Synaptophysin identified in metastases of neuroendocrine tumors by immunocytochemistry and immunoblotting.

Synaptophysin, an Mr 38,000 integral membrane glycoprotein of neurotransmitter vesicles, has been identified in diverse primary neuroendocrine (NE) tumors of both neural and epithelial origin (Wiedenmann and co-workers, Proc Natl Acad Sci USA 1986; 83: 3500-3504). In the present study, metastases of several types of NE tumors, including medullary thyroid carcinoma, gastrinoma, insulinoma, small (oat) cell carcinoma of the lung, gastrointestinal carcinoid, and neuroblastoma, were examined for the presence of synaptophysin by immunocytochemistry, with the use of tissue sections as well as centrifuged cell suspensions and by immunoblotting of tumor proteins. The results show that expression of synaptophysin can be maintained during formation of metastases.

Action of calcitonin gene-related peptide at the calcitonin receptor of the T47D cell line.

Some effects of calcitonin (CT) can also be produced by calcitonin gene-related peptide (CGRP), an alternative product of the calcitonin gene. This might be mediated by interaction of CGRP at the CT-receptor site. The human breast cancer cell line T47D possesses well characterized CT-receptors (KD = 2.

Procollagen-III peptide serum levels in Paget's disease of the bone.

A commercially available radioimmunoassay kit was used to determine aminoterminal procollagen-III peptide (pNcoll III) serum levels in patients with Paget's disease of the bone and control subjects. In patients with Paget's disease pNcoll III concentrations were significantly elevated. They decreased to varying degrees under chronic therapy with human and salmon calcitonin, disodium ethane 1-hydroxy 1,1-diphosphonate (EHDP), or a combination therapy of EHDP and human calcitonin.

[Katacalcin--a new tumor marker in C-cell cancer of the thyroid gland].

Katacalcin (KC) is situated on the C-terminal side of the procalcitonin molecule and is cleaved like calcitonin (CT) from this precursor peptide. Serum levels of KC were measured in 22 patients with C-cell carcinoma with a specific and sensitive radioimmunoassay (normal range, less than 0.1-0.

Neuron-specific enolase in medullary thyroid carcinoma: immunohistochemical demonstration, but no significance as serum tumor marker.

Neuron-specific enolase (NSE) is an enzyme detectable in nervous and neuroendocrine tissue. Increased serum levels of NSE are found in small cell lung cancer and in patients with neuroblastoma, in whom NSE is used as a serum tumor marker. We have investigated 32 patients with histologically proven medullary thyroid carcinoma, a tumor of neuroendocrine origin, in which the classical tumor marker calcitonin (CT) was pathologically elevated.

Inherited thyroxine-binding globulin excess. Study in a kindred.

A three-generation family with hereditary high thyroxine-binding globulin (TBG) serum levels has been studied. All patients were clinically euthyroid and did not have a goiter. Four females of the eleven members of the kindred had elevated TBG (range: 34-56 micrograms/ml), total thyroxine (T4) and total triiodothyronine (T3) levels, but normal free T4 (fT4) and normal response of thyroid stimulating hormone (TSH) to intravenous application of thyrotropin-releasing hormone (TRH).

Metastatic C-cell carcinoma: calcitonin and CEA production in monolayer culture.

Mechanically dissociated cells from a surgically removed mediastinal C-cell carcinoma (MTC) were cultured over a period of 4 months. The cells of the monolayer culture consisted of clusters of small epithelial-like cells. Using semithin and ultrathin sections, two different types of cells could be characterized by shape of nucleus and by content and distribution of secretory granules.

Secretion of calcitonin and carcinoembryonic antigen in long-term organ culture of human medullary thyroid carcinoma: biochemical and immunocytochemical studies.

Tissue cultures of four C-cell carcinomas (medullary thyroid carcinoma, MTC) were prepared to study the basal and stimulated calcitonin (CT) and carcinoembryonic antigen (CEA) release. Immunohistological staining of the explants for CT and CEA have been performed after various periods of culture. These MTC explants were able continuously to release CT and CEA for periods up to 157 days.

Pheochromocytoma in multiple endocrine neoplasia.

Three patients with a surgically confirmed and 1 with suspected pheochromocytoma as part of the syndrome of multiple endocrine neoplasia (MEN) type II are presented. Pheochromocytoma and medullary thyroid carcinoma (MTC) as well as other tumors are part of this heritable entity. Three cases were members of a MEN IIa family and 1 patient has suffered from a sporadic form of MEN IIb.

Reversible diminished calcitonin secretion in the rat during chronic hypercalcemia.

A transient increase in serum calcitonin (CT) concentration is induced by an acute iv calcium (Ca) load, whereas in the chronic hypercalcemic state, serum CT levels, as well as CT content of the thyroid, are equivocal. The secretion of CT was tested in three models of hypercalcemia in rats: tumor induced by the hypercalcemic Walker carcinosarcoma 256 (HWCS 256), chronic parenteral Ca administration, and chronic 1,25(OH)2D3 administration. In rats with HWCS 256, serum CT levels increased from basal values of 0.

Importance of early diagnosis and follow-up in multiple endocrine neoplasia (MEN II B).

Three patients with a sporadic form of multiple endocrine neoplasia (MEN) IIb are presented. MEN IIb is the association of medullary carcinoma of the thyroid (MTC), pheochromocytoma and multiple mucosal neuromata. The age at diagnosis and primary therapy of MTC was relatively late (8, 16, 18 years) although thyroid enlargement (two cases), typical marfanoid habitus (two cases) or multiple mucosal neuromata (one case) had been evident since early childhood.

Different effects of hypercalcemic state induced by Walker tumor (HWCS 256) and 1,25 (OH)D3 intoxication on rat thyroid C cells. An ultrastructural, immunocytochemical, and biochemical study.

Two different models of chronic C cell stimulation by the hypercalcemic state were compared with respect to their morphology, immunocytochemistry, and biochemistry. In the chronic hypercalcemic state due to the HWCS 256 strain of the Walker tumor C cells show signs of degeneration such as vacuolation, on day 7 after tumor implantation. On day 10 tumor induced hypercalcemia leads to irreversible cell damage with karyopyknosis and karyorrhexis.

Variations of plasma calcitonin levels measured by radioimmunoassay systems for human calcitonin.

Radioimmunoassay systems of different characteristics are available for routine determination of human calcitonin (hCT). The purity and calcitonin content of the used standards has to be observed, different antisera may yield discrepant absolute values from the same plasma samples. HCT measurements permit blood level control during treatment with this hormone.

[Tumor markers in C-cell cancer].

C-cell carcinoma (medullary thyroid carcinoma) is associated with increased serum calcitonin levels. In addition, increased serum levels of other tumour markers are also found: carcinoembryonic antigen (CEA), adrenocorticotrophic hormone (ACTH) and tissue polypeptide antigen (TPA). The relevance of these tumour markers as compared to calcitonin was evaluated in 46 patients with C-cell carcinoma.

The diagnosis and therapy of medullary thyroid carcinoma in childhood.

The influence of selective calcitonin blood level measurements and the radical surgical approach in the treatment of C-cell carcinoma of the thyroid is demonstrated using the case of an 11-year-old girl.