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 diagnosis, staging, therapy and follow-up of advanced epidermoid cervical carcinoma (FIGO stages IIB-III) have been studied in our university since January 1990. By December 1992, a team of specialists including radiologists, radiotherapists, gynecologists and pathologists divided 54 patients into two random treatment groups: group A patients, after systemic chemotherapy (CDP, 2 cycles) and diagnostic reevaluation, underwent radical surgery; group B patients received conventional radiotherapy alone (ERT 45 Gy+IRT or END-RT 20-25 Gy). All patients were examined by means of transrectal US (TRUS) and CT, after clinical examination under sedation, at staging and during the follow-up. The exams were performed periodically for group B patients and after systemic chemotherapy for group A patients. Imaging findings were compared with pathology only in group A. All imaging results were filed. The results confirm some literature data--e.g., 62% diagnostic accuracy for CT and 69% for TRUS, with higher diagnostic accuracy of the latter to evaluate cervical volume and to diagnose local relapses. As for parametrial involvement, both imaging methods tend to understage the early involvement, but only CT tends to overstage the lesions, especially in irradiated patients, due to fibrosclerosis phenomena. TRUS exhibited 69% accuracy, 70% sensitivity and 69% specificity, versus 61%, 62% and 60%, respectively, for CT; clinical examination under sedation had 58%, 60% and 60%, respectively. Both TRUS and CT are faster than endoscopic methods in evaluating vesical and/or rectal involvement. Lymph node metastases at staging, especially those in lumboaortic locations, proved to be unfavorable prognostic signs, as demonstrated by lumboaortic lymph node relapses in 5 group B patients (only 2 of them presented with lymph node metastases at staging; 3 patients had micronodules near the renal vessels), in spite of good local response after radiotherapy. In conclusion, we would like to point out that our team has had an MR unit at its disposal only recently: since the method is considered as the gold standard of imaging, especially in this kind of lesions, the study is still in progress.
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PMID:[Experience with the combined diagnosis and therapy of locally advanced carcinoma of the uterine cervix (stage FIGO IIB-III). Transrectal ultrasonography and CT in the staging and in follow-up after therapy. Preliminary results]. 827 50

During postnatal development, the formation of new blood vessels is possible only through angiogenesis. The initial growth of solid neoplasms, including childhood brain tumors, during the genetically determined stages of carcinogenesis, even at clinically undetectable sizes (a few mm3), depends upon the continuous formation of new blood capillaries [i.e. neovascularization (NV)/neoplasm-related angiogenesis (NRA)]. The generation of a malignant, invasive cellular immunophenotype (CIP) and distant metastases are also NRA-dependent processes. Endothelial cells undergo rapid proliferation during brain tumor related angiogenesis. Human endoglin (CD105/EDG), is a homodimeric cell surface component of the transforming growth factor-beta (TGF-beta) type I receptor complex and is also a proliferation-associated antigen (PAA) expressed at high density on endothelial cells. Formalin fixed, paraffin-wax embedded (3-5 microns thick), as well as frozen tissue sections (6 microns thick) of 62 childhood brain tumors [34 medulloblastomas (MEDs) and 28 astrocytomas (ASTRs)], were employed for the assessment of EDG expression. Both an indirect, four-step, alkaline phosphatase (AP) conjugated, biotin-streptavidin based (or a diamino-benzidine [DAB]) conjugated immunoperoxidase antigen detection technique were employed, utilizing the SN6h anti-EDG monoclonal antibody (DAKO Corp.). Another antigen detection method, based on the Histogold (Zymed) reaction was also employed using the same antibody on formalin fixed, paraffin-wax embedded tissues. Strong expression (A; +3 to +4) of EDG on endothelial cells and demonstrated in all 62 childhood brain tumor cases. The most striking feature of the newly formed tumor-related capillaries was the presence of a markedly enlarged perivascular space. Blood vessels in several normal human tissues (cortex, cerebellum, thymus, tonsil, spleen, lymph node, skin) used as control tissues contained significantly lower levels of EDG (B and mostly C; +/- to +), in accordance with the extremely slow turnover rate of normal endothelial cells. A close apposition between the capillaries and the adjacent parenchyma was also observed. Brain tumors, especially glioblastoma, are among the most vascularized human neoplasms, and thus are candidates for antiangiogenic therapy. VEGF/PF-R1 (flt-1) and VEGF/PF-R2 (flk-1) are formed de novo in a glioma progression-dependent manner. Further studies should substantiate the importance of EDG in the earliest possible detection, diagnosis and NRA inhibition-based treatment of mammalian solid neoplasms, especially childhood brain tumors.
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PMID:Upregulation of endoglin (CD105) expression during childhood brain tumor-related angiogenesis. Anti-angiogenic therapy. 967 60

The commencement of the complex process of carcinogenesis, and subsequent, rapid tumor growth and progression of mammalian neoplasms, including malignant melanomas, depends upon the continuous de novo formation of capillaries [i.e. neovascularization (NV)/neoplasm-related angiogenesis (NRA)]. The generation of a dedifferentiated, malignant, highly invasive cellular immunophenotype (CIP) and distant metastases, as aspects of constant neoplastic progression, are also NRA-dependent processes. Endothelial cells undergo rapid proliferation during malignant melanoma (MM) related angiogenesis. Human endoglin (CD105/EDG), is a homodimeric cell surface component of the transforming growth factor-beta (TGF-beta) type I receptor complex and is also a proliferation-associated antigen (PAA) expressed at high density on endothelial cells. Formalin fixed, paraffin-wax embedded, tissue sections (3-5 microns thick) of 25 MMs were employed for the assessment of EDG expression. An indirect, four-step, alkaline phosphatase (AP) (or diamino-benzidine [DAB]) conjugated, biotin-streptavidin based, antigen detection technique, employing the SN6h anti-EDG monoclonal antibody was conducted. Zymed's Histogold System was also utilized for immunocytological antigen detection. Strong expression (A; +3 to +4) of EDG on endothelial cells was demonstrated in all MM cases. The most striking feature of the newly formed neoplasm-related capillaries was the presence of an enlarged perivascular space. Blood vessels in several normal human tissues (cortex, cerebellum, thymus, tonsil, spleen, lymph node, skin) used as control tissues contained significantly lower levels of EDG (B and mostly C; +/- to +), in accordance with the extremely slow turnover rate of normal endothelial cells. Furthermore, a close apposition between the capillaries and the adjacent parenchyma was observed in these normal controls. MMs, like most mammalian neoplasms, are characterized by extensive neovascularization, and thus are candidates for anti-angiogenic therapy. Further studies should substantiate the importance of EDG expression in the earliest possible detection, diagnosis and NRA inhibition-based treatment of solid tumors, including MMs. The importance of TGF-beta in all of the various aspects of neoplastic transformation, as well as malignant disease progression should also be studied more extensively in the future.
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PMID:Immunocytochemical detection of endoglin is indicative of angiogenesis in malignant melanoma. 970 32

Transforming growth factor-betas (TGFbetas) play a prominent role in tumour growth and metastasis by enhancing angiogenesis and suppressing immune surveillance. Despite the increased interest in the effect of TGFbetas on tumour progression, little is known about the importance of TGFbeta3 and its receptor CD105 in breast cancer. In the present study, we measured the plasma levels of TGFbeta3, CD105-TGFbeta3 complexes and TGFbeta1 in 80 patients with untreated early-stage breast cancer using an enhanced chemiluminescence ELISA method. Of the 80 patients, 14 were histologically confirmed as having axillary lymph node metastases, while the remainder had no evidence of lymph node involvement. The results showed that levels of both TGFbeta3 and CD105-TGFbeta3 complex were significantly elevated in patients with positive lymph nodes compared to those without node metastasis. Furthermore, the levels of both TGFbeta3 and CD105-TGFbeta3 complex correlated with lymph node status. The only patient who died of the disease had very high plasma levels of TGFbeta3 and CD105-TGFbeta3 complex and positive lymph nodes; this patient developed lung metastases within 2 years of diagnosis. No significant correlation was seen between either TGFbeta3 or CD105-TGFbeta3 complex levels and tumour stage, size or histological grade. Plasma TGFbeta1 levels were not correlated with node metastasis, tumour stage, grade or size. Our data suggest that plasma levels of TGFbeta3 and CD105-TGFbeta3 complex may be of prognostic value in the early detection of metastasis of breast cancer.
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PMID:Role of transforming growth factor beta3 in lymphatic metastasis in breast cancer. 976 Nov 12

The commencement of the complex process of carcinogenesis, and subsequent, rapid tumor growth and progression of mammalian neoplasms, including breast carcinomas (BCs), depends upon the continuous de novo formation of capillaries [i.e. neovascularization (NV)/neoplasm-related angiogenesis (NRA)]. The generation of a malignant, invasive cellular immunophenotype (CIP) and distant metastases, as aspects of tumor progression, are also NRA-dependent processes. Endothelial cells undergo rapid proliferation during mammary carcinoma-related angiogenesis. Human endoglin (CD105/EDG), is a homodimeric cell surface component of the transforming growth factor-beta (TGF-beta) type I receptor complex and is also a proliferation-associated antigen (PM) expressed at high density on endothelial cells. Formalin fixed, paraffin-wax embedded, tissue sections (3-5 microns thick) of 15 BCs were employed for the assessment of EDG expression. An indirect, four-step, alkaline phosphatase (AP) (or diamino-benzidine [DAB]) conjugated, biotin-streptavidin based, antigen detection technique, employing the SN6h anti-EDG monoclonal antibody was conducted. Zymed's Histogold System was also utilized for immunocytological antigen detection. Strong expression (A; ++ + to ++ ++) of EDG on endothelial cells was demonstrated in all 15 BC cases. The most striking feature of the newly formed neoplasm-related capillaries was the presence of an enlarged perivascular space. Blood vessels in several normal human tissues (cortex, cerebellum, thymus, tonsil, spleen, lymph node, skin) used as control tissues contained significantly lower levels of EDG (B and mostly C; +/- to +), in accordance with the extremely slow turnover rate of normal endothelial cells. Furthermore, a close apposition between the capillaries and the adjacent parenchyma was observed in these normal controls. BCs, as most mammalian neoplasms, are characterized by extensive neovascularization and thus are candidates for anti-angiogenic therapy. Further studies should substantiate the importance of EDG expression in the earliest possible detection, diagnosis and NRA inhibition-based treatment of solid tumors, including BCs.
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PMID:Over-expression of endoglin (CD105): a marker of breast carcinoma-induced neo-vascularization. 985 49

CD105 (endoglin), a receptor for transforming growth factor (TGF) beta1 and beta3 in vascular endothelial cells, is highly up-regulated in blood vessels of tissues where neovascularisation occurs. It modulates endothelial-mesenchymal signalling and is essential for angiogenesis. Indeed, CD105 knock-out mice die from malvascularisation by 11.5 day p.c. In the present study CD105, TGFbeta1 and CD105/TGFbeta1 complexes were quantified in plasma samples from 77 healthy individuals and 92 patients with early stage breast cancer prior to any treatment. When compared with normal controls, both CD105 and CD105/TGFbeta1 complex levels were significantly elevated in breast cancer patients, whereas TGFbeta1 levels were lower in cancer patients. The most important finding to emerge was that CD105 levels were significantly increased in patients who developed distant metastasis compared with disease-free patients. While there was no significant difference between CD105 levels in controls compared to disease-free patients, it was significantly higher in patients with metastatic disease. Thus patients who had died following local relapse or distant metastases possessed the highest levels of CD105. Neither CD105/TGFbeta1 complex nor TGFbeta1 levels correlated with tumour progression. Our data indicate that CD105 might be a valuable novel angiogenic marker for identifying breast cancer patients who are at high risk of developing metastasis.
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PMID:Plasma levels of soluble CD105 correlate with metastasis in patients with breast cancer. 1075 88

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

Tumor angiogenesis plays an important role in tumor growth and metastasis. We evaluated endoglin (CD105) as an endothelial marker of angiogenesis in endometrial carcinoma (EC) and its prognostic significance. Fifty-five cases of EC, 10 cases of complex endometrial hyperplasia with atypia (CHA), and 10 cases of simple hyperplasia (SH) were immunohistochemically stained for endoglin, CD31, and vascular endothelial growth factor (VEGF). Positively stained microvessels (MV) were counted in densely vascular foci (hot spots) in a 400x field in each specimen. For VEGF, intensity of staining was scored on three-tiered scale. Results were correlated with other prognostic parameters using appropriate statistics. Endoglin staining demonstrated significantly more MV than did CD31 (mean 30.8 +/- 10.95 vs. 13.38 +/- 7.53, p < 0.001). There was a positive correlation of both endoglin and CD31 MV counts with tumor differentiation (p < 0.05) and the depth of invasion (p < 0.01). However, only endoglin counts correlated significantly with the presence of angiolymphatic invasion (p < 0.01), lymph nodes metastases (p < 0.01), and tumor stage (p < 0.001). VEGF expression in EC had a significant correlation with angiolymphatic invasion (p < 0.01) and lymph node status (p < 0.05) but not with other prognostic parameters. Endoglin and VEGF showed significant differences between CHA and SH (p < 0.001). Our study showed that endoglin, by staining the proliferating MV in EC, is a more specific and sensitive marker for tumor angiogenesis than is the commonly used pan-endothelial marker, CD31. Endoglin staining also had prognostic significance, with positive correlation with angiolymphatic invasion, lymph node metastases, and tumor stage.
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PMID:Endoglin (CD105) expression in endometrial carcinoma. 1281 91

Endoglin (CD105) has been shown to be a more useful marker to identify proliferating endothelium involved in tumor angiogenesis than panendothelial markers such as CD31. We investigated endoglin and vascular endothelial growth factor expression as possible prognostic markers in colorectal cancer. Surgical specimens from 150 patients with resected colorectal carcinomas were immunostained for endoglin, CD31 and vascular endothelial growth factor. Colorectal carcinoma cases consisted of 50 cases without lymph node metastases, 50 cases with only lymph node metastases and 50 cases with liver metastases (38 cases also had positive lymph nodes). Positively stained microvessels were counted in densely vascular foci (hot spots) at x 400 fields in each specimen. For vascular endothelial growth factor, intensity of staining was scored on a three-tiered scale. Results were correlated with other prognostic parameters. Endoglin demonstrated significantly more proliferating neoplastic microvessels than CD31 (31+/-10 vs 19+/-8/0.15 mm2 field, P<0.001). Low vascular endothelial growth factor expression within tumor cells was seen in 49 (33%) and high expression in 101 cases (67%). There was a positive correlation of endoglin, CD31 counts and vascular endothelial growth factor overexpression with the presence of angiolymphatic invasion and lymph node metastases (P<0.05). Only endoglin counts correlated significantly with liver metastases and positive vascular pedicle lymph nodes (P<0.05), while vascular endothelial growth factor showed significant correlation with the depth of invasion (P<0.01). Endoglin, by staining higher numbers of the proliferating vessels in colon carcinoma, is a more specific and sensitive marker for tumor angiogenesis than the commonly used panendothelial markers. Endoglin staining also showed prognostic significance with positive correlation with angiolymphatic invasion and metastases to lymph nodes and liver.
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PMID:Endoglin (CD105) and vascular endothelial growth factor as prognostic markers in colorectal cancer. 1465 50

There is strong published and unpublished evidence that our CD105 Mab E9, which is highly reactive with angiogenic endothelial cells, could be a useful reagent to target the vasculature of solid tumors in man. Since Mab E9 does not cross-react with animal tissues, we undertook here to evaluate its localization using human kidney as an ex vivo model. Perfusion was performed through the renal artery of 99Tcm-labeled purified CD105 Mab in freshly excised kidneys from 7 patients with renal carcinoma. In all 7 cases, immunoscintigraphs showed the presence of well-defined radioactive hot spots, which matched the positions of the tumors as identified by presurgery MRI scans and subsequent histopathologic examination. Importantly, in one instance, where a presurgery MRI scan had identified only one tumor, immunoscintigraphs showed 2 distinct hot spots of radioactivity. The pathology report confirmed that the additional hot spot corresponded to a small secondary well-vascularized tumor. The implication of this finding is that the radiolabeled Mab, E9, may be of use in the detection of metastatic disease. That the labeling of tumors was specific was confirmed when prior perfusion of unlabeled mab E9 in 2 kidneys completely blocked the localization of 99Tcm-conjugated Mab E9. Radioactivity in samples of tumor and normal tissue taken from 7 kidneys was counted in a gamma counter. In all cases, there was a greater uptake of radioactivity in tumors compared with the corresponding normal kidneys. The median values, adjusted per gram wet weight, for 99Tcm were 14.8 times (range, 4.8-113.0) greater in kidney tumors than in normal kidney tissue (p < 0.007). Immunofluorescent staining of cryostat sections of tumor tissues in each of the 7 cases showed strong and uniform localization of Mab E9 in tumor microvessels. Interestingly, chimeric staining of endothelial cells (ECs) was seen in an occasional microvessel segment. That is, while most of the ECs lining a microvessel were strongly stained, an occasional EC was negative. This was not an artifact of staining. Unstained ECs may be nonangiogenic or apoptotic since CD105 is a proliferation/activation-associated antigen. Further investigations are warranted to establish the pharmacokinetics of 99Tcm-labeled CD105 antibody in vivo. This would enable us to determine whether an apparently highly successful ex vivo study has the potential for tumor imaging/therapeutic vascular targeting in patients with cancer.
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PMID:Perfusion of 99Tcm-labeled CD105 Mab into kidneys from patients with renal carcinoma suggests that CD105 is a promising vascular target. 1496 84


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