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 neural cell adhesion molecule (NCAM) is highly expressed on the surface of small-cell-lung cancer (SCLC) cells. We have produced a monoclonal antibody, NY3D11, that binds to NCAM to investigate whether this antigen could be used to develop antibody-directed therapy for SCLC. 125I-labelled IgG and F(ab')2 fragments of NY3D11 localized selectively in human SCLC xenografts grown in nude mice. The human biodistribution of 131I-labelled NY3D11 after intravenous administration was investigated by gamma-camera imaging in six patients with SCLC. Three patients received IgG and three received F(ab')2. No evidence of localization to primary tumours or metastases was seen and antibody accumulated rapidly in the liver and bone marrow. The probable explanation for this distribution is that NY3D11 reacted with soluble NCAM or natural killer cells that possess the CD56 (NCAM) antigen.
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PMID:Biodistribution of a radiolabelled monoclonal antibody NY3D11 recognizing the neural cell adhesion molecule in tumour xenografts and patients with small-cell lung cancer. 945 53

As in the development of many human cancers, in a transgenic mouse model of beta-cell carcinogenesis (Rip1Tag2), expression of neural cell adhesion molecule (NCAM) changes from the 120-kDa isoform in normal tissue to the 140/180-kDa isoforms in tumors. NCAM-deficient RiplTag2 mice, generated by crossing Rip1Tag2 mice with NCAM knockout mice, develop metastases, a tumor stage that is not seen in normal Rip1Tag2 mice. In contrast, overexpression of NCAM 120 in NCAM-deficient Rip1Tag2 mice prevents tumor metastasis. The results indicate that the loss of NCAM-mediated cell adhesion is one rate-limiting step in the actual metastatic dissemination of beta tumor cells.
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PMID:Reduced expression of neural cell adhesion molecule induces metastatic dissemination of pancreatic beta tumor cells. 1008 83

We report one case of papillary meningioma located in the posterior fossa in a 3-year-old boy. Despite a gross total resection, a major recurrence occurred 6 months later that was operated on. Eight months later, another recurrence was observed with intracranial metastases and dissemination throughout the cerebrospinal fluid. The tumor had a papillary architecture more obvious in the recurrence. Areas of necrosis were numerous. Tumor cells had large clear atypical nuclei. Many mitotic figures were seen and Ki-67 labeling index was high. The tumor cells were immunoreactive for vimentin and polysialylated neural cell adhesion molecule only, ruling out a diagnosis of ependymoma or medulloblastoma. Diagnosis of meningioma was done by electron microscopy, which showed interdigitating cytoplasmic processes and cell junctions. Cytogenetic study revealed unusual karyotypic abnormalities.
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PMID:Cerebellar papillary meningioma in a 3-year-old boy: the usefulness of electron microscopy for diagnosis. 1040 9

To investigate the relationship between the expression of the cell adhesion molecules intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and neural cell adhesion molecule (NCAM) in uveal melanoma and the metastatic spread in the first 5 years after diagnosis, we performed a hospital-based case-control study with human tissue from 90 patients who underwent enucleation for primary uveal melanoma (iris melanoma excluded). Thirty-five patients developed metastasis within the first 5 years, and 55 patients lived metastasis-free for at least 5 years after enucleation. The paraffin-embedded and formalin-fixed globes were studied by immunohistochemistry with monoclonal antibodies for ICAM-1, VCAM-1 and NCAM. A strong ICAM-1 positivity (more than 75% of the tumor cells stained positive) was detected in 73 tumors (81%). The expression of 75% or less ICAM-1 positive cells in tumors was strongly associated with the development of metastases (odds ratio: 7.5, p = 0.001). Multiple logistic regression models showed that ICAM-1 is an independent risk factor for metastasis even after control for important prognostic markers like extraocular growth, ciliary body involvement, scleral infiltration and cell type. VCAM-1 was expressed in 24 out of 88 tumors (27.3%) and NCAM only in 14 out of 87 tumors (16%). Only spindle cells stained positive with anti-NCAM. NCAM and VCAM-1 expression was not related to metastasis. Our results show that the loss of ICAM-1 expression is associated with an increased risk of metastasis within the first 5 years after diagnosis.
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PMID:Expression of the cell adhesion molecules ICAM-1, VCAM-1 and NCAM in uveal melanoma: a clinicopathological study. 1064 45

Pituitary adenomas are usually benign neuroendocrine tumors. However, some of those that are histopathologically undistinguishable behave aggressively and metastasize. The polysialylated neural cell adhesion molecule (PSA-NCAM), which is highly expressed during the development of the brain and pituitary, is detected in some neuroendocrine tumors and might be relevant as a prognostic marker in pituitary tumors. In the present study, we have searched for PSA-NCAM expression in four lineages of rat pituitary transplantable tumors (SMtTW). Each lineage, maintained by serial tumor grafts under the kidney capsule and skin, differed in its GH/Prl secretion, growth rate, and malignant behavior. PSA-NCAM expression, detected by immunohistochemistry and Western blotting and quantified by ELISA, varied according to the SMtTW lineage. The benign tumors, SMtTW2, with a low growth rate never expressed PSA-NCAM. Another benign lineage, SMtTW3, with a high growth rate expressed a low amount of PSA-NCAM. The highest PSA-NCAM expression was seen in tumors that grew beneath the skin, invaded the kidney, and metastasized (SMtTW4). Tumors of the SMtTW10 lineage, which behaved as either benign or malignant tumors, were heterogeneous in terms of PSA-NCAM expression. In this rat transplantable pituitary tumor model, PSA-NCAM expression correlated in decreasing order with: (a) invasiveness (P < 0.0001), (b) metastases (P = 0.004), (c) ability to grow under the skin (P = 0.006), and (d) growth rate under the kidney capsule (P < 0.01), but not with hormone secretion (r = 0.207). This model, which is very similar to the human pathology, suggests that PSA-NCAM evaluation is of interest in the diagnosis of malignancy and the prognosis of human pituitary tumors. In addition, the SMtTW tumors could be instrumental in evaluating the effects of new therapeutic agents modulating PSA-NCAM expression.
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PMID:Polysialylated-neural cell adhesion molecule expression in rat pituitary transplantable tumors (spontaneous mammotropic transplantable tumor in Wistar-Furth rats) is related to growth rate and malignancy. 1064 57

Cell lines are valuable resources for the study of the malignancy and potential therapy of human breast cancer. A major problem with adapting fresh breast tumor specimens to grow in vitro is contamination by fibroblasts. Previously, we have reported a technique to overcome this problem (Nayak, S. K; Dillman, R. O. Clin. Biotechnol. 3:237-242; 1991). We have recently established two new breast cancer cell lines, HH315 and HH375, that were derived from abdominal and supraclavicular lymph node metastases from two patients. They were characterized by (1) growth kinetics; (2) staining with monoclonal antibodies (MoAbs) to cytokeratin-19, epithelial membrane antigen (EMA), anticarcinoembryonic antigen (CEA), breast cancer antigen 1 (BRST-1), breast cancer antigen 2 (BRST-2), Her2/neu, and p53; (3) expression of domains of urinary plasminogen activator (uPA), neural cell adhesion molecule (NCAM), and haptoglobin (Hp) (Harvey et al., 1997); and (4) karyotypic analysis. Growth kinetic studies showed that doubling times for both lines ranged from 48 to 96 h. These two cell lines were found to have characteristics of the metastatic breast cancer cells. Both lines stained positive with MoAbs to cytokeratin-19 and EMA, thus confirming their epithelial origin. They also strongly reacted with the pan-breast carcinoma MoAbs BRST-1 and BRST-2, and carcinoembryonic CEA MoAb. Both cell lines overexpressed the oncogene proteins Her2/neu and p53. The tumor cells were negative for estrogen and progesterone receptors. HH315 cells were poorly differentiated, whereas the HH375 cells exhibited adenocarcinoma morphology. Both cell lines showed intense cell surface and some cytoplasmic staining for uPA, NCAM, and Hp domains, which is a characteristic of malignant neoplasms (Harvey et al., 1997). The HH375 cell line showed two cell types, of which 60% were hyperdiploids with 60-70 chromosomes and 5-10 marker chromosomes. The remaining cells were polyploid with more than 200 chromosomes. Cell line HH315 consisted of only a polyploid population. These cell lines may be useful in breast cancer research.
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PMID:Characterization of cancer cell lines established from two human metastatic breast cancers. 1077 59

A new type of immuno-cell therapy called BRM-activated killer (BAK) therapy using non-MHC-restricted lymphocytes, CD56-positive cells, was devised. Peripheral blood lymphocytes were selected by immobilization with anti-CD3 monoclonal antibody and cultured for 2 weeks in the presence of IL-2. Thereafter, they were reactivated by 1,000 U/ml of IFN-alpha for 15 min. Twenty-six outpatients with cancer whose performance status were over 80% on Karnofsky scale were selected for this study. About 6 x 10(9) BAK cells were returned by intravenous drip infusion, at one month intervals at an outpatient clinic to each of 20 advanced cancer patients in whom many metastatic lesions were found postoperatively, and to 6 patients with no postoperatively detectable metastases. The proportion of CD56-positive cells increased from 20% to 50% with culture. CD56-positive cells have strong cytotoxic activity and produced 20 ng/10(9) cells of beta-endorphin, an intracerebral hormone. During the course of BAK therapy, we adopted the Face scale as a QOL indicator. The QOL of all patients remained satisfactory or improved. Beta-endorphin is thought to make patients feel well and maintains good QOL because of its potent analgesic, sedative activity. From that facts that CD56 is a neural cell adhesion molecule and a member of the Ig superfamily, and that the CD56-positive cell produces beta-endorphin, we concluded that the CD56-positive cell is a multifunctional, integrated NIE (neuro-immune-endocrine) cell. Administration of BAK cells allowed all 20 advanced cancer patients with metastases to survive for over one year. All 6 patients receiving the same therapy for prevention of postoperative metastasis have been recurrence-free for one to five years.
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PMID:Effector mechanism and clinical response of BAK (BRM-activated killer) immuno-cell therapy for maintaining satisfactory QOL of advanced cancer patients utilizing CD56-positive NIE (neuro-immune-endocrine) cells. 1147 30

Twelve cases of carcinoid tumors of the thymus were reviewed in terms of clinicopathologic, histochemical, and immunohistochemical features and DNA ploidy patterns. The collective consisted of nine male and three female patients, aged 34 to 74 years, of whom five (42%) had symptoms. Eleven patients underwent surgical resection, and one with systemic metastases was autopsied. In the 11 resected patients, tumors had invaded surrounding structures in four cases, and mediastinal lymph node metastases were detected in six. Recurrence occurred in two of the resected patients (18%), and the 5-year survival rate was 82%. Histologically, all tumors showed an organoid growth pattern with delicate fibrovascular stroma. In addition, three tumors had unusual morphologic features such as combined features of carcinoid tumor and thymoma and solid growth pattern with occasional large tumor cells. Mitotic counts ranged from 1 to 14 per 10 high-power fields with a mean count of 4.9. Central necrosis within solid nests was observed in nine tumors. Classification of this series using the WHO histologic classification system resulted in categorization of all 12 tumors as atypical carcinoids. All tumors were positive for Grimelius staining and for cytokeratin. Immunohistochemical staining documented the presence of moderately to strongly positive neuroendocrine markers such as neuron-specific enolase, chromogranin A, synaptophysin, and neural cell adhesion molecule. No correlation between proliferative activity based on the Ki67 labeling index and prognosis or lymph node metastasis was found. Concerning DNA ploidy patterns, only one tumor with multiple lymph node metastases was considered to be aneuploid. In conclusion, although all of our cases were histologically classified as atypical carcinoid tumors of the thymus, most were diploid, and the patients enjoyed a relatively good prognosis.
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PMID:Clinicopathologic and DNA cytometric analysis of carcinoid tumors of the thymus. 1159 68

Previously we observed that neural cell adhesion molecule (NCAM) deficiency in beta tumor cells facilitates metastasis into distant organs and local lymph nodes. Here, we show that NCAM-deficient beta cell tumors grew leaky blood vessels with perturbed pericyte-endothelial cell-cell interactions and deficient perivascular deposition of ECM components. Conversely, tumor cell expression of NCAM in a fibrosarcoma model (T241) improved pericyte recruitment and increased perivascular deposition of ECM molecules. Together, these findings suggest that NCAM may limit tumor cell metastasis by stabilizing the microvessel wall. To directly address whether pericyte dysfunction increases the metastatic potential of solid tumors, we studied beta cell tumorigenesis in primary pericyte-deficient Pdgfb(ret/ret) mice. This resulted in beta tumor cell metastases in distant organs and local lymph nodes, demonstrating a role for pericytes in limiting tumor cell metastasis. These data support a new model for how tumor cells trigger metastasis by perturbing pericyte-endothelial cell-cell interactions.
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PMID:Pericytes limit tumor cell metastasis. 1647 Feb 44

Prolactinoma is the most common pituitary tumour in adults. Macroprolactinomas, particularly in men, may occasionally exhibit a very aggressive clinical course as evidenced by progressive growth, invasion through bone into the sphenoid sinus, cavernous sinus, suprasellar region or the nasopharynx. Some may even progress to pituitary carcinoma with craniospinal or systemic metastases. Aggressive tumours have low cure rates despite appropriate medical and surgical treatment. The mechanisms underlying this aggressive biological behaviour have not yet been fully clarified. Recent immunohistochemical, molecular and genetic studies have provided some insight in this respect. Invasive prolactinomas may be associated with a high Ki-67/MIB-1 labelling index indicating increased cell proliferation, although this is not a universal finding. The AA polymorphism in the cyclin adenine (A)/guanine (G) gene is more frequently detected in invasive prolactinomas. Increased expression of the polysialylated neural cell adhesion molecule (NCAM) and reduced expression of the E-cadherin/catenin complex implies a contribution of altered cell-to-cell adhesion and cellular migration. Extracellular matrix components (ECM), matrix metalloproteinases (MMPs) and their inhibitors play important roles in the context of angiogenesis and invasion. The induction of fibroblast growth factor and vascular endothelial growth factor via oestrogen-induced overexpression of novel genes (PTTG, hst and Edpm5) enhance cell growth, proliferation and angiogenesis contributing to invasiveness in prolactinomas. Although mutations in proto-oncogenes like Ras are uncommon, loss of tumour suppressor genes at loci 11q13, 13q12-14, 10q and 1p seem to be associated with invasiveness. Of the described mechanisms, only reduced E-cadherin/catenin expression and overexpression of hst gene seem to be relatively specific markers for prolactinoma invasiveness compared with other pituitary adenomas. Further research is needed to clarify the molecular mechanisms behind the aggressive course of some prolactinomas to predict those with a potentially poor clinical outcome, and to devise treatments that will eventually enable the cure of these challenging tumours.
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PMID:What are the markers of aggressiveness in prolactinomas? Changes in cell biology, extracellular matrix components, angiogenesis and genetics. 1728 3


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