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

Epidemiologic studies suggest that alcohol may be an inducing factor in human colon tumorigenesis. As colon cells are frequently under autocrine control by growth factors, involvement of the EGFR pathway in alcohol-related colon tumor progression was investigated in the human colon adenocarcinoma-derived cell line Caco-2 which shows EGFR distribution mainly in basolateral cell membranes. EGF treatment results in almost complete downregulation of the basolateral receptor. Low concentrations of ethanol (0.22 mM, 0.1%) however, lead to significantly increased EGFR mRNA and protein expression and a raised mitotic rate mainly in basolaterally treated cells. Alcohol-induced overexpression of EGFR is paralleled by increased cyclin D1 expression. This suggests a possible mechanism for low blood levels of alcohol to stimulate in vivo proliferation of colonocytes by elevating transcription of a growth factor receptor as well as by modifying expression of a cell cycle regulator.
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PMID:Induction of epidermal growth factor receptor expression and mitogenesis by alcohol in human colon adenocarcinoma-derived Caco-2 cells. 1065 28

Despite multimodal therapy, glioblastoma multiforme (GBM) is associated with a poor prognosis with a median survival of less than 1 year. However, a small number of patients with GBM shows survival times of several years. Although clinical features like age and performance status at diagnosis are well known prognostic parameters, molecular markers for prognosis of overall survival are still lacking. Therefore, we compared 2 age- and gender-matched groups of GBM patients with different post-operative time to tumor progression (TTP), defined as 'short-term' for TTP of less than 6 months (n = 21), and 'long-term' for TTP of more than 24 months (n = 21) for genetic alterations of the PTEN, CDKN2A and TP53 genes as well as overexpression of the EGFR, p53 and Mdm2 proteins. For the GBMs with 'short-term' TTP vs. 'long-term' TTP, the studies revealed PTEN mutations in 4/21 vs. 2/21, TP53 mutations in 5/21 vs. 8/21, homozygous deletion of the CDKN2A gene in 5/21 vs. 6/21, overexpression of EGFR in 7/20 vs. 10/20, accumulation of p53 protein in 9/20 vs. 7/20 and of Mdm2 protein in 0/20 vs. 1/20 cases studied. Taken together, our data indicate that mutations of the PTEN and TP53 tumor suppressor genes, homozygous deletion of the CDKN2A gene as well as overexpression of the EGFR, p53 and Mdm2 proteins lack prognostic significance for overall survival time in patients with GBMs.
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PMID:Molecular analysis of the PTEN, TP53 and CDKN2A tumor suppressor genes in long-term survivors of glioblastoma multiforme. 1108 71

The work described in this review addresses the multifunctional roles of growth factors and their cognate receptors in normal development and in tumorigenesis. The concept of epithelial cell plasticity is described in the context of embryonic development during which frequent remodeling occurs in epithelial tissues. The critical role of one member of the FGF family of growth factors is demonstrated in lung branching morphogenesis. Several members of this family have been shown to induce an epithelial-mesenchymal transition in a bladder carcinoma line. In vivo the same factors act in an autocrine or paracrine mode to favor tumor progression. It is suggested that an EGFR-ligand autocrine loop exerts a positive role in tumor progression of human bladder carcinoma whereas FGFR2 acts as a phenotypic tumor suppressor gene. Unexpectedly, constitutive activating mutations in FGFR3 have been uncovered in the majority of the Ta superficial tumors which progress only very rarely to the invasive stages. In contrast, in situ carcinoma, which are considered to be associated with a strong malignant potential, do not carry the FGFR3 mutations. The presence or absence of the mutations defines two distinct oncogenic pathways in bladder carcinogenesis. The studies reveal the complexities in defining the putative functions of growth factors at different times and differentiation stages during development and in tumor progression. These results emphasize the need for caution in the interpretation of studies evaluating the potential of novel anti-cancer agents and for better designs of in vitro and in vivo biological assays.
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PMID:[Role of growth factor signaling in epithelial cell plasticity during development and in carcinogenesis]. 1197 24

Oncogenes, the abnormal forms of proto-oncogenes, were shown to be involved in malignant transformation and in tumor progression. c-erbB2/HER2/neu is member of EGFR family and encodes the p185 protein, which functions as a tyrosine-kinase. Gene amplification and/or p185 overexpression were reported to be associated with poor prognostic in cancer. Our purpose was to investigate p185 immunohistochemical expression in breast carcinomas and in the corresponding axillary lymph nodes metastases and to identify possible correlation between p185 and other factors of poor prognostic, such as loss of hormonal receptors expression. In our study, 40.91% of cases were erbB-2 positive, p185 expression being maintained from the primary tumors to axillary metastases and associated with positive nodal status and with the absence of hormonal receptors expression (p < 0.05). These findings support the hypothesis the c-erbB2 is an advantageous acquisition for the aggressive behavior of the tumor cell and for its ability to invade and metastasize.
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PMID:[Overexpression of c-erbB-2 gene product is associated with poor prognosis factors in breast carcinoma]. 1475 39

Glioblastoma is a rapidly growing tumor that accounts for more than 50% of all primary gliomas. Amplification of oncogenes and deletion of tumor suppressor genes frequently affects tumor progression. Thus, the goal of this study was to conduct a comprehensive analysis of gene aberrations of individual glioblastomas. A genome DNA microarray (GenoSensor Array 300), spotted with 287 target genes, was used to analyze resected tissue from 11 different high-grade gliomas. The average number of gene aberrations was 9.0 per case (WHO grade III) and 13.3 per case (WHO grade IV). EGFR was the most frequent amplified gene in this series (4 of 11 cases), and high-level amplification was also detected for EGFR, SAS/CDK4, and AKT1. A high frequency of deleted genes was observed in 6 of 11 cases (54.5%), including FGFR2, MTAP, and DMBT1. The detected gene aberrations were matched to the classical primary glioblastoma pathway in five of nine cases. We conclude that the GenoSensor Array 300 genomic DNA microarray is a useful method for the comprehensive identification of amplified and deleted genes in glioblastoma.
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PMID:Detection of gene amplification and deletion in high-grade gliomas using a genome DNA microarray (GenoSensor Array 300). 1475 42

The Kruppel-like transcription factor KLF6 is a novel tumor-suppressor gene mutated in a significant fraction of human prostate cancer. It is localized to human chromosome 10p14-15, a region that displays frequent loss of heterozygosity in glioblastoma multiforme (GBM). Indeed, mutations of the KLF6 gene have recently been reported in this tumor type. In this study, we report that the expression of KLF6 is attenuated in human GBM when compared with primary astrocytes. Expression of KLF6 in GBM cells reverts their tumorigenicity both in vitro and in vivo, which is correlated with its transactivation of the p21/CIP1/WAF1 promoter. Additionally, KLF6 inhibits cellular transformation induced by several oncogenes (c-sis/PDGF-B, v-src, H-Ras, and EGFR) that are components of signaling cascades implicated in GBM. Our results provide the first evidence of functional tumor suppression by KFL6, and its loss may contribute to glial tumor progression.
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PMID:Suppression of glioblastoma tumorigenicity by the Kruppel-like transcription factor KLF6. 1506 20

Although 1p/19q codeletions define "genetically favorable" oligodendrogliomas, eventual tumor progression and patient death remain constant. Genetic testing is often performed at the time of recurrence, though it is unclear whether these or other genetic alterations provide useful prognostic information. We characterized 138 of 189 (73%) available primary and recurrent oligodendroglial neoplasms from 80 patients, utilizing paired FISH probes for 1p32/1q42, 19p13/19q13, CEP7/EGFR, CEP9/p16, and PTEN/DMBT1. Patients were followed until death (49%), or a median follow-up of 8.9 years. Patients with 1p/19q codeleted tumors (71%) had an estimated overall median survival of 14.9 years with an estimated 3.9 years from first recurrence. In contrast, those lacking deletions had significantly lower estimated overall median survivals of 4.7 years and 1.0 year after first recurrence (both p < 0.001). This increased survival in patients with 1p/19q codeleted tumors remained significant when adjustments were made for age, tumor grade, type of surgical procedure, and treatment with radiation or chemotherapy. Only 1 recurrence showed focal EGFR amplification, while 5 developed 10q deletions, mostly in high-grade mixed oligoastrocytomas lacking 1p/19q deletions. In contrast, p16 (9p21) deletions were common and associated with both high grade (p < 0.001) and recurrence (p = 0.002). Our data suggest that in classic oligodendrogliomas: 1) 1p/19q tumor status is a powerful predictor of patient survival, even after recurrence; 2) p16 deletions are common progression-associated alterations; and 3) 10q deletions and EGFR amplifications are sufficiently rare to suggest the possibility of alternate diagnoses.
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PMID:Prognostic value of 1p, 19q, 9p, 10q, and EGFR-FISH analyses in recurrent oligodendrogliomas. 1509 21

It is widely established that angiogenesis is required during tumor progression. Emerging data, suggests that estrogens can mediate endothelial proliferation and differentiation. We investigated the role of estrogens in the formation and stabilization of capillary-like structures, and identified 17 beta -estradiol-driven pathways involved in vessel assembly. We show that estrogens induce MCF7 breast cancer cells to secrete TGF beta 1. In addition, TGF beta cross talks with EGFR signaling pathway with concomitant up-regulation of EGFR ligand, TGF alpha, promoting cord-like formations in HUVEC cultures. The action of 17 beta -estradiol was not restricted to endothelium, since 17 beta -estradiol also stimulated recovery and migration of a smooth muscle cell line (FLTR) to injured areas again by the cross talk between these two signaling pathways. Finally, given the relevant role of 17 beta -estradiol in vessel stabilization, co-cultures of HUVEC and FLTR cells were established in the presence of 17 beta -estradiol or TGF beta 1. By blocking TGF beta or EGFR signaling, we demonstrate that 17 beta -estradiol promoted vessel stabilization through the interplay of TGF beta 1 and EGFR signaling transduction pathways. Our data suggest that estrogen mediates endothelial cell stabilization and vessel assembly. These vessel protective effects involve TGF beta 1 and EGFR signaling transduction pathways.
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PMID:17 beta -estradiol-mediated vessel assembly and stabilization in tumor angiogenesis requires TGF beta and EGFR crosstalk. 1516 95

Glioblastoma can be divided into genetic subsets. The most prominent criterion for dividing glioblastomas into subsets is the dichotomy between TP53 mutation and EGFR amplification, two genetic alterations that almost never coincide in the same tumor. Approximately one third of glioblastomas have TP53 mutations, one third have EGFR amplification, and one third have neither. When viewed in terms of tumor progression, secondary glioblastomas have a much higher incidence of TP53 mutations than do primary glioblastomas. When viewed in terms of the age of tumor onset, glioblastomas in young adults are likely to have TP53 mutations. However, no correlations have yet been found between the tumor locations and the genetic subsets. In this study, we evaluated the associations between the glioblastoma sites and the genetic subsets defined by the presence of the TP53 mutation or EGFR amplification in nine deep-seated glioblastomas of the thalamus and basal ganglia. All nine tumors were clinically defined as primary glioblastomas. Our investigation revealed that all tumors had TP53 mutations and none had EGFR amplifications. These findings suggest that glioblastomas deep-seated in the thalamus and basal ganglia can be grouped into a subset of glioblastomas with TP53 mutations, akin to the subsets of secondary and younger adult glioblastomas. The locations where the glioblastomas originate may be associated with the genetic features.
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PMID:Molecular genetic analysis of deep-seated glioblastomas. 1532 97

Despite significant improvements in tumor management in general, the prognosis of lung cancer patients remains dismal. It is a hope that our increasing knowledge in molecular aspects of tumor development, growth and progression will open new targets for therapeutic interventions. In this review we discuss some of the more recent results of this field. This includes the susceptibility factors, an association between genetic changes in EGFR pathway and tyrosine kinase inhibitors, the role of gene hypermethylation and genetic profiling, as well as different molecular aspects of tumor progression. Available data all support that lung cancer is a group of diseases with not only distinct histological but with similarly different genetic characters. Accordingly, the diagnosis, prognosis and therapy must accommodate this heterogeneity.
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PMID:Genomics of lung cancer may change diagnosis, prognosis and therapy. 1580 Jun 76


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