Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endocrine factors involved in the transcriptional regulation of the oxytocin (OT) gene were investigated in heterologous expression systems. Plasmids having a 5'-flanking region of the rat OT gene (-363/+16) or the human OT gene (-382/+41) cloned in front of the firefly luciferase gene were co-transfected with an expression vector for the rat thyroid hormone receptor alpha in P19 embryonal carcinoma (EC) cells. Thyroid hormone (T3) stimulated the activity of the rat and human OT promoters about 10-fold. In MCF-7 breast tumor cells transfected with the human OT promoter-luciferase fusion gene, T3 stimulation through endogenous thyroid hormone receptors was about 5-fold. Co-transfection experiments in P19EC cells using 5' deletion mutants of the rat OT gene showed that thyroid hormone responsiveness was located in two regions, one located between nucleotides -195 and -172, the other between nucleotides -172 and -148. Each region accounted for about 3-fold T3 stimulation. Gel retardation analysis using extracts from HeLa cells over-producing the c-erbA/TR alpha protein showed specific binding to the -172/-148 element, while no binding occurred on the -195/-172 element. The -172/-148 element which contains the imperfect estrogen response element, GGTGACCTTGACC, has inverted as well as direct repeats of the TGACC motif. Mutagenesis of TGACC motifs separately reduced thyroid hormone responsiveness by about 50%. However, simultaneous mutation of two TGACC motifs abolished the responsiveness to T3 completely. There was no cooperativity between the activated thyroid hormone and estrogen receptors in transfected MCF-7 cells nor in thyroid hormone receptor and estrogen receptor co-transfected P19EC cells. Negative interactions between these two receptors were observed and gel retardation assays showed interaction between the two receptors proteins. It was shown in an in vivo experiment that treatment of rats with thyroid hormone increased hypothalamic OT mRNA levels, the pituitary OT content, as well as OT levels in blood. The results reveal thyroid hormone as a physiological regulator of OT gene expression, which stimulates OT promoter activity directly through interaction with a thyroid hormone-response element in the OT gene.
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PMID:Thyroid hormone regulates the oxytocin gene. 137 Dec 78

A unique characteristics of thyrotrope-specific gene expression is the coordinated expression and regulation of the alpha- and beta-subunits of TSH. A cell line (alpha TSH) derived from the transplantable mouse thyrotropic tumor MGH101A, which no longer expresses the TSH beta-subunit gene but continues to secrete large amounts of alpha-subunit, was used as a model to study alpha-subunit gene expression independent from the TSH beta-subunit gene and was compared with the expression in TSH-secreting TtT97 tumors. Transient transfection studies showed a striking similarity in the activity of 5' deletions of the mouse alpha-subunit gene promoter in both alpha TSH and TtT97 cells and localized two regions important for expression that spanned 100 base pairs, from -480 to -417 and from -417 to -381. These regions were found to have no activity in nonthyrotrope pituitary GH4 cells and L-cell fibroblasts. Analysis of the alpha-subunit 5' flanking DNA interactions with alpha TSH and TtT97 nuclear extracts showed two DNase I protected sequences, from -474 to -452 and from -447 to -400, both of which colocalized with the functionally important regions. Gel retardation analysis demonstrated the specificity of these interactions, and a similar migration of the DNA-protein complexes suggested that protein factors were similar in the two cell types. We conclude that the nuclear factors necessary for alpha-subunit expression in thyrotropes are retained in alpha TSH cells. Moreover, since alpha TSH cells do not express the TSH beta-subunit gene, the factors that determine the expression of the alpha-subunit may not be sufficient for TSH beta-subunit gene expression.
Thyroid 1992
PMID:A cell line that produces the glycoprotein hormone alpha-subunit contains specific nuclear factors similar to those present in thyrotropes. 138 77

The nuclear DNA contents of 50 thyroid tumors were measured paraffin block samples and needle biopsies by using microscopic photometry, and the diagnostic value of this measurement was examined. Thyroid tumors included 17 papillary carcinomas, 15 follicular carcinomas and 18 benign tumors. The results confirmed the possibility of discriminating between benign and malignant tumors except in cases of follicular carcinoma with minimal invasion. This method seemed to be most valuable in the diagnosis of cases with class III FNA. A review was made of the relation between DNA content and prognostic factors, for example the degree of invasiveness of the thyroid tumor, intra-tracheal invasion, intra-thyroid metastasis and lymphatic metastasis. DNA content was increased only in cases with intra-tracheal invasion.
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PMID:[Nuclear DNA pattern of thyroid tumor]. 140 17

We retrospectively reviewed the medical records of 65 consecutive patients with medullary thyroid carcinoma, who had had their primary surgical treatment at the Mayo Clinic during the years 1946 through 1970. Of these patients, 58 had sporadic and 7 had familial medullary thyroid carcinoma. Thyroid nodules were the most common initial manifestation. Near-total thyroidectomy was the most frequent initial operation. Survival was affected by the following factors: male sex, familial inheritance, size of the tumor, stage of the tumor (American Joint Committee on Cancer), and completeness of initial resection of the tumor. The mean duration of follow-up was 23.5 years, and the maximal follow-up was 36 years. Among 52 patients without initial distant metastatic involvement and with complete resection of the tumor, 20-year survival free of distant metastatic lesions was 81%. Overall 10- and 20-year survival rates were 63% and 44%, respectively. Because of the substantial morbidity and mortality associated with medullary thyroid carcinoma, early diagnosis and thorough initial resection of the tumor are important.
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PMID:Medullary thyroid carcinoma: clinicopathologic features and long-term follow-up of 65 patients treated during 1946 through 1970. 143 53

The National Toxicology Program data base on 343 mouse and rat carcinogenesis studies was reviewed to determine the frequency of and relationship between hyperplastic and neoplastic follicular lesions of the thyroid gland. The frequency of chemically related lesions in the thyroid was also compared to neoplastic lesions in the liver to investigate a possible correlation. The percentage of studies observed to have positive or equivocal chemically related thyroid proliferative lesions was rats: male, 14%, female, 11%; mice; male, 8%; female, 9%. When positive in one sex for a given chemical, there was a 60-80% chance of it being positive in the other sex of the same species, although interspecies correlation was not as strong. Thyroid follicular cell neoplasia without hyperplasia was uncommon in mice but was common in rats. Chemicals that caused thyroid proliferative changes were more likely (P less than 0.05) to produce liver neoplasms (both within and between species) than were chemicals causing no thyroid changes. However, this correlation was far from perfect, with many chemicals producing thyroid proliferative lesions, but not liver neoplasms and vice versa. This suggests that universal correlations are not supportable by the data and that individual chemicals should be evaluated on a case-by-case basis.
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PMID:Thyroid follicular cell carcinogenesis: results from 343 2-year carcinogenicity studies conducted by the NCI/NTP. 143 97

A 58-year-old male patient was admitted to the hospital complaining of weight loss. Abdominal computerized tomographic (CT) scan disclosed a mass shadow in the left kidney. From the results of further examination, including drip infusion pyelography (DIP) and angiography, he was preoperatively diagnosed as having a left renal tumor. Left radical nephrectomy was performed on March 15, 1990. The lesion was histologically diagnosed as renal cell carcinoma (clear cell subtype, grade 2) confined by the renal capsule (stage I). No distant metastases were detected. Interferon-alpha was administered every other day as adjuvant chemotherapy. After the patient experienced muscle pain in his thighs and shoulders after exercise on February 11, 1991, the serum creatine phosphokinase (CPK) level progressively increased up to 2,329 U/l. On the basis of the results of various examinations reflecting thyroid gland function, he was diagnosed as having primary hypothyroidism due to Hashimoto's disease. Thyroid function improved after administration of triiodothyronine and thyroxine. Interferon has been reported to influence thyroid function, and, in this case, interferon-alpha therapy may have induced the primary hypothyroidism associated with Hashimoto's disease.
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PMID:[Hypothyroidism followed by interferon-alpha as adjuvant therapy of renal cell carcinoma: a case report]. 148 77

Our aim was to determine whether fucosylation of glycoproteins begins in the rough endoplasmic reticulum (RER) of active thyrotrophs. This would contrast with most cells studied, in which fucosylation generally is associated with the Golgi apparatus. Mouse thyrotropic tumor tissue was incubated with [35S]methionine for 2, 5, 7, 10, 30, and 90 minutes. TSH and free alpha-subunits were immunoprecipitated from cell lysates, and they displayed a time-dependent increase in affinity for lentil lectin (which binds oligosaccharides having core fucose), even at short times. Since no 20-30 minute lag in onset of TSH- and free alpha-subunit-lentil binding was appreciated, as might have been expected had fucosylation begun only in the Golgi, it appeared that fucosylation was beginning in the RER of thyrotrophs. Pituitary tissue from euthyroid and hypothyroid mice was incubated with [3H]fucose, then subjected to electron microscopic autoradiography. The pituitaries of hypothyroid mice had numerous "thyroidectomy cells," which had 40% of silver grains over dilated cisternae of RER. "Nonthyroidectomy" cells had few silver grains over RER; most were over secretory granules and Golgi areas. Thus, active mouse thyrotrophs appear to shift the subcellular site of fucosylation partially from Golgi to RER, and this phenomenon may represent one cellular mechanism whereby the endocrine regulation of the structure of TSH oligosaccharides is accomplished.
Thyroid 1992
PMID:Fucosylation of glycoproteins begins in the rough endoplasmic reticulum of mouse active thyrotrophs. 149 77

In 14 patients with occult persisting medullary thyroid carcinoma, tumor tissue was removed by microsurgical reoperation in 13 of 14 patients. This resulted in biochemical improvement in all but 1 patient and biochemical cure in 3 patients (21%). The lateral compartment of the neck or the upper mediastinum was involved in all but 1 patient. Before microsurgical reoperation, selective venous catheterization (SVC) for serum sampling along with serum calcitonin (CT) determination was done and compared to other localization methods. Tumor tissue could be localized correctly by SVC in 89% (CT gradient 1.21-2.02), computed tomography in 38%, and ultrasound in 28%. In patients with an elevated CT level after initial surgery and clinically occult disease, SVC is recommended for localization of tumor tissue. The affected side of the neck should be reoperated on with microdissection of the central and lateral compartment of the neck and the upper mediastinum. With this procedure, the cure rate of reoperation in patients with persistent occult MTC can be improved.
Thyroid 1992
PMID:Localization of occult persisting medullary thyroid carcinoma before microsurgical reoperation: high sensitivity of selective venous catheterization. 152 78

Various drugs and hormones influence the light microscopic and especially the electron microscopic structure of the anterior pituitary and its tumors. Many structural effects are known only from animal experiments since specimens from human pituitaries are mostly not available. The structure of growth hormone (GH) cells is relatively stable. A massive GH cell hyperplasia is known only in rare cases with growth hormone releasing factor (GRF) excess from tumors. Prolactin cells can be stimulated by drugs, neurotransmitters, and hormones which decrease the dopamine inhibition. Adrenocorticotropic hormone (ACTH) cells are stimulated by stress, some hormones, loss of adrenals, and drugs which activate the alpha 1- and beta-receptors or inhibit the alpha 2-receptors. They are suppressed and changed into Crooke's cells by treatment with glucocorticoids. Thyroid-stimulating hormone (TSH) cells increase in number and size in states for overstimulation especially by thyrotropin releasing hormone (TRH). A decrease results from hyperthyroidism and possibly from somatostatin, L-dopa, and dopamine. Gonadotroph cells transform into castration cells in strongly hyperactive states (gonadectomy, antiandrogens, gonadotropin releasing hormone [Gn-RH]agonists, aminoglutethimide). Special types of pituitary adenomas can be treated with drugs which suppress hormone production and proliferation. Dopamine agonists and somatostatin reduce the tumor size of varying proportions of GH secreting adenomas in acromegaly. Ultrastructurally, a decrease of cytoplasmic and nuclear volume and an increase of lysosomes are found. Bromocriptine and other dopamine agonists are established in the treatment of prolactin secreting adenomas. They induce a shrinkage in many cases. Ultrastructurally, a reduction of cellular and nuclear size, an increase in number of secretory granules and of lysosomes, and a reduction of rough endoplasmic reticulum can be demonstrated.
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PMID:Effect of drugs on pituitary ultrastructure. 154 57

A 59-year-old man with metastatic renal cell carcinoma developed symptomatic thyroid dysfunction following interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) therapy. Thyroid evaluation prior to this therapy revealed evidence of subclinical Hashimoto's thyroiditis. Symptomatic thyrotoxicosis, including atrial fibrillation, developed after the initial two courses of intermittent intravenous bolus therapy with human recombinant IL-2 and IFN-alpha. At 4 weeks after initiation of immunotherapy, the thyroid antimicrosomal antibody (AMA) titer rose from 1:6,400 to 1:25,600; thyroid-stimulating immunoglobulin was negative. A technetium 99m-pertechnetate thyroid scan obtained while the patient was thyrotoxic showed diminished uptake in a symmetrically enlarged gland. The patient was temporarily treated with propranolol, digoxin, and quinidine. The atrial fibrillation quickly resolved, and thyrotoxicosis abated over the following 5 weeks, while the AMA titer rose further to 1:102,400. By 11 weeks after initiation of immunotherapy, hypothyroidism developed and persisted through two subsequent courses of cytokine therapy at Weeks 16 and 18. The tumor metastases partially responded to the immunotherapy. The patient has remained hypothyroid up to 27 weeks of follow-up. This case history suggests that IL-2 and IFN-alpha therapy may precipitate a fulminant autoimmune thyroiditis syndrome in a vulnerable patient with preexisting autoimmune thyroid disease.
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PMID:Transient thyrotoxicosis and persistent hypothyroidism due to acute autoimmune thyroiditis after interleukin-2 and interferon-alpha therapy for metastatic carcinoma: a case report. 155 92


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