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

One hundred thirty-nine surgically treated patients with medullary carcinoma of the thyroid gland (MTC) were seen in our institution between January, 1926 and December, 1973. The incidence of this tumor among all thyroid cancers was 8%. Twenty-nine patients had the familial form of MTC; they were subclassified, on the basis of the phenotype, into a group of 15 patients with Sipple syndrome (or multiple endocrine neoplasia (MEN) Type 2A) and a group of 14 patients with mucosal-neuroma phenotype (or MEN type 2B). Better survivorship was seen in the younger patients, in those with bilateral tumors, in familial MTC, and in patients whose tumor was confined to the thyroid gland at the initial surgery. The incidence of tumor recurrence was 34%. However, in those with adequate surgical treatment, the recurrence was only 23%. The 5- and 10-year survivorships were 80% and 67%, respectively. The best chance of cure lies in early diagnosis through the use of immunoreactive calcitonin measurement in family members at risk, and an aggressive surgical attack on the primary tumor and any cervical metastases.
 ...
PMID:Medullary carcinoma of the thyroid gland. 111 37

1. In the fifth year of followup, 8 of 12 original patients thyroidectomized for MTC, diagnosed solely by abnormal calcitonin values, are disease free by all criteria. Elevated calcitonin levels are the only manifestation of active disease in three patients with presumed metastases. 2. Routine annual screening of susceptible individuals is a practical measure and has in 6 cases detected the premalignant condition of G-cell hyperplasia and in 1 patient a premetastatic state of MTC. It is premature to conclude that yearly screening is sufficient to detect all cases of premetastatic disease and for this reason we are recommending a yearly screen with pentagastrin and calcium tests and the more convenient pentagastrin test at 6 month intervals for those in the high-risk age group between 8 and 18. If screening at such intervals proves to be ineffective in preventing the disease in every case, consideration must be given to prophylactic thyroidectomy although we are not currently recommending this precedure. 3. Pentagastrin injection is often a more effective secretagogue for calcitonin than is calcium infusion, but this is not uniformly true. We therefore recommend use of both tests as the most appropriate screening procedure. 4. Epinephrine is a major secretory product of pheochromocytomas in the J-kindred and sequential E/N ratios may be of use in the early detection of pheochromocytoma in other kindreds. 5. Adrenal medullary hyperplasia has been found in 3 adrenal glands and is probably a preneoplastic condition analogous to C-cell hyperplasia.
 ...
PMID:Natural history of the familial medullary thyroid carcinoma-pheochromocytoma syndrome and the identification of preneoplastic stages by screening studies: a five-year report. 122 35

To determine whether organ-derived fibroblasts differentially affect the growth of cells from tumors that preferentially metastasize to specific organs, we investigated the effect of medium conditioned with primary cultured rat fibroblasts from various organs on the in vitro growth of metastatic cell lines and clones of the rat 13762NF mammary adenocarcinoma. The conditioned medium from fibroblasts derived from rat mammary fat pad differentially stimulated tumor cell growth in monolayer culture and clonogenic growth in soft agarose of the highly metastatic clone MTLn3 in a dose-dependent manner. Conditioned medium from fibroblasts derived from the lung and liver also stimulated the growth of clone MTLn3 cells but to a lesser extent than did mammary fat pad fibroblasts. In contrast, poorly metastatic cell clones (MTC, MTPa) did not respond to the growth stimulatory factor(s) from the fibroblast-conditioned medium. The factor(s) responsible for the growth stimulation were inactivated by heat and trypsin treatment and inhibited by low pH and cycloheximide. The result suggest that fibroblasts in different organs have different effects on tumor cell growth, and they may determine, in part, the organ specificity of tumor development and metastasis.
Invasion Metastasis 1992
PMID:Preferential growth stimulation of metastatic rat mammary adenocarcinoma cells by organ-derived syngeneic fibroblasts in vitro. 129 39

Immunoreactivity with monoclonal antibody CD15 (Leu-M1) was investigated in the primary tumours, the metastases and local recurrences of 47 cases of sporadic medullary carcinoma of the thyroid (MTC). Of these tumours, 36.5% showed a varying degree of CD15 immunostaining; in 7 carcinomas the CD15 immunoreactivity was found to be significant (greater than 15% tumour cells positively stained). Staining of the amyloid stroma was observed in 3 tumours. Significantly higher epithelial CD15 positivity was seen more frequently in the group with larger tumours (greater than 4 cm) and was found exclusively in the presence of lymph node metastases. No substantial difference in the percentage of immunostained cells was seen between primary tumours and metastatic or recurrent lesions, except for two cases that revealed a significant increase in the number of CD15-immunostained cells in metastatic and recurrent lesions. Five of 7 patients with recurrences showing significant CD15 immunostaining died of cancer, while in the absence of significant CD15 staining all patients with recurrences were still alive at the conclusion of the study. The prognostic value of CD15 immunoreactivity, found by univariate analysis, becomes weaker after adjustment for the size and stage of tumour. Particularly in patients with tumour recurrences CD15 immunostaining may be of clinical relevance for the selection of patients in whom a more radical surgical approach would be justified.
 ...
PMID:Relationship of CD15 immunoreactivity and prognosis in sporadic medullary thyroid carcinoma. 135 85

Thyroid carcinoma may invade the mediastinum by direct extension of the primary tumor or metastases to the paratracheal or retroclavicular-parajugular lymph nodes. From 1975 to 1991 in 47 out of 622 thyroid cancer patients (7.6%) [14 papillary (PTC), 5 follicular (FTC), 16 medullary (MTC) and 12 undifferentiated carcinoma (UTC)] transsternal tumor resection has been performed. Four patients (UTC three, MTC one) deceased 7, 8, 35, and 41 days after resection of the primary tumor due to cardiac or tumor disease, and in one patient because of acute arteriotracheal haemorrhage after external irradiation; no patient deceased after transsternal resection as a result of cervicomediastinal lymphadenectomy. At the time of primary operation 80% of patients showed an advanced tumor stage (greater than pT3). In 34% of patients (PTC 64%, FTC 40%, MTC 13%, UTC 25%) no tumor recurrence was observed neither by imaging nor by biochemical methods. In 18 patients a transsternal microdissection of all four cervicomediastinal lymph node compartments has been performed. Histological analyses of excised and tumor involved lymph nodes revealed in 9 patients unilateral cervical and mediastinal and in 9 patients bilateral cervical and mediastinal lymph node metastases. In the case of unilateral cervicomediastinal lymph node metastases 2 out of 2 patients with papillary and 2 out of 6 patients with medullary thyroid carcinoma could be cured surgically. In the case of bilateral cervicomediastinal lymph node metastases 3 out of 4 patients with papillary thyroid carcinoma, but no other thyroid cancer patient were free of disease. In conclusion, main indications for transsternal cervicomediastinal resection in thyroid carcinoma are (1) primary tumors extending to the upper mediastinum, but without lymph node metastases, and (2) thyroid carcinomas with unilateral cervicomediastinal lymph node metastases. In the case of bilateral cervicomediastinal lymph node metastases probable only papillary thyroid carcinomas are supposed to be curable by transsternal multicompartmentectomy.
 ...
PMID:[Trans-sternal cervico-mediastinal primary tumor resection and lymphadenectomy in thyroid gland cancer]. 156 3

We used immunohistochemical procedures to study the cellular expression and distribution of cytokeratins (CKs) in rat 13762NF mammary adenocarcinoma cells growing at mammary fat pad sites and at spontaneous lymph node and lung sites. In order to establish CK distribution in normal rat mammary epithelia, immature, resting, and lactating rat mammary glands were probed with a panel of monospecific antibodies that recognize individual CKs. Basal/myepithelial cells were distinguished by expression of CKs 5 and 14 and coexpression of vimentin from luminal cells, which expressed CKs 8, 18, and 19. Antibody to CK 7 recognized luminal epithelium of immature and resting, but not lactating, mammary glands. Myoepithelial cells of lactating mammary gland were weakly recognized by antibodies to CKs 7 and 19. Tumors formed by cell lines and clones derived from parental 13762NF tumor (MTPa, MTC, MTA, and MTF7) were not recognized by any of the anti-CK antibodies. Only vimentin was expressed in these tumors and their metastases. In tumors and metastases generated from cell lines and clones derived from lymph node (MTLY) and lung metastases (MTLn2 and MTLn3) of the 13762NF tumor we observed heterogeneous CK phenotypes. Expression of CKs 5 and 18 was greatly reduced or lacking, while CK 14 was coexpressed with CKs 7, 8, and 19 with or without vimentin. Tumors from the highly metastatic clone MTLn3 had a dominant cellular phenotype, expressing CKs 7, 8, 14, and 19 and vimentin, a pattern that did not match normal mammary epithelia, whether luminal, basal/myoepithelial, or the dual-phenotype stem cell, in which CKs 5, 8, 14, and 18 were coexpressed. MTLn3 lymph node and lung metastases expressed the same cellular phenotype as the s.c. growing MTLn3 tumor. The results appear to contradict the belief that malignant mammary tumors may be distinguished from benign tumors or hyperplastic growths by the lack of basal/myoepithelial markers.
 ...
PMID:Coexpression of cytokeratins characteristic for myoepithelial and luminal cell lineages in rat 13762NF mammary adenocarcinoma tumors and their spontaneous metastases. 171 90

Medullary carcinoma of the thyroid (MTC) is exceptional in that the hormone calcitonin produced by the tumor cells represents a specific and sensitive tumor marker. Careful screening by serial calcitonin determinations following pentagastrin stimulation allows for the early detection of metastatic disease. We have adopted a method of meticulous modified radical neck dissection to eradicate persistent or recurrent MCT in 11 patients treated over a 15-month period. This surgical approach resulted in potentially curative treatment in two patients. Effective tumor reduction was achieved in another seven. Two patients have persistent or progressive disease despite maximum efforts to eradicate malignant tissue. Follow-up is presently incomplete in one patient. Postoperative complications included recurrent nerve paralysis (n = 3), hypoparathyroidism (n = 2), muscular weakness (n = 2) and Horner's syndrome (n = 3). The majority of nervous complications improved spontaneously. It is concluded that the adopted method of meticulous modified radical neck dissection offers the chance of cure to some patients and results in the removal of substantial tumor mass in the majority of others. Postoperative problems are mostly temporary and are deemed acceptable.
 ...
PMID:New operative strategy in the treatment of metastasizing medullary carcinoma of the thyroid. 197 10

The loss of intercellular junctional communication between rat 13762NF mammary carcinoma cells and their spontaneous metastatic potentials from the mammary fat pad show a high degree of correlation. We examined a stable, benign, completely junctionally coupled cell clone (MTC.4) of this system after calcium phosphate-mediated transfection with c-H-rasEJ/pSV2neo and control pSV2neo-containing plasmids. There was a good correlation between the copy numbers of c-H-rasEJ incorporated into MTC.4 cells and their contents of p21rasEJ; however, there was not always a correspondence between spontaneous metastatic potential and copy number of c-H-rasEJ or amount of p21rasEJ. After c-H-rasEJ/pSV2neo transfection, some MTC.4 cells lost intercellular junctional communication and became spontaneously metastatic, although some nonmetastatic transfectants also had low percentages of junctionally coupled cells. One of the control pSV2neo transfectants also became metastatic and lost intercellular junctional coupling, and calcium phosphate treatment itself resulted in increased growth rates at mammary fat pad sites and a marginal increase in incidence of spontaneous metastases, both of which preceded loss of intercellular junctional coupling in some cells. Examination of 12 subclones derived from two cloned transfectants, however, revealed a poor correlation between spontaneous metastatic potential and intercellular junctional coupling. The results suggest that loss of junctional communication between cells is often but not always associated with the progression of cells from benign to metastatic states.
 ...
PMID:Lack of correlation between intercellular junctional communication, p21rasEJ expression, and spontaneous metastatic properties of rat mammary cells after transfection with c-H-rasEJ or neo genes. 218 8

The value of radioiodinated metaiodobenzylguanidine (MIBG) in imaging thyroid medullary carcinoma (MTC) was investigated (18 studies) in 12 patients with proven MTC. Calcitonin (CT), carcinoembryonic antigen (CEA) and tissue polypeptide antigen (TPA) were also determined. The patients were divided into two groups. Group I comprised 7 patients who had relapsed; two of them were also studied before total thyroidectomy. In the 2 cases studied before total thyroidectomy 123/131I-MIBG imaged the primary tumor (partially) and the residual tumor involved lobe. The residual/recurrent tumor present in 4 and some of the remote metastases in 3 out of 5 were detected. Group II includes 5 patients studied postoperatively with no evidence of disease. A residual tumor in one of the 2 patients without evidence of disease on the basis of conventional diagnostic modalities but with elevated tumor markers was visualized; the outcome was correctly negative in 3. One patient underwent treatment with 131I-MIBG. A total dose of 27.1 GBq (733 mCi) was given. Relief of pain and partial regression of the lesions was achieved.
 ...
PMID:The possible use of radioiodinated metaiodobenzylguanidine (MIBG) in medullary thyroid carcinoma. 248 94

Circulating neutrophil (PMN) levels can increase in rats bearing subcutaneously growing clones of the 13762NF mammary adenocarcinoma and the level of increase correlates with the metastatic potential of the clone. In rats with poorly metastatic MTC tumors, numbers of circulating PMN did not rise, whereas PMN levels rose 50-fold in rats bearing highly metastatic MTLn3, 12-fold in rats with weakly metastatic MTLn2, and 14-fold in those with moderately metastatic MTF7 tumors. Neutrophilia was caused partly by tumor size, but metastatic potential was a stronger determinant, suggesting that PMNs may play a role in the metastatic process. To determine whether circulating PMNs indeed contribute to cellular metastatic potential, we examined effects of PMN on various aspects of the metastatic process. Experimental metastasis assays involving i.v. co-injections of PMNs yielded a dose-dependent increase in extrapulmonary metastases for MTLn3, but no change in lung colonization potential for any of the clones examined. The change in the metastatic profile was not due to any modification in in vivo distribution of i.v. injected tumor cells or in adhesion to endothelial monolayers in vitro. PMNs also had no effect on in vitro DNA, RNA or protein synthesis and were not cytolytic (E:T 100:1). However, PMNs collected from high-passage MTLn3 tumor-bearing rats had a 50% increase in heparanase and type-IV collagenolytic activity as compared to unstimulated PMNs isolated from normal rats. These results indicate that polymorphonuclear cells may contribute to the metastatic potential of highly metastatic clones from the 13762NF mammary adenocarcinoma cells by assisting in the degradation of basement membrane during extravasation.
 ...
PMID:The role of polymorphonuclear leukocytes (PMN) on the growth and metastatic potential of 13762NF mammary adenocarcinoma cells. 284 49


1 2 3 4 5 6 Next >>