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PubMed1991

[A simple method for detecting immature precursors after in vitro bone marrow treatment with ASTA-Z 7654].

Cyclophosphamide derivatives for in vitro use, such as mafosphamide L lysine (ASTA-Z 7654) are capable of removing residual leukaemic cells from the bone marrow used for autologous transplantation. ASTA-Z also removes committed stem cells detected in semi-solid cultures (CFU-GM). However, haemopoiesis is preserved by more immature progenitors, undetected in usual cultures but detectable in liquid culture of 21 days (MTC). After treating 15 normal bone marrow specimens with 100 microM ASTA-Z, CFU-GM cultures and medium-term cultures (MTC) are carried out. CFU-GM are cultured on the 21st day of incubation from the cell suspension of the MTC. The CFU-GM made the day of in vitro treatment (0.9 colonies/plate) reappear in the CFU-GM cultures performed on the 21st day of incubation of MTC (42 colonies/plate), although the figures attained in parallel controls without any treatment are not fully reached.

Bone Marrow Purging↗
PubMed1990

[A registry of medullary thyroid cancer in West Germany].

A register for medullary thyroid carcinoma (MTC) in FRG has been set up by the "German Medullary Thyroid Carcinoma Study Group" in 1988. The aim is to provide a basis for collaborative work on MTC especially in the hereditary forms (i.e. multiple endocrine neoplasia [MEN] type IIa, IIb). For these hereditary varieties reliable screening tests exist and, if the disease is detected by family screening in an early stage, curative surgery is possible. Until now 408 patients (234 female, 174 male) with MTC have been reported by 17 cooperative centers. The mean age at diagnosis was 45.5 years. 25% (n = 104) are hereditary forms, most of them MEN IIa (n = 86), 13 are MEN IIb and 18 belong to the familial variety without other endocrinopathy. The mean age at diagnosis for MEN IIa was 36.5 years, MEN IIb 26.9 and for the pure familial form 27.5 years. As 33 patients per year have been diagnosed since 1982, nearly 25% of all expected cases of MTC in FRG have been registered.

Adult↗
PubMedDate not supplied

Deletion mapping on the distal third region of chromosome 1p in multiple endocrine neoplasia type IIA.

Multiple endocrine neoplasia type IIA (MEN IIA) syndrome is an autosomal-dominant endocrine disorder that consists of medullary thyroid carcinoma (MTC), pheochromocytoma, and parathyroid hyperplasia. The susceptibility gene to this disorder has been mapped to chromosome 10. However, molecular studies of tumor cells from patients with familial and sporadic MTC and/or pheochromocytoma have shown a high frequency (50%) of abnormalities on chromosome 1p. In the present study, we examined MTC or pheochromocytoma tumor specimens from eight patients (familial and nonfamilial cases) to investigate gene losses on chromosomes 1 and 10 as potential mechanisms for the tumors' development. The patients studies had homozygous genotypes in their leukocyte DNAs for the chromosome 10 marker used in this study, and the patients were, therefore, uninformative. However, the patients were informative for the chromosome 1 markers and five of the patients' tumor-cell DNAs (63%) had allelic deletions at one or multiple loci on chromosome 1p, and one tumor DNA had evidence of possible gene rearrangement; in all six cases, the abnormalities involved the distal third of chromosome 1p. Furthermore, we determined that the common break point for the 1p deletions was at 1p32. These results suggest that a tumor suppressor gene in this defined region is involved in the development/progression of MTC and pheochromocytoma by being either lost or inactivated.

Adolescent↗
PubMed1990

[Multiple endocrine type 2 neoplasia in 3 families].

In the last 15 years, 29 subjects (13 males, 16 females) aged 8-69 years, belonging to 3 kindreds with multiple endocrine neoplasia type 2 (MEN-2) were studied with rapid i.v. calcium gluconate infusions (2 mg Ca++/kg in 1 minute) in order to detect the presence of medullary thyroid cancer (MTC). Serum samples were obtained at 0, 2, 5, 7 and 10 minutes. Calcitonin was measured by radioimmunoassay using a commercial kit. On the basis of the results obtained in a control group of 28 healthy volunteers, hypercalcitoninemia (HCT) was defined as basal and stimulated values above 100 and 200 pg/ml, respectively, in either sex. In 2 patients with nodular goiter, HCT correctly predicted the malignant nature of the lesions. Out of 22 clinically normal subjects, 3 had HCT: one refused consent for surgery, but in the remaining 2 MTC was found, without extraglandular extension. Seven patients with surgically proven MTC have been followed; 4 have shown HCT: 3 women refused permission for exploratory surgery, and a 46 year old male with enlarged lymph nodes in the neck was found to have metastatic papillary thyroid cancer. Both calcitonin and thyroglobulin were immunohistochemically discovered in metastases and the original thyroid tumor (differentiated thyroid cancer, intermediate type). There were 2 false negative tests in patients with metastatic disease. This type of biochemical screening in members of MEN-2 kindreds allows early detection of MTC and its prevention through thyroidectomy in a preneoplastic stage (C-cell hyperplasia).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Multilocular thymic cyst: an acquired reactive process. Study of 18 cases.

The clinical and pathologic features in 18 cases of multilocular thymic cyst (MTC) of the anterior mediastinum unassociated with Hodgkin's disease or seminoma were studied. The majority of cases were asymptomatic and discovered incidentally on routine chest x-ray. Several patients presented with acute symptoms of chest pain or discomfort, sometimes associated with dyspnea. Two cases had an incidental thymoma, and two had an incidental thymic carcinoma. The main histologic features of MTC included the following: multiple cystic cavities partially lined by squamous, columnar, or cuboidal epithelium (some having features of Hassall's corpuscles); scattered nests and islands of non-neoplastic thymic tissue within the cyst walls, often continuous with the cyst lining; severe acute and chronic inflammation accompanied by fibrovascular proliferation, necrosis, hemorrhage, and cholesterol granuloma formation; and reactive lymphoid hyperplasia with prominent germinal centers. These features suggest that MTC most likely results from the cystic transformation of medullary duct epithelium-derived structures (including Hassall's corpuscles) induced by an acquired inflammatory process. The changes are similar to those sometimes seen in association with thymic Hodgkin's disease and thymic seminoma, which are also probably due to the inflammation that accompanies these tumors rather than to the tumors themselves. We believe that MTC is pathogenetically analogous to a variety of cystic conditions of the head and neck region, for which the common denominator seems to be the induction of cystic transformation in ductular epithelial formations of branchial pouch or related derivation by an acquired inflammatory process.

Adolescent↗
PubMed1991

Rearrangement of the chromosome 11 bcl-1 locus in centrocytic lymphoma: analysis with multiple breakpoint probes.

Centrocytic lymphoma is a B-cell non-Hodgkin's lymphoma (NHL) composed of lymphocytes resembling cleaved follicular center cells (centrocytes). Previous studies have suggested an association between t(11;14) chromosomal translocations and bcl-1 rearrangement in centrocytic and related intermediate lymphocytic lymphomas. To further characterize the association between bcl-1 and centrocytic lymphoma, Southern blot analysis was performed on samples from 23 patients using four separate bcl-1 breakpoint probes spanning 63 kb of the chromosome 11 bcl-1 locus. Rearrangements were identified in six patients with the major translocation cluster (MTC) probe and in another six with probe p94PS, located about 24 kb 5' of MTC. Eleven of these 12 cases showed comigration of rearranged bcl-1 and Ig heavy chain-joining genes, consistent with the t(11;14) chromosomal translocation. No rearrangements were observed with the bcl-1 locus probes p210 or p11EH located 5' of p94PS, nor with bcl-2 or c-myc oncogene probes. No bcl-1 rearrangements were identified in B-cell follicular NHL (15), small noncleaved cell (Burkitt's and non-Burkitt's) NHL (8), T-cell NHL (4), multiple myeloma (14), and pre-B-cell acute lymphoblastic leukemia (9). One of 23 B-cell NHL of large cell type and one of 19 chronic lymphocytic leukemias or small lymphocytic NHL had MTC rearrangement. Thus, bcl-1 rearrangement occurred at MTC or p94PS in 12 of 23 centrocytic lymphomas (52%), confirming a nonrandom association and suggesting a pathogenetic role for the bcl-1 locus in this immunohistologic subtype of NHL.

Blotting, Southern↗
PubMed1990

[Effect of si jun zi tang on the macrophage cytotoxic activity in mice].

The effect of Si Jun Zi Tang (SJZT) on the activities of peritoneal macrophage (M phi) mediated MTC and ADCC in normal and immunosuppressed mice were examined by isotope releasing assay (51Cr, 125I-UdR). The results showed the SJZT no significantly increased peritoneal M phi-mediated cytotoxic activity (MTC, ADCC) in normal mice. After the injection of immuno-depressive cyclophosphamide (Cy) alone (ip), the cytotoxic activities were decreased, but by treatment with Cy and SJZT, the cytotoxic activities were significantly increased compared with Cy group, the enhancing rates amounted to 74.40% (M phi-MTC) and 121.03% (M phi-ADCC) respectively. It was demonstrated that the SJZT could protest against the effect that the Cy inhibited the activities of MTC and ADCC of peritoneal M phi in mice, but there was no significant effect on normal mice. It indicated that the function of SJZT's immunoregulation was related to the state of immune in body.

Animals↗
PubMed1989

The importance of screening for medullary thyroid carcinoma in families of patients with MEN 2.

Family screening for medullary thyroid cancer (MTC) is important for detecting members of multiple endocrine neoplasia type 2 (MEN 2) families who may be gene carriers but show no clinical evidence of the disease. Most members of our MEN 2 families are screened yearly by measuring basal and pentagastrin-stimulated calcitonin (CT) levels. A 15-year-old first-degree relative of an affected member of the D-kindred showed a normal basal and an elevated stimulated CT level. Clinical examination, ultrasonography, and scintigraphy were normal. Thyroidectomy and bilateral neck dissection revealed a multicentric MTC with no lymph node involvement. In the O-kindred we detected elevated basal and/or stimulated CT levels in three asymptomatic first-degree relatives. At surgery we found a small multicentric MTC in one family member, C-cell hyperplasia in another member, and bilateral lymph node metastases in one member who had been previously thyroidectomized. Basal and stimulated CT estimations in MEN 2 family members provide an effective method for detecting MTC in early, treatable stages.

Adolescent↗
PubMed1988

Medullary thyroid carcinoma: localization of a mediastinal metastasis with I-131 MIBG.

An I-131 metaiodobenzylguanidine (MIBG) scan was performed in a patient with a familial history of multiple endocrine neoplasia (MEN) type 2 and recurrent medullary thyroid carcinoma (MTC). The scan revealed a mediastinal metastasis from her MTC and there was also an imaging pattern of bilateral adreno-medullary hyperplasia. Although the literature indicates that I-131-MIBG scanning is not sufficiently sensitive for the detection of MTC, this procedure has proven to be of value in the management of chosen patients with MEN-associated MTC.

3-Iodobenzylguanidine↗
PubMed1987

Dopaminergic regulation of gonadotropin levels and pulsatility in normal women.

This study was done to define the concentration of dopamine (DA) that inhibits gonadotropin secretion and to study the effect of DA D-2 receptor blockade during the infusions. Normal women received 5-hour infusions of either glucose (n = 14) or DA at rates of 0.04 (n = 6), 0.4 (n = 6), and 4.0 micrograms/kg X minute (n = 9). After 3 hours, metoclopramide (MTC) was administered. Mean serum luteinizing hormone (LH) concentration declined during 0.4 (P less than 0.01) and 4.0 micrograms/kg X minute (P less than 0.05) infusion doses of DA. This effect of DA was not consistently (P greater than 0.05) antagonized by MTC. Six women received DA (4.0 micrograms/kg X minute) or glucose for 18 hours. After 17 hours, MTC was given. Blood samples were collected every 10 minutes during the last 8 hours. No significant effect on LH pulse frequency and pulse amplitude was observed (P greater than 0.05). A marked (P less than 0.01) rise in LH occurred after MTC administration. The authors conclude that (1) physiologic doses of DA may inhibit LH secretion with only little, if any, effect on the pulsatile release; and (2) low-affinity DA receptors responsive to DA D-2 antagonists may regulate LH secretion.

Adult↗
PubMed1988

[Comparative study of the effects of metoclopramide and metopimazine on the duodenojejunal motility during the interdigestive period: a manometric study in healthy subjects].

The objective of this paper was to compare the effects of metoclopramide (MTC) and of metopimazine (MTP) on intestinal motility in normal subjects in the period between digestion by injecting these two agents at a well-defined time of the migrating motor complex (MMC). Duodenojejunal motility was recorded by manometry (four microperfused catheters; study segment: 30 cm) during the period between phases of digestion (fasting greater than 12 hrs), for 4.6 hrs on average (3, 4, 6 hrs). 14 normal volunteer subjects (6 males, and 8 females 19 to 49 years of age) were randomly assigned to 2 study groups and were given MTC (10 mg) or MTP (10 mg) in slow IV injection (5 mins.) at a controlled rate, performed 25 mins after onset of a phase 3 (P3) in the study segment. As a reference, results obtained in a control group of seven subjects recorded under the same conditions are reported, in addition. Changes in MMC were evaluated in each group by the mean number of P3 hourly and the percent of subjects presenting a P3 within the two hours following injection of the test drug. Variations in phase 2 type motility (P2) were measured using motility indices (MI): the sum of the amplitudes, number of waves, per 5 minute interval. The number of hourly P3 was 0.40 for MTC vs 0.28 for MTP (control 0.47); 90 minutes after an injection, the first P3 appeared in 71% of patients in the MTC groups vs. 14% in the MTP group (control 57%). P3 recorded following injection were not different from the preceding in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

Cloning and biosynthetic studies of rat somatostatin.

The predicted amino acid sequence of rat preprosomatostatin has been obtained by cloning and subsequent DNA sequence analysis of a cDNA obtained from mRNA prepared from a rat medullary thyroid carcinoma (MTC). The predicted preprosomatostatin is 116 amino acid residues in length. Somatostatin-14 is located at the C-terminus of the preprohormone and the amino terminus contains a 'signal' peptide of 24 amino acids. A somatostatin amino terminal protein of 78 residues is found between the signal peptide and somatostatin-14. Both somatostatin-14 and somatostatin-28 are observed in the thyroid tumour C-cells. A comparison of the rat and human preprosomatostatin amino acid sequences shows only 4 substitutions observed in 116 amino acids. Patients with localized MTC often exhibit high serum calcitonin levels while patients showing cellular heterogeneity in the MTC appear to have lower calcitonin levels and a virulent neoplasia with a grave prognosis. Numerous rat MTCs have been examined by two dimensional gel electrophoresis. It is possible to distinguish characteristic differences in protein profiles of tumours producing high levels of calcitonin from those showing low calcitonin and high somatostatin levels. This analysis can be done with less than 1 mg of tissue and may represent a valuable prognostic tool in evaluating the clinical variability of MTC.

Amino Acid Sequence↗
PubMed1984

[Value of the assay of plasma carcinoembryonic antigen and thyrocalcitonin in the detection of medullary cancer of the thyroid with amyloid stroma. Results of a familial survey of 47 subjects].

During a study of 80 subjects from the same family, 47 persons underwent clinical examination and blood sampling for carcinoembryonic antigen and thyrocalcitonin. A preliminary investigation had shown that two members of the family had histologically confirmed amyloid stroma MTC, 2 others had probable malignant disease, 3 children died of intestinal obstruction in the neonatal period, and a fourth child operated for megacolon when 3 days old was the descendant of 2 subjects with probable thyroid carcinoma. Three years later, the study was updated and concentrated on the patients with the highest risk of developing malignant disease. The diagnosis was confirmed in one patient considered to have probable MTC. One case of malignant disease was discovered in a child considered to be normal 6 years previously. Three other patients, considered to be normal 6 years before had very probable MTC. These results indicated that familial investigations including plasma calcitonin measurements after pentagastrin stimulation, are valuable when amyloid stroma MTC is diagnosed in one member of the family. This test should be repeated periodically. The surgical indications in patients with abnormal responses should take into consideration the psychological context.

Adolescent↗
PubMed1984

[Role of radiotherapy in the treatment of medullary cancer of the thyroid].

Medullary thyroid carcinoma (MTC) is a rare tumor for which the main treatment is surgery. However, external radiation therapy (RT) plays an important part in well-defined patients. Out of the 115 patients with MTC treated at the Institute Gustave Roussy: Thirty-five MTC patients with residual cervical disease and without distant metastases had their thyroid region irradiated (60Co, 45 to 50 Gy in 5 weeks). The overall survival of these patients is similar to that of patients with limited cervical extension (n = 57) treated by surgery alone. The results of this study show the effectiveness of cervico-mediastinal irradiation treatment for MTC with extensive local tumor after incomplete surgery. Eight MTCs with inoperable cervical tumor were treated only by external RT. Median survival was 44 months. In six of them, long-term local control was observed: three are alive at 52, 62 and 70 months and 3 died from distant metastases at 36, 36, and 117 months after treatment. Sixteen MTCs with distant metastases were treated with RT on bone metastases (n = 10) or compressive lymph node metastases (n = 6) with good palliative effect. This study shows the efficacy of post-operative external RT in MTCs with extensive cervical tumors, as a curative treatment in non-surgically eradicable cervical tumors and as a palliative treatment for metastatic localisations. The technique of cervico-mediastinal RT is discussed.

Bone Neoplasms↗
PubMed1984

Heterogeneity in induced heat resistance and its relation to synthesis of stress proteins in rat tumor cell clones.

Tumor cell clones isolated from a rat 13762NF mammary adenocarcinoma and its spontaneous metastases were heterogeneous in their survival responses to continuous 42 degrees heating. Clones MTLn3 and MTF7 had similar initial survival responses; they were significantly less sensitive than clone MTC. Following the first decrease in survival, different magnitudes of induced thermal resistance were observed. When ratios of the first and resistant slopes of survival curves were compared (the thermotolerance ratio), the order of induced thermal resistance was MTLn3 greater than MTF7 greater than MTC. These clones were compared for the rates of synthesis of heat stress proteins (HSP). The same four major HSP at Mr 112,000, 90,000, 70,000, and 22,000 were induced or enhanced in all 3 clones. The rates of synthesis of these HSP were analyzed through a unique system of computer-assisted video densitometry and digitization. When all 4 HSP were analyzed as a group, the rates were significantly different (p less than 0.017), and the rank order of rates of synthesis was significant with MTLn3 greater than MTF7 greater than MTC. Induction kinetics of the individual HSP were different. Individually, the HSP at Mr 112,000, 90,000, and 22,000 were synthesized at significantly different rates between clones (p less than 0.001) but the Mr 70,000 HSP was not. Absolute total protein synthesis was highest for clone MTLn3, and MTF7 was higher than MTC but only marginally. Although absolute accumulations of these HSP could not be directly compared between these clones, the higher rates of HSP synthesis in these tumor cell clones correlated with more thermal resistance. These data support the working hypothesis that one or more of these HSP have a direct role in the mechanism(s) for inducing thermal resistance in rat tumor cells, but other factors such as total protein synthesis could modify the complex bio-chemical and phenotypic pathways involved in induced HSP and thermal resistance.

Adenocarcinoma↗
PubMed1984

[Chemotherapy for medullary cancer of the thyroid. Phase II trials with adriamycin and cis-platinum administered as monochemotherapy].

Medullary thyroid carcinoma (MTC) is a rare tumor, and patients with distant metastases have a poor prognosis. Chemotherapy efficacity is not well established and we have conducted a phase II trial of monochemotherapy with Adriamycin (ADR) and Cis-platinum (CDDP) in 18 patients. Fourteen MTC have been treated by ADR, the dose was 60 mg/m2 every 4 weeks. The mean number of administration has been 5.3. The results have been: 1 complete response (6 months), 1 partial response (36 months), 1 minor response, 4 stabilisations and 6 failures. The overall responses rate has been 15 per cent and the toxicity has been low. Fourteen MTC have been treated by CDDP. Ten patients had been treated before with ADR. The dose of CDDP was 90 mg/m2 in two hours perfusion with hyperhydration administered every 4 weeks. The mean number of treatment has been 5. The results have been: 1 complete response (9 months), 2 partial responses (16 and 48 months), 4 stabilisations and 7 failures. The overall responses rate has been 21 per cent. In conclusion, ADR and CDDP have some, but limited, efficiency in treatment of metastatic MTC. The effect of their association must be evaluated.

Adolescent↗
PubMedDate not supplied

Metastatic medullary thyroid carcinoma in sputum. A light and electron microscopic study.

Medullary thyroid carcinoma (MTC) was diagnosed in a 43-year-old male by light microscopy, electron microscopy and immunohistochemistry. Five years after thyroidectomy, malignant cells with the typical cytologic and electron microscopic features of MTC were seen in his sputum, and extensive pulmonary metastases from MTC were subsequently documented at autopsy. Sputum examination is a useful diagnostic technique in patients with MTC in whom pulmonary metastases are suspected.

Adult↗
PubMed1995

[Somatostatin receptor scintigraphy in medullary thyroid carcinomas, GEP and carcinoid tumors].

For this study, 24 patients with medullary thyroid cancer (MTC) and 10 with carcinoid-/GEP-tumours underwent scintigraphy with 123I-Tyr3-octreotide or 111In-DTPA-D-Phe1-octreotide (Octreoscan) or 99mTc-V-DMSA. Calcitonin and CEA were elevated in MTC patients, the other had tumour lesions on CT. Octreoscan-scintigraphy was positive in 68% of all suspicious cases. On the other hand, 123I-Tyr3-octreotide showed only rarely positive results. 99mTc-V-DMSA-scans in MTC patients were positive in 23%. Liver metastases could be seen only with Octreoscan in the non-MTC-group. These results showed better sensitivity of 111In-labelled octreotide.

Adult↗