Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiogenesis is a biological process by which new capillaries are formed from preexisting vessels. It occurs in physiological and pathological conditions, such as tumors, where a specific turning point is the transition from the avascular to the vascular phase. Tumor angiogenesis depends mainly on the release by neoplastic cells of growth factors specific for endothelial cells able to stimulate the growth of the host's blood vessels. In neuroblastoma, the most common extracranial solid tumor of infancy and childhood, angiogenesis also appears to play an important role in determining tumor phenotype. The nature of the angiogenic balance in neuroblastoma is complex, and a spectrum of angiogenesis stimulators, such as vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2), and inhibitors, such as tissue inhibitors of matrix metalloproteinases (MMPs), have been detected in neuroblastoma tumors. Moreover, an increased production of MMP-2 and -9 has been also observed in advanced stages of tumor, favoring degradation of extracellular matrix and enhancing tumor dissemination. High tumor vascularity is correlated with widely disseminated disease, MYCN amplification, unfavorable histology, and poor outcome. In contrast, low tumor vascularity is associated with prognostically favorable features, such as a localized disease and favorable histology. It is becoming increasingly evident that agents that interfere with blood vessel formation also block tumor progression. Preclinical studies suggest that antiangiogenic strategies may be effective in the treatment of neuroblastoma. A major goal is the determination of whether inhibition of angiogenesis is a realistic way of inhibiting tumor cell dissemination and formation of metastasis in neuroblastoma.
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PMID:Angiogenesis in neuroblastoma. 1565 Feb 39

There was 100% solid tumor formation following inoculation of MCF-7 cells. However, MCF-7 tumor progression was significantly greater in the mice exposed to 17beta-estradiol (17beta-E2) compared to unexposed mice. WISP-2/CCN5 mRNA expression was correspondingly increased in 17beta-E2 exposed MCF-7 tumors compared to unexposed xenografts. Moreover, estrogen exposure followed by anti-estrogen tamoxifen treatment drastically inhibited the tumor growth and WISP-2 expression in nude mice. Therefore, the study suggests that higher WISP-2/CCN5 expression by estrogen may be associated with the estrogen-induced growth of MCF-7 tumors in vivo. Finally, overexpression of WISP-2/CCN5 may be considered as a prognostic marker of estrogen-sensitive tumor growth.
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PMID:Stimulation of MCF-7 tumor progression in athymic nude mice by 17beta-estradiol induces WISP-2/CCN5 expression in xenografts: a novel signaling molecule in hormonal carcinogenesis. 1570 14

Neuroblastoma (NB) is the most common extracranial solid tumor of childhood and the third most common pediatric cancer. Although numerous factors including patient age, disease stage and genetic abnormalities have been shown to be predictive of outcome, the mechanisms responsible for the highly variable clinical behavior of this tumor remain largely unknown. In order to gain new insights into the biology of this tumor, we performed microarray analysis and compared the gene expression patterns of NB detected by mass screening, characterized by highly probable spontaneous regression, versus stage 4 NB with poor prognosis. The bioinformatics analysis revealed a set of 19 discriminatory genes that may play a significant role in the natural progression of the disease. Validation of these results and further mechanistic studies would shed new light on the biology of tumor progression, and provide new tools to predict clinical outcome in children with NB.
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PMID:Genome-wide analysis of gene expression in neuroblastomas detected by mass screening. 1592 63

Administration of active TG2 to two different in vitro angiogenesis assays resulted in the accumulation of a complex extracellular matrix (ECM) leading to the suppression of endothelial tube formation without causing cell death. Matrix accumulation was accompanied by a decreased rate of ECM turnover, with increased resistance to matrix metalloproteinase-1. Intratumor injection of TG2 into mice bearing CT26 colon carcinoma tumors demonstrated a reduction in tumor growth, and in some cases tumor regression. In TG2 knockout mice, tumor progression was increased and survival rate reduced compared to wild-type mice. In wild-type mice, an increased presence of TG2 was detectable in the host tissue around the tumor. Analysis of CT26 tumors injected with TG2 revealed fibrotic-like tissue containing increased collagen, TG2-mediated crosslink and reduced organized vasculature. TG2-mediated modulation of cell behavior via changes in the ECM may provide a new approach to solid tumor therapy.
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PMID:Matrix changes induced by transglutaminase 2 lead to inhibition of angiogenesis and tumor growth. 1629 9

Growth factors are signaling molecules which bind to cell surface receptors and mediate a myriad of intracellular functions. Growth factor signaling is vital for growth and differentiation of cells under normal physiological conditions. However, aberrant signaling of these molecules via their receptors enables the cells to acquire abnormal characteristics most commonly observed in tumor cells. Tumor biology studies have revealed a central role for growth factor receptors in tumor progression. This review discusses the involvement of growth factor receptors in solid tumor formation and their value as potential anticancer drug targets.
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PMID:Growth factor receptors: implications in tumor biology. 1637 Mar 90

Apoptosis mediated by the proapoptotic BCL-2 family members BCL-2-associated X-protein (BAX) and BCL-2 antagonist/killer (BAK) is part of the antiviral response at the cellular level to limit virus replication. Viruses, in turn, have evolved to encode antiapoptotic BCL-2 homologs (v-BCL-2s) to prevent the premature death of the infected host cell to sustain virus replication. These same v-BCL-2 proteins cooperate with loss of retinoblastoma protein and p53 tumor suppressor function, by inactivating the BAX and BAK apoptotic pathway to promote epithelial solid tumor growth and resistance to chemotherapy. Analogously to infected cells, failure of apoptosis in tumors permits the survival of abnormal, damaged cells displaying chromosome instability that may further promote tumor progression. Thus, both infected cells and tumor cells require inhibition of the apoptotic host defense mechanism, the insights from which can be exploited for therapy development.
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PMID:Mechanisms of apoptosis regulation by viral oncogenes in infection and tumorigenesis. 1667 7

The B16-F10 mouse model of melanoma is a widely used model to study many aspects of cancer biology and therapeutics in a solid tumor. Melanomas aggressively progress within a dynamic microenvironment containing in addition to tumor cells, stroma cells and components such as fibroblasts, immune cells, vascular cells, extracellular matrix (ECM) and extracellular molecules. The goal of this study was to elucidate the processes of tumor progression by identifying differentially expressed proteins in the tumor mass during specific stages of tumor growth. A comparative proteome analysis was performed on B16-F10 derived tumors in C57BL/6 mice at days 3, 5, 7, and 10. Statistical approaches were used to determine quantitative differential protein expression at each tumor time stage. Hierarchical clustering of 44 protein spots (p < 0.01) revealed a progressive change in the tumor mass when all 4 time stages were classified together, but there was a clear switch in expression of these proteins between the day 5 and the day 7 tumors. A trend analysis showed 53 protein spots (p < 0.001) following 6 predominant kinetic paths of expression as the tumor progressed. The protein spots were then identified using MALDI-TOF mass spectrometry. Proteins involved in glycolysis, inflammation, wounding, superoxide metabolism, and chemotaxis increased during tumorigenesis. From day 3 to day 7 VEGF and active cathepsin D were induced 7-fold and 4-fold, respectively. Proteins involved in electron transport, protein folding, blood coagulation, and transport decreased during tumorigenesis. This work illustrates changes in the biology of the B16-F10 tumor mass during tumor progression.
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PMID:Proteomic analysis of tumor establishment and growth in the B16-F10 mouse melanoma model. 1679 90

Activation of ErbB receptor tyrosine kinases (RTKs) must be precisely regulated to ensure the fidelity of developmental and homeostatic processes mediated by growth factors. Insufficient receptor stimulation will lead to defects in tissue development, while excessive stimulation can lead to hyperplastic events associated with cancer and other diseases. A coordinated balance of the intensity and timing of receptor signaling, achieved through both receptor activation and negative regulatory mechanisms, is required for signaling fidelity. While considerable effort has gone into understanding mechanisms by which ErbB receptors are activated, our understanding of the suppression of growth factor receptor activity remains limited. While ligand-stimulated receptor degradation is the most thoroughly examined mechanism for preventing hyper-signaling by ErbBs, recent studies indicate that several other mechanisms act directly on receptors to suppress receptor levels, or the magnitude or duration of receptor signaling. ErbB receptor overexpression or aberrant activation contributes to the progression of numerous solid tumor types. Hence, tumor cells must overcome these endogenous receptor negative regulatory mechanisms before they can exploit ErbB receptors to achieve uncontrolled growth. Here we will discuss several proteins that directly interact with ErbB receptors to suppress signaling, highlighting the potential impact of their loss on tumor progression.
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PMID:ErbB receptor negative regulatory mechanisms: implications in cancer. 1686 34

Improvements in our understanding of the molecular basis of cancer have led to the clinical development of protein kinase inhibitors, which target pivotal molecules involved in intracellular signaling pathways implicated in tumorigenesis and progression. These novel targeted agents have demonstrated activity against a wide range of solid tumors, are generally better tolerated than standard chemotherapeutics, and may revolutionize the management of advanced refractory cancer. The ubiquitous Raf serine/threonine kinases are pivotal molecules within the Raf/mitogen extracellular kinase (MEK)/extracellular signal-related kinase (ERK) signaling pathway, which regulates cellular proliferation and survival. Raf kinase isoforms (wild-type Raf-1 or the b-raf V600E oncogene) are overactivated in a variety of solid tumor types, including renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), non-small cell lung cancer (NSCLC), melanoma, and papillary thyroid carcinoma. In this review, the role of Raf in normal cells and in cancer is discussed, and an overview is given of Raf inhibitors currently in development, focusing on sorafenib tosylate (BAY 43-9006 or sorafenib). Sorafenib is the first oral multi-kinase inhibitor to be developed that targets Raf kinases (Raf-1, wild-type B-Raf, and b-raf V600E), in addition to receptor tyrosine kinases associated with angiogenesis (vascular endothelial growth factor receptor [VEGFR]-2/-3, platelet-derived growth factor receptor [PDGFR]-beta) or tumor progression (Flt-3, c-kit). Preclinical and clinical sorafenib data that led to its recent approval for the treatment of advanced RCC are summarized, along with current thinking on sorafenib's mechanism of effect on the tumor and tumor vasculature in melanoma and RCC.
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PMID:Role of Raf kinase in cancer: therapeutic potential of targeting the Raf/MEK/ERK signal transduction pathway. 1689 Jul 95

Adenocarcinoma cells from the pleural effusion of a patient with breast cancer were injected into the mammary glands of nude mice and grown into solid tumors. A cell line derived from these tumors expressed alpha-smooth muscle actin but not human cytokeratin 7, indicating "activated" stroma of mouse origin. Cells in mitosis exhibited mainly polyploid mouse karyotypes, but 30% had mixed mouse and human chromosomes, among which 8% carried mouse/human translocations. Nuclei of interphase cells were 64% hybrid. Hybrid mouse/human nuclei were also detected in the primary xenograft. Thus, synkaryons formed in the solid tumor by spontaneous fusion between the malignant human epithelium and the surrounding normal host mouse stroma. The transformed stroma-derived cells are tumorigenic with histopathologic features of malignancy, suggesting a new mechanism for tumor progression.
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PMID:Spontaneous fusion with, and transformation of mouse stroma by, malignant human breast cancer epithelium. 1691 8


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