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)

Tumor cell extravasation is a determinant step in the process of hematogenous metastasis. The signal transduction pathways involved in the interactions between tumor cells and the vascular endothelium during transendothelial migration are still undefined. In the present study, we have investigated the influence of human breast adenocarcinoma cells (MCF7) on human umbilical vein endothelial cell (HUVEC) intracellular Ca2+ concentration ([Ca2+]i). We show that the contact between MCF7 cells and a confluent HUVEC monolayer induces an immediate and transient increase in HUVEC [Ca2+]i. This [Ca2+]i rise could not be elicited by tumor cell-conditioned medium, isolated tumor cell membranes, inert beads or normal breast epithelial cells, demonstrating the involvement of specific recognition mechanisms between MCF7 cells and HUVEC. Depletion of HUVEC intracellular Ca2+ stores by the endoplasmic reticulum Ca2+-ATPase inhibitor thapsigargin as well as the selective depletion of inositol 1,4,5-triphosphate (IP3)-sensitive Ca2+ stores by prior activation of HUVEC using histamine resulted in a complete inhibition of tumor cell-induced [Ca2+]i elevation. Similar results were obtained when HUVEC monolayers were treated with the tyrosine kinase inhibitor herbimycin A, suggesting a role for tyrosine kinase-associated cell surface receptors in tumor cell-endothelial cell interactions. The depletion of HUVEC intracellular Ca2+ stores by thapsigargin was also shown to delay MCF7-induced endothelial cell disjunction, to prevent their spreading on the subendothelial extracellular matrix and transendothelial migration in vitro. These results suggest that transient changes in endothelial [Ca2+]i may govern multiple steps of tumor cell extravasation.
Clin Exp Metastasis 1998 Jan
PMID:Endothelial cell intracellular Ca2+ concentration is increased upon breast tumor cell contact and mediates tumor cell transendothelial migration. 950 74

Parachordomas are rare cutaneous tumors that show virtually identical histologic findings to chordomas. Therefore, the major differential diagnosis in a case of parchordoma is metastatic chordoma. Parachordomas are benign neoplasms and most often develop on the extremities adjacent to tendons, synovium or osseous structures, as opposed to chordomas, which are malignant tumors located along the craniospinal axis. While recurrences may occur in cases of parachordoma, metastases have not been reported. In this report, two cases of parachordomas are reported and the literature reviewed. By light microscopy, parachordomas show eosinophilic bands of fibrous tissue separating lobules of cells with variably vacuolated cytoplasm (physaliphorous cells) admixed with more epithelioid cells in a myxoid stroma. Parachordomas and chordomas share immunohistochemical and ultrastructural features. Both stain with S-100 protein and vimentin, and ultrastructurally both demonstrate cytoplasmic vacuoles, intermediate filaments, pinocytotic vesicles, celljunctions, and cytoplasmic membranes with microvillous processes. Chordomas more frequently express cytokeratin (98% vs. 66% in parachordomas) and epithelial membrane antigen (90% vs. 20% in parachordomas) and chordomas have a larger number of rough endoplasmic reticulum-mitochondrial complexes. Thus, positive staining with epithelial membrane antigen and the identification of a large number of rough endoplasmic reticulum-mitochondrial complexes are suggestive of metastatic chordoma. However, the definitive distinction remains a clinical one after appropriate radiologic studies of the skull and spinal chord.
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PMID:Cutaneous parachordoma. A light microscopic and immunohistochemical report of two cases and review of the literature. 969 95

The ultrastructural pathology of non-invaded hepatocytes located in close proximity to metastases from diverse gastrointestinal carcinomas was studied. Observed abnormalities included swelling of rough and smooth endoplasmic reticulum, proliferation of lysosomes, and mitochondrial alterations as presence of granules and paracrystalline inclusions, marked pleomorphism, and lack of cristae. These results show that, contrary to the classical conception, the non-invaded cells surrounding primary tumours or their metastases could be abnormal.
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PMID:Ultrastructure of hepatocyte abnormalities in perimetastatic areas. 972 97

Using reverse genetics methods, we constructed three different transfectant influenza A viruses encoding an Ld-restricted, nine amino-acid-long fragment, corresponding to amino-acid residues 876-884, of beta-galactosidase (beta-gal). Sequences encoding this epitope were nested within the hemagglutinin (HA) or neuraminidase (NA) open reading frames. Alternatively, an independent beta-gal mini-gene, preceded by an endoplasmic reticulum insertion signal sequence, was placed in a bicistronic arrangement in the NA RNA segment of the virus. All three transfectants mediated the presentation of the epitope to a beta-gal-specific CTL clone. Furthermore, each of the three transfectant viruses expressing the beta-gal fragment elicited specific cytolytic responses in vivo. Most importantly, these H1N1 transfectants mediated the regression of established murine pulmonary metastases. Tumor regression in mice was also achieved in the presence of preexisting immunity against an H3N2 influenza A virus serotype. Nononcogenic and nonintegrating, transfectant influenza A viruses are attractive candidates for development as antitumor vaccines.
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PMID:Transfectant influenza A viruses are effective recombinant immunogens in the treatment of experimental cancer. 974 Jul 80

Invasion and metastases are the main causes of death from cancer, and prognosis is best correlated with invasion of malignant cells into initial lymphatics and dissemination to regional lymph nodes. Using both light and transmission electron microscopy, we examined human gastric and colonic cancers and their relation to initial lymphatics. Invasion of malignant tumor cells into the initial lymphatics was characterized by interdigitating and overlapping endothelium giving way to open junctions as lymphatic endothelial cells were apparently dissolved and destroyed. Cytoplasmic vesicles, mitochondria, and rough endoplasmic reticulum were qualitatively increased as demonstrated by image analysis.
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PMID:Structural studies of initial lymphatics adjacent to gastric and colonic malignant neoplasms. 1038 14

We have pursued our analysis of antigens recognized by autologous cytolytic T lymphocytes (CTLs) on the melanoma cells of patient LB33. This patient enjoys an unusually favorable evolution, which is associated with a strong and sustained antitumor CTL response. We reported previously the analysis of two melanoma cell lines, MEL.A and MEL.B, which were derived from metastases removed from the patient at 5 years' distance. Autologous CTL clones derived from blood lymphocytes recognized several antigens presented by different HLA class I molecules on MEL.A. The MEL.B cells resisted lysis by these CTLs because they have lost expression of most HLA molecules, suggesting that they were selected in vivo by the anti-MEL.A CTL response. One of the MEL.A antigens was shown to result from a point mutation in the tumor. Here we report the cloning of a gene that encodes two other MEL.A antigens. This new gene, MUM-2, is expressed ubiquitously. In the melanoma cells of patient LB33, it contains a point mutation that changes one amino acid in the translated protein. Two different antigenic peptides, one presented to CTL by HLA-B44 molecules and another by HLA-C6 molecules, overlap and contain the mutated residue. Gene MUM-2 is homologous to an essential yeast gene, bet5, that was recently shown to be implicated in the vesicular transport of proteins from the endoplasmic reticulum to the Golgi. In a mutant yeast with a disrupted bet5 gene, both the wild-type and the mutated MUM-2 genes could complement for bet5 function. These results indicate that the antigenic mutation does not destroy the function of the protein, a function that is conserved in eukaryotic cells. The identification of these antigens suggests that point mutations could be the major cause of the strong immunogenicity of MEL.A cells.
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PMID:Two antigens recognized by autologous cytolytic T lymphocytes on a melanoma result from a single point mutation in an essential housekeeping gene. 1058

A case of so-called congenital fibro(leio)myosarcoma of the small intestine in a 18-day-old female baby, treated only with surgical resection, was studied by immunohistochemistry and electron microscopy in order to investigate the proliferating cell type. The tumour cells showed positivity only for vimentin and CD 34 and were negative for smooth muscle actin, desmin, alpha-sarcomeric actin, factor VIIIR: Ag and S-100 protein. Ultrastructural findings showed oval nuclei with prominent nucleoli, rare intracytoplasmic mitochondria and well developed rough endoplasmic reticulum. According to histoimmunological and electron microscopy findings the proliferating cells were likely to be of fibroblastic origin. A 7-year follow-up showed a favourable clinical evolution thus confirming that surgical resection can be a sufficient therapeutic approach. The morphological findings and clinical behaviour suggest that more appropriate terminology for this tumour would be "aggressive congenital fibromatosis" which better highlights its local progressive invasion without metastases.
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PMID:Aggressive congenital fibromatosis of the small intestine in the newborn. Report of a case and review of the literature. 1066 58

Fischer 344/CRJ rats harbor a G633R substitution in dipeptidyl peptidase IV (DPP IV) that leads to retention and degradation of the mutant protein in the endoplasmic reticulum (Tsuji E, Misumi Y, Fujiwara T et al. Biochemistry 1992; 31 (47): 11921-7). However, when these rats were used as a 'protein knock-out' model in further evaluating the previously established role of DPP IV in metastasis, lung colonization of the highly metastatic MTF7 rat breast cancer cell line was reduced by only 33% relative to normal Fischer 344 rats. To examine whether lung endothelia leak expression of mutant DPP IV and whether mutant DPP IV exhibits the same adhesion qualities as wild type DPP IV, detailed immunohistochemical, biochemical, transfection, and FACS analyses were performed to assess the surface expression of mutant DPP IV on lung endothelia and transfected HEK293 cells and adhesion assay to compare the adhesion qualities of wild-type and mutant DPP IV. Both endothelial and transfected HEK293 cells expressed mutant, enzymatically inactive DPP IV on their surfaces, albeit at greatly reduced levels when compared to expression of wild type DPP IV. Purified mutant DPP IV had identical adhesion qualities for lung-metastatic MTF7 cells as wild type DPP IV, and competitive inhibition of MTF7 lung colonization by truncated DPP IV confirmed involvement of mutant DPP IV in lung metastasis of Fischer 344/CRJ rats. Although metastasis appears to be mediated by several, often parallel mechanisms involving multiple tumor and host factors, these data indicate that altered expression of a single component can drastically change the outcome of metastatic disease.
Clin Exp Metastasis 1999
PMID:Is the Fischer 344/CRJ rat a protein-knock-out model for dipeptidyl peptidase IV-mediated lung metastasis of breast cancer? 1084 60

Pituitary carcinomas are very rare. Defined as adenohypophysial tumors that undergo craniospinal and/or systemic metastasis, most are PRL- or ACTH-producing. Their ultrastructural features, particularly relative to benign adenomas of similar functional type, have not been sufficiently explored. Eleven cases of immunohistochemically characterized pituitary carcinoma with documented cerebrospinal and/or systemic metastases were collected from various institutions and studied by transmission electron microscopy. The tumors were surgically removed from 7 women and 4 men ranging in age between 28 and 74 years (mean, 50 years). All were endocrinologically functioning. Six tumors secreted PRL; three were ACTH-producing; one each was GH/PRL- and TSH-producing. The patients with the ACTH-producing tumors had all presented with Cushing's disease and two of them had undergone adrenalectomy (Nelson syndrome). In most cases significant cellular atypia and mitotic activity were observed. In terms of morphologic features of functional differentiation, electron microscopy revealed that in 9 cases the tumor cells maintained at least some ultrastructural markers of their basic phenotype. A unique feature in 2 ACTH carcinomas was the variable admixture of smooth endoplasmic reticulum with intermediate (cytokeratin) filaments. In 2 cases, both PRL-producing carcinomas, the cell type comprising the tumor could not be identified on an ultrastructural basis alone. Ultrastructural investigation of pituitary carcinomas confirms their endocrine nature and, in most but not all cases, reveals their functional differentiation. Despite the diagnostic utility of electron microscopy in the assessment of these rare tumors, the distinction of pituitary carcinoma from pituitary adenoma cannot be firmly made on ultrastructural grounds alone.
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PMID:Pituitary carcinoma: an ultrastructural study of eleven cases. 1146 79

Bilateral adrenal tumors were detected in a 72-year-old man who had a history of hepatic inflammatory pseudotumor. Computet tomography (CT)-guided fine needle aspiration cytology (FNAC) of the adrenal glands was performed. The cytologic findings were similar to the previous diagnosis of "inflammatory pseudotumor" in the liver. However, the origin of some aggregated large atypical cells observed in the adrenal FNAC specimens was not known. Immunocytochemically, these large atypical cells were positive for vimentin and negative for cytokeratin and chromogranin A. An electron-microscopic study showed that these large atypical cells contained mitochondria with tubulovesicular cristae and smooth endoplasmic reticulum arranged in whorled and laminated patterns, and these findings confirmed diagnosis of primary adrenal cortical carcinoma. The histopathological diagnosis of the resected bilateral adrenal tumor was adrenal cortical carcinoma. The patient died 7 months after surgery, with recurrence of the bilateral adrenal cortical carcinoma and extensive metastases. A diagnosis of primary adrenal cortical carcinoma with extensive metastases was finally demonstrated by autopsy. Retrospectively, the previous liver tumor was determined to be a metastatic lesion.
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PMID:Use of electron microscopic evaluation for the diagnosis of adrenal cortical carcinoma in fine needle aspiration cytology: a case report and review of the literature. 1179 96


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