Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Murine experimental autoimmune thyroiditis (EAT) is a T-cell-mediated disease, but the T cell receptor (TCR) Vbeta gene usage in pathogenesis has not been well delineated. One approach is to utilize bacterial superantigens, such as staphylococcal enterotoxin (SE) A and B, to stimulate known sets of TCR Vbeta families in mouse thyroglobulin (mTg)-primed cells for thyroiditis transfer. Our previous use of SEB to activate mTg-primed cells led to no thyroiditis transfer, despite a major increase in Vbeta8(+) T cells. Unlike SEB, SEA activation did transfer thyroiditis. To determine which thyroiditogenic Vbeta(+) T cells were involved, SEA-activated T cells have now been analyzed. After repeated SEA activation in vitro, both mTg-reactive and thyroiditogenic cells persisted. FACS analysis indicated that most Vbeta13(+) cells were "large" cells (IL-2R(+)) and expressed the activation marker, transferrin receptor (CD71). RT-PCR analysis also showed the presence of both Vbeta13(+) and SEA-reactive Vbeta1(+) cells. Since our previous analyses by RT-PCR of the thyroid infiltrate after either induction or adoptive transfer have implicated both Vbeta13(+) and Vbeta1(+) cells, their activation by SEA to transfer thyroiditis further supports their role.
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PMID:Participation of Vbeta13(+) and Vbeta1(+) T cells in transfer thyroiditis after activation of mouse thyroglobulin-primed T cells by superantigen staphylococcal enterotoxin A. 1183 77

From collagenase digests of human thyroid, endothelial cells were separated from follicular cells by their greater adherence to gelatin-coated plates. Endothelial cells were further purified using fluorescence-activated cell sorting, selecting for cells expressing factor VIII-related antigen. Isolated cells were negative for thyroglobulin and calcitonin when examined by immunostaining. The receptor for the angiopoietins, Tie-2, was expressed by the cells, and expression was increased by agents that elevate cAMP. Nitric oxide synthase (NOS) 3, the endothelial form of NOS, was expressed by the cells and similarly regulated. Cells responded strongly to the mitogen fibroblast growth factor (FGF)-2 in growth assays but only weakly to vascular endothelial growth factor (VEGF). VEGF was, however, able to stimulate nitric oxide release from the cells consistent with their endothelial origin. The FGF receptor (FGFR1) was full length (120 kDa) and immunolocalized to the cytosol and nucleus. Thyrotropin (TSH) did not regulate FGFR1, but its expression was increased by VEGF. Thrombospondin, a product of follicular cells, was a growth inhibitor, but neither TSH nor 3,5,3'-triiodothyronine had direct mitogenic effects. Thyroid follicular cell conditioned medium contained plasminogen activator activity and stimulated the growth of the endothelial cells, but when treated with plasminogen to produce the endothelial-specific inhibitor, angiostatin, growth was inhibited. Human thyroid endothelial cell cultures will be invaluable in determining the cross talk between endothelial and follicular cells during goitrogenesis.
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PMID:Isolation and characterization of human thyroid endothelial cells. 1962 78

In the literature, sufficient attention has not been paid to the precise subcellular localization of immunohistochemical signals, the knowledge of which is essential for proper interpretation of immunostains and distinction of genuine staining from biotin-associated or other nonspecific stainings. The subcellular localization of the signals can in fact be easily deduced from the known biologic or ultrastructural characteristics of the antigens. Extracellular antigens obviously are located in the extracellular compartment. Cellular antigens fall into 3 major groups: membranous, nuclear, and cytoplasmic. Membranous antigens include cell adhesion molecules (such as E-cadherin, N-CAM), cell surface/transmembrane receptors and proteins (such as tyrosine kinase receptors, most leukocyte antigens, CD10, CEA), and molecules linking surface molecules to cytoskeleton (such as beta-catenin, dystrophin). Nuclear antigens include cell cycle-associated proteins (such as cyclins, p16, Ki-67), nuclear enzymes (such as TdT), transcription factors (such as TTF-1, CDX-2, myogenin, PAX-5), tumor suppressor gene products (such as p53, p63, WT1, Rb), steroid hormone receptors (such as ER, PR), calcium-binding proteins (such as S-100 protein, calretinin), and some viral proteins (such as CMV, herpes). Cytoplasmic antigens can take up a granular pattern due to localization in organelles, granules, or secretory vesicles (such as chromogranin, hormones, lysozyme, HMB-45), fibrillary pattern attributable to the filamentous nature of the molecules (intermediate filaments and microfilaments), or diffuse or patchy pattern due to localization in the cytosol or large vesicles (such as myoglobin, albumin, thyroglobulin). Aberrant localization of the molecules, when present, can provide important insight into disease processes and aid in their diagnosis, such as loss of membranous E-cadherin expression in lobular breast carcinoma, aberrant nuclear localization of beta-catenin in colorectal adenocarcinoma, pattern of ALK staining in anaplastic large cell lymphoma correlating with the different types of chromosomal translocations, presence of additional cytoplasmic CD10 staining in the enterocytes indicative of microvillous inclusion disease, and "reversed" staining for EMA in micropapillary mammary carcinoma.
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PMID:Subcellular localization of immunohistochemical signals: knowledge of the ultrastructural or biologic features of the antigens helps predict the signal localization and proper interpretation of immunostains. 1530 32

Rhabdoid tumor of the thyroid gland is a very rare neoplasm, characterized by significant metastatic potential. All of the 6 cases reported in the recent literature had poor outcomes. We report an additional case involving, to our knowledge, the oldest patient reported so far. A 67-year-old woman had a nodular goiter for all of her adult life and presented with a rapidly growing mass in the right lobe. Histologic examination showed a highly cellular neoplasm with a solid infiltrative growth pattern. Extracapsular invasion was evident. Rhabdoid cells were large, with abundant cytoplasm, eosinophilic inclusions, and eccentric nuclei containing distinct nucleoli. Immunohistochemistry identified vimentin, sarcomeric actin, myoglobin, and cytokeratin expression in the tumor cells; they were negative for desmin, thyroglobulin, and calcitonin. Scattered follicles with nuclear features of papillary thyroid carcinoma were detected; these cells were immunoreactive for thyroglobulin and TTF-1. Reverse transcriptase polymerase chain reaction using specific primers for RET/PTC1 and RET/PTC3 fusion genes identified a RET/PTC3 gene rearrangement in the rhabdoid tumor. Despite radiotherapy, the neoplasm rapidly progressed, with massive local and mediastinal metastasis leading to death 5 months after presentation. The hypothesis that rhabdoid tumor is a variant of anaplastic thyroid carcinoma is supported by the identification of a RET/PTC gene rearrangement, a feature of carcinomas of follicular cell derivation.
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PMID:Rhabdoid tumor of the thyroid gland: a variant of anaplastic carcinoma. 1573 50

Among thyroid carcinomas, thyroglobulin is a good tumor marker for differentiated carcinoma (papillary carcinoma, follicular carcinoma). In particular, it is widely used for monitoring of patients with total or near-total thyroidectomy. On the other hand, medullary thyroid caricima has a very sensitive and specific tumor marker, calcitonin. In inherited medullary carcinoma (multiple endocrine neoplasia type 2), RET protooncogene analysis is the best for detecting early medullary thyroid carcinoma.
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PMID:[Thyroid carcinoma]. 1585 29

Struma ovarii (SO) is usually asymptomatic and only in a few cases it is associated with thyrotoxicosis. The presurgical diagnosis is very uncommon. In the majority of cases a pelvic mass is discovered at physical examination or by abdominal ultrasound. Only the hystopathologic examination is able to reveal the characteristic features of SO, with thyroid cells organized in follicles as the main tumoral tissue constituent. The histologic recognition of malignancy is not easy and usually requires an exhaustive sampling of the lesion to evaluate the extracapsular invasion. We report the case of a 59-year-old woman who came to our observation for the fortuitous finding of elevated serum thyroglobulin (Tg) levels (600-800 ng/mL). Because the thyroid function was normal and the ultrasound showed only a subcentrimetric nodule, the clinical suspicious of a SO was considered. Ultrasound examination of the abdomen showed a solid mass of 2 cm in the left ovary. A (131)I uptake was observed at scintiscan in the site of the solid mass. Three months after the resection of the left ovary serum Tg levels were markedly reduced (106 ng/mL), and its values continued to decrease down to 34 ng/mL at last control. The histology showed that the ovarian mass was mainly constituted of thyroid tissue (98%), with no malignant features. The molecular analysis of several thyroid differentiation gene mRNAs in the SO tissue showed an abundant expression of all genes but pendrin (PDS). A reduced PDS mRNA expression might explain the defective thyroxine (T(4)) production. Despite the absence of malignant features, the expression of RET/PTC3 rearrangement was found, raising the possibility of a potential malignant nature of the tumor. A cancer-free period of 3-4 years, as in our patient, is not long enough to definitively exclude a late onset metastatic disease but, unfortunately, the patient died of nonmedical reasons. In conclusion, we report a case of SO that, to our knowledge, is the first in which the clinical suspicion arose from the inappropriately elevated presurgical serum levels of Tg. A quite exhaustive molecular analysis of thyroid specific genes and oncogenes provided two interesting findings: the low PDS mRNA expression, which may explain the low hormonal production and the absence of thyrotoxicosis and the presence of a RET/PTC3 rearrangement, which prompts the possibility of a late malignant evolution.
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PMID:RET/PTC3 rearrangement and thyroid differentiation gene analysis in a struma ovarii fortuitously revealed by elevated serum thyroglobulin concentration. 1640 8

We report the characteristics of three cell lines (designated, SNU-80, SNU-373 and SNU-790), which were established from two papillary carcinomas and one anaplastic carcinoma obtained from three Korean thyroid carcinoma patients. All cell lines grow as adherent cells. Electron microscopy characteristically showed cytoplasmic invaginations of nuclei and intranuclear cytoplasmic inclusions. SNU-80 and SNU-790 cells showed a positive reaction to anti-cytokeratin antibody, and SNU-790 cells positivity for CK-19. All lines were free of mycoplasma or bacteria and were proven unique by DNA fingerprinting analysis. The p15 and p16 genes are deleted in the SNU-790 line. Mutations of the p53 gene were found in two lines (SNU-80 and SNU-373), but no mutations in the RET or MEN1 genes were observed. Mutations of the BRAF gene were found in the SNU-80 (G468R) and the SNU-790 (V599E) cell lines, but no mutations in the K-ras gene were present. SNU-80 and SNU-790 cells showed a positive reaction to anti-cytokeratin antibody, and no evidence of the production of thyroglobulin or calcitonin was observed. The cell lines were unable to trap radioactive iodine but did not contain TSH receptor. In addition, we investigated the mRNA expression levels of Tg, TSHR, TTF-1, PAX-8, NIS, IL-6, and LIF, and of the alpha, beta and gamma retinoic acid receptors in these cell lines. IL-6 was down-regulated in all three cell lines by all-trans-retinoic acid treatment. RAR-alpha was expressed but RAR-beta was not expressed in the three cell lines, and RAR-gamma was not expressed in SNU-790. Interestingly, RAR-beta (SNU-80 and SNU-373) and RAR-gamma (SNU-790) was up-regulated by all-trans-retinoic acid treatment. We believe that these well-characterized thyroid carcinoma cell lines may be useful tools for investigations on the biological characteristics of thyroid carcinoma, particularly for investigations related to gene alterations, especially of the BRAF gene. These cell lines may also be useful for redifferentiation therapy studies on thyroid carcinoma using all-trans-retinoic acid.
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PMID:Establishment and characterization of cell lines from three human thyroid carcinomas: responses to all-trans-retinoic acid and mutations in the BRAF gene. 1713 24

A series of biochemical parameters are useful for the diagnosis and follow-up of differentiated thyroid carcinomas. The measurement of serum thyroglobulin (Tg) is considered for the post-surgical/radioiodine follow-up of papillary/follicular carcinomas. Other than in basal conditions, the importance of Tg levels during TSH stimulation is underlined, either by discontinuation of L-T4 therapy or by recombinant human TSH test. The finding of undetectable Tg levels during TSH stimulation is highly correlated with clinical remission; otherwise, peak Tg levels > 1-2 ng/ml can be suggestive of recurrence/persistence of the disease. The accuracy of Tg measurements for the detection of metastases seems to be higher when compared to 131-1 whole-body scan. The evaluation of basal serum calcitonin levels is recommended for the screening of medullary thyroid carcinoma (MTC). High basal levels suggest the presence of a tumor but a calcitonin increase can be observed also in parafollicular C cell hyperplasia (CCH) and other extra-thyroidal conditions. The pentagastrin test can by pass this obstacle as the calcitonin response seems to be typical of pathological thyroid C cells. The cut-off value of calcitonin response between patients with MTC and CCH remains to be established; the latter condition, however, being considered by some authors as pre-cancerous. After thyroid surgery the measurement of calcitonin constitutes a valid tool for the detection of cure and/or recurrence of the disease. The screening by means of RET oncogene analysis is also described for patients with MTC with Multiple Endocrine Neoplasia (MEN) type 2 syndrome.
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PMID:[Useful and limits of the biochemical markers for the diagnosis of thyroid carcinoma]. 1713 35

Thyroid cancer is the most common endocrine malignancy. Most patients with thyroid cancer have a great chance for successful treating. There is, however, a group of patients with poor prognosis. The present researches of thyroid tumor markers have related to permanent diagnostic progress of circulating markers analysis (thyroglobulin, thyroid peroxidase, calcitonin and carcinoembryonic antigen), cellular markers determination and interpretation of results, also. A number of molecular markers have been studied. Diagnostic value of some of them, e.g. TSHR, RET Ras, is well known. Others have investigated continually. Overexpression of BRAF, Met, and p53 has been correlated with aggressiveness of the cancer. Markers said to be of prognostic value in thyroid cancer are CD82, c- myc and Plk-1. The combination of markers: galectin-3, fibronectin and HBME-1 have proven to be sensitive for differentiated thyroid cancer. Further studies on new cellular thyroid markers are essential. The current review presents data concerning the well known cellular markers in thyroid cancer.
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PMID:[Cellular tumor markers in thyroid cancer]. 1768 30

Approximately 10% of thyroid cancers are present in patients less than 21 years of age, representing 3% of all cancers of children and adolescents, with predominance in females 2:1 in relation to males. Thyroid cancers in this age group are usually papillary (90%), bilateral, multifocal and bigger in size compared to adults. Capsule invasion and lymphatic and pulmonary metastases are more frequent in children. Radiation sensitivity seems to represent an important factor in prepubertal patients. Familial history is reported in 5% of the cases. Genes such as RET/PTC, RAS and BRAF are usually involved in thyroid carcinogenesis in this age group. Cervical adenomegaly is a common clinical presentation, but does not represent a poor prognostic factor in children. Ultrasound and fine needle aspiration biopsy are valuable diagnostic procedures. Surgery is the preferred treatment including thyroidectomy and ganglionary excision, followed by ablative radioiodine therapy. L-thyroxine replacement with suppressive dosage should be employed targeting chronic TSH suppression. Long-term prognosis is usually better in children when compared with adults. Plasma thyroglobulin measurement is also useful to detect residual thyroid cancer disease.
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PMID:[Thyroid carcinoma in children and adolescents]. 1789 Dec 39


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