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

Ovarian cancer presents as disseminated disease in the majority of cases. Tumor metastasis to the peritoneal and/or pleural cavity is evident in two-thirds of cases at diagnosis and relapse is most often detected at this anatomic site. Despite the fact that the primary tumor is amenable to surgical removal in the majority of cases, ovarian cancer research, including the evaluation of therapeutic targets, has concentrated on primary disease. In recent years, we analyzed the site-dependent expression of cancer-associated and regulatory molecules in primary tumors, effusions and solid metastases. Our data show that some molecules (e.g., Ets transcription factors) are expressed at all anatomic sites in ovarian carcinoma and that their expression in primary and metastatic disease is associated with poor prognosis. However, the majority of molecules (e.g., cadherins, integrins, and nerve growth factor receptors) are differentially expressed along tumor progression and have different prognostic value depending on the organ sampled. Specifically, cancer-associated molecules with a well-characterized clinical significance in solid tumors (e.g., matrix metalloproteinases) have no such role in effusions. Finally, a growing number of molecules are differentially expressed in primary diagnosis (pre-chemotherapy) and disease recurrence (post-chemotherapy) specimens, reflecting the effect of disease progression and chemotherapy. This review will present the current knowledge in this area.
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PMID:Anatomic site-related expression of cancer-associated molecules in ovarian carcinoma. 1730 82

Mutations in the p53 tumor suppressor are very frequent in human cancer. Often, such mutations lead to the constitutive overproduction of mutant p53 proteins, which may exert a cancer-promoting gain of function. We now report that cancer-associated mutant p53 can augment the induction of nuclear factor kappaB (NFkappaB) transcriptional activity in response to the cytokine tumor necrosis factor alpha (TNFalpha). Conversely, down-regulation of endogenous mutant p53 sensitizes cancer cells to the apoptotic effects of TNFalpha. Analysis of human head and neck tumors and lung tumors reveals a close correlation between the presence of abundant mutant p53 proteins and the constitutive activation of NFkappaB. Together, these findings suggest that p53 mutations may promote cancer progression by augmenting NFkappaB activation in the context of chronic inflammation.
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PMID:Mutant p53 enhances nuclear factor kappaB activation by tumor necrosis factor alpha in cancer cells. 2633 8

Genomic alterations lead to cancer complexity and form a major hurdle for comprehensive understanding of the molecular mechanisms underlying oncogenesis. In this review, we describe recent advances in studying cancer-associated genes from a systems biology point of view. The integration of known cancer genes onto protein and signaling networks reveals the characteristics of cancer genes within networks. This approach shows that cancer genes often function as network hub proteins which are involved in many cellular processes and form focal nodes in information exchange between many signaling pathways. Literature mining allows constructing gene-gene networks, in which new cancer genes can be identified. The gene expression profiles of cancer cells are used for reconstructing gene regulatory networks. By doing so, genes which are involved in the regulation of cancer progression can be picked up from these networks, after which their functions can be further confirmed in the laboratory.
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PMID:Cancer systems biology: exploring cancer-associated genes on cellular networks. 1741 19

Dysadherin is a cancer-associated cell membrane glycoprotein that promotes experimental cancer metastasis. Here we review recent work that has provided insights into possible mechanisms of action of this newly recognized player in the cancer progression process. Dysadherin modulates cell phenotype in a number of ways, including down-regulation of E-cadherin-mediated cell adhesion, and up-regulation of chemokine production. In this way, expression of dysadherin in a tumor can influence both the tumor cell itself and the stromal compartment, so as to create conditions that are more permissive for metastatic spread. Dysadherin expression is also an independent prognostic indicator of metastasis and survival for many different types of human cancer. Thus, dysadherin may represent a new molecular target for the visualization, prevention or treatment of advanced cancer.
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PMID:Dysadherin: a new player in cancer progression. 1744 82

Many investigations of cancer development have pursued the mechanisms by which genetic mutations stimulate tumor development through activation of oncogenes or loss of tumor suppressor genes. However, there is an increasing awareness that signals provided by the stroma can induce the genetic alterations that underlie tumor formation, can stimulate tumor growth and progression, and can dictate both therapeutic response and ultimate clinical outcome. This principle is particularly clear in breast cancer, where recent investigations using sophisticated three-dimensional cell culture models and transgenic animals have been used to define how altered signals from the microenvironment contribute to breakdown of tissue structure, increased cellular proliferation, and transition to the malignant phenotype. We review here recent studies identifying new roles for cancer-associated fibroblasts in promoting tumor progression, through stimulation of inflammatory pathways and induction of extracellular matrix-remodelling proteases. These studies identify mechanisms by which development of a reactive tumor stroma causes mammary hyperproliferation, progression to fibrosis, development of neoplasia, increasing invasiveness, and eventual metastasis, and how intervention in these processes may provide new avenues for therapy.
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PMID:Stromal induction of breast cancer: inflammation and invasion. 1744 44

We demonstrate the use of combination therapy to overcome the limitations of cancer DNA vaccines by adding radioiodine gene therapy in an animal cancer model. We established a stable cell line (CT26/hMUC1-hNIS-Fluc: CMNF) expressing the hMUC1, hNIS and Fluc genes using a retro- and lentivirus system. The survival rates (%) of CMNF cells were determined using clonogenic assays after (131)I treatment. After i.m. immunization to 4 groups of Balb/c mice (pcDNA3.1, pcDNA3.1+(131)I, pcDNA3-hMUC1+PBS and pcDNA3-hMUC1+(131)I groups) with pcDNA3-hMUC1 or pcDNA3.1 once a week for 2 weeks, 1 x 10(5) CMNF cells were injected s.c. into the right thighs of mice in each group. Twenty-one days after tumor transplantation, (131)I was administered i.p. to the pcDNA3.1+(131)I and pcDNA3-hMUC1+ (131)I groups. Tumor progression was monitored in the 4 groups by bioluminescent and scintigraphic imaging and by taking caliper measurements. Tumor masses were extracted and weighted at 39 days post-tumor challenge. We confirmed that CMNF cells highly express hMUC1, hNIS and Fluc by FACS, (125)I uptake, and luciferase assay. The survival rates of CMNF were markedly reduced to (14.6 +/- 1.5)% after (131)I treatment compared with the survival rates of parental cells (p < 0.001). Tumor growth inhibition was significant only in the pcDNA3-hMUC1+ (131)I group at 39 days post challenge. Tumor masses in pcDNA3-hMUC1+ (131)I group were smaller than those of the other groups. This study shows that the weak preventive effects of cancer DNA vaccine can be overcome by radioiodine gene therapy utilizing sodium iodide symporter.
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PMID:Human sodium iodide symporter gene adjunctive radiotherapy to enhance the preventive effect of hMUC1 DNA vaccine. 1756 43

Transforming growth factor-beta (TGF-beta) is overexpressed at sites of wound repair and in most adenocarcinomas including prostate cancer. In stromal tissues, TGF-beta regulates cell proliferation, phenotype and matrix synthesis. To address mechanisms of TGF-beta action in cancer-associated reactive stroma, we developed prostate stromal cells null for TGF-beta receptor II (TbetaRII) or engineered to express a dominant-negative Smad3 to attenuate TGF-beta signaling. The differential reactive stroma (DRS) xenograft model was used to evaluate altered stromal TGF-beta signaling on LNCaP tumor progression. LNCaP xenograft tumors constructed with TbetaRII null or dominant-negative Smad3 stromal cells exhibited a significant reduction in mass and microvessel density relative to controls. Additionally, decreased cellular fibroblast growth factor-2 (FGF-2) immunostaining was associated with attenuated TGF-beta signaling in stroma. In vitro, TGF-beta stimulated stromal FGF-2 expression and release. However, stromal cells with attenuated TGF-beta signaling were refractory to TGF-beta-stimulated FGF-2 expression and release. Re-expression of FGF-2 in these stromal cells in DRS xenografts resulted in restored tumor mass and microvessel density. In summary, these data show that TGF-beta signaling in reactive stroma is angiogenic and tumor promoting and that this effect is mediated in part through a TbetaRII/Smad3-dependent upregulation of FGF-2 expression and release.
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PMID:Fibroblast growth factor-2 mediates transforming growth factor-beta action in prostate cancer reactive stroma. 1763 43

Epithelial-mesenchymal transition (EMT) describes the differentiation switch between polarized epithelial cells and contractile and motile mesenchymal cells, and facilitates cell movements and generation of new tissue types during embryogenesis. Many secreted polypeptides are implicated in the EMT process and their corresponding intracellular transduction pathways form highly interconnected networks. Transforming growth factor-beta, Wnt, Notch and growth factors acting through tyrosine kinase receptors induce EMT and often act in a sequential manner. Such growth factors orchestrate the concerted regulation of an elaborate gene program and a complex protein network, needed for establishment of new mesenchymal phenotypes after disassembly of the main elements of epithelial architecture, such as desmosomes, as well as tight, adherens and gap junctions. EMT of tumor cells occurs during cancer progression and possibly generates cell types of the tumor stroma, such as cancer-associated myofibroblasts. EMT contributes to new tumor cell properties required for invasiveness and vascular intravasation during metastasis. Here we present some of the current mechanisms that mediate the process of EMT and discuss their relevance to cancer progression.
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PMID:Signaling networks guiding epithelial-mesenchymal transitions during embryogenesis and cancer progression. 1764 76

Histone deacetylases (HDACs) regulate the expression and activity of numerous proteins involved in both cancer initiation and cancer progression. By removal of acetyl groups from histones, HDACs create a non-permissive chromatin conformation that prevents the transcription of genes that encode proteins involved in tumorigenesis. In addition to histones, HDACs bind to and deacetylate a variety of other protein targets including transcription factors and other abundant cellular proteins implicated in control of cell growth, differentiation and apoptosis. This review provides a comprehensive examination of the transcriptional and post-translational mechanisms by which HDACs alter the expression and function of cancer-associated proteins and examines the general impact of HDAC activity in cancer.
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PMID:Histone deacetylases and cancer. 1769 83

Carbohydrate antigen sialyl Lewis a (CA19-9) is the most frequently applied serum tumor marker for diagnosis of cancers in the digestive organs. Recent progress disclosed the presence of a normal counterpart of the determinant, namely disialyl Lewis a, which is predominantly expressed in non-malignant epithelial cells of the digestive organs, while sialyl Lewis a is preferentially expressed in cancers. The disialyl Lewis a determinant carries one extra sialic residue attached through a 2 --> 6 linkage to the GlcNAc moiety compared to cancer-associated sialyl Lewis a, which carries only one 2 --> 3 linked sialic acid residue (monosialyl Lewis a). Disialyl Lewis a in normal epithelial cells serves as a ligand for immunosuppressive receptors such as sialic acid binding immunoglobulin (Ig)-like lectins (siglec-7) and -9 expressed on resident monocytes/macrophages and maintains immunological homeostasis of mucosal membranes in digestive organs. Epigenetic silencing of a gene for a 2 --> 6 sialyl-transferase in the early stages of carcinogenesis results in an impairment of 2 --> 6 sialylation, leading to incomplete synthesis and accumulation of sialyl Lewis a, which lacks the 2 --> 6 linked sialic acid residue, in cancer cells. Simultaneous determination of serum levels of sialyl- and disialyl Lewis a, and calculation of the monosialyl/disialyl Lewis a ratio provide information useful for excluding a false-positive serum diagnosis, and also for averting the undesired influence of the Lewis blood group of patients on serum antigen levels. During the course of cancer progression in locally advanced cancers, tumor hypoxia induces transcription of several glycogenes involved in sialyl Lewis a synthesis. Expression of the determinant, consequently, is further accelerated in more malignant hypoxia-resistant cancer cell clones, which become predominant clones in advanced stage cancers and frequently develop hematogenous metastasis. Sialyl Lewis a, as well as its positional isomer sialyl Lewis x, serves as a ligand for vascular cell adhesion molecule E-selectin and facilitates hematogenous metastasis through mediating adhesion of circulating cancer cells to vascular endothelium. Patients having both strong sialyl Lewis a expression on cancer cells and enhanced E-selectin expression on vascular beds are at a greater risk of developing distant hematogenous metastasis.
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PMID:Carbohydrate antigen sialyl Lewis a--its pathophysiological significance and induction mechanism in cancer progression. 1776 Feb 70


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