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)

Studies on normal bone marrow and Daudi Burkitt lymphoma cells were performed to determine the efficacy of selective, in vitro chemopurging with methylprednisolone (MP). We found that MP reduces the number of lymphoma cells without significant damage to bone marrow cells. This information is important because we need to improve the existing in vitro purging regimens used to cleanse autologous marrows of metastatic disease before transplantation into cancer patients who have received high-dose chemotherapy. Normal human bone marrow (NBM) and Daudi lymphoma cells were treated in parallel with various purging regimens, NBM death was evaluated using soft-agar culture, while Daudi cell death was evaluated using one-week liquid culture. A protocol of 2.0 mg/mL of MP for four hours demonstrated optimal selectivity. When treatment was followed by cryopreservation, a 1.7 log purge of Daudi cells was increased to 2.3 logs while preserving 36% of committed NBM precursors. We repeated these experiments on a simulated contaminated marrow to model closely the mixture of normal and malignant cells found in advanced, metastatic disease. We evaluated this mixed system by flow cytometric immunoanalysis using the two-color CD10/CD20 markers to detect residual, viable Daudi cells. Our initial results were reproducible in this mixed-cell system, further supporting the evidence for effective in vitro purging of bone marrow using MP.
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PMID:Assessment of methylprednisolone purging efficacy on Daudi burkitt lymphoma cells from normal bone marrow. 189 5

The clinical presentation of cervical metastases in a young woman presenting with cervical lymphadenopathy is described. The clinical, histological, ultrastructural and immunological findings establishing the diagnosis of a renal primary tumour are seen. The significance of mixed tumour cell expression of antigens specific for the proximal tubule (CD10, DPP4 and aminopeptidase N) and of Tamm Horsfall protein, normally expressed on the thick ascending limb of loop of Henle and distal tubule, is discussed.
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PMID:Tamm Horsfall protein expression by a small renal cell carcinoma presenting with metastases. 196 77

Immunoperoxidase localization of monoclonal antibodies in sections of melanoma has been used to identify histological features which may be of prognostic importance in melanoma, in particular whether certain structures on melanoma cells may determine the degree and nature of lymphoid infiltrates and whether these may be related to prognosis. Monoclonal antibodies to lymphocyte subpopulations were used to identify and quantitate lymphoid infiltrates in 15 primary melanomas and 8 cutaneous metastases. These were correlated with histological features identified in routine sections. There was a wide variation in the numbers of mononuclear cells associated with both primary and metastatic melanoma. T cells and to a lesser extent macrophages accounted for the majority of the cells, B cells and natural killer (NK) cells for only 2% of the infiltrates. The Leu 3a (helper) T cell subpopulation predominated in primary tumours, OKT8 positive (suppressor/cytotoxic) cells in metastases. Infiltrates in which OKT8 cells predominated were associated with ulceration, a high mitotic rate and thick primary tumours. The converse applied to Leu 3a infiltrates. Infiltrates with a high proportion of Leu 3a positive cells tended to be associated with Thy-1 positive, DR antigen negative tumours. Thy-1 antigens were predominantly expressed on primary tumours and rarely on metastases whereas the converse applied to expression of the acute lymphoblastic leukemia antigen (CALLA) on melanoma cells. These findings suggest that certain melanoma antigens may be related to the nature of the lymphoid infiltrate associated with melanoma and possibly with the behaviour of the tumour in the host. They further suggest that identification of cell surface structures and lymphoid infiltrates by these techniques may be a valuable extension of routine histopathological assessment of prognosis in melanoma.
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PMID:Current research on immunopathology of melanoma: analysis of lymphocyte populations in relation to antigen expression and histological features of melanoma. 286 82

Neutral endopeptidase 24.11 (NEP, CD10) is a cell-surface enzyme expressed by prostatic epithelial cells that cleaves and inactivates neuropeptides implicated in the growth of androgen-independent prostate cancer (PC). NEP substrates such as bombesin and endothelin-1 induce cell migration. We investigated the mechanisms of NEP regulation of cell migration in PC cells, including regulation of phosphorylation on tyrosine of focal adhesion kinase (FAK). Western analyses and cell migration assays revealed an inverse correlation between NEP expression and the levels of FAK phosphorylation and cell migration in PC cell lines. Constitutively expressed NEP, recombinant NEP, and induced NEP expression using a tetracycline-repressive expression system inhibited bombesin- and endothelin-1-stimulated FAK phosphorylation and cell migration. This results from NEP-induced inhibition of neuropeptide-stimulated association of FAK with cSrc protein. Expression of a mutated catalytically inactive NEP protein also resulted in partial inhibition of FAK phosphorylation and cell migration. Coimmunoprecipitation experiments show that NEP associates with tyrosine-phosphorylated Lyn kinase, which then binds the p85 subunit of phosphatidylinositol 3-kinase (PI3-K) resulting in an NEP-Lyn-PI3-K protein complex. This complex competitively blocks FAK-PI3-K interaction, suggesting that NEP protein inhibits cell migration via a protein-protein interaction independent of its catalytic function. These experiments demonstrate that NEP can inhibit FAK phosphorylation on tyrosine and PC cell migration through multiple pathways and suggest that cell migration which contributes to invasion and metastases in PC cells can be regulated by NEP.
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PMID:Neutral endopeptidase inhibits prostate cancer cell migration by blocking focal adhesion kinase signaling. 1110 93

We investigated the biologic behavior of gastric phenotype carcinoma of the stomach, especially in association with degradation of the extracellular matrix. One hundred fourteen lesions of intramucosal gastric carcinoma (IMGC) of differentiated type were studied. IMGCs were classified into 4 phenotypic categories--complete intestinal type (C type), incomplete intestinal type (I type), gastric type (G type), and unclassified type--through a combination of the expression of CD10, MUC2, HGM, and Con A. The expression of MMP-2, MMP-9, TIMP-2, and type IV collagen was investigated by immunohistochemical staining. The incidence of C-type IMGC, I-type IMGC, and G-type IMGC was 7.9%, 55.3%, and 36.8%, respectively. The incidence of positive MMP-9 expression in G-type IMGCs (57%) was significantly higher than that in C-type IMGCs (11%) or I-type IMGCs (35%) (P < .01). There was no significant correlation between phenotypes and expression of MMP-2, TIMP-2, or type IV collagen. There was a reverse correlation between the expression of type IV collagen and the expression of type IV collagenase (P < .001). In conclusion, gastric phenotype carcinomas have been shown to be highly invasive and metastatic, However, although they can potentially degrade the extracellular matrix via overexpression of MMPs compared with intestinal phenotype carcinoma, our data show no statistically significant separation of subtypes of intramucosal gastric cancer based on gross classification, histologic type, lymphatic or venous invasion, or lymph node metastases.
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PMID:Relationship between biologic behavior and phenotypic expression in intramucosal gastric carcinomas. 1182 76

The CD10 antigen is a neutral endopeptidase expressed by a variety of mesenchymal tumours (haemopoietic or not), including a subset of malignant melanomas. We investigated the expression of CD10 in formalin-fixed, paraffin-embedded tissue specimens of 72 cutaneous melanomas (28 primary, 26 metastatic to the skin and 18 lymph node metastases). The CD10 antigen was expressed by 18 of the 26 (69%) and 11 of the 18 (61%) melanomas metastatic to the skin or lymph nodes, respectively; in contrast, only six of the 28 primary melanomas (21.4%) expressed appreciable CD10 reactivity, and expression was usually lower (in terms of the percentage of immunoreactive cells) than that found in metastatic tumours. The sensitivity, specificity, and positive and negative predictive values of CD10 positivity for metastatic malignant melanoma were calculated to be 0.66, 0.79, 0.83 and 0.6, respectively. Our results suggest that the CD10 antigen is upregulated during the process of metastasis in melanomas. From a diagnostic point of view, the expression of CD10 appears to be an additional feature for the histological differential diagnosis between primary and metastatic melanomas.
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PMID:Differential expression of the CD10 antigen (neutral endopeptidase) in primary versus metastatic malignant melanomas of the skin. 1214 Mar 80

We report the clinicopathologic features of 24 uterine primary and metastatic endometrial stromal sarcomas with fibromyxoid features (ESS-F) and smooth muscle differentiation (ESS-SM) (endometrial stromal sarcoma variants). Two groups of tumors were retrieved from the surgical pathology files at Memorial Sloan-Kettering Cancer Center: 1) gynecologic mesenchymal neoplasms with striking smooth muscle or fibroblastic differentiation that did not meet the clinical or histologic criteria for leiomyosarcoma or other established neoplasms containing smooth muscle; and 2) metastatic lesions showing ovoid and spindle cell morphology, involving lung, originally diagnosed as low-grade leiomyosarcoma, low-grade smooth muscle neoplasm, intravenous leiomyomatosis, fibrous hamartoma, and benign metastasizing leiomyoma. We identified 12 patients with 30 tumors; 24 were available for review. The mean age was 51 years (range 21-74 years). Follow-up >1 year was available for eight patients, with a mean time of 8.5 years. Each patient had a uterine primary and 10 experienced metastases. Mean time to recurrence was 6.8 years. Sites of metastasis included lung, retroperitoneum, right atrium/inferior vena cava, colon, and ovaries. No patient died of disease, but in many cases the follow-up period ended with the discovery of a metastasis. Four patients were originally diagnosed with endometrial stromal sarcoma, but other presenting diagnoses included benign metastasizing leiomyoma, fibroleiomyomatous tumor of lung, smooth muscle tumor of uncertain or low malignant potential, and intravascular leiomyomatosis. On review each patient had at least one tumor (primary and/or metastasis) that was determined to be an endometrial stromal sarcoma variant. Review diagnoses were as follows: endometrial stromal sarcoma (nonvariant), ESS-F, and ESS-SM. Eight of 10 primary tumors with available slides were endometrial stomal sarcoma variants (six ESS-F and two ESS-SM). When these variant features were present, they comprised between 50% and 100% of the neoplasm. The variant histology tumors exhibited prominent spiral arterioles, perivascular edema, and stromal cell condensation around blood vessels. All metastases but one were variant tumors; eight were ESS-F and five were ESS-SM. Four metastases did not resemble the uterine primary. Desmin marked smooth muscle mostly but not specifically. h-Caldesmon marked smooth muscle exclusively. Endometrial stromal cells as well as some fibroblasts and smooth muscle cells expressed CD10. We conclude that the presence of even focal endometrial stromal differentiation in an invasive uterine mesenchymal lesion with a predominant low-grade smooth muscle, fibroblastic, and/or myxoid phenotype should permit classification as low-grade sarcoma-they should be considered endometrial stromal sarcomas.
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PMID:Endometrial stromal sarcomas with unusual histologic features: a report of 24 primary and metastatic tumors emphasizing fibroblastic and smooth muscle differentiation. 1221 70

Dissemination of a malignant tumour is the result of a cascade of events beginning with detachment of cells from primary tumour followed by extravasation and growth at secondary sites. The differences in metastatic ability could be attributed to properties intrinsic to the various tumour types. Thus the clonal selection of tumour cells from successive metastases apparently results in cells better equipped for survival and formation of colonies in secondary sites, indicating that survival is not a random phenomenon. Many studies of malignant cells have correlated the overexpression of adhesion receptors such as integrins and the production of cysteine proteases and glycosidases with the progression of malignancy. The interaction of cysteine proteases with basement membrane components has been implicated in tumour invasion, activation of hormones and growth factors. On the other hand, the expression of the heparanase gene and its protein has been associated with the metastatic potential of several human and mouse tumour cell lines. This study aimed to investigate the correlations between the metastatic properties of clones with high and low metastatic potential and their ability to adhere to the extracellular matrix and to degrade proteins and sulphated glycosaminoglycans present there. Clonal selection of the B16F10 cell line was performed, and the clones were examined for the expression of an integrin-type laminin receptor. A significantly higher level was detected in a high metastatic clone. Enzymatic assays showed higher activity for alpha-d-N-acetylglucosaminidase, beta-d-N-acetylgalactosaminidase and beta-d-glucuronidase in conditioned medium from low metastatic clones compared with that from high metastatic clones. However, higher endopeptidase activity was observed in conditioned medium from high metastatic clones. In summary, these results showed a positive correlation between high metastatic potential and endopeptidase secretion. Similarly, a positive correlation was observed between low metastatic cells and the secretion of glycosaminoglycan-degrading glycosidases.
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PMID:Enzyme and integrin expression by high and low metastatic melanoma cell lines. 1256 79

The diagnosis of primary clear cell carcinoma of the ovary or kidney is usually straightforward. However, problems in ascertaining the site of the primary tumor may arise when there is widespread metastatic disease or when clear cell carcinoma is present in both the ovary and kidney. In this study, the value of a panel of antibodies in distinguishing between an ovarian and renal clear cell carcinoma was evaluated. The panel comprised cytokeratin (CK)7 and 20, vimentin, estrogen receptor (ER), CD10, and renal cell carcinoma (RCC) marker. Ovarian clear cell carcinomas (n=14) were positive with CK7 (14/14), vimentin (6/14), ER (2/14), and RCC marker (2/14). All were negative with CD10 and CK20. Renal clear cell carcinomas (n=14) were positive with CD10 (14/14), RCC marker (14/14), vimentin (7/14), CK7 (2/14), and CK20 (1/14). All were negative with ER. This panel allows clear cell carcinomas of the ovary and kidney to be distinguished with a high degree of certainty and is a useful adjunct to histologic examination. Primary ovarian clear cell carcinomas are characterized by CK7 positivity, whereas primary renal neoplasms are characterized by positivity for CD10 and RCC marker and negative staining with CK7.
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PMID:A panel of immunohistochemical stains assists in the distinction between ovarian and renal clear cell carcinoma. 1281 95

The differential diagnosis between hepatocellular carcinoma (HCC) and metastatic carcinoma, especially in moderate-poorly differentiated (MPD) HCC and poorly differentiated carcinoma, can be challenging in fine-needle aspiration biopsy (FNAB) of the liver. Recent studies demonstrate that canalicular staining for CD10 appears to be a highly specific marker for hepatocytic differentiation. The objective of this study was to test the utility of CD10 in differentiating HCC from metastatic carcinoma in FNAB of the liver. Formalin-fixed, paraffin-embedded cell blocks of 55 cases (22 HCC, 23 metastases, and 10 benign hepatic lesions) of FNAB of the liver were immunostained using monoclonal antibody against CD10, with microwave oven antigen retrieval, followed by a standard ABC method. Nineteen (86%) of 22 HCC cases were positive for CD10 with a canalicular staining pattern. Among them, 9 (82%) of 11 well-differentiated (WD) HCC and 10 (91%) of 11 MPD HCC were positive for CD10. Three (13%) of 23 metastatic carcinomas were positive for CD10, demonstrating a contrasting cytoplasmic and membranous staining pattern. The three positive cases were metastatic renal cell carcinoma (RCC), choriocarcinoma, and adenocarcinoma of the lung. All 10 cases of benign hepatic lesions showed positivity for CD10 with a canalicular and focal membranous staining pattern. In conclusion, CD10 appears to be a useful marker in discriminating between HCC and metastatic carcinoma when applied to FNAB of the liver. CD10 does not provide discrimination between WD HCC and benign hepatocytes.
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PMID:Diagnostic utility of CD10 in differentiating hepatocellular carcinoma from metastatic carcinoma in fine-needle aspiration biopsy (FNAB) of the liver. 1475 58


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