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)

The ultrastructural appearances of 7 primitive neuroepithelial tumours (PNETs) originating in soft tissues and bone are described. Three of the tumours represented primary soft tissue lesions, while locally recurrent tumour or pulmonary metastases were studied from the 4 skeletal tumours, all of which had been diagnosed previously as Ewing's sarcomas. Rosettes were present in one of the soft tissue lesions and although not seen in the primary skeletal neoplasms, they were identified by light microscopy (LM) in 2 of 3 pulmonary metastases, one of which had the morphology of a neuroepithelioma, with innumerable Homer Wright rosettes. Conventional TEM revealed cytoplasmic processes in all cases and rosettes in varying stages of development were also evident, but the appearances did not achieve the level of cellular organization seen in neuroblastoma: microtubules were few, while dense-core granules varied in number but were generally sparse and pleomorphic, resembling lysosomes. However, typical neurosecretory granules were found in one lung metastasis; the neoplastic cells comprising the same tumour also had epithelial markers in the form of well constructed desmosomes, while freeze-fracture analysis demonstrated elaborate tight junctions. In thin sections, junctions in the other tumours appeared rudimentary, but freeze-fracture of a further case revealed small collections of membrane particles suggesting extremely poorly developed desmosomes. Immunocytochemical study of 4 tumours (2 originating in soft tissue and 2 in bone) demonstrated weak to moderate immunostaining for neurone-specific enolase and with several monoclonal antibodies reactive with neuroblastomas, but there was no evidence of immunolabelling for tyrosine hydroxylase.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Primitive neuroepithelial tumours of soft tissues and of bone: further ultrastructural and immunocytochemical clarification of 'Ewing's sarcoma', including freeze-fracture analysis. 264 32

An immunohistochemical study on tyrosine hydroxylase (TH), a rate-limiting enzyme in the catecholamine synthesizing pathway, was made on three craniocervical region paragangliomas, two of which showed metastases to the cervical lymph nodes. In all of the original tumors, the majority of tumor cells showed positive immunostaining for TH of variable intensity in their cytoplasm regardless of their cytological features such as cellular and nuclear pleomorphism. The finding suggests that most tumor cells are capable of production of catecholamines and are derived from chief cells in the normal paraganglia. In cervical lymph nodes, however, no positive immunostaining for TH was observed in metastatic tumor cells, in contrast with the findings in the original tumors. The absence of TH immunoreactivity in metastatic tumor cells appears to be noteworthy in considering their malignant potential. Application of the TH immunohistochemistry to further cases appears important for the better understanding of this neoplasm, a catecholamine-producing tumor.
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PMID:Paragangliomas of the craniocervical region. An immunohistochemical study on tyrosine hydroxylase. 288 82

A case of esthesioneuroepithelioma was investigated ultrastructurally and immunohistochemically, using antibodies against neurofilament protein (NFP), glial fibrillary acidic protein (GFAP), keratin, neuron-specific enolase (NSE), S-100 protein (S-100), and tyrosine hydroxylase (TH). The tumor initially manifested as an epidural mass in the anterior cranial fossa in a 64-year-old man, and about 3 1/2 years later, autopsy further revealed extensive metastases to the lymph nodes of the neck and thoracic cavity. In the cranial and nasal cavities, the tumor was composed of fairly uniform, ill-defined cells arranged in nests which were surrounded by a fibrovascular stroma. These histological features were reproduced in the metastatic tumor nodules with frequent occurrence of tubular arrangements of the tumor cells. Ultrastructurally, two different cell types were well recognized by their characteristic morphological features, which were reminiscent of sensory neurons and sustentacular cells of the olfactory epithelium. No dense-cored secretory granules were observed in the tumor cells. Immunohistochemically, the tumor showed a variable number of cells positive for NFP, keratin, NSE and S-100. NFP was present in a relatively small number of cells, which were found diffusely in the nests. Keratin was observed in the cells mainly located at the periphery. NSE-positive cells tended to form irregular clusters in the center. A few S-100-positive cells were found, without any particular arrangement.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Esthesioneuroepithelioma: a tumor of true olfactory epithelium origin. An ultrastructural and immunohistochemical study. 343 22

We report the histological, immunohistochemical and ultrastructural changes in mice containing a chimeric glucagon-simian virus 40 T antigen (SV40Tag) gene. Transgene expression was detected in endocrine cells of pancreas, small and large intestine. Hyperplasia of glucagon-containing cells developed in pancreas and large bowel by gestational day 19. In large bowel, hyperplastic cells increased in number postnatally and invasive carcinomas were identified at 4 weeks; several animals had lymph node metastases. In contrast, no pathology was detected in the small bowel in any of the transgenic mice. Colonic tumours expressed SV40Tag, proglucagon-derived peptides and peptide YY (PYY); scattered cells contained cholecystokinin or glycoprotein hormone alpha-subunit. Somatostatin or serotonin was also detected in some tumours. By electron microscopy, the colonic tumours retained features of endocrine differentiation, but secretory granules were smaller than those of non-tumorous intestinal glucagon-producing L cells. In postnatal pancreas, atypical cells containing SV40Tag and glucagon were initially clustered at the periphery of islets; this atypical hyperplasia progressed to neoplasia by 11-12 weeks. Some neoplastic pancreatic cells contained glucagon, PYY or vasoactive intestinal peptide immunopositivity, but most were negative for all peptides; they contained immunoreactivity for tyrosine hydroxylase and by electron microscopy, pancreatic tumour cells had neuronal features. Pancreatic polypeptide was not detected in the non-tumorous islets of transgenic animals. This line of transgenic mice provides a model for the analysis of endocrine tumour progression in the gut and pancreas.
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PMID:Development of colonic and pancreatic endocrine tumours in mice expressing a glucagon-SV40 T antigen transgene. 860 71

While not all circulating tumor cells survive, one could postulate that patients with circulating tumor cells might be candidates for adjuvant chemotherapy because of the risk of relapse. Recently, reverse transcriptase-polymerase chain reaction (RT-PCR) for the detection of circulating tumor cells has been suggested as a potential technique for staging of cancer. In malignant melanoma, the detection of circulating melanoma cells by tyrosinase RT-PCR correlated with the clinical stage of patients and was an independent prognostic factor for recurrence. A strong association was found between the detection of neuroblastoma cells in circulation by tyrosine hydroxylase RT-PCR with bone marrow micrometastasis. This method may be of use to identify early signs of relapse in disease-free patients. In prostatic cancer, the frequency of positivity for detection of circulating tumor cells in peripheral blood by PSA RT-PCR increased with tumor stages but a significant proportion of patients with metastatic disease were negative. The prognostic significance of the detection of tumor cell in blood in other epithelial tumors is not established and will require further long-term follow-up study.
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PMID:[Molecular diagnostic detection of circulating tumor cells and their prognostic implications]. 905 Nov 25

Plasma levels of chromogranin A (CgA) were measured by ELISA in 22 patients with pheochromocytoma (18 non-metastatic, 3 metastatic, and 1 mixed neuroendocrine-neural tumor), 9 patients with primary hyperparathyroidism, and 9 patients with pituitary adenoma. The plasma levels of CgA were compared with norepinephrine, epinephrine, parathyroid hormone and pituitary hormones, i.e., growth hormone and prolactin. In pheochromocytoma, CgA in preoperative plasma of the patients without metastasis was 228 +/- 38 U/L (mean +/- SEM) and significantly higher than healthy controls (30 +/- 11 U/L, n = 40). Plasma CgA was decreased after removal of the tumors (28 +/- 6.0 U/L), except in three patients with metastatic pheochromocytoma and a mixed neuroendocrine neural tumor. The concentration of CgA in the patients with non-metastatic pheochromocytoma was significantly correlated with that of plasma norepinephrine (P < 0.005, r = 0.68) and urinary norepinephrine (P < 0.05, r = 0.65), but not with that of epinephrine. There was an exceptional case in which CgA was extremely high, but the CA level was normal. This tumor was a highly malignant pheochromocytoma with extensive metastases composed of small tumor cells which were occasionally positive for tyrosine hydroxylase immunohistochemically. These cells were considered to be poorly differentiated tumor cells and synthesized a very small amount of norepinephrine. Plasma levels of the patients with primary hyperparathyroidism and the patients with pituitary adenoma were 44 +/- 4 U/L and 48 +/- 8 U/L, respectively. Only one patient with a growth hormone-producing pituitary adenoma had a high level of CgA. Plasma CgA is a useful tumor marker for pheochromocytoma, even for malignant pheochromocytoma without elevated CA level, but not for hyperparathyroidism, or pituitary adenoma.
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PMID:Plasma chromogranin A in pheochromocytoma, primary hyperparathyroidism and pituitary adenoma in comparison with catecholamine, parathyroid hormone and pituitary hormones. 922 69

Hepatic arterial infusion (HAI) chemotherapy as treatment for human colorectal liver metastases is promising, but not entirely satisfactory. Improved drug delivery during HAI may be achieved by manipulating the different control mechanisms of normal versus tumour blood vessels. The peptidergic/aminergic innervation of vessels in normal liver and in two animal models of liver metastasis (Lister Hooded rat with syngeneic MC28 sarcoma; athymic (nude) rat with human HT29 carcinoma) was investigated to assess the suitability of these models for future pharmacological studies. Normal liver and metastases were studied immunohistochemically for the presence of protein gene product 9.5 (PGP), neuropeptide Y (NPY), tyrosine hydroxylase (TH), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP) and substance P (SP). Perivascular innervation was also examined by transmission electron microscopy. In Lister rat normal livers, perivascular immunoreactive nerve fibres containing PGP, NPY, TH, CGRP and SP were observed around the interlobular blood vessels near the hilum and in the portal tracts. The highest density was seen for PGP, followed in decreasing order, by NPY, TH, CGRP and SP. VIP-immunoreactive nerves were absent. No immunoreactive nerves were observed in the hepatic lobule. In athymic rat livers, the pattern of innervation was similar, except that SP immunoreactivity was more sparse. No perivascular immunoreactive nerves were observed in either MC28 or HT29 tumours. Electron microscopy confirmed the absence of perivascular nerves. Smooth muscle cells were not observed in tumour blood vessel walls. These results are comparable with previous observations on human liver metastases and suggest that the animal models may be suitable for pharmacological studies on vascular manipulation of HAI chemotherapy.
Clin Exp Metastasis 1997 Sep
PMID:Blood vessels in liver metastases from both sarcoma and carcinoma lack perivascular innervation and smooth muscle cells. 924 51

Oncocytic neoplasms of the adrenal gland are rare. We describe the clinicopathologic and immunohistochemical findings of seven oncocytic adrenocortical neoplasms, five oncocytomas, and two oncocytic neoplasms of uncertain malignant potential. Three tumors were studied using electron microscopy. These neoplasms occurred in five women and two men (median age, 55 years) with no clinical evidence that the neoplasms were functional. The size of the neoplasms varied from 5.0 cm to 13.5 cm. Histologically, each neoplasm was composed exclusively of oncocytes. The oncocytomas had very low or absent mitotic activity and no evidence of necrosis. The two oncocytic neoplasms of uncertain malignant potential had increased mitotic activity and necrosis but no evidence of invasion or metastases. Nuclear atypia, either focal or generalized, was found in all neoplasms. Immunohistochemical studies performed using fixed, paraffin-embedded sections showed strong reactivity with the mitochondrial antibody mES-13 in all neoplasms. Four of five oncocytomas and one oncocytic neoplasm of uncertain malignant potential expressed keratin, predominantly keratin 18, as shown using the CAM 5.2 and AE3 antibodies. Two neuroendocrine-associated markers, neuron specific enolase and synaptophysin, were positive in seven and five neoplasms, respectively. However, all neoplasms were negative for the other neuroendocrine markers tested, including chromogranin A, tyrosine hydroxylase, and dopamine beta-hydroxylase, as well as for epithelial membrane antigen, S100, and p53. Using the MIB-1 (Ki-67) antibody, proliferative activity was increased in both oncocytic neoplasms of uncertain malignant potential. All six patients with available clinical follow-up data are alive without evidence disease, although the follow-up interval is relatively short (< 2 years) for the two patients with oncocytic neoplasms of uncertain malignant potential. We conclude that oncocytic adrenocortical neoplasms are nonfunctional tumors that can become large before they are detected by radiologic studies. The majority of neoplasms are benign and should not be misdiagnosed as carcinoma.
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PMID:Oncocytic adrenocortical neoplasms: a report of seven cases and review of the literature. 959 31

Neuroblastoma is a malignant solid tumor of childhood with a poor prognosis. The growth of solid tumors has been shown to be dependent on new blood vessel formation, i.e. angiogenesis. Several steps in the metastatic process have also been found to be angiogenesis-dependent. Neuroblastomas grow quickly, are highly vascularized, and metastasize early, and hence inhibition of angiogenesis--angiostatic therapy--may be indicated in this disease. In order to investigate the effects of angiostatic agents in this disease, a new animal experimental model for human neuroblastoma was developed. Three angiostatic agents were tested in the model: TNP-470, the synthetic analogue of fumagillin, given subcutaneously, and the endogenous steroid 2-methoxyestradiol and its derivative 2-propynylestradiol, given orally. TNP-470 administration resulted in a significant reduction of the tumor growth rate and microvascular counts, and of the fraction of viable tumor cells, compared to controls. The fraction of apoptotic tumor cells increased threefold, while that of proliferative cells remained unaltered. This can explain the reduced net growth. Treatment with the angiostatic and chemotherapeutic steroids 2-methoxyestradiol and 2-propynylestradiol yielded similar results. However, the mechanism of action of these steroids was bimodal; the effect occurring both through inhibition of tumor angiogenesis and through induction of tumor cell apoptosis. It was shown for the first time that inhibition of angiogenesis regardless of agent induces striking chromaffin differentiation, observed as increased expression of insulin-like growth factor II gene, tyrosine hydroxylase, and chromogranin A, and increased formation of cellular processes. It is suggested that inhibition of angiogenesis induces metabolic stress, resulting in chromaffin differentiation and apoptosis. Such agonal differentiation may be the link between angiostatic therapy and tumor cell apoptosis. Angiostatic agents administered as single therapy have an objective tumoristatic effect in our neuroblastoma model. Angiostatic treatment of neuroblastoma is a new and promising treatment modality that merits clinical investigation.
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PMID:Angiostatic treatment of neuroblastoma. 1037 67

We investigated, morphologically and immunohistochemically, 74 medullary adrenal tumors, including 64 pheochromocytomas (14 malignant and 50 benign), 9 ganglioneuromas, and 1 malignant schwannoma. The tumors were detected in 2-year-old Wistar and Sprague-Dawley rats from carcinogenicity studies. Morphologically, benign pheochromocytomas were characterized by monomorphic, small, basophilic cells with almost absence of mitoses. Malignant pheochromocytomas presented a low grade of pleomorphism, higher rate of mitoses, necrosis, infiltrative growth and in 1 case metastases in the lung. Ganglioneuromas were characterized by ganglion and neuron-like cells embedded in an eosinophilic matrix containing neurites, Schwann cells, and scant fibrovascular elements. All pheochromocytomas were strongly immunoreactive for tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis. Subpopulations of chromaffin cells expressed chromogranin A (CGA) positivity. Matrix and Schwann cells were positive for S-100 and for glial fibrillary acidic protein (GFAP). In focal areas of the tumors, ganglion cells and axons were positive for neurofilament proteins (NFP) and synaptophysin. Ganglion cells exhibited peripherin and beta-tubulin. Proliferative activity of the tumors was assessed by immunostaining the endogenous cell proliferation associated-antigen Ki-67 and the proliferating cell nuclear antigen (PCNA). As expected, cell proliferation indices were much higher in malignant pheochromocytomas than in benign, yet ganglioneuromas remained immunonegative. Considering that Ki-67 antigen is more specific for cell proliferation, it should be regarded as marker of choice for supporting the differential diagnosis between benign and malignant pheochromocytomas.
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PMID:Pheochromocytomas and ganglioneuromas in the aging rats: morphological and immunohistochemical characterization. 1218 40


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