Biomedical subjects

Q Y Duh

Publications and source records attributed to Q Y Duh.

At least 73 records · Page 4Linked to original sources

PubMed1997

Vascular endothelial growth factor expression is higher in differentiated thyroid cancer than in normal or benign thyroid.

Vascular endothelial growth factor (VEGF) is an angiogenic factor, and its expression has been rarely demonstrated in thyroid tumors. We, therefore, investigated the expression of VEGF messenger RNA (mRNA) and production of VEGF protein in cell lines from human primary and metastatic follicular (FTC-133, FTC-236, and FTC-238), papillary (TPC-1), Hürthle cell (XTC-1), and medullary thyroid cancers (MTC-1.1 and MTC-2.2), and in human thyroid tissues (papillary, follicular, medullary, and Hürthle cell cancers, follicular adenomas, and Graves' thyroid tissue) by Northern blot, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA) studies. All thyroid cell lines expressed a 4.2-kilobase VEGF mRNA. The VEGF mRNA levels were higher in the thyroid cancer cell lines than in primary cultures of normal thyroid cells, and higher in thyroid cancers of follicular than those of parafollicular cell origin. The VEGF mRNA levels were similar in primary and metastatic thyroid tumors. Immunohistochemical staining and Northern blot analysis of the cell lines correlated positively, thus thyroid cancer cell lines stained more intensely than normal thyroid cells and follicular tumor cells more intensely than parafollicular tumor cells. Again, no difference was noted in VEGF staining between primary and metastatic thyroid tumors. Deparafinized sections of papillary, follicular, and Hürthle cell cancers also stained much stronger than those of medullary thyroid cancers, benign, or hyperplastic (Graves' disease) thyroid tissue. Thyroid cancer cell lines (XTC-1 > TPC-1 > FTC-133 > MTC-1.1) also secreted more VEGF protein as measured by ELISA than did normal thyroid cells. VEGF secretion of cell lines derived from primary and metastatic thyroid tumors were similar. VEGF mRNA is therefore expressed, and VEGF protein is secreted by normal, hyperplastic, and neoplastic thyroid tissues. The higher levels of VEGF expression in differentiated thyroid cancers of follicular cell origin suggests a role in oncogenesis.

Adenocarcinoma↗

PubMed1996

Tamoxifen antagonizes proliferation and invasion of estrogen receptor-negative metastatic follicular thyroid cancer cells via protein kinase C.

Tamoxifen inhibits invasion and growth of estrogen-receptor negative follicular thyroid cancer (FTC) cells in vitro and in vivo. To study the mechanisms involved, we documented the effects of tamoxifen and staurosporine on three metastatic FTC-cell lines. TPA (10 ng/ml) enhanced invasion and growth of FTC by 15% (P < 0.02). Tamoxifen (1.5 micromol/l) inhibited invasion of FTC133 by 36% (FTC236 30%; FTC238 32%; P < 0.01). TPA reversed the tamoxifen-mediated inhibition of invasion by 35% in FTC133 and 30% in FTC238 (P < 0.02). Staurosporine (10 ng/ml) inhibited invasion and growth of all FTC. At 0.1-1 ng/ml it enhanced the inhibitory effects of tamoxifen, but did not further inhibit invasion or growth at higher concentrations. We conclude that the antiproliferative and antiinvasive effects of tamoxifen on follicular thyroid cancer cells are at least partly mediated by an inhibition of protein kinase C.

Alkaloids↗

PubMed1996

Reoperation for persistent or recurrent primary hyperparathyroidism.

OBJECTIVE: To analyze the causes and outcomes of reoperation for persistent or recurrent primary hyperparathyroidism. DATA SOURCES: Medical records of 102 patients with persistent or recurrent primary hyperparathyroidism who underwent reoperation by 1 surgeon between 1985 and 1995. STUDY SELECTION: Only patients with persistent or recurrent primary hyperparathyroidism were selected; patients with secondary hyperparathyroidism, parathyroid cancer, familial hyperparathyroidism, and previous thyroid operations were omitted. DATA EXTRACTION: Performed by a single unblinded researcher. DATA SYNTHESIS: Reasons for failed parathyroid operations included tumor in ectopic position (53%), incomplete resection of multiple abnormal glands (37%), adenoma in normal position missed during previous surgery (7%), and regrowth of previously resected tumor (3%). Of the ectopic glands, 28% were paraesophageal, 26% in the mediastinum (nonthymic), 24% intrathymic, 11% intrathyroidal, 9% in the carotid sheath, and 2% in a high cervical position. Eighty-three percent of ectopic glands were accessible via cervical incision. The success rate of reoperations was 95%. One patient (1%) became permanently hypocalcemic after reoperation; 1 patient (1%) suffered permanent unilateral vocal cord paralysis. The sensitivities of preoperative localization studies were as follows: technetium Tc 99m sestamibi scan, 77%; magnetic resonance imaging, 77%; selective venous catheterization for intact parathyroid hormone, 77%; thallium-technetium scan, 68%; ultrasonography, 57%; and computed tomography, 42%. CONCLUSIONS: Repeated parathyroidectomy can be avoided in more than 95% of patients if an experienced surgeon performs bilateral cervical exploration during the initial parathyroid operation. For patients with persistent or recurrent primary hyperparathyroidism, preoperative localization studies and a focused surgical approach can result in a 95% success rate with minimum complications.

Adult↗

PubMed1996

Laparoscopic adrenalectomy. Comparison of the lateral and posterior approaches.

OBJECTIVE: To compare the lateral transabdominal and posterior retroperitoneal laparoscopic methods for performing adrenalectomy. DESIGN: Nonrandomized. SETTING: Hospitals affiliated with the University of California, San Francisco. PATIENTS: Thirty-six patients (15 men and 21 women), aged 5 to 78 years (mean age, 49 years), were treated for the following conditions: aldosteronoma, 18 patients; pheochromocytoma, 4 patients; Cushing syndrome, 6 patients; androgen-secreting tumor, 1 patient; nonfunctioning adenoma, 3 patients; adrenal hemorrhage, 1 patient; metastatic neoplasm, 2 patients; and myelolipoma, 1 patient. INTERVENTIONS: Twenty-three lateral and 14 posterior laparoscopic adrenalectomies. MAIN OUTCOME MEASURES: Success rate, operating time, complications, and length of hospital stay. RESULTS: The tumors, which ranged in size from 1 to 13 cm (mean, 4.2 cm; median, 2.5 cm), were all successfully resected laparoscopically. All 8 tumors larger than 6 cm were resected by the lateral approach. One critically ill patient died. No patient required blood transfusions or conversion to laparotomy. Mean operating time was 3.8 hours vs 3.4 hours (median, 3.5 hours vs 3 hours) and mean hospital stay was 2.2 days vs 1.5 days (median, 2 days vs 1 day) for the lateral and posterior approaches, respectively. All patients without concomitant procedures were ready to be discharged within 48 hours. CONCLUSIONS: Both approaches were effective and safe. We prefer the lateral approach for tumors larger than 6 cm and the posterior approach for bilateral tumors.

Adolescent↗

PubMed1996

Desensitization of cyclic adenosine 3,5'-monophosphate response to thyrotropin in normal and primary or metastatic papillary thyroid cancer cells in vitro.

BACKGROUND: Desensitization is an important physiologic process resulting in a decreased functional response after continuous or repeated stimulation. Prior exposure of normal human thyroid tissue to thyrotropin either in vivo or in vitro causes desensitization of adenylate cyclase. Little is known, however, about whether the thyrotropin-adenylate cyclase-cyclic adenosine 3,5'-monophosphate (cAMP) signal transduction system desensitizes in human thyroid carcinomas. Failure to desensitize could result in increased growth or metastases. METHODS: Cell cultures from Chinese hamster ovary (CHO) cells transfected with normal human thyrotropin receptor (hTSHr) and thyroid neoplasms including one papillary carcinoma and one papillary lymph node metastases were evaluated for desensitization. CHO cells were stably transfected with plasmid DNA containing hTSHr. Cells were incubated with thyrotropin (10 mU/ml) for different periods (1 to 24 hours). A second incubation (30 minutes) was done with and without thyrotropin in medium including 3-isobutyl-1-methylxanthine (1 mmol/L). Intracellular cAMP accumulation was determined by means of radioimmunoassay. RESULTS: Maximal stimulation and desensitization to thyrotropin were observed at 30 minutes and 4 hours, respectively. The cAMP response to a second incubation with thyrotropin was 52% and 48% lower than the initial response to thyrotropin in CHO-hTSHr and papillary thyroid cancer cells, respectively (p < 0.001). A papillary carcinoma lymph node metastases had an increased basal cAMP level and also an increased cAMP level in response to thyrotropin stimulation (227%) but failed to desensitize (p < 0.001). CONCLUSIONS: Desensitization of the cAMP response to thyrotropin occurred in a papillary thyroid cancer but not in a metastatic thyroid cancer. Failure to desensitize might play a role in tumor progression.

Animals↗

PubMed1996

Thyroid-stimulating hormone promotes the secretion of vascular endothelial growth factor in thyroid cancer cell lines.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a vascular endothelial cell-specific mitogen secreted by some cancer cells and is a major regulator of angiogenesis. Because thyroid-stimulating hormone (TSH) promotes growth and progression of thyroid cancers, we postulated that TSH may increase the production and secretion of VEGF by thyroid cancer cells. METHODS: We examined primary cultures of normal human thyroid (NT 1.0), medullary thyroid cancer (MTC 1.1), and cell lines derived from the papillary (TPC-1), follicular (FTC-133), and Hürthle cell (XTC-1) thyroid cancer. We quantified the concentration of VEGF in conditioned medium by means of enzyme-linked immunosorbent assay. RESULTS: Cell lines derived from thyroid secrete VEGF. Basal VEGF secretion was similar in normal and thyroid cancer cells, except XTC-1, which has high basal secretion (p < 0.01). All thyroid cancer cells secrete significantly more VEGF than normal thyroid cells after TSH (10 mIU/ml) stimulation (p < 0.05). TSH stimulated secretion of VEGF in FTC-133 (8.2 ng/dl versus 18.8 ng/dl), TPC-1 (5.5 ng/dl versus 26.9 ng/dl), and MTC 1.1 (5.9 ng/dl versus 13.4 ng/dl) cell lines (p < 0.01), but not in NT 1.0 (8.4 ng/dl versus 9.9 ng/dl) and XTC-1 (25.4 ng/dl versus 31.2 ng/dl) cells. CONCLUSIONS: These results suggest that VEGF secretion is constitutively activated in some thyroid cancers and that VEGF secretion is stimulated by TSH; thus TSH may promote growth in some thyroid cancers by stimulating VEGF secretion and angiogenesis.

Endothelial Growth Factors↗

PubMed1996

The regulation of proliferation and invasion in differentiated thyroid cancer by growth factors.

Invasion and metastasis are the primary cause of death in patients with follicular thyroid cancer (FTC). The thyroid is a micro-economic system in which proliferation and differentiation was supposed to be under the major control of only a single hormone (thyroid stimulating hormone-TSH). It has shown, however, that a complex network of various growth factors regulates growth and invasion of thyroid cancer cells. A growing literature has established the close association between malignant tumor progression and growth regulatory aberrations in cancer cells. Most of these studies have focused on the phenomenon, that advanced and more aggressive tumors or metastases lost the sensitivity to growth inhibitors, such as transforming growth factor beta. These findings highlight two aberrations of growth regulation which may favour progression of malignant disease and acquisition of metastatic competence: (1) Resistance to growth factor inhibitors and (2) growth autonomy of metastatic follicular thyroid cancer cells.

Adenoma↗

PubMed1996

Immunocytochemical detection of p53 in human thyroid carcinomas is associated with mutation and immortalization of cell lines.

Mutations in the tumor suppressor gene p53 are the most-common mutations found in human cancers. In thyroid cancers, p53 mutations generally are found only in poorly differentiated and undifferentiated tumors and in cell lines. To determine the prevalence of p53 mutations in thyroid neoplasms and thyroid cell lines, we screened 58 thyroid tissues and 3 thyroid cell lines, p53 primers bracketing exons 4, 5/6, 7, and 8 were used to amplify genomic DNA using the PCR. Mutations were screened by denaturing gradient gel electrophoresis and confirmed by sequencing. The two papillary thyroid cancer cell lines and the follicular thyroid carcinoma cell line (positive control) had transitions (CGT->CAT) in exon 8, codon 273, resulting in the replacement of arginine with histidine. No normal thyroid tissues or primary tumors from which the cell lines were derived demonstrated exon 8 mutations, using this technique. p53 immunocytochemistry demonstrated a progression of p53 immunopositivity between synchronous and metachronous neoplasms, paralleling the neoplastic progression from a benign adenoma to primary carcinoma, regional, and distant metastasis and ultimately, the cell lines, where intense immunopositivity is noted. In addition, fluorescence in situ hybridization, using probes specific for the p53 locus, revealed the presence of 3 homologues of p53 in the follicular cell line and 2 homologues in the papillary and Hürthle cell lines. These results suggest that a point mutation present in a small number of original tumor cells and amplification of the mutant allele may be responsible for immortalizing well-differentiated thyroid cancer cells into cell lines.

Adenocarcinoma, Follicular↗

PubMed1996

Somatostatin analog octreotide inhibits the growth of differentiated thyroid cancer cells in vitro, but not in vivo.

Somatostatin and its analogs are antiproliferative in a wide range of normal and neoplastic tissues. In this study we investigated the effect of octreotide (SMS 201-995) on the invasion and growth of three follicular thyroid cancer (FTC) cell lines from one patient in vitro and in vivo. FTC133 was established from the primary tumor, FTC236 from a cervical lymph node metastasis, and FTC238 from a lung metastasis. Invasion was the ability of tumor cells to penetrate 8-microns pore polycarbonate membranes coated with Matrigel. Invasion and proliferation were analyzed using the MTT assay. For in vivo experiments, athymic nude mice were sc inoculated with 500,000 calls of FTC133. The animals were treated twice daily with octreotide sc (100-300 micrograms/kg). RIA studies yielded dose-dependent high plasma levels of octreotide (3.43-6.5 ng/mL). Octreotide had a biphasic effect, enhancing growth at low concentrations (1-10 nmol/mL) and inhibiting it at high concentrations (100 nmol to 1 mumol/mL). Octreotide had also a dose-dependent biphasic effect on the invasion of FTC, inhibiting the invasion of all follicular thyroid cancer lines at high concentrations. However, it affected invasion less than growth. Octreotide (10 nmol/mL) stimulated the invasion of FTC133 by 13%, whereas stimulation was lower in both FTC metastases (FTC236, 6%; FTC238, 7%; P < 0.01). At higher concentrations (100 nmol to 1 mumol/mL), octreotide inhibited invasion of FTC133 by 17% (FTC236, 15%; FTC238, 17%; P < 0.01). During a 3-week treatment period, octreotide had no antiproliferative effect on the growth of FTC133 cells in nude mice. In conclusion, octreotide at low concentrations stimulates and at high concentrations inhibits the growth and invasion of follicular thyroid cancer cells in culture. However, it has no effect on the growth of FTC cells in animal experiments. Thus, the value of octreotide as an antitumoral agent in follicular thyroid cancer must be critically questioned.

Animals↗

PubMed1995

The laminin alpha 1 chain Ile-Lys-Val-Ala-Val (IKVAV)-containing peptide promotes liver colonization by human colon cancer cells.

Laminin, a major basement membrane-specific glycoprotein, promotes the attachment, migration, and invasion of a variety of tumor cells. Since laminin is present in the perisinusoidal matrix of the liver, we studied its effects on liver colonization by human colon cancer cells (HM7, LiM6) previously shown to have liver-metastasizing ability in athymic mice. These malignant cells expressed high levels of a 32-kDa laminin-binding protein on Western blot analysis when compared to the low metastatic parental cell line. Coinjection of laminin alpha chain-derived peptides which contain the amino acid sequence Ile-Lys-Val-Ala-Val (IKVAV) significantly stimulated liver colonization as determined by liver weight (P < 0.005) and number of tumor nodules (P < 0.02) 3 weeks after splenic-portal inoculation into nude mice. No stimulation was seen with a control peptide containing the same amino acids but in a scrambled sequence. In contrast, the Tyr-Ile-Gly-Ser-Arg peptide from the laminin beta 1 chain significantly inhibited HM7 liver colonization. These differences were not due to alterations in the number of cells initially reaching the liver as determined by injection of [125I]iododeoxyuridine-labeled tumor cells, but retention in the liver was stimulated by the IKVAV-containing peptides. Flow analysis indicated that the IKVAV peptide may act, in part, by stimulating homotypic adhesion of tumor cells. These data suggest that interactions of colon cancer cells with the IKVAV site on laminin may play a role in the formation of metastatic foci in the liver through cell-cell or cell-substratum interactions which promote metastasis.

Adenocarcinoma↗

PubMed1995

Familial nonmedullary thyroid cancer. An emerging entity that warrants aggressive treatment.

OBJECTIVE: To determine whether familial nonmedullary thyroid carcinoma behaves like sporadic carcinoma of follicular cell origin. DESIGN: Retrospective review. SETTING: University medical center. PATIENTS: Fourteen patients were treated for familial nonmedullary thyroid carcinoma between 1980 and 1994. Thirteen families were identified, with 30 affected individuals. INTERVENTIONS: Patients were treated with total or completion total thyroidectomy. Thirteen additional operations were performed to control recurrent disease. MAIN OUTCOME MEASURES: Stage, recurrence, and survival. Patients were followed up for a mean of 6.5 years. RESULTS: In our 14 patients, 13 tumors were multifocal, and six of these were bilateral. The incidences of lymph node metastasis and local invasion were both 57% (n = 8). Seven patients (50%) had recurrences during follow-up. CONCLUSIONS: Familial nonmedullary thyroid carcinoma has a high incidence of multifocality and invasion and a high rate of local recurrence. Aggressive initial treatment and careful follow-up seem to be indicated.

Adult↗

PubMed1995

Persistent or recurrent hyperparathyroidism in patients with double adenomas.

BACKGROUND: Are double parathyroid adenomas a discrete clinical entity or are all hyperplastic parathyroid glands of varying size? This investigation was done to determine whether patients with persistent or recurrent hyperparathyroidism and double adenomas (DA) differ in clinical profile or in response to treatment from patients with hyperplasia. METHODS: From 1982 to 1993, 37 unselected patients with persistent (11) or recurrent hyperparathyroidism (26) were treated. Twenty-one had DA and 16 had hyperplasia. DAs were defined as two abnormal and two normal parathyroid glands. RESULTS: Patients with persistent or recurrent hyperparathyroidism caused by DA were older and had more muscle weakness, neuropsychiatric disorders, constipation, and weight loss (p < 0.001) than patients with persistent or recurrent hyperparathyroidism caused by hyperplasia. Nephrolithiasis was more common in patients with recurrent hyperparathyroidism caused by hyperplasia than in patients with recurrent hyperparathyroidism caused by DA (p < 0.001). Serum Ca2+ levels before operation were similar in these groups with variable parathyroid hormone levels. No recurrences occurred in either group (DA [mean, 6 yr]; hyperplasia [mean, 5 yr]). Postoperative levels of serum Ca2+ and parathyroid hormone were normal in both groups. CONCLUSIONS: Patients with persistent or recurrent hyperparathyroidism caused by DA are older, have different clinical manifestations, and are cured by resection of the second adenoma. These findings support the concept that DA and hyperplasia are distinct entities.

Adenoma↗

PubMed1995

Thyroid growth factors, signal transduction pathways, and oncogenes.

Growth of thyroid cancer cells is stimulated by various growth factors via signal transduction pathways. TSH, EGF, IGF, and TGF-alpha stimulate and TGF-beta inhibits thyroid cell growth. TSH stimulates thyroid cells via both the adenylate cyclase-PKA and the PLC-PKC-Ca signal transduction pathways. TSH-r, ras, gsp, ret, trk, and myc are oncogenes that are activated in some thyroid neoplasms. P53 and RB are tumor suppressor genes that are inactivated in some thyroid cancers.

Epidermal Growth Factor↗

PubMed1995

Immunoprecipitation isolates multiple TSH receptor forms from human thyroid tissue.

Attempts to purify the thyroid-stimulating hormone receptor (TSHR) have been complicated by its susceptibility to proteolysis and its low level of expression in thyrocytes and many transfected cells. Controversy exists over its size and structure. Multiple, single-polypeptide forms of the TSHR (230, 187, and 95-100 kDa) have been recently identified in immunoblots of crude plasma membranes prepared from COS-7 cells transfected with rat or human cDNA, but the relationship of these receptor species to the TSHR in human thyroid tissue has been heretofore unknown. We have developed a technique for immunoprecipitation of the TSHR which employed IgG purified from a polyclonal rabbit antiserum to TSHR residues 352-366. We have used immunoprecipitation to isolate the previously characterized 95-100 kDa TSH-holoreceptor, 187 kDa intermediate, and 230 kDa precursor forms of the TSHR from plasma membrane prepared from transfected COS-7 cells and human thyroid tissue. The presence of all three forms was not altered by the addition of reducing agent to the sample buffer, demonstrating the single polypeptide structure of the TSHR. This is, to our knowledge, the first report of the purification from transfected COS-7 cells of these TSHR species identified previously only in immunoblots of crude plasma membrane, and the first report of the identification by any means of these TSHR forms in human thyroid tissue. The isolation of TSHR from human thyroid tissue requires confirmation by direct means, but promises to make the receptor available in a soluble form for studies of its structure and function.

Cell Line↗

PubMed1995

Biphasic effects of thyrotropin on invasion and growth of papillary and follicular thyroid cancer in vitro.

The rationale for TSH suppression in the treatment of follicular thyroid cancer (FTC) and papillary thyroid cancer (PTC) is to inhibit tumor growth, prevent recurrent disease, and eventually prolong survival. We analyzed the effects of TSH on invasion and growth of 3 FTC cell lines from 1 patient (FTC133, primary; FTC236, lymph node; FTC238, lung metastasis) and 2 PTC cell lines (PTC-UC1, PTC-UC3). Cell growth and invasion through an 8-micron pore polycarbonate membrane coated with Matrigel were measured using the MTT assay. The dose-response to TSH was biphasic, stimulating invasion and growth of FTC and PTC at low concentrations (0.1-10 mU/mL), and inhibiting them at high concentrations (100 mU/mL). Interestingly, the metastatic FTC cell lines had higher basal invasion, but were less responsive to TSH than the primary tumor. TSH (1 mU/mL) stimulated invasion of FTC133 by 21%, FTC236 by 8%, and FTC238 by 8% (p < 0.01). At 100 mU/mL, TSH inhibited invasion of FTC133 by 21%, compared to 11% in FTC236 and 12% in FTC238. Also, TSH dose-dependently influenced proliferation of follicular thyroid cancer cells. At low concentrations it stimulated growth of FTC133 (20%) and inhibited it at high concentrations (23%; p < 0.01). Again, the amplitude of TSH effects was significantly smaller in the cell lines from metastatic tumors. TSH affected invasion and growth of PTC-UC1 and PTC-UC3 also biphasically. These results show that TSH may act as a mitogenic and antimitogenic growth factor for invasion and proliferation of well-differentiated thyroid cancer cells in vitro.

Adenocarcinoma, Follicular↗

PubMed1995

Clinical manifestations of primary hyperparathyroidism before and after parathyroidectomy. A case-control study.

BACKGROUND: There has been an National Institutes of Health consensus meeting concerning the management of patients with "asymptomatic" primary hyperparathyroidism, yet there is no clear definition of this condition. The authors, therefore, documented the clinical manifestations and frequencies of these manifestations in unselected patients with primary hyperparathyroidism and determined whether these clinical manifestations resolved after parathyroidectomy. METHOD: The authors studied 152 unselected consecutive patients with primary hyperparathyroidism and 132 control patients with nontoxic thyroid disorders who were treated by parathyroidectomy or thyroidectomy, respectively, between January 1986 and June 1991. All patients received a questionnaire during their initial office visits and the same questionnaire again after their operations. Patients were also questioned about their perception of the success of the operation. Eighty percent of the parathyroid patients and 70.5% of the thyroid patients completed the questionnaires, and the mean follow-up time was 20 months. RESULTS: Only 7 (4.6%) patients with primary hyperparathyroidism had no symptoms, and 26 (17.1%) had no associated conditions despite 74.3% of these patients having serum calcium levels less than 12 mg/dL. Symptoms including fatigue, exhaustion, weakness, polydipsia, polyuria, nocturia, joint pain, bone pain, constipation, depression, anorexia, nausea, heartburn, and associated conditions, including nephrolithiasis, and hematuria occurred more often in patients with primary hyperparathyroidism than in the thyroid control patients (p < 0.05). After parathyroidectomy, only eight (5.3%) patients failed to have any improvement in symptoms or associated conditions. Fifty-seven percent of the parathyroid patients versus 30% of the thyroid patients felt better overall after the operation, strength subjectively improved in 29% of parathyroid patients versus 13% in thyroid patients; thirty-seven percent of the parathyroid patients versus 13% of the thyroid patients claimed they were less depressed. CONCLUSION: When examined thoroughly, few patients with primary hyperparathyroidism were asymptomatic or without associated conditions, and most patients experienced subjective improvement after successful parathyroidectomy.

Adolescent↗

PubMed1995

Tamoxifen inhibits growth, migration, and invasion of human follicular and papillary thyroid cancer cells in vitro and in vivo.

Prognosis of differentiated thyroid cancer is best in young women. It has been proposed that sex steroids protect premenopausal women from aggressive thyroid malignancies. Some thyroid tissues have estrogen receptors, and estrogen stimulates human thyroid cells. Tamoxifen is thought to exert its antiproliferative effects mainly by blocking estrogen stimulation. However, recently, mechanisms independent of estrogen interactions were found to be important for the favorable effect. We investigated the effect of tamoxifen on the growth, migration, and invasion in three follicular thyroid cancer cell lines (FTC133, primary; FTC236, lymph node; and FTC238, lung metastasis) from one patient and two papillary lines (PTC-UC1 and PTC-UC3). Growth was measured by dimethylthiazol-diphenyltetrazolium bromide assays, and migration was determined by the ability of cells to penetrate 8-microns pore membranes, which were covered by Matrigel for invasion assays. For in vivo experiments, we used xenografts of FTC133 in nude mice. Tamoxifen (1.5 mumol/L) inhibited the growth of all thyroid cancer cell lines (FTC133, 59%; FTC236, 42%; FTC238, 46%; P < 0.01). This effect was less pronounced in PTC-UC1 (25%) and PTC-UC3 (19%; P < 0.006) cell lines. Tamoxifen also inhibited migration and invasion of FTC more than PTC. Invasion of FTC133 was inhibited by 36% (P < 0.01), FTC236 by 30%, and FTC238 by 32%. Immunohistochemistry showed no estrogen receptors in any cell line. Also, estradiol had no significant effect on the growth, migration, or invasion of FTC or PTC. Tamoxifen treatment inhibited the growth of FTC133 xenografts in nude mice by 52% compared to that in placebo-treated controls (P < 0.002). In conclusion, tamoxifen inhibited the growth, migration, and invasion of differentiated thyroid cancer cells in vitro and in vivo. This was not reversed by estrogen. Tamoxifen acts independently of estrogen interactions and may be useful as an adjuvant treatment for some differentiated human thyroid malignancies.

Animals↗

PubMed1995

Epidermal growth factor (EGF)- and transforming growth factor alpha-stimulated invasion and growth of follicular thyroid cancer cells can be blocked by antagonism to the EGF receptor and tyrosine kinase in vitro.

We have shown recently that epidermal growth factor (EGF) enhanced invasion and growth of differentiated thyroid cancer cells in vitro and in vivo. The present study analyzed the effects of transforming growth factor alpha (TGF-alpha) on invasion and growth of a follicular thyroid cancer cell line (FTC133) and whether blocking the EGF receptor by a monoclonal antibody (Mab528) or blocking the tyrosine kinase of the receptor by genistein abolished the EGF- and TFG-alpha-mediated effects. Growth and invasion (penetration of 8-microns pore polycarbonate membranes coated with Matrigel) were determined by the dimethylthiazol-diphenyltetrazolium bromide assay. Epidermal growth factor (10 ng/l) stimulated invasion of FTC133 by 42% and TGF-alpha (10 ng/l) stimulated invasion of FTC133 by 27% (p < 0.02). Both growth factors also enhanced growth by 62% (EGF) and 30% (TGF-alpha) (p < 0.003). Epidermal growth factor receptor antibodies (1 microgram/ml) abolished EGF-mediated stimulation of invasion and growth completely and that of TGF-alpha by 93%. At 100 ng/ml genistein reversed EGF and TGF-alpha stimulation, and at 1 microgram/ml it inhibited invasion (27%) and growth (40%) of unstimulated FTC133 (p < 0.02). We conclude that TGF-alpha stimulates invasion and growth of follicular thyroid cancer by binding to the EGF receptors, that EGF- and TGF-alpha-mediated effects can be blocked by antagonism to the EGF receptor and to tyrosine kinase, and that genistein not only neutralized EGF and TGF-alpha effects but also inhibited invasion and growth of unstimulated FTC133.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗