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)

Recent studies have demonstrated that the p53 tumor suppressor gene plays an important role in controlling tumor angiogenesis. We examined the expression of p53 and vascular endothelial growth factor (VEGF), a well-characterized angiogenic inducer, together with microvessel density to investigate the role of p53 in the regulation of angiogenesis and its clinical significance in human colorectal carcinoma. Surgically resected specimens of 163 colorectal carcinomas were studied by immunohistochemical staining for p53 protein, VEGF and factor VIII-related antigen. Positive p53 protein accumulation and VEGF expression was found in 41.7% and 49.1% of tumors, respectively. p53 and VEGF staining status was identical in 65.6% of tumors. The incidence of p53- or VEGF-positive tumors was significantly higher in patients with venous invasion and liver metastases than in those without. The microvessel count (MVC) in p53- or VEGF-positive tumors was significantly higher than that in negative tumors, and MVC in both p53- and VEGF-positive tumors was significantly higher than that in the other subgroups. Neither synchronous nor metachronous hepatic metastases were found in patients with p53- and VEGF-negative tumors, while 52.2% of patients with both-positive tumors had liver metastases and had a poorer prognosis than those with both-negative tumors. Our findings suggest the presence of a p53-VEGF pathway regulating tumor angiogenesis in human colorectal carcinoma. Combined analysis of p53 and VEGF expression might be useful for predicting the occurrence of liver metastasis in patients with this disease.
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PMID:Combined analysis of p53 and vascular endothelial growth factor expression in colorectal carcinoma for determination of tumor vascularity and liver metastasis. 935 71

Angiogenesis is essential for tumor growth and metastasis. In the present study we investigated the prognostic significance of microvessels (MV) density using immunohisto-localization of factor VIII antigen in 51 breast cancer patients. We counted microvessels per 200x field in the most active areas of neovascularization by staining factor VIII related antigen and graded MV density and correlated with stage, LN involvement and histologic grade. Patients who subsequently developed metastases had significantly high MV counts than patients without metastatic disease (p < 0.001). Patients who subsequently died of the disease had significantly high mean microvessels counts than patients who remained alive at the end of 5 years (p < 0.001). As density of factor VIII antigen staining increased the survival decreased (p < 0.001). All the patients having > 25 MV per 200x field had tumor recurrence faster as compared with patients having < 25 MV (p < 0.02). Thus, the MV count correlates with the prediction for metastasis and poor survival. Such an indicator would be useful in selection of a subgroup of patients with breast cancer who are at high risk for having occult metastasis at presentation and subsequently would benefit from aggressive therapy.
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PMID:Prognostic significance of tumor angiogenesis in advanced breast carcinoma: an Indian experience. 937 57

Tumor metastasis can be prevented by inhibiting angiogenesis. In the present study, we have demonstrated that the angiogenesis inhibitor TNP-470 also suppresses the development of primary hepatic nodules. Hepatocarcinogenesis was performed by the feeding of 2-acetylaminofluorene to hepatectomized rats during 8-14 weeks of age. Predominantly arterial-to-portal circulation and sinusoidal capillarization were determined by the staining of nodules with arterially infused ink and immunostaining for factor VIII-related antigen, respectively. Intraperitoneal administration of 30 mg/kg b.w. of TNP-470 twice a week significantly reduced the number of hepatic nodules. Among the nodules, hyperplastic nodules stained with ink, atypical hyperplastic nodules and hepatocellular carcinoma, all of which possess structurally altered sinusoidal endothelial cells or capillary-type endothelial cells, were dramatically decreased in number. Suppression was observed equally in nodules of all sizes. TNP-470 was more effective when administered during 8-20 weeks than during 14-26 weeks. In contrast, ink-non-stained hyperplastic nodules, which have normal sinusoidal endothelial cells, were not affected at all. The present results indicate that TNP-470 suppresses the development of primary hepatic nodules whose microvessels are capillaries or transitional forms from sinusoids to capillaries.
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PMID:Suppressive effect of the angiogenesis inhibitor TNP-470 on the development of carcinogen-induced hepatic nodules in rats. 954 41

Three cases of intravenous leiomyomatosis (IVL) of the uterus, a rare benign smooth-muscle tumor, are described. A preoperative diagnosis of IVL was not made in any of the patients, all of which presented with a pelvic mass with the presumptive diagnosis of leiomyoma. Surgical exploration confirmed the presence of uterine mass and two of the three cases showed extra-uterine extension into the ovarian or uterine veins. Histological examination demonstrated a fascicular pattern of bland spindle-shaped smooth-muscle cells, which extended to veins inside the myometrium or to extrauterine veins. This was confirmed by immunohistochemical stain for desmin and factor VIII. Despite their histological benignity, these lesions have a tendency to metastasize and are closely related to the conditions called "benign metastasizing leiomyoma" and "intracaval mass and cardiac extension". The primary treatment of IVL is hysterectomy and excision of any extrauterine tumor, when technically feasible. Anti-estrogenic therapy has been suggested as potentially useful in controlling of unresectable tumor. According to the literature, the follow-up must be long and periodic postoperative ultrasonic or magnetic nuclear resonance imaging studies may be useful in detecting growth of residual intravascular tumor.
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PMID:Intravenous leiomyomatosis of the uterus. A report of three cases. 955 21

A cohort of 109 patients with primary transitional cell carcinomas, stages T2-T3, grade 2 or higher, was identified and further divided into two groups based on lymphatic metastasis at the time of cystectomy (n = 57 cases) or absence of detectable metastatic disease over a minimum of 5 years of follow-up after cystectomy (n = 52). Blocks corresponding to the primary tumor lesions were sectioned and distributed to different laboratories to be analyzed. Immunohistochemistry on deparaffinized tissue sections was conducted for evaluation of p53 nuclear overexpression (monoclonal antibody PAb1801), assessment of proliferative index (Ki-67 antigen-monoclonal antibody MIB1), and microvascular counts (factor VIII-related antigen). DNA content/ploidy studies were performed on material obtained from thick sections. A double-blinded strategy was used for the evaluation of laboratory data versus clinical parameters. The cutoff value for p53 nuclear overexpression was > or =20% of tumor cells displaying nuclear staining. The median values for MIB1 (> or =18% of tumor nuclear cell staining) and microvascular counts (> or =40 microvessels/area screened) were used as cutoff points for these two variables. The assessment of DNA content was conducted by classifying cases as diploid, tetraploid, or aneuploid. Statistical analyses were performed using the Fisher's Exact Test (2-tailed). Results revealed that none of the markers studied had a statistically significant correlation with the end point of the study, i.e., the presence of lymph node metastatic disease, in the cohort of patients studied, although an obvious trend for p53 was noted. It is concluded that alterations of p53, Ki-67 proliferative index, microvascular counts, and ploidy are not strongly associated with lymph node status in patients affected with high-stage, high-grade bladder cancer.
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PMID:Biomarker study of primary nonmetastatic versus metastatic invasive bladder cancer. National Cancer Institute Bladder Tumor Marker Network. 960 86

Epithelioid hemangioendothelioma arising in the skin is extremely rare, and the majority of documented cases have developed in association with an underlying bone tumor. We report eight patients with an age range of 29-84 years (mean 53), who presented with primary cutaneous tumors at a variety of sites including the palm, shin, neck, knee, nose, back, and penis with a duration of between 6 and 12 months. Histologically, all eight cases presented as circumscribed nodules with an overlying acanthotic epidermis, three showing striking acrosyringeal proliferation, reminiscent of eccrine syringofibroadenoma. The tumors were composed of an admixture of slightly pleomorphic spindle and epithelioid cells with abundant, sharply defined eosinophilic cytoplasm and vesicular nuclei containing single nucleoli. Mitoses were generally sparse. All tumors showed intracytoplasmic lumina and intraluminal erythrocytes were occasionally apparent. The tumor cells were embedded in a myxoid or hyaline matrix. In contrast to visceral lesions, a vascular origin was not evident in any of our cases. The tumor cells variably expressed CD31, CD34, factor VIII-Rag, and smooth-muscle actin but not pankeratin or epithelial membrane antigen. Follow-up ranged from 4 months to 3 years. None of the lesions has thus far recurred and there have been no metastases.
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PMID:Epithelioid hemangioendothelioma presenting in the skin: a clinicopathologic study of eight cases. 985 48

To evaluate the potential actions of vascular endothelial growth factor (VEGF) on capillary permeability and drug transport, tumorigenic human glioma cell lines were developed that expressed different levels of VEGF. Three human glioma cell lines (i.e. U373, SF126, SF188) were screened for VEGF under normoxic and hypoxic (i.e. induced by CoCl2) conditions by Western blot analysis. Subsequent to these results, sense and antisense VEGF164 cDNA transfections were conducted. It was found that parental SF188 (SF188/V-) and SF188/V+ (sense transfected) cells could serve as an appropriate in vivo model based on their divergent levels of VEGF expression. Media derived from SF188/V+ cells stimulated endothelial cell growth by 30-60%, and enhanced endothelial cell clonogenicity by 5-10-fold compared to SF188/V- or empty vector transfected cells. Nude rats implanted with either SF188/V- or SF188/V+ cells subcutaneously and intracerebrally formed tumors, with those derived from SF188/V+ cells growing at a faster rate. Immunohistochemistry analysis indicated that the expression of VEGF and number of capillaries (factor VIII assay) were approximately 3-fold greater in SF188/V+ tumors compared to SF188/V- tumors. Pharmacological assays, such as measurements of cytotoxicity and DNA adducts, in SF188/V- and SF188/V+ cells treated with carmustine or temozolomide were similar. Therefore, other than differences in VEGF expression and growth in vivo, SF188/V- and SF188/V+ cells possess a similar phenotype, and can serve as models to evaluate the influence of VEGF on drug transport.
Clin Exp Metastasis 1998 Aug
PMID:Modulation of angiogenesis by human glioma xenograft models that differentially express vascular endothelial growth factor. 987 3

In HCC specimens from 25 patients, the levels of nm23-H1 and H-ras mRNA were analyzed by quantitative reverse transcription-polymerase-chain reaction (RT-PCR). Tumor microvessel density (MDV), the essential factor of microenvironment and proliferating cell nucleus antigen (PCNA), indexes as tumor cell proliferating in its microenvironment are also analyzed by immunohistochemical methods using antibodies against endothelial protein factor VIII related antigen (F8RA) and antibody PC-10. Results show that The MDV and PCNA index in the group with intrahepatic metastasis is remarkably higher than that in without one (p<0.01), but the abundance of nm23-H mRNA is opposite (p<0.01). The abundance of H-ras mRNA shows little difference (p>0.05). MDV index shows directly relationship with PCNA index (p<0.01), the abundance of nm23-H1 mRNA show an inverse one with PCNA index (p<0.05). We conclude that in HCC, tumor in situ microenvironment, especially a deteriorative one, plays an important selective role. The decline of nm23-H1 mRNA abundance implies the increase of highly potential metastatic cancer cells which adapt to their microenvironment.
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PMID:The abundance of NM23-H1 mRNA is related with in situ microenvironment and intrahepatic metastasis in hepato-cellular carcinoma. 989 72

The PTEN tumor suppressor gene encodes a dual-specificity protein phosphatase that may play a key role in modulating integrin-mediated signals. Inactivation of the PTEN gene has been detected in a small percentage of clinically localized prostate cancers but is common in metastatic disease. It has been shown in glioblastoma cell lines that loss of chromosome 10q, where the PTEN gene is located, is associated with increased angiogenic activity in the conditioned medium attributable to downregulation of thrombospondin-1, a negative regulator of angiogenesis. Therefore, we wished to determine whether inactivation of PTEN might be associated with increased angiogenesis in prostate cancers, because increased angiogenesis in localized cancers is associated with development of metastatic disease. Angiogenesis was assessed by counting microvessels in areas of maximal neovascularization after immunostaining with anti-factor VIII-related antigen antibodies in eight cases with proven homozygous deletion of the PTEN gene and 24 control cases. There was a statistically significant correlation between PTEN inactivation and increased microvessel counts. The microvessel density was higher at all Gleason scores in the cases with PTEN inactivation compared with control cases with the same score. To determine whether the increased angiogenesis in cases with PTEN inactivation was caused by downregulation of expression of the angiogenesis inhibitor thrombospondin-1, we analyzed a subset of the cases by immunostaining with anti-thrombospondin-1 antibody. Approximately 25% of cases showed decreased staining of prostate cancer cells, but there was no correlation with PTEN inactivation. Thus, PTEN inactivation is associated with increased angiogenesis, but the increased angiogenesis is not attributable to downregulation of thrombospondin-1 expression.
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PMID:Inactivation of the PTEN tumor suppressor gene is associated with increased angiogenesis in clinically localized prostate carcinoma. 1020 63

We report the case of a 56-year-old man with advanced gastric cancer that manifested as multiple subcutaneous nodules. Histology showed irregularly shaped cells with large nuclei and it also showed frequent mitotic figures clustered throughout the dermis. To predict whether metastasis was likely to occur, we performed a controlled study using gastric cancer cells from patients with or without metastases. Tumor cells that had metastasized showed more positive staining for Ki67, PCNA and p53 than those that had not metastasized, although there were no marked differences between the reactivities of these 2 groups for factor VIII related antigen, CEA, EGF, or p21 staining. We conclude that immunohistochemical staining for Ki67, PCNA or p53 might be very useful in predicting the possible risk of metastasis of cancer cells.
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PMID:Immunohistochemical evaluation of the probability of skin metastasis in gastric cancer. 1021 Jul 88


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