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)

A murine melanoma variant (B16-F10ir6), resistant to lymphocytic cytolysis, has been shown previously to produce lower numbers of tumor nodules in the lung of C57BL/6J mice following i.v. inoculations. These differences found in tumor implantation and lymphocyte recognition may be due to changes in surface properties of this cell line. Therefore, membrane-bound sialic acid (released by Vibrio cholerae neuraminidase treatment), ectosialyltransferase activity, and total cellular glycosidase levels were measured in this cell line and compared with levels in its parent melanoma tumor cell line, B16-F10, which was selected for its enhanced ability to form tumor nodules. The results of these studies indicate a correlation between the degree of lung implantation and the amount of tumor cell sialic acid accessible to neuraminidase cleavage, tumor cell surface sialyltransferase activity, and several cellular glycosidase activities. These results are consistent with the idea that membrane structural changes in the glycocalyx may account for the ability of a tumor cell to implant and metastasize.
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PMID:A correlation between cell surface sialyltransferase, sialic acid, and glycosidase activities and the implantability of B16 murine melanoma. 723 26

Two lines of mouse tumor cells were shown to be capable of aggregating mouse and rabbit platelets in vitro. This process required higher Mg2+ concentrations than were needed by other commonly used platelet-aggregating agents. Platelet-aggregating activity was also found in tumor cell membrane fragments. This membrane-bound platelet-aggregating material contained protein, lipid, and carbohydrate moieties. The presence of all three appeared to be essential for stimulating platelet aggregation. Destruction of any component abolished its activity: protein by trypsin; lipid by phospholipase A2 and non-ionic detergents; and sialic acid by neuraminidase. Platelet aggregation induced by tumor cell membrane fragments was associated with a secretory release reaction. In this process, growth-promoting activity for tumor cells was also released from platelets. These results underline the importance of platelets in establishing tumor metastases.
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PMID:Characterization of the platelet-aggregating activity of tumor cells. 735 51

We report a case of primary renal carcinoid, which is a very rare neoplasm: to our knowledge, only 19 cases have been previously reported. The tumor displayed histologic features typical of carcinoid tumors from other sites, including growth in nests and ribbons, uniform cells with finely granular, eosinophilic cytoplasm, and stippled chromatin. Electron microscopy confirmed the presence of membrane-bound dense-core granules. Immunohistochemical analysis revealed staining for chromogranin A, neuron-specific enolase, Leu-7, and synaptophysin, as well as pancreatic polypeptide. An interesting finding was the positive staining for prostatic acid phosphatase, while staining for prostate-specific antigen was negative. Although prostatic acid phosphatase is commonly seen in primary gastrointestinal hindgut carcinoids, in this case a primary hindgut carcinoid was ruled out by clinical examination and endoscopy. The patient developed metastases to the liver, but was well and without symptoms 15 months after diagnosis.
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PMID:Primary renal carcinoid. Case report and literature review. 768 15

The cases of three patients with primary carcinoid tumor of the testis were reported. The patients were 41, 44, and 83 years of age. At initial examination, all three had testicular masses with or without associated pain, and none had the carcinoid syndrome. The tumors measured 4.3 cm, 3.0 cm, and 6.5 cm in dimension. All three tumors manifested classic histologic features of carcinoid tumors. The neoplastic cells exhibited argyrophilia, and all were immunoreactive to chromogranin, serotonin, neuron-specific enolase, and cytokeratin. Two tumors had positive test results for gastrin and one had positive test results for substance P and vasoactive intestinal polypeptide. No tumors reacted with somatostatin, insulin, pancreatic polypeptide, or placental alkaline phosphatase. Intracytoplasmic, membrane-bound, round-to-elliptical pleomorphic granules were identified by ultrastructural analysis in all cases. DNA flow cytometric analysis revealed a low degree (near-diploid) DNA aneuploidy in all cases, with a DNA index of 1.15 in two tumors and 1.3 in the third tumor. The three patients are alive and well 11 years, 7 years, and 6 months, respectively, after diagnosis. A total of 57 cases of this entity, including the 3 reported here, have been reported. Of these, 43 were pure carcinoid, and 14 were associated with teratoma; 6 (11.6%) patients developed metastases. Tumor size and the presence of carcinoid syndrome have been found to correlate with metastatic potential. Neither tumor necrosis nor local tumor invasion (into vessels, tunica albuginea, etc.) correlated with adverse prognosis. Carcinoid tumor of the testis is a rare indolent neoplasm with potential for distant metastases.
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PMID:Primary carcinoid tumor of testis. Immunohistochemical, ultrastructural, and DNA flow cytometric study of three cases with a review of the literature. 768 60

CD59 (protectin) and CD46 (membrane cofactor protein, MCP) are membrane-bound complement regulator proteins which inhibit complement-mediated cytolysis of autologous cells. CD59, a phosphatidyl-inositol-anchored glycoprotein, inhibits the formation of the terminal membrane attack complex (MAC) of complement and was found to be a second ligand for CD2 contributing to T-cell activation. In 20 colorectal normal mucosa samples, in ten adenomas, 71 carcinomas and in ten liver metastases derived thereof, CD59 was inconsistently expressed in the epithelial compartment. In carcinomas CD59 expression in the whole neoplastic compartment was more often found in well- and moderately differentiated tumours. By contrast, focal expression or even complete lack of CD59 was more often found in poorly differentiated tumours (P = 0.021). In addition, carcinomas without metastases at the time of operation (Dukes A/B) more often expressed CD59 in the entire neoplastic population compared to those carcinomas which had already metastasised (P = 0.018). There was no correlation between the mode of CD59 expression in colorectal carcinomas and the tumour type or location. CD46 has C3b/C4b binding and factor-I dependent cofactor activity and is broadly expressed in various cells and tissues. In the epithelial compartment of normal colorectal mucosa, of all adenomas, carcinomas and their liver metastases, CD46 was expressed throughout the epithelial compartment. Since CD46 was consistently expressed in colorectal carcinomas the low expression or even lack of CD59 in a subset of tumours might not lead to critical complement-mediated attack of CD59-negative tumour cells. Regarding CD59 as a natural T-cell ligand involved in cognate T-cell-target-cell interaction, however, loss of CD59 might well be a selection advantage, provided that tumour antigen-mediated T-cell toxicity in colorectal carcinoma exists.
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PMID:Expression of CD59, a complement regulator protein and a second ligand of the CD2 molecule, and CD46 in normal and neoplastic colorectal epithelium. 769 19

The aim of the investigation was to study directly the IL-2 receptor (IL-2R) and its subunits, p55 and p75 chains, either membrane-bound or soluble, on PBMC of patients with solid malignancies and, indirectly, the same patients' PBMC ability to produce IL-2. Fifty-eight cancer patients, 29 men and 29 women, were studied: their mean age was 57.3 yr, range 35-79. Twenty-two healthy age-sex-matched subjects served as controls. The tumors were the most common and the most representative among human cancers, i.e., breast, lung, head and neck, digestive tract and liver, prostate and gynecologic cancers: they were generally in advanced stages and in 23 cases metastatic. The PBMC proliferative response to PHA, PHA plus IL-2, and IL-2 was evaluated along with the response to PHA in the presence of anti-p55, anti-p75 monoclonal antibodies, or both. Moreover, membrane-bound IL-2R (p55 and p75 chains) on PHA-stimulated PBMC was detected, along with soluble IL-2R in the serum and in the culture supernatants. The conclusions suggest that in solid malignancies: the membrane-bound IL-2Rs, both p55 and p75 chains, are expressed normally, there is an high serum level of soluble IL-2R, there is a normal release of soluble IL-2R in culture, and there is an indirect evidence of a lack of IL-2 production. Therefore, no primary impairment of IL-2R was found in solid tumors. Moreover, in our study we have found no difference in any parameter studied between patients with and patients without metastases.
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PMID:Membrane-bound and soluble IL-2 receptors (p55 and p75 chains) on peripheral blood mononuclear cells from patients with solid malignancies. 788 44

The multiple actions of somatostatin are mediated by specific membrane-bound receptors present in all somatostatin target tissues, such as brain, pituitary, pancreas, gastrointestinal tract, and kidney. For instance, in the human gastrointestinal tract, three different types of tissue compartments express somatostatin receptors: the gastrointestinal mucosa, the peripheral nervous system, and the gut-associated lymphoid tissue, where the receptors are preferentially located in germinal centers. In all these cases, somatostatin binding is of high affinity and specific for bioactive somatostatin analogues. Somatostatin receptors are also expressed in pathological states, such as cancers. A particular abundance is found in neuroendocrine tumors of the gastrointestinal tract. Ninety percent of the carcinoids and a majority of islet cell carcinomas, including their metastases, usually have a high density of somatostatin receptors. Several different somatostatin-receptor subtypes can be expressed by these tumors, the SSTR2 subtype being the most frequently and abundantly expressed. The somatostatin receptors in tumors are identified with in vitro-binding methods, molecular biology techniques, or in vivo-imaging techniques; the latter allow the precise localization of the tumors and their metastases in the patients. Because somatostatin receptors in human gastroenteropancreatic tumors are functional, their identification can be used to predict the therapeutical efficacy of octreotide to inhibit excessive hormone release. Of differential diagnostic importance is the fact that other pathological processes in the gastrointestinal tract may be associated with a high density of somatostatin receptors. Ninety percent of lymphomas, including those with intestinal involvement express somatostatin receptors. Furthermore, a moderate number of colorectal carcinomas contain somatostatin receptors, whereas exocrine pancreatic carcinomas do not. Finally, an increased expression of SS receptors in nonneoplastic conditions, such as in intestinal veins in inflammatory bowel disease, has been recently observed. These observations demonstrate the ability of the human body to regulate SS receptors in a wide number of tissues and conditions.
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PMID:Expression of somatostatin receptors in normal, inflamed, and neoplastic human gastrointestinal tissues. 797 60

Two Merkel cell tumor cultures (MC-MA1, MC-MA2) have been established from metastases of typical Merkel cell tumors. The mestastases in vivo were characterized by co-expression of cytokeratins 8, 18, 19, 20 and neurofilaments, presence of intermediate filament whirls, expression of synaptophysin, neuron-specific enolase, and chromogranin A, rare and weak immunostaining for plakoglobin but absence of cadherins and desmoplakins. Both cultures grow, using supplemented RPMI medium on human irradiated fibroblast feeder layers, as loosely arranged floating small aggregates. Their karyotypes are mostly hyperdiploid. The mean doubling times were about 84 h in the first 8 months and later increased. Ultrastructural and immunoelectron microscopic studies of the Merkel cell tumor cells in vitro (MC-MA1, MC-MA2) revealed sparse membrane-bound neuroendocrine granules and typical IFs that were partly arranged in paranuclear whirls and were labeled by antibodies against cytokeratins and neurofilaments. In immunocytochemical studies using antibodies to cytokeratins 8, 18, 19, and 20 and neurofilament protein NF-L, Merkel cell tumor cells in vitro showed a uniform staining appearing as paranuclear whirls and cytoplasmic fibrils as well. Double-labeling experiments showed a co-localization of both intermediate filament types in most cells. Biochemically we found cytokeratins 8, 18, 19, and 20, and NF-L in tumor cells in vitro. Immunocytochemical staining was negative for desmoplakins, various cadherins, and cell adhesion molecules, whereas plakoglobin was only rarely detectable in some Merkel cell tumor cells in vitro. By immunoluminometric assay chromogranin A was detected in cell homogenates and culture supernatants as well. Immunocytochemically, synaptophysin and neuron-specific enolase were detectable additionally in some of the cells. These established cell cultures will allow further studies devoted to the biology, differentiation, and hormone secretion of Merkel cell tumors that may also increase our knowledge about normal Merkel cells.
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PMID:Establishment and characterization of two Merkel cell tumor cultures. 812 Apr 18

The value of immunoscintigraphy in patients with metastatic malignant melanoma of the head and neck is compared with clinical, radiological and histological findings. 25 immunoscintigraphic examinations in 16 patients were evaluated. Scintigraphy was performed during primary and follow-up diagnosis of head and neck melanoma of the skin (n = 8), nose and sinuses (n = 3), petrosal bone (n = 1) and sclera (n = 1) as well as in cervical lymph node metastases of distant melanoma (n = 2) and melanoma of an unknown primary tumour (n = 1). Immunoscintigraphy was performed with 99mTc-radiolabelled melanoma specific antibodies against a melanoma-associated cell membrane-bound antigen (glycopolypeptide). The sensitivity of the method was 88%, specificity was 80%. The prior significance of immunoscintigraphy is based on the detection of occult cervical lymph node metastases not detectable by means of palpation and radiography. Pulmonary and liver manifestations could not be safely identified due to the physiological enhanced blood pool in these organs. The results obtained indicate that immunoscintigraphy may yield more information about the status of pathologically altered tissue and in certain cases may influence the therapeutic procedure.
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PMID:[Immunoscintigraphic detection of metastasis in malignant melanoma in the head and neck area]. 816 16

The aim of this article is to present a case of primary neuroendocrine tumor (typical carcinoid) of the mandible that occurred in a 46-year-old black woman who was seropositive for the human immunodeficiency virus. Radiologically the lesion presented as a poorly circumscribed honeycomb radiolucency that extended from tooth 21 to the ascending ramus. Histologically the tumor cells were variously arranged in small islands, trabeculae, follicles, and slitlike spaces lined by a single layer of palisaded low-columnar cells. The follicles contained an eosinophilic colloid-like substance. Immunocytochemical staining showed diffuse, intense positivity for MAK 6, pancytokeratin, S-100, and neuron-specific enolase and focal, intense, positive staining for chromogranin A. Electron microscopy showed the presence of interdigitating cell membranes, rudimentary cell attachments, and varying numbers of membrane-bound dense core granules. Special investigations failed to reveal a primary tumor, and no metastases were found. Urine and hematologic assessment did not show any evidence of functional activity. The tumor was resected, and no recurrence or spread has been seen for 2 years. Origin from foregut-derived, immature, and functionally uncommitted endocrine cells is presumed.
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PMID:Neuroendocrine (carcinoid) tumor of the mandible: a case report and review of the literature. 885 Apr 88


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