Detection and characterization of a pancreatic tumor inhibitory factor.

Numerous growth factors which stimulate cellular proliferation have been identified and characterized. Little information is available on autocrine factors that inhibit growth. The objective of this study was to determine if an established human pancreatic cancer cell line, RWP-1, produced such a tumor growth inhibitory factor (TIF). RWP-1 serum-free conditioned media (CM) was concentrated and its effect on DNA synthesis was determined by measuring incorporation of [3H]thymidine. CM inhibited [3H]thymidine incorporation in a dose-dependent and nontoxic manner with all cell lines tested. TIF activity was stable at 56 degrees C, labile at 95 degrees C and partially inactivated by acid, reduction/alkylation, and enzymatic digestion. The TIF exhibited differential activity against the tested cell lines and was found to be active against a normal murine fibroblast line. The TIF appears to be a polypeptide with a molecular weight greater than 5000 Da. Attempts at isolation of TIF with affinity and ion-exchange chromatography have thus far been unsuccessful, implying that more than one factor may be involved. RWP-1 TIF is a potentially important factor because of its role in the regulation of cellular proliferation.

Radioiodine total body scan versus serum thyroglobulin levels in follow-up of patients with thyroid cancer.

Two groups of patients were studied to compare the efficacy of serum thyroglobulin (Tg) levels to 131I total body scans in the follow-up of patients with thyroid cancer. All of the group of 30 patients without recurrence had undetectable Tg levels on and off thyroid hormone replacement, and all had negative total body scan results although eight patients showed uptake in remnant thyroid tissue. In the second group of 37 patients with documented recurrent or metastatic disease, 34 (92%) had positive serum Tg levels, although the levels in five of these patients were undetectable while on thyroid replacement, and 31 (84%) had positive total body scan results. The false negative results of the two tests were not overlapping, and of those with positive Tg levels, 29 showed a significant increase once thyroid hormone therapy had been withdrawn. We conclude that although the percentages of positive Tg levels and body scan results in patients with recurrent disease are similar, both tests are required to minimize the number of patients with undiagnosed metastases. Second, thyroid-stimulating hormone suppression has a definite although unpredictable effect on serum Tg levels in patients with thyroid cancer, and thyroid hormone should be withdrawn prior to measurement of serum Tg to minimize the number of false negative results.

Effect of TSH stimulation on serum thyroglobulin in metastatic thyroid cancer.

Thyroglobulin (TG) is a glycoprotein which has been found to be produced by almost all nonmedullary thyroid cancers, and is present in elevated levels in the serum of most patients with metastatic thyroid cancer. It has long been a clinical impression that many metastatic thyroid cancers are "responsive" to TSH suppression as manifested by a decrease in the size and/or symptoms of the tumor. Five athyroid patients with metastatic thyroid cancer were studied to determine the effect of TSH stimulation on their serum TG levels and attempt to correlate this effect with their clinical response. Three of the five patients showed a definite rise in their serum TG once serum thyroxine (T4Y replacement was withdrawn, which correlated with an increase in TSH, and two of these patients have had no progression of their disease while on T4 suppression. The remaining two patients have shown no change in their TG levels after T4 withdrawal, and both have had progression of their metastatic disease while on T4 suppression. Thus, we see that in some patients, TG production by their metastatic thyroid cancer is responsive to TSH suppression, and there is some suggestion that TSH-responsive cancers are less aggressive; but it will require further studies to determine this.

Thyroglobulin in benign and malignant thyroid disease.

Thyroglobulin (TG) is a 19S glycoprotein produced by normal thyroids and almost all nonmedullary thyroid cancers. Radioimmunoassays measure serum levels of TG, and these levels are abnormally elevated in patients with metastatic thyroid cancer. Data from our study show that TG measurement is not effective in screening high-risk populations for thyroid cancer. Nevertheless, serum TG determinations are useful for assessing the presence and possibly the extent of residual or recurrent nonmedullary thyroid cancer in patients who have undergone total thyroidectomy.

Serum clearance rates of immunologically reactive thyroglobulin.

Serum thyroglobulin levels have been shown to have a role in detecting the presence of residual or recurrent disease in most patients who have undergone total thyroidectomy for thyroid cancer. It has not yet been determined at what interval postoperatively to begin following serum thyroglobulin levels in these patients to detect residual disease. Eight patients who underwent total thyroidectomy were studied to determine the clearance rate of this glycoproteint. Serial samples were obtained pre- and postoperatively and clearance rate curves were plotted for each patient. The average half-life of thyroglobulin was 14 hours, with a range of 8 to 22 hours. Based upon these results, it appears that 4 weeks is a sufficient period of time to allow for the clearance of the residual thyroglobulin in patients undergoing total thyroidectomy. Elevated levels of serum thyroglobulin after this time represent residual thyroid tissue or the presence of metastatic thyroid carcinoma.

Serum thyroglobulin and recurrent thyroid cancer.

Many thyroid malignancies are sufficiently differentiated to produce thyroglobulin both in situ and in perpipheral blood. Since patients who have undergone total thyroidectomy for malegnancy should not have normally circulating thyroglobulin, their serum thyroglobulin may provide a simple and specific tumour marker for recurrent disease. Of 30 such athyroid patients who were studied, all of the 20 patients who were disease-free ten years after thyroidectomy had minimal (less than15 ng/ml) serum-thyroglobulin levels while all of 10 patients with recurrences had raised levels (greater than 90 ng/ml). Controls ranged from 0 to 60 ng/ml. This assay should prove valuable in following patients who have undergone total thyroidectomy for recurrent thyroid malignancy.