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

The main objective of this study was to differentiate between lymph nodes infiltrated by estrogen receptor-positive (ER+) and estrogen receptor-negative (ER-) breast carcinoma. Lymph nodes were obtained from 40 postmenopausal cancer patients, 10 from each disease stage. Six patients from each group had estrogen receptor-positive (BCaER+) and four estrogen receptor-negative (BCaER-) tumors. Both tumor-containing (T) and uninvolved (N) lymph nodes from the same patient were examined by the following parameters: magnitude of lymph node nucleic acid hybridization with cDNA probes from breast cancer MCF-7ER+ and MCF-7ER- cells; and binding capacity of 3H-estradiol, 125I-EGF, and 125I-PDGF binding and protein kinase C activities of the lymph nodes. Concomitant with the appearance of transformed cells, several events occur: Tumor cells induce stimulation of mononuclear cells and macrophages and evoke T- and B-cell proliferation, leading to the synthesis of tumor cell membrane-associated antibodies. In estrogen receptor-positive (ER+) breast carcinoma, estrogens and host hormonal modulatory mechanisms stimulate production and release of epithelial growth (EGF) and platelet-derived growth factors (PDGF). These factors are characterized by protein kinase C activities. There is infiltration of tumor cells into the lymph node and infiltration of leukocytes into the tumor site. In the lymph node, tumor progression depends on tumor cell proliferation rate and metastatic aggressiveness. The experiments described in this study document the changes that occur in lymph nodes, with differences between nodes infiltrated with BCaER+ and BCaER- breast carcinomas. Hybridization of 32P-cDNA from MCF-7ER+ cells with cellular RNA from BCaER+ involved (T) lymph nodes is greater than with cellular RNA from uninvolved (N) lymph nodes. The magnitude of hybridization correlated (P less than 0.005) with the disease stage.
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PMID:Prognostic significance of mRNA-encoding estrogen receptor and epithelial growth factor receptor in breast carcinoma progression into lymph nodes: 1. Estrogen receptor encoding mRNA. 253 80

It has been demonstrated that angiogenesis is required in the process of tumor progression and metastasis. Microvessel density (MVD) estimates tumor angiogenesis and is an independent indicator for predicting tumor metastasis in a variety of carcinomas. Platelet-derived endothelial cell growth factor (PD-ECGF) is known to be an angiogenic factor in vitro and in vivo. Of 55 patients with oral squamous cell carcinoma (OSCC), regional metastasis was absent in 35 and present in 20. Cases with lymph node metastasis showed significantly higher MVD (mean 61.0 +/- 28.8) than those without metastasis (mean 29.3 +/- 15.1; p < 0.001). A total of 37 cases (67.3%) were PD-ECGF-positive with a high MVD (mean 47.8 +/- 27.9) and 18 (32.7%) showed a negative PD-ECGF expression with a low MVD (mean 26.6 +/- 13.2). PD-ECGF expression was significantly correlated with the increment of MVD (p < 0.01). We suggest that MVD can be used as an independent prognostic indicator for predicting metastasis and that PD-ECGF activity plays an important role in the neovascularization of OSCC.
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PMID:Angiogenesis and expression of platelet-derived endothelial cell growth factor in oral squamous cell carcinoma. 921 58

The angiogenic factor platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) is expressed at higher levels in a wide variety of solid tumors compared to adjacent normal tissues. Patients with PD-ECGF/TP-positive colon and esophageal tumors have a poorer prognosis than those with negative tumors. The expression of PD-ECGF/TP is a prognostic factor independent of microvessel density suggesting that TP has effects on tumor progression independent of its angiogenic activity. Evidence that hypoxia and apoptosis affect tumor growth prompted us to determine whether increased expression of PD-ECGF/TP prevents apoptosis induced by hypoxia. KB/TP cells transfected with a PD-ECGF/TP cDNA were resistant to hypoxia-induced apoptosis. Among the degradation products of thymidine produced by PD-ECGF/TP, 2-deoxy-D-ribose and thymine partially prevented hypoxia-induced apoptosis. The ability of 1 microM 2-deoxy-D-ribose in combination with the same concentration of thymine to prevent hypoxia-induced apoptosis was similar to that of the overexpressed TP in KB cells. A concentration of 1 microM 2-deoxy-L-ribose abrogated the effects of these degradation products of thymidine. These findings suggested that TP can confer resistance to apoptosis induced by hypoxia and the degradation products of thymidine are involved in this resistance. Expression of PD-ECGF/TP may play an important role in the progression of solid tumors, and inhibitors of TP and analogs of the degradation products of thymidine may suppress the growth of tumors by promoting apoptosis.
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PMID:Prevention of hypoxia-induced apoptosis by the angiogenic factor thymidine phosphorylase. 991 7

Morphologic examinations of mammary neoplasias arising in BALB/c (H-2d) mice carrying the activated rat HER-2/neu oncogene (BALB-NeuT), and in FVB (H-2q) mice bearing the wild-type proto-oncogene (FVB-NeuN), indicate that both conditions result in a very human-like lobular carcinoma of alveolar type, whose histotype is the result of the preferential expression of HER-2/neu products in the epithelium of lobular ducts and lobules. Detailed analysis of tumor progression indicates that transition from lobular hyperplasia to overt carcinoma is associated with a high epithelial proliferation rate, as assessed by anti-proliferating cell nuclear antigen immunostaining, and coincides with the activation and maximal extension of tumor angiogenic process as assessed by microvessel count (anti-CD31), anti-beta3 integrin, and anti-laminin immunostaining. Neovascularization is accompanied by vascular endothelial cell growth factor and basic fibroblast growth factor production by hyperplastic epithelial cells. By contrast with the BALB-NeuT tumors, E-cadherin expression is almost nonexistent in those arising in FVB-NeuN mice and this may explain their high metastatic potential. Despite their different kinetics, however, the lung metastases observed in both strains are histologically similar and resemble the primary tumor. Both strains can thus be proposed as models for "in vivo" investigation of the origin and progression of the alveolar type of lobular mammary carcinoma and the testing of new therapeutic approaches.
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PMID:Analysis of mammary carcinoma onset and progression in HER-2/neu oncogene transgenic mice reveals a lobular origin. 1053 89

In tumors, the switch to the angiogenic phenotype is thought to be controlled by a balance of positive and negative angiogenic factors. Tissue factor (TF) produced by tumor cells has been implicated in the regulation of this "angiogenic switch" through its ability to concurrently induce the expression of angiogenic molecules such as vascular endothelial cell growth factor (VEGF), while inhibiting the expression of anti-angiogenic molecules such as thrombospondin 2. We have examined TF expression and its relationship to angiogenesis and tumor progression in human prostate carcinomas. Most of the prostate carcinoma specimens examined (73%; n = 67) express high levels of TF. Immunohistochemical analysis localized TF expression to the epithelial cells of malignant glands. TF expression was significantly correlated with tumor angiogenesis as measured by the microvessel density (MVD). In addition, TF expression was correlated with the preoperative PSA level, a strong predictor of recurrence in prostate carcinomas. Our findings show that TF expression by the malignant glands in prostate cancer is common and suggest a role for this molecule in regulating prostate cancer progression and angiogenesis.
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PMID:Tissue factor expression and angiogenesis in human prostate carcinoma. 1082 84

It has been demonstrated that vascular endothelial growth factor (VEGF) is associated with tumor progression as an angiogenic factor in esophageal squamous cell carcinoma (SCC)s. However, the role of other angiogenic factors such as transforming growth factor-alpha (TGF-alpha), platelet-derived endothelial cell growth factor (PD-ECGF), and basic fibroblast growth factor (bFGF) are still unknown in esophageal SCCs. In this study, we detected the expression of VEGF, TGF-alpha, PD-ECGF and bFGF in tissue specimens from 96 patients with SCC of the esophagus by immunohistochemical staining. To evaluate angiogenesis, endothelial cells were stained immunohistochemically and microvessel density (MVD) was counted in 24 cases. The positive rates for VEGF, TGF-alpha, PD-ECGF and bFGF were 65% (62/96), 67% (64/96), 66% (63/96), and 49% (47/96), respectively. Only TGF-alpha expression had a strong correlation with the average MVD (p=0.0059). However, the MVD increased as the number of positive factors for these 4 factors increased (p=0.0023). The expression of all of these factors significantly correlated to the depth of tumor invasion, and lymph node metastasis. Finally, survival analysis of the patients revealed that VEGF, TGF-alpha, and PD-ECGF were significant prognostic factors. However, multivariate analysis revealed that these factors were not prognostic. Thus, we suggest that TGF-alpha as well as VEGF, PD-ECGF and bFGF may be associated with angiogenesis, and the progression and metastasis of esophageal squamous cell carcinoma.
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PMID:TGF-alpha as well as VEGF, PD-ECGF and bFGF contribute to angiogenesis of esophageal squamous cell carcinoma. 1093 83

The capacity of vascular endothelial cells to modulate their phenotype in response to changes in environmental conditions is one of the most important characteristics of this cell type. Since different growth factors may play an important signalling role in this adaptive process we have investigated the effect of endothelial cell growth factor (ECGF) on morphological, physiological and molecular characteristics of cerebral endothelial cells (CECs). CECs grown in the presence of ECGF and its cofactor heparin exhibit an epithelial-like morphology (type I CECs). Upon removal of growth factors, CECs develop an elongated spindle-like shape (type II CECs) which is accompanied by the reorganization of actin filaments and the induction of alpha-actin expression. Since one of the most important functions of CECs is the creation of a selective diffusion barrier between the blood and the central nervous system (CNS), we have studied the expression of junction-related proteins in both cell types. We have found that removal of growth factors from endothelial cultures leads to the downregulation of cadherin and occludin protein levels. The loss of junctional proteins was accompanied by a significant increase in the migratory activity and an altered protease activity profile of the cells. TGF-beta1 suppressed endothelial migration in all experiments. Our data provide evidence to suggest that particular endothelial functions are largely controlled by the presence of growth factors. The differences in adhesiveness and migration may play a role in important physiological and pathological processes of endothelial cells such as vasculogenesis or tumor progression.
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PMID:Growth factor-induced morphological, physiological and molecular characteristics in cerebral endothelial cells. 1104

We analyzed the expression of vascular endothelial growth factor (VEGF) messenger ribonucleic acid (mRNA) isoforms and platelet-derived endothelial cell growth factor (PDECGF) mRNA in bladder cancer. We also attempted to determine if correlation exists between their expression level and conventional clinical variables in patients with bladder cancer. Tissues obtained from 60 patients with bladder carcinoma were used for analysis. Expression levels of VEGF isoforms and PDECGF were examined using reverse transcription-polymerase chain reaction (RT-PCR). Correlations between the expression levels of each VEGF isoform and PDECGF and histopathologic findings were evaluated. Four VEGF isoforms corresponding to VEGF121, 165, 189, and 206 were detected in bladder cancer tissue by RT-PCR. Gene expression of all VEGF isoforms as a ratio of the target to glyceraldehyde 3-phosphate dehydrogenase (GAPDH) showed no correlation with pathologic stage of bladder cancer. However, with regard to relative expression levels of VEGF isoform, which is the ratio to the sum of total VEGF isoforms, the levels of VEGF206 and VEGF189 in tumor samples of grade pT2 or higher were significantly lower than those in tumors of grade pT1 or lower (P<.05). In contrast, the levels of VEGF121 in >/=pT2 tumors tended to be higher than those in </=pT1 tumors (P=.056). The expression level of PDECGF as a ratio to GAPDH in pT2</= tumors was significantly higher than that in either pTa or pT1 tumors (P<.05). Moreover, a higher expression level of PDECGF was observed in G3 tumors than in G1 tumors (P<.05). The results indicated that gene expression of VEGF isoforms do not play a significant role in tumor progression or invasion; however, the distribution of VEGF isoforms may play a role in tumor progression of bladder cancer. A high expression level of PDECGF correlated significantly with the tumor progression of bladder cancer.
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PMID:Expression of vascular endothelial growth factor isoforms and platelet-derived endothelial cell growth factor in bladder cancer. 1111 67

Several studies have supported the hypothesis that adrenocortical tumor formation is the result of a multistep process. The angiogenic switch has been proposed to be a key step in tumor progression from adenoma to carcinoma. In this study we measured the cytosolic concentrations of three proteins involved in angiogenesis [namely platelet-derived endothelial cell growth factor vascular endothelial cell growth factor A (VEGF-A), and thrombospondin-1 (TSP1)] in a series of 43 human sporadic adrenocortical tumors. The tumors were classified as adenomas (n = 18), transitional tumors (n = 12), or carcinomas (n = 13) according to the histological criteria defined by Weiss. Platelet-derived endothelial cell growth factor/thymidine phosphorylase levels were not significantly different among these three groups. One hundred percent of the adenomas and 73% of the transitional tumors showed VEGF-A concentrations under the threshold value of 107 ng/g protein, whereas 75% of the carcinomas had VEGF-A concentrations above this threshold value. Similarly, 89% of the adenomas showed TSP1 concentrations above the threshold value of 57 microg/g protein, whereas only 25% of the carcinomas and 33% of the transitional tumor samples did so. Insulin-like growth factor II overexpression, a common genetic alteration of adrenocortical carcinomas, was significantly correlated with higher VEGF-A and lower TSP1 concentrations. The tumors from the 6 patients with tumor recurrence after surgical ablation showed significantly higher VEGF-A values than the carcinomas and the transitional tumors from patients that did not relapse. Taken together, these data suggest that a decrease in TSP1 expression is an event that precedes an increase in VEGF-A expression during adrenocortical tumor progression. The population of premalignant tumors with low TSP1 and normal VEGF-A levels could represent a selective target for antiangiogenic therapies.
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PMID:Expression of the angiogenesis markers vascular endothelial growth factor-A, thrombospondin-1, and platelet-derived endothelial cell growth factor in human sporadic adrenocortical tumors: correlation with genotypic alterations. 1113 36

Pancreatic cancer has an incidence of approximately 8 to 10 cases per 100,000 citizens in Western industrialized countries, and the incidence has been increasing throughout the last decades. Insensitivity to antigrowth and apoptotic signals as well as self-sufficiency in growth signals are hallmarks of malignant growth. Pancreatic cancers often exhibit alterations in growth inhibitory pathways such as Smad4 mutations and Smad6 and Smad7 overexpression, and evade apoptosis through p53 mutations and aberrant expression of apoptosis regulating genes. In addition, in pancreatic cancer a variety of growth factors are expressed at increased levels. For example, the concomitant presence of the EGF-receptor and its ligands EGF, TGF-alpha, and/or amphiregulin is associated with enhanced tumor aggressiveness and shorter survival periods following tumor resection. Furthermore, a number of other growth factors and their receptors, such as fibroblast growth factors, nerve growth factor, platelet-derived growth factors, and insulin-like growth factors and their respective receptors are expressed at increased levels in pancreatic cancer and are thought to contribute to its malignant phenotype. Taken together, the disturbance of growth inhibitory and apoptotic pathways and the abundance of growth promoting factors give pancreatic cancer cells a distinct growth advantage which clinically results in rapid tumor progression and poor survival prognosis.
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PMID:Growth factors and their receptors in pancreatic cancer. 1113 19


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