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)

Integrins are cell surface molecules that mediate cell adhesion, but are also important regulators of tumor cell interactions with their microenvironment, tumor cell survival and growth. In addition, the alpha(v)beta3-integrins appear to be critical for microvessel formation in tumor-induced neoangiogenesis. The present study is the first to investigate the effects of therapeutic alpha(v)beta3-integrin inhibition in a chemically induced tumor model that largely resembles human colon carcinomas. Tumor induction was performed in 47 male Sprague-Dawley rats using 1,2 dimethylhydrazin (21 mg/kg) twice a week. After 20 weeks of tumor induction, 100% of the animals developed adenocarcinomas with a median of 13.5 macroscopic tumor nodules (range 12-17), but no distant metastases. During further tumor induction for an additional 10 weeks, rats were treated three times/week with (a) 15 mg/kg RGDfV-peptide that can block vitronectin and fibronectin receptors; (b) an equimolar amount of an ineffective cyclic control peptide; or (c) with equimolar amounts of a linear RGDS-peptide. At the end of this treatment period, rats were sacrificed, and tumor load was quantified macroscopically and confirmed by histological examination. For investigation of the involvement of tumor-induced neoangiogenesis microvessel, density was determined using CD31-immunostaining. After 30 weeks, control animals (group B) had 5-18 tumors (median 14.5). If rats were treated with RGDfV-peptide (group A), the number of tumor nodules was significantly reduced (P < 0.005) to a median of seven macroscopic tumors (range 2-10 tumors), which also represented a significant reduction (P < 0.005) compared with prior to treatment. Application of noncylic RGDS-peptides (group C) did not affect the number of tumor nodules (median 18; range 10-30 tumors). The diameters of tumor nodules were comparable (3.2-6.1 mm) in animals of all groups. In addition, microvessel density was significantly (P < 0.05) reduced in tumors in group A compared to control rats. The major side effect in the treatment group was increased susceptibility to respiratory infections. Our results demonstrate that alpha(v)beta3-integrin-receptor inhibition appears to be a therapeutic strategy for colorectal cancer. In our therapeutic model, late onset of treatment with integrin-blocking peptides resulted in an inhibition of tumor growth and a reduced tumor load which appeared to be mediated, at least in part, by inhibition of neoangiogenesis.
Clin Exp Metastasis 2002
PMID:Inhibition of tumor progression and neoangiogenesis using cyclic RGD-peptides in a chemically induced colon carcinoma in rats. 1255 71

We report a case of non-functioning adrenal cortical carcinoma (ACC) presenting with metastatic disease to the tongue, which is an extremely uncommon onset for this neoplasm. Histologically, the lesion had the appearance of an anaplastic neoplasm, and a panel of immunohistochemical markers including vimentin, MART-1, S100 protein, HMB-45, smooth muscle actin, common muscle actin, desmin, CD31, CD34, CD68, EMA and cytokeratins, was helpful in excluding melanoma, as well as other mesenchymal and epithelial neoplasms.
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PMID:Non-functioning adrenal cortical carcinoma presenting with metastasis to the tongue. 1258 89

Angiosarcomas of the oral and salivary gland area are extremely rare, mostly presented as case reports. We wanted to study the clinicopathologic features of a series of oral and salivary gland angiosarcomas. Cases coded as "angiosarcoma" were retrieved from the Oral and Maxillofacial Pathology Department of the Armed Forces Institute of Pathology. Patient folders and pathology were reviewed and recorded; immunohistochemistry and follow-up were obtained. Inclusion required oral or salivary gland location, vasoformative growth, cytologic atypia, mitoses, and vascular markers. Skin, bone, and subcutaneous angiosarcomas were excluded. Primary and secondary (metastatic) oral angiosarcomas were included. The 22 primary angiosarcomas involved tongue (n = 9), parotid (n = 4), lip (n = 4), submandibular gland (n = 3), and 1 each of soft and hard palate. The 7 secondary angiosarcomas involved the gingiva (n = 4) and parotid gland (n = 3). Overall, patient ages ranged from 6-90 years (mean, 55 years). There were 15 males and 14 females. Symptoms included a mass with recent enlargement and bleeding. Tumor sizes ranged from 0.8-7.0 cm (mean, 2.6 cm). Histologically, all tumors were vasoformative; 86% had solid and 17% had distinctive papillary areas. Eight (28%) were classified as the epithelioid subtype. Immunohistochemical stains showed that the tumor cells were positive for Factor VIIIrag in 19/21, CD31 in 16/19, CD34 in 7/12, and Ulex in 1/1. Primary tumors were classified as low grade (n = 7, in all locations except salivary gland), intermediate (n = 7), and high grade (n = 8); all secondary tumors were high grade. Follow-up was available on 14/22 primary and 7/7 secondary angiosarcomas. Of primary tumors, two tongue angiosarcoma patients died at 1 and 9 years, but 4 were alive without disease over a mean of 7.3 years (range, 1-13 years). Four primary salivary gland angiosarcoma patients were alive without disease over a mean of 5.8 years (range, 1-14 years), and 1 had only a late (15 years) metastasis and death (at 20 years). Three primary lip angiosarcoma patients were without disease over a mean of 14.3 years (range, 13-16 years). Of secondary tumors, three salivary gland angiosarcoma patients died within 1 year, and all four secondary gingival angiosarcoma patients died of disease within 3 years. Assessing follow-up of primary oral and salivary gland angiosarcoma patients by grade, 5 patients with high-grade tumors had no evidence of disease over a mean of 7.6 years (range, 1-16 years), 3 patients with intermediate-grade tumors had no evidence of disease over a mean of 12.7 years (range, 11-14 years), 2 patients with intermediate-grade tumors died of disease at 9 and 20 years, 3 patients with low-grade tumors had no evidence of disease over a mean of 6.3 years (range, 1-14 years), and 1 patient with low-grade tumor died of disease at 1 year. Primary oral and salivary gland angiosarcomas, albeit rare, mostly involve the tongue, parotid gland, and lip of adults, often with relatively good outcome. Although the most common angiosarcoma morphology in this area is spindled vasoformative and solid, almost one third of oral and salivary gland angiosarcomas are the rare epithelioid angiosarcoma variant. Most gingival and few parotid angiosarcomas appear to be metastases from other locations, with many patients succumbing to death within 3 years. Despite predominantly high- or intermediate-grade morphology, patients with primary angiosarcoma of the tongue, salivary gland, and lip have a better prognosis than do patients with primary cutaneous or deep soft tissue angiosarcoma, including those patients with secondary oral and salivary gland involvement.
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PMID:Oral and salivary gland angiosarcoma: a clinicopathologic study of 29 cases. 1264 Jan 7

Metaplastic breast carcinomas are rare neoplasms showing both carcinomatous and sarcomatous elements. In this report we describe eleven cases of metaplastic breast carcinoma focusing on pathological features and the clinical behaviour of six patients with breast carcinoma with chondroid metaplasia (MCC). We collected eleven cases from 1996 to 2001: immunohistochemical tests were performed in order to obtain data on estrogen and progesterone receptors and the production of p53 gene and HER/2 neu. Neoangiogenesis was studied counting vessels immunohistochemically-stained with CD31 antibody. Six cases showed chondroid metaplasia, three cases were spindle cell carcinoma and two were metaplastic squamous carcinoma. The majority of patients (64%) had pT2 tumors without axillary node metastases: only two cases with spindle or squamous metaplasia showed nodal involvement. Fifty percent of MCC were pT1b-c tumors: no axillary metastases were observed. Vascular invasion was observed in all squamous and spindle cell types and in 66% of MCC: estrogen and progesterone receptors were absent in 90% of the tumors. Immunohistochemical staining for HER2/neu was detected in 72% of spindle cell and squamous carcinomas and in 33% of MCC. Three cases staining highly for p53 were chondroid carcinomas: the staining was uniform both in carcinomatous and in sarcomatous tissue. The majority of metaplastic carcinomas had high angionesis. One patient with a chondroid metaplastic carcinoma was found to be a carrier of a BRCA1 mutation similar to the one responsible for sickle cell disease, possibly altering the spatial structure of the gene product. Only six patients had follow-up periods longer than 36 months: five women were alive and disease-free: one patient with pT2N1 squamous metaplastic carcinoma died of disease 14 months after diagnosis. The six women with MCC were alive and disease-free. Surgical and adjuvant treatment should follow the guidelines for the other most common breast cancers even if the need for chemotherapy is unknown due to the absence of large series randomized or observational data.
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PMID:Metaplastic breast carcinoma: pathology and clinical outcome. 1268 Jan 65

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

We report the clinicopathologic, immunophenotypic, DNA ploidy, and MIB-1 proliferative findings of five adenomatoid tumors of the adrenal gland. All patients were male, and tumors were incidental radiologic, surgical, or autopsy findings. Mean patient age at diagnosis was 41 years (range 31-64 years). The tumors ranged from 1.2 to 3.5 cm (mean 2.8 cm; median 3.2 cm) in greatest dimension, and all originated within the adrenal gland. The tumors were composed of anastomosing variably sized tubules lined by epithelioid as well as flattened cells. Signet-ring-like cells were present in all cases. The previously described histologic patterns of adenomatoid tumor, adenoid, angiomatoid, cystic, and solid, were observed, and each tumor contained multiple histologic patterns. In three of five cases, there was extra-adrenal extension of tumor into periadrenal adipose tissue. All adenomatoid tumors infiltrated the adrenal cortex, and in four cases the adrenal medulla was involved. All tumors exhibited strong immunoreactivity for calretinin, cytokeratins AE1/AE3, and CAM 5.2, cytokeratin 7, and vimentin. Tumors showed weak and focal immunoreactivity for cytokeratin 5/cytokeratin 6 and were negative for CD15, CD31, CD34, cytokeratin 20, MOC31, and polyclonal carcinoembryonic antigen. Ploidy analysis using Feulgen-stained sections and image analysis showed that three tumors were diploid and two were tetraploid. Tumors exhibited low MIB-1 proliferative activity, ranging from 0.2% to 2.7% (mean 1.6%). In three cases with clinical follow-up, no recurrence or metastases occurred. Adrenal gland adenomatoid tumors are morphologically and immunophenotypically identical to adenomatoid tumors of the genital tract and appear benign.
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PMID:Adenomatoid tumor of the adrenal gland: a clinicopathologic study of five cases and review of the literature. 1282 89

Tumour angiogenesis is essential for tumour growth and appears to play an important role both at the transition from hyperplasia to invasive growth and at a late stage in the dissemination process. Basal cell carcinomas (BCCs) and trichoepitheliomas (TEs) are related tumours that share the properties of invasive growth but without the capacity to metastasize. Squamous cell carcinomas (SCCs) of the skin are derived from a similar cell type and they have both invasive and metastatic potential. The aim of this study was to investigate whether the behaviour of these tumours could be explained by differences in their microvasculature. The study looked both qualitatively and quantitatively at the microvasculature of BCCs (n=50) and TEs (n=33) and compared them with normal skin (n=6) and with SCCs of the skin (n=22). Vessel counts were performed using a standard graticule count method after immunohistochemical staining for CD31. Counts were made of blood vessels in the stroma surrounding the tumour and also for vessels in the body of the tumour. The stromal counts for all the tumour groups differed significantly from normal skin. The SCC counts differed significantly from the counts for the BCCs and TEs. There was no significant difference between the counts for different subtypes of BCC or TE groups. While vessels could be found in the body of the SCCs, none was seen in the nodular BCC or the TE groups. There was no correlation between the vascular density and the depth of invasion. Overall, invasive growth correlated with an angiogenic response in the stroma, while metastatic potential correlated with microvessels being present in the body of the tumour.
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PMID:Differences in the vascular patterns of basal and squamous cell skin carcinomas explain their differences in clinical behaviour. 1284 26

Glucose transporter-1 protein (GLUT1) and carbonic anhydrase IX (CAIX) are regulated by hypoxia inducible factor-1 (HIF-1) and have been studied as putative intrinsic cellular markers for hypoxia. This study directly compares CAIX and GLUT1 with pimonidazole binding in a prospective series of bladder cancer patients and also studies the prognostic significance of the markers, in combination with vascularity and proliferation, in a retrospective series of bladder cancer patients treated in a phase II trial of radical radiotherapy with carbogen and nicotinamide (ARCON). A total of 21 patients with a diagnosis of transitional cell carcinoma of the bladder received 0.5 g m(-2) pimonidazole. Serial tumour sections were stained for pimonidazole, GLUT1 and CAIX and compared. Tissue sections obtained from a series of 64 patients previously treated for invasive bladder cancer using ARCON were stained for GLUT1 and CAIX together with Ki-67 and CD31/34. There was a good geographical colocalisation of both intrinsic markers with pimonidazole and a highly significant agreement in individual patients; correlation coefficients were 0.82 (P=0.0001) for GLUT1 and 0.74 (P<0.0001) for CAIX. In both series of patients, the intrinsic hypoxia markers were highly correlated with each other and a correlation with proliferation was also evident in the retrospective study. In univariate and multivariate analyses, GLUT1 and CAIX were independent predictors for overall and cause specific survival. The hypoxia markers did not predict for local control or metastases-free survival although higher Ki-67 indices showed a trend towards local failure. The data suggest that both hypoxia modification and accelerated treatment may be valid treatment options in bladder cancer.
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PMID:GLUT1 and CAIX as intrinsic markers of hypoxia in bladder cancer: relationship with vascularity and proliferation as predictors of outcome of ARCON. 1452 Apr 62

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

Recent studies have demonstrated that tumor angiogenesis is a prognostic factor for various malignant neoplasms. Specifically, in non-small-cell lung carcinomas (NSCLCs) most reports show an association between neovascularization and vascular endothelial growth factor (VEGF) expression as well as the presence of metastases and survival, although a few reports do not agree with these findings. Angiogenesis is not clearly characterized in small-cell lung carcinomas (SCLCs), since they are rarely treated by surgery, and thus the available tissue for biological characterization is sparse. The aim of the present study was to investigate angiogenesis and the expression of VEGF in lung tumors. We examined 88 non-small-cell and 39 small-cell lung carcinomas. Angiogenesis was estimated by determining microvessel counts, with the use of anti-CD31 and anti-factor VIII antibodies and expression of VEGF was also evaluated immunohistochemically. Our data showed that in NSCLCs angiogenesis was more prominent in poorly-differentiated neoplasms and correlated with VEGF expression, therefore it is at least in part mediated by the latter. Interestingly, in SCLCs a higher vascularization was noted. However, there was no strong association with VEGF expression. Thus, small-cell lung carcinoma may represent a suitable neoplasm for testing antiangiogenic drugs in combination with chemotherapy. Nevertheless, antiangiogenic therapy should not be targeted specifically to the VEGF pathway, since in SCLCs other mediators of angiogenesis may be important as well.
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PMID:Expression of vascular endothelial growth factor (VEGF) and association with microvessel density in small-cell and non-small-cell lung carcinomas. 1470 69


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