UMLS:C0178874 - FACTA Search

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Query: UMLS:C0178874 (tumor progression)
40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We screened for surface proteins expressed only by the early progenitor cells present in low-passage, low-density cultures of the adult stem/progenitor cells from bone marrow referred to as mesenchymal stem cells or multipotent stromal cells (MSCs). Six proteins were identified that were selectively expressed in the early progenitors: podocalyxin-like protein (PODXL), alpha6-integrin (CD49f), alpha4-integrin (CD49d), c-Met, CXCR4, and CX3CR1. All were previously shown to be involved in cell trafficking or tumor progression. Antibodies to CD49f and PODXL, a sialomucin in the CD34 family, were the most robust for FACScan assays. PODXL(hi)/CD49f(hi) MSCs were more clonogenic and differentiated more efficiently than PODXL(lo)/CD49f(lo) cells. Inhibition of expression of PODXL with RNA interference caused aggregation of the cells. Furthermore, PODXL(hi)/CD49f(hi) MSCs were less prone to produce lethal pulmonary emboli, and larger numbers were recovered in heart and kidney after intravenous infusion into mice with myocardial infarcts.
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PMID:The CD34-like protein PODXL and alpha6-integrin (CD49f) identify early progenitor MSCs with increased clonogenicity and migration to infarcted heart in mice. 1881 95

This study examines whether the expression of cyclooxgenase-2 (COX-2) in urothelial carcinoma (UC) is associated with macrophage infiltration, hypoxia-inducible factor-1alpha (HIF-1alpha) expression and angiogenesis. We investigated the expression of COX-2 associated with HIF-1alpha and performed double immunohistochemical analysis of 216 UCs for COX-2 expression and the correlation with tumor-associated-macrophage (TAM) density and microvessel density (MVD) in situ. A high expression of COX-2 was positively correlated with tumor invasiveness, histologic grade and HIF-1alpha expression in UC (p<0.0001, p=0.003, p<0.0001, respectively). Quantification of double staining of COX-2/CD34 and COX-2/CD68 showed that a higher MVD and TAM density was found in COX-2 high-expression than in COX-2 low-expression tumor fields (p<0.0001). Adjacent to the principal of COX-2 expression areas, MVD value and TAM density were significantly increased in HIF-1alpha high-expression specimens compared with HIF-1alpha low-expression ones (p<0.0001). Interestingly, our data revealed that high COX-2 expression (p=0.002), high HIF-1alpha expression (p<0.0001) and TAM density (p<0.0001) were all associated with high MVD value. Our results suggest that COX-2 may produce a cooperative effect in promoting tumor progression and may be involved in the process of angiogenesis through increasing TAM infiltration or HIF-1alpha regulation by hypoxia.
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PMID:Overexpression of cyclooxygenase-2 in urothelial carcinoma in conjunction with tumor-associated-macrophage infiltration, hypoxia-inducible factor-1alpha expression, and tumor angiogenesis. 1924 90

Monocyte chemoattractant protein-1 (MCP-1) has been demonstrated to play a role in tumor progression. The present study examined the MCP-1 expression of colorectal liver metastases and determined whether MCP-1 is related to tumor progression and is a predictive marker for survival after hepatic resection of colorectal liver metastases. Eighty-seven patients with colorectal liver metastases were evaluated by immunohistochemistry of MCP-1, Angiopoietin-2, CD68, and CD34 for determination of microvessel density. Clinicopatholgical data were also examined. In a separate experiment, immunohistochemistry of MCP-1 was performed to investigate the expression of primary colorectal tumor according to the clinical stage. MCP-1 mRNA expression was determined in colorectal cancer cell lines. Forty-nine patients (56%) showed high expression of MCP-1 of colorectal liver metastases. High MCP-1 expression was related to multiple colorectal liver metastases. When the degree of MCP-1 expression increased, microvessel density count significantly increased compared with low MCP-1 expression. The MCP-1 expression correlated with Angiopoietin-2 expression. MCP-1 expression of the primary colorectal cancer increased as the clinical stage advanced. The increased MCP-1 mRNA expression was observed in cancer cell lines which have high metastasis potency. Univariate analysis demonstrated that the timing of metastases, tumor size, number of metastases, and MCP-1 expression were significant prognostic factors. Multivariate analysis demonstrated that MCP-1 expression was a significant prognostic factor in hepatic disease-free survival. The MCP-1 expression in colorectal liver metastases, at least in part, may be associated with angiogenesis and be a predictive marker for hepatic recurrence after hepatic resection for colorectal liver metastases.
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PMID:Significance of monocyte chemoattractant protein-1 in angiogenesis and survival in colorectal liver metastases. 1928 49

Desmoplastic reaction of the stroma is a part and parcel of several malignancies. It may be seen within or at a site distant from the main tumour. Irrespective of the site of fibrosis in tumours, it portends a poor prognosis as it is generally associated with invasion and metastasis. In this report, we present a unique case of a 78-year-old male patient with clear cell renal carcinoma (CCRC) who presented with a lump in the right loin. On magnetic resonance imaging scan, the mass was arising from the middle part of the right kidney. The nephrectomy was done and specimen on examination revealed a variegated tumour with another whitish solid mass in the surrounding perirenal fat. The kidney tumour showed features of CCRC, whereas whitish mass was entirely composed of proliferating spindle cells. Therefore, the mass mimicked a second tumour not only on gross but even on microscopy. The special stains (Elastic-van Gieson, Masson-Trichrome, Periodic acid schiff's, alcian blue and mucicarmine), immunostaining (cytokeratin, vimentin, epithelial membrane antigen, smooth muscle actin, S-100, HMB-45, CD34 and CD117) patterns and ultrastructural features all, however, favoured it to be an extensive peritumoural fibrotic reaction rather than a neoplasm. The observation provokes important questions like whether the reaction in the index case is an example of tumour-induced fibrosis or is an unassociated phenomenon and, in the case of former, what are factors that govern the extent and site of fibrosis, i.e. intratumoural, peritumoural or away from the tumour. The finding may also help in further research and understanding of the role of stroma in cancer progression and developing stromal antigen-targeted therapies in CCRC.
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PMID:Unusual appearance of perirenal fibrosis in renal cell carcinoma simulating a tumour. 1959 64

According to World Health Organization (WHO) and Daumas-Duport grading systems, progression of oligodendrogliomas (ODGs) to a higher grade (WHO grade III, grade B) is associated with increased angiogenesis. Based on multivariate assessment of molecular, pathological, and radiological parameters, we further assessed the influence of tumor angiogenesis on tumor progression and patient survival. Patients with a diagnosis of ODG, consecutively treated in a single institution, were reviewed and reclassified according to WHO and Daumas-Duport grading systems. MRI scans were reviewed to assess contrast enhancement and necrosis. Tissue sections were used for pathology review and to evaluate immunostaining of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor (VEGF-R), Ki-67, and CD34. Multivariate analysis was performed to assess the impact of tumor angiogenesis-related pathological and radiological factors on patient survival. One hundred thirty-four patients with pure ODG were included in this study. Multivariate analysis identified four independent poor prognostic factors: necrosis, absence of seizure, increased vascularization, and age >55 years. A subgroup of patients with tumor necrosis, increased vascularization, and absence of seizures had a significantly worse outcome than predicted, with a median overall survival of 14.2 months. VEGF expression was significantly higher in this subgroup and correlated with disease progression regardless of histologic grade. Based on the presence of radiological or pathological necrosis, contrast enhancement or endothelial hyperplasia, and absence of seizures, a high risk group of ODG can be identified with significantly worse overall survival. Also, VEGF over-expression in ODG constitutes an early marker for predicting tumor progression.
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PMID:Assessment of tumor angiogenesis as a prognostic factor of survival in patients with oligodendroglioma. 1961 20

Cytotoxic chemotherapy is ineffective in metastatic renal cancer. However, systemic administration of interleukin 2 (IL-2) or infusion of dendritic cells (DCs) loaded with tumor extracts can lead to some response rates with concomitant survival improvements. We report the results of a phase I-II pilot study combining DCs and IL-2 where six patients were included. DCs were derived from bone marrow CD34+ cells and loaded with autologous tumor extracts. CD34-DC vaccines were infused subcutaneously at day 45, 52, 59, 90 and 120 following surgery in combination with IL-2, that was subsequently administrated after the 3rd and 4th DC vaccinations. Preparation of tumor extracts and CD34-DCs were satisfactory in all patients but one. Due to rapid tumor progression, one patient was excluded before vaccination. In the 4 remaining patients, two received 3 vaccinations, while the 2 others received 5 vaccinations and the full IL-2 treatment. No adverse effect due to the vaccinations was observed. A specific immune response against autologous tumor cells was observed in the 2 patients who completed the treatment. Interestingly, these 2 patients had a more prolonged survival than the patients receiving 3 vaccinations. Importantly, a transient and massive increase of circulating natural regulatory T-cells (nTregs) was evidenced in 3 patients following IL-2 administration. Overall, the use of CD34-DC vaccines is feasible, safe and non-toxic. A specific anti-tumor immune response can be detected. However, our data highlights that IL-2 is a potent inducer of nTregs in vivo and as such may have a negative impact on cancer immunotherapy.
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PMID:Massive expansion of regulatory T-cells following interleukin 2 treatment during a phase I-II dendritic cell-based immunotherapy of metastatic renal cancer. 1963 77

Angiogenesis is essential to the survival, growth, invasion, and metastasis of various human solid tumors. We compared the microvessel density (MVD) and clinicopathologic features of two different groups of hepatocellular carcinoma (HCC), namely HCC with cirrhosis (HCC-C) and without cirrhosis (HCC-NC). A tissue microarray composed of 20 normal livers, 20 cirrhotic livers, tumor and adjacent background non-neoplastic liver tissues from 20 HCC-C and 20 HCC-NC were constructed and stained immunohistochemically with antibodies against the antigen CD34. The MVD was determined by the measurement of the area and density of CD34 positive sinusoidal endothelial cells using the Image Pro Plus software. There was a trend of increased MVD in cirrhotic liver compared to normal liver and in cirrhotic background non-neoplastic liver adjacent to the tumor compared to the non-cirrhotic background non-neoplastic liver. Tumor tissue of HCC-C and HCC-NC both showed significantly higher MVD than their adjacent background non-neoplastic liver tissue. There was no statistical difference in MVD between HCC-C and HCC-NC. A higher value of MVD was seen in tumors of intermediate size (5-10 cm), high histologic grade, the presence of lymphvascular space invasion, and the underlying etiology of hepatitis C and alcoholic steatohepatitis. This data indicates that MVD may play an important role in liver carcinogenesis and neoplastic progression. The difference in clinical behavior between HCC-C and HCC-NC does not seem to be associated with differences in tumor MVD. Objective measurement of MVD using standardized computer software could potentially be used as a clinical marker to predict patients' prognosis.
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PMID:Microvessel density and clinicopathologic characteristics in hepatocellular carcinoma with and without cirrhosis. 1966 92

Dedifferentiation is a well recognized, if sometimes controversial, form of tumor progression in certain types of soft tissue and bone sarcoma, and confers a worse prognosis when compared with the low-grade counterpart. To date, dedifferentiation has not been described in solitary fibrous tumor (SFT). Among 948 cases of both intrathoracic and extrathoracic SFTs in our files accessioned between 1988 and 2008, we identified 8 cases of conventional SFT with a discrete anaplastic component, which we believe represents dedifferentiation. These occurred in 3 men and 5 women, 40 to 76 years old (median 60 y), and measured 3.4 to 20.0 cm (median 8.5 cm). Two cases were intrathoracic, 2 were located in the deep soft tissue of thigh, and single cases were located in the omentum, scalp, retroperitoneum, and abdominal wall. In addition to typical features of benign-appearing SFT there was an abrupt transition to nondistinctive high-grade sarcoma in all cases. The latter included epithelioid, round cell, and/or spindle cell components with increased mitotic activity, necrosis, and cystic degeneration. By immunohistochemistry, 7 of 8 cases were CD34 positive in the usual SFT areas, whereas 5 showed loss of CD34 in the poorly differentiated component. Six of 7 cases stained for p53 and p16 showed either negative or scattered positive cells in well-differentiated SFT areas, in contrast to positive or stronger and more diffuse staining in the high-grade component. Follow-up information available in 7 patients ranged from 1 to 58 months (mean 24 mo). Three patients with the largest tumors (9.0, 17.0, and 20.0 cm) died of disease, whereas 3 patients whose tumors measured 8.0 cm or less were treated by surgical excision only, and show no evidence of disease but with only limited follow-up. One patient with an 11.5 cm intrathoracic tumor is alive with disease at 58 months after recurrence and metastasis. We describe, apparently for the first time, what seems, at least in our view, to be dedifferentiation in primary SFT. Our results demonstrate that dedifferentiation in SFT, comparable with that in other low grade/intermediate soft-tissue tumors, poses a higher risk of tumor recurrence and/or metastasis, most notably in large and deep-seated tumors. Similar to other dedifferentiated sarcomas, abrupt transition between low grade and high-grade areas is typically observed with loss of CD34 positivity. The p53 and p16 overexpression in the high-grade component is common as in other dedifferentiated lesions, perhaps pertaining to the underlying molecular mechanism.
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PMID:Expanding the spectrum of malignant progression in solitary fibrous tumors: a study of 8 cases with a discrete anaplastic component--is this dedifferentiated SFT? 1971 88

We show the molecular and functional characterization of a novel population of lineage-negative CD34-negative (Lin(-)CD34(-)) hematopoietic stem cells from chronic myelogenous leukemia (CML) patients at diagnosis. Molecular karyotyping and quantitative analysis of BCR-ABL transcript demonstrated that approximately one-third of CD34(-) cells are leukemic. CML Lin(-)CD34(-) cells showed kinetic quiescence and limited clonogenic capacity. However, stroma-dependent cultures induced CD34 expression on some cells and cell cycling, and increased clonogenic activity and expression of BCR-ABL transcript. Lin(-)CD34(-) cells showed hematopoietic cell engraftment rate in 2 immunodeficient mouse strains similar to Lin-CD34(+) cells, whereas endothelial cell engraftment was significantly higher. Gene expression profiling revealed the down-regulation of cell-cycle arrest genes and genes involved in antigen presentation and processing, while the expression of genes related to tumor progression, such as angiogenic factors, was strongly up-regulated compared with normal counterparts. Phenotypic analysis confirmed the significant down-regulation of HLA class I and II molecules in CML Lin(-)CD34(-) cells. Imatinib mesylate did not reduce fusion transcript levels, BCR-ABL kinase activity, and clonogenic efficiency of CML Lin(-)CD34(-) cells in vitro. Moreover, leukemic CD34(-) cells survived exposure to BCR-ABL inhibitors in vivo. Thus, we identified a novel CD34(-) leukemic stem cell subset in CML with peculiar molecular and functional characteristics.
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PMID:Molecular and functional analysis of the stem cell compartment of chronic myelogenous leukemia reveals the presence of a CD34- cell population with intrinsic resistance to imatinib. 1985 80

The insulin-like growth factor (IGF) system is involved in cell migration, which plays an important role in cancer progression. It has been shown that cancer progression correlates with the level of circulating human hematopoietic stem and progenitor cells (HSPCs) expressing CD34 and/or CD133. However, it is unknown whether factors released from cancer cells, including soluble compounds of the IGF system, recruit these HSPCs via enhancing their migration. Our study showed the expression of type I IGF receptor (IGF-IR) in human HSPCs expressing CD34 and/or CD133. In an indirect co-culture model, soluble factors released from human lung epithelial cancer cells (H358, H322) increased the migration of CD34-/CD133+ cells towards cancer cells, whereas migration of CD34+/CD133+ or CD34+/CD133- cells remained unchanged. The lung epithelial cancer cell lines H358 and H322, exhibited a high expression of IGFBP-2, -4 and -6 but not IGF-I and IGFBP-3. Subsequent analyses with those soluble compounds of the IGF system revealed a dose-dependent stimulating effect of the IGFBP-2 and -4 on the migration of CD34-/CD133+ cells. In contrast, IGF-I and IGFBP-3 and -6 did not influence the migration of CD34-/CD133+ cells. Because IGFBPs are involved in cell migration via IGF-dependent and -independent mechanisms, our study indicates that IGFBP-2 and -4, which are expressed in lung epithelial cancer cells, enhance the migration of CD34-/CD133+ HSPCs independent of IGF-I.
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PMID:Insulin-like growth factor binding proteins-2 and -4 enhance the migration of human CD34-/CD133+ hematopoietic stem and progenitor cells. 1995 6

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