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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A series of 102 benign osteoblastic tumors of multiple skeletal sites was reviewed, and on the basis of their clinical, radiologic, and pathologic features they were classified into three diagnostic categories: osteoid osteoma, osteoblastoma, and aggressive osteoblastoma. A historic review of the development of the nomenclature of benign osteoblastic tumors, with special emphasis on the evolving concept of aggressive and malignant behavior, is presented. Histologic criteria for the recognition of aggressive osteoblastoma are presented and illustrated in connection with the 15 cases so classified in the present series. The differential diagnosis of aggressive osteoblastoma and low-grade osteosarcoma is discussed. In defining the problem of differentiating locally aggressive osteoblastic lesions from potentially metastasizing tumors, the authors propose that four categories of these osteoblastic tumors can be defined: (1) Innocuous-appearing low-grade osteosarcomas that resemble osteoblastomas histologically. This mimicry accounts for most errors in diagnosis. (2) Rare osteoblastomas that have undergone spontaneous transformation into osteosarcomas. (3) Very rare, clinically and radiologically typical osteoblastomas that show pseudosarcomatous histologic features but pursue a benign course. (4) Locally aggressive osteoblastomas that are likely to recur, do not metastasize, and show characteristic and recognizable histologic features.
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PMID:Borderline osteoblastic tumors: problems in the differential diagnosis of aggressive osteoblastoma and low-grade osteosarcoma. 660 Jan 12

Tumors require a blood supply for growth and hematogenous dissemination. Much attention has been focused on the role of angiogenesis-the recruitment of new vessels into a tumor from pre-existing vessels. However, angiogenesis may not be the only mechanism by which tumors acquire a microcirculation. Highly aggressive and metastatic melanoma cells are capable of forming highly patterned vascular channels in vitro that are composed of a basement membrane that stains positive with the periodic acid-Schiff (PAS) reagent in the absence of endothelial cells and fibroblasts. These channels formed in vitro are identical morphologically to PAS-positive channels in histological preparations from highly aggressive primary uveal melanomas, in the vertical growth phase of cutaneous melanomas, and in metastatic uveal and cutaneous melanoma. The generation of microvascular channels by genetically deregulated, aggressive tumor cells was termed "vasculogenic mimicry" to emphasize their de novo generation without participation by endothelial cells and independent of angiogenesis. Techniques designed to identify the tumor microcirculation by the staining of endothelial cells may not be applicable to tumors that express vasculogenic mimicry. Although it is not known if therapeutic strategies targeting endothelial cells will be effective in tumors whose blood supply is formed by tumor cells in the absence of angiogenesis, the biomechanical and molecular events that regulate vasculogenic mimicry provide opportunities for the development of novel forms of tumor-targeted treatments. The unique patterning characteristic of vasculogenic mimicry provides an opportunity to design noninvasive imaging techniques to detect highly aggressive neoplasms and their metastases.
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PMID:Vasculogenic mimicry and tumor angiogenesis. 1066 63

The question of whether some blood vessels in tumors of non-vascular origin are lined by cancer cells has been discussed for many years because of the relevance to metastasis, access of drugs to tumor cells, and the effectiveness of angiogenesis inhibitors. Most evidence favoring the existence of tumor cell-lined vessels has come from observations of standard histopathological tissue sections or from transmission and scanning electron microscopic studies. However, it has been difficult to determine convincingly just how abundant these vessels are in tumors. On the one hand, virtually the entire microvasculature is supposedly lined by tumor cells in aggressive uveal melanomas, assuming the presence of vasculogenic mimicry where tumor cells masquerading as endothelial cells create the channels for blood flow. On the other hand, morphometric studies using immunohistochemistry and green fluorescent protein-transfected tumor cells suggest that human colon cancer cells constitute only 3% of the vessel surface in tumors grown orthotopically in mice. This commentary weighs evidence that cancer cells are located in the wall of tumor vessels and discusses the pitfalls in identifying such vessels. Published data along with new observations illustrate the challenges of making an unequivocal identification of tumor cells in vessel walls. Taken together, current evidence suggests that cancer cells contribute at most only a small proportion of the lining of blood vessels in tumors and may be migrating through vessel walls or exposed by defects in the endothelium. Even in aggressive uveal melanomas, blood flow probably occurs mainly through channels lined by endothelial cells, not tumor cells, and most existing data do not support a functionally significant contribution of vasculogenic mimicry. Innovative new approaches that distinguish pleomorphic tumor cells from abnormal endothelial cells in vessel walls will help to define the incidence and importance of tumor cell-lined blood vessels in drug delivery and metastasis via the bloodstream.
Cancer Metastasis Rev 2000
PMID:Endothelial cells of tumor vessels: abnormal but not absent. 1119 Oct 49

During development, the formation and remodeling of primary vascular networks occurs by vasculogenesis and angiogenesis. Recently, the term "vasculogenic mimicry" has been used by our laboratory and collaborators to reflect the embryonic-like ability of aggressive, but not nonaggressive, melanoma tumor cells to form a pattern of matrix-rich networks (containing channels) surrounding spheroids of tumor cells in three-dimensional culture, concomitant with their expression of vascular cell markers. Ovarian cancer is usually diagnosed as advanced stage disease in most patients when widespread metastases have already been established within the peritoneal cavity. In this study, we explored whether invasive ovarian carcinoma cells could engage in molecular vasculogenic mimicry reflected by their plasticity, compared with their normal cell counterparts. The data revealed that the invasive ovarian cancer cells, but not normal ovarian surface epithelial cells, formed patterned networks containing solid and hollow matrix channels when grown in three-dimensional cultures containing Matrigel or type I collagen, in the absence of endothelial cells or fibroblasts. Immunohistochemical analysis showed that matrix metalloproteinases (MMP)-1, -2, and -9, and MT1-MMP were discretely localized to these networks, and the formation of the networks was inhibited by treatment with MMP inhibitors. Furthermore, the RNase protection assay revealed the expression of multiple vascular cell-associated markers by the invasive ovarian cancer cells. In patient tumor sections from high-stage, high-grade ovarian cancers, 7 to 10% of channels containing red blood cells were lined by tumor cells. By comparison, all vascular areas in benign tumors and low-stage cancers were endothelial lined. These results may offer new insights and molecular markers for consideration in ovarian cancer diagnosis and treatment strategies based on molecular vascular mimicry by aggressive tumor cells.
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PMID:Molecular determinants of ovarian cancer plasticity. 1129 May 46

The molecular analysis of cancer has benefited tremendously from the sequencing of the human genome integrated with the science of bioinformatics. Microarray analysis technology has the potential to classify tumors based on the differential expression of genes. In the current study, a collaborative, multidisciplinary approach was utilized to study the molecular determinants of human uveal melanoma invasion and metastasis. Uveal melanoma is considered the most common primary intraocular cancer in adults, resulting in the death of approximately 50% of patients affected. Unfortunately, at the time of diagnosis, many patients already harbor microscopic metastases, thus underscoring a critical need to identify prognostic markers indicative of metastatic potential. The investigative strategy consisted of isolating highly invasive vs. poorly invasive uveal melanoma cells from a heterogeneous tumor derived from cells that had metastasized from the eye to the liver. The heterogeneous tissue explant MUM-2 led to the derivation of two clonal cell lines: MUM-2B and MUM-2C. Further morphological and functional analyses revealed that the MUM-2B cells were epithelioid, interconverted (expressing mesenchymal and epithelial phenotypes) highly invasive, and demonstrated vasculogenic mimicry. The MUM-2C cells were spindle-like, expressed only a vimentin mesenchymal phenotype, poorly invasive, and were incapable of vasculogenic mimicry. The molecular analysis of the MUM-2B vs. the MUM-2C clones resulted in the differential expression of 210 known genes. Overall, the molecular signature of the MUM-2B cells resembled that of multiple phenotypes--similar to a pluripotent, embryonic-like genotype. Validation of select genes that were upregulated and down-regulated was conducted by semiquantitative RT-PCR measurement. This study provides a molecular profile that will hopefully lead to the development of new molecular targets for therapeutic intervention and possible diagnostic markers to predict the clinical outcome of patients with uveal melanoma.
Clin Exp Metastasis 2002
PMID:Molecular determinants of human uveal melanoma invasion and metastasis. 1206 4

Tumors require a blood supply for growth and hematogenous metastases. Until recently, most research in this area has focused on the role of angiogenesis, the recruitment of new vessels into a tumor from preexisting vessels. Previously, in a study of breast cancer (IBC), in which we used established inflammatory breast cancer (IBC) xenografts (WIBC-9) originating from a patient with IBC (Shirakawa et al., Cancer Res 2001:61:445-451), we reported observing vasculogenic mimicry (VM), a condition in which bloodstreams within cancer tissue are not accompanied by a lining of endothelial cells (ECs) (Shirakawa et al., Cancer Res 2002:62:560-566). In the present study, we examined 331 surgically resected breast cancer specimens for evidence of VM, using immunohistochemistry and laser-captured microdissection (LCM) followed by nested reverse transcriptase polymerase chain reaction (RT-PCR). Surprisingly, 7.9% (26 specimens) of the 331 specimens exhibited evidence of VM. Of these 26 VM specimens, 84.6% (22 specimens) exhibited pseudo-comedo formation. RT-PCR analysis of 8 microdissected typical VM specimens revealed expression of Tie-2, Flt-1, thrombin receptor and CD31 in 63, 50, 0 and 0% of specimens, respectively. In contrast, results of RT-PCR analysis of 8 specimens from non-VM tumors were negative for expression of these genes. The 26 VM cases tended to have a higher percentage of hematogenous recurrence (p = 0.059) and a lower percentage of 5-year survival (p = 0.071) than the 305 non-VM cases. However, there were no significant differences in tumor size, lymph node metastasis, estrogen receptors or progesterone receptors between the 2 groups (p > 0.1). Our results suggest that the existence of VM increases the likelihood of hematogenous metastases and is in inverse proportion to prognosis.
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PMID:Vasculogenic mimicry and pseudo-comedo formation in breast cancer. 1211 83

Human breast cancers are known to preferentially metastasize to skeletal sites, however, the mechanisms that mediate the skeletal preference (orthotropism) of specific types of cancers remains poorly understood. There is a significant clinical correlation between the expression of bone sialoprotein (BSP) and skeletal metastasis of breast cancers. Our laboratory, as well as others, have proposed the concept that skeletal selective metastasis and associated disease may be attributable to a mimicry of skeletal cellular phenotypes by metastasizing cancer cells. We hypothesize that breast cancer cell expression of phenotypic properties of skeletal cell types, including BSP as one component of that phenotype, is the result of ectopic expression or activity of one or more central transcriptional regulators of bone cell gene expression. To test this hypothesis, we examined the molecular mechanisms that regulate bsp expression in human breast cancer cell lines with previously characterized metastatic potentials. Our results demonstrate that the majority of the distal bsp promoter sequences act to repress BSP expression in cancer cells and that most of the promoter activity resides in the proximal -110 bp of the bsp promoter. In this region, we identified a putative Runx binding element providing a basis for a mechanism for skeletal gene activation. Our results demonstrate that Runx2 is ectopically expressed in breast cancer cells and that one isoform of Runx2 can activate bsp expression in these cells. In addition, we observe that bsp expression is additionally regulated by the homeodomain factor Msx2, another regulator of osteoblast-associated genes. Thus, this is the first report of osteoblast-related transcription factors being expressed in human breast cancer cells and provides a component of a mechanism that may explain the osteoblastic phenotype of human breast cancer cells that preferentially metastasize to bone.
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PMID:Osteoblast-related transcription factors Runx2 (Cbfa1/AML3) and MSX2 mediate the expression of bone sialoprotein in human metastatic breast cancer cells. 1275 Feb 90

We report three cases of solitary fibrous tumor of the breast. The patients were adult to elderly women and complained of a slowly but relentless growing lump. The tumors were fairly circumscribed and cured by means of lumpectomy or, in one case, simple mastectomy. Histologically, they featured the customary "patternless pattern" of short spindle cells haphazardly arranged in fascicles within a collagenized or myxoid ground substance. In two cases, a prominent hemangiopericytic arrangement of tumor cells around a rich vascular framework could be noticed. Cellular areas were often present and showed nuclear overlapping, clumping of chromatin, and a brisk mitotic activity. No atypical mitosis was recognized. Tumor cells were immunoreactive for CD34, bcl2, and vimentin only. On follow-up there was no evidence of either local recurrence or distant metastases. Solitary fibrous tumors of the breast may represent a significant diagnostic problem because of the close mimicry to numerous benign and malignant mammary lesions composed of spindle cells; diagnostic clues may be further obscured in cellular and actively proliferating tumors. A brief overview of mammary solitary fibrous tumor taxonomy along with the principal differential diagnoses within the breast is presented.
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PMID:Solitary fibrous tumor of the mammary gland: a potential pitfall in breast pathology. 1518 57

Chondrosarcoma is a malignant disease of cartilage. Systemic embolisation usually arises from cancerous invasion of pulmonary vessels or the left atrium but cerebral embolisation or ischaemia is rarely recognised. We report a man with left leg amputation for tibial myxoid chondrosarcoma who suffered multiple cerebral embolisms one year later. Cerebral angiography and aortogram did not reveal luminal stenosis and a cardiac survey was normal. Lupus anticoagulant (LAC) and a prolonged activated partial thromboplastin time were detected. A molecular mimicry between prothrombin and paracrine hormones may have accounted for his LAC. A procoagulant autoantibody reacting against metastatic cancer cells may contribute to cancerous thrombosis, such as in chondrosarcoma.
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PMID:Chondrosarcoma, lupus anticoagulant and cerebral ischaemia. 1585 Oct 89

The histological detection of laminin-rich vasculogenic mimicry patterns in human primary uveal melanomas is associated with death from metastases. We therefore hypothesized that highly invasive uveal melanoma cells forming vasculogenic mimicry patterns after exposure to a laminin-rich three-dimensional microenvironment would differentially express genes associated with invasive and metastatic behavior. However, we discovered that genes associated with differentiation (GDF15 and ATF3) and suppression of proliferation (CDKNa1/p21) were up-regulated in highly invasive uveal melanoma cells forming vasculogenic mimicry patterns, and genes associated with promotion of invasive and metastatic behavior such as CD44, CCNE2 (cyclin E2), THBS1 (thrombospondin 1), and CSPG2 (chondroitin sulfate proteoglycan; versican) were down-regulated. After forming vasculogenic mimicry patterns, uveal melanoma cells invaded only short distances, failed to replicate, and changed morphologically from the invasive epithelioid to the indolent spindle A phenotype. In human tissue samples, uveal melanoma cells within vasculogenic mimicry patterns assumed the spindle A morphology, and the expression of Ki67 was significantly reduced in adjacent melanoma cells. Thus, the generation of vasculogenic mimicry patterns is accompanied by dampening of the invasive and metastatic uveal melanoma genotype and phenotype and underscores the plasticity of these cells in response to cues from the microenvironment.
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PMID:Tumor cell plasticity in uveal melanoma: microenvironment directed dampening of the invasive and metastatic genotype and phenotype accompanies the generation of vasculogenic mimicry patterns. 1700 93


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