Search PubMed⌕ Search

Biomedical subjects

S Tezelman

Publications and source records attributed to S Tezelman.

26 records · Page 2Linked to original sources

Thyrotropin stimulates invasion and growth of follicular thyroid cancer cells via PKC- rather than PKA-activation.

The signal transduction of TSH in invasion and growth of FTC 133, a human follicular thyroid cancer cell line, was investigated. TSH (0.01-1 mIU/ml) stimulated invasion of FTC 133 by 21% and growth by 20% of basal. Cyclic AMP-stimulators and inhibitors had no effect at any concentration. The PKC-agonist TPA enhanced invasion and growth by 15%, whereas staurosporine, a PKC-antagonist, inhibited them by 32% and 60%, respectively. The latter also reversed TSH stimulation. EGF enhanced invasion (42%) and growth of FTC 133 (25%). Staurosporine did not reverse EGF stimulation. The tyrosine kinase antagonist genistein reversed EGF, but not TSH stimulation. Pertussis toxin inhibited invasion (18%) and growth (22%). Cholera toxin was less inhibitive. We demonstrated for the first time, that TSH stimulates invasion and growth of human thyroid cancer cells in vitro by PKC- rather than PKA-stimulation.

Alkaloids↗

Tumoral calcinosis. Controversies in the etiology and alternatives in the treatment.

OBJECTIVE: To examine our experience and review the literature concerning the diagnosis, origin, and treatment of tumoral calcinosis (TC). DESIGN/SETTING: Case series based on patients with TC treated in University of California-San Francisco hospitals from 1981 to 1992 and the review of the patients described in the English-language literature. PATIENTS: The study included a total of 17 patients: 10 women and seven men. MAIN OUTCOME MEASURES: Sex, age, origin, symptoms, localization, treatment, and morbidity. RESULTS: Seven men and six women, from 32 to 62 years of age, had known disorders of calcium metabolism, and four women, from 37 to 84 years of age, did not. The main causes of the calcium metabolic disorder were secondary hyperparathyroidism in 11 patients (85%) and primary hyperparathyroidism in two patients. In three patients there was a history of trauma at the involved site and in one patient the origin was unknown. Swelling and pain are the most common presenting complaints. Generalized pruritus was observed in 54% of the patients with metabolic disorders (P < .001) but not in patients without metabolic disorders. Among our patients with metabolic disorders, TC occurred most frequently at the shoulder (46%) and elbow (31%). Eleven patients with secondary hyperparathyroidism had received calcium carbonate to bind phosphate, a high level of calcium in the dialysate, and calcitriol (1,25-vitamin D) either orally, intravenously, or both, and three received epoetin alfa (Epogen). Following parathyroidectomy, the patients with hyperparathyroidism improved symptomatically, although calcifications did not change in size. One patient had the calcifications resected and did well, whereas another was treated by subtotal resection and had a recurrence 3 years later. All four of our patients without a metabolic disorder had complete resection of TC with no recurrence. CONCLUSION: We believe TC is becoming more common in uremic patients with secondary hyperparathyroidism because of recent changes in the medical treatment of these patients. The increased use of calcium carbonate to bind phosphate as well as calcitriol and calcium to suppress parathyroid function and possibly epoetin alfa are causing more patients to develop TC.

Adult↗

Concurrent hyperthyroidism and thyroid carcinoma.

Between 1986 and 1991, thyroidectomy was performed on 138 patients with hyperthyroidism. Thyroid carcinoma was found in eight patients (5.8 per cent). Eighty (58.0 per cent) of the 138 patients had toxic nodular goitre, 33 (23.9 per cent) toxic diffuse goitre and 25 (18.1 per cent) toxic adenoma. Concurrent carcinoma was more frequent in patients with toxic adenoma (8 per cent) than in those with Graves' disease (6 per cent) and toxic nodular goitre (5 per cent). Papillary carcinoma was found in seven patients and follicular carcinoma in one. Three papillary carcinomas were occult with a diameter less than 1.5 cm. Five patients received 100 mCi 131I after operation. There was no morbidity. During follow-up of 10-45 months, there was neither death nor recurrence.

Adenocarcinoma, Follicular↗

Double parathyroid adenomas. Clinical and biochemical characteristics before and after parathyroidectomy.

OBJECTIVE: There is considerable debate about whether double parathyroid adenomas are a discrete entity or represent hyperplasia with parathyroid glands of varying sizes. This distinction is important because it impacts on the extent of parathyroid resection and the success of the parathyroid operation. SUMMARY BACKGROUND DATA: Double parathyroid adenomas have been reported to occur in 1.7% to 9% of patients with primary hyperparathyroidism (HPT). It is important for surgeons to differentiate between double adenoma and hyperplasia with glands of varying sizes using gross examination during the initial procedure because microscopic findings of a small biopsy specimen at frozen-section examination may not be diagnostic. METHODS: From 1982 to 1992, 416 unselected patients (309 women and 107 men) with primary HPT without familial HPT or multiple endocrine neoplasia (MEN) were treated by one surgeon at the University of California at San Francisco. Double adenoma occurred in 49 patients, solitary adenoma in 309 patients, and hyperplasia in 58 patients. The authors analyzed the clinical manifestations, the preoperative and postoperative serum levels of calcium, phosphate, and parathyroid hormone (PTH), and the success rate and outcome after parathyroidectomy and compared their results in 49 patients with double adenomas to the results for patients with solitary adenomas or hyperplasia. RESULTS: Ten of the patients with double adenomas (20.4%) were referred for persistent HPT after removal of one abnormal parathyroid gland. The ages of the patients with double adenoma, single adenoma, and hyperplasia were 61 +/- 14, 56 +/- 15, and 58 +/- 7 years, respectively. Fatigue, muscle weakness, and bone pain were common in patients with double adenomas, whereas nephrolithiasis occurred more frequently in patients with solitary adenoma (p = 0.0001). Serum calcium and PTH levels (per cent of upper limit of normal) fell from 11.5 +/- 1.2 mg/dL and 487% to 9.5 +/- 0.8 mg/dL and 61% for patients with double adenomas; from 11.9 +/- 0.9 mg/dL and 378% to 9.3 +/- 1.4 mg/dL and 101% for patients with single adenoma; and from 10.9 +/- 0.5 mg/dL and 418% to 9.1 +/- 0.7 mg/dL and 94% for patients with hyperplasia, respectively. There was no recurrence in the patients with double adenomas with a mean follow-up time of 5.8 years. CONCLUSIONS: Double adenomas are a discrete entity and occur more often in older patients. Patients with double adenomas can be successfully treated by removal of the two abnormal glands.

Adenoma↗

Thyroid-stimulating hormone activates phospholipase C in normal and neoplastic thyroid tissue.

BACKGROUND: Thyroid-stimulating hormone (TSH) stimulates thyroid growth through two signal transduction pathways: the G protein-adenylate cyclase system and the G protein-phospholipase C (PLC) system. The adenylate cyclase system has been studied extensively, but there is little information available concerning PLC activity in thyroid neoplasms. METHODS: Human thyroid membranes were incubated for 30 minutes at 37 degrees C in the presence or absence of bovine TSH (300 mU/ml). PLC activity was assayed by liberation of inositol phosphates from the enzymatic hydrolysis of tritiated phosphatidylinositol bisphosphate. Fifty-six tissues were assayed (normal, 23; multinodular goiter, 5; follicular adenoma, 9; and differentiated thyroid cancer, 19 [9 low risk and 10 high risk]). RESULTS: TSH significantly increased PLC activity in normal, benign, and most malignant thyroid neoplasms. Although there were no differences in basal or TSH-stimulated PLC activity between the groups of normal thyroid, multinodular goiter, follicular adenoma, or the cancers, one half of the high-risk cancers had an aberrant PLC response. CONCLUSIONS: This is the first demonstration that TSH stimulates PLC activity in normal and neoplastic human thyroid tissue. Aberrant TSH-stimulated PLC activity was present in half of the aggressive thyroid neoplasms.

Enzyme Activation↗

Transhiatal oesophagectomy for oesophageal carcinoma.

Between 1979 and 1990 transhiatal oesophagectomy and reconstruction with stomach was performed in 148 patients with carcinoma of the oesophagus. Ninety-seven patients were men and 51 were women; ages ranged from 21 to 88 years with a mean of 57.4 years. Dysphagia and weight loss were the usual clinical symptoms. The mean duration of symptoms was 14 weeks. Squamous cell carcinoma was present in 129 patients (87.2 per cent), 18 patients (12.2 per cent) had adenocarcinoma, and one had lymphoma (0.7 per cent). In two-thirds of the patients tumours were located in the middle thoracic (50 of 148 patients) or distal thoracic oesophagus (59 of 148 patients). Three-quarters of the patients had tumours determined as stage III. The mean length of hospital stay after operation was 12.8 days. Anastomotic leakage occurred in 15 cases (10.1 per cent). Pulmonary complications other than pneumothorax were observed in 36 cases (24.3 per cent). The 30-day postoperative mortality rate was 8.1 per cent (12 of 148 patients). Respiratory insufficiency was observed as the major cause of death (six of 12 patients). Mediastinitis due to necrosis of the transposed stomach in the mediastinum was the cause of death in three cases. Two-year actuarial survival rates in patients with cervical, upper, middle and lower thoracic tumours were 20, 22, 26 and 30 per cent respectively. Transhiatal oesophagectomy is safe and offers limited morbidity and mortality, although pulmonary complications and anastomotic leakage in the early postoperative period still pose a significant risk, especially for elderly patients in poor condition.

Adult↗

Radioiodine-associated thyroid cancers.

Numerous investigations document that exposure to low dose external therapeutic radiation leads to the development of benign and malignant thyroid neoplasms. There is considerable controversy, however, concerning whether radioactive iodine (131I) causes thyroid cancer. The aim of this investigation was to examine our experience and that in the literature related to this problem. From 1982 to March 1993 seven of 373 patients (1.9%) with thyroid cancer who were treated by one surgeon had a history of treatment with radioactive iodine for Graves' disease and toxic nodular goiter. Sixty-five patients have previously been reported in the literature from 1957 to present. Our patients (five women, two men) ranged in age from 26 to 80 years (mean 57 years). The interval between the exposure to the internal radiation and development of cancer ranged from 3 to 29 years (mean 11.4 years), and the mean age at the time of 131I treatment was 45 years (18-76 years). The therapeutic dose of 131I was 5 to 100 mCi (mean 25.3 mCi) in our patients. Two of our patients received 131I twice. The age of patients reported in the literature at the time of 131I treatment ranged from 7 to 74 years (mean 48 years). The mean therapeutic dose of 131I was 20.6 mCi (1.25-180.0 mCi) and the latent period was documented for a mean 8.7 years (0.25-28.0 years) in these patients. Three of 29 patients in the literature received 131I twice. Fine-needle aspiration cytology of thyroid nodules was positive for cancer in six of our patients (86%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma, Follicular↗

Expression of bcl-2 in papillary thyroid cancers and its prognostic value.

PURPOSE: Papillary thyroid cancer has a good prognosis. This favourable prognosis may be attributed to the apoptotic tendency of the cancer cells. This study aims to evaluate the expression of bcl-2, which is an antidote of apoptosis, and aims to evaluate the value of bcl-2 as a prognostic marker in papillary thyroid cancer. MATERIAL-METHODS: Bcl-2 expression in the archival materials of 31 patients with papillary thyroid cancer was examined with immunohistochemical methods using bcl-2 and p-53 stains. The results were compared with 31 normal thyroid tissue specimens, which consisted of the contralateral lobes of these patients. The results were then analyzed in accordance with the clinical features of the patients. RESULTS: Thirty (96.7%) patients of the control group were positive for bcl-2 whilst one (3.3%) was negative. The staining for bcl-2 was positive in 12 (%75) patients with microcarcinomas (p < 0.05) and 13 (86.6%) with papillary cancers (p > 0.05). Two cases of the papillary cancer group were admitted to the hospital with local recurrence (6.4%) and both were positive for bcl-2 (p > 0.05). All cases (4/31), whose MACIS scores were higher than 7 were positive for bcl-2. Twenty-one of 27 cases whose MACIS scores were lower than 7 (77.7%) were positive for bcl-2 (p > 0.05). All tumours of this series were negative for p-53 immunstaining. CONCLUSION: The rate of bcl-2 expression in microcarcinomas of papillary thyroid cancer decreases when compared to normal thyroid tissue. This may be an early sign of oncogenesis, and a reason for the favourable prognosis in microcarcinomas. However, bcl-2 cannot be used as a prognostic marker.

Adult↗