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Cytoplasmic microtubules in human neutrophil degranulation: reversible inhibition by the colchicine analogue 2-methoxy-5-(2',3',4'-trimethoxyphenyl)-2,4,6-cycloheptatrien-1- one.

The colchicine analogue 2-methoxy-5-(2',3',4'-trimethoxyphenyl)-2,4,6-cycloheptatrien-1-on e (MTC) was found to inhibit concanavalin A- and formyl-methionyl-leucyl-phenylalanine-stimulated human neutrophil degranulation and to depolymerize the microtubule network at low concentrations. The inhibitory capacity of MTC for neutrophil degranulation was similar to that of nocodazole and taxol. The mechanistically distinct actions of these three drugs on microtubules support the notion that microtubules are required for neutrophil enzyme release in response to different stimuli. MTC affected both degranulation and microtubule integrity rapidly and reversibly, after only a 5-min preincubation. At these short periods of incubation, colchicine irreversibly affected neutrophil degranulation only at concentrations in the millimolar range and behaved similarly to its microtubule-inactive analogue lumicolchicine. At longer times of incubation (30-60 min), low concentrations of both MTC and colchicine induced a drastic shortening and depolymerization of microtubules, preserving the microtubule-organizing center, but only MTC was able to completely inhibit the secretory response of neutrophils. These results suggest that the colchicine effect on neutrophil degranulation is not specifically mediated by its action on the microtubule network of these cells. In contrast, the specific and reversible effects of the colchicine analogue MTC suggest that it may be a useful agent with which to study the role of microtubules in this cellular function.

Cell Degranulation↗

An autoreactive T cell clone that can be activated to provide both helper and suppressor function.

To understand further the biologic significance of the autologous mixed lymphocyte reaction, we determined the functional properties of autoreactive T cell lines and clones. Initially, we found that cells in an uncloned autoreactive Leu-3+ T cell line helped immunoglobulin production when added to cultures containing fresh T and non-T cells in the absence of pokeweed mitogen (PWM) but suppressed immunoglobulin production in the same cultures in the presence of PWM. To explain this phenomenon, we studied the immunoregulatory potential of an autoreactive T cell clone termed MTC-4. This clone bore the phenotype Leu-3+, 2-, 8-, 11-, DR+ and underwent proliferation when co-cultured with autologous, but not allogeneic non-T cells. Of interest, the immunoregulatory potential of the MTC-4 cells varied according to how the cells were activated. When MTC-4 cells were cultured with autologous non-T cells in the absence of antigen or mitogen (unactivated non-T cells), polyclonal immunoglobulin production (detected by reverse PFC assay) was observed. This helper activity was MHC-restricted in that it was elicited only by autologous non-T cells or MHC-matched allogeneic non-T cells; however, once activated by autologous non-T cells, it could also help allogeneic non-T cells. In contrast, when MTC-4 cells were cultured with autologous non-T cells in the presence of PWM (activated non-T cells), immunoglobulin production was greatly suppressed. This suppression was also observed when MTC-4 cells were added to cultures containing exogenous T cell help (such as that provided by autologous fresh T cells) and was not due to a direct effect of PWM on the T cell clone, because preincubation of MTC-4 cells with PWM before culture with non-T cells did not result in suppression. On the basis of these data, we conclude that autoreactive T cells can have dual immunoregulatory function that is manifest, at least in part, at the single cell level. Moreover, these regulatory functions are differentially elicited depending on the state of activation of the stimulating autologous non-T cells: when stimulated by MHC antigens present on unactivated B cells, they provide helper activity; and when stimulated by MHC antigens present on activated B cells, they act as suppressor cells. Autoreactive T cells with dual regulatory potential appear to make up a substantial proportion of all autoreactive T cells and are cells that are uniquely adapted to maintain immunologic homeostasis.

Antigens, Differentiation, T-Lymphocyte↗

The changing patterns of occurrence and management in primary mediastinal tumors and cysts in the People's Republic of China.

Primary mediastinal tumors and cysts (MTC) constitute a common problem in thoracic operations done in the People's Republic of China. Data from 4,357 instances of MTC diagnosed in China between 1963 and 1985, including 307 from our own facility, are presented. Teratoid tumors are the most common of the MTC in the northern part of China contrasting with thymomas and neurogenic tumors which are the most common in the southern part of China; a finding that notes a significant difference (p less than 0.01). Beyond this, the distribution of MTC is different than in North America. In patients we studied, we were able to predict the correct histopathologic diagnosis 80 per cent of the time by considering the history of the patient and the results of a conventional roentgenogram of the chest. This was increased to 91.4 per cent when needle biopsy was added. Optimal therapy for MTC is complete surgical resection. We present a scheme for localization of the various types of MTC and an operative approach.

Adolescent↗

C-cell hyperplasia and medullary thyroid carcinoma in the rat. An immunohistochemical and ultrastructural analysis.

Medullary thyroid carcinoma (MTC) is a distinctive neoplasm which is derived from the calcitonin-producing intrathyroidal C-cell system and which develops commonly in untreated rats of various strains. Thyroid glands of Long-Evans rats ranging in age from 3 months to 3 years showed a spectrum of C-cell proliferative abnormalities. As compared to 3-month-old control rats, thyroids from 9- to 12-month-old animals exhibited mild diffuse C-cell hyperplasia (CCH). Thyroids from animals ranging from 1 to 3 years of age exhibited progressively more severe C-cell abnormalities including severe diffuse CCH, nodular CCH, and/or MTC. In contrast to the normal basal serum calcitonin levels in controls and in animals with mild diffuse CCH, animals with severe diffuse CCH, nodular CCH, or MTC had elevated basal serum calcitonin values. Nodular CCH was characterized by the replacement and enlargement of individual follicles by C-cells. Larger foci of nodular CCH were characterized by similar changes in multiple adjacent follicles or by an irregular expansion of individual follicles. MTC was characterized by penetration of the follicular basal lamina by C-cells with extension into the adjacent thyroid stroma. In addition to the high incidence of thyroidal C-cell abnormalities, diffuse and/or nodular parathyroid hyperplasia was commonly found. There was no evidence of chronic renal failure in these animals, and the serum calcium levels were within normal limits. Although the stimulus for the initial C-cell proliferation remains unknown, the appearance of MTC is preceded by relatively prolonged phases of CCH. These findings are essentially identical with those noted in human familial MTC and indicate that the rat provides a useful model system for studying the regulation of C-cell proliferation during the processes of neoplastic development and progression.

Aging↗

[Gastrointestinal hormone profile in medullary thyroid carcinoma].

Medullary thyroid carcinoma (MTC) can be important for gastroenterologists because 20-30% of patients with MTC suffer from chronic diarrhea and the tumor is capable of producing--besides other bioactive substances--a multitude of gastroenteropancreatic hormones. Gastrointestinal hormone profiles of 5 patients with MTC were determined both basally and after intravenous stimulation with secretin and calcium respectively. Diagnosis of MTC was confirmed histologically or cytologically and by demonstration of elevated serum concentration of calcitonin both basally and after calcium stimulation. 4/5 patients had chronic diarrhea. Normal values or only borderline increases were found for the following hormones: vasoactive intestinal polypeptide (VIP), neurotensin, substance P, growth hormone releasing hormone (GRH), glucagon, neurokinin A, peptide YY, and pancreatic polypeptide. Somatostatin was elevated after calcium stimulation in 1/5 patients only. The main findings were increased basal concentrations for GAWK in 5/5 patients and elevated concentrations for gastrin-releasing peptide (GRP, human bombesin) after calcium stimulation in 4/5. Probably as a consequence of the GRP increase, an increase in gastrin occurred in parallel, indicating bioactivity of the GRP released from the tumor. Besides calcitonin as the main tumor marker for MTC, determination of GAWK and GRP seems to provide helpful additional markers in laboratory diagnosis of MTC. GRP determination after i.v. calcium infusion allowed identification of patients with normal basal plasma GRP concentration.

Adult↗

[Medullary thyroid cancer--screening].

It is possible to screen for medullary thyroid cancer (MTC) with biochemical tests, imaging and genetic testing in families with multiple endocrine neoplasia type 2. The recommendation is based on a consensus statement made by the Members of the European Community concerted action for MTC. The prognostic characteristics are based on 117 patients with MTC diagnosed in Denmark between 1970-1991. Twenty percent of all MTC patients were members of families with two or more thyroid cancer patients. More than half of all MTC patients had neck lymph node involvement at the time of diagnosis. The frequency of neck lymph node involvement was however only 20% amongst those with familiar MTC.

Carcinoma, Medullary↗

Pathobiology of the C-cells.

This brief review of the pathobiology of C-cells has stressed cellular and molecular aspects of MTC development. In the genetic forms of MTC, an alteration in one or more genes on chromosome 10, through an as yet unknown series of events, results in initial hyperproliferation of C-cells. Subsequent genetic steps, possibly at other chromosome loci, presumably result in selected clonal transformation of the hyperproliferative C-cells at risk for tumor development. Some of these same molecular events are probably operative in the development of sporadic MTC as well. Once MTC has developed, it has the potential to undergo tumor progression events which result in loss of C-cell differentiation. Studies in a culture model of these events have revealed that activation of signal transduction pathways, similar to those active in differentiation of other neural crest-derived cells, can restore differentiation features of normal C-cells to MTC. Continued identification of the molecular factors mediating this restoration should teach us much about the relationships between general neural crest differentiation and that of normal C-cells. It will also reveal much about the pathobiology of C-cells contributing to each step of MTC development.

Carcinoma↗

Heterogeneous mutation of the RET proto-oncogene in subpopulations of medullary thyroid carcinoma.

Mutations in the RET proto-oncogene are associated with the pathogenesis of medullary thyroid carcinoma (MTC). In an attempt to understand this process, we examined microdissected subpopulations from MTC and multiple metastases from these tumors. Approximately 80% of sporadic MTC's had at least one subpopulation with the RET codon 918 mutation, which is a mutation previously detected in sporadic MTC as a somatic mutation and in multiple endocrine neoplasia type 2B as a germline mutation. However, the distribution of this mutation was nonhomogeneous, occurring only in subpopulations in most tumors and among subsets of multiple metastases, thus implying that although the codon 918 mutation could be an early event, it is not necessarily an early or essential event in tumorigenesis. This heterogeneity suggests either that the codon 918 mutation can arise as an event in progression within a metastatic clone or within a single tumor, or that MTC can be of polyclonal origin. Of significance, one of two multiple endocrine neoplasia type 2A MTCs carried a somatic mutation at codon 918, in addition to the RET mutation present in the germline. We found no correlation between the presence of other somatic genetic events, such as loss of heterozygosity on chromosome arms 1p and 22q, and RET mutation status in the various subpopulations of MTC.

Carcinoma, Medullary↗

[Analysis of the RET gene and medullary cancer of the thyroid. Contribution to the diagnosis and treatment].

MTC occurs sporadically or as part of multiple endocrine neoplasia type 2 (MEN 2) syndromes or as familial MTC (FMTC). 97% of the patients affected with MEN 2B show a germline mutation in codon 918 (exon 16) within the tyrosine kinase domain of the RET protooncogene. In 97% of MEN 2A patients, the germline mutation affects one of five cysteine codons within exons 10 and 11 in the extracellular domain. Only 65% of FMTC patients are found to have a germline mutation of RET. These mutations affect either the cysteine rich domain (as MEN 2A mutations) or codons 768 (exon 13) or 804 (exon 14) within the tyrosine kinase domain. In families affected with hereditary form of MTC, mutation analysis is now commonly used to determine genetic status. Individuals without the mutation would be considered unaffected and would not require further biochemical screening. Individuals who inherit the MEN 2 mutation would undergo biochemical screening tests and have thyroidectomy as soon as these tests are abnormal. Risk of phaeochromocytoma in affected patients depends on the position of RET mutation. This risk is high if the patient has a codon 634 mutation and low if he has a mutation within exon 10, 13 or 14. Frequency of adrenal follow-up could so be adapted with regards to the localisation of RET germline mutation. When a new MTC case is diagnosed, the distinction between a true sporadic and a de novo hereditary case is important for future clinical management of both the patient and his family. The absence of RET exons 10, 11, 13, and 14 germline mutations appears to rule out MEN 2A to a high probability. However the presence of a familial form of MTC cannot be excluded conclusively. Since codon 918 somatic mutations are found in 25% of MTC from truly sporadic cases, mutation analysis of RET in tumour DNA may help in distinguishing the sporadic cases from those that are in fact heritable.

Carcinoma, Medullary↗

[Causes of death in patients with medullary cancer of the thyroid. GETC. Groupe d'Etude des Tumeurs à Calcitonine].

OBJECTIVE: Medullary thyroid carcinoma (MTC) is characterized by different clinical forms and a possible prolonged survival, despite presence of metastases. In the present study, we have studied the clinical and biological characteristics of 119 decreased MTC patients. METHODS: Our data were retrieved retrospectively from the French medullary thyroid cancer study group (GETC). RESULTS: Our results showed that the cause of death was basically MTC (87%) but not exclusively, depending on the clinical forms and the age. Patients with type IIb multiple endocrine meoplasia (MEN) died earlier from their carcinoma. Patients with type IIa MEN died of causes other than MTC, especially pheochromocytoma. Two-thirds of the patients with sporadic forms of MTC, died with advanced metastases, usually from MTC. CONCLUSION: A significant number of deaths in patients with medullary thyroid carcinoma result from non-cancerous causes. This study established the clinical and biological characteristics of patients at risk of death.

Adolescent↗

111In-pentetreotide scintigraphy in the post-thyroidectomy follow-up of patients with medullary thyroid carcinoma.

Local and lymphnodal recurrences of medullary thyroid carcinoma (MTC) in thyroidectomy patients with elevated plasma levels of calcitonin and/or CEA can be detected using 111In-pentetreotide (Octreoscan: OCT) scintigraphy, although the sensitivity of this technique in localizing an intrathyroid recurrence of tumor is affected by the low target/non-target uptake ratio. The survival rate of patients with MTC, who have undergone thyroidectomy and who show evidence of a rise in plasma levels of calcitonin and/or CEA is closely linked to the number and localization of the metastases. However the role of conventional imaging techniques (X-rays, US, CT, and MR) in the follow-up after thyroidectomy is controversial. Numerous radiocompounds are currently being used to detect local and distant recurrences of MTC. The present study evaluated OCT and pentavalent 99mTc-dimercapto-succinic-acid (99mTc-DMSA-V) scintigraphy performed in 13 patients with a histologic diagnosis of MTC and in one with MEN 2A, all of whom had undergone thyroidectomy between 3 months and 15 years before. The patients also underwent 123I (NaCI) scintigraphy to evaluate the sites and extension of thyroidal remnants. 111In-pentetreotide scintigraphy was positive in 9/14 patients (64%); the 99mTc-DMSA-V was positive in 5/14 patients (35%). 111In-pentetreotide scintigraphy recognized 18 sites of abnormal uptake (12 in the neck); 9mmTc-DMSA-V detected 9 MTC recurrences in the same patients. In conclusion, 111In-OCT scintigraphy represents, in the authors' experience, a useful method, more sensitive than 9mmTc-DMSA-V, to detect MTC recurrences in patient follow-up post-thyroidectomy.

Adult↗

Radiolabeled somatostatin analog scintigraphy in medullary thyroid carcinoma and carcinoid tumor.

The aim of this study was to evaluate the effectiveness of a recently developed radiolabelled somatostatin analog (111In-pentetreotide) for the detection and localization of both medullary thyroid carcinoma (MTC) and carcinoid tumors, and to compare the results obtained with the results of 99mTc(V)-DMSA, and radioiodinated MIBG imaging. 111In-pentetreotide scintigraphy was performed in 9 patients with MTC and in 9 patients with carcinoid tumor. Whole body and SPECT studies were performed at 4 and 24 hours post-injection. SMS scintigraphy gave a positive result in 5 out of 7 patients with proven MTC lesions, and in 7 out of 9 patients with known lesions of carcinoid tumor. It gave a negative result in 2 MTC patients with high levels of calcitonin but with no evidence of disease at conventional diagnostic modalities. The scintigraphic results were comparable with those obtained with 99mTc(V)-DMSA in MTC and were superior to those of radioiodinated MIBG in both MTC and carcinoid tumors. When compared with the modifications of calcitonin levels brought about by the acute administration of octreotide ("Octeotride test"), these correlated well in 8 out of 9 patients studied.

3-Iodobenzylguanidine↗

bcl-1 gene rearrangements in mantle cell lymphoma: a comprehensive analysis of 118 cases, including B-5-fixed tissue, by polymerase chain reaction and Southern transfer analysis.

We evaluated 118 cases of mantle cell lymphoma by polymerase chain reaction (PCR) for the major translocation cluster (MTC) region and another breakpoint corresponding to probe p94PS, located 24 kb telomeric to the MTC locus on chromosome 11. The specimens included 64 frozen, 19 formalin-fixed, and 9 B-5-fixed lymph nodes and 26 B-5-fixed bone marrow biopsy specimens. We also analyzed DNA from the 64 frozen lymph nodes by Southern transfer analysis (SB) using three separate bcl-1 breakpoint probes. Gene rearrangements were identified in 17 (PCR) and 18 (SB) of 64 frozen lymph nodes and by PCR in 6 of 19 formalin-fixed lymph nodes, 3 of 9 B-5-fixed lymph nodes, and 12 of 26 B-5-fixed bone marrow cores with MTC locus primers and probe. Only one case showed rearrangement with the p11EH probe that corresponds to breakpoints situated 63 kb telomeric to the MTC locus. No rearrangements were detected by PCR or SB for the breakpoint site corresponding to the p94PS probe, but we identified a polymorphic restriction site with HinD III digest in approximately 25% of the cases. In agreement with other studies, these results confirmed that breakpoints in the MTC region of the bcl-1 locus are tightly clustered and associated with 30 to 40% of mantle cell lymphomas. Other breakpoints in the bcl-1 locus seem to be heterogeneous and cannot be detected by PCR or SB with use of existing probes or primer sequences. The most important finding of our study is optimization of the methodology for the detection of immunoglobulin heavy chain gene rearrangement and MTC region breakpoints by PCR from the DNA isolated from B-5-fixed, paraffin-embedded lymph nodes and bone marrow biopsy specimens. The results obtained from these tissues are comparable to those obtained from frozen or formalin-fixed tissue.

Blotting, Southern↗

TFF1 gene expression in human medullary thyroid carcinoma.

Medullary thyroid carcinoma (MTC) is an uncommon tumour of calcitonin-secreting C-cells of the thyroid gland. This cancer represents an important potential model for the study of mechanisms of human epithelial cell transformation. Although recent studies have identified the gene involved in familial forms of MTC, little is known about the molecular pathogenesis of the sporadic variants of this tumour. The biological and prognostic significance of TFF1 expression, particularly in diverse human malignancies, suggests that the TFF1 protein could have a role in human neoplasia. Furthermore, in prostate cancer it has been demonstrated that TFF1 expression is closely associated with premalignant changes and neuroendocrine differentiation. In the present study, the expression of TFF1 was analysed in 18 human MTCs, comprising sporadic and familial tumours, C-cell hyperplasia, and one case of lymph gland metastasis. TFF1 expression was also examined in the cultures of a human MTC-derived tumour cell line (TT cell line). The results showed that ten sporadic tumours, three hereditary tumours (including C-cell hyperplasia), and one lymph gland metastasis displayed TFF1 immunoreactivity. Indirect fluorescence immunocytochemistry and Western blotting revealed that the TFF1 protein was strongly expressed in the TT cells. Northern analysis revealed that tumours and TT cells expressed the TFF1 transcript. Although the function of TFF1 protein in the carcinogenesis of MTC remains to be elucidated, its expression in the majority of cases of both sporadic and hereditary tumours, metastatic tumours, and in C-cell hyperplasia suggests that it may contribute to the pathogenesis of MTC.

Adolescent↗

The detection of elevated plasma levels of carcinoembryonic antigen in patients with suspected or established medullary thyroid carcinoma.

Plasma levels of carcinoembryonic antigen (CEA) and calcitonin (CT) were measured in 35 normal control subjects and in 37 patients with suspected or established medullary thyroid carcinoma (MTC). None of the normal control subjects had elevated basal plasma levels of either CEA (greater than 5 ng/ml) or CT (greater than 0.25 ng/ml). However, of the 37 patients with suspected or established MTC, 23 (62%) had elevated basal plasma levels of CEA (range 9.8--7,000 ng/ml) and 27 (73%) had elevated basal plasma CT values (range 0.30--500 ng/ml). Generally, patients with clinically apparent MTC, either primary or metastatic, had higher plasma CEA and CT levels than those with occult disease. A positive correlation was found (r = 0.785, p less than 0.01) when comparing basal plasma CEA and stimulated plasma CT levels in 20 patients. A marked increase above the basal plasma level of CT but not CEA was detected in each of six MTC patients following intravenous calcium or pentagastrin. These data demonstrate that basal plasma levels of CEA and CT were increased in a large percentage of patients with MTC. Plasma calcitonin levels unlike plasma CEA levels were more often elevated in patients with occult disease and were increased above basal following the intravenous administration of either calcium gluconate or pentagastrin.

Adolescent↗

Prognostic factors in medullary thyroid carcinomas. Survival in relation to age, sex, stage, histology, immunocytochemistry, and DNA content.

Patients with medullary thyroid carcinomas (MTC) were analyzed according to age, sex, and tumor stage. In addition, the MTC were screened for the predominant histologic pattern, immunocytochemical spectrum (60 tumors), and DNA content (DNA cytophotometry and DNA flow cytometry, 25 tumors). These findings were correlated with follow-up data available for 45 of these patients. Forty-eight percent of the tumors revealed a polygonal cell pattern, whereas 22% showed spindle-cell predominance. All tumors contained cytokeratin, chromogranin A, and calcitonin (CT). Calcitonin gene-related peptide (CGRP) was present in 92%, carcinoembryonic antigen (CEA) in 77%, neuron-specific enolase (NSE) in 75%, and vimentin in 53% of cases. Positivity for neurotensin, somatostatin, neurofilaments, bombesin, and alpha human chorionic gonadotropin (a-hCG) and serotonin ranged between 3% and 27%. All MTC were negative for substance P, adrenocorticotropic hormone (ACTH), thyroglobulin (TG), or S-100 protein. Local recurrences and regional lymph node metastases revealed identical staining patterns as the primaries. Prognosis of MTC was found not to be related to histologic features (dominant architectural pattern, cellular shape, presence of amyloid deposits) or immunocytochemical pattern. Instead, survival was significantly correlated to age, sex, and stage of disease. The best prognosis was seen in women younger than 40 years and revealing an early stage of disease. DNA measurements added valuable information in assessing the prognosis of MTC.

Adult↗

Clinical characteristics in sporadic and familial medullary thyroid carcinoma. A nationwide study of 249 patients in Sweden from 1959 through 1981.

All patients with medullary thyroid carcinoma (MTC) diagnosed in Sweden during 1959 through 1981 were recruited for study from the Swedish Cancer Registry. Among a total of 249 patients, 66 were diagnosed in 1959 through 1969 and 183 from 1970 through 1981. Apparently sporadic MTC was present in 186 patients, and familial MTC in 63. Twenty-seven patients with familial MTC were diagnosed from clinical symptoms and 36 by screening. In both the sporadic group and the symptomatic familial group, approximately 80% of the patients had palpable thyroid tumors. Lymph node metastases were present in 44% of the sporadic group and in 37% of the group with symptomatic familial MTC, and distant metastases in approximately 20% of the patients in each of these groups. The patients detected by screening differed significantly from the two groups of symptomatic cases by having a lower frequency of palpable thyroid lesions (50%), smaller tumors, and lower frequencies of cervical lymph node metastases (14%) and distant metastases (0%). Multivariate analyses revealed no significant differences between sporadic cases and symptomatic familial cases regarding tumor size or stage. Large tumors (greater than 3 cm) were more frequently accompanied by palpable cervical lymph nodes and were associated with an approximately four times higher risk of distant metastases than tumors smaller than 1 cm. Women had significantly smaller tumors and a more favorable stage distribution than age-related men.

Adult↗

The intratumoral immunoassayable somatostatin concentration is frequently elevated in medullary thyroid carcinoma. Results in 34 cases.

The current work has been performed by the Cooperative French Group of Medullary Thyroid Carcinoma (GETC). A systematic evaluation of RIA somatostatin (SRIH) was performed in 34 medullary thyroid carcinomas (MTC) (25 inherited, seven sporadic). Plasma SRIH was measured by radioimmunoassay in parallel with calcitonin (CT) and carcinoembryonic antigen (CEA). Immunoassayable SRIH was tested in fresh tumoral tissue samples from the same 34 MTC and, for comparison, in 10 nontumoral thyroid extracts (less than 6 pmol/g wet). Although plasma SRIH was only slightly elevated in two of 20 cases, tumoral SRIH was elevated in 70.6% of our MTC (10 to 3973 pmol/g). The chromatography of two tumoral extracts showed that somatostatin 14 was the major molecular form. We found no correlation (P greater than 0.1) between tumoral SRIH and the following: (1) tumor size (r = 0.227); (2) epidemiologic form of MTC (r = 0.144); (3) plasma SRIH (r = 0.045), plasma CT (R = 0.095) or (4) plasma CEA (r = 0.032). Thus, in the authors' experience, SRIH appears as a major product of tumoral C-cell in human MTC, even when plasma SRIH is normal and SRIH immunohistochemical staining is scarce. Multiple hormonal production of these tumors may explain its presence but SRIH may act also as a regulator, since negative influence of SRIH on CT is demonstrated in normal as well in tumoral conditions.

Adolescent↗