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)

In this study, we examined the effect of triflavin, an Arg-Gly-Asp (RGD)-containing snake venom peptide, on human cervical carcinoma (HeLa) cell- and B16-F10 mouse melanoma cell-induced platelet aggregation (TCIPA) in heparinized platelet-rich plasma. TCIPA appears to play an important role in the development of certain experimental tumor metastases. Two ADP-scavenging agents, apyrase (10 U/ml) and creatine phosphate (CP) (5 mM)/creatine phosphokinase (CPK) (5 U/ml) completely inhibited B16-F10 TCIPA, but hirudin (5 U/ml) had no effect. In contrast, apyrase and CP/CPK did not inhibit HeLa TCIPA while hirudin completely inhibited it. Furthermore, HeLa cells initially induced platelet aggregation and then blood coagulation at a later stage. In addition, HeLa cells shortened, in a concentration-dependent manner, the recalcification time of normal as well as factor VIII- and IX-deficient human plasma, but did not affect the recalcification time of factor VII-deficient plasma. This suggests that HeLa TCIPA occurs via activation of the extrinsic pathway, probably owing to tumor cell expression of tissue factor-like activity. HeLa cell-induced thrombin generation was confirmed by detection of amidolytic activity towards a chromogenic substrate, S-2238 (H-D-Phe-Pip-Arg-p-NA). Triflavin and GRGDS inhibited, in a dose-dependent manner, TCIPA caused by either cell line. On a molar basis, triflavin was 10,000-30,000 times more potent than GRGDS in this regard. Moreover, monoclonal antibodies raised against glycoprotein (GP) IIb/IIIa complex (i.e., 7E3 and AP2) and against GP Ib (i.e., AP1) completely inhibited HeLa TCIPA. 7E3 and AP2 inhibited B16-F10 TCIPA by up to 80% whereas AP1 showed only 30% inhibition of B16-F10 TCIPA. In conclusion, the inhibitory effect of triflavin on HeLa and B16-F10 TCIPA may be mediated principally by the binding of triflavin to the fibrinogen receptor associated with GP IIb/IIIa complex on the platelet surface. However, GP Ib is also involved in HeLa TCIPA as thrombin formation is the key factor in triggering platelet aggregation caused by HeLa cells.
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PMID:Triflavin, an Arg-Gly-Asp-containing peptide, inhibits tumor cell-induced platelet aggregation. 822 81

Abundant evidence has shown that tumor growth and metastasis are dependent upon tumor angiogenesis (TA). TA refers to the growth of new vessels toward and within the tumor. Until TA occurs, tumors grow no larger than 2-4 mm in diameter. Also, TA is necessary at the beginning and at the end of the metastatic cascade of events. Thus, it seems reasonable that increasing intratumoral microvascular density (iMVD) might correlate with greater tumor aggressiveness, such as a higher frequency of metastases and/or decreased survival. Indeed, in 1991 my colleagues and I reported a statistically significant association between greater incidence of metastases in patients with breast carcinoma and increasing iMVD. Microvessel density was measured with a light microscope in a single area of invasive tumor (200x field or 0.74 mm2) representative of the highest microvessel density (neovascular "hot spot"). This was done after endothelial cells, lining the microvessels, had been highlighted with anti-factor VIII-related antigen/von Willebrand's factor (F8RA/vWF). Subsequent studies by other investigators, using either anti-F8RA/vWF or other relatively vessel-specific reagents such as anti-CD31, have shown that the association of greater tumor aggressiveness with increasing iMVD exists not only in breast carcinoma, but also in other solid tumors. This article reviews the methods of highlighting intratumoral vessels and describes the techniques for counting these vessels for assessing iMVD.
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PMID:Current pathologic methods for measuring intratumoral microvessel density within breast carcinoma and other solid tumors. 853 65

Invasion-inhibiting factor 2 (IIF-2) and its albumin conjugate have been reported to inhibit spontaneous metastasis of highly metastatic cancer cells with no effect on primary tumor growth. To confirm the inhibitory effects of the IIF-2 conjugate on tumor invasion and spontaneous metastasis, we administered the conjugate intra-peritoneally (i.p.) to female nude mice bearing transplanted tumors with MKL-4 cells, which are MCF-7 human breast cancer cells cotransfected with fibroblast growth factor 4 and lacZ. Neither 10 nor 20 mg/kg doses of the conjugate caused any inhibition of primary tumor growth, but 20 mg/kg significantly inhibited tumor invasion and spontaneous metastasis. Tumor invasion was measured by a novel computer-assisted image analysis. Spontaneous microscopic metastases into lymph nodes and distant organs were measured by whole organ staining for beta-galactosidase activity and observed with a dissecting microscope. The dose of 10 mg/kg significantly inhibited tumor invasion but not metastasis. Interestingly, the number of factor VIII-positive microvessels in the tumors was not reduced by treatment at either dose level. These findings suggest that the anti-invasive effect of the IIF-2 conjugate may reduce both lymphatic and hematogenous metastases in this MKL-4 metastasis model without affecting angiogenesis.
Clin Exp Metastasis 1996 Mar
PMID:Invasion-inhibiting factor 2-albumin conjugate inhibits invasion and spontaneous metastasis of MKL-4 human breast cancer cells transplanted into female nude mice. 860 32

The objective of this article is to determine the relationship between microvascular invasion and seminal vesicle invasion in prostatic adenocarcinoma. Radical prostatectomies with seminal vesicle involvement were examined histologically and immunohistochemically with antibodies directed against S-100 protein and factor VIII. Microvascular invasion of the seminal vesicles showed a positive correlation with microvascular and capsular invasion of the prostate (P = 0.006 and 0.048, respectively) and lymph node metastases. Tumor progression was found in 8 of 14 (57%) patients with microvascular invasion of the seminal vesicles, compared with 3 of 22 (14%) without microvascular invasion (P = 0.001). Microvascular invasion of the seminal vesicles is predictive of tumor progression and lymph node metastases in prostatic adenocarcinoma.
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PMID:Microvascular invasion of the seminal vesicles in adenocarcinoma of the prostate. 865 72

To investigate the correlation between tumor angiogenesis with axillary metastasis in breast cancer, we analyzed a series of 130 cases of infiltrating ductal carcinoma N.O.S. Tissue sections were stained with factor VIII-RA and microvessel quantitation was performed at x 400 magnification in the most vascular areas and expressed in vessels per mm2. Other variables such as tumor size, histologic grade, mitotic count, tumor necrosis, vascular invasion, skin involvement, anti-P.C.N.A. (proliferative cell nuclear antigen) and estradiol and progesterone receptors measured by an immunohistochemical method were determined. Statistical analysis of variance (AN-OVA) and Pearson's correlation coefficient were applied. The average of vessels per mm2 in tumors with metastases (n = 70) was 82.0 (median 74, SD 37.5), whereas in tumors without metastases (n = 60), it was 67.1 (median 64, SD 28.1). The difference was statistically significant (p < 0.01). However, the significance was lost when tumor size was introduced as a co-factor in a multifactorial analysis of variance. The number of vessels was unassociated with menopausal status, histologic grade, mitotic count, tumor necrosis, vascular invasion, skin involvement, estradiol and progesterone receptors and proliferative activity measured with anti-P.C.N.A. We conclude that in breast ductal invasive carcinoma, when tumor size is taken into consideration, angiogenesis is not associated with axillary lymph node metastases.
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PMID:Microvessel quantitation in breast ductal invasive carcinoma. Correlation with proliferative activity, hormonal receptors and lymph node metastases. 869 12

Squamous cell carcinoma of the head and neck induces neovascularization to support tumor growth and facilitate the metastatic spread. Others have suggested that the density of microvessels within the tumor correlates with the neovascularization process and therefore with clinical behavior and outcome. To ascertain the value of the microvessel count as an independent prognostic indicator for squamous cel carcinoma of the head and neck, we studied the primary tumors of 44 patients. Histological slides were stained for factor VIII and the individual microvessels were counted on a 200 x field (0.49 mm). No statistically significant difference was found between the microvessel counts of tumors that metastasize or recur locally, as compared with tumors that did not. The possibility of a beta-error due to the small number of cases mandates a larger possibly multi-institutional, study to better ascertain the significance of a microvessel count as an independent prognostic indicator.
Invasion Metastasis 1995
PMID:Tumor angiogenesis as a predictor of tumor aggressiveness and metastatic potential in squamous cell carcinoma of the head and neck. 876 94

A case of metastatic intracranial angiosarcoma in a 17-year-old female is presented. The patient underwent a sternotomy for treatment of a primary angiosarcoma arising from the pericardium. The postoperative course was uneventful but the patient died as a result of multiple metastases. The metastatic intracranial tumor had features characteristic of angiosarcoma as revealed by light microscopy with positive immunohistochemical staining of factor VIII-related antigen. Only a few cases of intracranial metastasis from cardiac angiosarcoma have been reported in the literature.
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PMID:Brain metastasis from pericardial angiosarcoma. 877 57

Epithelioid hemangioendothelioma of soft tissues (EHE) represents a distinct entity with an unpredictable clinical course. We analyzed the clinicopathologic and immunohistochemical features in a series of 30 patients. Patient age range was 16-74 years (median 50); 18 of 30 patients were female. Eight tumors arose in the lower and two in the upper extremities, seven on the trunk, five each in the head/ neck and anogenital regions, two in the mediastinum, and one in the abdomen. Seventeen neoplasms were located in deep soft tissues, nine were subcutaneous or perifascial, and four were dermal; size ranged from 0.4 to 10 cm; in 11 cases the tumor was > 5 cm. Tumors with an infiltrative growth pattern were more common than entirely circumscribed lesions. The tumors were composed histologically of short strands, cords, or small clusters of epithelioid, round, to slightly spindled endothelial cells that formed at least focally, intracellular lumina and were set in a frequently myxohyaline stroma. Thirteen of 30 lesions showed angiocentric growth, which was occlusive in many cases. Immunohistochemically, all cases tested were positive for at least one endothelial marker (CD31, CD34, factor VIII, Ulex europaeus), six of 23 (26%) were positive for cytokeratin, and five of 11 (45%) were positive for alpha-smooth muscle actin. Median follow-up of 36 months (range 2-96) in 24 cases showed local recurrence in three cases and systemic metastases in five cases (21%); four patients (17%) died of tumor. Although more aggressive histologic features (striking nuclear atypia in eight cases, numerous spindled cells in 10, more than two mitoses per 10 high-power fields in nine, and small, more solid angiosarcomalike foci in four cases) tended to be related to poor clinical outcome, there was no clear correlation. Two metastasizing cases showed no histologically atypical features whatever. We suggest that EHE of soft tissue is better regarded as a fully malignant, rather than borderline, vascular neoplasm, albeit the prognosis is better than in conventional angiosarcoma.
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PMID:Epithelioid hemangioendothelioma of skin and soft tissues: clinicopathologic and immunohistochemical study of 30 cases. 913 Sep 82

To examine the phenotype of the sinusoidal endothelial cells (SECs) surrounding tumor cells and the process of capillarization in hepatocellular carcinoma (HCC), 51 primary HCCs, 4 adrenal metastases, and 3 portal tumor thrombi were immunohistochemically stained with monoclonal antibodies (MAbs) for CD4, CD14 (lipopolysaccharide-binding protein complex receptors), and CD32 (Fc gamma receptor II), which are specifically found on the SECs in normal liver, but not on ordinary vascular endothelial cells (ECs). Immunostaining was also performed for CD36 (thrombospondin receptors), EN4 antigen (Ag) (a pan-vascular endothelial cell Ag), PAL-E Ag (a venous and capillary EC Ag), factor VIII-related Ag (FVIIIRAg), and laminin. MAb 25F9, which identifies macrophages, was simultaneously used with the other MAbs to distinguish macrophages from SECs in HCCs (HCC SECs). CD4, CD14, and/or CD32 were found on HCC SECs only in 12 well-differentiated primary HCCs showing a thin trabecular or pseudoglandular tumor cell arrangement. These 12 tumors were smaller than those without CD4-, CD14-, and/or CD32-positive SECs (P < .05). Among them, 7, 5, and 11 tumors were negative or only partially positive for laminin, PAL-E Ag, and FVIIIRAg, respectively. Staining for laminin and PAL-E Ag showed an inverse relationship to the expression of CD4, CD14, and CD32 on HCC SECs and the tumor differentiation. In conclusion, the phenotypes of the SECs in early and well-differentiated HCC are thought to be similar to those of the SECs in normal liver. With progressing tumor dedifferentiation the HCC SECs lose the phenotypes peculiar to liver SECs and acquire the characteristics of capillary ECs, though both types of phenotypical change occur independently of each other.
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PMID:Immunohistochemical studies on endothelial cell phenotype in hepatocellular carcinoma. 925 52

A case of multicentric gastrointestinal angiosarcoma suffering from severe melena is presented. Endoscopical examination revealed two polyps in the stomach and duodenum. Histological examination showed angiosarcoma. Although a gastroduodenectomy was performed, severe melena continued, and the patient developed respiratory failure and died. At autopsy, multiple hemorrhagic tumors were present from the duodenum to the cecum. Histologically the tumors demonstrated vasoformative structure and were immunohistochemically positive for von Willebrand factor (factor VIII related antigen), CD34, and CD31. Numerous metastases were found in various organs, including the lungs, bones, liver, gall-bladder, and lymph nodes. The patient had received hemodialysis for 21 years due to chronic renal failure. Long-term dialysis had been associated with various malignancies. Multicentric development of angiosarcoma in the present case may also be related to long-term dialysis.
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PMID:Multicentric angiosarcoma of the gastrointestinal tract. 929 36


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