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)

Evidence is presented for two different breast epithelial antigens that some epitopes have greater tumor specificity and are more effective targets for radioimmunotherapy than others. The two antigens, which are major components of the human milk fat globule membrane, are breast mucin and a M(r) 46,000 glycoprotein (BA46). Of five monoclonal antibodies (Mc5, Mc1, BrE-1, BrE-2, and BrE-3) against breast mucin, all recognize overlapping amino acid epitopes on the tandem repeat domain. However, each have unique and different tissue and tumor specificities and unique epitope structures on the fully glycosylated breast mucin. In preclinical studies, radioimmunoconjugates of all five monoclonal antibodies inhibit growth of transplantable breast tumors in immunodeficient mice. In human clinical trials, radioiodinated Mc5 was very poor in localizing breast tumor metastases. On the other hand, 111In-labeled BrE-3 imaged almost 90% of breast tumors and showed promise in radioimmunotherapy when labeled with 90Y. The failure of Mc5 in clinical trials may be partly attributed to the high levels of its epitope on circulating mucin compared to the epitope of BrE-3. The Mc5 binding affinity increased significantly with glycosylation, while the BrE-3 epitope was masked by glycosylation. The BA46 glycoprotein is a breast tumor-associated membrane antigen containing an NH2-terminal, epidermal growth factor-like domain into which a cell adhesion sequence (RGD) is inserted and a COOH-terminal domain with homology to the phospholipid binding C1/C2 domain of coagulation factors V and VIII. It promotes cell attachment in an RGD-dependent manner. Monoclonal antibody Mc8, which binds to the C2-like domain, is only moderately effective in experimental radioimmunotherapy, while Mc3, which binds an epitope in the EGF-like RGD domain, was highly effective in destroying breast tumors in nude mice. With 90Y-labeled Mc3, 6 of 7 mice are cured of the tumors. These results indicate that by selecting appropriate monoclonal antibodies, a normal antigen can be used as a target for radioimmunotherapy.
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PMID:Selection of tumor-specific epitopes on target antigens for radioimmunotherapy of breast cancer. 749 58

Six cases of spindle cell hemangioendothelioma (SCH) are presented with immunohistochemical and flow cytometric analyses. One case was associated with Maffucci's syndrome. All lesions were solitary or multifocal in the extremities, and prepresentation duration ranged from years to decades. One case recurred but none had metastases. Histologically, in four of the six cases the main lesions appeared to arise within vessels, predominantly muscular vessels. All lesions consisted of cavernous hemangioma-like areas and solid cellular areas resembling Kaposi's sarcoma. Cellular atypia was minimal. At the periphery of the lesions, a cluster of large thick or thin walled, and probably malformed, vessels were observed. Immunohistochemically, factor-VIII related antigen, CD34, vimentin, and lectin binding Ulex europaeus agglutinin 1 stained endothelial cells lining vascular channels, and vacuolated, or epithelioid cells. Spindle cells in the solid areas were negative for these endothelial markers except for vimentin, but showed divergent positive immunoreactions of HHF35, alpha-smooth muscle actin, desmin, and collagen type IV. Five cases were diploid and one was aneuploid. There was no significant correlation among DNA ploidy, S-phase fraction, and local recurrence in SCH although the number of cases examined was small. These results suggest SCH may be a benign lesion, probably a reactive process, rather than a low-grade angiosarcoma.
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PMID:Spindle cell hemangioendothelioma: an immunohistochemical and flow cytometric study of six cases. 749 4

We have investigated the expression of platelet-derived endothelial-cell growth factor/thymidine phosphorylase (PD-ECGF/dThdPase) in human breast-cancer tissues by the immunocytochemical method using anti-PD-ECGF/dThdPase monoclonal antibody. Out of 100 invasive-ductal-carcinoma tissue samples, 39 (39%) were evaluated as PD-ECGF/dThdPase-positive. The expression of PD-ECGF/dThdPase was identified mainly in the cytoplasma of tumor cells. The expression of PD-ECGF/dThdPase was significantly associated with the microvessel density assessed by immunostaining to factor-VIII-related-antigen (p < 0.05). However, there was no correlation between expression of PD-ECGF/dThdPase and menopausal status, tumor size, axillary lymph-node metastases, hormone-receptor status, epidermal-growth-factor receptor, or erb-B-2-protein and p53-protein expression. We suggest that expression of PD-ECGF/dThdPase plays an important role in the promotion of angiogenesis in human breast cancer.
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PMID:Expression of platelet-derived endothelial cell growth factor/thymidine phosphorylase in human breast cancer. 754 28

Histopathologic features alone fail to reliably stratify patients with clinical Stage A nonseminomatous germ cell tumors of the testis into groups with high and low risk for occult metastatic disease. Previous flow cytometric studies at Indiana University demonstrated a significant correlation between high proliferative activity and metastatic disease. The current study evaluated the prognostic significance of immunohistochemical markers related to tumor proliferation and aggressiveness in a consecutive series of clinical Stage A nonseminomatous germ cell tumors patients who underwent retroperitoneal lymph node dissection. Archival material of the orchiectomy specimens of 62 patients (45 pathologic Stage A, 17 with metastatic disease) was reviewed and immunohistochemically stained for Ki-67 antigen (MIB-1), proliferation-associated nuclear antigen (PC10), p53 protein (Pab1801), and Factor-VIII-related antigen (neovascularization). Staining with MIB-1 was significantly higher in the metastatic group (mean 80.2%, standard deviation [SD] 15.5) than in pathologic Stage A cases (66.3%, SD 27.9; P = 0.0032) and was predictive of metastatic status with a sensitivity of 82% and specificity of 69%. In this study, no patient with a MIB-1 value less than 52% had metastases. Proliferation-associated nuclear antigen and p53 staining correlated with MIB-1 values (R = 0.63 and 0.55, respectively) but did not correlate with metastatic status. Tumor angiogenesis was also not predictive of metastatic status. Assessment of proliferation rates using MIB-1 antibody in clinical Stage A nonseminomatous germ-cell-tumor patients may prove helpful in predicting metastatic status.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prognostic significance of immunohistochemical proliferation markers (Ki-67/MIB-1 and proliferation-associated nuclear antigen), p53 protein accumulation, and neovascularization in clinical stage A nonseminomatous testicular germ cell tumors. 754 14

Prostatic carcinoma obtained from 41 patients (pT2N0, 5; pT2N+, 2; pT3N0, 16; pT3N+, 16; pT4N0, 1; and pT4N+, 1) ranging from 45 to 79 years of age were investigated in the present study. A total of 410 tumor areas of different grades were analyzed (G1, n = 116; G2, n = 98; and G3, n = 196). Vascular structures were labeled immunohistochemically using factor-VIII-associated antigen. The vascular surface density (VSD), the microvessel number (NVES), and the maximum microvessel number (NVES-MAX) were assessed by means of stereology, and the results were related to tumor stage, nodal status, and grade of differentiation. NVES and NVES-MAX showed a significant increase with rising pT stage ranging from 25.5 +/- 1.48 in controls to 135.0 +/- 5.5 microvessels/mm2 in pT4 tumors. Discrimination of different pT stages was more accurate with NVES-MAX. The VSD was significantly higher in pT2 tumors compared with controls, whereas there were no significant differences between pT3 tumors, pT4 tumors, and controls, although the values in pT3 and pT4 tumors were distinctly lower than in pT2 tumors (P < .05). The VSD and the NVES were not able to discriminate between the pN0 and the pN+ group. Both parameters were slightly higher in patients with metastatic disease. Only NVES-MAX values differed between the two groups with an average of additional 21 microvessels/mm2 in the pN+ group (P < .05). Concerning the grade of tumor differentiation the VSD continuously decreased from G1 (14.58 +/- 2.24 mm(-1) to G3 tumor areas (5.41 +/- 1.46 mm(-1). Only G1 tumors showed significant differences compared with controls (6.65 +/- 0.38 mm(-1). The NVES increased with rising tumor grade with significant differences between all four groups ranging from 25.5 +/- 1.5 in controls to 136.9 +/- 37.2 microvessels/mm2 in pT4 tumors.
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PMID:Assessment of the vascularization in prostatic carcinoma: a morphometric investigation. 895 3

Tumour angiogenesis (antifactor VIII-related antigen antibody), p53 overexpression (DO-1) and proliferative activity (MIB-1) were immunohistochemically analysed for the prediction of long-term survival in 113 patients with squamous cervical carcinoma. The median follow-up time was 82 months (range 72-99). In early stages (IB-IIA), neovascularisation was significantly related to tumour size. Significantly more patients in stage IIA had high tumour vascularity compared to stage IB (P < 0.01) but no significant difference was found between early and advanced stages (IIB-IVB) of cervical carcinoma. p53 overexpression was correlated to the stage of disease (P < 0.01). No relationship was found between tumour angiogenesis, p53 overexpression or MIB-1 and pelvic lymph node metastases, histological subtype or differentiation. Tumours with more than 50% p53 overexpression was significantly correlated with survival in the univariate analysis, but no independent predictive value was found. It is concluded that immunohistochemically detectable p53 overexpression as measured by DO-1 and proliferative activity as measured by MIB-1 seems of no clinical value for the prediction of long-term survival in squamous cervical carcinoma. The predictive value of tumour angiogenesis for survival outcome has still to be determined in squamous cervical carcinoma.
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PMID:The impact of tumour angiogenesis, p53 overexpression and proliferative activity (MIB-1) on survival in squamous cervical carcinoma. 947 Aug 36

The alterations of the haemostatic system (platelet count, activated partial thromboplastin time [APTT], thromboplastin time [standard test, modified test], thrombin time, fibrinogen concentration, activity of the coagulation factors II, V, VII, X, VIII:C, IX, XI, XII, of prekallikrein, high molecular weight kininogen, antithrombin III, protein C, plasminogen and alpha 2-plasmin inhibitor, concentration of soluble fibrin and fibrin(ogen) degradation products [FDP], resonance thrombogram) were described in seven dogs with haemorrhagic diathesis in consequence of an infiltrative, growing mammary carcinoma with multifocal invasion of lymphatic and blood vessels. In most of the cases metastases in different organs could be demonstrated. In every case a serious stage of disseminated intravascular coagulation and hyperfibrinolysis was existent. This was indicated by the distinctly increased concentration (p < 0.0001) of soluble fibrin (27.7 [16.0-79.2] micrograms/ml, median [minimum-maximum], reference range [RR.]: < 9.4 micrograms/ml) and FDP (340 [50-860] micrograms/ml, RR.: < 18 micrograms/ml) as well as a diminished plasma level of nearly all components of the coagulation and fibrinolytic system concerning especially the concentration of fibrinogen (0.16 [0.01-0.46] g/l, RR.: 1.17-3.09 g/l), the activity of factors V (30 [21-40]%, RR.: 75-158%) and VIII:C (9 [4-16]%, RR.: 72-136%) as well as the activity of protein C (8 [3-13]%, RR.: 68-139%) (each: p < 0.0001).
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PMID:[Disseminated intravascular coagulation and hyperfibrinolysis in dogs with metastasizing mammary carcinoma]. 986 56

Radical hepatectomy was carried out on a patient with hepatocellular carcinoma (HCC) located in segment VIII of the liver. The patient was a 56-year-old man who showed positive for hepatitis C antibody and negative for hepatitis B surface antigen. Six months after hepatectomy, a lumbar plane X-ray and computed tomography examination revealed bone metastases in the lumbar vertebrae. The patient was subsequently treated by radiation to the lumbar vertebrae in response to lumbago. The metastatic lesion has been well controlled by radiotherapy on an outpatient basis with no recurrence for 5 years and 3 months. The prognosis of patients with HCC with distant metastases is poor. It is believed that the long survival of this patient can be attributed to successful radiotherapy of the bone metastasis after hepatectomy and the lack of recurrence in the liver.
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PMID:A case of hepatocellular carcinoma with bone metastasis responding to radiotherapy after successful hepatectomy of primary lesion. 1021 62

Sixty female dogs with untreated mammary carcinoma, comprising equal numbers of dogs in tumour stages I to IV, were evaluated for haemostatic abnormalities using the following tests: platelet count, prothrombin time, activated partial thromboplastin time, thrombin time, plasma activity of factor V, VIII and X, plasma concentration of fibrinogen, fibrin monomers and fibrinogen degradation products, and plasma antithrombin III activity. Two-thirds of all dogs had one or more haemostatic test abnormality of which the likelihood and frequency was increased in those with stage III and IV neoplasia. Haemostatic abnormalities were more frequently observed in dogs which had mammary tumours with distant metastases, extended tumour necrosis, inflammatory carcinomas, tumours fixed to underlying structures, or tumours in which there was penetration of the tumour capsule by tumour cells. As in humans with mammary carcinoma, these haemostatic abnormalities might be used as prognostic indicators, but their clinical importance remains unknown.
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PMID:Correlation of haemostatic abnormalities with tumour stage and characteristics in dogs with mammary carcinoma. 1044 52

Microvessel density (MVD) was estimated in a series of 202 vertical growth phase (VPG) melanomas and 68 corresponding metastases, using a marker for angiogenic endothelial cells (CD105) and Factor-VIII. The expression pattern of vascular endothelial growth factor (VEGF), FLT-1, KDR and thrombospondin-1 (TSP-1) was studied by immunohistochemistry, in situ hybridization and reverse-transcriptase polymerase chain reaction. CD105 stained significantly less vessels, but gave only limited additional prognostic information compared with Factor-VIII, and MVD was an independent prognostic factor for both markers. Ninety-eight percent of all cases showed expression of VEGF, and higher expression was found significantly more frequent in thinner and less vascularized tumors. Possible autocrine loops were suggested by co-expression of VEGF and its two receptors in tumor cells, and by a significant correlation between KDR and tumor cell proliferation (Ki-67) in the subgroup of thicker tumors. Staining of VEGF receptors in endothelium was not correlated with MVD. Strong expression of TSP-1 in tumor stroma was found in 43% of the primary tumors, and was significantly correlated with increased thickness, proliferation and MVD, as well as decreased survival. These data suggest that MVD is associated with prognosis in cutaneous melanomas, and that the VEGF system and particularly TSP-1 seem to be involved in the regulation of angiogenesis and progression of these tumors.
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PMID:Expresson of vascular endothelial growth factor, its receptors (FLT-1, KDR) and TSP-1 related to microvessel density and patient outcome in vertical growth phase melanomas. 1143 69


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