation, but there is no scientific basis to believe that internal radiation cannot induce the thyroid cancer. Thyroid dosimetry after Chernobyl accident in near and far field is essential for calculation of the thyroid cancer risk coefficient due to radiation. 1 tab.

Radio-guided surgery in differentiated thyroid cancer: report of four cases

International Nuclear Information System (INIS)

Kallel, F.; Hamza, F.; Charfeddine, S.; Guermazi, F.; Ghorbel, A.

2009-01-01

Radio-guided surgery is a technique using the ability of a tumour tissue to uptake a radiopharmaceutical, in order, to facilitate its location with an intraoperative gamma probe. This technique was first used in the detection of recurrent thyroid cancer. We present our experience in this indication in four cases which were followed in our department. (authors)

Selective in vitro targeting of GRP and NMB receptors in human tumours with the new bombesin tracer 177Lu-AMBA

International Nuclear Information System (INIS)

Waser, Beatrice; Eltschinger, Veronique; Reubi, Jean C.; Linder, Karen; Nunn, Adrian

2007-01-01

To investigate the in vitro binding properties of a novel radiolabelled bombesin analogue, 177 Lu-AMBA, in human neoplastic and non-neoplastic tissues selected for their expression of the bombesin receptor subtypes GRP-R, NMB-R and BRS-3. In vitro receptor autoradiography was performed in cancers expressing the various bombesin receptor subtypes. The novel radioligand 177 Lu-AMBA was used and compared with established bombesin radioligands such as 125 I-Tyr 4 -bombesin and 125 I-[D-Tyr 6 ,β-Ala 11 ,Phe 13 ,Nle 14 ]-bombesin(6-14). In vitro incidence of detection of each of the three bombesin receptor subtypes was evaluated in each tumour. 177 Lu-AMBA identified all GRP-R-expressing tumours, such as prostatic, mammary and renal cell carcinomas as well as gastrointestinal stromal tumours. 177 Lu-AMBA also identified all NMB-expressing tumours, but did not detect BRS-3-expressing tumours or BRS-3-expressing pancreatic islets. GRP-R-expressing peritumoural vessels were heavily labelled with 177 Lu-AMBA. In contrast to the strongly GRP-R-positive mouse pancreas, the human pancreas was not labelled with 177 Lu-AMBA unless chronic pancreatitis was diagnosed. In general, the sensitivity was slightly better with 177 Lu-AMBA than with the conventional bombesin radioligands. The present in vitro study suggests that 177 Lu-AMBA may be a very useful in vivo targeting agent for GRP-R-expressing tumours, NMB-R-expressing tumours and GRP-R-expressing neoangiogenic vessels. (orig.)

Radiation and host factors in human thyroid tumors following thymus irradiation

International Nuclear Information System (INIS)

Shore, R.E.; Pasternack, B.S.; Woodard, E.D.; Hempelmann, L.H.

1980-01-01

Thyroid tumor data from the 1971 survey of the Rochester, New York thymus irradiated population are further analyzed to study radiobiological and host factors. The analyses were based on the approx. 2650 irradiated subjects and 4800 sibling controls who had 5 or more years of follow-up. Twenty-four thyroid cancers and 52 thyroid adenomas were found in the irradiated group, and O thyroid cancers and 6 adenomas among the controls. The overall risk estimates were 3.8 thyroid cancers/10 6 persons/yr/rad and 4.5 thyroid adenomas/10 6 persons/yr/rad. The dose-response data (thyroid dose range of 5 to > 1000 rad) for thyroid cancer indicate both a linear and a dose-squared component, but no dose-squared component is evident for thyroid adenomas. At lower total doses (< 400 rad) there was a suggestion that dose fractionation diminished the thyroid cancer response, but a similar fractionation effect was not found for thyroid adenomas. The temporal pattern of tumors suggested an extended plateau of excess tumor production, rather than a wavelike temporal pattern. There was no evidence for an inverse relationship between thyroid radiation dose and thyroid cancer latency. Female and Jewish subjects had a higher risk of radiation-induced thyroid cancer than did their respective counterparts. The additive and multiplicative models of radiation effects were compared with respect to sex differences; neither model provided a superior fit to the data. The tentative nature of the conclusions is stressed because of the relatively small number of thyroid cancers. (author)

Inhibitory effects of CP on the growth of human gastric adenocarcinoma BGC-823 tumours in nude mice.

Science.gov (United States)

Wang, Hai-Jun; Liu, Yu; Zhou, Bao-Jun; Zhang, Zhan-Xue; Li, Ai-Ying; An, Ran; Yue, Bin; Fan, Li-Qiao; Li, Yong

2018-05-01

Objective To investigate the potential antitumour effects of [2-(6-amino-purine-9-yl)-1-hydroxy-phosphine acyl ethyl] phosphonic acid (CP) against gastric adenocarcinoma. Methods Human BGC-823 xenotransplants were established in nude mice. Animals were randomly divided into control and CP groups, which were administered NaHCO 3 vehicle alone or CP dissolved in NaHCO 3 (200 µg/kg body weight) daily, respectively. Tumour volume was measured weekly for 6 weeks. Resected tumours were assayed for proliferative activity with anti-Ki-67 or anti-proliferating cell nuclear antigen (PCNA) antibodies. Cell apoptosis was examined using terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assays and with caspase-3 immunostaining. Proteins were measured by Western blotting. Results There was a significant reduction in tumour volume and a reduced percentage of Ki-67-positive or PCNA-positive cells in the CP group compared with the control group. The percentage of TUNEL-positive or caspase 3-positive cells significantly increased following CP treatment compared with the control group. Tumours from the CP group had higher levels of phosphorylated-extracellular signal-regulated kinase (p-ERK) and phosphorylated-AKT (p-AKT) compared with control tumours. Conclusion CP treatment inhibited tumour growth and induced tumour cell apoptosis in a nude mouse model of BGC-823 gastric adenocarcinoma. Activation of the AKT and ERK signalling pathways may mediate this antitumour activity.

Human antiiodothyronine antibodies in patients with thyroid disorders and their effect on RIA of Iodothyronines

International Nuclear Information System (INIS)

Merlin, P.; Balsamo, A.; Mongardi, L.; Rapetti, C.; de Filippis, V.

1983-01-01

Human antiiodothyronine antibodies have been reported to occur with several thyroid conditions, associated or not with anti-thyroglobulin and/or anti-microsomes antibodies. These antibodies interfere in RIA of iodothyronines (T 3 ), giving an underestimation or an overestimation of total hormone levels when using a non-specific precipitation method (e.g. charcoal, PEG) or a specific method (e.g. double antibody), respectively. The presence of anti-iodothyronine antibodies was investigated in seven thyroid patients. The effect of the human anti-T 3 in RIA of total T 3 was ckecked by using different precipitation methods; the results showed that in the presence of circulating antibodies the only reliable method for the evaluation of total hormone is the RIA of serum ethanol extract

Thyroid Hormone Receptor Mutations in Cancer and Resistance to Thyroid Hormone: Perspective and Prognosis

Directory of Open Access Journals (Sweden)

Meghan D. Rosen

2011-01-01

Full Text Available Thyroid hormone, operating through its receptors, plays crucial roles in the control of normal human physiology and development; deviations from the norm can give rise to disease. Clinical endocrinologists often must confront and correct the consequences of inappropriately high or low thyroid hormone synthesis. Although more rare, disruptions in thyroid hormone endocrinology due to aberrations in the receptor also have severe medical consequences. This review will focus on the afflictions that are caused by, or are closely associated with, mutated thyroid hormone receptors. These include Resistance to Thyroid Hormone Syndrome, erythroleukemia, hepatocellular carcinoma, renal clear cell carcinoma, and thyroid cancer. We will describe current views on the molecular bases of these diseases, and what distinguishes the neoplastic from the non-neoplastic. We will also touch on studies that implicate alterations in receptor expression, and thyroid hormone levels, in certain oncogenic processes.

Sciatica as a presenting feature of thyroid follicular adenocarcinoma in a 79-year-old woman.

LENUS (Irish Health Repository)

Ogbodo, Elisha

2011-01-01

The authors describe an unusual case of metastatic thyroid follicular adenocarcinoma presenting with sciatica in a 79-year-old woman. The primary thyroid tumour was undiagnosed until this clinical presentation. The patient gave a short history of back pain and right-sided sciatica, which was progressive and nocturnal in nature. Neuroimaging revealed an enhancing intradural mass lesion, which was completely excised through a right L1-L3 hemilaminectomy. Histopathological examination of the excised tissue revealed a follicular thyroid carcinoma. Subsequent metastatic investigation revealed a heterogeneously attenuating mixed solid cystic mass in a retrosternal thyroid gland, with multiple solid pulmonary nodules suggestive of metastatic disease. She opted for palliative radiotherapy for the primary thyroid cancer and made remarkable postoperative improvement. The authors conclude that surgical treatment of solitary metastatic lesion may produce good symptomatic relief irrespective of patient\\'s age and primary pathology, while emphasising the need for detailed clinical evaluation of patients with \\'red flag\\' symptoms.

The acute in vitro and in vivo radiosensitivity of human lung tumour lines

International Nuclear Information System (INIS)

Duchesne, G.M.; Peacock, J.H.; Steel, G.G.

1986-01-01

Eleven human lung tumour lines have been established in xenograft or tissue culture, and the responses to acute irradiation of the 10 lines which cloned in soft agar were assayed. In vitro radiosensitivity was evaluated using the multitarget and linear quadratic models of cell survival and the surviving fraction at 2 Gy. Significant differences in the response of the different cell types were found, the large-cell phenotype exhibiting radioresistance, and small-cell carcinomas and adenocarcinomas being radiosensitive. No differences in the capacity of the different tumour types to repair radiation damage were demonstrated. In vivo and spheroid response was modified by the effects of hypoxia and cell-contact phenomena. The results suggested that hyperfractionation would be useful in the clinical management of adenocarcinoma and small-cell carcinoma. (Auth.)

Testicular germ cell tumours in dogs are predominantly of spermatocytic seminoma type and are frequently associated with somatic cell tumours

DEFF Research Database (Denmark)

Bush, J M; Gardiner, D W; Palmer, J S

2011-01-01

Unlike seminomas in humans, seminomas in animals are not typically sub-classified as classical or spermatocytic types. To compare testicular germ cell tumours (TGCT) in dogs with those of men, archived tissues from 347 cases of canine testicular tumours were morphologically evaluated...... in canine TGCT. None of the canine TGCT evaluated demonstrated the presence of carcinoma in situ cells, a standard feature of human classical seminomas, suggesting that classical seminomas either do not occur in dogs or are rare in occurrence. Canine spermatocytic seminomas may provide a useful model...... and characterized using human classification criteria. Histopathological and immunohistological analysis of PLAP, KIT, DAZ and DMRT1 expression revealed that canine seminomas closely resemble human spermatocytic seminomas. In addition, a relatively frequent concomitant presence of somatic cell tumours was noted...

Somatostatin receptor scintigraphy using (99m)Tc-EDDA/HYNIC-TOC in patients with medullary thyroid carcinoma

NARCIS (Netherlands)

Czepczynski, Rafal; Parisella, Maria Gemma; Kosowicz, Jerzy; Mikolajczak, Renata; Ziemnicka, Katarzyna; Gryczynska, Maria; Sowinski, Jerzy; Signore, Alberto

2007-01-01

Purpose Several new somatostatin analogues have been developed for the diagnosis and therapy of different tumours. Since somatostatin receptors are often over-expressed in medullary thyroid carcinoma (MTC), the aim of our study was to evaluate the utility of scintigraphy with the somatostatin

Human α-defensin (DEFA) gene expression helps to characterise benign and malignant salivary gland tumours

International Nuclear Information System (INIS)

Winter, Jochen; Wenghoefer, Matthias; Pantelis, Annette; Kraus, Dominik; Reckenbeil, Jan; Reich, Rudolf; Jepsen, Soeren; Fischer, Hans-Peter; Allam, Jean-Pierre; Novak, Natalija

2012-01-01

Because of the infrequence of salivary gland tumours and their complex histopathological diagnosis it is still difficult to exactly predict their clinical course by means of recurrence, malignant progression and metastasis. In order to define new proliferation associated genes, purpose of this study was to investigate the expression of human α-defensins (DEFA) 1/3 and 4 in different tumour entities of the salivary glands with respect to malignancy. Tissue of salivary glands (n=10), pleomorphic adenomas (n=10), cystadenolymphomas (n=10), adenocarcinomas (n=10), adenoidcystic carcinomas (n=10), and mucoepidermoid carcinomas (n=10) was obtained during routine surgical procedures. RNA was extracted according to standard protocols. Transcript levels of DEFA 1/3 and 4 were analyzed by quantitative realtime PCR and compared with healthy salivary gland tissue. Additionally, the proteins encoded by DEFA 1/3 and DEFA 4 were visualized in paraffin-embedded tissue sections by immunohistochemical staining. Human α-defensins are traceable in healthy as well as in pathological altered salivary gland tissue. In comparison with healthy tissue, the gene expression of DEFA 1/3 and 4 was significantly (p<0.05) increased in all tumours – except for a significant decrease of DEFA 4 gene expression in pleomorphic adenomas and a similar transcript level for DEFA 1/3 compared to healthy salivary glands. A decreased gene expression of DEFA 1/3 and 4 might protect pleomorphic adenomas from malignant transformation into adenocarcinomas. A similar expression pattern of DEFA-1/3 and -4 in cystadenolymphomas and inflamed salivary glands underlines a potential importance of immunological reactions during the formation of Warthin’s tumour

Recovery from radiation-induced damage in primary cultures of human epithelial thyroid cells

International Nuclear Information System (INIS)

Miller, R.C.; Hiraoka, Toshio; Enno, Masumi; Takeichi, Nobuo.

1985-01-01

Human thyroid epithelial tissues from 23 individuals were obtained from surgical tissue, and cultured in vitro. Dose response survival curves showed thyroid cells, when compared to mammary epithelial and skin fibroblast cells of human origin, to be only slightly more radiosensitive to X-rays. Cell survival curves from the cell strains showed wide variability in radiation sensitivity. Of the 23 cell strains tested, 21 strains displayed significant shoulders (nonzero quasi-threshold (D q ) values and extrapolation number (n) values greater than 1) at low dose exposures. The ability of human cells to recover from radiation damage was further studied by dose fractionation. Two cell strains were given a total X-ray dose of 304 cGy in two equal fractions separated by varying time intervals. Maximal cell survival was observed when the time interval exceeded two hours. When the two cell strains were exposed to 152 cGy of X-rays followed four hours later by second graded doses, cell survival was enhanced as compared to survival after single dose exposures. However, no benefit of dose splitting was observed when cells were exposed to low second doses. These results support previous studies showing that human cells are capable of repair but require relatively large doses to elicit a repair response. (author)

Recovery from radiation-induced damage in primary cultures of human epithelial thyroid cells

International Nuclear Information System (INIS)

Miller, R.C.; Hiraoka, Toshio; Enno, Masumi; Takeichi, Nobuo.

1985-09-01

Human thyroid epithelial tissue from 23 individuals was obtained from surgical tissue, and cultured in vitro. Dose-response survival curves showed thyroid cells, when compared to mammary epithelial and skin fibroblast cells of human origin, to be only slightly more radiosensitive to X rays. Cell survival curves from the cell strains showed wide variability in radiation sensitivity. Of the 23 cell strains tested, 21 strains displayed significant shoulders (nonzero quasi-threshold (Dsub(q)) values and extrapolation number (n) values greater than 1)* at low dose exposures. The ability of human cells to recover from radiation damage was further studied by dose fractionation. Two cell strains were given a total X-ray dose of 304 cGy in two equal fractions separated by varying time intervals. Maximal cell survival was observed when the time interval exceeded two hours. When the two cell strains were exposed to 152 cGy of X rays followed four hours later by second graded doses, cell survival was enhanced as compared to survival after single dose exposures. However, no benefit of dose splitting was observed when cells were exposed to low second doses. These results support previous studies showing that human cells are capable of repair but require relatively large doses to elicit a repair response. (author)

The clinical application of fluorescent-enzyme immunoassay to detect human thyroid peroxidase autoantibody quantitatively

International Nuclear Information System (INIS)

Chai Jinyan; Fang Peihua; Li Ning; Zhang Yanli

2010-01-01

Objective: To establish a fluorescent-enzyme immunoassay (FEIA) with recombinant human thyroid peroxidase (hTPO) as the antigen. Methods: Sera of 326 healthy people, 119 cases of Hashimoto's thyroiditis (HT), 116 cases of Graves disease (untreated), 28 cases of nodular goiter, 10 ca-ses of subacute thyroiditis and 6 cases of simple goiter were measured by the FEIA with recombinant hTPO as the antigen. Rrank sum test and χ 2 -test were used in inter-groups. Results: (1) Concentration above 4000 U/L was considered to be positive. (2) The intra-assay coefficient of variation (CV) and the inter-as-say CV were 4.59% ∼ 6.52% and 17.37% ∼ 17.45%. (3) The values measured by the FEIA were positively correlated with the values measured by hTPO antibody (hTPOAb) commercial kit (r=0.80, P 2 = 53.45, 39.30, 15.41 and 21.74, all P < 0.01). Conclusions: The method can be applied in the serum measurement of thyroid disease. HT presented the highest positive rate, therefore, the FEIA was an effective method in diagnosing HT. (authors)

Thyroid hormone antibodies and Hashimoto's thyroiditis in mongrel dogs

Energy Technology Data Exchange (ETDEWEB)

Rajatanavin, R.; Fang, S.L.; Pino, S.; Laurberg, P.; Braverman, L.E.; Smith, M.; Bullock, L.P.

1989-05-01

Abnormally elevated serum T3 concentrations measured by RIA were observed in 19 clinically euthyroid or hypothyroid mongrel dogs. The serum T4 concentrations in these sera were low, normal, or high. Measurement of the intensity of thyroid hormone binding to serum proteins was determined by equilibrium dialysis. A marked decrease in the percent free T3 was observed in these abnormal sera. Polyacrylamide gel electrophoresis, pH 7.4, of normal dog serum enriched with tracer /sup 125/I-labeled thyroid hormones demonstrated binding of (/sup 125/I)T4 to transthyretin, thyroid hormone-binding globulin, and albumin and of (/sup 125/I)T3 primarily to thyroid hormone-binding globulin. In all abnormal sera, polyacrylamide gel electrophoresis demonstrated strikingly higher binding of T3 to immunoglobulin (Ig). Eleven of 16 abnormal sera had minimal to moderate binding of T4 to Ig. The percent free T4 was lower only in dogs whose sera demonstrated markedly increased binding of T4 to Ig. All abnormal sera tested had positive antithyroglobulin antibodies, consistent with the diagnosis of autoimmune lymphocytic thyroiditis. As in humans, antibodies to thyroid hormones in dogs are more common in the presence of Hashimoto's thyroiditis and should be considered when elevated serum thyroid hormone concentrations are observed in the absence of clinical thyrotoxicosis. When an antibody to only one thyroid hormone is present, a marked discrepancy in the serum concentrations of T3 and T4 will be observed.

The prognostic value of pimonidazole and tumour pO2 in human cervix carcinomas after radiation therapy: a prospective international multi-center study

DEFF Research Database (Denmark)

Nordsmark, Marianne; Loncaster, Julie; Aquino-Parsons, Christina

2006-01-01

BACKGROUND AND PURPOSE: Hypoxia adversely affects treatment outcome in human uterine cervical cancer. Here, we present the results of a prospective international multi-centre study evaluating the prognostic value of pre-treatment tumour oxygen partial pressure (pO(2)) and the hypoxia marker pimon...... pimonidazole (pimo). MATERIALS AND METHODS: One hundred and twenty-seven patients with primary cervix cancer were entered. Pre-treatment tumour pO(2) measurements were obtained, and reported by the median tumour pO(2), the fraction of pO(2) values......BACKGROUND AND PURPOSE: Hypoxia adversely affects treatment outcome in human uterine cervical cancer. Here, we present the results of a prospective international multi-centre study evaluating the prognostic value of pre-treatment tumour oxygen partial pressure (pO(2)) and the hypoxia marker...

[18F]DOPA PET/ceCT in diagnosis and staging of primary medullary thyroid carcinoma prior to surgery.

Science.gov (United States)

Rasul, Sazan; Hartenbach, Sabrina; Rebhan, Katharina; Göllner, Adelina; Karanikas, Georgios; Mayerhoefer, Marius; Mazal, Peter; Hacker, Marcus; Hartenbach, Markus

2018-05-15

Medullary thyroid carcinoma (MTC) is characterized by a high rate of metastasis. In this study we evaluated the ability of [ 18 F]DOPA PET/ceCT to stage MTC in patients with suspicious thyroid nodules and pathologically elevated serum calcitonin (Ctn) levels prior to total thyroidectomy and lymph node (LN) dissection. A group of 32 patients with sonographically suspicious thyroid nodules and pathologically elevated basal Ctn (bCtn) and stimulated Ctn (sCtn) levels underwent DOPA PET/ceCT prior to surgery. Postoperative histology served as the standard of reference for ultrasonography and DOPA PET/ceCT region-based LN staging. Univariate and multivariate regression analyses as well as receiver operating characteristic analysis were used to evaluate the correlations between preoperative and histological parameters and postoperative tumour persistence or relapse. Primary MTC was histologically verified in all patients. Of the 32 patients, 28 showed increased DOPA decarboxylase activity in the primary tumour (sensitivity 88%, mean SUVmax 10.5). Undetected tumours were exclusively staged pT1a. The sensitivities of DOPA PET in the detection of central and lateral metastatic neck LN were 53% and 73%, in contrast to 20% and 39%, respectively, for neck ultrasonography. Preoperative bCtn and carcinoembryonic antigen levels as well as cN1b status and the number of involved neck regions on DOPA PET/ceCT were predictive of postoperative tumour persistence/relapse in the univariate regression analysis (P PET/ceCT cN1b status remained significant in the multivariate analysis (P = 0.016, relative risk 4.02). This study revealed that DOPA PET/ceCT has high sensitivity in the detection of primary MTC and superior sensitivity in the detection of LN metastases compared to ultrasonography. DOPA PET/ceCT identification of N1b status predicts postoperative tumour persistence. Thus, implementation of a DOPA-guided LN dissection might improve surgical success.

I131-meta-iodobenzylguanidine in the diagnosis and treatment of neural crest tumours

International Nuclear Information System (INIS)

Hoefnagel, C.A.; Hartog Jager, F.C.A. den; Taal, B.G.; Engelsman, E.; Kraker, J. de; Voute, P.A.

1988-01-01

Iodine-131-meta-iodobenzylguanidine (I-131-MIBG) was used for scintigraphic detection and therapy of neural crest tumours. The methodology of both techniques is described. Based upon experience with I-131-MIBG-scintigraphy in 170 patients with neural crest tumours, of whom 46 received multiple therapeutic doses of I-131-MIBG, and upon the cumulative reports in the literature, the role of I-131-MIBG in diagnosis and treatment of each of these diseases is indicated. I-131-MIBG-scintigraphy is one of the most sensitive and specific techniques for the diagnosis, staging and follow-up of phaeochromocytoma and neuroblastoma and I-131-MIBG-therapy may induce remission in a number of these patients. In carcinoid and medullary thyroid carcinoma the diagnostic sensitivity is less; however, once the diagnosis has been made, it is useful to establish that the tumour concentrates I-131-MIBG, to see if the patients at some point in time may be amenable to I-131-MIBG-therapy

[Autoimmune diseases of the thyroid gland].

Science.gov (United States)

Allelein, S; Feldkamp, J; Schott, M

2017-01-01

Autoimmune diseases of the thyroid gland are considered to be the most frequent cause of thyroid gland disorders. Autoimmune thyroid diseases consist of two subgroups: autoimmune thyroiditis (AIT) and Graves' disease. The AIT is the most common human autoimmune disease. Infiltration of the thyroid gland with cytotoxic T‑cells can lead to an initial thyrotoxicosis und during the course to hypothyroidism due to destruction of the thyroid gland. Substitution with Levothyroxine is indicated for manifest hypothyroidism and subclinical hypothyroidism with increased thyroid antibodies with the intention of normalizing the serum thyroid stimulating hormone (TSH). Graves' disease is characterized by the appearance of stimulating TSH receptor antibodies leading to hyperthyroidism. Endocrine ophthalmopathy may also occur. Ablative therapy with radioiodine therapy or thyroidectomy is administered to patients with Graves' disease without remission after at least 1 year of antithyroid drug therapy.

Clinicopathologic Predictive Factors of Cervical Lymph Node Metastasis in Differentiated Thyroid Cancer.

Science.gov (United States)

Sun, Ronghao; Zhang, Hua; Liu, Kun; Fan, Jinchuan; Li, Guojun; Song, Xicheng; Li, Chao

Cervical lymph node metastasis (LNM) has been proven to be a predictor for locoregional recurrence in differentiated thyroid carcinoma (DTC). Clinicopathological features could be effective predictive factors for central and lateral LNM of DTC, and provide references to surgeons for cervical neck dissection. Retrospective analysis of clinicopathological data was performed on 420 patients who underwent initial surgery from 2010 to 2015. The incidence of central and lateral LNM was calculated. Of 420 patients, 247 (58.8%) exhibited central LNM, and 185 (44.1%) exhibited lateral LNM. There were 29 (6.9%) cases confirmed to have skip metastasis. Univariate and multivariate analysis revealed that tumour location, tumour size, multifocality, capsular invasion, affected lobes, and age were independent predictors of central LNM. Tumour location, capsular invasion, affected lobes, and tumour size were independent predictors of lateral LNM. Our findings suggest that tumour location, affected lobes, capsular invasion, age, tumour size and multifocality may be taken as predictive factors for cervical LNM of DTC. Meticulous perioperative evaluation of cervical LNM and prophylactic cervical lymph node dissection that aims to remove the occult lymph nodes may be an option for DTC with risk factors. Copyright © 2017. Publicado por Elsevier España, S.L.U.

The molecular biological characteristics of childhood thyroid carcinoma

International Nuclear Information System (INIS)

Cherstvoy, E; Nerovnya, A.; Voskoboinic, L.; Bogdanova, T.; Tronko, N.D.; Tonnachera, M.; Dumont, J.E.; Lamy, F.; Keller, G.; Boehm, J.; Hoefler, H.; Vecchio, G.C.; Viglietto, G.; Chiappetta, G.; Williams, G.H.; Thomas, G.A.; Williams, E.D.

1996-01-01

We have used molecular biology to study mutation and expression of key oncogenes in childhood thyroid carcinomas from Belarus and Ukraine. All cases were histologically verified by two or more pathologists including at least one from the CIS and one from the EU. We chose to study six genes which have been shown to be involved in thyroid carcinogenesis in adults: ret. Ha, Ki and N ras genes, p53 and the TSH receptor. Expression of the ret oncogene, which has been shown to be activated by translocation in a proportion of papillary carcinomas has been studied by two independent methods. The first, used by the Cambridge group uses RT-PCR to identify the expression of the tyrosine kinase domain of the gene; as the gene is normally silent in follicular cells, this approach allows demonstration of activation of ret, but does not identify the particular translocation involved. The second approach, used by the Naples group, also uses RT-PCR, but amplifies across the breakpoint of each of the three translocations already identified to provide information on the proportion of tumors which express the individual translocations of this gene. Mutations in the TSH receptor, a key modulator of thyroid follicular growth have been sought by the Brussels group using SSCP and direct sequencing. The Munich group have analyzed the samples for presence of mutation in p53, which is believed to play a role in genetic instability which is a features of carcinomas derived from may different tissues. Mutations in the common sites of the ras oncogenes have been studied by the Cambridge group. Analysis of 26 papillary carcinomas so far studied has shown that mutations in the TSH receptor and in p53 do not play a significant role in the genesis of the tumours studied. The proportion of tumours showing ret expression does not differ significantly from that found in a control non exposed population from the UK. However, the pathological study shows that nearly all the increased number of thyroid

Dosimetric Comparison of Simulated Human Eye And Water Phantom in Investigation of Iodine Source Effects on Tumour And Healthy Tissues

International Nuclear Information System (INIS)

Sadi, A.S.; Masoudi, F.S. K.N.Toosi University of Technology

2011-01-01

For better clinical analysis in ophthalmic brachytherapy dosimetry, there is a need for the dose determination in different parts of the eye, so simulating the eye and defining the material of any parts of that, is helpful for better investigating dosimetry in human eye. However in brachytherapy dosimetry, it is common to consider the water phantom as human eye globe. In this work, a full human eye is simulated with MCNP-4C code by considering all parts of the eye like; lens, cornea, retina, choroid, sclera, anterior chamber, optic nerve, bulk of the eye comprising vitreous body and tumour. The average dose in different parts of this full model of human eye is determined and the results are compared with the dose calculated in water phantom. The central axes depth dose and the dose in whole of the tumour for these two simulated eye model are calculated too, and the results are compared. At long last, as the aim of this work is comparing the result of investigating dosimetry between two water phantom as human eye and simulated eye globe, the ratios of the absorbed dose by the healthy tissues to the absorbed dose by the tumour are calculated in these simulations and the comparison between results is done eventually.

Selective in vitro targeting of GRP and NMB receptors in human tumours with the new bombesin tracer {sup 177}Lu-AMBA

Energy Technology Data Exchange (ETDEWEB)

Waser, Beatrice; Eltschinger, Veronique; Reubi, Jean C. [University of Berne, Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, P.O. Box 62, Bern (Switzerland); Linder, Karen; Nunn, Adrian [Bracco Research USA Inc, Princeton, NJ (United States)

2007-01-15

To investigate the in vitro binding properties of a novel radiolabelled bombesin analogue, {sup 177}Lu-AMBA, in human neoplastic and non-neoplastic tissues selected for their expression of the bombesin receptor subtypes GRP-R, NMB-R and BRS-3. In vitro receptor autoradiography was performed in cancers expressing the various bombesin receptor subtypes. The novel radioligand {sup 177}Lu-AMBA was used and compared with established bombesin radioligands such as {sup 125}I-Tyr{sup 4}-bombesin and {sup 125}I-[D-Tyr{sup 6},{beta}-Ala{sup 11},Phe{sup 13},Nle{sup 14}]-bombesin(6-14). In vitro incidence of detection of each of the three bombesin receptor subtypes was evaluated in each tumour. {sup 177}Lu-AMBA identified all GRP-R-expressing tumours, such as prostatic, mammary and renal cell carcinomas as well as gastrointestinal stromal tumours. {sup 177}Lu-AMBA also identified all NMB-expressing tumours, but did not detect BRS-3-expressing tumours or BRS-3-expressing pancreatic islets. GRP-R-expressing peritumoural vessels were heavily labelled with {sup 177}Lu-AMBA. In contrast to the strongly GRP-R-positive mouse pancreas, the human pancreas was not labelled with {sup 177}Lu-AMBA unless chronic pancreatitis was diagnosed. In general, the sensitivity was slightly better with {sup 177}Lu-AMBA than with the conventional bombesin radioligands. The present in vitro study suggests that {sup 177}Lu-AMBA may be a very useful in vivo targeting agent for GRP-R-expressing tumours, NMB-R-expressing tumours and GRP-R-expressing neoangiogenic vessels. (orig.)

A young woman with a supraclavicular swelling; some diagnostic aspects of thyroid carcinoma

International Nuclear Information System (INIS)

Logmans, S.C.; Jobsis, A.C.; Schoot, J.V. van der; Schipper, M.E.I.; Kromhout, J.G.

1983-01-01

The case is reported of a woman aged 24 years who presented a supraclavicular swelling caused by a lymph-node metastasis of an adenopapillary carcinoma. The primary tumour was found in the thyroid in which palpation and scintigraphy failed to reveal any abnormalities. The diagnosis and the diagnostic value of scintigraphic and immunohistological examination are considered. (Auth.)

Environmental Issues in Thyroid Diseases.

Science.gov (United States)

Ferrari, Silvia Martina; Fallahi, Poupak; Antonelli, Alessandro; Benvenga, Salvatore

2017-01-01

Environmental factors are determinant for the appearance of autoimmune thyroid diseases (AITD) in susceptible subjects. Increased iodine intake, selenium, and vitamin D deficiency, exposure to radiation, from nuclear fallout or due to medical radiation, are environmental factors increasing AITD. Cigarette smoking is associated with Graves' disease and Graves' ophthalmopathy, while it decreases the risk of hypothyroidism and thyroid autoimmunity. Viral infections are important environmental factors in the pathogenesis of AITD, too, particularly human parvovirus B19 (EVB19) and hepatitis C virus. Among the many chemical contaminants, halogenated organochlorines and pesticides variably disrupt thyroid function. Polychlorinated biphenyls and their metabolites and polybrominated diethyl ethers bind to thyroid transport proteins, such as transthyretin, displace thyroxine, and disrupt thyroid function. Among drugs, interferon- and iodine-containing drugs have been associated with AITD. Moreover intestinal dysbiosis causes autoimmune thyroiditis. To reduce the risk to populations and also in each patient, it is necessary to comprehend the association between environmental agents and thyroid dysfunction.

Recombinant Kunjin virus replicon vaccines induce protective T-cell immunity against human papillomavirus 16 E7-expressing tumour

International Nuclear Information System (INIS)

Herd, Karen A.; Harvey, Tracey; Khromykh, Alexander A.; Tindle, Robert W.

2004-01-01

The persistence of the E7 oncoprotein in transformed cells in human papillomavirus (HPV)-associated cervical cancer provides a tumour-specific antigen to which immunotherapeutic strategies may be directed. Self-replicating RNA (replicon) vaccine vectors derived from the flavivirus Kunjin (KUN) have recently been reported to induce T-cell immunity. Here, we report that inclusion of a CTL epitope of HPV16 E7 protein into a polyepitope encoded by a KUN vector induced E7-directed T-cell responses and protected mice against challenge with an E7-expressing epithelial tumour. We found replicon RNA packaged into virus-like particles to be more effective than naked replicon RNA or plasmid DNA constructed to allow replicon RNA transcription in vivo. Protective immunity was induced although the E7 CTL epitope was subdominant in the context of other CTL epitopes in the polyepitope. The results demonstrate the efficacy of the KUN replicon vector system for inducing protective immunity directed towards a virally encoded human tumour-specific antigen, and for inducing multi-epitopic CTL responses

Comparison of therapeutic efficacy and clinical parameters between recombinant human thyroid stimulating hormone and thyroid hormone withdrawal in high-dose radioiodine treatment with differentiated thyroid cancer

Energy Technology Data Exchange (ETDEWEB)

Choi, Se Hun; Na, Chang Ju; Kim, Jeong Hun; Han, Yeon Hee; KIm, Hee Kwon; Jeong, Hwan Jeong; Sohn, Myung Hee; Lim, Seok Tae [Dept. of Nuclear Medicine, Chonbuk National University Medical School and Hospital, Jeonju (Korea, Republic of)

2015-06-15

High-dose radioiodine treatment (HD-RIT) after injection of recombinant human thyroid stimulating hormone (rh-TSH) has become widely used. This study compared the therapeutic efficacy of HD-RIT and clinical parameters between rh-TSH supplement and thyroid hormone withdrawal (THW) after total thyroidectomy in patients with differentiated thyroid cancer. We retrospectively reviewed 266 patients (47 male and 219 female; age, 49.0 ± 10.9 years) with differentiated thyroid cancer detected from September 2011 to September 2012. Patients comprised THW (217, 81.6 %) and rh-TSH (49, 18.4 %). Inclusion criteria were: first HD-RIT; any TN stage; absence of distant metastasis. To evaluate the complete ablation of the remnant thyroid tissue or metastasis, we reviewed stimulated serum thyroglobulin (sTg), I-123 whole-body scan (RxWBS) on T4 off-state, and thyroid ultrasonography (US) or [F-18]-fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) 6–8 months after HD-RIT. We defined a complete ablation state when all three of the follow-up conditions were satisfied; <2.0 ng/ml of the sTg, I-123 RxWBS (−), and thyroid US or F-18 FDG PET/CT (−). If one of the three was positive, ablation was considered incomplete. We also compared various clinical biomarkers (body weight, body mass index, liver and kidney function) between THW and rh-TSH groups. The rates of complete ablation were 73.7 % (160/217) for the THW group and 73.5 % (36/49) for the rh-TSH group. There was no significant difference between the two groups (p = 0.970). The follow-up aspartate transaminase (p = 0.001) and alanine transaminase (p = 0.001) were significantly higher in the THW group. The renal function parameters of blood urea nitrogen (p = 0.001) and creatinine (p = 0.005) tended to increase in the THW group. The change of body weight was + Δ0.96 (±1.9) kg for the THW group and was decreased by -Δ1.39 (±1.5) kg for the rh-TSH group. The change

Genetic and molecular analysis of radon-induced rat lung tumours

International Nuclear Information System (INIS)

Guilly, M.N.; Joubert, Ch.; Levalois, C.; Dano, L.; Chevillard, S.

2002-01-01

We have a model of radon-induced rat lung tumours, which allow us to analyse the cytogenetic and molecular alterations of the tumours. The aim is to better understand the mechanisms of radio-induced carcinogenesis and to define if it exists a specificity of radio-induced genetic alterations as compared to the genetic alterations found in the sporadic tumours. We have started our analysis by developing global cytogenetic and molecular approaches. We have shown that some alterations are recurrent. The genes that are potentially involved are the oncogene MET and the tumour suppressor Bene p16, which are also frequently altered in human lung tumours. Simultaneously, we have focussed our analysis by targeting the search of mutation in the tumour suppressor gene TP3. We have found that 8 of 39 tumours were mutated by deletion in the coding sequence of TP53. This high frequency of deletion, which is not observed in the human p53 mutation database could constitute a signature of radio-induced alterations. On this assumption, this type of alteration should not be only found on TP53 Bene but also in other suppressor genes which are inactivated by a mutation such as p16 for example. The work we are carrying out on radio-induced tumours among humans and animals is directed to this end. (author)

Anti-tumour activity in RAS-driven tumours by blocking AKT and MEK

Science.gov (United States)

Tolcher, Anthony W.; Khan, Khurum; Ong, Michael; Banerji, Udai; Papadimitrakopoulou, Vassiliki; Gandara, David R.; Patnaik, Amita; Baird, Richard D.; Olmos, David; Garrett, Christopher R.; Skolnik, Jeffrey M.; Rubin, Eric H.; Smith, Paul D.; Huang, Pearl; Learoyd, Maria; Shannon, Keith A.; Morosky, Anne; Tetteh, Ernestina; Jou, Ying-Ming; Papadopoulos, Kyriakos P.; Moreno, Victor; Kaiser, Brianne; Yap, Timothy A.; Yan, Li; de Bono, Johann S.

2014-01-01

Purpose KRAS is the most commonly mutated oncogene in human tumours. KRAS-mutant cells may exhibit resistance to the allosteric MEK1/2 inhibitor selumetinib (AZD6244; ARRY-142886) and allosteric AKT inhibitors (such as MK-2206), the combination of which may overcome resistance to both monotherapies. Experimental Design We conducted a dose/schedule-finding study evaluating MK-2206 and selumetinib in patients with advanced treatment-refractory solid tumours. Recommended dosing schedules were defined as MK-2206 135 mg weekly and selumetinib 100 mg once-daily. Results Grade 3 rash was the most common dose-limiting toxicity (DLT); other DLTs included grade 4 lipase increase, grade 3 stomatitis, diarrhoea, and fatigue, and grade 3 and grade 2 retinal pigment epithelium detachment. There were no meaningful pharmacokinetic drug-drug interactions. Clinical anti-tumour activity included RECIST 1.0-confirmed partial responses in non-small cell lung cancer and low-grade ovarian carcinoma. Conclusion Responses in KRAS-mutant cancers were generally durable. Clinical co-targeting of MEK and AKT signalling may be an important therapeutic strategy in KRAS-driven human malignancies (Trial NCT number NCT01021748). PMID:25516890

Casein kinase II is elevated in solid human tumours and rapidly proliferating non-neoplastic tissue

DEFF Research Database (Denmark)

Münstermann, U; Fritz, G; Seitz, G

1990-01-01

Protein kinase CKII (i.e. casein kinase II, CKII, NII) is expressed at a higher level in rapidly proliferating tissues and in solid human tumours (e.g. colorectal carcinomas) when compared to the corresponding non-neoplastic colorectal mucosa. This could be shown by (a) Western blotting of cellular...

Viruses and thyroiditis: an update

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Hober Didier

2009-01-01

Full Text Available Abstract Viral infections are frequently cited as a major environmental factor involved in subacute thyroiditis and autoimmune thyroid diseases This review examines the data related to the role of viruses in the development of thyroiditis. Our research has been focused on human data. We have reviewed virological data for each type of thyroiditis at different levels of evidence; epidemiological data, serological data or research on circulating viruses, direct evidence of thyroid tissue infection. Interpretation of epidemiological and serological data must be cautious as they don't prove that this pathogen is responsible for the disease. However, direct evidence of the presence of viruses or their components in the organ are available for retroviruses (HFV and mumps in subacute thyroiditis, for retroviruses (HTLV-1, HFV, HIV and SV40 in Graves's disease and for HTLV-1, enterovirus, rubella, mumps virus, HSV, EBV and parvovirus in Hashimoto's thyroiditis. However, it remains to determine whether they are responsible for thyroid diseases or whether they are just innocent bystanders. Further studies are needed to clarify the relationship between viruses and thyroid diseases, in order to develop new strategies for prevention and/or treatment.

Viruses and thyroiditis: an update

Science.gov (United States)

Desailloud, Rachel; Hober, Didier

2009-01-01

Viral infections are frequently cited as a major environmental factor involved in subacute thyroiditis and autoimmune thyroid diseases This review examines the data related to the role of viruses in the development of thyroiditis. Our research has been focused on human data. We have reviewed virological data for each type of thyroiditis at different levels of evidence; epidemiological data, serological data or research on circulating viruses, direct evidence of thyroid tissue infection. Interpretation of epidemiological and serological data must be cautious as they don't prove that this pathogen is responsible for the disease. However, direct evidence of the presence of viruses or their components in the organ are available for retroviruses (HFV) and mumps in subacute thyroiditis, for retroviruses (HTLV-1, HFV, HIV and SV40) in Graves's disease and for HTLV-1, enterovirus, rubella, mumps virus, HSV, EBV and parvovirus in Hashimoto's thyroiditis. However, it remains to determine whether they are responsible for thyroid diseases or whether they are just innocent bystanders. Further studies are needed to clarify the relationship between viruses and thyroid diseases, in order to develop new strategies for prevention and/or treatment. PMID:19138419

Promoter methylation-associated loss of ID4 expression is a marker of tumour recurrence in human breast cancer

International Nuclear Information System (INIS)

Noetzel, Erik; Veeck, Jürgen; Niederacher, Dieter; Galm, Oliver; Horn, Felicitas; Hartmann, Arndt; Knüchel, Ruth; Dahl, Edgar

2008-01-01

Inhibitor of DNA binding/Inhibitor of differentiation 4 (ID4) is a critical factor for cell proliferation and differentiation in normal vertebrate development. ID4 has regulative functions for differentiation and growth of the developing brain. The role of ID1, ID2 and ID3 are expected to be oncogenic due to their overexpression in pancreatic cancer and colorectal adenocarcinomas, respectively. Aside from these findings, loss of ID3 expression was demonstrated in ovarian cancer. The aim of the present study was to reveal the factual role of ID4 in carcinogenesis in more detail, since its role for the pathogenesis of human breast cancer has been discussed controversially, assigning both oncogenic and tumour suppressive functions. ID4 promoter methylation, ID4 mRNA expression and ID4 protein expression were analysed in primary human breast cancer specimens using methylation-specific PCR (MSP) (n=170), semiquantitative realtime RT-PCR (n=46) and immunhistochemistry (n=3), respectively. In order to demonstrate a functional association of ID4 promoter methylation with its gene silencing, we performed DNA demethylation analysis with four human breast cell lines using MSP and semiquantitative realtime RT-PCR. In addition, we performed correlations of ID4 promoter methylation with ID4 mRNA and ID4 protein expression in matched samples of breast tumour and corresponding normal tissue. We carried out statistical analyses in order to find correlations between ID4 promoter methylation and clinicopathological parameters. Frequent ID4 promoter methylation was observed in primary breast cancer samples (69%, 117/170). We found a tight correlation (P<0.0001) between ID4 promoter methylation and loss of ID4 expression in primary breast cancer 3 specimens. Demethylating treatment with breast cancer cell lines was associated with clear ID4 mRNA re-expression. Tumours with ID4 promoter methylation showed distinct loss of ID4 expression on both transcription and protein level

Comparison of clinicopathological features in incidental and nonincidental papillary thyroid carcinomas in 308 patients

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Nuray Can

2017-11-01

Full Text Available Incidental papillary thyroid carcinomas (IPTCs consist of a significant portion of increasing incidence in papillary thyroid carcinomas. This study investigated the clinicopathological features of IPTCs from different perspectives and by comparing nonincidental PTCs (NIPTCs in patients who underwent total thyroidectomy and lymph node dissection. Basic results were as follows. IPTC was present in 27.9% of 308 patients. IPTCs were significantly accompanied by lymphocytic thyroiditis (LT, particularly, multinodular hyperplasia (MNH. IPTCs were more common in older patients (51.3 years vs. 47.2 years and in female patients. IPTCs significantly differed from NIPTCs in terms of smaller tumour size, lymphatic vessel invasion (2.6% vs. 97.4%, extrathyroidal extension (4.3% vs. 95.7%, lymph node metastasis (3.6% vs. 96.4%, multifocality (21.2% vs. 78.8%, bilaterality (5.3% vs. 94.7%, and BRAFV600 mutation (6.7% vs. 93.3%. Older age, bilaterality, encapsulation, and radioactive iodine (RAI were significantly more common in IPTCs > 5 mm than in those ≤ 5 mm. In conclusion, IPTCs are more commonly associated with LT and MNH. IPTCs may have a more favourable prognosis than NIPTCs, and tumour size > 5 mm may predict bilaterality and need for RAI. Nevertheless, the patient-based clinical approach in IPTCs may have benefits in the management of IPTCs.

Fluorine-18 fluorodeoxyglucose positron emission tomography in the follow-up of differentiated thyroid cancer

International Nuclear Information System (INIS)

Gruenwald, F.; Schomburg, A.; Bender, H.; Klemm, E.; Menzel, C.; Bultmann, T.; Palmedo, H.; Ruhlmann, J.; Kozak, B.; Biersack, H.J.

1996-01-01

Whole-body fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging was performed during the follow-up of 33 patients suffering from differentiated thyroid cancer. Among them there were 26 patients with papillary and seven with follicular tumours. Primary tumour stage (pT) was pT1 in six cases, pT2 in eight cases, pT3 in three cases and pT4 in 14 cases. FDG PET was normal in 18 patients. In three patients a slightly increased metabolism was observed in the thyroid bed, assumed to be related to remnant tissue. In one case local recurrence, in ten cases lymph node metastases (one false-positive, caused by sarcoidosis) and in three cases distant metastases were found with FDG PET. In comparison with whole-body scintigraphy using iodine-131 (WBS) there were a lot of discrepancies in imaging results. Whereas three patients had distant metastases (proven with 131 I) and a negative FDG PET, in four cases 131 I-negative lymph node metastases were detectable with PET. Even in the patients with concordant ''staging'', differences between 131 I and FDG were observed as to the exact lesion localization. Therefore, a coexistence of 131 I-positive/FDG-negative, 131 I-negative/FDG-positive and 131 I-positive/FDG-positive malignant tissue can be assumed in these patients. A higher correlation of FDG PET was observed with hexakis (2-methoxyisobutylisonitrile) technetium-99m (I) (MIBI) scintigraphy (performed in 20 cases) than with WBS. In highly differentiated tumours 131 I scintigraphy had a high sensitivity, whereas in poorly differentiated carcinomas FDG PET was superior. The clinical use of FDG PET can be recommended in all cases of suspected or proven recurrence and/or metastases of differentiated thyroid cancer and is particularly useful in cases with elevated serum thyroglobulin levels and negative WBS. (orig.). With 3 figs., 2 tabs

Nuclear translocation of β-catenin and decreased expression of epithelial cadherin in human papillomavirus-positive tonsillar cancer: an early event in human papillomavirus-related tumour progression?

Science.gov (United States)

Stenner, Markus; Yosef, Basima; Huebbers, Christian U; Preuss, Simon F; Dienes, Hans-Peter; Speel, Ernst-Jan M; Odenthal, Margarete; Klussmann, Jens P

2011-06-01

High-risk human papillomaviruses (HPVs) constitute an important risk factor for tonsillar cancer. This study describes changes in cell adhesion molecules during metastasis of HPV-related and HPV-unrelated tonsillar carcinomas. We examined 48 primary tonsillar carcinoma samples (25 HPV-16 DNA-positive, 23 HPV-16 DNA-negative) and their respective lymph node metastases for their HPV status and for the expression of p16, epithelial cadherin (E-cadherin), β-catenin, and vimentin. A positive HPV-specific polymerase chain reaction finding correlated significantly with p16 overexpression in both primary tumours and their metastases (P<0.0001 for both). In HPV-unrelated carcinomas, the expression of E-cadherin was significantly lower in metastases than in primary tumours (P<0.001). In contrast, the expression of nuclear β-catenin was significantly higher in metastases than in primary tumours (P=0.016). In HPV-related carcinomas, nuclear localization of β-catenin expression was already apparent in primary tumours (P=0.030). The expression of vimentin significantly correlated with the grading of the primary tumour (P=0.021). Our data indicate that the down-regulation of E-cadherin and the up-regulation of nuclear β-catenin expression might be crucial steps during tumour progression of tonsillar carcinomas, being already present in primary tumours in HPV-driven carcinomas, but becoming apparent in HPV-unrelated tumours later in the process of metastasis. © 2011 Blackwell Publishing Limited.

Cytogenetic and molecular characterization of human radio-induced tumours

International Nuclear Information System (INIS)

Lefevre, S.

2002-09-01

After a brief recall of some fundamentals regarding radiobiology, this research thesis discusses some epidemiological aspects of radio carcinogenesis, based on epidemiological studies performed on people having survived to Hiroshima, Nagasaki and Chernobyl, but also performed on people submitted to domestic or professional exposures to radon, or to medicine-related exposures. The author highlights some predispositions to radio-induced cancers. Then, she discusses the genetic mechanisms of radio-induced carcinogenesis and the genetic alterations observed in human radio-induced tumours. She discusses and comments the genomic instability, its mechanisms and some models observed on mice, and describes the various forms of radio-induced genomic instability. After a discussion of all these aspects, the author draws some perspectives for future research works

Core I gene is overexpressed in Hürthle and non-Hürthle cell microfollicular adenomas and follicular carcinomas of the thyroid

International Nuclear Information System (INIS)

Máximo, Valdemar; Preto, Ana; Crespo, Ana; Rocha, Ana Sofia; Machado, José Carlos; Soares, Paula; Sobrinho-Simões, Manuel

2004-01-01

Most of the steps involved in the initiation and progression of Hürthle (oncocytic, oxyphilic) cell carcinomas of the thyroid remain unknown. Using differential display and semiquantitative RT-PCR we found, among other alterations, overexpression of the gene encoding the Core I subunit of the complex III of the mitochondrial respiratory chain in a follicular carcinoma composed of Hürthle cells. Similar high levels of Core I gene expression were detected in nine follicular carcinomas (seven with Hürthle cell features), in seven microfollicular adenomas (one with Hürthle cell features) and in one micro/macrofollicular adenoma, in contrast to a lower/normal expression in nine papillary carcinomas (three with Hürthle cell features) and five macrofollicular adenomas (one of which displaying Hürthle cell features). No significative correlation was found between Core I overexpression and the proliferative activity of the lesions. We conclude that Core I overexpression in thyroid tumours is not associated with malignancy, Hürthle cells or proliferative activity. The pathogenetic mechanism linking Core I overexpression to the microfollicular pattern of growth of thyroid tumours remains to be clarified

Complications of acromegaly: thyroid and colon.

Science.gov (United States)

Tirosh, Amit; Shimon, Ilan

2017-02-01

In acromegaly the long-term exposure to high growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels may result in specific complications in different human organs, including the thyroid gland and the colon. We will review here the evidence available regarding the characteristic thyroid and colon complications in acromegaly. This review summarizes the published data observing noncancerous structural abnormalities (thyroid nodules, colonic polyps) and thyroid and colon cancer in patients diagnosed with acromegaly. Thyroid micro-carcinomas are probably over-diagnosed among acromegalic patients. In regard to colon cancer, there is no sufficient data to suggest that colon cancer risk is higher in acromegaly compared to the general population.

Predicting Chernobyl childhood thyroid cancers from incoming data

International Nuclear Information System (INIS)

Thomas, P.J.

1997-01-01

Data on childhood thyroid cancers contracted in Belarus, the Ukraine and Russia's Bryansk and Kaluga regions have been analysed under the working hypothesis that the excess cancers have been caused by iodine-131 from Chernobyl fallout. It is postulated that the variation in latency period between different individuals is most likely to conform to either a normal or a normal logarithmic distribution. Optimal values of the mean and geometric mean latency period, together with their associated standard deviations, have been found using Belarus data. Both resulting distributions predict significant incidence of childhood thyroid cancer much earlier than ten years after the accident, a length of time widely understood in the past to be the approximate minimum for the development of a radiation-induced, solid tumour. The two distributions incorporating these optimal values have been tested against independent data from the Ukraine and Russian and each distribution has passed the statistical tests to date. Predictions are given for the annual incidence of childhood thyroid cancer in each country and for the total number of excess cases over all years. Tolerances are assigned to the latter figure. (Author)

Mendelian analysis of a metastasis-prone substrain of BALB/c nude mice using a subcutaneously inoculated human tumour

DEFF Research Database (Denmark)

Schou, M; Brünner, N; Spang-Thomsen, M

2006-01-01

Most nude mice do not allow the formation of metastases after heterotransplantation of human malignant tumours. Here we describe a substrain of BALB/c nude mice (BALB/c/AnNCr) that reproducibly allows some human cancers to metastasize. By Mendelian analysis of hybrids between this substrain and C57...

Regulation of Thyroid Hormone Bioactivity in Health and Disease

NARCIS (Netherlands)

R.P. Peeters (Robin)

2005-01-01

textabstractTThyroid hormone plays an essential role in a variety of metabolic processes in the human body. Examples are the effects of thyroid hormone on metabolism and on the heart. The production of thyroid hormone by the thyroid is regulated by thyroid stimulating hormone (TSH) via the TSH

Oxidative stress specifically downregulates survivin to promote breast tumour formation.

Science.gov (United States)

Pervin, S; Tran, L; Urman, R; Braga, M; Parveen, M; Li, S A; Chaudhuri, G; Singh, R

2013-03-05

Breast cancer, a heterogeneous disease has been broadly classified into oestrogen receptor positive (ER+) or oestrogen receptor negative (ER-) tumour types. Each of these tumours is dependent on specific signalling pathways for their progression. While high levels of survivin, an anti-apoptotic protein, increases aggressive behaviour in ER- breast tumours, oxidative stress (OS) promotes the progression of ER+ breast tumours. Mechanisms and molecular targets by which OS promotes tumourigenesis remain poorly understood. DETA-NONOate, a nitric oxide (NO)-donor induces OS in breast cancer cell lines by early re-localisation and downregulation of cellular survivin. Using in vivo models of HMLE(HRAS) xenografts and E2-induced breast tumours in ACI rats, we demonstrate that high OS downregulates survivin during initiation of tumourigenesis. Overexpression of survivin in HMLE(HRAS) cells led to a significant delay in tumour initiation and tumour volume in nude mice. This inverse relationship between survivin and OS was also observed in ER+ human breast tumours. We also demonstrate an upregulation of NADPH oxidase-1 (NOX1) and its activating protein p67, which are novel markers of OS in E2-induced tumours in ACI rats and as well as in ER+ human breast tumours. Our data, therefore, suggest that downregulation of survivin could be an important early event by which OS initiates breast tumour formation.

Obtaining of stimulating hormone of the thyroid (hTSH) of Human Hypophysis

International Nuclear Information System (INIS)

Ayala, Jorge H; Carvajal G, Claudia; Anzola V, Cecilia; Gomez de, Myrian

1993-01-01

Thyroid-stimulating hormone (TSH) was extracted from human frozen pituitary glands using a method for the integral extraction of most hormones present in the gland. A specific immunoradiometric method (IRMA) was standardized and used for the analysis of TSH content. The immunology potency of the final TSH preparation was 1365 mUI/mg by IRMA. Characterization by SDS-PAGE demonstrated the multicomponent nature of the hormone

Phthalates Are Metabolised by Primary Thyroid Cell Cultures but Have Limited Influence on Selected Thyroid Cell Functions In Vitro.

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Juliana Frohnert Hansen

Full Text Available Phthalates are plasticisers added to a wide variety of products, resulting in measurable exposure of humans. They are suspected to disrupt the thyroid axis as epidemiological studies suggest an influence on the peripheral thyroid hormone concentration. The mechanism is still unknown as only few in vitro studies within this area exist. The aim of the present study was to investigate the influence of three phthalate diesters (di-ethyl phthalate, di-n-butyl phthalate (DnBP, di-(2-ethylhexyl phthalate (DEHP and two monoesters (mono-n-butyl phthalate and mono-(2-ethylhexyl phthalate (MEHP on the differentiated function of primary human thyroid cell cultures. Also, the kinetics of phthalate metabolism were investigated. DEHP and its monoester, MEHP, both had an inhibitory influence on 3'-5'-cyclic adenosine monophosphate secretion from the cells, and MEHP also on thyroglobulin (Tg secretion from the cells. Results of the lactate dehydrogenase-measurements indicated that the MEHP-mediated influence was caused by cell death. No influence on gene expression of thyroid specific genes (Tg, thyroid peroxidase, sodium iodine symporter and thyroid stimulating hormone receptor by any of the investigated diesters could be demonstrated. All phthalate diesters were metabolised to the respective monoester, however with a fall in efficiency for high concentrations of the larger diesters DnBP and DEHP. In conclusion, human thyroid cells were able to metabolise phthalates but this phthalate-exposure did not appear to substantially influence selected functions of these cells.

Cost-effectiveness of using recombinant human thyroid-stimulating hormone before radioiodine ablation for thyroid cancer treatment in Spanish hospitals.

Science.gov (United States)

Vallejo, J A; Muros, M A

In thyroid cancer treatment, the thyroid-stimulating hormone (TSH) must be elevated before radioiodine ablation, either by exogenous (with recombinant human thyrotropin [rhTSH]) or endogenous stimulation by thyroid hormone withdrawal (THW). The use of rhTSH avoids hypothyroidism and favours the subsequent elimination of radioiodine, but involves the cost of the product. For this reason, a cost-effectiveness analysis was performed, taking into account all costs involved and the benefits associated with the use of this therapy. Using a Markov modelling with two analysis arms (rhTSH and THW), stratified into high (100mCi/3700 MBq) and low (30mCi/1110 MBq) radioiodine doses, and using 17 weekly cycles, the incremental cost per quality-adjusted life-year (QALY) related to the use of rhTSH was determined. The clinical inputs included in the model were based on published studies and in a treatment survey conducted in Spain. Radioablation preparation with rhTSH is superior to THW, showing additional benefits (0.048 AVAC), as well as cost savings (-€614.16), with an incremental cost-effectiveness rate (ICER) of -€12,795/QALY. The univariate and multivariate sensitivity analyses showed the result to be robust. The use of rhTSH previous to radioablation in Spain has cost savings, as well as a series of health benefits for the patient, making it highly cost-effective. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

Reproductive tract tumours: the scourge of woman reproduction ails Indian rhinoceroses.

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Robert Hermes

Full Text Available In Indian rhinoceros, extensive leiomyoma, a benign smooth muscle tumour, was sporadically diagnosed post mortem and commonly thought of as contributing factor for reduced fecundity of this species in captivity. However, to date, the prevalence of reproductive tract tumours and their relevance for fecundity are unknown. Our analysis of the international studbook now reveals that females cease reproducing at the age of 18.1±1.2 years; equivalent to a reproductive lifespan of just 9.5±1.3 years. This short reproductive life is in sharp contrast to their longevity in captivity of over 40 years. Here we show, after examining 42% of the captive female population, that age-related genital tract tumours are highly prevalent in this endangered species. Growth and development of these tumours was found to be age-related, starting from the age of 10 years. All females older than 12 years had developed genital tumours, just 7-9 years past maturity. Tumour sizes ranged from 1.5-10 cm. With age, tumours became more numerous, sometimes merging into one large diffuse tumour mass. These tumours, primarily vaginal and cervical, presumably cause widespread young-age infertility by the age of 18 years. In few cases, tumour necrosis suggested possible malignancy of tumours. Possible consequences of such genital tract tumour infestation are hindered intromission, pain during mating, hampered sperm passage, risk of ascending infection during pregnancy, dystocia, or chronic vaginal bleeding. In humans, leiomyoma affect up to 80% of pre-menopause women. While a leading cause for infertility, pregnancy is known to reduce the risk of tumour development. However, different from human, surgical intervention is not a viable treatment option in rhinoceroses. Thus, in analogy to humans, we suggest early onset and seamless consecutive pregnancies to help reduce prevalence of this disease, better maintain a self-sustained captive population and improve animal welfare.

Immunoproteasome overexpression underlies the pathogenesis of thyroid oncocytes and primary hypothyroidism: studies in humans and mice.

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Hiroaki J Kimura

2009-11-01

Full Text Available Oncocytes of the thyroid gland (Hürthle cells are found in tumors and autoimmune diseases. They have a unique appearance characterized by abundant granular eosinophilic cytoplasm and hyperchromatic nucleus. Their pathogenesis has remained, thus far, unknown.Using transgenic mice chronically expressing IFNgamma in thyroid gland, we showed changes in the thyroid follicular epithelium reminiscent of the human oncocyte. Transcriptome analysis comparing transgenic to wild type thyrocytes revealed increased levels of immunoproteasome subunits like LMP2 in transgenics, suggesting an important role of the immunoproteasome in oncocyte pathogenesis. Pharmacologic blockade of the proteasome, in fact, ameliorated the oncocytic phenotype. Genetic deletion of LMP2 subunit prevented the development of the oncocytic phenotype and primary hypothyroidism. LMP2 was also found expressed in oncocytes from patients with Hashimoto thyroiditis and Hürthle cell tumors.In summary, we report that oncocytes are the result of an increased immunoproteasome expression secondary to a chronic inflammatory milieu, and suggest LMP2 as a novel therapeutic target for the treatment of oncocytic lesions and autoimmune hypothyroidism.

Specific Cytotoxicity Against Autologous Tumour and Proliferative Responses of Human Lymphocytes Grown in Interleukin 2

Science.gov (United States)

1981-08-11

reactivity against tumour cells. These cellular reagents will be useful in defining the antigenicity of human neoplasms and possibly in therapy . S, N 0) 02...Stjernswird. of human neoplasms and possibly in therapy . 1979; Vose et al., 1978; Vinky et al., 1979). Purifica- The derivation of cultured T cells...mononuclear cells were sepa- had increased 100- to 200-fold. Cells were cultured in rated by floatation on Ficoll-Hypaque (LSM, Litton- medium without IL-2 for

Correlation between micronuclei frequency in peripheral blood lymphocytes and retention of 131-I in thyroid cancer patients

International Nuclear Information System (INIS)

Vrndic, O.B.; Milosevic-Djordjevic, O.M.; Mijatovic Teodorovic, L.C.; Zivancevic Simonovic, S.T.; Jeremic, M.Z.; Stosic, I.M.; Grujicic, D.V.

2013-01-01

Differentiated thyroid cancers (DTCs) derive from thyroid follicular cells and include papillary and follicular cancers. In patients with DTCs, the initial treatment includes thyroidectomy and radioactive iodine (131-I) therapy. The objective of this study was to examine whether the intensity of DNA damage in peripheral blood lymphocytes (PBLs) of DTC patients depends on the amount of 131-I retained in the selected regions of interest (thyroid and abdominal region) as well as in the whole-body 72 hours after therapy. In addition, the possible influence of other factors that may affect micronuclei (MN) frequency, such as age, gender, smoking habits, and histological type of tumour was analyzed. The study population consisted of 22 DTC patients and 20 healthy donors. Data on the distribution of 131-I were obtained from the whole-body scans. MN frequency and cytokinesis-block proliferation index (CBPI) were measured using cytokinesis-block micronucleus assay. 131-I therapy significantly increased the MN frequency (19.50±6.90 vs. 27.10±19.50 MN) and significantly decreased the CBPI (1.52±0.20 vs. 1.38±0.17) in patients' lymphocytes. There was a clear correlation between the increased MN frequency and 131-I accumulation in the thyroid region in patients without metastases. The MN values did not differ in relation to the factors that could affect MN, such as age, gender, smoking habits, and histological type of tumour. In conclusion, the MN frequency in PBLs of DTC patients without metastases depends on the accumulation of 131-I in the thyroid region and does not depend on the other factors examined. (author)

Cell Transformation by PTP1B Truncated Mutants Found in Human Colon and Thyroid Tumors.

Science.gov (United States)

Mei, Wenhan; Wang, Kemin; Huang, Jian; Zheng, Xinmin

2016-01-01

Expression of wild-type protein tyrosine phosphatase (PTP) 1B may act either as a tumor suppressor by dysregulation of protein tyrosine kinases or a tumor promoter through Src dephosphorylation at Y527 in human breast cancer cells. To explore whether mutated PTP1B is involved in human carcinogenesis, we have sequenced PTP1B cDNAs from human tumors and found splice mutations in ~20% of colon and thyroid tumors. The PTP1BΔE6 mutant expressed in these two tumor types and another PTP1BΔE5 mutant expressed in colon tumor were studied in more detail. Although PTP1BΔE6 revealed no phosphatase activity compared with wild-type PTP1B and the PTP1BΔE5 mutant, its expression induced oncogenic transformation of rat fibroblasts without Src activation, indicating that it involved signaling pathways independent of Src. The transformed cells were tumourigenic in nude mice, suggesting that the PTP1BΔE6 affected other molecule(s) in the human tumors. These observations may provide a novel therapeutic target for colon and thyroid cancer.

Selective targeting of tumour neovasculature by a radiohalogenated human antibody fragment specific for the ED-B domain of fibronectin

International Nuclear Information System (INIS)

Demartis, S.; Tarli, L.; Neri, D.; Borsi, L.; Zardi, L.

2001-01-01

Angiogenesis is a characteristic feature of many aggressive tumours and other disorders. Antibodies capable of binding to new blood vessels, but not to mature vessels, could be used as selective targeting agents for immunoscintigraphic and radioimmunotherapeutic applications. Here we show that scFv(L19), a recombinant human antibody fragment with sub-nanomolar affinity for the ED-B domain of fibronectin, a marker of angiogenesis, can be stably labelled with iodine-125 and astatine-211 with full retention of immunoreactivity, using a trimethyl-stannyl benzoate bifunctional derivative. Biodistribution studies in mice bearing two different types of tumour grafted subcutaneously, followed by ex vivo micro-autoradiographic analysis, revealed that scFv(L19) rapidly localises around tumour blood vessels, but not around normal vessels. Four hours after intravenous injection of the stably radioiodinated scFv(L19), tumour to blood ratios were 6:1 in mice bearing the F9 murine teratocarcinoma and 9:1 in mice bearing an FE8 rat sarcoma. As expected, all other organs (including kidney) contained significantly less radioactivity than the tumour. Since the ED-B domain of fibronectin has an identical sequence in mouse and man, scFv(L19) is a pan-species antibody and the results presented here suggest clinical utility of radiolabelled scFv(L19) for the scintigraphic detection of angiogenesis in vivo. Furthermore, it should now be possible to investigate scFv(L19) for the selective delivery of 211 At to the tumour neovasculature, causing the selective death of tumour endothelial cells and tumour collapse. (orig.)

Expression of FGFR3 during human testis development and in germ cell-derived tumours of young adults

DEFF Research Database (Denmark)

Ewen, Katherine A; Olesen, Inge A; Winge, Sofia B

2013-01-01

development and to ascertain whether FGFR3 signalling is linked to germ cell proliferation and the pathogenesis of testicular germ cell tumours (TGCTs) of young adult men. Using RT-PCR, immunohistochemistry and Western blotting, we examined 58 specimens of human testes throughout development for FGFR3...... expression, and then compared expression of FGFR3 with proliferation markers (PCNA or Ki67). We also analysed for FGFR3 expression 30 TGCTs and 28 testes containing the tumour precursor cell, carcinoma in situ (CIS). Fetal and adult testes expressed exclusively the FGFR3IIIc isoform. FGFR3 protein expression...... was restricted to the cytoplasm/plasma membrane of spermatogonia and was most prevalent at mid-gestation, infancy and from puberty onwards. Phosphorylated (p)FGFR was detected in pre-spermatogonia at mid-gestation and in spermatogonia during puberty and in the adult testis. Throughout normal human testis...

Estrogen receptors in human thyroid gland. An immunohistochemical study

International Nuclear Information System (INIS)

Arain, Shaukat A.; Shah, Munawar H.; Jamal, Qamar; Meo, Sultan A.

2003-01-01

The objective of this study is to determine the estrogen receptors (ER) status (present in the nucleous of cell) in the thyroid gland tissues. For this purpose 50 previously diagnosed cases of various thyroid lesions were selected from the Surgical Pathology Records of Pathology Department, Basic Medical Sciences Institute,Jinnah Postgraduate. Medical Center,Karachi,Pakistan between March and August 2000.The staining was performed on formalin fixed paraffin embeded tissues using monoclonal anti-ER anti-body (clone1D5).Out of 50 cases,8 were noduler goiter,9 cases of adenoma 19 papillary carcinoma, 10 follicular and 4 cases were of medullary carcinoma. Surrounding normal tissue was available in 25 (50%) cases, 4 non-neoplastic and 21 neoplastic lesions.Out of 50 cases ,10(20%) and 40(80%) were females, the youngest patient was a 15-year-old female and the eldest patient was a 56-years-old male. Despite the availability of normal thyroid tissue and a wide range of lesions, none of our cases showed the positive staining. In contrary to many earlier reports by immunohistochemical method using monoclonal antibody (clone1D5) on formalin- fixed praffin-embedded thyroid tissues, the ER is not detectable. The effect of Estrogen on thyroid gland may be indirect one. (author)

Germ cell tumours in neonates and infants: a distinct subgroup?

NARCIS (Netherlands)

Veltman, I.M.; Schepens, M.T.M.; Looijenga, L.H.J.; Strong, L.C.; Geurts van Kessel, A.H.M.

2003-01-01

Human germ cell tumours (GCTs) constitute a heterogeneous group of tumours that can be classified into four major subgroups. One of these subgroups encompasses (immature) teratomas and yolk sac tumours of patients under the age of 5 years. In this paper we review the various clinical, histological

[Hashimoto's thyroiditis(chronic thyroiditis), IgG4-related thyroiditis].

Science.gov (United States)

Itoh, Mitsuyasu

2012-11-01

Hashimoto's thyroiditis emerges in patients who have genetic preponderance such as SNPs of CTLA-4 and risk factors such as excess intake of iodine, pregnancy or postpartum period, and smoking. Such risk factors also affect the entire clinical course. One of the major outcomes in Hashimoto's thyroiditis appears to be increased in cardio-vascular risks through subclinical hypothyroidism and concomitant metabolic syndrome, but in most cases, treatment with L-T4 has little effects on cardio-vascular benefit or quality of life. The pregnant women also have risks for obstetric complications and postpartum thyroid dysfunction. The women who have anti-TPO antibodies, type 1 diabetes, or previous history of post-partum thyroid dysfunction are recommended to be measured their TSH. It is noteworthy that Hashimoto's thyroiditis is sometimes complicated with encephalopathy, papillary carcinoma, or IgG4-related thyroiditis. IgG4-related thyroiditis is partly similar but partly discerned from a variant of Hashimoto's thyroiditis. The pathogenetic roles of this variant on autoimmune-based thyroiditis remain unclear.

31P NMR spectroscopy studies of phospholipid metabolism in human melanoma xenograft lines differing in rate of tumour cell proliferation.

Science.gov (United States)

Lyng, H; Olsen, D R; Petersen, S B; Rofstad, E K

1995-04-01

The concentration of phospholipid metabolites in tumours has been hypothesized to be related to rate of cell membrane turnover and may reflect rate of cell proliferation. The purpose of the study reported here was to investigate whether 31P NMR resonance ratios involving the phosphomonoester (PME) or phosphodiester (PDE) resonance are correlated to fraction of cells in S-phase or volume-doubling time in experimental tumours. Four human melanoma xenograft lines (BEX-t, HUX-t, SAX-t, WIX-t) were included in the study. The tumours were grown subcutaneously in male BALB/c-nu/nu mice. 31P NMR spectroscopy was performed at a magnetic field strength of 4.7 T. Fraction of cells in S-phase was measured by flow cytometry. Tumour volume-doubling time was determined by Gompertzian analysis of volumetric growth data. BEX-t and SAX-t tumours differed in fraction of cells in S-phase and volume-doubling time, but showed similar 31P NMR resonance ratios. BEX-t and WIX-t tumours showed significantly different 31P NMR resonance ratios but similar fractions of cells in S-phase. The 31P NMR resonance ratios were significantly different for small and large HUX-t tumours even though fraction of cells in S-phase and volume-doubling time did not differ with tumour volume. None of the 31P NMR resonance ratios showed significant increase with increasing fraction of cells in S-phase or significant decrease with increasing tumour volume-doubling time across the four xenograft lines.(ABSTRACT TRUNCATED AT 250 WORDS)

Statins as a new therapeutic approach in dedifferentiated thyroid cancer? A case report

International Nuclear Information System (INIS)

Hofmann, A.; John, P.; Sinzinger, H.; Staudenherz, A.; Schaffarich, M.P.

2005-01-01

Full text: In general differentiated thyroid tumours are removed surgically and afterwards treated with radioiodine. However, still about one third of patients with differentiated tumours, metastasise. Also 30 percent of recurrent thyroid carcinomas do not respond to iodine treatment due to loss of differentiation. Retinoic acid, biological metabolites of vitamin A, are considered to induce re-differentiation of the thyrocyte and thereby induce tumor regression. In follicular carcinoma cells, it also plays an important role in inducing iodine uptake. Retinoids, however, cannot be used in liver disease as they may induce hepatic enzyme increase. In addition 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are reported to induce on the one hand cellular apoptosis and on the other hand, in a lower dosage, differentiation in anaplastic thyroid carcinoma cells in vitro. We are presenting a 79 years old female patient with an oxyphilic follicular thyroid carcinoma and histologically verified autoimmune hepatitis. The first post therapeutic scan, showed only focal cervical localized iodine uptake. Also 3 months later no pathologic iodine uptake was recognized on the diagnostic scan, whereas the FDG-PET showed solid uptake of FDG cervical, in both lungs, in the mediastinum, the pelvis and the right hip. Due to contraindication for retinoic acid the patient was treated with usual dose statin for about 4 weeks to induce re-differentiation. Following, the patient was administered 9,25 GBq I-131 again and the post therapeutic scan showed iodine uptake cervical and in the right femur. We conclude that the administration of Statins, at low dose (20 mg/day) even over a short period of time, only may induce re-differentiation as well as an antiproliferative effect in vivo. (author)

Atrophic thyroiditis in long-term Segment III beagles

International Nuclear Information System (INIS)

Stephens, L.C.; Norrdin, R.W.; Benjamin, S.A.; Brewster, R.D.; Brooks, R.K.

1981-01-01

Lymphocytic thyroiditis associated with progressive thyroid atrophy is described in CRHL beagles. Depressed thyroid function was present in many of these dogs, as evidenced by clinical signs of hypothyroidism, elevation of serum cholesterol levels, depressed serum triiodothyronine levels, and alteration of basophils of the antero-medial region and/or unilateral or bilateral obliteration of the thyroid glands by neoplasia. Microscopic changes in the thyroid glands included lymphocytic thyroiditis, thyroid follicular atrophy, adenomatous hyperplasia of follicula cells and C-cells, and follicular cells neoplasia. This disease occurred with no sex predisposition in dogs 2 through 11 years of age. The disease does not appear to be influenced by previous radiation exposure but may be familial. In contrast to thyroid disease in some other beagle colonies, the disease in CRHL beagles more closely resembles atrophic thyroiditis of man rather than human Hashimoto's thyroiditis

Carcinogenicity/tumour promotion by NDL PCB

Energy Technology Data Exchange (ETDEWEB)

Schrenk, D. [Kaiserslautern Univ. (Germany). Food Chemistry and Environmental Toxicology

2004-09-15

Polychlorinated biphenyls (PCBs) belong to the group of persistent environmental pollutants exhibiting neurotoxic, teratogenic and tumour-promoting effects in experimental animal models. PCB congeners can be divided into 'dioxinlike' and 'non-dioxinlike' congeners on the basis of their ability to act as aryl hydrocarbon receptor (AhR) agonists. Like the most toxic dioxin congener 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) 'dioxinlike' PCBs bind to the AhR and show characteristic effects on the expression of AhR-regulated genes including the induction of cytochrome P450 (CYP) 1A1. On the other hand, 'non-dioxinlike' PCB congeners have a lower or no binding affinity to the AhR, but exhibit a 'phenobarbital-type' induction of CYP 2B1/2 activity. A carcinogenic potential of PCBs has been demonstrated with technical mixtures such as Aroclors or Clophens. In these studies the liver and the thyroid gland were found to be the principal target organs of PCB-mediated carcinogenesis in rodents. No studies have been published, however, on the carcinogenicity of individual congeners. In two-stage initiation-promotion protocols in rats, both technical mixtures and individual 'dioxinlike' and 'non-dioxinlike' congeners were reported to act as liver tumour promoters.

The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part A: Renal, Penile, and Testicular Tumours.

Science.gov (United States)

Moch, Holger; Cubilla, Antonio L; Humphrey, Peter A; Reuter, Victor E; Ulbright, Thomas M

2016-07-01

The fourth edition of the World Health Organization (WHO) classification of urogenital tumours (WHO "blue book"), published in 2016, contains significant revisions. These revisions were performed after consideration by a large international group of pathologists with special expertise in this area. A subgroup of these persons met at the WHO Consensus Conference in Zurich, Switzerland, in 2015 to finalize the revisions. This review summarizes the most significant differences between the newly published classification and the prior version for renal, penile, and testicular tumours. Newly recognized epithelial renal tumours are hereditary leiomyomatosis and renal cell carcinoma (RCC) syndrome-associated RCC, succinate dehydrogenase-deficient RCC, tubulocystic RCC, acquired cystic disease-associated RCC, and clear cell papillary RCC. The WHO/International Society of Urological Pathology renal tumour grading system was recommended, and the definition of renal papillary adenoma was modified. The new WHO classification of penile squamous cell carcinomas is based on the presence of human papillomavirus and defines histologic subtypes accordingly. Germ cell neoplasia in situ (GCNIS) of the testis is the WHO-recommended term for precursor lesions of invasive germ cell tumours, and testicular germ cell tumours are now separated into two fundamentally different groups: those derived from GCNIS and those unrelated to GCNIS. Spermatocytic seminoma has been designated as a spermatocytic tumour and placed within the group of non-GCNIS-related tumours in the 2016 WHO classification. The 2016 World Health Organization (WHO) classification contains new renal tumour entities. The classification of penile squamous cell carcinomas is based on the presence of human papillomavirus. Germ cell neoplasia in situ of the testis is the WHO-recommended term for precursor lesions of invasive germ cell tumours. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All

Black Thyroid Associated with Thyroid Carcinoma

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Emad Kandil

2010-01-01

Full Text Available Objective. Black thyroid is a rare pigmented change seen almost exclusively in patients upon minocycline ingestion, and the process has previously been thought to be generally benign. There have been 61 reported cases of black thyroid. We are aware of 13 cases previously reported in association with thyroid carcinoma. This paper reports six patients with black thyroid pigmentation in association with thyroid carcinoma. Design. The medical records of six patients who were diagnosed with black thyroid syndrome, all of whom underwent thyroid surgery, were reviewed. Data on age, gender, race, preoperative fine needle aspiration biopsy (FNA, thyroid function levels, and pathology reports were collected. Main Outcome. The mean age was 60 years. There were 5 females, 4 of whom were African American. All patients were clinically and biochemically euthyroid. Black pigmentation was not diagnosed in preoperative FNA, and only one patient had a preoperative diagnosis of papillary thyroid carcinoma. The other patients underwent surgery and were found to have black pigmentation of the thyroid associated with carcinoma. Conclusions. FNA does not diagnose black thyroid, which is associated with thyroid carcinoma. Thyroid glands with black pigmentation deserve thorough pathologic examination, including several sections of each specimen.

First-trimester maternal serum human thyroid-stimulating hormone in chromosomally normal and Down syndrome pregnancies

NARCIS (Netherlands)

Pratt, JJ; de Wolf, BTHM; Mantingh, A

Maternal serum human thyroid-stimulating hormone (TSH) levels were investigated in chromosomally normal and Down syndrome pregnancies to determine whether TSH can be used as a marker for Down syndrome in the first trimester. Measurements were conducted on stored serum samples collected from 23 Down

Inhibition of 125I organification and thyroid hormone release by interleukin-1, tumor necrosis factor-alpha, and interferon-gamma in human thyrocytes in suspension culture

International Nuclear Information System (INIS)

Sato, K.; Satoh, T.; Shizume, K.; Ozawa, M.; Han, D.C.; Imamura, H.; Tsushima, T.; Demura, H.; Kanaji, Y.; Ito, Y.

1990-01-01

To elucidate the mechanism of decreased 131I uptake by the thyroid gland in patients with subacute thyroiditis and painless thyroiditis, human thyroid follicles were cultured with interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF alpha), and/or interferon-gamma (IFN gamma), and the effects of these cytokines on thyroid function were studied in vitro. When human thyrocytes were cultured in RPMI-1640 medium containing 0.5% fetal calf serum and TSH for 5-8 days, the cells incorporated 125I, synthesized de novo [125I]iodotyrosines and [125I]iodothyronines, and secreted [125I]T4 and [125I]T3 into the medium. IL-1 alpha and IL-1 beta inhibited 125I incorporation and [125I]iodothyronine release in a concentration-dependent manner. The minimal inhibitory effect was detected at 10 pg/ml. Electron microscopic examination revealed a marked decrease in lysosome formation in IL-1-treated thyrocytes. TNF alpha and IFN gamma also inhibited thyroid function in a concentration-dependent manner. Furthermore, when thyrocytes were cultured with IL-1, TNF alpha and IFN gamma, these cytokines more than additively inhibited thyroid function. Although the main mechanism of 131I uptake suppression in the thyroid gland in subacute thyroiditis is due to cellular damage and suppression of TSH release, our present findings suggest that IL-1, TNF alpha, and IFN gamma produced in the inflammatory process within the thyroid gland further inhibit iodine incorporation and at least partly account for the decreased 131I uptake by the thyroid gland in destruction-induced hyperthyroidism

The flame retardant DE-71 (a mixture of polybrominated diphenyl ethers) inhibits human differentiated thyroid cell function in vitro.

Science.gov (United States)

Kronborg, Thit Mynster; Hansen, Juliana Frohnert; Rasmussen, Åse Krogh; Vorkamp, Katrin; Nielsen, Claus Henrik; Frederiksen, Marie; Hofman-Bang, Jacob; Hahn, Christoffer Holst; Ramhøj, Louise; Feldt-Rasmussen, Ulla

2017-01-01

Normal thyroid function is essential for general growth and metabolism, but can be affected by endocrine disrupting chemicals (EDCs). Polybrominated diphenyl ethers (PBDEs) have been used worldwide to reduce flammability in different materials and are suspected to be EDCs. The production of the commercial Penta- and OctaBDE mixtures is banned, but DecaBDEs and existing products may leak PBDEs into the environment. Our aim was to investigate the effect of the PentaBDE mixture DE-71 on human thyroid cells in vitro. Primary human thyroid cells were obtained as paraadenomatous tissue and cultured in monolayers. The influence of DE-71 on cyclic adenosine monophosphate (cAMP) and thyroglobulin (Tg) production was examined in the culture medium by competitive radioimmunoassay and enzyme-linked immunosorbent assay, respectively. Real-time quantitative PCR analysis of thyroid-specific genes was performed on the exposed cell cultures. PBDE concentrations were determined in cellular and supernatant fractions of the cultures. DE-71 inhibited Tg-release from TSH-stimulated thyrocytes. At 50 mg/L DE-71, mean Tg production was reduced by 71.9% (range: 8.5-98.7%), and cAMP by 95.1% (range: 91.5-98.8%) compared to controls). Expression of mRNA encoding Tg, TPO and TSHr were significantly inhibited (pproduction, respectively, as well as expression of mRNA encoding Tg, TPO and TSHr. Our findings suggest an inhibiting effect of PBDEs on thyroid cells.

Human thyroid peroxidase: complete cDNA and protein sequence, chromosome mapping, and identification of two alternately spliced mRNAs

International Nuclear Information System (INIS)

Kimura, S.; Kotani, T.; McBride, O.W.; Umeki, K.; Hirai, K.; Nakayama, T.; Ohtaki, S.

1987-01-01

Two forms of human thyroid peroxidase cDNAs were isolated from a λgt11 cDNA library, prepared from Graves disease thyroid tissue mRNA, by use of oligonucleotides. The longest complete cDNA, designated phTPO-1, has 3048 nucleotides and an open reading frame consisting of 933 amino acids, which would encode a protein with a molecular weight of 103,026. Five potential asparagine-linked glycosylation sites are found in the deduced amino acid sequence. The second peroxidase cDNA, designated phTPO-2, is almost identical to phTPO-1 beginning 605 base pairs downstream except that it contains 1-base-pair difference and lacks 171 base pairs in the middle of the sequence. This results in a loss of 57 amino acids corresponding to a molecular weight of 6282. Interestingly, this 171-nucleotide sequence has GT and AG at its 5' and 3' boundaries, respectively, that are in good agreement with donor and acceptor splice site consensus sequences. Using specific oligonucleotide probes for the mRNAs derived from the cDNA sequences hTOP-1 and hTOP-2, the authors show that both are expressed in all thyroid tissues examined and the relative level of two mRNAs is different in each sample. The results suggest that two thyroid peroxidase proteins might be generated through alternate splicing of the same gene. By using somatic cell hybrid lines, the thyroid peroxidase gene was mapped to the short arm of human chromosome 2

Somatostatin reduces 3H-thymidine incorporation and c-myc, but not thyroglobulin ribonucleic acid levels in human thyroid follicular cells in vitro

International Nuclear Information System (INIS)

degli Uberti, E.C.; Hanau, S.; Rossi, R.; Piva, R.; Margutti, A.; Trasforini, G.; Pansini, G.; del Senno, L.

1991-01-01

The action of somatostatin (SRIH) on 3 H-thymidine (thy) incorporation and on c-myc and thyroglobulin RNA levels in a suspension of follicles from normal and goitrous human thyroid was examined. SRIH, at 10 - 7 M concentration, inhibited basal thy incorporation (maximally by 4 h lasting for up 24 h), which effect was greater in goiter than in normal thyroid and was also detected in growing adherent epithelial cells. Moreover, in a follicle suspension SRIH prevented TSH-stimulated thy incorporation, both in normal and in goitrous thyroid. Basal expression of c-myc RNA was not affected by SRIH in either tissue, whereas the TSH-stimulated c-myc RNA level was significantly reduced in goiter. No effect of SRIH was observed on basal or TSH-stimulated thyroglobulin RNA levels. SRIH did not alter basal cAMP concentrations in normal or goitrous follicles, but it significantly reduced TSH-stimulated cAMP accumulation both in normal thyroid and in goiter. Overall, our data indicate a direct inhibitory action of SRIH on growth, but not on differentiation, of human thyroid, probably by a mechanism not entirely cAMP dependent

Hyperactivity and learning deficits in transgenic mice bearing a human mutant thyroid hormone beta1 receptor gene.

Science.gov (United States)

McDonald, M P; Wong, R; Goldstein, G; Weintraub, B; Cheng, S Y; Crawley, J N

1998-01-01

Resistance to thyroid hormone (RTH) is a human syndrome mapped to the thyroid receptor beta (TRbeta) gene on chromosome 3, representing a mutation of the ligand-binding domain of the TRbeta gene. The syndrome is characterized by reduced tissue responsiveness to thyroid hormone and elevated serum levels of thyroid hormones. A common behavioral phenotype associated with RTH is attention deficit hyperactivity disorder (ADHD). To test the hypothesis that RTH produces attention deficits and/or hyperactivity, transgenic mice expressing a mutant TRbeta gene were generated. The present experiment tested RTH transgenic mice from the PV kindred on behavioral tasks relevant to the primary features of ADHD: hyperactivity, sustained attention (vigilance), learning, and impulsivity. Male transgenic mice showed elevated locomotor activity in an open field compared to male wild-type littermate controls. Both male and female transgenic mice exhibited impaired learning of an autoshaping task, compared to wild-type controls. On a vigilance task in an operant chamber, there were no differences between transgenics and controls on the proportion of hits, response latency, or duration of stimulus tolerated. On an operant go/no-go task measuring sustained attention and impulsivity, there were no differences between controls and transgenics. These results indicate that transgenic mice bearing a mutant human TRbeta gene demonstrate several behavioral characteristics of ADHD and may serve a valuable heuristic role in elucidating possible candidate genes in converging pathways for other causes of ADHD.

Hyperactivity and Learning Deficits in Transgenic Mice Bearing a Human Mutant Thyroid Hormone β1 Receptor Gene

Science.gov (United States)

McDonald, Michael P.; Wong, Rosemary; Goldstein, Gregory; Weintraub, Bruce; Cheng, Sheue-yann; Crawley, Jacqueline N.

1998-01-01

Resistance to thyroid hormone (RTH) is a human syndrome mapped to the thyroid receptor β (TRβ) gene on chromosome 3, representing a mutation of the ligandbinding domain of the TRβ gene. The syndrome is characterized by reduced tissue responsiveness to thyroid hormone and elevated serum levels of thyroid hormones. A common behavioral phenotype associated with RTH is attention deficit hyperactivity disorder (ADHD). To test the hypothesis that RTH produces attention deficits and/or hyperactivity, transgenic mice expressing a mutant TRβ gene were generated. The present experiment tested RTH transgenic mice from the PV kindred on behavioral tasks relevant to the primary features of ADHD: hyperactivity, sustained attention (vigilance), learning, and impulsivity. Male transgenic mice showed elevated locomotor activity in an open field compared to male wild-type littermate controls. Both male and female transgenic mice exhibited impaired learning of an autoshaping task, compared to wild-type controls. On a vigilance task in an operant chamber, there were no differences between transgenics and controls on the proportion of hits, response latency, or duration of stimulus tolerated. On an operant go/no-go task measuring sustained attention and impulsivity, there were no differences between controls and transgenics. These results indicate that transgenic mice bearing a mutant human TRβ gene demonstrate several behavioral characteristics of ADHD and may serve a valuable heuristic role in elucidating possible candidate genes in converging pathways for other causes of ADHD. PMID:10454355

Thyroid dysfunction in human immunodeficiency virus-infected children and its correlation with CD4 + T lymphocyte count

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Satyakumar Thongam

2015-01-01

Full Text Available Context: Thyroid dysfunction has been reported in human immunodeficiency virus (HIV-infected individuals including children. Some studies have reported that thyroid dysfunction may be a marker of severity or progression of HIV. Aims: The aim was to study thyroid function in HIV-infected children with and without highly active anti-retroviral therapy (HAART. Settings and Design: Cross-sectional study carried out at a teaching hospital with Anti-Retroviral Therapy Centre (Centre of Excellence of National AIDS Control Organization. Subjects and Methods: Thyroid stimulating hormone (TSH, total thyroxine (T4, and total tri-iodothyronine (T3 were analyzed in 60 pediatric HIV cases: 30 on HAART and 30 HAART naive. Correlation of T3, T4, and TSH with CD4 count was assessed. Statistical Analysis Used: Data reported as mean ± standard deviation and as the number of cases and percentages. Comparison between groups was done by independent sample t-test and χ2 -test. Spearman′s correlation coefficient is used to assess the association between thyroid dysfunction and CD4 count. Results: Thyroid function abnormality was seen in five out of 30 patients in both patients on HAART or without HAART therapy. Among patients on HAART, three had hypothyroidism, and two had biochemical feature of sick euthyroid syndrome. Among the HAART naive group, sub-clinical hypothyroisim was seen in four, and one had biochemical feature of sick euthyroid syndrome. None of the patients had clinical features of thyroid dysfunction. There is a highly significant correlation (P = 0.01 between TSH and CD4 count. Conclusions: Thyroid dysfunction is quite common among pediatric HIV cases. An inverse correlation is seen between TSH and CD4 count indicating trend for hypothyroidism as HIV disease progress.

Silent somatotroph tumour revisited from a study of 80 patients with and without acromegaly and a review of the literature.

Science.gov (United States)

Chinezu, Laura; Vasiljevic, Alexandre; Trouillas, Jacqueline; Lapoirie, Marion; Jouanneau, Emmanuel; Raverot, Gérald

2017-02-01

Silent somatotroph tumours are growth hormone (GH) immunoreactive (IR) pituitary tumours without clinical and biological signs of acromegaly. Their better characterisation is required to improve the diagnosis. Twenty-one silent somatotroph tumours were compared to 59 somatotroph tumours with acromegaly. Tumours in each group were classified into GH and plurihormonal (GH/prolactin (PRL)/±thyroid-stimulating hormone (TSH)) and into densely granulated (DG) and sparsely granulated (SG) types. The two groups were then compared with regards to proliferation (Ki-67, p53 indexes and mitotic count), differentiation (expression of somatostatin receptors SSTR 2A -SSTR 5 and transcription factor Pit-1) and secretory activity (% of GH- and PRL-IR cells). The silent somatotroph tumours represented 2% of all tested pituitary tumours combined. They were more frequent in women than in men (P = 0.002), more frequently plurihormonal and SG (P acromegaly. They all expressed SSTR 2A , SSTR 5 and Pit-1. The plurihormonal (GH/PRL/±TSH) tumours were mostly observed in women (sex ratio: 3/1) and in patients who were generally younger than those with acromegaly (P acromegaly. A low secretory activity of these tumours might explain the normal plasma values for GH and insulin-like growth factor 1 (IGF1) and the absence of clinical signs of acromegaly. © 2017 European Society of Endocrinology.

Chromosomal Rearrangements in Post-Chernobyl Papillary Thyroid Carcinomas: Evaluation by Spectral Karyotyping and Automated Interphase FISH

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Ludwig Hieber

2011-01-01

Full Text Available Structural genomic rearrangements are frequent findings in human cancers. Therefore, papillary thyroid carcinomas (PTCs were investigated for chromosomal aberrations and rearrangements of the RET proto-oncogene. For this purpose, primary cultures from 23 PTC have been established and metaphase preparations were analysed by spectral karyotyping (SKY. In addition, interphase cell preparations of the same cases were investigated by fluorescence in situ hybridisation (FISH for the presence of RET/PTC rearrangements using RET-specific DNA probes. SKY analysis of PTC revealed structural aberrations of chromosome 11 and several numerical aberrations with frequent loss of chromosomes 20, 21, and 22. FISH analysis for RET/PTC rearrangements showed prevalence of this rearrangement in 72% (16 out of 22 of cases. However, only subpopulations of tumour cells exhibited this rearrangement indicating genetic heterogeneity. The comparison of visual and automated scoring of FISH signals revealed concordant results in 19 out of 22 cases (87% indicating reliable scoring results using the optimised scoring parameter for RET/PTC with the automated Metafer4 system. It can be concluded from this study that genomic rearrangements are frequent in PTC and therefore important events in thyroid carcinogenesis.

Mutual regulation of TGF-β1, TβRII and ErbB receptors expression in human thyroid carcinomas

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Mincione, Gabriella, E-mail: g.mincione@unich.it [Department of Experimental and Clinical Sciences, University ‘G. d' Annunzio of Chieti-Pescara, Chieti (Italy); Center of Excellence on Aging, Ce.S.I., ‘G. d' Annunzio’ University Foundation, Chieti (Italy); Tarantelli, Chiara [Department of Experimental and Clinical Sciences, University ‘G. d' Annunzio of Chieti-Pescara, Chieti (Italy); Vianale, Giovina [Department of Experimental and Clinical Sciences, University ‘G. d' Annunzio of Chieti-Pescara, Chieti (Italy); Center of Excellence on Aging, Ce.S.I., ‘G. d' Annunzio’ University Foundation, Chieti (Italy); Di Marcantonio, Maria Carmela [Department of Experimental and Clinical Sciences, University ‘G. d' Annunzio of Chieti-Pescara, Chieti (Italy); Cotellese, Roberto [Department of Experimental and Clinical Sciences, University ‘G. d' Annunzio of Chieti-Pescara, Chieti (Italy); Unit of General and Laparoscopic Surgery, SS Annunziata Hospital, Chieti (Italy); Francomano, Franco [Unit of General and Laparoscopic Surgery, SS Annunziata Hospital, Chieti (Italy); Di Nicola, Marta; Costantini, Erica [Department of Experimental and Clinical Sciences, University ‘G. d' Annunzio of Chieti-Pescara, Chieti (Italy); Cichella, Annadomenica [Unit of General and Laparoscopic Surgery, SS Annunziata Hospital, Chieti (Italy); Muraro, Raffaella [Department of Experimental and Clinical Sciences, University ‘G. d' Annunzio of Chieti-Pescara, Chieti (Italy); Center of Excellence on Aging, Ce.S.I., ‘G. d' Annunzio’ University Foundation, Chieti (Italy)

2014-09-10

The role of EGF and TGF-β1 in thyroid cancer is still not clearly defined. TGF-β1 inhibited the cellular growth and migration of follicular (FTC-133) and papillary (B-CPAP) thyroid carcinoma cell lines. Co-treatments of TGF-β1 and EGF inhibited proliferation in both cell lines, but displayed opposite effect on their migratory capability, leading to inhibition in B-CPAP and promotion in FTC-133 cells, by a MAPK-dependent mechanism. TGF-β1, TβRII and EGFR expressions were evaluated in benign and malignant thyroid tumors. Both positivity (51.7% and 60.0% and 80.0% in FA and PTC and FTC) and overexpression (60.0%, 77.7% and 75.0% in FA, PTC and FTC) of EGFR mRNA correlates with the aggressive tumor behavior. The moderate overexpression of TGF-β1 and TβRII mRNA in PTC tissues (61.5% and 62.5%, respectively), counteracted their high overexpression in FTC tissues (100% and 100%, respectively), while EGFR overexpression was similar in both carcinomas. Papillary carcinomas were positive to E-cadherin expression, while the follicular carcinomas lose E-cadherin staining. Our findings of TGF-β1/TβRII and EGFR overexpressions together with a loss of E-cadherin observed in human follicular thyroid carcinomas, and of increased migration ability MAPK-dependent after EGF/TGF-β1 treatments in the follicular thyroid carcinoma cell line, reinforced the hypothesis of a cross-talk between EGF and TGF-β1 systems in follicular thyroid carcinomas phenotype. - Highlights: • We reinforce the hypothesis of a cross talk between EGF and TGF-β1 in follicular thyroid carcinoma. • Increased migration MAPK-dependent is observed after EGF+TGF-β1 treatment in follicular thyroid carcinoma cells. • EGF and TGF-β1 caused opposite effect on the migratory ability in B-CPAP and in FTC-133 cells. • TGF-β1, TβRII and EGFR are overexpressed in follicular thyroid carcinoma.

Mutual regulation of TGF-β1, TβRII and ErbB receptors expression in human thyroid carcinomas

International Nuclear Information System (INIS)

Mincione, Gabriella; Tarantelli, Chiara; Vianale, Giovina; Di Marcantonio, Maria Carmela; Cotellese, Roberto; Francomano, Franco; Di Nicola, Marta; Costantini, Erica; Cichella, Annadomenica; Muraro, Raffaella

2014-01-01

The role of EGF and TGF-β1 in thyroid cancer is still not clearly defined. TGF-β1 inhibited the cellular growth and migration of follicular (FTC-133) and papillary (B-CPAP) thyroid carcinoma cell lines. Co-treatments of TGF-β1 and EGF inhibited proliferation in both cell lines, but displayed opposite effect on their migratory capability, leading to inhibition in B-CPAP and promotion in FTC-133 cells, by a MAPK-dependent mechanism. TGF-β1, TβRII and EGFR expressions were evaluated in benign and malignant thyroid tumors. Both positivity (51.7% and 60.0% and 80.0% in FA and PTC and FTC) and overexpression (60.0%, 77.7% and 75.0% in FA, PTC and FTC) of EGFR mRNA correlates with the aggressive tumor behavior. The moderate overexpression of TGF-β1 and TβRII mRNA in PTC tissues (61.5% and 62.5%, respectively), counteracted their high overexpression in FTC tissues (100% and 100%, respectively), while EGFR overexpression was similar in both carcinomas. Papillary carcinomas were positive to E-cadherin expression, while the follicular carcinomas lose E-cadherin staining. Our findings of TGF-β1/TβRII and EGFR overexpressions together with a loss of E-cadherin observed in human follicular thyroid carcinomas, and of increased migration ability MAPK-dependent after EGF/TGF-β1 treatments in the follicular thyroid carcinoma cell line, reinforced the hypothesis of a cross-talk between EGF and TGF-β1 systems in follicular thyroid carcinomas phenotype. - Highlights: • We reinforce the hypothesis of a cross talk between EGF and TGF-β1 in follicular thyroid carcinoma. • Increased migration MAPK-dependent is observed after EGF+TGF-β1 treatment in follicular thyroid carcinoma cells. • EGF and TGF-β1 caused opposite effect on the migratory ability in B-CPAP and in FTC-133 cells. • TGF-β1, TβRII and EGFR are overexpressed in follicular thyroid carcinoma

[Thyroiditis].

Science.gov (United States)

Buffet, Camille; Groussin, Lionel

2013-02-01

The diagnosis of thyroiditis encompasses a broad spectrum of thyroid disorders. Analysis of signs and symptoms, biochemical changes, neck ultrasound characteristics and radioactive iodine uptake values allows an accurate diagnosis. Recent studies of the whole genome have helped to identify many susceptibility genes for autoimmune thyroiditis. However, none of these genes contribute to a significant increase in risk of developing this thyroiditis. Clinical awareness of the characteristic presentations of exceptional thyroiditis (acute suppurative thyroiditis, Riedel's thyroiditis) is an important issue. Selenium administration seems to be beneficial for reducing the incidence of thyroiditis. Finally, certain drug-induced thyroiditis remains a therapeutic challenge for the physician.

Use of 177Lu-dotatate in the treatment of iodine refractory thyroid carcinomas.

Science.gov (United States)

Oliván-Sasot, P; Falgás-Lacueva, M; García-Sánchez, J; Vera-Pinto, V; Olivas-Arroyo, C; Bello-Arques, P

In a patient with a differentiated thyroid cancer the standard treatment protocol to be followed is surgery, ablation of thyroid remnants with 131 Iodine ( 131 I), and TSH suppression. However, the treatment with 131 I is not effective in some cases, and it no longer becomes a therapeutic option due to cell de-differentiation with loss of 131 I uptake. Systemic treatment can be used as other options, although patients are not always responsive; thus, the disease may progress and therapeutic options may run out. Endocrine tumours may express somatostatin receptors,and this characteristic has been used, not only for diagnosis, but also for their treatment through somatostatin analogue labelling with radioactive isotopes. This was the case of a patient suffering from iodine-refractory follicular thyroid carcinoma, with somatostatin receptors expression, treated with 177 Lu-DOTATATE, showing an excellent clinical and analytical response. Copyright © 2016 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

Inhibition of sup 125 I organification and thyroid hormone release by interleukin-1, tumor necrosis factor-alpha, and interferon-gamma in human thyrocytes in suspension culture

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Sato, K.; Satoh, T.; Shizume, K.; Ozawa, M.; Han, D.C.; Imamura, H.; Tsushima, T.; Demura, H.; Kanaji, Y.; Ito, Y. (Institute of Clinical Endocrinology, Tokyo (Japan))

1990-06-01

To elucidate the mechanism of decreased 131I uptake by the thyroid gland in patients with subacute thyroiditis and painless thyroiditis, human thyroid follicles were cultured with interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF alpha), and/or interferon-gamma (IFN gamma), and the effects of these cytokines on thyroid function were studied in vitro. When human thyrocytes were cultured in RPMI-1640 medium containing 0.5% fetal calf serum and TSH for 5-8 days, the cells incorporated 125I, synthesized de novo (125I)iodotyrosines and (125I)iodothyronines, and secreted (125I)T4 and (125I)T3 into the medium. IL-1 alpha and IL-1 beta inhibited 125I incorporation and (125I)iodothyronine release in a concentration-dependent manner. The minimal inhibitory effect was detected at 10 pg/ml. Electron microscopic examination revealed a marked decrease in lysosome formation in IL-1-treated thyrocytes. TNF alpha and IFN gamma also inhibited thyroid function in a concentration-dependent manner. Furthermore, when thyrocytes were cultured with IL-1, TNF alpha and IFN gamma, these cytokines more than additively inhibited thyroid function. Although the main mechanism of 131I uptake suppression in the thyroid gland in subacute thyroiditis is due to cellular damage and suppression of TSH release, our present findings suggest that IL-1, TNF alpha, and IFN gamma produced in the inflammatory process within the thyroid gland further inhibit iodine incorporation and at least partly account for the decreased 131I uptake by the thyroid gland in destruction-induced hyperthyroidism.

The flame retardant DE-71 (a mixture of polybrominated diphenyl ethers inhibits human differentiated thyroid cell function in vitro.

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Thit Mynster Kronborg

Full Text Available Normal thyroid function is essential for general growth and metabolism, but can be affected by endocrine disrupting chemicals (EDCs. Polybrominated diphenyl ethers (PBDEs have been used worldwide to reduce flammability in different materials and are suspected to be EDCs. The production of the commercial Penta- and OctaBDE mixtures is banned, but DecaBDEs and existing products may leak PBDEs into the environment. Our aim was to investigate the effect of the PentaBDE mixture DE-71 on human thyroid cells in vitro.Primary human thyroid cells were obtained as paraadenomatous tissue and cultured in monolayers. The influence of DE-71 on cyclic adenosine monophosphate (cAMP and thyroglobulin (Tg production was examined in the culture medium by competitive radioimmunoassay and enzyme-linked immunosorbent assay, respectively. Real-time quantitative PCR analysis of thyroid-specific genes was performed on the exposed cell cultures. PBDE concentrations were determined in cellular and supernatant fractions of the cultures.DE-71 inhibited Tg-release from TSH-stimulated thyrocytes. At 50 mg/L DE-71, mean Tg production was reduced by 71.9% (range: 8.5-98.7%, and cAMP by 95.1% (range: 91.5-98.8% compared to controls. Expression of mRNA encoding Tg, TPO and TSHr were significantly inhibited (p<0.0001, p = 0.0079, and p = 0.0002, respectively. The majority of DE-71 added was found in the cell fraction. No cytotoxicity was found.DE-71 inhibited differentiated thyroid cell functions in a two phase response manner and a concentration-dependent inhibition of Tg and cAMP production, respectively, as well as expression of mRNA encoding Tg, TPO and TSHr. Our findings suggest an inhibiting effect of PBDEs on thyroid cells.

Thyroiditis

Science.gov (United States)

... Hypothyroidism in Children and Adolescents Pediatric Differentiated Thyroid Cancer Thyroid Nodules in Children and Adolescents Thyroiditis Resources Thyroiditis Brochure PDF Thyroiditis FAQs PDF En Español Tiroiditis El folleto de Tiroiditis Tiroiditis, Preguntas Frecuentes (FAQ) Search ...

Neurohypophysis granular cell tumours. Upon neurohypophysis rare tumours

International Nuclear Information System (INIS)

Barrande, G.; Kujas, M.; Gancel, A.; Turpin, G.; Bruckert, E.; Kuhn, J.M.; Luton, J.P.

1995-01-01

Granular cell tumours of neurohypophysis are rare. These tumours are more often encountered as incidental autopsy findings seen in up to 17 % of unselected adult autopsy cases. There are few reports of para-sellar granular cell tumours large enough to cause symptoms. We present three cases of neurohypophysis granular cell tumour and a review of the literature. In one patient, the asymptomatic granular cell tumour was incidentally discovered at surgical removal of a corticotrophic micro-adenoma. The remaining 2 patients had a symptomatic tumour which caused neurological symptoms such as visual disturbance and headaches and endocrine disorders such as hypopituitarism or hyper-prolactinaemia. In these 2 cases, computerized tomography showed a well-circumscribed, contrast-enhanced, intra-sellar and supra-sellar mass. Magnetic resonance imaging demonstrated an isointense gadolinium-enhanced mass in T1-weighted-images. Trans-sphenoidal partial resection was performed and histology was interpreted as a granular cell tumour. The immunohistochemical study was positive for glial fibrillary acidic protein (GEAP) and neuron specific enolase (NSE) in 1 of the 2 tumours and positive for S100 protein and vimentin in both tumours but negative for CD68. The histogenesis of neurohypophysis granular cell tumours is still controversial but ultrastructural and immunohistochemical studies support the theory that may arise from pituicytes, the glial cells of neurohypophysis. Management of these benign, slow growing, tumours is based mainly on neurosurgical resection. Data from the literature do not support a beneficial effect of post operative radiation therapy on postoperative recurrences. (authors). 23 refs., 4 figs., 1 tab

Unravelling the biology of human papillomavirus (HPV) related tumours to enhance their radiosensitivity

International Nuclear Information System (INIS)

Vozenin, M.C.; Lord, H.K.; Deutsch, E.; Vozenin, M.C.; Hartl, D.

2010-01-01

HPV infection is associated with most squamous cell carcinomas (SCC) of the uterine cervix and many head and neck SCC. While recent understanding of the mechanisms of HPV-induced carcinogenesis has lead to the development of prophylactic vaccines, the principal modality of treatment is radiotherapy and despite concurrent chemotherapy, outcomes remain suboptimal. Improving the radiotherapeutic index thus remains an important challenge as well as defining predictive assays for treatment outcome of HPV-related tumours. Therefore elucidating the influence of the HPV virus on tumour radiosensitivity is of major interest due to the prevalence of HPV-related tumours worldwide and due to evidence that head and neck HPV-tumours have markedly different clinical outcomes compared to non-HPV-related tumours. This difference may allow for different treatment strategies to be developed. The present review aims to summarize the current understanding of radiosensitivity and HPV-related tumour biology in order to subsequently develop new approaches to enhance the therapeutic index. This review also emphasizes the relevance of E6 and E7 onco-proteins to tumour cell response to radiotherapy suggesting that specific targeted approaches such as concomitant modulation of additional pathways using targeted therapies should offer new therapeutic avenues. (authors)

SELENIUM SUBSTITUTION – EFFECT ON THYROID FUNCTION

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Milica Pešić

2015-03-01

Full Text Available The understanding of the essential role of selenium (Se in thyroid hormone synthesis, metabolism and action, as well as normal thyroid function, increased during the past decades. The thyroid gland is among the human tissues with the highest Se content per mas unit, similar to other endocrine organs and brain. Biological actions of Se are mediated, in most cases, through the expression of at least 30 selenoproteins coded by 25 selenoprotein genes in the human. Via the selenoproteins, selenium can influence the cell function through antioxidant activites, modifying redox status and thyroid hormone synthesis and metabolism. Selenoproteins iodothyronine deiodinases are present in most tissues and have a role to increase the production of bioactive tri-iodothyronine. Futhermore, Se has been shown to be important in the regulation of immune function. Se deficiency is accompained by the loss of immune competence. The links between Se deficiency, altered immune function and inflamation have prompted studies in humans to examine if Se suplementation can modify auto-antibodies production in patients with chronic autoimmune thyroiditis. Until now, several randomised prospective clinical trials have been performed in patients with established chronic autoimmune thyrioditis. The clinical endpoint of each study was the decrease in TPO antibodies concentration after 3-12 months of treatment. Ussualy, the dosage of daily Se supplementation was 200µg. Selenium suplemetation had no significant effect on the concentration of TSH or thyroid hormone concentrations. These studies indicate that Se treatment result in reduced inflammatory activity, but it does not cure chronc autoimmune process.

Fluorine-18 fluorodeoxyglucose positron emission tomography in the follow-up of differentiated thyroid cancer

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Gruenwald, F [Department of Nuclear Medicine, University of Bonn, Sigmund-Freud-Strasse 25, D-53127 Bonn (Germany); Schomburg, A [Department of Nuclear Medicine, University of Bonn, Sigmund-Freud-Strasse 25, D-53127 Bonn (Germany); Bender, H [Department of Nuclear Medicine, University of Bonn, Sigmund-Freud-Strasse 25, D-53127 Bonn (Germany); Klemm, E [Department of Nuclear Medicine, University of Bonn, Sigmund-Freud-Strasse 25, D-53127 Bonn (Germany); Menzel, C [Department of Nuclear Medicine, University of Bonn, Sigmund-Freud-Strasse 25, D-53127 Bonn (Germany); Bultmann, T [Department of Nuclear Medicine, University of Bonn, Sigmund-Freud-Strasse 25, D-53127 Bonn (Germany); Palmedo, H [Department of Nuclear Medicine, University of Bonn, Sigmund-Freud-Strasse 25, D-53127 Bonn (Germany); Ruhlmann, J [Department of Nuclear Medicine, University of Bonn, Sigmund-Freud-Strasse 25, D-53127 Bonn (Germany); Kozak, B [Department of Nuclear Medicine, University of Bonn, Sigmund-Freud-Strasse 25, D-53127 Bonn (Germany); Biersack, H J [Department of Nuclear Medicine, University of Bonn, Sigmund-Freud-Strasse 25, D-53127 Bonn (Germany)

1996-03-01

Whole-body fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging was performed during the follow-up of 33 patients suffering from differentiated thyroid cancer. Among them there were 26 patients with papillary and seven with follicular tumours. Primary tumour stage (pT) was pT1 in six cases, pT2 in eight cases, pT3 in three cases and pT4 in 14 cases. FDG PET was normal in 18 patients. In three patients a slightly increased metabolism was observed in the thyroid bed, assumed to be related to remnant tissue. In one case local recurrence, in ten cases lymph node metastases (one false-positive, caused by sarcoidosis) and in three cases distant metastases were found with FDG PET. In comparison with whole-body scintigraphy using iodine-131 (WBS) there were a lot of discrepancies in imaging results. Whereas three patients had distant metastases (proven with {sup 131}I) and a negative FDG PET, in four cases {sup 131}I-negative lymph node metastases were detectable with PET. Even in the patients with concordant ``staging``, differences between {sup 131}I and FDG were observed as to the exact lesion localization. Therefore, a coexistence of {sup 131}I-positive/FDG-negative, {sup 131}I-negative/FDG-positive and {sup 131}I-positive/FDG-positive malignant tissue can be assumed in these patients. A higher correlation of FDG PET was observed with hexakis (2-methoxyisobutylisonitrile) technetium-99m (I) (MIBI) scintigraphy (performed in 20 cases) than with WBS. In highly differentiated tumours {sup 131}I scintigraphy had a high sensitivity, whereas in poorly differentiated carcinomas FDG PET was superior. The clinical use of FDG PET can be recommended in all cases of suspected or proven recurrence and/or metastases of differentiated thyroid cancer and is particularly useful in cases with elevated serum thyroglobulin levels and negative WBS. (orig.). With 3 figs., 2 tabs.

Dental x-rays and the risk of thyroid cancer: A case-control study

International Nuclear Information System (INIS)

Memon, Anjum; Godward, Sara; Williams, Dillwyn; Siddique, Iqbal; Al-Saleh, Khalid

2010-01-01

The thyroid gland is highly susceptible to radiation carcinogenesis and exposure to high-dose ionising radiation is the only established cause of thyroid cancer. Dental radiography, a common source of low-dose diagnostic radiation exposure in the general population, is often overlooked as a radiation hazard to the gland and may be associated with the risk of thyroid cancer. An increased risk of thyroid cancer has been reported in dentists, dental assistants, and x-ray workers; and exposure to dental x-rays has been associated with an increased risk of meningiomas and salivary tumours. Methods. To examine whether exposure to dental x-rays was associated with the risk of thyroid cancer, we conducted a population-based case-control interview study among 313 patients with thyroid cancer and a similar number of individually matched (year of birth ± three years, gender, nationality, district of residence) control subjects in Kuwait. Results. Conditional logistic regression analysis, adjusted for other upper-body x-rays, showed that exposure to dental x-rays was significantly associated with an increased risk of thyroid cancer (odds ratio = 2.1, 95% confidence interval: 1.4, 3.1) (p=0.001) with a dose-response pattern (p for trend <0.0001). The association did not vary appreciably by age, gender, nationality, level of education, or parity. Discussion. These findings, based on self-report by cases/controls, provide some support to the hypothesis that exposure to dental x-rays, particularly multiple exposures, may be associated with an increased risk of thyroid cancer; and warrant further study in settings where historical dental x-ray records may be available.

Dental x-rays and the risk of thyroid cancer: A case-control study

Energy Technology Data Exchange (ETDEWEB)

Memon, Anjum (Div. of Primary Care and Public Health, Brighton and Sussex Medical School (United Kingdom)), E-mail: a.memon@bsms.ac.uk; Godward, Sara (Dept. of Public Health and Primary Care, Univ. of Cambridge (United Kingdom)); Williams, Dillwyn (Thyroid Carcinogenesis Research Group, Strangeways Research Laboratories, Univ. of Cambridge (United Kingdom)); Siddique, Iqbal (Dept. of Medicine, Faculty of Medicine, Kuwait Univ. (Kuwait)); Al-Saleh, Khalid (Kuwait Cancer Control Centre, Ministry of Health (Kuwait))

2010-05-15

The thyroid gland is highly susceptible to radiation carcinogenesis and exposure to high-dose ionising radiation is the only established cause of thyroid cancer. Dental radiography, a common source of low-dose diagnostic radiation exposure in the general population, is often overlooked as a radiation hazard to the gland and may be associated with the risk of thyroid cancer. An increased risk of thyroid cancer has been reported in dentists, dental assistants, and x-ray workers; and exposure to dental x-rays has been associated with an increased risk of meningiomas and salivary tumours. Methods. To examine whether exposure to dental x-rays was associated with the risk of thyroid cancer, we conducted a population-based case-control interview study among 313 patients with thyroid cancer and a similar number of individually matched (year of birth +- three years, gender, nationality, district of residence) control subjects in Kuwait. Results. Conditional logistic regression analysis, adjusted for other upper-body x-rays, showed that exposure to dental x-rays was significantly associated with an increased risk of thyroid cancer (odds ratio = 2.1, 95% confidence interval: 1.4, 3.1) (p=0.001) with a dose-response pattern (p for trend <0.0001). The association did not vary appreciably by age, gender, nationality, level of education, or parity. Discussion. These findings, based on self-report by cases/controls, provide some support to the hypothesis that exposure to dental x-rays, particularly multiple exposures, may be associated with an increased risk of thyroid cancer; and warrant further study in settings where historical dental x-ray records may be available.

Molecular pathobiology of thyroid neoplasms.

Science.gov (United States)

Tallini, Giovanni

2002-01-01

Tumors of thyroid follicular cells provide a very interesting model to understand the development of human cancer. It is becoming apparent that distinct molecular events are associated with specific stages in a multistep tumorigenic process with good genotype/ phenotype correlation. For instance, mutations of the gsp and thyroid-stimulating hormone receptor genes are associated with benign hyperfunctioning thyroid nodules and adenomas while alterations of other specific genes, such as oncogenic tyrosine kinase alterations (RET/PTC, TRK) in papillary carcinoma and the newly discovered PAX8/peroxisome proliferator-activated receptor gamma rearrangement, are distinctive features of cancer. Although activating RAS mutations occur at all stages of thyroid tumorigenesis, evidence is accumulating that they may also play an important role in tumor progression, a role that is well documented for p53. Environmental factors (iodine deficiency, ionizing radiations) have been shown to play a crucial role in promoting the development of thyroid cancer, influencing both its genotypic and phenotypic features. It is possible that the follicular thyroid cell has unique ways to respond to DNA damage. Similarly to leukemia or sarcomas (and unlike most epithelial cancers), numerous specific rearrangements are being discovered in thyroid cancer suggesting preferential activation of DNA repair instead of cell death programs after environmentally induced genetic alterations.

Effect of tumour promoter iodoacetate on γ-radiation induced chromosomal aberrations in human lymphocytes

International Nuclear Information System (INIS)

Anjaria, K.B.; Shirsath, K.B.; Bhat, N.N.; Sreedevi, B.

2010-01-01

It has been reported that tumour-promoting agents potentiate a number of genetic events induced by initiating agents in vitro Iodoacetate (IA) is reported to be a tumour promoter of moderate potency and although to the best of our knowledge, tumour promoting ability of IA in animals has not been reported, a large number of studies have reported various types of effects of IA, which may result in tumour promotion. In this paper, the modifying effects of tumour promoter IA on radiation induced dicentrics in peripheral blood lymphocytes have been reported

Scintigraphic diagnosis of suprarenal tumours. Comparative advantages of 131I-19-iodocholesterol and 6-methyl-75Se-selenocholesterol

International Nuclear Information System (INIS)

Chatal, J.F.; Charbonnel, B.; Guihard, D.

The value of scintigraphy for the diagnosis of supranenal tumours is demonstrated on 11 cases covering all tumoral diseases of the adrenal glands (Cushing's tumour, Conn's adenoma, masculinizing suprarenal tumour, pheochromocytomas). In 10 of these cases a positive and topographic suprarenal tumour diagnosis was obtained correctly by scintigraphy, the only error being the poor location of a pheochromocytoma. The data contained in the images are on the whole no different according to whether 131 I-19-iodocholesterol or 6-methyl- 75 Se-selenocholesterol is used, but practical considerations tend to give preference to the latter. The tagging is stable in vitro and at room temperature for several weeks, which in view of the half-life of selenium 75 implies permanent availability in the hospital service. Irradiation of the thyroid is no longer a danger. The count yield of 75 Se is higher than that of 131 I for the same activity and the injected dose may therefore be reduced. Where dosimetric problems are concerned the gonad irradiation from the two products is the same [fr

Clinical Significance of Cannabinoid Receptors CB1 and CB2 Expression in Human Malignant and Benign Thyroid Lesions

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Eleftheria Lakiotaki

2015-01-01

Full Text Available The endocannabinoid system is comprised of cannabinoid receptors (CB1 and CB2, their endogenous ligands (endocannabinoids, and proteins responsible for their metabolism participate in many different functions indispensable to homeostatic regulation in several tissues, exerting also antitumorigenic effects. The present study aimed to evaluate the clinical significance of CB1 and CB2 expression in human benign and malignant thyroid lesions. CB1 and CB2 proteins’ expression was assessed immunohistochemically on paraffin-embedded thyroid tissues obtained from 87 patients with benign (n=43 and malignant (n=44 lesions and was statistically analyzed with clinicopathological parameters, follicular cells’ proliferative capacity, and risk of recurrence rate estimated according to the American Thyroid Association (ATA staging system. Enhanced CB1 and CB2 expression was significantly more frequently observed in malignant compared to benign thyroid lesions (p=0.0010 and p=0.0005, resp.. Enhanced CB1 and CB2 expression was also significantly more frequently observed in papillary carcinomas compared to hyperplastic nodules (p=0.0097 and p=0.0110, resp.. In malignant thyroid lesions, elevated CB2 expression was significantly associated with the presence of lymph node metastases (p=0.0301. Enhanced CB2 expression was also more frequently observed in malignant thyroid cases with presence of capsular (p=0.1165, lymphatic (p=0.1989, and vascular invasion (p=0.0555, as well as in those with increased risk of recurrence rate (p=0.1165, at a nonsignificant level though, whereas CB1 expression was not associated with any of the clinicopathological parameters examined. Our data suggest that CB receptors may be involved in malignant thyroid transformation and especially CB2 receptor could serve as useful biomarker and potential therapeutic target in thyroid neoplasia.

FA1 immunoreactivity in endocrine tumours and during development of the human fetal pancreas; negative correlation with glucagon expression

DEFF Research Database (Denmark)

Tornehave, D; Jensen, Charlotte Harken; Teisner, B

1996-01-01

Fetal antigen 1 (FA1) is a glycoprotein containing six epidermal growth factor (EGF)-like repeats. It is closely similar to the protein translated from the human delta-like (dlk) cDNA and probably constitutes a proteolytically processed form of dlk. dlk is homologous to the Drosophila homeotic...... proteins delta and notch and to the murine preadipocyte differentiation factor Pref-1. These proteins participate in determining cell fate choices during differentiation. We now report that FA1 immunoreactivity is present in a number of neuroectodermally derived tumours as well as in pancreatic endocrine...... tumours. A negative correlation between FA1 and glucagon immunoreactants in these tumours prompted a reexamination of FA1 immunoreactants during fetal pancreatic development. At the earliest stages of development, FA1 was expressed by most of the non-endocrine parenchymal cells and, with ensuing...

Multimodal imaging utilising integrated MR-PET for human brain tumour assessment

International Nuclear Information System (INIS)

Neuner, Irene; Kaffanke, Joachim B.; Langen, Karl-Josef; Kops, Elena Rota; Tellmann, Lutz; Stoffels, Gabriele; Weirich, Christoph; Filss, Christian; Scheins, Juergen; Herzog, Hans; Shah, N. Jon

2012-01-01

The development of integrated magnetic resonance (MR)-positron emission tomography (PET) hybrid imaging opens up new horizons for imaging in neuro-oncology. In cerebral gliomas the definition of tumour extent may be difficult to ascertain using standard MR imaging (MRI) only. The differentiation of post-therapeutic scar tissue, tumour rests and tumour recurrence is challenging. The relationship to structures such as the pyramidal tract to the tumour mass influences the therapeutic neurosurgical approach. The diagnostic information may be enriched by sophisticated MR techniques such as diffusion tensor imaging (DTI), multiple-volume proton MR spectroscopic imaging (MRSI) and functional MRI (fMRI). Metabolic imaging with PET, especially using amino acid tracers such as 18 F-fluoroethyl-l-tyrosine (FET) or 11 C-l-methionine (MET) will indicate tumour extent and response to treatment. The new technologies comprising MR-PET hybrid systems have the advantage of providing comprehensive answers by a one-stop-job of 40-50 min. The combined approach provides data of different modalities using the same iso-centre, resulting in optimal spatial and temporal realignment. All images are acquired exactly under the same physiological conditions. We describe the imaging protocol in detail and provide patient examples for the different imaging modalities such as FET-PET, standard structural imaging (T1-weighted, T2-weighted, T1-weighted contrast agent enhanced), DTI, MRSI and fMRI. (orig.)

Multimodal imaging utilising integrated MR-PET for human brain tumour assessment

Energy Technology Data Exchange (ETDEWEB)

Neuner, Irene [Institute of Neuroscience and Medicine 4, INM 4, Juelich (Germany); RWTH Aachen University, Department of Psychiatry, Psychotherapy and Psychosomatics, Aachen (Germany); JARA-BRAIN-Translational Medicine, Aachen (Germany); Kaffanke, Joachim B. [Institute of Neuroscience and Medicine 4, INM 4, Juelich (Germany); MR-Transfer e.K., Wuppertal (Germany); Langen, Karl-Josef; Kops, Elena Rota; Tellmann, Lutz; Stoffels, Gabriele; Weirich, Christoph; Filss, Christian; Scheins, Juergen; Herzog, Hans [Institute of Neuroscience and Medicine 4, INM 4, Juelich (Germany); Shah, N. Jon [Institute of Neuroscience and Medicine 4, INM 4, Juelich (Germany); RWTH Aachen University, Department of Neurology, Aachen (Germany); JARA-BRAIN-Translational Medicine, Aachen (Germany)

2012-12-15

The development of integrated magnetic resonance (MR)-positron emission tomography (PET) hybrid imaging opens up new horizons for imaging in neuro-oncology. In cerebral gliomas the definition of tumour extent may be difficult to ascertain using standard MR imaging (MRI) only. The differentiation of post-therapeutic scar tissue, tumour rests and tumour recurrence is challenging. The relationship to structures such as the pyramidal tract to the tumour mass influences the therapeutic neurosurgical approach. The diagnostic information may be enriched by sophisticated MR techniques such as diffusion tensor imaging (DTI), multiple-volume proton MR spectroscopic imaging (MRSI) and functional MRI (fMRI). Metabolic imaging with PET, especially using amino acid tracers such as {sup 18}F-fluoroethyl-l-tyrosine (FET) or {sup 11}C-l-methionine (MET) will indicate tumour extent and response to treatment. The new technologies comprising MR-PET hybrid systems have the advantage of providing comprehensive answers by a one-stop-job of 40-50 min. The combined approach provides data of different modalities using the same iso-centre, resulting in optimal spatial and temporal realignment. All images are acquired exactly under the same physiological conditions. We describe the imaging protocol in detail and provide patient examples for the different imaging modalities such as FET-PET, standard structural imaging (T1-weighted, T2-weighted, T1-weighted contrast agent enhanced), DTI, MRSI and fMRI. (orig.)

Functional insulin receptors are overexpressed in thyroid tumors: is this an early event in thyroid tumorigenesis?

Science.gov (United States)

Frittitta, L; Sciacca, L; Catalfamo, R; Ippolito, A; Gangemi, P; Pezzino, V; Filetti, S; Vigneri, R

1999-01-15

Insulin receptor (IR), a member of the receptor tyrosine kinase family, is expressed in normal thyroid cells and affects thyroid cell proliferation and differentiation. The authors measured IR content in benign and malignant thyroid tumors by three independent methods: a specific radioimmunoassay, 125I-insulin binding studies, and immunohistochemistry. The results obtained were compared with the IR content in paired, adjacent, normal thyroid tissue. To assess IR function in thyroid carcinoma cells, glucose uptake responsiveness to insulin was also studied in a human transformed thyroid cell line (B-CPAP) and in follicular carcinoma cells in primary culture. In 9 toxic adenomas, the average IR content was similar to that observed in the 9 paired normal thyroid tissue specimens from the same patients (2.2+/-0.3 vs. 2.1+/-0.3). In 13 benign nonfunctioning, or "cold," adenomas, the average IR content was significantly higher (P thyroid tissue (4.0+/-0.4 vs. 1.6+/-0.2 and 5.6+/-1.0 vs. 1.8+/-0.2, respectively). The finding of a higher IR content in benign "cold" adenomas and in thyroid carcinomas was confirmed by both binding and immunostaining studies. The current studies indicate that 1) IR content is elevated in most follicular and papillary differentiated thyroid carcinomas, and 2) IR content is also elevated in most benign follicular adenomas ("cold" nodules) but not in highly differentiated, hyperfunctioning follicular adenomas ("hot" nodules), which very rarely become malignant. This observation suggests that increased IR expression is not restricted to the thyroid malignant phenotype but is already present in the premalignant "cold" adenomas. It may contribute, therefore, to thyroid tumorigenesis and/or represent an early event that gives a selective growth advantage to transformed thyroid cells.

Radiation absorbed dose to the human fetal thyroid

International Nuclear Information System (INIS)

Watson, E.E.

1992-01-01

The embryo/fetus is recognized to be particularly susceptible to damage from exposure to radiation. Many advisory groups have studied available information concerning radiation doses and radiation effects with the goal of reducing the risk to the embryo/fetus. Of particular interest are radioactive isotopes of iodine. Radioiodine taken into the body of a pregnant woman presents a possible hazard for the embryo/fetus. The fetal thyroid begins to concentrate iodine at about 13 weeks after conception and continues to do so throughout gestation. At term, the organic iodine concentration in the fetal blood is about 75% of that in the mother's blood. This paper presents a review the models that have been proposed for the calculation of the dose to the fetal thyroid from radioisotopes of iodine taken into the body of the pregnant woman as sodium iodide. A somewhat different model has been proposed, and estimates of the radiation dose to the fetal thyroid calculated from this model are given for each month of pregnancy from 123 I , 124 I , 125 I , and 131 I

Dual ectopic thyroid associated with thyroid hemiagenesis.

Science.gov (United States)

Nakamura, Shigenori; Masuda, Teruyuki; Ishimori, Masatoshi

2018-01-01

We report a case of a 15-year-old girl with a midline neck mass that was first noted 2 or 3 years previously. She had been treated with levothyroxine (L-T4) for congenital hypothyroidism until 11 years of age. Ultrasonography revealed an atrophic right thyroid (1.0 × 1.6 × 2.6 cm in size) and a mass (2.3 × 1.0 × 3.5 cm in size) in the upper part of the neck. No left lobe of the thyroid was detected. On further evaluation, Tc-99m pertechnetate thyroid scintigraphy and CT showed ectopic thyroid tissue in the lingual region and infrahyoid region. Thus, she was diagnosed as having dual ectopic thyroid and thyroid hemiagenesis. The atrophic right thyroid was thought be non-functional. Treatment with L-T4 was started to reduce the size of the dual ectopic thyroid tissue. This may be the first reported case of dual ectopic thyroid associated with hemiagenesis detected only by ultrasonography. Ultrasonography can confirm the presence or absence of orthotopic thyroid tissue in patients with ectopic thyroid.The cause of congenital hypothyroidism should be examined.Clinical manifestation of ectopic thyroid may appear when the treatment with L-T4 is discontinued.Annual follow-up is needed in all children when their thyroid hormone replacement is stopped.

Human-centered design of the human-system interfaces of medical equipment: thyroid uptake system

International Nuclear Information System (INIS)

Monteiro, Jonathan K.R.; Farias, Marcos S.; Santos, Isaac J.A. Luquetti; Monteiro, Beany G.

2013-01-01

Technology plays an important role in modern medical centers, making healthcare increasingly complex, relying on complex technical equipment. This technical complexity is particularly noticeable in the nuclear medicine. Poorly design human-system interfaces can increase the risks for human error. The human-centered approach emphasizes the development of the equipment with a deep understanding of the users activities, current work practices, needs and abilities of the users. An important concept of human-centered design is that the ease-of-use of the equipment can be ensured only if users are actively incorporated in all phases of the life cycle of design process. Representative groups of users are exposed to the equipment at various stages in development, in a variety of testing, evaluation and interviewing situations. The users feedback obtained is then used to refine the design, with the result serving as input to the next interaction of design process. The limits of the approach are that the users cannot address any particular future needs without prior experience or knowledge about the equipment operation. The aim of this paper is to present a methodological framework that contributes to the design of the human-system interfaces, through an approach related to the users and their activities. A case study is described in which the methodological framework is being applied in development of new human-system interfaces of the thyroid uptake system. (author)

PRDM1 expression via human parvovirus B19 infection plays a role in the pathogenesis of Hashimoto thyroiditis.

Science.gov (United States)

Wang, Lu; Zhang, Wei-Ping; Yao, Li; Zhang, Wei; Zhu, Jin; Zhang, Wei-Chen; Zhang, Yue-Hua; Wang, Zhe; Yan, Qing-Guo; Guo, Ying; Fan, Lin-Ni; Liu, Yi-Xiong; Huang, Gao-Sheng

2015-12-01

Ectopic lymphoid follicle infiltration is a key event in Hashimoto thyroiditis (HT). Positive regulatory domain zinc finger protein 1 (PRDM1), which is induced by antigen stimulation, can regulate all lymphocyte lineages. Several groups independently demonstrated that human parvovirus B19 (PVB19) is closely associated with HT. Hence, we determined whether PRDM1 is expressed in HT thyroid tissue and whether there is any correlation between PRDM1 expression and PVB19 in the pathogenesis of HT. We detected PRDM1 expression in HT (n = 86), normal thyroid tissue (n = 30), and nontoxic nodular goiter (n = 20) samples using immunohistochemistry. We also detected PVB19 protein in HT samples in a double-blind manner and analyzed the correlation between the 2 proteins using immunofluorescence confocal detection and coimmunoprecipitation. Furthermore, we detected changes of the expression levels of PRDM1 and PVB19 in transfected primary thyroid follicular epithelial cells using real-time quantitative polymerase chain reaction. We found that PRDM1 protein is significantly highly expressed in the injured follicular epithelial cells in HT (83/86 cases) than in normal thyroid cells (0/30 cases) or in nontoxic nodular goiter cells (0/20 cases) (P thyroid epithelial cells also showed PRDM1 up-regulation after PVB19 NS1 transfection. Our findings suggest a previously unrecognized role of PRDM1 and PVB19 in the pathogenesis of HT. Copyright © 2015 Elsevier Inc. All rights reserved.

Calcitonin-negative primary neuroendocrine tumor of the thyroid ...

African Journals Online (AJOL)

nonmedullary" in humans is a rare tumor that arises primarily in the thyroid gland and may be mistaken for medullary thyroid carcinoma; it is characterized by the immunohistochemical (IHC) expression of neuroendocrine markers and the absence of ...

Postpartum Thyroiditis

Science.gov (United States)

American Thyroid Association ® Postpartum Thyroiditis www.thyroid.org What is the thyroid gland? The thyroid gland is a butterfly-shaped endocrine gland that ... as they should. What are the symptoms of postpartum thyroiditis? Thyroiditis is a general term that refers ...

Radiolabelled peptides for tumour therapy: current status and future directions. Plenary lecture at the EANM 2002

International Nuclear Information System (INIS)

Jong, Marion de; Kwekkeboom, Dik; Valkema, Roelf; Krenning, Eric P.

2003-01-01

On their plasma membranes, cells express receptor proteins with high affinity for regulatory peptides, such as somatostatin. Changes in the density of these receptors during disease, e.g. overexpression in many tumours, provide the basis for new imaging methods. The first peptide analogues successfully applied for visualisation of receptor-positive tumours were radiolabelled somatostatin analogues. The next step was to label these analogues with therapeutic radionuclides for peptide receptor radionuclide therapy (PRRT). Results from preclinical and clinical multicentre studies have already shown an effective therapeutic response when using radiolabelled somatostatin analogues to treat receptor-positive tumours. Infusion of positively charged amino acids reduces kidney uptake, enlarging the therapeutic window. For PRRT of CCK-B receptor-positive tumours, such as medullary thyroid carcinoma, radiolabelled minigastrin analogues are currently being successfully applied. The combination of different therapy modalities holds interest as a means of improving the clinical therapeutic effects of radiolabelled peptides. The combination of different radionuclides, such as 177 Lu- and 90 Y-labelled somatostatin analogues, to reach a wider tumour region of high curability, has been described. A variety of other peptide-based radioligands, such as bombesin and NPY(Y 1 ) analogues, receptors for which are expressed on common cancers such as prostate and breast cancer, are currently under development and in different phases of (pre)clinical investigation. Multi-receptor tumour targeting using the combination of bombesin and NPY(Y 1 ) analogues is promising for scintigraphy and PRRT of breast carcinomas and their lymph node metastases. (orig.)

Association of RET Genetic Polymorphisms and Haplotypes with Papillary Thyroid Carcinoma in the Portuguese Population: A Case-Control Study

Science.gov (United States)

Santos, Marina; Azevedo, Teresa; Martins, Teresa; Rodrigues, Fernando J.; Lemos, Manuel C.

2014-01-01

Thyroid cancer has a multifactorial aetiology resulting from the interaction of genetic and environmental factors. Several low penetrance susceptibility genes have been identified but their effects often vary between different populations. Somatic point mutations and translocations of the REarranged during Transfection (RET) proto-oncogene are frequently found in thyroid cancer. The aim of this case-control study was to determine the effect of four well known RET single nucleotide polymorphisms (SNPs) on the risk for differentiated thyroid carcinoma. A total of 545 Portuguese patients and 543 controls were genotyped by PCR and restriction enzyme analysis, for the following SNPs: G691S (exon 11, rs1799939 G/A), L769L (exon 13, rs1800861 T/G), S836S (exon 14, rs1800862 C/T), and S904S (exon 15, rs1800863 C/G). The minor allele of S836S was overrepresented in patients with papillary thyroid carcinoma (PTC) when compared to controls (OR 1.57; 95% CI 1.05–2.35; p = 0.026). The GGTC haplotype was also overrepresented in PTC (OR 2.51; 95% CI 1.07–5.91; p = 0.029). No associations were found in follicular thyroid carcinoma (FTC). Multivariate logistic regression analysis showed no differences regarding gender, age at diagnosis, lymph node or distant metastasis. However, a near significant overrepresentation of the minor alleles of G691S and S904S was found in patients with tumours greater than 10 mm of diameter at diagnosis. These data suggest that the RET S836S polymorphism in exon 14 and the GGTC haplotype are risk factors for PTC, but not FTC, and that the G691S/S904S polymorphisms might be associated with tumour behaviour. PMID:25330015

Recurrent Silent Thyroiditis as a Sequela of Postpartum Thyroiditis

Science.gov (United States)

Kim, Paul

2014-01-01

Thyroiditis encompasses a group of disorders characterized by thyroid inflammation. Though clinically indistinguishable from silent thyroiditis, postpartum thyroiditis occurs in women within 12 months after delivery. Recurrent postpartum thyroiditis in subsequent pregnancies is common, but recurrent silent thyroiditis is rare. We reported a case of patient with recurrent episodes of thyroiditis, unrelated to pregnancy, after an episode of postpartum thyroiditis. It is of interest that postpartum thyroiditis and silent thyroiditis could occur closely to each other; however, the link between these disorders is not well established. This report is to remind physicians of the possibility of recurrent silent thyroiditis in women with a history of postpartum thyroiditis. PMID:24987536

The management of differentiated thyroid cancer in Europe in 1988

International Nuclear Information System (INIS)

Baldet, L.; Jaffiol, C.; Percheron, C.; Manderscheid, J.-C.; Coste-Seignovert, B.; Glinoer, D.

1989-01-01

In order to know how thyroid nodules and differentiated thyroid cancers are investigated and treated in 1988, an international inquiry was performed by mean of a questionnaire based on a well-defined case report of a 35-year-old female with a solitary small thyroid nodule. Clinicians were asked to indicate their diagnostic and therapeutic approaches to the reported case and to some variations. Analysis of the 157 responses from thyroid experts showed that three in vitro tests (sensitive-TSH, free T 4 and total T 4 ) and three in vivo tests ( 99m Tc or radioiodide scintiscan, fine needle aspiration and ultrasonography) were performed most frequently. In the case of a solid and cold nodule and in the absence of fine needle aspiration results, 19% of respondents advocated suppressive therapy and 81% surgery. In the same clinical case, but whom fine needle aspiration had been performed and cytology was benign, surgery was advocated by 24%, suppressive therapy by 48% and a regular follow-up without treatment by 28% of respondents. When surgery was performed and the diagnosis was a differentiated thyroid cancer, (near) total thyroidectomy was more frequently chosen than partial thyroidectomy in both papillary (60 and 40%, respectively, of respondents) and follicular (74 and 26%, respectively, of respondents) cancers; 80% of clinicians did not change their surgical technique in relation to histological type of the tumour. Total thyroidectomy was more often recommended in most of the clinical or anatomical variations compared with the basic case repot. Pre- og postoperative hormonal therapy was initiated with L-T 4 and TSH suppression was controlled by sensitive-TSH and thyroblobulin determinations. After total thyroidectomy, 131 I was used with similar modalities for papillary and follicular cancers to ablate a thyroid remnant. (author)

Effects of thyroid hormone status on metabolic pathways of arachidonic acid in mice and humans: A targeted metabolomic approach.

Science.gov (United States)

Yao, Xuan; Sa, Rina; Ye, Cheng; Zhang, Duo; Zhang, Shengjie; Xia, Hongfeng; Wang, Yu-cheng; Jiang, Jingjing; Yin, Huiyong; Ying, Hao

2015-01-01

Symptoms of cardiovascular diseases are frequently found in patients with hypothyroidism and hyperthyroidism. However, it is unknown whether arachidonic acid metabolites, the potent mediators in cardiovascular system, are involved in cardiovascular disorders caused by hyperthyroidism and hypothyroidism. To answer this question, serum levels of arachidonic acid metabolites in human subjects with hypothyroidism, hyperthyroidism and mice with hypothyroidism or thyroid hormone treatment were determined by a mass spectrometry-based method. Over ten arachidonic acid metabolites belonging to three catalytic pathways: cyclooxygenases, lipoxygenases, and cytochrome P450, were quantified simultaneously and displayed characteristic profiles under different thyroid hormone status. The level of 20-hydroxyeicosatetraenoic acid, a cytochrome P450 metabolite, was positively correlated with thyroid hormone level and possibly contributed to the elevated blood pressured in hyperthyroidism. The increased prostanoid (PG) I2 and decreased PGE2 levels in hypothyroid patients might serve to alleviate atherosclerosis associated with dyslipidemia. The elevated level of thromboxane (TX) A2, as indicated by TXB2, in hyperthyroid patients and mice treated with thyroid hormone might bring about pulmonary hypertension frequently found in hyperthyroid patients. In conclusion, our prospective study revealed that arachidonic acid metabolites were differentially affected by thyroid hormone status. Certain metabolites may be involved in cardiovascular disorders associated with thyroid diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

Human papilloma viruses and cervical tumours: mapping of integration sites and analysis of adjacent cellular sequences

International Nuclear Information System (INIS)

Klimov, Eugene; Vinokourova, Svetlana; Moisjak, Elena; Rakhmanaliev, Elian; Kobseva, Vera; Laimins, Laimonis; Kisseljov, Fjodor; Sulimova, Galina

2002-01-01

In cervical tumours the integration of human papilloma viruses (HPV) transcripts often results in the generation of transcripts that consist of hybrids of viral and cellular sequences. Mapping data using a variety of techniques has demonstrated that HPV integration occurred without obvious specificity into human genome. However, these techniques could not demonstrate whether integration resulted in the generation of transcripts encoding viral or viral-cellular sequences. The aim of this work was to map the integration sites of HPV DNA and to analyse the adjacent cellular sequences. Amplification of the INTs was done by the APOT technique. The APOT products were sequenced according to standard protocols. The analysis of the sequences was performed using BLASTN program and public databases. To localise the INTs PCR-based screening of GeneBridge4-RH-panel was used. Twelve cellular sequences adjacent to integrated HPV16 (INT markers) expressed in squamous cell cervical carcinomas were isolated. For 11 INT markers homologous human genomic sequences were readily identified and 9 of these showed significant homologies to known genes/ESTs. Using the known locations of homologous cDNAs and the RH-mapping techniques, mapping studies showed that the INTs are distributed among different human chromosomes for each tumour sample and are located in regions with the high levels of expression. Integration of HPV genomes occurs into the different human chromosomes but into regions that contain highly transcribed genes. One interpretation of these studies is that integration of HPV occurs into decondensed regions, which are more accessible for integration of foreign DNA

Association of thyroid function with human serum ghrelin and leptin levels

International Nuclear Information System (INIS)

Wang Jinping; Xu Hao; Wu Qiulian

2008-01-01

Objective: To investigate the effect of different status of thyroid function (hypothyroidism and hyperthyroidism as well as euthyroid status) on serum ghrelin and leptin levels. Methods: The levels of serum ghrelin and leptin were determined by radio immunoassay in 46 untreated subjects with hyperthyroidism, 15 hyperthyroid patients achieved a euthyroid status after radioiodine 131 I therapy, 21 cases of hypothyroidism and 18 cases of normal controls, respectively. Meanwhile, the serum levels of free triiodothyronine (FT 3 ), free thyroxine (FT 4 ) and thyroid-stimulating hormone (TSH) were measured by chemiluminescence immune assay. Results: (1) The levels of serum ghrelin in untreated hyperthyroidism were significantly lower than those in hyperthyroid patients achieved a euthyroid status (t=3.21, P 3 (r=-0.29, P 4 (r=-0.26, P< 0.05), positively correlated with serum TSH (r=0.36, P<0.05); serum leptin levels did not correlate with thyroid hormone. Conclusion: The levels of serum ghrelin were differently under different thyroid functional status and correlated with thyroid hormone, while serum leptin were not. (authors)

Role of 188Re(V)DMSA in the diagnosis and therapy of medullary thyroid carcinoma: a pilot study in an animal model

International Nuclear Information System (INIS)

Learoyd, D.L.; Roach, P.J.; Snowdon, G.M.; Dadachova, K.; Moreau, A.M.; Robinson, B.G.

1999-01-01

Full text: 99 Tc m (V)DMSA has been reported to be highly sensitive in the diagnosis of medullary thyroid cancer (MTC). Rhenium-188, a beta emitter, has potential for therapy of MTC. However, initial studies with 188 Re indicate high renal uptake which may interfere with potential therapeutic applications of this radiopharmaceutical. A modified radiolabelling method has been shown to reduced the renal uptake of 188 Re(V)DMSA in control animals. The aims of this study were to determine whether there is uptake of modified 188 Re(V)DMSA in nude mice injected with an MTC cell line and whether there is potential for MTC therapy. Two groups of mice were injected in the left flank (SC) with TT cell line, and in mice showing tumour growth a low-dose (400 kBq) of 188 Re(V)DMSA was injected via a tail vein 8 weeks later. Biodistribution was performed on several mice and several others were given 'therapy' injections (8 MBq) to determine whether tumour shrinkage could be objectively observed. Tracer uptake was highest in bone and kidneys but tumour uptake was relatively low. However, no new tumour growth was seen in any of the mice subsequent to therapy injections and 1 mouse showed complete remission within 5 weeks of injection. Further animal and human studies will need to be performed to determine the potential role of this modified 118 Re(V)DMSA in patients with MTC

Screening for thyroid cancer in children

International Nuclear Information System (INIS)

Nagataki, S.; Ashizawa, K.

1996-01-01

In the screening of the thyroid diseases in the radiation exposed cohort, it is essential to make correct diagnosis and to measure radiation dose in every subjects in the cohort and to analyze the dose response relationship by the most appropriate statistical method. Thus, thyroid cancer, thyroid adenoma and autoimmune hypothyroidism were confirmed to be radiation-induced thyroid diseases among atomic bomb survivors. A group of investigators from Nagasaki university have been working in the thyroid part of Chernobyl Sasakawa Health and Medical Cooperation Project, and more than 80000 children were screened in 5 diagnostic centers (Mogilev, Gomel, Kiev, Korosten and Klincy). In order to make correct diagnosis, thyroid echo-tomography, measurements of serum levels of free thyroxine, TSH, titers of anti-thyroid antibodies were performed in every children in the cohort and aspiration biopsy was performed when necessary. Whole body Cs 137 radioactivity was also determined in every subjects. Children with thyroid cancer confirmed by histology (biopsy or operation) were 2 in Mogilev, 19 in Gomel, 6 in Kiev, 5 in Korosten and 4 in Klincy (until 1994). Since children screened in each center were less than 20000, prevalence of thyroid cancer was remarkably high (lowest 100 and highest 1000/million children) when compared to the other parts of the world (0.2 to 5/million/year). However, there was no dose response relationship between the prevalence of cancer or nodule and whole body Cs 137 radioactivity. Although a significant correlation between thyroid cancer and reconstructed thyroid I 131 dose was presented, there are no previous reports to prove that I 131 produces thyroid cancer in human. Investigation on external radiation and short lived isotopes along with I 131 may be important to elucidate the cause of thyroid cancer

Upregulated expression of human neutrophil peptides 1, 2 and 3 (HNP 1-3) in colon cancer serum and tumours: a biomarker study

International Nuclear Information System (INIS)

Albrethsen, Jakob; Bøgebo, Rikke; Gammeltoft, Steen; Olsen, Jesper; Winther, Benny; Raskov, Hans

2005-01-01

Molecular markers for localized colon tumours and for prognosis following therapy are needed. Proteomics research is currently producing numerous biomarker studies with clinical potential. We investigate the protein composition of plasma and of tumour extracts with the aim of identifying biomarkers for colon cancer. By Surface Enhanced Laser Desorption/Ionisation – Time Of Flight / Mass spectrometry (SELDI-TOF/MS) we compare the protein profiles of colon cancer serum with serum from healthy individuals and the protein profiles of colon tumours with normal colon tissue. By size exclusion chromatography, we investigate the binding of HNP 1-3 to high mass plasma proteins. By microflow we investigate the effect of HNP 1-3 on mammalian cells. Human Neutrophil Peptides -1, -2 and -3 (HNP 1-3), also known as alfa-defensin-1, -2 and -3, are present in elevated concentrations in serum from colon cancer patients and in protein extracts from colon tumours. A fraction of HNP 1-3 in serum is bound to unidentified high mass plasma proteins. HNP 1-3 purified from colon tumours are lethal to mammalian cells. HNP 1-3 may serve as blood markers for colon cancer in combination with other diagnostic tools. We propose that HNP 1-3 are carried into the bloodstream by attaching to high mass plasma proteins in the tumour microenvironment. We discuss the effect of HNP 1-3 on tumour progression

Stem cell pluripotency factor NANOG is expressed in human fetal gonocytes, testicular carcinoma in situ and germ cell tumours

DEFF Research Database (Denmark)

Hoei-Hansen, C E; Almstrup, K; Nielsen, J E

2005-01-01

AIMS: NANOG is a key regulator of embryonic stem cell (ESC) self-renewal and pluripotency. Our recent genome-wide gene expression profiling study of the precursor of testicular germ cell tumours, carcinoma in situ testis (CIS), showed close similarity between ESC and CIS, including high NANOG...... earlier than for OCT-4. We detected no expression at the protein level in normal testis. CONCLUSIONS: NANOG is a new marker for testicular CIS and germ cell tumours and the high level of NANOG along with OCT-4 are determinants of the stem cell-like pluripotency of the preinvasive CIS cell. Timing of NANOG...... expression. In the present study we analysed the protein expression of NANOG during normal development of human testis and in a large series of neoplastic/dysgenetic specimens. METHODS AND RESULTS: We detected abundant expression of NANOG in CIS and in CIS-derived testicular tumours with marked differences...

Thyroid cancer in lingual thyroid and thyroglossal duct cyst.

Science.gov (United States)

Sturniolo, Giacomo; Vermiglio, Francesco; Moleti, Mariacarla

2017-01-01

Ectopy is the most common embryogenetic defect of the thyroid gland, representing between 48 and 61% of all thyroid dysgeneses. Persistence of thyroid tissue in the context of a thyroglossal duct remnant and lingual thyroid tissue are the most common defects. Although most cases of ectopic thyroid are asymptomatic, any disease affecting the thyroid may potentially involve the ectopic tissue, including malignancies. The prevalence of differentiated thyroid carcinoma in lingual thyroid and thyroglossal duct cyst is around 1% of patients affected with the above thyroid ectopies. We here review the current literature concerning primary thyroid carcinomas originating from thyroid tissue on thyroglossal duct cysts and lingual thyroid. Copyright © 2016 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

A Histological Autopsy Study of the Thyroid gland in Human ...

African Journals Online (AJOL)

SITWALA COMPUTERS

Objective: The aim of the study was to determine the histological appearances of adult thyroid glands in patients who died of HIV related diseases at UTH in the period 2010 to 2012. Materials and Methods: This research was a descriptive retrospective study of adult thyroid glands collected at autopsy during the period 2010 ...

Recurrent Silent Thyroiditis as a Sequela of Postpartum Thyroiditis

OpenAIRE

Hanseree, Preaw; Salvador, Vincent Bryan; Sachmechi, Issac; Kim, Paul

2014-01-01

Thyroiditis encompasses a group of disorders characterized by thyroid inflammation. Though clinically indistinguishable from silent thyroiditis, postpartum thyroiditis occurs in women within 12 months after delivery. Recurrent postpartum thyroiditis in subsequent pregnancies is common, but recurrent silent thyroiditis is rare. We reported a case of patient with recurrent episodes of thyroiditis, unrelated to pregnancy, after an episode of postpartum thyroiditis. It is of interest that postpar...

Thyroid Surgery

Science.gov (United States)

... Hypothyroidism in Children and Adolescents Pediatric Differentiated Thyroid Cancer Thyroid Nodules in Children and Adolescents Thyroid Surgery Resources Thyroid Surgery Brochure PDF Thyroid Surgery FAQs PDF En Español Cirugia De La Tiroides El folleto de Cirugia De La Tiroides Search Thyroid ...

Radioiodine treatment for malignant thyroid disease

Energy Technology Data Exchange (ETDEWEB)

Berg, Gertrud [Sahlgrenska Univ. Hospital, Goeteborg (Sweden). Dept. of Oncology

2006-12-15

Radioiodine treatment for thyroid disease has been given for half a decade in Sweden. The most common indication for treatment is hyperthyroidism, when iodine uptake is high. The situation in which radioiodine treatment is used in thyroid cancer is less favourable and measures therefore have to be taken to optimize the treatment. Treatment should be performed early in the course of the disease to achieve the highest possible differentiation. Before treatment the iodine and goitrogen intake should be kept low. Stimulation of the thyrocytes by thyroid-stimulating hormone (TSH) should be high. It is conventionally achieved by thyroid hormone withdrawal rendering the patient hypothyroid, or by the recently available recombinant human TSH (rhTSH) which can be recommended for ablation of the thyroid remnant after thyroidectomy and for treatment of metastases in fragile patients unable to undergo hypothyroidism. Finally, stunning - the negative effect of a prior test dose from radioactive iodine - should be avoided.

[Thyroid emergencies : Thyroid storm and myxedema coma].

Science.gov (United States)

Spitzweg, C; Reincke, M; Gärtner, R

2017-10-01

Thyroid emergencies are rare life-threatening endocrine conditions resulting from either decompensated thyrotoxicosis (thyroid storm) or severe thyroid hormone deficiency (myxedema coma). Both conditions develop out of a long-standing undiagnosed or untreated hyper- or hypothyroidism, respectively, precipitated by an acute stress-associated event, such as infection, trauma, or surgery. Cardinal features of thyroid storm are myasthenia, cardiovascular symptoms, in particular tachycardia, as well as hyperthermia and central nervous system dysfunction. The diagnosis is made based on clinical criteria only as thyroid hormone measurements do not differentiate between thyroid storm and uncomplicated hyperthyroidism. In addition to critical care measures therapy focusses on inhibition of thyroid hormone synthesis and secretion (antithyroid drugs, perchlorate, Lugol's solution, cholestyramine, thyroidectomy) as well as inhibition of thyroid hormone effects in the periphery (β-blocker, glucocorticoids).Cardinal symptoms of myxedema coma are hypothermia, decreased mental status, and hypoventilation with risk of pneumonia and hyponatremia. The diagnosis is also purely based on clinical criteria as measurements of thyroid hormone levels do not differ between uncomplicated severe hypothyroidism and myxedema coma. In addition to substitution of thyroid hormones and glucocorticoids, therapy focusses on critical care measures to treat hypoventilation and hypercapnia, correction of hyponatremia and hypothermia.Survival of both thyroid emergencies can only be optimized by early diagnosis based on clinical criteria and prompt initiation of multimodal therapy including supportive measures and treatment of the precipitating event.

The study on mutations of the gene of extracellular domain of human thyrotropin receptor in the patients with thyroid diseases

International Nuclear Information System (INIS)

Zhang Zuncheng; Fang Peihua; Tan Jian; Lu Mei

2002-01-01

Objective: To define the sequence of the gene of extracellular domain of normal human thyrotropin receptor (hTSHR) and to investigate the mutations of the gene in the patients with thyroid diseases. Methods: Total RNAs were extracted from the thyroid tissue of four normal controls, twelve Graves' disease, four Hashimoto's thyroiditis and eleven nodular goiter patients. The extracellular domain of hTSHR genes were amplified by reverse transcription-polymerase chain reaction (RT-PCR) and sequenced with CEQ 2000 Genetic Analyzer. Results: The normal controls and the patients with thyroid disease had the same gene sequences of the extracellular domain of hTSHR. No mutation was found, except a silent base exchange in exon 7 (Asn187) at 661 base, in which 20 samples were 'T', 11 samples were 'C', without changes of amino acid of the TSHR. Conclusions: This study has not revealed mutations in the gene of extracellular domain of hTSHR. Other molecular pathogenetic mechanisms may be involved and more research is demanded

Thyroid stimulating hormone and subclinical thyroid dysfunction

International Nuclear Information System (INIS)

Guo Yongtie

2008-01-01

Subclinical thyroid dysfunction has mild clinical symptoms. It is nonspecific and not so noticeable. It performs only for thyroid stimulating hormone rise and decline. The value of early diagnosis and treatment of thyroid stimulating hormone in subclinical thyroid dysfunction were reviewed. (authors)

Primary thyroid lymphoma: a rare thyroid malignancy

International Nuclear Information System (INIS)

Mukhtar, R.; Khattak, R.; Mateen, A.

2011-01-01

Incidence of thyroidal masses is very high with predominance in females. Most of these masses are benign. Malignancy can be of thyroid or non-thyroid origin. Surgery is treatment of choice in the former but not in latter. Primary thyroid lymphoma (PTL) is a rare cause of thyroid malignancy of non-thyroid origin which is highly treatable without surgery but early diagnosis is important requisite to have better outcome. Fine needle aspiration cytology (FNAC) is an important tool in early diagnosis of PTL, which enables doctors to treat patient better without major surgery and its morbidity. Two cases of primary thyroid lymphoma are hereby presented. The patient diagnosed on FNAC had better outcome than the one who had major surgery. (author)

Iodine intake not radiation is the probable major influence on the morphology, aggressiveness and latency of papillary thyroid carcinomas (PTC)

International Nuclear Information System (INIS)

Williams, Dill; Vowler, Sarah; Bogdanova, Tania; Tronko, Nikol; Ito, Masah; Livolsi, Virg; Thomas, Gerry; Demidchik, Evg

2005-01-01

Full text: This study set out to investigate whether radiation induced thyroid cancers differ in morphology and aggressiveness from non radiation induced cancers, and whether other factors such as iodine intake are important. Chernobyl-related thyroid carcinomas, almost all PTCs, are reportedly typically morphologically solid, RET-PTC3 positive, and aggressive. We have studied 152 PTCs, 84 Chernobyl related (Chernobyl Tumour Bank), 23 unexposed children from the same area, and 45 from other countries. We quantified morphological changes and invasion, and found no significant differences between age-matched radiation-exposed and unexposed groups from the Chernobyl regions (papillary differentiation 34.3 v 35.2%, invasion 62 v 65 %). Age-matched tumours from Japan, a country with high dietary iodine, showed significantly more well-differentiated papillary architecture (80.8 v 43.3%, p<0.0001) and significantly less invasion (30 v 57 %, p<0.01) than tumours from Chernobyl regions. PTCs from England and Wales, iodine intake intermediate between Japan and the iodine deficient Chernobyl regions, showed intermediate features. We and others have shown that papillary architecture correlates with RET-PTC1 and solid morphology with RET-PTC3; the proportion of RET-PTC3 positive tumours has declined with increasing latency. We have also previously shown that solid morphology in Chernobyl-related PTCs correlates with short latency irrespective of age at exposure. Conclusion: We conclude that in the 19 years since the Chernobyl accident the radiation and non radiation-induced induced papillary carcinomas from the same areas do not differ in morphology and aggressiveness but both differ significantly from tumours from an iodine rich country. We suggest that these features and the surprisingly short latency after Chernobyl compared to other radiation incidents are influenced by the low dietary iodine intake. (author)

Potentially lethal damage repair in cell lines of radioresistant human tumours and normal skin fibroblasts

International Nuclear Information System (INIS)

Marchese, M.J.; Minarik, L.; Hall, E.J.; Zaider, M.

1985-01-01

Radiation cell survival data were obtained in vitro for three cell lines isolated from human tumours traditionally considered to be radioresistant-two melanomas and one osteosarcoma-as well as from a diploid skin fibroblast cell line. One melanoma cell line was much more radioresistant than the other, while the osteosarcoma and fibroblast cell lines were more radiosensitive than either. For cells growing exponentially, little potentially lethal damage repair (PLDR) could be demonstrated by comparing survival data for cells in which subculture was delayed by 6 h with those sub-cultured immediately after treatment. For the malignant cells in plateau phase, which in these cells might be better termed 'slowed growth phase', since an appreciable fraction of the cells are still cycling, a small amount of PLDR was observed, but not as much as reported by other investigators in the literature. The normal fibroblasts, which achieved a truer plateau phase in terms of noncycling cells, showed a significantly larger amount of PLDR than the tumour cells. (author)

Specific receptors for epidermal growth factor in human bone tumour cells and its effect on synthesis of prostaglandin E2 by cultured osteosarcoma cell line

International Nuclear Information System (INIS)

Hirata, Y.; Uchihashi, M.; Nakashima, H.; Fujita, T.; Matsukura, S.; Matsui, K.

1984-01-01

Using tumour cell lines derived from human bone tumours, specific binding sites for epidermal growth factor (EGF), a potent growth stimulator in many tissues, and its effect on synthesis of prostaglandin (PG) E 2 , a potent bone-resorbing factor, by cultured osteosarcoma cell line were studied. Three tumour cell lines, one osteosarcoma (HOSO) and two giant cell tumours of the bone (G-1 and G-2), all possessed specific binding sites for 125 I-labelled EGF: the apparent dissociation constant was approximately 4-10 x 10 -10 M and the maximal binding capacity was 50 000-80 000 sites/cell. EGF had no mitogenic effect in these cell lines. However, these cell lines did not have specific binding sites for 125 I-labelled parathyroid hormone (PTH) or calcitonin. HOSO line produced and secreted PGE 2 into medium, while no significant amount of PGE 2 was demonstrated in G-1 or G-2 line. EGF significantly stimulated PGE 2 production in HOSO line in a dose-dependent manner (0.5-50 ng/ml); its stimulatory effect was completely abolished by indomethacin, an inhibitor of PG biosynthesis. Exogenous PGE 1 significantly stimulated cyclic AMP formation in HOSO line, whereas PGFsub(2α) PTH, calcitonin, or EGF had no effect. None of these calcium-regulating hormones affected cyclic AMP generation in either G-1 of G-2 line. These data indicate that human bone tumour cells have specific EGF receptors unrelated to cell growth, and suggest that EGF may be involved in bone resorption through a PGE 2 -mediated process in human osseous tissues. (author)

Image-based computational quantification and visualization of genetic alterations and tumour heterogeneity.

Science.gov (United States)

Zhong, Qing; Rüschoff, Jan H; Guo, Tiannan; Gabrani, Maria; Schüffler, Peter J; Rechsteiner, Markus; Liu, Yansheng; Fuchs, Thomas J; Rupp, Niels J; Fankhauser, Christian; Buhmann, Joachim M; Perner, Sven; Poyet, Cédric; Blattner, Miriam; Soldini, Davide; Moch, Holger; Rubin, Mark A; Noske, Aurelia; Rüschoff, Josef; Haffner, Michael C; Jochum, Wolfram; Wild, Peter J

2016-04-07

Recent large-scale genome analyses of human tissue samples have uncovered a high degree of genetic alterations and tumour heterogeneity in most tumour entities, independent of morphological phenotypes and histopathological characteristics. Assessment of genetic copy-number variation (CNV) and tumour heterogeneity by fluorescence in situ hybridization (ISH) provides additional tissue morphology at single-cell resolution, but it is labour intensive with limited throughput and high inter-observer variability. We present an integrative method combining bright-field dual-colour chromogenic and silver ISH assays with an image-based computational workflow (ISHProfiler), for accurate detection of molecular signals, high-throughput evaluation of CNV, expressive visualization of multi-level heterogeneity (cellular, inter- and intra-tumour heterogeneity), and objective quantification of heterogeneous genetic deletions (PTEN) and amplifications (19q12, HER2) in diverse human tumours (prostate, endometrial, ovarian and gastric), using various tissue sizes and different scanners, with unprecedented throughput and reproducibility.

Tumour location within the breast: Does tumour site have prognostic ability?

Science.gov (United States)

Rummel, Seth; Hueman, Matthew T; Costantino, Nick; Shriver, Craig D; Ellsworth, Rachel E

2015-01-01

Tumour location within the breast varies with the highest frequency in the upper outer quadrant (UOQ) and lowest frequency in the lower inner quadrant (LIQ). Whether tumour location is prognostic is unclear. To determine whether tumour location is prognostic, associations between tumour site and clinicopathological characteristics were evaluated. All patients enrolled in the Clinical Breast Care Project whose tumour site-UOQ, upper inner quadrant (UIQ), central, LIQ, lower outer quadrant (LOQ)-was determined by a single, dedicated breast pathologist were included in this study. Patients with multicentric disease (n = 122) or tumours spanning multiple quadrants (n = 381) were excluded from further analysis. Clinicopathological characteristics were analysed using chi-square tests for univariate analysis with multivariate analysis performed using principal components analysis (PCA) and multiple logistic regression. Significance was defined as P location, 30 had bilateral disease. Tumour location in the UOQ (51.5%) was significantly higher than in the UIQ (15.6%), LOQ (14.2%), central (10.6%), or LIQ (8.1%). Tumours in the central quadrant were significantly more likely to have higher tumour stage (P = 0.003) and size (P location as a prognostic factor revealed that although tumours in the central region are associated with less favourable outcome, these associations are not independent of location but rather driven by larger tumour size. Tumours in the central region are more difficult to detect mammographically, resulting in larger tumour size at diagnosis and thus less favourable prognosis. Together, these data demonstrate that tumour location is not an independent prognostic factor.

Efficiency of the Bethesda System for Thyroid Cytopathology.

Science.gov (United States)

Mora-Guzmán, Ismael; Muñoz de Nova, José Luis; Marín-Campos, Cristina; Jiménez-Heffernan, José Antonio; Cuesta Pérez, Juan Julián; Lahera Vargas, Marcos; Torres Mínguez, Emma; Martín-Pérez, Elena

2018-03-28

Fine-needle aspiration biopsies are a key tool for preoperative assessment of thyroid nodules, and the Bethesda system is the preferred method to report cytological analysis. The purpose of this study is to assess the efficiency of the Bethesda system to identify the malignancy risk of thyroid nodules. Patients who underwent thyroid surgery between June 2010 and June 2017 were included. Samples were classified into 6categories according to rates of malignancy associated with each diagnostic category. In order to investigate the correlation between categories, a statistical analysis compared the categories with pathology reports. Diagnostic indicators were calculated as a screening test (categories IV, V, VI as true-positive) and as a method to identify malignancy (V, VI as true-positive). In a series of 522 patients, we found 184 (35.2%) malignant tumours, papillary carcinoma being the most prevalent with 155 cases (84.2%). Malignant rates for diagnostic categories were: I, 0%; II, 1.5%; III, 6.4%; IV, 31%; V, 86.5%; VI, 100%. A robust correlation was identified between categories on statistical analysis. For the «screening test» analysis, sensitivity was 98.9%, specificity 84.4%, positive predictive value 69.6%, negative predictive value 99.5%, and diagnostic accuracy 88.2%. Analysing the accuracy to detect malignancy, values were: sensitivity 98.6%, specificity 97.6%, positive predictive value 93.5%, negative predictive value 99.5%, diagnostic accuracy 97.9%. The Bethesda system is a clear and reliable approach to report thyroid cytology and therefore is an effective tool to identify malignancy risk and guide clinical management. Copyright © 2018 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

Effect of 30 mCi radioiodine on multinodular goiter previously treated with recombinant human thyroid-stimulating hormone

Energy Technology Data Exchange (ETDEWEB)

Paz-Filho, G.J.; Mesa-Junior, C.O.; Boguszewski, C.L.; Carvalho, G.A.; Graf, H. [Universidade Federal do Parana (UFPR), Curitiba, PR (Brazil). Hospital de Clinicas. Servico de Endocrinologia e Metabologia; Olandoski, M. [Pontificia Univ. Catolica do Parana, Curitiba, PR (Brazil). Nucleo de Bioestatistica; Woellner, L.C. [Centro de Medicina Nuclear, Curitiba, PR (Brazil); Goedert, C.A. [Centro de Tomografia Computadorizada, Curitiba, PR (Brazil)

2007-12-15

Recombinant human thyroid-stimulating hormone (rhTSH) enhances {sup 131}I uptake, permitting a decrease in radiation for the treatment of multinodular goiter (MNG). Our objective was to evaluate the safety and efficacy of a single 0.1-mg dose of rhTSH, followed by 30 mCi {sup 131}I, in patients with MNG. Seventeen patients (15 females, 59.0 {+-} 13.1 years), who had never been submitted to {sup 131}I therapy, received a single 0.1-mg injection of rhTSH followed by 30 mCi {sup 131}I on the next day. Mean basal thyroid volume measured by computed tomography was 106.1 {+-} 64.4 mL. {sup 131}I 24-h uptake, TSH, free-T4, T3, thyroglobulin, anti-thyroid antibodies, and thyroid volume were evaluated at regular intervals of 12 months. Mean {sup 131}I 24-h uptake increased from 18.1 {+-} 9.7 to 49.6 {+-} 13.4% (P < 0.001), a median 2.6-fold increase (1.2 to 9.2). Peak hormonal levels were 10.86 {+-} 5.44 mU/L for TSH (a median 15.5-fold increase), 1.80 {+-} 0.48 ng/dL for free-T4, 204.61 {+-} 58.37 ng/dL for T3, and a median of 557.0 ng/mL for thyroglobulin. The adverse effects observed were hyperthyroidism (17.6%), painful thyroiditis (29.4%) and hypothyroidism (52.9%). Thyroid volume was reduced by 34.3 {+-} 14.3% after 6 months (P < 0.001) and by 46.0 {+-} 14.6% after 1 year (P < 0.001). Treatment of MNG with a single 0.1-mg dose of rhTSH, followed by a fixed amount of radioactivity of {sup 131}I, leads to an efficacious decrease in thyroid volume for the majority of the patients, with a moderate incidence of non-serious and readily treatable adverse effects. (author)

Effect of 30 mCi radioiodine on multinodular goiter previously treated with recombinant human thyroid-stimulating hormone

Directory of Open Access Journals (Sweden)

G.J. Paz-Filho

2007-12-01

Full Text Available Recombinant human thyroid-stimulating hormone (rhTSH enhances 131I uptake, permitting a decrease in radiation for the treatment of multinodular goiter (MNG. Our objective was to evaluate the safety and efficacy of a single 0.1-mg dose of rhTSH, followed by 30 mCi 131I, in patients with MNG. Seventeen patients (15 females, 59.0 ± 13.1 years, who had never been submitted to 131I therapy, received a single 0.1-mg injection of rhTSH followed by 30 mCi 131I on the next day. Mean basal thyroid volume measured by computed tomography was 106.1 ± 64.4 mL. 131I 24-h uptake, TSH, free-T4, T3, thyroglobulin, anti-thyroid antibodies, and thyroid volume were evaluated at regular intervals of 12 months. Mean 131I 24-h uptake increased from 18.1 ± 9.7 to 49.6 ± 13.4% (P < 0.001, a median 2.6-fold increase (1.2 to 9.2. Peak hormonal levels were 10.86 ± 5.44 mU/L for TSH (a median 15.5-fold increase, 1.80 ± 0.48 ng/dL for free-T4, 204.61 ± 58.37 ng/dL for T3, and a median of 557.0 ng/mL for thyroglobulin. The adverse effects observed were hyperthyroidism (17.6%, painful thyroiditis (29.4% and hypothyroidism (52.9%. Thyroid volume was reduced by 34.3 ± 14.3% after 6 months (P < 0.001 and by 46.0 ± 14.6% after 1 year (P < 0.001. Treatment of MNG with a single 0.1-mg dose of rhTSH, followed by a fixed amount of radioactivity of 131I, leads to an efficacious decrease in thyroid volume for the majority of the patients, with a moderate incidence of non-serious and readily treatable adverse effects.

Thyroid hormones and adult-type Leydig cell development

NARCIS (Netherlands)

Rijntjes, E.

2008-01-01

Alterations in thyroid hormone levels are well known to influence key functions in growth and development. Although in many countries the diet is fortified with iodide, essential for thyroid hormone synthesis, still not all humans have access to fortified diets, leaving a substantial part of the

Isotopic ratios of 129I/127I in mammalian thyroid glands in Japan

International Nuclear Information System (INIS)

Seki, R.; Hatano, T.

1994-01-01

The isotopic ratios of 129 I/ 127 I in cattle thyroid glands collected from various areas of Japan were measured by neutron activation analysis with combustion pre-treatment. Pig and human thyroid glands were also analyzed by the same method. The iodine isotopic ratio in cattle thyroid glands in Japan is comparable with that observed in Europe. The isotopic ratio in human thyroid glands in Japan is remarkably lower than that in Europe, which has been reported to be comparable to that of cattle. The isotopic ratio in pig thyroid glands is also lower than that in cattle. (author) 7 refs.; 3 figs.; 5 tabs

Contributions to the study of albumins from thyroid

International Nuclear Information System (INIS)

Netto, M.

1975-01-01

72 human thyroid were analysed from which 27 corresponded to normal tissue, 30 to nodular goiters(21 'cold' nodules and 9 'hot' nodules), 10 to adenocarcinomas, 3 to ganglionar metastasis of thyroidal adenocarcinoma and 2 to Hashimoto's thyroiditis. The concentration of total albumin and serumalbumin were determined in these tissues thus permitting the estimation of thyralbumin concentration. The results obtained showed a significantly higher concentration of thyralbumin as compared to serumalbumin in all tissue samples. A significant correlation between the content of blood in the thyroid extracts and its concentration of thyralbumin was also found. The hypothesis that thyralbumin was produced in the gland was therefore accepted. Furthermore, the thyralbumin content of abnormal tissues was always higher than that found in normal thyroids [pt

Radioiodine-labelled compounds previously or currently used for tumour localization

International Nuclear Information System (INIS)

Beierwaltes, W.H.

1976-01-01

131 I-labelled human serum albumin, though not used for tumour localization today, is an excellent ''standard'' with which to compare uptake of ''tumour-specific'' radiolabelled compounds. 131 I-labelled fibrinogen and antibodies to fibrinogen have a non-specific uptake in tumours. Nungester, Beierwaltes and Knorpp are credited by Mahaley as first treating a human for cancer with 131 I-labelled antibody globulins (malignant melanoma). Although many theoretical problems remain in obtaining diagnostic localization of 131 I-IgG, Quinones, Mizejewski and Beierwaltes demonstrated the uptake of 131 I-labelled immune antibodies in Syrian hamster cheeck pouch with chorionic gonadotropic hormone as the specific tumour-associated antigen. This model was then used successfully by Goldenberg and Hoffer for demonstrating colon carcinoma by using antibodies to carcinoembryonic antigen. A 131 I-labelled chloroquine analogue, synthesized by Counsell, has been demonstrated by Beierwaltes et al. to concentrate diagnostically and therapeutically in the malignant melanotic melanoma. 131 I-19-iodocholesterol, synthesized by Counsell, has been demonstrated by Beierwaltes et al. to concentrate diagnostically in the human adrenal cortex. It has many unique diagnostic capabilities not available with other routine diagnostic methods available today. (author)

Histological characteristics of human papilloma-virus-positive and -negative invasive and in situ squamous cell tumours of the penis

DEFF Research Database (Denmark)

Krustrup, Dorrit; Jensen, Helle Lone; van den Brule, Adriaan J C

2009-01-01

A high prevalence of cervical cancer associated high-risk types of human papillomavirus (hrHPV) has been demonstrated in premalignant and invasive squamous cell lesions of the penis, but large studies correlating histological characteristics with HPV status are few in number. Tumour tissues from...

Mechanism for the anti-thyroid action of minocycline

Energy Technology Data Exchange (ETDEWEB)

Doerge, D.R.; Divi, R.L.; Deck, J. [National Center for Toxicological Research, Jefferson, AR (United States); Taurog, A. [Univ. of Texas, Dallas, TX (United States)

1997-01-01

Administration of minocycline (MN), a tetracycline antibiotic, produces a black pigment in the thyroids of humans and several species of experimental animals and antithyroid effects in rodents. We have previously shown that these effects appear to be related to interactions of MN with thyroid peroxidase (TPO), the key enzyme in thyroid hormone synthesis. In the present study, the mechanisms for inhibition of TPO-catalyzed iodination and coupling reactions by MN were investigated. 37 refs., 7 figs., 3 tabs.

Early death, late death and repair factor in three human tumour cell lines

International Nuclear Information System (INIS)

Courdi, A.; Gioanni, J.; Mari, D.; Chauvel, P.

1997-01-01

The in vivo colony method used to generate survival curves following exposure to ionizing irradiation allows to score large clones, representing surviving cells, and small colonies, representing late reproductive death. By subtraction, early-dying cells can be estimated. In the three human tumour cell lines examined, we have observed that early cell death is a major mode of action of irradiation. The contribution of early cell death to total mortality increases as the dose increases. Moreover, repair due to dose-splitting and delayed plating in densely-inhibited cells is not observed in early-dying cells. (authors)

Collision tumours, squamous cell carcinoma of larynx, papillary thyroid carcinoma, metastatic lymphatic node. Clinical Presentation

International Nuclear Information System (INIS)

Villalba, V; Gomez, R; Yoffe, I.; Liu, T.; Arias, J.; Quiroz, J.; Gonzalez, M; Ayala, E.

2010-01-01

Male patient with 35 years old, merchant from Capiata, no history of smoking or alcoholism, with 2 months history of bilateral neck nodes, sore throat, weight loss of 8 kg., dysphonia, progressive dyspne a on medium efforts dyspne a at rest so you see the urgency of the Hospital de Clinicas. On examination: lucid, collaborator, normosomico, with dysphonia, stri dor and dyspne a. P S: 2. No hemodynamic or fever. Neck: tumor mass of 6 cm in diameter, infrahiodea right, accompanying the movement of swallowing, bilateral jugular carotid lymphadenopathy high of 2 cm in diameter, solid-elastic smooth, mobile; lymphadenopathy average lower right carotid and jugular similar characteristics. Laryngoscopy smooth, submucosal, nodular lesion on right vocal cord, paralytic in middle position; aritenoides edematous law, glottal gap of 10%. Mobile left vocal cord. Remainder of the examination: Normal. Emergency tracheotomy performed. Biopsy of the lesion: invasive carcinoma, without other specifications. Laboratory tests: Hb: 11gr% eosinophilia. ECG, Rx. Chest and abdominal ultrasound: within normal limits. CT: tumor mass of 4.5 cm in diameter in right vocal cord, which is in middle position, and infiltrates the thyroid cartilage soft tissue. In thyroid lobe right: node 5 cm diameter. Cervical lymphadenopathy 2 cm in diameter in bilateral high carotid jugular region, medium and low carotid jugular right. 2/9/09 Surgery: Tumor infiltrating infrahiodea right muscles, jugular Total laryngectomy with bilateral carotid dissection, level 2,3 and 4. Right Thyroid lobectomy. Infrahiodea muscle resection. Pathology: 1-larynx neoplasms consist collision, poorly differentiated right infraglotis (3.2 cm.) Keratinizing squamous carcinoma infiltrating focally in depth the laryngeal cartilage through it, and a papillary carcinoma right thyroid lobe (3.4 cm.) massively infiltrating peritiroideo fibroadipose and skeletal muscle tissue infiltrating through the laryngeal cartilage and extending to

Thyroid hormone synthesis and anti-thyroid drugs

Indian Academy of Sciences (India)

The inhibition of thyroid hormone synthesis is required for the treatment of hyperthyroidism and this can be achieved by one or more anti-thyroid drugs. The most widely used anti-thyroid drug methimazole (MMI) inhibits the production of thyroid hormones by irreversibly inactivating the enzyme TPO. Our studies show that the ...

Thyroid exposure of Belarusian and Ukrainian children due to the Chernobyl accident and resulting thyroid cancer risk. Final report of BfS project StSch 4240

Energy Technology Data Exchange (ETDEWEB)

Jacob, P; Meckbach, R; Ulanovski, A; Schotola, C; Proehl, G [GSF-Institute of Radiation Protection, Neuherberg (Germany); Kenigsberg, J; Buglova, E; Kruk, J [Institute of Radiation Medicine and Endocrinology, Minsk (Belarus); Likhtarev, I; Kovgan, L; Vavilov, S; Chepurniy, M [Ukrainian Radiation Protection Inst., Kyiv (Ukraine); Tronko, M; Bogdanova, T [Institute of Endocrinolgoy and Metabolism of the Academy of Medical Sciences of Ukraine, Kyiv (Ukraine); Shinkarev, S; Gavrilin, Y [All-Russian Public Organization of Invalids ' Chernobylets' , Scientific Center ' FENIX' , Moscow (Russian Federation); Demidchik, Y [Thyroid Cancer Center, Minsk (Belarus)

2005-07-01

Main objectives of the BfS Project StSch4240 Thyroid Exposure of Belarusian and Ukrainian Children due to the Chernobyl Accident and Resulting Thyroid Cancer Risk were: to establish improved estimates of average thyroid dose for both genders and for each birth-year cohort of the period 1968 - 1985 in Ukrainian and Belarusian settlements, in which more than 10 measurements of the {sup 131}I activity in the human thyroid have been performed in May/June 1986, to explore, whether this dosimetric database can be extended to neighboring settlements, to establish improved estimates of average thyroid dose for both genders and for each birth-year cohort of the period 1968 - 1985 in Ukrainian and Belarusian oblasts (regions) and larger cities, to document the thyroid cancer incidence for the period 1986 - 2001 in Ukraine and Belarus and describe morphological characteristics of the cancer cases, to assess the contribution of the baseline incidence to the total thyroid cancer incidence in the two countries and identify regional and temporal dependencies, to perform analyses of excess risks in settlements with more than 10 measurements of the {sup 131}I activity in the human thyroid. The project has been conducted in the period 6 December 1999 to 31 March 2004. (orig.)

Thyroid exposure of Belarusian and Ukrainian children due to the Chernobyl accident and resulting thyroid cancer risk. Final report of BfS project StSch 4240

International Nuclear Information System (INIS)

Jacob, P.; Meckbach, R.; Ulanovski, A.; Schotola, C.; Proehl, G.; Kenigsberg, J.; Buglova, E.; Kruk, J.; Likhtarev, I.; Kovgan, L.; Vavilov, S.; Chepurniy, M.; Tronko, M.; Bogdanova, T.; Shinkarev, S.; Gavrilin, Y.; Demidchik, Y.

2005-01-01

Main objectives of the BfS Project StSch4240 Thyroid Exposure of Belarusian and Ukrainian Children due to the Chernobyl Accident and Resulting Thyroid Cancer Risk were: to establish improved estimates of average thyroid dose for both genders and for each birth-year cohort of the period 1968 - 1985 in Ukrainian and Belarusian settlements, in which more than 10 measurements of the 131 I activity in the human thyroid have been performed in May/June 1986, to explore, whether this dosimetric database can be extended to neighboring settlements, to establish improved estimates of average thyroid dose for both genders and for each birth-year cohort of the period 1968 - 1985 in Ukrainian and Belarusian oblasts (regions) and larger cities, to document the thyroid cancer incidence for the period 1986 - 2001 in Ukraine and Belarus and describe morphological characteristics of the cancer cases, to assess the contribution of the baseline incidence to the total thyroid cancer incidence in the two countries and identify regional and temporal dependencies, to perform analyses of excess risks in settlements with more than 10 measurements of the 131 I activity in the human thyroid. The project has been conducted in the period 6 December 1999 to 31 March 2004. (orig.)

Modelling cell population growth with applications to cancer therapy in human tumour cell lines.

Science.gov (United States)

Basse, Britta; Baguley, Bruce C; Marshall, Elaine S; Wake, Graeme C; Wall, David J N

2004-01-01

In this paper we present an overview of the work undertaken to model a population of cells and the effects of cancer therapy. We began with a theoretical one compartment size structured cell population model and investigated its asymptotic steady size distributions (SSDs) (On a cell growth model for plankton, MMB JIMA 21 (2004) 49). However these size distributions are not similar to the DNA (size) distributions obtained experimentally via the flow cytometric analysis of human tumour cell lines (data obtained from the Auckland Cancer Society Research Centre, New Zealand). In our one compartment model, size was a generic term, but in order to obtain realistic steady size distributions we chose size to be DNA content and devised a multi-compartment mathematical model for the cell division cycle where each compartment corresponds to a distinct phase of the cell cycle (J. Math. Biol. 47 (2003) 295). We then incorporated another compartment describing the possible induction of apoptosis (cell death) from mitosis phase (Modelling cell death in human tumour cell lines exposed to anticancer drug paclitaxel, J. Math. Biol. 2004, in press). This enabled us to compare our model to flow cytometric data of a melanoma cell line where the anticancer drug, paclitaxel, had been added. The model gives a dynamic picture of the effects of paclitaxel on the cell cycle. We hope to use the model to describe the effects of other cancer therapies on a number of different cell lines. Copyright 2004 Elsevier Ltd.

A Placebo-Controlled, Blinded and Randomised Study on the Effects of Recombinant Human Thyrotropin on Quality of Life in the Treatment of Thyroid Cancer

DEFF Research Database (Denmark)

Nygaard, Birte; Bastholt, Lars; Bennedbæk, Finn Noe

2013-01-01

BACKGROUND: It is well known that thyroid hormone withdrawal (THW) in thyroid cancer patients can induce a decrease in quality of life (QOL). Recombinant human thyrotropin (rh-TSH) has been used to avoid this; however, no blinded studies have ever documented the effect. OBJECTIVE: To compare QOL...... in patients with differentiated thyroid cancer (DTC) treated with either rh-TSH or liothyronine (L-T3) THW for 10 days. STUDY DESIGN: Double-blind, randomised cross-over. PATIENTS: Fifty-six patients with DTC treated by total thyroidectomy and indication for postsurgery radioiodine (RI) ablation therapy...

The thyroid nodule. Thyrotropin and peripheral thyroid hormones

International Nuclear Information System (INIS)

Zimny, M.

2008-01-01

Thyrotropin, free triodothyronine and thyroxine represent the standard serological parameters for the diagnostic work-up of the thyroid but only a minority of thyroid nodules present with subclinical or overt thyroid disorders. Besides a review of the regulation and principle of function of thyroid hormones as well as the effects of subclinical or overt hyperthyroidism, the significant role of these parameters beyond the assessment of hyperthyroidism in thyroid nodules is discussed. There is evidence that the level of thyrotropin within the normal range is predictive for the relevance of autonomous functioning nodules and the risk of malignancy of non-functioning thyroid nodules. Furthermore, the ratio of triodothyronine and thyroxine indicates the etiology of hyperthyroidism. Thyrotropin represents the main parameter to determine the adequate dose of thyroid hormone therapy of thyroid nodules. (orig.)

A monograph proposing the use of canine mammary tumours as a model for the study of hereditary breast cancer susceptibility genes in humans.

Science.gov (United States)

Goebel, Katie; Merner, Nancy D

2017-05-01

Canines are excellent models for cancer studies due to their similar physiology and genomic sequence to humans, companion status and limited intra-breed heterogeneity. Due to their affliction to mammary cancers, canines can serve as powerful genetic models of hereditary breast cancers. Variants within known human breast cancer susceptibility genes only explain a fraction of familial cases. Thus, further discovery is necessary but such efforts have been thwarted by genetic heterogeneity. Reducing heterogeneity is key, and studying isolated human populations have helped in the endeavour. An alternative is to study dog pedigrees, since artificial selection has resulted in extreme homogeneity. Identifying the genetic predisposition to canine mammary tumours can translate to human discoveries - a strategy currently underutilized. To explore this potential, we reviewed published canine mammary tumour genetic studies and proposed benefits of next generation sequencing canine cohorts to facilitate moving beyond incremental advances.

Modulation of actin dynamics as potential macrophage subtype-targeting anti-tumour strategy.

Science.gov (United States)

Pergola, Carlo; Schubert, Katrin; Pace, Simona; Ziereisen, Jana; Nikels, Felix; Scherer, Olga; Hüttel, Stephan; Zahler, Stefan; Vollmar, Angelika M; Weinigel, Christina; Rummler, Silke; Müller, Rolf; Raasch, Martin; Mosig, Alexander; Koeberle, Andreas; Werz, Oliver

2017-01-30

Tumour-associated macrophages mainly comprise immunosuppressive M2 phenotypes that promote tumour progression besides anti-tumoural M1 subsets. Selective depletion or reprogramming of M2 may represent an innovative anti-cancer strategy. The actin cytoskeleton is central for cellular homeostasis and is targeted for anti-cancer chemotherapy. Here, we show that targeting G-actin nucleation using chondramide A (ChA) predominantly depletes human M2 while promoting the tumour-suppressive M1 phenotype. ChA reduced the viability of M2, with minor effects on M1, but increased tumour necrosis factor (TNF)α release from M1. Interestingly, ChA caused rapid disruption of dynamic F-actin filaments and polymerization of G-actin, followed by reduction of cell size, binucleation and cell division, without cellular collapse. In M1, but not in M2, ChA caused marked activation of SAPK/JNK and NFκB, with slight or no effects on Akt, STAT-1/-3, ERK-1/2, and p38 MAPK, seemingly accounting for the better survival of M1 and TNFα secretion. In a microfluidically-supported human tumour biochip model, circulating ChA-treated M1 markedly reduced tumour cell viability through enhanced release of TNFα. Together, ChA may cause an anti-tumoural microenvironment by depletion of M2 and activation of M1, suggesting induction of G-actin nucleation as potential strategy to target tumour-associated macrophages in addition to neoplastic cells.

Thyroid Hemiagenesis Associated with Hashimoto’s Thyroiditis

Directory of Open Access Journals (Sweden)

D. Nsame

2013-01-01

Full Text Available Thyroid hemiagenesis is a rare congenital anomaly resulting from failure of one thyroid lobe development. We report a 23-year-old female presented with Hashimoto’s thyroiditis in left lobe, associated with hemiagenesis of right lobe and isthmus which was previously diagnosed as Graves’ hyperthyroidism, but developed further into Hashimoto’s thyroiditis after being treated with antithyroid drugs. The symptoms of hyperthyroidism in the current case led to the diagnostic confirmation by scintiscanning of an absent lobe. The antithyroid pharmacotherapy by thiamazole was used. However, due to symptoms of hypothyroidism, it was discontinued two months later, so thyroid hormone substitution was reintroduced. Antithyroid antibody studies and ultrasonography documented the presence of Hashimoto’s thyroiditis.

Transurethral laser therapy of tumours of the bladder

International Nuclear Information System (INIS)

Noeske, H.D.; Rothauge, C.F.; Kraushaar, J.

1979-01-01

Surgical treatment of tumours of the bladder is still not generally accepted, and its results are unsatisfactory. To ameliorate this situation, the new energy source of laser is now being tested in transurethral treatment. There are several groups of scientists who study the use of lasers suited for human medicine: CO 2 laser (Tel Aviv), YAG neodymium laser (Munich), and argon laser (Giessen). In the urological university hospital at Giessen, where a human bladder carcinoma received laser treatment for the first time in the world in 1976, 45 argon laser operations on 38 patients are investigated. There were 37 bladder tumours of different stages and one haemangioma. Laser monotherapy was applied in 11 cases. The bulk of the cases, however, was treated by combined electro-laser-surgical treatment where the tumour bed and its immediate neighbourhood were irradiated after TUR. The results do not give a satisfactory answer as to the therapeutic value of laser. Advantages over TUR will probably be purely technical. (orig.) [de

Expression of new human inorganic pyrophosphatase in thyroid diseases: Its intimate association with hyperthyroidism

International Nuclear Information System (INIS)

Koike, Eisuke; Toda, Shuji; Yokoi, Fumiaki; Izuhara, Kenji; Koike, Norimasa; Itoh, Kouichi; Miyazaki, Kohji; Sugihara, Hajime

2006-01-01

Inorganic pyrophosphatase (PPase) controls the level of inorganic pyrophosphate produced by biosynthesis of protein, RNA, and DNA. Thus, PPase is essential for life. PPase expression is unclear in the thyroid. We cloned a new human PPase, phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPPase), and established a rabbit polyclonal anti-LHPPase antibody. This is First study to determine the PPase expression by immunohistochemistry and Western blot. Intranuclear LHPPase expression of thyrocytes was enhanced most prominently in Graves' disease and autonomously functional thyroid nodule. To estimate a regulating factor of subcellular localization of LHPPase, we examined its expression of Graves' disease-derived thyrocytes in vitro with the disease-originated serum. Nuclear expression of LHPPase was lost in cultured thyrocytes even with the serum, while its cytoplasmic expression was retained. The data suggest that increased expression of LHPPase is associated with hyperthyroidism. Intranuclear expression of LHPPase may not be regulated by Graves' disease-derived serum factors

Evaluation of two over-the-counter natural thyroid hormone preparations in human volunteers.

Science.gov (United States)

Csako, G; Corso, D M; Kestner, J; Bokser, A D; Kennedy, P E; Pucino, F

1992-04-01

To determine the pharmacologic activity of over-the-counter (OTC) thyroid preparations. In vitro analysis and a prospective, crossover study in vivo. Tertiary care center. Two healthy adult volunteers. Three OTC preparations (Thyrotrophin PMG [bovine thyroid PMG extract], Thyro Forte [thyroid lymphogland concentrate with synergistic complex], and Thyro Complex [thyroid lyophilized gland concentrate with synergistic complex]) were analyzed in vitro. Volunteers were administered two times the manufacturer's maximum recommended daily dose of either Thyrotrophin PMG or Thyro Forte for one week, washed out for four to five weeks, and crossed over to receive the opposite tablet preparation for an additional week. The triiodothyronine (T3) and thyroxine (T4) contents of OTC preparations were measured by HPLC. Vital signs, serum total and free T4, total T3, thyroid stimulating hormone, thyroxine binding globulin, thyroglobulin, and general chemistry tests (including glucose and cholesterol) were monitored before, during, and between administration of the products. HPLC analysis of the three OTC preparations showed no T4 but did show possible T3 in two of these products. We found no definite clinical or laboratory evidence of thyroid hormone excess with either product. Healthcare professionals should advise against the use of these scientifically unsound and relatively expensive OTC thyroid preparations, of which the therapeutic efficacy is unknown.

Total {sup 18}F-dopa PET tumour uptake reflects metabolic endocrine tumour activity in patients with a carcinoid tumour

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Fiebrich, Helle-Brit; Walenkamp, Annemiek M.; Vries, Elisabeth G.E. de [University Medical Centre Groningen, Department of Medical Oncology, Groningen (Netherlands); Jong, Johan R. de; Koopmans, Klaas Pieter; Dierckx, Rudi A.J.O.; Brouwers, Adrienne H. [University Medical Centre Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen (Netherlands); Kema, Ido P. [University Medical Centre Groningen, Department of Laboratory Medicine, Groningen (Netherlands); Sluiter, Wim; Links, Thera P. [University Medical Centre Groningen, Department of Endocrinology, Groningen (Netherlands)

2011-10-15

Positron emission tomography (PET) using 6-[{sup 18}F]fluoro-L-dihydroxyphenylalanine ({sup 18}F-dopa) has an excellent sensitivity to detect carcinoid tumour lesions. {sup 18}F-dopa tumour uptake and the levels of biochemical tumour markers are mediated by tumour endocrine metabolic activity. We evaluated whether total {sup 18}F-dopa tumour uptake on PET, defined as whole-body metabolic tumour burden (WBMTB), reflects tumour load per patient, as measured with tumour markers. Seventy-seven consecutive carcinoid patients who underwent an {sup 18}F-dopa PET scan in two previously published studies were analysed. For all tumour lesions mean standardised uptake values (SUVs) at 40% of the maximal SUV and tumour volume on {sup 18}F-dopa PET were determined and multiplied to calculate a metabolic burden per lesion. WBMTB was the sum of the metabolic burden of all individual lesions per patient. The 24-h urinary serotonin, urine and plasma 5-hydroxindoleacetic acid (5-HIAA), catecholamines (nor)epinephrine, dopamine and their metabolites, measured in urine and plasma, and serum chromogranin A served as tumour markers. All but 1 were evaluable for WBMTB; 74 patients had metastatic disease. {sup 18}F-dopa PET detected 979 lesions. SUV{sub max} on {sup 18}F-dopa PET varied up to 29-fold between individual lesions within the same patients. WBMTB correlated with urinary serotonin (r = 0.51) and urinary and plasma 5-HIAA (r = 0.78 and 0.66). WBMTB also correlated with urinary norepinephrine, epinephrine, dopamine and plasma dopamine, but not with serum chromogranin A. Tumour load per patient measured with {sup 18}F-dopa PET correlates with tumour markers of the serotonin and catecholamine pathway in urine and plasma in carcinoid patients, reflecting metabolic tumour activity. (orig.)

Photoacoustic spectroscopic differences between normal and malignant thyroid tissues

Science.gov (United States)

Li, Li; Xie, Wengming; Li, Hui

2012-12-01

The thyroid is one of the main endocrine glands of human body, which plays a crucial role in the body's metabolism. Thyroid cancer mortality ranks only second to ovarian cancer in endocrine cancer. Routine diagnostic methods of thyroid diseases in present clinic exist misdiagnosis and missed diagnosis to varying degrees. Those lead to miss the best period of cancer treatment--early. Photoacoustic spectroscopy technology is a new tool, which provides an effective and noninvasive way for biomedical materials research, being highly sensitive and without sample pretreatment. In this paper, we use photoacoustic spectroscopy technology (PAST) to detect the absorption spectrum between normal and malignant thyroid tissues. The result shows that the photoacoustic spectroscopy technology (PAST) could differentiate malignant thyroid tissue from normal thyroid tissue very well. This technique combined with routine diagnostic methods has the potential to increase the diagnostic accuracy in clinical thyroid cancer diagnosis.

Phthalates Are Metabolised by Primary Thyroid Cell Cultures but Have Limited Influence on Selected Thyroid Cell Functions In Vitro

DEFF Research Database (Denmark)

Hansen, Juliana Frohnert; Brorson, Marianne Møller; Boas, Malene

2016-01-01

Phthalates are plasticisers added to a wide variety of products, resulting in measurable exposure of humans. They are suspected to disrupt the thyroid axis as epidemiological studies suggest an influence on the peripheral thyroid hormone concentration. The mechanism is still unknown as only few...... in vitro studies within this area exist. The aim of the present study was to investigate the influence of three phthalate diesters (di-ethyl phthalate, di-n-butyl phthalate (DnBP), di-(2-ethylhexyl) phthalate (DEHP)) and two monoesters (mono-n-butyl phthalate and mono-(2-ethylhexyl) phthalate (MEHP......)) on the differentiated function of primary human thyroid cell cultures. Also, the kinetics of phthalate metabolism were investigated. DEHP and its monoester, MEHP, both had an inhibitory influence on 3'-5'-cyclic adenosine monophosphate secretion from the cells, and MEHP also on thyroglobulin (Tg) secretion from...

Ultrasonographic Findings of Papillary Thyroid Cancer with or without Hashimoto's Thyroiditis

International Nuclear Information System (INIS)

Park, Jun Young; Lee, Tae Hyun; Park, Dong Hee

2010-01-01

This study was designed to compare the ultrasonographic features of papillary thyroid carcinoma with and without Hashimoto's thyroiditis. This retrospective study included 190 patients with papillary thyroid carcinoma which was proven by neck surgery. The difference in the ultrasonographic findings between papillary thyroid carcinoma with Hashimoto's thyroiditis and papillary thyroid carcinoma without Hashimoto's thyroiditis were calculated statistically. Hashimoto's thyroiditis was diagnosed in 61 of 190 patients following neck surgery. The incidence of coexisting papillary thyroid carcinoma with Hashimoto's thyroiditis was significantly higher in women (p=0.0026). In addition, the frequency of macrocalcification in patients with Hashimoto's thyroiditis was also significantly higher (p=0.0009). Conversely,other ultrasonographic findings including the shape, margin, echogenicity and calcifications, for patients with papillary thyroid carcinoma with Hashimoto's thyroiditis and papillary thyroid carcinoma without Hashimoto's thyroiditis, were not statistically significant. We also found that patients with Hashimoto's thyroiditis who showed no calcification on ultrasonography tended not to detect the papillary carcinoma at a higher frequency. On ultrasonography, macrocalcifications occurred more frequently in patients with Hashimoto's thyroiditis than those without Hashimoto's thyroiditis. Malignant thyroid nodules without calcifications in patients with Hashimoto's thyroiditis more often could not be detected. Therefore, it is important carefully examine patients with Hashimoto's thyroiditis

Use of recombinant human thyroid-stimulating hormone for evaluation of thyroid function in guinea pigs (Cavia porcellus).

Science.gov (United States)

Mayer, Jörg; Wagner, Robert; Mitchell, Mark A; Fecteau, Kellie

2013-02-01

To evaluate the effects of administration of recombinant human (rh) thyroid-stimulating hormone (TSH) for evaluation of thyroid function in euthyroid guinea pigs (Cavia porcellus). Prospective, experimental study. 10 healthy, sexually intact, pet guinea pigs (approx 1 year of age). Guinea pigs were given rhTSH (100 μg, IM); plasma thyroxine concentrations were determined prior to and 3 and 4 hours after rhTSH injection. The animals were housed in 2 groups on the basis of sex and fed different commercial maintenance diets according to their husbandry. There was no significant difference in thyroxine concentrations between males and females before or after rhTSH injection. There was also no difference between thyroxine concentrations at 3 versus 4 hours after rhTSH injection. There was a significant difference between thyroxine concentrations before (median, 9.05 nmol/L [0.70 μg/dL]; 10% to 90% range, 7.39 to 16.99 nmol/L [0.57 to 1.32 μg/dL]) and after (mean ± SD, 23.95 ± 4.2 nmol/L) rhTSH injection. Euthyroid guinea pigs had plasma thyroxine concentrations of at least 7.30 nmol/L (0.57 μg/dL) and an increase of at least 2.6 times prestimulation thyroxine concentrations at 3 or 4 hours after stimulation. The results suggested that rhTSH administered IM can be used for the TSH stimulation testing in guinea pigs. We suggest thyroxine concentration in a euthyroid guinea pig should at least double 3 to 4 hours after rhTSH injection.

The influence of liver and pancreas surgery on the thyroid function

Directory of Open Access Journals (Sweden)

Wojciechowska-Durczynska Katarzyna

2012-12-01

Full Text Available Abstract Background Nowadays, the increasing number of oncologic patients with liver or pancreatic tumours are subjected to surgical treatment, as it can provide a long-term survival or sometimes cure. As a result, numerous new clinical questions regarding metabolic disturbances in these patients have been arisen. Among others, the impact of the pancreas and liver surgery extent in relation to the thyroid function remains to be elucidated. Materials and methods The study comprised 51 patients (25 men and 26 women, mean age ± SD 61.6 ± 10.4 yrs, mean ± SD with pancreatic or liver tumours, qualified for abdominal operation. Serum levels of FT3, FT4 and TSH were measured on the day before (time “0” and on the 1st, 3rd and 5th day after surgery in two (2 subgroups reflecting the extent of surgery: twenty seven (27 patients (14 men and 13 women, mean age ± SD 61.5 ± 11.8 yrs after major surgery (Whipple’s surgery, right and left hemihepatectomy, segmentectomy of the liver, distal pancreatectomy, total duodenopancreatectomy and twenty four (24 patients (11 men and 13 women, mean age ± SD 61.8 ± 8.9 yrs after minor, palliative surgery (exploratory laparotomy, gastroenterostomy, triple by-pass, liver tumour embolization, hepaticojejunostomy. Additionally, the obtained results were analyzed in relation to the type of the disease (pancreatic surgery vs liver surgery. Results Mean serum FT3 level decreased significantly during the study in major and minor surgery subgroups (prd and 5th day after major surgery was lower in pancreatic tumour patients in comparison to liver tumour patients (p=0.002, p=0.032, respectively. Similarly, mean FT3 concentration on the 3rd day in minor surgery subgroup was lower in pancreatic tumour patients in comparison to liver tumour patients (p=0.015. Discussion Our findings have confirmed essential reduction of FT3 values after abdominal surgery, independently of surgery extent. Additionally, pancreatic tumour

Endoplasmic reticulum stress as a novel mechanism in amiodarone-induced destructive thyroiditis.

Science.gov (United States)

Lombardi, Angela; Inabnet, William Barlow; Owen, Randall; Farenholtz, Kaitlyn Ellen; Tomer, Yaron

2015-01-01

Amiodarone (AMIO) is one of the most effective antiarrhythmic drugs available; however, its use is limited by a serious side effect profile, including thyroiditis. The mechanisms underlying AMIO thyroid toxicity have been elusive; thus, identification of novel approaches in order to prevent thyroiditis is essential in patients treated with AMIO. Our aim was to evaluate whether AMIO treatment could induce endoplasmic reticulum (ER) stress in human thyroid cells and the possible implications of this effect in AMIO-induced destructive thyroiditis. Here we report that AMIO, but not iodine, significantly induced the expression of ER stress markers including Ig heavy chain-binding protein (BiP), phosphoeukaryotic translation initiation factor 2α (eIF2α), CCAAT/enhancer-binding protein homologous protein (CHOP) and spliced X-box binding protein-1 (XBP-1) in human thyroid ML-1 cells and human primary thyrocytes. In both experimental systems AMIO down-regulated thyroglobulin (Tg) protein but had little effect on Tg mRNA levels, suggesting a mechanism involving Tg protein degradation. Indeed, pretreatment with the specific proteasome inhibitor MG132 reversed AMIO-induced down-regulation of Tg protein levels, confirming a proteasome-dependent degradation of Tg protein. Corroborating our findings, pretreatment of ML-1 cells and human primary thyrocytes with the chemical chaperone 4-phenylbutyric acid completely prevented the effect of AMIO on both ER stress induction and Tg down-regulation. We identified ER stress as a novel mechanism contributing to AMIO-induced destructive thyroiditis. Our data establish that AMIO-induced ER stress impairs Tg expression via proteasome activation, providing a valuable therapeutic avenue for the treatment of AMIO-induced destructive thyroiditis.

Review article: Pathogenesis and management of gastric carcinoid tumours.

Science.gov (United States)

Burkitt, M D; Pritchard, D M

2006-11-01

Gastric carcinoid tumours are rare, but are increasing in incidence. To discuss tumour pathogenesis and outline current approaches to patient management. Review of published articles following a Pubmed search. Although interest in gastric carcinoids has increased since it was recognized that they are associated with achlorhydria, to date there is no definite evidence that humans taking long-term acid suppressing medication are at increased risk. Type I tumours are associated with autoimmune atrophic gastritis and hypergastrinaemia, type II are associated with Zollinger-Ellison syndrome, multiple endocrine neoplasia-1 and hypergastrinaemia and sporadic type III carcinoids are gastrin-independent and carry the worst prognosis. Careful investigation of these patients is required, particularly to identify the tumour type, the source of hypergastrinaemia and the presence of metastases. Treatment can be directed at the source of hypergastrinaemia if type I or II tumours are still gastrin responsive and not growing autonomously. Type III tumours should be treated surgically. Advances in our understanding of the pathogenesis of gastric carcinoids have led to recent improvements in investigation and management. Challenges remain in identifying the genetic and environmental factors, in addition to hypergastrinaemia, that are responsible for tumour development in susceptible patients.

Monoclonal antibodies for radioimmunodetection of tumours and for targeting

International Nuclear Information System (INIS)

Baldwin, R.W.; Embleton, M.J.; Pimm, M.V.

1983-01-01

A monoclonal antibody 791T/36 prepared against human osteogenic sarcoma has been used to detect primary and metastatic colorectal carcinomas by external imaging of patients following injection of 131 I-labelled antibody. In 10 of 11 patients radiolabelled 791T/36 antibody localized in tumours, the tumour/non tumour ratio of radioactivity ranging from 1.5:1 to 8.1. 791T/36 antibody was also evaluated for its potential for targeting anti-tumour agents including cytotoxic drugs (Vindesine) and immunomodulating agents (interferon). Vindesine-791T/36 conjugates were preferentially cytotoxic in vitro for target cells expressing the 791T/36 anti-body defined antigen. Also interferon conjugated to 791T/36 antibody, like free interferon activated peripheral blood natural killer cell activity. These in vitro tests together with related studies on antibody localization in vivo indicate the potential of monoclonal antibody targeting of anti-tumour agents

Do Thyroid Disrupting Chemicals Influence Foetal Development during Pregnancy?

Science.gov (United States)

Hartoft-Nielsen, Marie-Louise; Boas, Malene; Bliddal, Sofie; Rasmussen, Åase Krogh; Main, Katharina; Feldt-Rasmussen, Ulla

2011-01-01

Maternal euthyroidism during pregnancy is crucial for normal development and, in particular, neurodevelopment of the foetus. Up to 3.5 percent of pregnant women suffer from hypothyroidism. Industrial use of various chemicals—endocrine disrupting chemicals (EDCs)—has been shown to cause almost constant exposure of humans with possible harmful influence on health and hormone regulation. EDCs may affect thyroid hormone homeostasis by different mechanisms, and though the effect of each chemical seems scarce, the added effects may cause inappropriate consequences on, for example, foetal neurodevelopment. This paper focuses on thyroid hormone influence on foetal development in relation to the chemicals suspected of thyroid disrupting properties with possible interactions with maternal thyroid homeostasis. Knowledge of the effects is expected to impact the general debate on the use of these chemicals. However, more studies are needed to elucidate the issue, since human studies are scarce. PMID:21918727

Thyroid Diseases

Science.gov (United States)

... beats. All of these activities are your body's metabolism. Thyroid problems include Goiter - enlargement of the thyroid gland Hyperthyroidism - when your thyroid gland makes more thyroid hormones ...

MRI of pineal region tumours: relationship between tumours and adjacent structures

International Nuclear Information System (INIS)

Satoh, H.; Kurisu, K.

1995-01-01

A variety of tumours may arise in the pineal region; accurate diagnosis is important in the selection of treatment and prognosis. A retrospective analysis of the MRI studies of 25 patients with pathologically proven pineal region tumours was performed, focused on the relationship between the tumour and neighbouring structures. Compression of the tectal plate was classified as expansive or invasive, and compression of the corpus callosum as inferior, anterior or posterior. In 10 of the 14 patients (71 %) with germ cell tumours tectal compression was of the invasive type; 8 patients (57 %) had multiple tumours and in 13 (93 %) the tumour margins were irregular. Teratomas were readily diagnosed because of characteristic heterogeneous signal intensity. Pineal cell tumours were differentiated from germ cell tumours by their rounded shape, solid nature, sharp margins, and expansive type of tectal compression. Meningiomas were characterised by their falcotentorial attachments, posterior callosal compression, and a low-intensity rim on T2-weighted images. Gd-DTPA injection enabled clear demonstration of the site and extent of tumour spread and was useful in differentiating cystic and solid components. The appearances described, while not pathognomonic, are helpful in the differential diagnosis of pineal region tumours, and valuable in planning appropriate treatment. (orig.). With 4 figs., 6 tabs

Radiation-induced thyroid disease

International Nuclear Information System (INIS)

Maxon, H.R.

1985-01-01

Ionizing radiation has been demonstrated to result in a number of changes in the human thyroid gland. At lower radiation dose levels (between 10 and 1500 rads), benign and malignant neoplasms appear to be the dominant effect, whereas at higher dose levels functional changes and thyroiditis become more prevalent. In all instances, the likelihood of the effect is related to the amount and type of radiation exposure, time since exposure, and host factors such as age, sex, and heredity. The author's current approach to the evaluation of patients with past external radiation therapy to the thyroid is discussed. The use of prophylactic thyroxine (T4) therapy is controversial. While T4 therapy may not be useful in preventing carcinogenesis when instituted many years after radiation exposure, theoretically T4 may block TSH secretion and stimulation of damaged cells to undergo malignant transformation when instituted soon after radiation exposure

Quantitative Adverse Outcome Pathway for Neurodevelopmental Effects of Thyroid Peroxidase-Induced Thyroid Hormone Synthesis Inhibition

Data.gov (United States)

U.S. Environmental Protection Agency — Adequate levels of thyroid hormones (TH) are needed for proper brain development, deficiencies may lead to adverse neurological outcomes in humans and animal models....

2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer

Science.gov (United States)

Alexander, Erik K.; Bible, Keith C.; Doherty, Gerard M.; Mandel, Susan J.; Nikiforov, Yuri E.; Pacini, Furio; Randolph, Gregory W.; Sawka, Anna M.; Schlumberger, Martin; Schuff, Kathryn G.; Sherman, Steven I.; Sosa, Julie Ann; Steward, David L.; Tuttle, R. Michael; Wartofsky, Leonard

2016-01-01

Background: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the American Thyroid Association's (ATA's) guidelines for the management of these disorders were revised in 2009, significant scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, researchers, and health policy makers on published evidence relating to the diagnosis and management of thyroid nodules and differentiated thyroid cancer. Methods: The specific clinical questions addressed in these guidelines were based on prior versions of the guidelines, stakeholder input, and input of task force members. Task force panel members were educated on knowledge synthesis methods, including electronic database searching, review and selection of relevant citations, and critical appraisal of selected studies. Published English language articles on adults were eligible for inclusion. The American College of Physicians Guideline Grading System was used for critical appraisal of evidence and grading strength of recommendations for therapeutic interventions. We developed a similarly formatted system to appraise the quality of such studies and resultant recommendations. The guideline panel had complete editorial independence from the ATA. Competing interests of guideline task force members were regularly updated, managed, and communicated to the ATA and task force members. Results: The revised guidelines for the management of thyroid nodules include recommendations regarding initial evaluation, clinical and ultrasound criteria for fine-needle aspiration biopsy, interpretation of fine-needle aspiration biopsy results, use of molecular markers, and management of benign thyroid nodules. Recommendations regarding the initial management of thyroid cancer include those relating to screening for thyroid cancer, staging and risk assessment, surgical management, radioiodine remnant ablation and therapy

Diagnostic accuracy of surface coil MRI in assessing cartilaginous invasion in laryngeal tumours. Do we need contrast-agent administration?

International Nuclear Information System (INIS)

Preda, Lorenzo; Conte, Giorgio; Bonello, Luke; Giannitto, Caterina; Tagliabue, Elena; Raimondi, Sara; Ansarin, Mohssen; De Benedetto, Luigi; Cattaneo, Augusto; Maffini, Fausto; Bellomi, Massimo

2017-01-01

To assess the diagnostic accuracy of MRI performed using surface coils, with and without contrast medium, in predicting thyroid and cricoid cartilage infiltration in laryngeal tumours, and to investigate whether the radiologist's experience influences diagnostic accuracy. We retrospectively enrolled patients with biopsy-proven laryngeal cancer who had undergone preoperative staging MRI and open surgery. Two radiologists with different experience (senior vs. junior) reviewed the MR images without (session A1) and with contrast medium (session A2) separately. We calculated the accuracy of MRI with and without contrast medium in detecting infiltration of the thyroid and cricoid cartilages. Interobserver agreement was calculated by Cohen's Kappa (k). Forty-two patients were enrolled, for a total of 62 cartilages. In session A1 the senior and junior radiologists showed an accuracy of 85% and 71%, respectively, with k = 0.53 (0.33-0.72). In session A2 the senior and junior radiologists showed an accuracy of 84% and 77%, respectively, with k = 0.68 (0.49-0.86). Staging of laryngeal tumours with surface coil MRI showed good diagnostic accuracy in assessing cartilaginous infiltration. We observed similar values of diagnostic accuracy for the analysis performed with and without contrast medium for the senior radiologist. (orig.)

Diagnostic accuracy of surface coil MRI in assessing cartilaginous invasion in laryngeal tumours. Do we need contrast-agent administration?

Energy Technology Data Exchange (ETDEWEB)

Preda, Lorenzo [Universita degli Studi di Pavia, Department of Clinical-Surgical Diagnostic and Pediatric Sciences, Pavia (Italy); Division of Radiology, National Center of Oncological Hadrontherapy (CNAO Foundation), Pavia (Italy); Conte, Giorgio [Universita degli Studi di Milano, Postgraduation School in Radiodiagnostics, Milan (Italy); Bonello, Luke [Division of Radiology, Poliambulanza Hospital, Brescia (Italy); Giannitto, Caterina [European Institute of Oncology, Division of Radiology, Milan (Italy); Tagliabue, Elena; Raimondi, Sara [European Institute of Oncology, Division of Epidemiology and Biostatistics, Milan (Italy); Ansarin, Mohssen; De Benedetto, Luigi; Cattaneo, Augusto [European Institute of Oncology, Division of Head and Neck Surgery, Milan (Italy); Maffini, Fausto [European Institute of Oncology, Division of Pathology, Milan (Italy); Bellomi, Massimo [European Institute of Oncology, Division of Radiology, Milan (Italy); Universita degli Studi di Milano, Oncology and Haematology/Oncology Department, Milan (Italy)

2017-11-15

To assess the diagnostic accuracy of MRI performed using surface coils, with and without contrast medium, in predicting thyroid and cricoid cartilage infiltration in laryngeal tumours, and to investigate whether the radiologist's experience influences diagnostic accuracy. We retrospectively enrolled patients with biopsy-proven laryngeal cancer who had undergone preoperative staging MRI and open surgery. Two radiologists with different experience (senior vs. junior) reviewed the MR images without (session A1) and with contrast medium (session A2) separately. We calculated the accuracy of MRI with and without contrast medium in detecting infiltration of the thyroid and cricoid cartilages. Interobserver agreement was calculated by Cohen's Kappa (k). Forty-two patients were enrolled, for a total of 62 cartilages. In session A1 the senior and junior radiologists showed an accuracy of 85% and 71%, respectively, with k = 0.53 (0.33-0.72). In session A2 the senior and junior radiologists showed an accuracy of 84% and 77%, respectively, with k = 0.68 (0.49-0.86). Staging of laryngeal tumours with surface coil MRI showed good diagnostic accuracy in assessing cartilaginous infiltration. We observed similar values of diagnostic accuracy for the analysis performed with and without contrast medium for the senior radiologist. (orig.)

2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer

OpenAIRE

Haugen, Bryan R; Alexander, Erik K; Bible, Keith C; Doherty, Gerard M; Mandel, Susan J; Nikiforov, Yuri E; Pacini, Furio; Randolph, Gregory W; Sawka, Anna M; Schlumberger, Martin; Schuff, Kathryn G; Sherman, Steven I; Sosa, Julie Ann; Steward, David L; Tuttle, R. Michael

2016-01-01

Background: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the American Thyroid Association's (ATA's) guidelines for the management of these disorders were revised in 2009, significant scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, researchers, and health policy makers on published evidence relating to the diagnosis and management of thyroid nodules and d...

[Autoimmune thyroiditis and thyroid cancer].

Science.gov (United States)

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.

Sonographic features of thyroid nodules that may help distinguish clinically atypical subacute thyroiditis from thyroid malignancy.

Science.gov (United States)

Pan, Fu-shun; Wang, Wei; Wang, Yan; Xu, Ming; Liang, Jin-yu; Zheng, Yan-ling; Xie, Xiao-yan; Li, Xiao-xi

2015-04-01

The purpose of this study was to evaluate sonographic features for distinguishing clinically atypical subacute thyroiditis from malignant thyroid nodules. A total of 165 hypoechoic thyroid nodules without calcification in 135 patients with histologic diagnosis were included in this study. These nodules were classified into 2 groups: a thyroiditis group (55 nodules in 36 patients) and a malignancy group (110 nodules in 99 patients). The sonographic features of the groups were retrospectively reviewed. No significant differences were detected for the variables of marked echogenicity, a taller-than-wide shape, and mixed vascularity. However, a poorly defined margin was detected more frequently in the thyroiditis group than the malignancy group (P thyroiditis, with sensitivity and specificity of 87.3% and 80.9%, respectively. Centripetal reduction echogenicity was observed exclusively in the thyroiditis group, with high specificity (100%) but low sensitivity (21.8%) for atypical subacute thyroiditis diagnosis. All of the thyroiditis nodules with a positive color signal showed noninternal vascularity (negative predictive value, 100%). There is a considerable overlap between the sonographic features of atypical subacute thyroiditis and thyroid malignancy. However, the margin, echogenicity, and vascularity type are helpful indicators for differential diagnosis of atypical subacute thyroiditis. © 2015 by the American Institute of Ultrasound in Medicine.

TUMOUR VACCINE

NARCIS (Netherlands)

Wagner, Ernst; Kircheis, Ralf; Crommelin, D.; Van Slooten, Maaike; Storm, Gert

1999-01-01

The invention relates to a tumour vaccine with a tumour antigen base. In addition to a source of tumour antigens, the vaccine contains a release system for the delayed release of the active agent IFN- gamma , the active dose of IFN- gamma being 50 ng to 5 mu g. The IFN- gamma is released over a

Identification of genes involved in the biology of atypical teratoid/rhabdoid tumours using Drosophila melanogaster

Science.gov (United States)

Jeibmann, Astrid; Eikmeier, Kristin; Linge, Anna; Kool, Marcel; Koos, Björn; Schulz, Jacqueline; Albrecht, Stefanie; Bartelheim, Kerstin; Frühwald, Michael C.; Pfister, Stefan M.; Paulus, Werner; Hasselblatt, Martin

2014-06-01

Atypical teratoid/rhabdoid tumours (AT/RT) are malignant brain tumours. Unlike most other human brain tumours, AT/RT are characterized by inactivation of one single gene, SMARCB1. SMARCB1 is a member of the evolutionarily conserved SWI/SNF chromatin remodelling complex, which has an important role in the control of cell differentiation and proliferation. Little is known, however, about the pathways involved in the oncogenic effects of SMARCB1 inactivation, which might also represent targets for treatment. Here we report a comprehensive genetic screen in the fruit fly that revealed several genes not yet associated with loss of snr1, the Drosophila homologue of SMARCB1. We confirm the functional role of identified genes (including merlin, kibra and expanded, known to regulate hippo signalling pathway activity) in human rhabdoid tumour cell lines and AT/RT tumour samples. These results demonstrate that fly models can be employed for the identification of clinically relevant pathways in human cancer.

The prognostic value of pimonidazole and tumour pO2 in human cervix carcinomas after radiation therapy: A prospective international multi-center study

International Nuclear Information System (INIS)

Nordsmark, Marianne; Loncaster, Julie; Aquino-Parsons, Christina; Chou, S.-C.; Gebski, Val; West, Catharine; Lindegaard, Jacob C.; Havsteen, Hanne; Davidson, Susan E.; Hunter, Robin; Raleigh, James A.; Overgaard, Jens

2006-01-01

Background and purpose: Hypoxia adversely affects treatment outcome in human uterine cervical cancer. Here, we present the results of a prospective international multi-centre study evaluating the prognostic value of pre-treatment tumour oxygen partial pressure (pO 2 ) and the hypoxia marker pimonidazole (pimo). Materials and methods: One hundred and twenty-seven patients with primary cervix cancer were entered. Pre-treatment tumour pO 2 measurements were obtained, and reported by the median tumour pO 2 , the fraction of pO 2 values ≤10 mmHg (HP 1 ), ≤5 mmHg (HP 5 ) and ≤2.5 mmHg (HP 2.5 ). Following intravenous pimonidazole administration, biopsies were taken, stained for pimonidazole adducts, and scored for the area of labelled tumour cells on a scale from 0 to 4. Treatment modalities were surgery (11%), radiotherapy (98%), chemotherapy (33%) and carbogen (14%). Results: None of the hypoxia descriptors were statistically significant prognostic factors for loco-regional tumour control or overall survival when analyzed as continuous variables or divided by the sample median. By univariate analysis only tumour size and nodal status were significant prognostic factors for local control. Tumour size and FIGO stage were significant for overall survival. In a multivariate analysis stratified by centre, only tumour size above 5 cm and lower pre-treatment haemoglobin predicted poorer overall survival among FIGO stage, nodal involvement, tumour size, pre-treatment haemoglobin dichotomized at 12 g/dl and pimo 1, pimo 4 and HP 5 as continuous variables. Conclusion: Neither Eppendorf nor pimonidazole should be dismissed based on the current results. However, further investigations are needed to readdress the hypotheses of the current study having optimized statistical designs, and a population of sufficient size treated more homogenously following rigorous protocols

A biophysical approach to the optimisation of dendritic-tumour cell electrofusion

International Nuclear Information System (INIS)

Sukhorukov, Vladimir L.; Reuss, Randolph; Endter, Joerg M.; Fehrmann, Steffen; Katsen-Globa, Alisa; Gessner, Petra; Steinbach, Andrea; Mueller, Kilian J.; Karpas, Abraham; Zimmermann, Ulrich; Zimmermann, Heiko

2006-01-01

Electrofusion of tumour and dendritic cells (DCs) is a promising approach for production of DC-based anti-tumour vaccines. Although human DCs are well characterised immunologically, little is known about their biophysical properties, including dielectric and osmotic parameters, both of which are essential for the development of efficient electrofusion protocols. In the present study, human DCs from the peripheral blood along with a tumour cell line used as a model fusion partner were examined by means of time-resolved cell volumetry and electrorotation. Based on the biophysical cell data, the electrofusion protocol could be rapidly optimised with respect to the sugar composition of the fusion medium, duration of hypotonic treatment, frequency range for stable cell alignment, and field strengths of breakdown pulses triggering membrane fusion. The hypotonic electrofusion consistently gave a tumour-DC hybrid rate of up to 19%, as determined by counting dually labelled fluorescent hybrids in a microscope. This fusion rate is nearly twice as high as that usually reported in the literature for isotonic media. The experimental findings and biophysical approach presented here are generally useful for the development of efficient electrofusion protocols, especially for rare and valuable human cells

[Non-autoimmune thyroiditis].

Science.gov (United States)

Rizzo, Leonardo F L; Mana, Daniela L; Bruno, Oscar D

2014-01-01

The term thyroiditis comprises a group of thyroid diseases characterized by the presence of inflammation, including autoimmune and non-autoimmune entities. It may manifest as an acute illness with severe thyroid pain (subacute thyroiditis and infectious thyroiditis), and conditions in which the inflammation is not clinically evident evolving without pain and presenting primarily thyroid dysfunction and/or goiter (drug-induced thyroiditis and Riedel thyroiditis). The aim of this review is to provide an updated approach on non-autoimmune thyroiditis and its clinical, diagnostic and therapeutic aspects.

Thyroid autoimmunity

NARCIS (Netherlands)

Wiersinga, Wilmar M.

2014-01-01

Autoimmune thyroid disease (AITD) is a multifactorial disease in which autoimmunity against thyroid antigens develops against a particular genetic background facilitated by exposure to environmental factors. Immunogenicity of the major thyroid antigens thyroid peroxidase, thyroglobulin (TG) and

Abnormal number cell division of human thyroid anaplastic carcinoma cell line, SW 1736

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Keiichi Ikeda

2015-12-01

Full Text Available Cell division, during which a mother cell usually divides into two daughter cells during one cell cycle, is the most important physiological event of cell biology. We observed one-to-four cell division during imaging of live SW1736 human thyroid anaplastic carcinoma cells transfected with a plasmid expressing the hybrid protein of green fluorescent protein and histone 2B (plasmid eGFP-H2B. Analysis of the images revealed a mother cell divided into four daughter cells. And one of the abnormally divided daughter cells subsequently formed a dinucleate cell.

Low tumour cell content in a lung tumour bank: implications for molecular characterisation.

Science.gov (United States)

Goh, Felicia; Duhig, Edwina E; Clarke, Belinda E; McCaul, Elizabeth; Passmore, Linda; Courtney, Deborah; Windsor, Morgan; Naidoo, Rishendren; Franz, Louise; Parsonson, Kylie; Yang, Ian A; Bowman, Rayleen V; Fong, Kwun M

2017-10-01

Lung cancer encompasses multiple malignant epithelial tumour types, each with specific targetable, potentially actionable mutations, such that precision management mandates accurate tumour typing. Molecular characterisation studies require high tumour cell content and low necrosis content, yet lung cancers are frequently a heterogeneous mixture of tumour and stromal cells. We hypothesised that there may be systematic differences in tumour cell content according to histological subtype, and that this may have implications for tumour banks as a resource for comprehensive molecular characterisation studies in lung cancer. To investigate this, we estimated tumour cell and necrosis content of 4267 samples resected from 752 primary lung tumour specimens contributed to a lung tissue bank. We found that banked lung cancer samples had low tumour cell content (33%) generally, although it was higher in carcinoids (77.5%) than other lung cancer subtypes. Tumour cells comprise a variable and often small component of banked resected tumour samples, and are accompanied by stromal reaction, inflammation, fibrosis, and normal structures. This has implications for the adequacy of unselected tumour bank samples for diagnostic and molecular investigations, and further research is needed to determine whether tumour cell content has a significant impact on analytical results in studies using tissue from tumour bank resources. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Thyroid Function Tests

Science.gov (United States)

... Home » Thyroid Function Tests Leer en Español Thyroid Function Tests FUNCTION HOW DOES THE THYROID GLAND FUNCTION? ... Cancer Thyroid Nodules in Children and Adolescents Thyroid Function Tests Resources Thyroid Function Tests Brochure PDF En ...

Painless thyroiditis associated to thyroid carcinoma: role of initial ultrasonography evaluation.

Science.gov (United States)

Valentini, Raisa Bressan; Macedo, Bruno Mussoi de; Izquierdo, Rogério Friedrich; Meyer, Erika Laurini Souza

2016-04-01

Even though it is a rare event, most associations of thyroid carcinoma with subacute thyroiditis described in the literature are related to its granulomatous form (Quervain's thyroiditis). We present a patient with subacute lymphocytic thyroiditis (painless thyroiditis) and papillary thyroid cancer that was first suspected in an initial ultrasound evaluation. A 30-year old female patient who was referred to the emergency room due to hyperthyroidism symptoms was diagnosed with painless thyroiditis established by physical examination and laboratory findings. With the presence of a palpable painless thyroid nodule an ultrasound was prescribed and the images revealed a suspicious thyroid nodule, microcalcification focus in the heterogeneous thyroid parenquima and cervical lymphadenopathy. Fine needle aspiration biopsy was taken from this nodule; cytology was assessed for compatibility with papillary thyroid carcinoma. Postsurgical pathology evaluation showed a multicentric papillary carcinoma and lymphocytic infiltration. Subacute thyroiditis, regardless of type, may produce transitory ultrasound changes that obscure the coexistence of papillary carcinoma. Due to this, initial thyroid ultrasound evaluation should be delayed until clinical recovery. We recommended a thyroid ultrasound exam for initial evaluation of painless thyroiditis, particularly in patients with palpable thyroid nodule. Further cytological examination is recommended in cases presenting with suspect thyroid nodule and/or non-nodular hypoechoic (> 1 cm) or heterogeneous areas with microcalcification focus.

Adenoviral gene transfer of angiostatic ATF-BPTI inhibits tumour growth

International Nuclear Information System (INIS)

Lefesvre, Pierre; Attema, Joline; Bekkum, Dirk van

2002-01-01

The outgrowth of new vessels – angiogenesis – in the tumour mass is considered to be a limiting factor of tumour growth. To inhibit the matrix lysis that is part of the tumour angiogenesis, we employed the chimeric protein mhATF-BPTI, composed of the receptor binding part of the urokinase (ATF) linked to an inhibitor of plasmin (BPTI). For delivery, recombinant adenovirus encoding the transgene of interest was injected intravenously or locally into the tumour. The anti tumour effect of this compound was compared to that of human endostatin and of mhATF alone in two different rat bronchial carcinomas growing either as subcutaneous implants or as metastases. Significant inhibition of the tumour growth and decrease of the number of lung metastasis was achieved when the concentration of mhATF-BPTI at the tumour site was above 400 of ng / g tissue. This concentration could be achieved via production by the liver, only if permissive to the recombinant adenovirus. When the tumour cells could be transduced, local delivery of the vector was enough to obtain a response. In the case of metastasis, the capacity of the lung tissue to concentrate the encoded protein was essential to reach the required therapeutic levels. Further, endostatin or mhATF could not reproduce the effects of mhATF-BPTI, at similar concentrations (mhATF) and even at 10-fold higher concentration (endostatin). The ATF-BPTI was shown to inhibit tumour growth of different rat lung tumours when critical concentration was reached. In these tumour models, endostatin or ATF induce almost no tumour response

Development of a new type thyroid glands dosimeter

International Nuclear Information System (INIS)

He Lihua; Song Yiyang; Chen Qin; Chen Yannan

2000-01-01

A new dosimeter of 125 I in thyroid gland is described. The dosimeter consists of NaI(Tl) detector and intelligent data recorder. Single-chip-microcomputer is used for data handling. The activity of 125 I in thyroid glands of human being is measured directly, rapidly, and accurately. Furthermore, it can calculate and display the intake, committed dose equivalent and committed effective dose equivalent. The measuring range of 125 I in thyroid glands is 10-2 x 10 6 Bq. The dosimeter has been operating continuously for a long time with high stability

Thyroid Disease

Science.gov (United States)

... Institute. (2014). Thyroid Cancer . Bomeli, S.R., LeBeau, S.O., Ferris, R.L. (2010). Evalution of a Thyroid Nodule . ... Institute. (2014). Thyroid Cancer . Bomeli, S.R., LeBeau, S.O., Ferris, R.L. (2010). Evalution of a Thyroid Nodule . ...

Follicular thyroid carcinoma masquerading as subacute thyroiditis diagnosis using ultrasonography and radionuclide thyroid angiography

International Nuclear Information System (INIS)

Prakash, R.; Jayaram, G.

1991-01-01

The rare presentation of a follicular thyroid carcinoma mimicking the clinical and radionuclide features of subacute thyroiditis is described. Granulomatous thyroiditis was initially suspected on the clinical basis. Repeat fine needle aspiration cytology was suggestive of acinar proliferation with hyperfunction. Ultrasonography revealed a solid nodule with a peripheral sonolucent halo. Radionuclide angiography showed intense arterial flow of Tc-99m pertechnetate through the right lobe thyroid enlargement suggestive of malignant thyroid pathology. Surgical excision and histopathological examination revealed a follicular carcinoma involving the right lobe. 31 refs., 4 figs

SPECTRUM OF NEUROENDOCRINE TUMOURS- A TERTIARY CARE CENTRE EXPERIENCE

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Pasupuleti Prathima

2016-11-01

Full Text Available BACKGROUND Neuroendocrine tumours occur at various sites in the human body. They are considered as one of the close differentials for many tumours. Various benign and malignant tumours undergo neuroendocrine differentiation. Its incidence is slightly increasing due to advanced imaging modalities. Although rare, they can be seen in breast, gallbladder and skin. The aim of the study is to study the spectrum of neuroendocrine tumours from various sites, their clinical presentation, histomorphological features with immunohistochemistry and review of literature. MATERIALS AND METHODS This is a retrospective study for a period of 3 years (June 2013-June 2016. Surgical resection specimens were included in the study. Out of the total specimens received, 24 cases were of neuroendocrine tumours. Differential diagnosis of small round cell tumours also was considered and a panel of immunohistochemical markers were included to rule out them. Biopsy specimens were excluded from the study. RESULTS Out of the 24 cases, 18 cases were benign lesions. 6 cases were malignant lesions. Female preponderance was noted. Peak incidence was seen in 20-30 years of age group. CONCLUSION Neuroendocrine tumours can occur anywhere in the body and it should be considered in one of the differential diagnosis. Diagnosis must be accurately made.

Concomitant expression of several peptide receptors in neuroendocrine tumours: molecular basis for in vivo multireceptor tumour targeting

International Nuclear Information System (INIS)

Reubi, Jean Claude; Waser, Beatrice

2003-01-01

Peptide receptors have been found to represent excellent targets for in vivo cancer diagnosis and therapy. Recent in vitro studies have shown that many cancers can overexpress not only one but several peptide receptors concomitantly. One of the challenges for nuclear medicine in this field in the coming decade will be to take advantage of the co-expression of peptide receptors for multireceptor tumour targeting. In vitro receptor studies can reveal which peptide receptor is overexpressed in which tumour and which receptors are co-expressed in an individual tumour; such knowledge is a prerequisite for successful in vivo development. One group of tumours of particular interest in this respect is the neuroendocrine tumours, which have previously been shown often to express peptide receptors. This review summarises our investigations of the concomitant expression of 13 different peptide receptors, in more than 100 neuroendocrine tumours of the human intestine, pancreas and lung, using in vitro receptor autoradiography with subtype-selective ligands. The incidence and density of the somatostatin receptors sst 1 -sst 5 , the VIP receptors VPAC 1 and VPAC 2 , the CCK 1 and CCK 2 receptors, the three bombesin receptor subtypes BB 1 (NMB receptor), BB 2 (GRP receptor) and BB 3 , and GLP-1 receptors were evaluated. While the presence of VPAC 1 and sst 2 was detected in the majority of these neuroendocrine tumours, the other receptors, more differentially expressed, revealed a characteristic receptor pattern in several tumour types. Ileal carcinoids expressed sst 2 and VPAC 1 receptors in virtually all cases and had CCK 1 , CCK 2 , sst 1 or sst 5 in approximately half of the cases; they were the only tumours of this series to express NMB receptors. Insulinomas were characterised by a very high incidence of GLP-1, CCK 2 and VPAC 1 receptors, with the GLP-1 receptors expressed in a particularly high density; they expressed sst 2 in two-thirds and sst 1 in approximately half of

Thyroid disease

Energy Technology Data Exchange (ETDEWEB)

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.

Thyroid disease

International Nuclear Information System (INIS)

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

Bioactive albumin-based carriers for tumour chemotherapy.

Science.gov (United States)

Shahzad, Yasser; Khan, Ikram Ullah; Hussain, Talib; Alamgeer; Serra, Christophe A; Rizvi, Syed A A; Gerber, Minja; du Plessis, Jeanetta

2014-01-01

Proteins are posed as the natural counterpart of the synthetic polymers for the development of drug delivery systems and few of them, have been regarded safe for drug delivery purposes by the United States Food and Drug Administration (FDA). Serum albumin is the most abundant protein in human blood. Interest in the exploration of pharmaceutical applications of albumin-based drug delivery carriers, especially for the delivery of chemotherapeutic agents, has increased in recent years. Albumin has several advantages over synthetic polymers, as it is biocompatible, biodegradable, has low cytotoxicity and has an excellent binding capacity with various drugs. Micro- and nano-carriers not only protect active pharmaceutical ingredients against degradation, but also offer a prolonged release of drugs in a controlled fashion. Since existing tumour chemotherapeutic agents neither target tumour cells, nor are they specific to tumour cells, a slow release of drugs from carriers would be beneficial in targeting carcinogenic cells intracellularly. This article aims at providing an overview of pharmaceutical applications of albumin as a drug delivery carrier in tumour chemotherapy.

p53 in differentiation of thyroid cancer

International Nuclear Information System (INIS)

Seyama, Toshio; Ito, Takashi; Akiyama, Mitoshi; Hayashi, Yuzo; Dohi, Kiyohiko.

1993-01-01

P53 is a tumor suppressor gene with such a recessive nature and is inactivated in many carcinomas. DNA was extracted from 10 primary papillary adenocarcinomas and eight undifferentiated carcinomas of the thyroid, using three 5 μm sliced paraffin segments, and then amplified by PCR. The products were analyzed for mutations in the p53 gene exons 5 to 8 by the direct sequencing method and for allelic deletion by the RFLP method. In five human thyroid carcinomas, DNA was extracted from each tissue and analyzed. Mutations in the p53 gene exons 5 to 8 and p53 gene deletions were not detected in the 10 papillary adenocarcinomas, mutations were detected in seven of eight cases and allelic deletions was detected in three of the five cases examined. In each of the five cases which had both differentiated and undifferentiated tissues in the same tumor, p53 gene mutations were not detected in the differentiated tissues while mutations and gene deletions were detected in the undifferentiated sections. The p53 gene was analyzed using paraffin-embedded tissues by the combined use of the direct sequencing and PCR methods and by the RFLP method. It was found that the progression of human thyroid carcinoma is closely related to the p53 genetic changes. Furthermore, the analysis of differentiated and undifferentiated tissues in the same tumor showed that human undifferentiated thyroid carcinomas develop from differentiated carcinomas. (J.P.N.)

Von Reckling-hausen disease associated to thyroid carcinoma and malignant schwannoma of the chest wall. A case

International Nuclear Information System (INIS)

Diaz P, J.; Tantalean, E.; Guzman, R.; Pomatanta P, J.; Grados M, J.; Vilela, C.

1999-01-01

The multiple neurofibromatosis is an autosomal dominant hereditary disease associated to malignant schwannoma in about 3% of the cases and very rarely to others cancers. The study provides information on the case of a 32 year-old woman who suffers from this disease and presented two synchronous cancers: a papillary carcinoma of thyroid and a malignant schwannoma of the chest wall. The thyroid tumour was managed with hemithyroidectomy, hormonotherapy and radiotherapy, and the lesion of the thoracic wall was treated with local radical resection application of Marlex mesh and rotation of a musculocutaneous flap of the dorsal muscle. A review of the literature on the clinical aspects of this association and the surgical techniques employed to cover the defect of the chest wall is presented. (authors)

Pasteurization of bone for tumour eradication prior to reimplantation – An in vitro & pre-clinical efficacy study

Science.gov (United States)

Kode, Jyoti; Taur, Prasad; Gulia, Ashish; Jambhekar, Nirmala; Agarwal, Manish; Puri, Ajay

2014-01-01

Background & objectives: In current era of limb-salvage therapy, pasteurization of bone sarcomas is receiving growing attention as a potential extracorporeal treatment and cost-effective alternative to allografts and radiation before surgical reimplantation. Detailed in vitro and in vivo pre-clinical study to evaluate efficacy of pasteurization to eradicate malignant cells has not been reported yet. The present study was carried out to assess the efficacy of pasteurization to kill tumour cells both in vitro and in vivo. Methods: Surgically resected specimens of osteosarcomas (n=4) were cut into equal halves and one section was pasteurized by heating at 60°C to 65°C for 40 min. Paired samples before and after pasteurization were studied in vitro for DNA ploidy, evaluation of histological change and elimination of mitotic activity. These tissues were transplanted in immune-deficient NOD-SCID mice to evaluate effect on tumour-generating ability, presence of human nuclei, osteopontin and cytokine/chemokines released in tumour-transplanted mice. Results: Non-pasteurized tumour samples had viable tumour cells which exhibited significant growth in culture, increased proliferative ability and clonogenic potential while respective pasteurized tumour tissues did not grow in culture and did not exhibit clonogenicity. Flow cytometry revealed that propidium iodide positive dead cells increased significantly (Ppasteurization. Seven of 12 non-pasteurized tumour transplanted mice demonstrated tumour-forming ability as against 0 of 12 in pasteurized tumour transplanted mice. Solid tumour xenografts exhibited strong expression of anti-human nuclei and osteopontin by immunohistochemistry as well as secretary human interluekin-6 (IL-6) while pasteurized mice failed to express these markers. Interpretation & conclusions: This study has provided a basis to establish pasteurization as being efficacious in ensuring tumour eradication from resected bone tumour specimens. Pasteurized

Thyroid gland disorder emergencies: thyroid storm and myxedema coma.

Science.gov (United States)

Hampton, Jessica

2013-01-01

Although thyroid dysfunction will develop in more than 12% of the US population during their lifetimes, true thyroid emergencies are rare. Thyroid storm and myxedema coma are endocrine emergencies resulting from thyroid hormone dysregulation, usually coupled with an acute illness as a precipitant. Careful assessment of risk and rapid action, once danger is identified, are essential for limiting morbidity and mortality related to thyroid storm and myxedema coma. This article reviews which patients are at risk, explains thyroid storm and myxedema coma, and describes pharmacological treatment and supportive cares.

Metastatic Follicular Thyroid Carcinoma Secreting Thyroid Hormone and Radioiodine Avid without Stimulation: A Case Report and Literature Review

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Syed A. Abid

2014-01-01

Full Text Available Introduction. This is an extremely rare case of a patient with metastatic follicular thyroid cancer who continued to produce thyroid hormone and was iodine scan positive without stimulation after thyroidectomy and radioiodine (I-131 therapy. Patient Findings. A 76-year-old Caucasian male was diagnosed with metastatic follicular thyroid carcinoma on lung nodule biopsy. Total thyroidectomy was performed and he was ablated with 160 mCi of I-131 after recombinant human thyrotropin (rhTSH stimulation. Whole body scan (WBS after treatment showed uptake in bilateral lungs, right sacrum, and pelvis. The thyroglobulin decreased from 2,063 to 965 four months after treatment but rapidly increased to 2,506 eleven months after I-131. Thyroid stimulating hormone (TSH remained suppressed and free T4 remained elevated after I-131 therapy without thyroid hormone supplementation. He was treated with an additional 209 mCi with WBS findings positive in lung and pelvis. Despite I-131, new metastatic lesions were noted in the left thyroid bed and large destructive lesion to the first cervical vertebrae four months after the second I-131 dose. Conclusions. This case is exceptional because of its rarity and also due to the dissociation between tumor differentiation and aggressiveness. The metastatic lesions continued to secrete thyroid hormone and remained radioiodine avid with rapid progression after I-131 therapy.

Polybrominated diphenyl ethers (PBDEs) and thyroid hormones in cord blood

International Nuclear Information System (INIS)

Ding, Guodong; Yu, Jing; Chen, Limei; Wang, Caifeng; Zhou, Yijun; Hu, Yi; Shi, Rong; Zhang, Yan; Cui, Chang; Gao, Yu; Tian, Ying; Liu, Fang

2017-01-01

Human exposure to polybrominated diphenyl ethers (PBDEs) has been increasing over the last three decades in China and around the world. Animal studies suggest that PBDEs could reduce blood levels of thyroid hormones, but it is unclear whether PBDEs disrupt thyroid function in humans. We used data from a prospective birth cohort of 123 pregnant women who were enrolled between September 2010 and March 2011 in Shandong, China. We measured the concentrations of eight PBDE congeners (n = 106) and five thyroid hormones (n = 107) in cord serum samples. We examined the relationship between prenatal exposure to PBDEs and thyroid function (n = 90). Median concentrations of BDEs 47, 99, 100, and 153 (detection frequencies > 75%) were 3.96, 8.27, 3.31, and 1.89 ng/g lipid, respectively. A 10-fold increase in BDE-99 and Σ 4 PBDEs (the sum of BDEs 47, 99, 100, and 153) concentrations was associated with a 0.41 μg/dL (95% confidence interval [CI]: 0.10 to 0.72) and 0.37 μg/dL (95% CI: 0.06 to 0.68) increase in total thyroxine levels (TT 4 ), respectively. No associations were found between other individual congeners and any of the five thyroid hormones. Our study suggests that prenatal exposure to PBDEs may be associated with higher TT 4 in cord blood. Given the inconsistent findings across existing studies, our results need to be confirmed in additional studies. - Highlights: • Human exposure to PBDEs has been increased over recent decades in China. • PBDEs reduce thyroid hormones in animal studies, but it is unclear in humans. • We examined the relation of PBDE levels with thyroid hormones in cord blood. • Prenatal exposure to PBDEs is associated with higher total thyroxine levels. • The findings may have implications for fetal development. - Exposure to PBDEs is associated with higher total thyroxine levels in cord blood, and the findings may have implications for fetal development.

Aftercare of malignant thyroid growth

International Nuclear Information System (INIS)

Boerner, W.; Reiners, C.

1982-01-01

The 'standard programme of aftercare for patients with malignant thyroid growths' practised in our department comprises the following measures: - Searching for residual tissues and recurrences in the neck/throat region and for metastases by means of physical examination, scintigraphy, x-ray diagnosis and laboratory tests (including determination of tumour markers); - monitoring and treatment of side effects by thyroidectomy (recurrent paresis, parathyroprival tetany); - prevention, detection and treatment of side effects of high-dosed radio-iodine therapy (on salivary glands and bone marrow) or those of cytostatic treatment (on heart muscle and bone marrow); - monitoring substitutive and suppressive treatment with thyroxines; - psychological guidance and genetic counselling. Corresponding to therapeutic approach, the overall aftercare programme is aimed primarily at papillary and follicular carcinoma and C-cell carcinoma. However, aftercare is hardly effective with anaplastic carcinoma owing to its persistently bad prognosis and its 50% survival time of some three months. (orig./MG) [de

Recurrent pregnancy loss in patients with thyroid dysfunction

Directory of Open Access Journals (Sweden)

Debanjali Sarkar

2012-01-01

Full Text Available Purpose of the Review: Thyroid disturbances are common in women during their reproductive years. Thyroid dysfunction interferes with human reproductive physiology, reduces the likelihood of pregnancy and adversely affects pregnancy outcome, thus becoming relevant in the algorithm of reproductive dysfunction. This review highlights the "gap" in knowledge regarding the contribution of thyroid dysfunction in reproduction. Literature Reviewed: Following implantation, the maintenance of the pregnancy is dependent on a multitude of endocrinological events that will eventually aid in the successful growth and development of the fetus. It is estimated that approximately 8-12% of all pregnancy losses are the result of endocrine factors. Autoimmune thyroid disease is present in around 4% of young females and up to 15% are at risk because they are thyroid antibody-positive. There is a strong relationship between thyroid immunity on one hand and infertility, miscarriage, and thyroid disturbances in pregnancy and postpartum, on the other hand. Even minimal hypothyroidism can increase rates of miscarriage and fetal death and may also have adverse effects on later cognitive development of the offspring. Hyperthyroidism during pregnancy may also have adverse consequences. Summary: Pregnant women with subclinical hypothyroidism or thyroid antibodies have an increased risk of complications, especially pre-eclampsia, perinatal mortality, and miscarriage. Universal screening for thyroid hormone abnormalities is not routinely recommended at present, but thyroid function must be examined in female with fetal loss or menstrual disturbances. Practitioners providing health care for women should be alert to thyroid disorders as an underlying etiology for recurrent pregnancy loss.

Burkitts primary thyroid lymphoma coexistence with Hashimoto's thyroiditis

International Nuclear Information System (INIS)

Higuera, A.; Vicente, J.; Lazaro, J. C.

2000-01-01

Th primary thyroid lymphoma is a rare neoplasm, above all in children. We present a case of a child with Burkitt's thyroid lymphoma as the only manifestation of this disease, associated to lymphocytic thyroiditis. Clinically, it initiated as a rapidly growing goiter with compressive symptomatology. The X-ray findings are described: hypoechoic and hypodense multiple nodes that affect the right thyroid lobe and isthmus, with extraglandular extension to the vascular space and to the mediastinum. The differential diagnosis is considered with other more frequent thyroid pathologies in this age group. (Author) 14 refs

Environmental radioiodine in thyroids of grazing animals

International Nuclear Information System (INIS)

Van Middlesworth, L.

1990-01-01

Animal thyroids are excellent indicators of environmental contamination from radioiodine, a fact largely unappreciated before 1954. From continuous monitoring of excised thyroids in Nal well-detectors, we know that high-altitude releases of mixed fission products caused increases of 10 3 to 10 5 times the minimal detectable level of 131 I (3.7 mBq/g) in sheep thyroids from the United States, Europe, Asia, Australia, and New Zealand. Within 6 weeks after high-altitude releases, sheep thyroids from different continents of the same hemisphere contained comparable concentrations of 131 I: more than 10 4 times greater concentrations than cow's milk and 5 x 10 3 times greater concentrations than human thyroids from similar areas. In contrast, during the low-altitude Chernobyl release, average 131 I concentrations in animal thyroids, at distances greater than 1,200 km from Chernobyl, were distributed as the inverse square of the distance from the source. 129 I concentrations measured since 1984 with a germanium well-detector in thyroids of sheep slaughtered in Birmingham, England, ranged from 3 to 50 mBq/g organ weight. Similar quantities of 125 I were present intermittently in thyroids of sheep slaughtered in Birmingham since 1986. The source of the 125 I, which is not a fission product, is not clear. For comparison, deer thyroids from the Savannah River Reservation, USA, contained 10 to 7 x 10 5 mBq 129 I/g. Although this isotope is not a biological hazard, it is a long-lived tracer of fission products

Dual thyroid ectopia

International Nuclear Information System (INIS)

Al-Akeely, Mohammed H.

2003-01-01

Ectopic thyroid gland is a rare embryological fault of thyroid development .Dual ectopic thyroid is more rare and only 8 cases have been reported in the literature. The author presents a case of dual ectopic thyroid in a 16 year old boy with an anterior red neck mass, which is gradually growing in size particularly in last 2 years. The initial diagnosis was thyroglossal duct cyst. Thyroid function test revealed elevated thyroid-stimulating hormone. Ultrasound of the neck did not show thyroid gland in its normal pre tracheal position. Thyroid scan (Technetium 99)revealed the diagnosis of dual thyroid ectopia(lingual and subhyoid). (author)

Nicotinamide and carbogen: relationship between pO2 and radiosensitivity in three tumour lines

International Nuclear Information System (INIS)

Martin, L.M.; Thomas, C.D.; Guichard, M.

1994-01-01

The effects of carbogen breathing, nicotinamide injection and their combination on tumour radiosensitivity were correlated with changes in tumour O 2 tension to determine the relationship between radiosensitivity and measured pO 2 . The radiosensitivity (in vivo-in vitro colony assay) and O 2 tension (computerized pO 2 histograph KIMOC 6650) of two human xenografted tumours (HRT18 and NA11 +) and one murine tumour (EMT6) were measured under similar experimental conditions. (author)

Development of a PBPK model of thiocyanate in rats with an extrapolation to humans: A computational study to quantify the mechanism of action of thiocyanate kinetics in thyroid

International Nuclear Information System (INIS)

Willemin, Marie-Emilie; Lumen, Annie

2016-01-01

Thyroid homeostasis can be disturbed due to thiocyanate exposure from the diet or tobacco smoke. Thiocyanate inhibits both thyroidal uptake of iodide, via the sodium-iodide symporter (NIS), and thyroid hormone (TH) synthesis in the thyroid, via thyroid peroxidase (TPO), but the mode of action of thiocyanate is poorly quantified in the literature. The characterization of the link between intra-thyroidal thiocyanate concentrations and dose of exposure is crucial for assessing the risk of thyroid perturbations due to thiocyanate exposure. We developed a PBPK model for thiocyanate that describes its kinetics in the whole-body up to daily doses of 0.15 mmol/kg, with a mechanistic description of the thyroidal kinetics including NIS, passive diffusion, and TPO. The model was calibrated in a Bayesian framework using published studies in rats. Goodness-of-fit was satisfactory, especially for intra-thyroidal thiocyanate concentrations. Thiocyanate kinetic processes were quantified in vivo, including the metabolic clearance by TPO. The passive diffusion rate was found to be greater than NIS-mediated uptake rate. The model captured the dose-dependent kinetics of thiocyanate after acute and chronic exposures. Model behavior was evaluated using a Morris screening test. The distribution of thiocyanate into the thyroid was found to be determined primarily by the partition coefficient, followed by NIS and passive diffusion; the impact of the latter two mechanisms appears to increase at very low doses. Extrapolation to humans resulted in good predictions of thiocyanate kinetics during chronic exposure. The developed PBPK model can be used in risk assessment to quantify dose-response effects of thiocyanate on TH. - Highlights: • A PBPK model of thiocyanate (SCN − ) was calibrated in rats in a Bayesian framework. • The intra-thyroidal kinetics of thiocyanate including NIS and TPO was modeled. • Passive diffusion rate for SCN − seemed to be greater than the NIS

Development of a PBPK model of thiocyanate in rats with an extrapolation to humans: A computational study to quantify the mechanism of action of thiocyanate kinetics in thyroid

Energy Technology Data Exchange (ETDEWEB)

Willemin, Marie-Emilie; Lumen, Annie, E-mail: Annie.Lumen@fda.hhs.gov

2016-09-15

Thyroid homeostasis can be disturbed due to thiocyanate exposure from the diet or tobacco smoke. Thiocyanate inhibits both thyroidal uptake of iodide, via the sodium-iodide symporter (NIS), and thyroid hormone (TH) synthesis in the thyroid, via thyroid peroxidase (TPO), but the mode of action of thiocyanate is poorly quantified in the literature. The characterization of the link between intra-thyroidal thiocyanate concentrations and dose of exposure is crucial for assessing the risk of thyroid perturbations due to thiocyanate exposure. We developed a PBPK model for thiocyanate that describes its kinetics in the whole-body up to daily doses of 0.15 mmol/kg, with a mechanistic description of the thyroidal kinetics including NIS, passive diffusion, and TPO. The model was calibrated in a Bayesian framework using published studies in rats. Goodness-of-fit was satisfactory, especially for intra-thyroidal thiocyanate concentrations. Thiocyanate kinetic processes were quantified in vivo, including the metabolic clearance by TPO. The passive diffusion rate was found to be greater than NIS-mediated uptake rate. The model captured the dose-dependent kinetics of thiocyanate after acute and chronic exposures. Model behavior was evaluated using a Morris screening test. The distribution of thiocyanate into the thyroid was found to be determined primarily by the partition coefficient, followed by NIS and passive diffusion; the impact of the latter two mechanisms appears to increase at very low doses. Extrapolation to humans resulted in good predictions of thiocyanate kinetics during chronic exposure. The developed PBPK model can be used in risk assessment to quantify dose-response effects of thiocyanate on TH. - Highlights: • A PBPK model of thiocyanate (SCN{sup −}) was calibrated in rats in a Bayesian framework. • The intra-thyroidal kinetics of thiocyanate including NIS and TPO was modeled. • Passive diffusion rate for SCN{sup −} seemed to be greater than the NIS

Fine needle aspiration biopsy of three cases of squamous cell carcinoma presenting as a thyroid mass: cytological findings and differential diagnosis.

Science.gov (United States)

Rosa, M; Toronczyk, K

2012-02-01

Primary squamous cell carcinomas of the thyroid gland are extremely rare, comprising about 1% of thyroid malignancies. Although squamous cell carcinomas are readily identified as such on aspiration cytology in the majority of cases, the differentiation of primary versus metastatic tumour might not always be easy. Herein, we report three cases of squamous cell carcinomas involving the thyroid gland. Fine needle aspiration cytology (FNAC) was performed in three patients with a thyroid mass using standard guidelines. Smears were stained with Diff-Quik and Papanicolaou stains. Two patients were male and one was female, aged 59, 45 and 35 years, respectively. In all three patients a thyroid mass was present. FNAC smears in all cases showed cytological features of squamous cell carcinoma including keratinization and necrosis. After clinical and cytological correlation, one case appeared to be primary, one case metastatic, and in the third case no additional clinical information or biopsy follow-up was available for further characterization. Because primary squamous cell carcinoma of the thyroid is a rare finding, metastatic squamous cell carcinoma should always be excluded first. Metastatic disease usually presents in the setting of widespread malignancy, therefore a dedicated clinical and radiological investigation is necessary in these cases. In both clinical scenarios the patient's prognosis is poor. © 2010 Blackwell Publishing Ltd.

Parasitic thyroid nodule in a patient with Hashimoto's chronic thyroiditis

International Nuclear Information System (INIS)

Santos, Vitorino Modesto dos; Lima, Marcus Aurelho de; Marinho, Euripedes Oliveira; Marinho, Marco Aurelio de Oliveira; Santos, Lister Arruda Modesto dos; Raphael, Cristiane Mendes

2000-01-01

A case of parasitic thyroid nodule is presented. The patient was a non symptomatic 53-year-old white woman, on irregular course of L-thyroxine to treat hypothyroidism due to Hashimoto's thyroiditis. Without a history of thyroid trauma or surgery, she presented a 1.6 x 0.7 x 0.5 cm right pre-laryngeal lymph node-like mass which, on ultrasonography, appeared distinct from the gland. TSH, thyroid peroxidase antibody and thyroglobulin antibody serum levels were elevated and T4-free level was normal. Thyroid and total body 99m Tc isonitrile scintiscan showed a topic thyroid without radionuclide uptake in the nodule. Fine-needle aspiration of the nodule showed epithelial cells with nuclear atypia and oncocitic changes plus intense lymphoid infiltration and germinative center formation, simulating lymph node metastasis of papillary thyroid carcinoma. Conventional biopsy revealed a parasitic thyroid nodule with Hashimoto's chronic thyroiditis. Parasitic thyroid nodule must always be remembered so that unnecessary surgical assessment and undesirable sequels may be avoided. (author)

Impact of lymphocytic thyroiditis on incidence of pathological incidental thyroid carcinoma.

Science.gov (United States)

Farrell, Eric; Heffron, Cynthia; Murphy, Matthew; O'Leary, Gerard; Sheahan, Patrick

2017-01-01

The purpose of this study was to investigate the impact of lymphocytic thyroiditis on incidence of incidental thyroid cancers. We conducted a retrospective review of 713 consecutive patients who underwent thyroidectomies. Incidental thyroid cancer was defined as an unexpected cancer discovered on pathological examination outside the index nodule undergoing preoperative cytology. We excluded 65 cases because of preoperative diagnosis of thyroid cancer, and 68 because of nonincidental cancer within the index nodule. Among the remaining 580 cases, there were 43 cases (7.4%) of incidental thyroid cancers. Incidental thyroid cancers were significantly associated with moderate/severe lymphocytic thyroiditis (relative risk = 2.5; p = .03). Sixteen of 56 patients with moderate/severe lymphocytic thyroiditis had Graves' disease, none of whom had incidental thyroid cancer. The risk of incidental thyroid cancer associated with moderate/severe lymphocytic thyroiditis was significantly higher in non-Graves' than patients with Graves' disease (p = .05). The risk of incidental thyroid cancer is significantly increased in patients with moderate/severe lymphocytic thyroiditis. Moderate/severe lymphocytic thyroiditis associated with Graves' disease seems to have a lower risk of incidental thyroid cancer. © 2016 Wiley Periodicals, Inc. Head Neck 39: 122-127, 2017. © 2016 Wiley Periodicals, Inc.

Flavonoid rutin increases thyroid iodide uptake in rats.

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Carlos Frederico Lima Gonçalves

Full Text Available Thyroid iodide uptake through the sodium-iodide symporter (NIS is not only an essential step for thyroid hormones biosynthesis, but also fundamental for the diagnosis and treatment of different thyroid diseases. However, part of patients with thyroid cancer is refractory to radioiodine therapy, due to reduced ability to uptake iodide, which greatly reduces the chances of survival. Therefore, compounds able to increase thyroid iodide uptake are of great interest. It has been shown that some flavonoids are able to increase iodide uptake and NIS expression in vitro, however, data in vivo are lacking. Flavonoids are polyhydroxyphenolic compounds, found in vegetables present in human diet, and have been shown not only to modulate NIS, but also thyroperoxidase (TPO, the key enzyme in thyroid hormones biosynthesis, besides having antiproliferative effect in thyroid cancer cell lines. Therefore, we aimed to evaluate the effect of some flavonoids on thyroid iodide uptake in Wistar rats in vivo. Among the flavonoids tested, rutin was the only one able to increase thyroid iodide uptake, so we decided to evaluate the effect of this flavonoid on some aspects of thyroid hormones synthesis and metabolism. Rutin led to a slight reduction of serum T4 and T3 without changes in serum thyrotropin (TSH, and significantly increased hypothalamic, pituitary and brown adipose tissue type 2 deiodinase and decreased liver type 1 deiodinase activities. Moreover, rutin treatment increased thyroid iodide uptake probably due to the increment of NIS expression, which might be secondary to increased response to TSH, since TSH receptor expression was increased. Thus, rutin might be useful as an adjuvant in radioiodine therapy, since this flavonoid increased thyroid iodide uptake without greatly affecting thyroid function.

Evaluation of diffuse thyroid diseases and thyroid nodules by CT

International Nuclear Information System (INIS)

Okamoto, Kyoko; Imanishi, Yoshimasa; Nakaji, Shunsuke; Shinagawa, Toshihito

2007-01-01

Imanishi et al. have previously reported that the changes in CT values reveal not only the change in iodine concentration in thyroid follicles, but also represent secondary changes in follicular content and follicular cells and/or interstitial structures. Thus, we performed thyroid CT without contrast material in 138 controls, 417 cases with diffuse thyroid diseases, and 279 cases with thyroid nodules, and evaluated the CT images based on the relation between the change in CT values and pathological changes. In 89% of the controls and 43% of patients with diffuse thyroid diseases, the thyroid CT revealed diffuse high density. In contrast, the 94% of thyroids that demonstrated diffuse low density were from patients with diffuse thyroid diseases. Eighty-four percent of malignant nodules and 64% of benign nodules had inhomogeneous densities, and only 26% of benign thyroid nodules had homogeneous density. However, 71% of nodules that showed high and low densities with regular and clear borders, and 82% of nodules that showed papillary proliferation in a cyst pattern were benign. Although only 58% of nodules with calcification were malignant, 66% of nodules with calcification in the central portion, and 86% of nodules with calcification of a disseminated and convergent pattern in distribution were malignant. Sixty-two percent of thyroids that surrounded nodules had chronic thyroiditis, hypoplasia and/or adenomatous goiter. Thus, unclear borders between a nodule and the surrounding thyroid tissue did not increase the possibility of malignancy. However, the unclear and/or lobulated border between a nodule and extra thyroid tissue increased the possibility of malignancy. We concluded that thyroid CT without contrast material is useful for the diagnosis of thyroid diseases. (author)

Lymphocyte-dependent antibody-mediated cytotoxicity in Hashimoto thyroiditis

Science.gov (United States)

Calder, Elizabeth A.; Penhale, W. J.; McLeman, Dena; Barnes, E. W.; Irvine, W. J.

1973-01-01

In the presence of normal human lymphocytes, decomplemented sera from twentynine out of thirty-nine patients with Hashimoto thyroiditis caused significant lysis of thyroglobulin-coated chicken red blood cells, as estimated by the release of 51Cr; the mean% specific 51Cr release being 14·1 ± 1·9 (SEM). Serum from twenty-one control subjects studied concurrently caused no significant lysis of thyroglobulin-coated chicken red blood cells; the mean% specific 51Cr release being −1·6±0·7 (SEM). The degree of cytotoxicity correlated with the titre of thyroglobulin antibodies in the serum, determined by tanned red cell haemagglutination. The active component in the Hashimoto serum was localized in the 19S fraction, was unaffected by pre-absorption with anti-human IgM serum, but was neutralized by pre-absorption with anti-human IgG serum. These findings suggest that the cytotoxic activity of serum from patients with Hashimoto thyroiditis is due to the presence of thyroglobulin antibody of the IgG class in the form of complexes, either alone or with antigen. It is postulated that non-specific lymphocytes may play an important role in the pathogenesis of Hashimoto thyroiditis, being activated by the presence in the gland of thyroglobulin antibody, either alone or in the form of complexes attached to thyroid cells. PMID:4740445

Gastric Calcifying Fibrous Tumour

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Tan Attila

2006-01-01

Full Text Available Intramucosal gastric tumours are most commonly found to be gastrointestinal stromal tumours or leiomyomas (smooth muscle tumours; however, a variety of other uncommon mesenchymal tumours can occur in the stomach wall. A rare benign calcifying fibrous tumour is reported and the endoscopic appearance, ultrasound findings and morphology are documented. A review of the literature found only two similar cases.

p53 constrains progression to anaplastic thyroid carcinoma in a Braf-mutant mouse model of papillary thyroid cancer

Science.gov (United States)

McFadden, David G.; Vernon, Amanda; Santiago, Philip M.; Martinez-McFaline, Raul; Bhutkar, Arjun; Crowley, Denise M.; McMahon, Martin; Sadow, Peter M.; Jacks, Tyler

2014-01-01

Anaplastic thyroid carcinoma (ATC) has among the worst prognoses of any solid malignancy. The low incidence of the disease has in part precluded systematic clinical trials and tissue collection, and there has been little progress in developing effective therapies. v-raf murine sarcoma viral oncogene homolog B (BRAF) and tumor protein p53 (TP53) mutations cooccur in a high proportion of ATCs, particularly those associated with a precursor papillary thyroid carcinoma (PTC). To develop an adult-onset model of BRAF-mutant ATC, we generated a thyroid-specific CreER transgenic mouse. We used a Cre-regulated BrafV600E mouse and a conditional Trp53 allelic series to demonstrate that p53 constrains progression from PTC to ATC. Gene expression and immunohistochemical analyses of murine tumors identified the cardinal features of human ATC including loss of differentiation, local invasion, distant metastasis, and rapid lethality. We used small-animal ultrasound imaging to monitor autochthonous tumors and showed that treatment with the selective BRAF inhibitor PLX4720 improved survival but did not lead to tumor regression or suppress signaling through the MAPK pathway. The combination of PLX4720 and the mapk/Erk kinase (MEK) inhibitor PD0325901 more completely suppressed MAPK pathway activation in mouse and human ATC cell lines and improved the structural response and survival of ATC-bearing animals. This model expands the limited repertoire of autochthonous models of clinically aggressive thyroid cancer, and these data suggest that small-molecule MAPK pathway inhibitors hold clinical promise in the treatment of advanced thyroid carcinoma. PMID:24711431