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)

To continue our studies on the influence of T3 on TSH regulation in the Walker 256 carcinoma-bearing rat model of nonthyroidal disease, we measured the effect of T3 on pituitary content of beta TSH mRNA and rat (r) TSH in hypothyroid control (C) and tumor-bearing (T) rats. The effect of T3 on TSH regulation was compared to effects on GH mRNA and rGH in the same animals. mRNA content was normalized to a pool of pituitaries from euthyroid rats (= 1.0). beta TSH mRNA increased 18-fold in both hypothyroid C and T rats and then decreased similarly with increasing T3 infusion to a value of 0.1. GH mRNA content decreased to 0.11 +/- 0.01 in hypothyroid C rats, but to only 0.38 +/- 0.02 in T rats (P less than 0.001). The pituitary contents of GH mRNA and rGH in hypothyroid T rats was significantly greater than those in C rats at all T3 infusion rates. These data together with our previous report of decreased nuclear T3 in T rats suggest that regulation of beta TSH mRNA by T3 is intact in T rats, but occurs at a lower concentration of nuclear T3. In contrast, the GH mRNA response is enhanced, displaying differential regulation of these two T3-responsive gene products in this model of nonthyroidal illness.
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PMID:Differential response to L-triiodothyronine of anterior pituitary growth hormone messenger ribonucleic acid (mRNA) and beta-thyrotropin mRNA in a hypothyroid Walker 256 carcinoma-bearing rat model of nonthyroidal disease. 229 8

Clinical and radioimmunoassay investigations performed in 162 patients with different thyroid diseases, have shown that changes in the levels of T3, T4 and TSH do not allow assessment of the nature of a tumor process. The level of calcitonin is a tumor marker of medullary carcinoma and C-cell thyroid adenomas. In the absence of pathological changes in the thyroid an increase in the level of thyroglobulin can be regarded as a tumor marker of metastatic growth of papillary and papillary-follicular cancer.
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PMID:[The differential diagnosis of thyroid cancer using radioimmunologic analysis]. 231 97

The long-acting somatostatin analogue SMS 201-995 has been used efficaciously in the therapy of metastatic carcinoid tumor, vasoactive intestinal peptide producing islet cell carcinoma, acromegaly, and TSH secreting pituitary tumors. We report the development of a gallstone in a patient treated for 23 months with a long acting somatostatin analogue for a metastatic carcinoid tumor. Symptomatic improvement and a reduction in the urinary excretion of 5-hydroxyindoleacetic acid occurred. There was no evidence of a gallstone on ultrasound and CT scan of the abdomen prior to somatostatin therapy. A progressively enlarging, asymptomatic gallstone developed during therapy.
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PMID:Chronic treatment with a long-acting somatostatin analogue in a patient with intestinal carcinoid tumor: occurrence of cholelithiasis. 231 10

Fifty-four clinically euthyroid patients were evaluated 1 up to 17 yr after external irradiation to the neck for Hodgkin's disease. T4 level was decreased in 6%, while basal TSH level was increased in 44%, and TSH response to TRH was increased in 66% of the patients with normal basal TSH level. Thyroid iodine content (TIC), measured in 50 patients, was below 5 mg in 18. The 29 patients with normal basal TSH level had a mean TIC (6.8 +/- 2.7 mg) significantly lower (p less than 0.01) than the control population (14.6 +/- 5 mg). A significant positive correlation was found between log T4 and log TIC (r = 0.55, p less than 0.01). Thyroglobulin (Tg) level was increased in 53% of the patients with no palpable thyroid abnormality. It was not related to TSH level but was related to younger age at irradiation. T4 treatment decreased Tg level to the normal range in 5 of 8 patients. These facts suggest subclinical thyroid abnormalities and patients with elevated Tg levels should be considered at risk for developing a thyroid tumor.
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PMID:Thyroid iodine content and serum thyroglobulin level following external irradiation to the neck for Hodgkin's disease. 236 55

In a surgical series of 277 consecutive patients operated on the thyroid for benign diseases, a high prevalence rate (10.5%) of occult papillary carcinoma was found by means of an accurate histologic examination. Indications for surgery were euthyroid multinodular goiter in 25 patients, autonomously hyperfunctioning adenoma in 2 and Graves' disease in 2 patients. Neoplastic foci were unilaterally found in 25 cases but multifocally in 6 and bilaterally in 4 cases: the diameters ranged from 2-10 mm. After operation (14 subtotal and 15 total thyroidectomies), all patients received TSH-suppressive doses of T4. At a mean follow-up of 5.6 years, neither local recurrences nor lymph node or distant metastases had occurred; no patient died of the tumor. In keeping with other surgical and autopsy series, the prevalence of occult thyroid carcinoma in a normal population is calculated to be about 5-10%, whereas it is known that the prevalence of clinically evident thyroid cancer is only 0.05%. This means that only 1-2% of occult carcinomas may evolve in an overt tumor during life. In view of such an epidemiologic difference and the favorable course of our patients, although the mean follow-up is rather short, we suggest that lobectomy plus T4 treatment may be considered an adequate therapeutic approach in patients with occult papillary thyroid carcinoma.
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PMID:High prevalence of occult papillary thyroid carcinoma in a surgical series for benign thyroid disease. 236 70

The activity of T4 5'-monodeiodinase (5'D) in the pituitary was measured in 12 patients with pituitary adenoma (3 patients with acromegaly, 2 with prolactinoma, 1 with Cushing's disease, 1 with TSH-producing tumor, and 5 with nonfunctioning tumor) and, as a control, in a patient who died of parotid cancer. The pituitaries, obtained at operation or autopsy, were homogenized in 0.1 mol/L potassium phosphate buffer, pH 7.0, and centrifuged at 800 x g. Supernatants were incubated with [125I]T4 and 20 mmol/L dithiothreitol (DTT) at 37C for 90 min. T4 5'-D was measured by the release of 125I- with the ion exchange method. The activity of T4 5'-D in the pituitaries from patients with prolactinoma and parotid cancer was dependent on protein concentration, incubation time, incubation temperature, and T4 concentration, and was labile to prior heating at 70 C for 30 min. T4 5'-D was not inhibited by 1 mmol/L propylthiouracil, but was inhibited 95% by 0.1 mmol/L iopanoic acid. The apparent Km and maximum velocity for T4 5'-D in homogenates of prolactinoma at 20 mmol/L DTT were 11 nmol/L and 1.54 pmol/mg protein.h, respectively. This reaction followed sequential-type reaction kinetics when the DTT concentration was varied. All other homogenates of pituitary tumors, except two nonfunctioning tumors, also demonstrated T4 5'-D activity. These results indicate that 1) the human pituitary express a low Km and PTU-insensitive T4 5'-D activity which is very similar to the type II enzyme activity in the rat pituitary; and 2) various types of pituitary tumor cells contain T4 5'-D activity.
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PMID:Thyroxine 5'-deiodinase in human anterior pituitary tumors. 238 Mar 33

Dedifferentiation of human thyroid tumors is frequently found in humans. The effect of retinoids (13 cis-RA) was studied on the proliferation and differentiation of a human follicular cell line in vitro (UCLA R0 82 W-1). A significant and dose-dependent reduction (P less than 0.001) in cell number and [3H] thymidine uptake was found in cells exposed to 13 cis-RA up to 10 microM. Higher concentrations of 13 cis-RA, however, led to a dose-dependent restoration of cell proliferation. Various parameters of differentiation increased under the influence of 13 cis-RA (10 microM) over nonexposed cells. The 125I uptake increased 4-fold over that in control nonexposed cells (P less than 0.05). [125I] Epidermal growth factor binding increased 5-fold, and [125I] human TSH binding increased significantly after exposure to 13 cis-RA (P less than 0.02). Deiodinase activity, however, was significantly lower in 13 cis-RA exposed cells than in control cells. The present study shows that 13 cis-RA (10 microM) drives the tumor cells toward a more normal state of proliferation and differentiation.
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PMID:Effects of 13 cis-retinoic acid on growth and differentiation of human follicular carcinoma cells (UCLA R0 82 W-1) in vitro. 239 77

Glycoprotein-secreting pituitary tumors are uncommon. With increased awareness that pituitary tumors may secrete FSH, LH, TSH, and the alpha-subunit, either as a sole product or in any combination, these tumors are more likely to be recognized. The standard therapy is surgical resection and, possibly, postoperative radiotherapy for residual tumor mass or persistent hormonal secretion. We report a patient with a FSH- and alpha-subunit-secreting tumor who refused surgery and was treated with the dopamine agonist bromocriptine as primary therapy. Bromocriptine treatment resulted in reduction of serum FSH and alpha-subunit levels to normal, improvement of visual field defects, and improvement in hypogonadism despite lack of demonstrable change in tumor size, as assessed by computed tomographic scan. Chromatographic analysis of the serum revealed distinct peaks corresponding to those of labeled FSH and alpha-subunit. The clinical and biochemical responses in this patient suggest that some glycoprotein-secreting tumors may be responsive to dopamine agonist therapy.
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PMID:Follicle-stimulating hormone- and alpha-subunit-secreting pituitary tumor treated with bromocriptine. 241 Apr 44

We have recently documented the spontaneous development of a mouse pituitary tumor line (MGH 101A) secreting only the alpha-subunit of the glycoprotein hormones. Secretion of alpha-subunit by MGH 101A was not inhibited by either physiological or pharmacological levels of thyroid hormones. The present study demonstrates that combined treatment with bromocriptine and pharmacological doses of T4 for 1 month significantly decreased both tumor growth and alpha-subunit secretion of MGH 101A in thyroidectomized host mice. Either treatment alone was ineffective. The fall in plasma alpha-subunit concentrations after the combined treatment was probably due to the inhibition of tumor growth, since the decreases in plasma alpha-subunit levels and tumor weights were quantitatively similar, and there was no significant change in tumor steady state concentrations of alpha-subunit mRNA. In two of three experiments, the combined treatment resulted in a significant fall in tumor total DNA concentrations; this suggests that decreased tumor growth was at least in part due to inhibition of tumor cell replication. To compare the effects of the various treatments on the pure alpha-subunit-producing pituitary tumor with their effects on non-tumorous pituitary, we also measured secretion of TSH and PRL into plasma by the host pituitary. Treatment with T4 alone profoundly suppressed plasma concentrations of TSH and significantly reduced plasma PRL levels compared to levels in the thyroidectomized controls. Surprisingly, both thyroidectomized and euthyroid tumor hosts treated with bromocriptine alone showed no suppression of plasma PRL levels. However, combined treatment with bromocriptine and pharmacological doses of T4 resulted in plasma PRL concentrations significantly lower than those after treatment with T4 alone. Thus, the tumor and nontumorous host pituitaries differed in their responses to T4 alone. However, the two tissues were similar in their responses to bromocriptine alone and to combined treatment with bromocriptine and T4. We conclude that combined treatment with T4 and bromocriptine inhibited the growth and secretion of the pure alpha-subunit-secreting tumor MGH 101A. The data on PRL secretion by the host pituitary suggest that T4 may have acted by enhancing the function of dopamine receptors.
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PMID:Pure alpha-subunit-secreting mouse pituitary tumor: inhibition of growth and secretion by combined treatment with thyroxine and bromocriptine. 241 27

We have investigated the relationship between T3 nuclear receptor occupancy and the T3-mediated responses of TSH subunit gene expression. Hypothyroid mice bearing TtT 97 thyrotropic tumors were injected daily for 12 days with 0-10 micrograms T3/100 g BW, ip. T3 levels were measured in plasma and in tumor nuclei, and the maximal T3-binding capacity of tumor nuclei and the fractional occupancy of T3 nuclear receptors at each dose were calculated. T3-mediated decreases in TSH secretion were half-maximal at a dose of 0.2-0.3 micrograms/100 g BW, which resulted in plasma T3 levels of 0.98-1.2 ng/ml. Responses at the TSH subunit gene levels followed a similar pattern. Transcription of TSH beta and alpha-subunit genes was decreased maximally from 384 to 26 ppm for TSH beta and from 424 to 112 ppm for alpha-subunit. Inhibition of transcription was half-maximal at plasma T3 concentrations of 0.8 and 1.0 ng/ml for TSH beta and alpha-subunit, respectively. The half-maximal effective doses of T3 for decreases in TSH gene transcription were in good agreement with the amount of T3 necessary to saturate 50% of nuclear T3 receptors in the tumor, calculated at 1.07 ng/ml T3. A plot of fractional decrease in TSH subunit gene transcription vs. fractional T3 nuclear receptor occupancy demonstrated a straight line relationship for both TSH beta and alpha-subunit. Thus, the response of both TSH subunit genes to T3, a decrease in TSH beta and alpha-subunit gene transcription, is directly proportional to nuclear T3 receptor occupancy.
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PMID:Triiodothyronine (T3) regulation of thyrotropin subunit gene transcription is proportional to T3 nuclear receptor occupancy. 241 54


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