Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

mRNA isolated from medullary carcinoma of the thyroid (MTC) in six patients with the inherited multiple endocrine neoplasia syndrome type 2 and cervical metastases in two patients with sporadic MTC was screened for the presence of calcitonin and proopiomelanocortin (POMC) related sequences by blot hybridization analysis. All tumors were found to contain mRNA hybridizing to a calcitonin-specific probe. However, POMC-related sequences were detected only in RNA preparations purified from the metastases of MTC. Compared with the POMC mRNA occurring in the human pituitary gland, the size of the RNA species hybridizing to the POMC-specific probe was larger in the metastases of both of the patients investigated. cDNA complementary to mRNA from one of the metastases was cloned into pBR 322. From this library two plasmids were isolated containing inserts which were completely homologous to a sequence of 190 nucleotides from the 3'-end of human pituitary POMC mRNA. In conclusion, 1) hybridization and nucleotide sequence analyses demonstrate that the POMC gene is expressed in MTC metastases; 2) the observed length difference between MTC and pituitary mRNAs suggests differences in expression or processing; 3) no expression of the POMC gene was found in six primary tumors.
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PMID:Expression of the proopiomelanocortin gene in human medullary thyroid carcinoma. 654 64

We have examined cell clones obtained from a 13762 mammary adenocarcinoma tumor and its spontaneous lung metastasis for phenotypic stability during serial culture passage in vitro. Two clones that varied markedly in their metastatic properties were chosen for further examination. One of these clones (MTC) obtained from the parental transplanted tumor initially failed to metastasize within 23 days post-injection s.c. but gained the ability to form spontaneous pulmonary metastases after several serial passages in vitro. Another clone (MTLn3) derived from a spontaneous lung metastasis was initially higher metastatic from short-term culture, but lost the potential to form large numbers of spontaneous lung metastases with long-term culture. In contrast to MTA, clone MTLn3 displayed lymph-node metastasis, and the frequency of lymph-node involvement increased when late-passage cultures of MTLn3 cells were assayed in vivo. Both clones from late-passage cultures produced larger tumor sizes at the primary (mammary fat pad) injection sites compared to early passage cells. The morphologies of MTC cells changed with serial tissue culture passage, while the morphologies of MTLn3 cells did not change. The display of fibronectin on MTC cells by immunofluorescence did not change with culture passage; fibronectin was not detected in cultures of clone MTLn3. Fibronectin was also found on MTC cells by cell surface labelling using lactoperoxidase-catalyzed iodination-sodium dodecylsulfate polyacrylamide gel electrophoresis-autoradiography. Iodination of fibronectin on MTC cells did not vary with culture passage, and as in immunofluorescence experiments it was not detected on MTLn3 cells. There was a decrease in exposure of certain cell surface proteins on MTC cells with culture passage, but we did not detect modifications with this procedure that correlated with culture passage of MTLn3 cells. We conclude that prolonged culture in vitro can result in modifications fo metastatic and cell-surface properties of tumor cell clones.
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PMID:Phenotypic drift of metastatic and cell-surface properties of mammary adenocarcinoma cell clones during growth in vitro. 703 55

In this paper we have briefly outlined our views on the management of hereditary MTC. We have stressed the fact that although many patients with the usual form of disease have an indolent clinical course there exists a population of patients who may be at risk for widely disseminated virulent tumour. Also, some patients can have marked invasion of adjacent tissues in the cervical region from localized tumour. Hence it seems rational to attempt removal of the primary tumour prior to the development of regional or distant metastases. The role of the combined calcium-pentagastrin provocative test to identify patients with preclinical disease has been outlined. The only definitive treatment for the disease is total thyroidectomy with resection of adjacent cervical nodes. Many patients who are treated at a time when the disease has become clinically detectable will have residual tumour or recurrence as indicated by abnormal calcitonin levels in the blood. Since most of these patients seem to take an indolent clinical course, it is suggested that they should not be treated with radiation therapy and/or chemotherapy, even though residual MTC is known to be present. Even in patients with advanced stages of MTC, the use of chemotherapy and radiation therapy has not been encouraging. However, some aspects of the management of patients with aggressive disease are discussed. Finally, the lack of features to predict which patients may have a poor prognosis is outlined and some new approaches to defining such parameters are discussed.
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PMID:Management of hereditary medullary thyroid carcinoma. 728 85

Mutational changes in the p53 tumor suppressor gene are the most frequent genetic alterations in human malignant tumors. Studies have shown a correlation of p53 expression in breast cancer with tumor prognosis. In contrast to mutational activation of ras and GSP in thyroid tumors, little is known about the role of p53 in thyroid tumor development. Therefore thyroid tumors and thyroid tumor cell lines were studied for the presence of p53 mutations. Snap-frozen tissues from 57 differentiated thyroid carcinomas (DTCs) and 5 goiters were studied by immunohistochemical methods. A panel of six antibodies (pAb 240, 421, 1620, 1801, DO7, and CM1) was employed by using the ABC technique. Five cell lines from DTCs (FTC133, 236, 238, PTC337, MTC164) were examined by the same technique. Additionally, genomic DNA from the cells was amplified by the polymerase chain reaction (PCR) and the PCR product studied for p53 mutations (R273H) by mutation-specific oligonucleotide hybridization (MOH) and temperature gradient gel electrophoresis (TGGE) for the p53 exon 8. None of the benign thyroid tumors and 7 of 57 (12%) DTCs strongly express p53 with a heterogeneous distribution in the tumor tissue. All seven patients have metastatic disease or dedifferentiated tumors G3 (three of seven). CM1 was positive in two cell lines (FTC-133, PTC-337), questionable in FTC-238, and negative in FTC-236 and MTC-164. All three follicular cell lines, however, and the original tumor tissue showed the same p53 mutation (R273H) in MOH analysis and TGGE. P53 mutations are rare in thyroid tumors, but the presence of p53 mutations indicates a poor prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Significance of P53 in human thyroid tumors. 772 41

Increased expression of EGF receptor (EGFR) in metastases of human mammary carcinoma as compared to cells of the primary cancer suggests a contribution of EGFR to mammary carcinoma metastasis. To test for a positive causative link, we investigated 13762NF rat mammary adenocarcinoma cloned tumor cell lines of high (MTLn3) or low (MTC) metastatic potential. While MTC cells expressed barely detectable amounts of EGFR, MTLn3 cells expressed readily detectable levels of functional receptors. A full length cDNA of the human EGFR (HER) was introduced by infection with a retroviral vector into MTC cells. Expression of HER was stable and receptors were functional with respect to surface expression, ligand binding and EGF-stimulated phosphorylation. Independent clones of the transfectants were isolated and characterized. Ligand stimulation of MTC HER cells and derived clones led to enhanced adhesion of cells to extracellular matrix proteins. Implantation of cells intravenously into female nu/nu mice revealed ligand-dependent enhancement of lung colonizing potential of EGFR-expressing cells.
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PMID:Ligand mediated activation of ectopic EGF receptor promotes matrix protein adhesion and lung colonization of rat mammary adenocarcinoma cells. 775 57

We characterized three clones of different metastatic capacity (MTC, MTLn2 and MTLn3) derived from the 13762NF rat mammary adenocarcinoma for their production and response to TGF-beta. All three clones expressed comparable amounts of TGF-beta 1 mRNA and secreted 100-300 pg/10(6) cells/24 h in a soluble latent form. TGF-beta was found in extracellular matrices produced by all three tumor clones. Addition of exogenous TGF-beta induced different responses. While the low metastatic clone MTC was highly sensitive to the growth inhibitory effect of TGF-beta (ID50 approximately 50 pg/ml), a 6-fold higher dose was necessary for the high metastatic clone MTLn3 (ID50 approximately 300 pg/ml). The clone with intermediate metastatic potential MTLn2 was unresponsive to TGF-beta (1 pg/ml to 3 ng/ml). Our data suggest that tumor cells can modulate their biological properties in an autocrine and/or paracrine fashion by virtue of expression of TGF-beta.
Invasion Metastasis 1993
PMID:Transforming growth factor-beta production and induction of cellular responses in 13762NF rat mammary adenocarcinoma cell clones. 796 May 77

Lymph node metastases at presentation are common in PTC and MTC (about one third of patients at presentation), but are rare in other types of thyroid malignancy, though HCC frequently recurs in lymph nodes. Nodal metastases can be detected by a variety of means, but high resolution ultrasonography may be the method of choice. Unlike other epithelial malignancies, in thyroid cancer neither prognostic significance nor optimal treatment of nodal metastasis are known with certainty. For PTC lymph node metastases at presentation do not seem to adversely affect survival, but do increase the risk of locoregional tumor recurrence. By contrast, in FTC nodal metastases at presentation may adversely affect cause-specific mortality, but because of their rarity definite conclusions are impossible. Except for the oxyphilic variant of FTC (HCC) nodal recurrence in FTC is rare. The most firm evidence of prognostic relevance for nodal metastases in thyroid malignancies exists in medullary thyroid cancer, where most studies suggest that survival and recurrence are both adversely affected by node-positive status at presentation. Primary treatment of nodal metastases is removal of macroscopically affected nodes at initial surgery, optionally supplemented with adjuvant radioiodine treatment in an attempt to reduce recurrence risk. The value, however, of postoperative radioiodine in preventing either nodal recurrence or cancer death in patients with papillary and follicular thyroid cancer remains controversial. Extensive lymph node dissection at presentation offers no advantage (and may cause increased morbidity) in papillary carcinoma, but may be useful in medullary thyroid carcinoma, where nodal metastases seem to increase the risk of cause-specific mortality. In all tumor types postoperative nodal recurrences should primarily be treated surgically.
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PMID:Thyroid cancer nodal metastases: biologic significance and therapeutic considerations. 878 93

A large number of endocrine tumors express somatostatin receptors, and the use of radiolabeled somatostatin analogs has been recently introduced for their localization. Using in vivo scintigraphy with 111In-pentetreotide, primary tumor localizations were demonstrated in 3/3 carcinoids (2 intestinal carcinoids and 1 lung ACTH-secreting carcinoid; in 2 patients liver metastases larger than 1 cm were visualized), in 1/1 GH-secreting pituitary macroadenoma, and in 1/1 thyroid localization of MTC. Bone and/or lymph node metastases were imaged in 2/4 patients previously treated for MTC, with persistently high CT and CEA levels; in the other 2 patients the other scintigraphic techniques were also negative. Octreotide scintigraphy was negative in 2/2 insulinomas and in 2/2 ACT-producing pituitary adenomas. In 2 patients with carcinoid syndrome and 1 patient with Cushing syndrome due to ectopic ACTH, octreotide therapy induced a significant decrease in tumoral markers. Our preliminary data are in agreement with the results of larger series reported in literature: octreotide scintigraphy is a useful noninvasive tool to detect endocrine tumors expressing somatostatin receptors, particularly for carcinoids. It is of great use in the differential diagnosis of Cushing syndrome due to ectopic ACTH. Moreover, 111In-pentetreotide scintigraphy may be useful in selecting patients who may benefit from octreotide therapy to control hormonal hypersecretion effects.
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PMID:111In-octreotide scintigraphy in endocrine tumors. Preliminary data. 900 67

Scintigraphy using [111In-DTPA-d-Phe1]-pentetreotide or pentavalent technetium-99m-dimercaptosuccinic acid [99mTc(V)-DMSA] has been shown to localize well-differentiated and slowly growing neuroendocrine tumours, whereas increased fluorodeoxyglucose (FDG) uptake is associated with malignancy. The aim of this study was to compare the value of fluorine-18 FDG positron emission tomography (PET) with that of somatostatin receptor scintigraphy (SS-R) and dual-radionuclide scintigraphy [SS-R and 99mTc(V)-DMSA = DNS] in detecting malignant neuroendocrine tumours. Fifteen patients with metastasizing gastroenteropancreatic tumours (GEP tumours; n = 7), medullary thyroid carcinomas (MTCs; n = 8) and elevated tumour markers [GEP tumours: 5-hydroxyindoleacetic acid, insulin; MTCs: calcitonin, carcinoembryonic antigen (CEA)] were studied. Prior to PET, all patients with GEP tumours underwent SS-R. DNS was performed in all patients with MTC. Patients had been fasting for at least 12 h and normal glucose plasma levels were confirmed. Sixty minutes after intravenous administration of 18F-FDG (mean: 374 MBq) whole-body PET and regional scans were performed. In addition, the resected tissues were prepared for immunocytochemistry examination (cell cycle-associated Ki-67 antigen). In two patients with less-differentiated GEP tumours associated with high proliferative activity and increased FDG uptake, SS-R failed to detect any lesion. In comparison, in four patients with well-differentiated GEP tumours showing low proliferative activity, SS-R localized four primary tumours, 22 lymph node metastases and 18 malignant liver lesions, whereas 18F-FDG PET demonstrated normal distribution. In one patient with a metastasizing carcinoid (medium proliferative activity) SS-R localized multiple metastases, whereas PET demonstrated low FDG uptake in all known metastases. In patients with recurrent MTC and rapidly increasing CEA levels DNS detected only three lesions in two patients, whereas PET demonstrated one pulmonary, three osseous, 20 mediastinal, ten locoregional, and four liver metastases in seven patients. Twenty-nine malignant lesions were confirmed by follow-up and nine lymph node metastases could be surgically removed. In conclusion, PET imaging of gastroenteropancreatic tumours revealed increased glucose metabolism only in less-differentiated GEP tumours with high proliferative activity and metastasizing MTC associated with rapidly increasing CEA levels. Therefore, additional 18F-FDG PET should be performed only if SS-R or DNS is negative.
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PMID:Limited value of fluorine-18 fluorodeoxyglucose positron emission tomography for the imaging of neuroendocrine tumours. 939 78

We investigated 5 MTC patients, 3 preoperatively for staging purpose, and 2 after surgery, during the follow-up, because of the persistence of elevated serum tumoral markers. FDG PET results were compared with conventional radiologic (US, CT scan, MRI) and scintigraphic non-invasive techniques (99mTc-MIBI and 99mTc-MDP scans). In all the 3 patients preoperatively studied, PET, as well as the other imaging modalities, detected the primitive tumor and the loco-regional lymphnode metastases. Furthermore, in one case, PET was the only technique that revealed an additional localization to the lungs. One false negative result was recorded with PET, as well as with the conventional imaging, in a MTC patient with a MEN II syndrome and with some liver micrometastases, 2 to 5 mm sized, showed only at laparotomy. PET was the only method capable of early visualizing a mediastinal relapse of the tumor in one of the 2 patients studied during the follow-up. This patient was re-operated and serum calcitonin levels became undetectable. On the basis of our preliminary results on MTC, PET with FDG seems to be an accurate, non-invasive technique, for staging purpose before surgery, and, during the follow-up for visualizing tumoral spread in patients with increased serum tumoral markers.
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PMID:Potential role of fluorine-18-deoxyglucose (FDG) positron emission tomography (PET) in the staging of primitive and recurrent medullary thyroid carcinoma. 941 6


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