Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Trauma produced by amputation of a limb bearing the primary tumor influenced pulmonary metastases of the Carcinosarcoma of Walker 256 of the rat. This enhancement was present in 38% of the animals following the removal of a limb bearing the primary tumor; and in 29% of those in which the controlateral limb without tumor was amputated. A significant prolongation of the clotting time, an elevation of fibrinogen factor II and VII and a rapid consumption of factor VIII present soon after trauma may have been the parameter responsible for the increase of pulmonary metastases seen in this study.
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PMID:Role of operative trauma: explosive metastases of similar size following amputation of the primary leg tumor. 51 75

The first requirement of a new prognostic indicator is that it should possess a clear biological significance. Indeed, much evidence shows that tumor growth and metastasis depend on neovascularization. Tumor angiogenesis (TA) refers to the growth of new vessels toward and within the tumor; unless tumor neovascularization occurs, cell proliferation reaches a steady state, and the tumor grows no larger than about 2 mm greatest diameter. Moreover, for tumor cells to metastasize, they must gain access to the vasculature from the primary tumor, survive the circulation, localize in the target organ, and induce angiogenesis in that target organ. TA is necessary both at the beginning and at the end of the metastatic cascade of events. Recently, my colleagues and I showed that a statistically significant correlation exists between incidence of metastases and microvessel density (MVD) of primary invasive breast carcinomas. Now, subsequent studies have shown that the association of prognosis with MVD exists not only in breast carcinoma but also in non-small-cell lung carcinoma, prostate carcinoma, and head-and-neck carcinoma. This article reviews the concepts and mechanisms of TA, the evidence supporting its role in growth and metastasis of solid tumors, and how measuring MVD within invasive tumors correlates with factor VIII-related antigen, blood vessel.
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PMID:Tumor angiogenesis: review of current applications in tumor prognostication. 751 Dec 50

Increased numbers of blood vessels (angiogenesis or neovascularization) in certain primary tumors correlates with an increased risk for metastatic disease. We therefore conducted a blinded review of the resected testicular germ cell tumors of 65 clinical stage A patients to evaluate the usefulness of angiogenesis in identifying those patients with clinically occult nodal metastases (pathological stage B). Angiogenesis was assessed in the primary tumors using an immunohistochemical stain for factor VIII-related antigen assay for quantitation of microvessel counts. Of 65 clinical stage A patients, 43 had pathological stage B disease at retroperitoneal lymph node dissection. Eleven patients had microvessel counts > 30 microvessels/x 400 high powered field, and all of these patients had pathological stage B disease (P = 0.02 in univariate analysis). Multiple regression analysis using microvessel count and other histological findings found to be prognostic (venous invasion, lymphatic invasion, presence of embryonal carcinoma, and absence of yolk sac tumor) showed that only the absence of a yolk sac tumor component was significantly predictive of occult metastases. This study shows that angiogenesis, as measured by quantitation of microvessel counts in the primary tumor of germ cell neoplasms, is significantly predictive of occult nodal metastatic disease by univariate analysis in clinical stage A patients. The prospective use of angiogenesis quantitation needs to be defined.
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PMID:Neovascularization in clinical stage A testicular germ cell tumor: prediction of metastatic disease. 751 56

To clarify the correlation between tumor angiogenesis and tumor growth in head and neck carcinomas, we investigated the number of microvessels, using immunohistochemical factor VIII. No correlations among this number, differences in the primary lesion, histological differentiation and T classification were detected. The incidence of neck lymph node metastases increased as microvessel numbers increased in tumor sites. The number of microvessels increased as N and Stage classification progressed. The number of microvessels in CR cases after induction chemotherapy were increased. The numbers of microvessels in patients without recurrence were apparently greater than those in patients with recurrence. The results of this study suggest that the number of microvessels in a primary tumor correlates with the metastatic ability of the tumor.
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PMID:[Angiogenesis in head and neck tumor]. 768 79

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.
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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

Cardiac myxoma is the most common primary tumor of the heart. A detailed evaluation of cell types in 41 cardiac myxomas by light microscopy and in 30 cases by immunohistochemistry was made. Reactivity to the various antisera were observed in the surface lining cells, the stromal myxoma cells and the cells in the perivascular location. Factor VIII-related antigen (FVIIIR-Ag) and Ulex europaeus agglutinin (UEA-1), both endothelial markers, were positive in 23 cases each. UEA-1 was found to be a more sensitive marker than factor VIII. Desmin and myoglobin were positive in 16 and 24 cases, respectively. Reactivity for cytokeratin was noted in ten cases, one of which showed glandular differentiation. Vimentin and S-100 positivity was obtained in 16 and 14 cases respectively. Thus, cardiac myxoma appears to arise from multipotent cells which have the potential to differentiate along several mesenchymal cells or epithelial cells and may also concurrently exhibit reactivity for both mesenchymal and epithelial markers.
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PMID:Phenotypic characterization of cellular components of cardiac myxoma: a light microscopy and immunohistochemistry study. 889 90

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

Within the past 5 years, research has increasingly addressed molecular alterations in prostate cancer (CaP). Mutations of tumor suppressor gene p53 have been found in a variety of cancers, including urologic neoplasms. Several studies have been conducted on CaP specimens, citing frequencies of p53 alterations in localized cancers ranging from 4 to 60% and with more advanced hormone refractory disease, as high as 94%. The majority of studies have revealed a low percentage of p53 abnormalities in early-stage (clinically organ-confined) CaP. The overwhelming bulk of evidence suggests that the frequency of p53 abnormalities does increase with disease progression and is highest in tissues from patients with hormone-refractory prostate cancer. More recently, our group and others have found that focal p53 expression in the primary tumor by immunohistochemistry is predictive of cancer recurrence after radical prostatectomy. bcl-2 is an oncogene critically involved in the apoptosis, or programmed cell death. Overexpression of bcl-2 protein by immunohistochemistry has been commonly detected in advanced hormone refractory CaP. Our group recently has also shown that bcl-2 protein expression in primary CaP is a predictor of cancer recurrence after radical prostatectomy. Furthermore, the combination of p53 and bcl-2 protein expression were both independent predictors of recurrence after surgery. Most recently, we have shown that even though p53 and bcl-2 are predictive biomarkers when sampling the radical prostatectomy specimen, they are not useful to predict postoperative recurrence when sampling the pretreatment needle biopsy. Ki-67 is an antigen of cellular proliferation. Immunohistochemical staining for Ki-67 in archival material can be performed using the MIB-1 antibody. Unlike our results with p53 and bcl-2, Ki-67 protein expression by immunohistochemistry using MIB-1 was not an independent prognostic marker for cancer recurrence after radical prostatectomy although it may have clinical utility in subsets of patients. Assessment of MIB-1 staining in CaP needle biopsy samples is underway. Tumor neovascularity, or angiogenesis, is necessary for cancers to grow and metastasize. Angiogenesis in CaP as a prognostic marker has received recent attention. Most studies have used factor VIII immunohistochemical staining and increased angiogenesis has been suggested as a staging and prognostic marker. Our group has recently conducted a large study of radical prostatectomy patients and used CD34 antigen immunohistochemistry to assess neovascularity. We did not find that this biomarker assessment was an independent prognostic marker of cancer recurrence after radical prostatectomy. Further work is being conducted in needle biopsy samples. More research is needed to assess new biomarkers and, most importantly, to standardize the methodology for sampling and assaying biomarkers in heterogeneous and multifocal prostate cancer.
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PMID:Angiogenesis, p53, bcl-2 and Ki-67 in the progression of prostate cancer after radical prostatectomy. 1032 96

One objection to using cell cultures for studying the proliferation of tumors is the potential for phenotypic changes that may occur in vitro. Here, we compared the antigen pattern expression of cultured meningioma cells with that of the primary tumor. Cell cultures established from 9 intracranial meningiomas and deparaffinized sections of the resected tumors were analyzed for immunophenotyping with the following antibodies: vimentin, cytokeratin, epithelial membrane antigen, S-100, neuron-specific enolase, synaptophisin, factor VIII-related antigen, CD4, CD31, CD34, CD45RB, CD68-PGM1, CD68-KP, and myeloid/histiocyte antigen (MAC387). Overall, the cultured meningioma cells retained the main feature of the primary tumor, being positive both for mesenchymal antigens and for epithelial antigens. Interestingly, the cultured meningioma cells abundantly expressed the CD68 antigens at early passage. The CD68 antigens, which are normally found on hematopoietic cells like macrophages and monocytes, were not detectable on meningioma cells in situ. Our results show that phenotypic changes on human meningioma cells may occur in vitro. This phenomenon suggests caution when transposing the in vitro results to the in vivo condition.
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PMID:Phenotypic change of human cultured meningioma cells. 1113 90

To provide an investigative tool for the study of osteosarcoma (OSA) biology we have developed a syngeneic (balb/c) murine model of OSA, using cell lines derived from a spontaneously occurring murine OSA (Schmidt et al. Differentiation 1988; 39: 151-60). This model is characterized by orthotopic primary tumor growth, a period of minimal residual disease, spontaneous pulmonary metastasis, and clonally related variants (K7M2 and K12) that differ in pulmonary metastatic potential. Primary tumor and pulmonary metastasis histology was consistent with OSA in human patients. Expression of bone sialoprotein, biglyan, decorrin, and osteopontin was suggestive of bone lineage cells. The development and use of a more aggressive OSA cell line (K7M2) resulted in spontaneous metastasis to the lungs in over 90% of mice, whereas metastases were seen in only 33% of mice when a less aggressive OSA cell line (K12; Schmidt et al. Differentiation 1988; 39: 151-60) was used. Death from metastasis occurred at a median of 76 days using K7M2 whereas no median was achieved after 140 days using K12. Angiogenic potential, characterized by CD31 and factor VIII staining of primary tumors and pulmonary metastases, was greater in the K7M2 model compared to the K12 model. No significant differences in the in vitro or in vivo expression of angiogenesis associated genes (flt1, flt4, TIE1, TIE2, and VEGF) was found between K7M2 and K12. This well characterized and relevant model of OSA will be a valuable resource to improve our understanding of the biology and treatment of metastasis in OSA.
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PMID:An orthotopic model of murine osteosarcoma with clonally related variants differing in pulmonary metastatic potential. 1131


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