Vascular endothelial growth factor, p53, Rb, Bcl-2 expression and response to chemotherapy in advanced non-small cell lung cancer

Ludovini, Vienna; Gregorc, Vanesa; Pistola, Lorenza; Mihaylova, Zornitsa; Floriani, Irene; Darwish, Samir; Stracci, Fabrizio; Tofanetti, Francesca Romana; Ferraldeschi, M.; Carlo, L. Di; Ragusa, Mark; Daddi, G; Tonato, Maurizio

doi:10.1016/j.lungcan.2004.03.018

Cited by 44 publications

(44 citation statements)

References 32 publications

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“…Also for other tumor histotypes, evidence of correlation between RB family members expression and angiogenetic markers are emerging. In preinvasive breast pathologies, pRb expression does not correlate with vascularity (Heffelfinger et al, 2000), whereas immunohistochemical evaluation of advanced non-small cell lung cancer biopsy specimens demonstrates a negative correlation between pRb and VEGF expression (Ludovini et al, 2004). Furthermore, in both hepatocellular carcinoma and endometrial cancer specimens, pRb2/p130 expression is inversely correlated with VEGF level and tumor aggressiveness (Claudio et al, 2004;Sanseverino et al, 2006).…”

Section: Correlation Of Retinoblastoma Family Members and Vegf Expresmentioning

confidence: 99%

Involvement of RB gene family in tumor angiogenesis

Gabellini¹,

Bufalo²,

Zupi³

2006

Oncogene

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Angiogenesis, the development of new blood vessels from pre-existing vessels, represents a fundamental step in tumor progression and metastatization. The induction of vasculature is required for growth of the tumor mass, to ensure an adequate supply of oxygen and metabolites to the tumor beyond a critical size. Tumor angiogenesis is a highly regulated process that is controlled physiologically by the tumor microenvironment and genetically by alteration of several oncogenes or tumor suppressor genes. We will focus on recent demonstrations regarding the involvement of the retinoblastoma family proteins (phosphorylated retinoblastoma (pRb), p107 and pRb2/p130) at different levels of the angiogenic process. pRb and its homologs can regulate the expression of pro-and antiangiogenic factors, such as the vascular endothelial growth factor, through an E2F-dependent mechanism. Moreover, pRb is able to modulate also the transcriptional activity of several angiogenesis-related factors like HIF-1, Id2 and Oct-1. pRb2/p130 is required for both differentiation and mobilization of bone marrow-derived endothelial cell precursors and endothelial sprouting from neighboring vessels. The involvement of the pRb pathway in the angiogenesis process has also been demonstrated by different cellular models expressing viral oncoproteins, like human papilloma virus. Moreover, some natural and synthetic compounds demonstrate their antiangiogenetic activity with a mechanism of action involving pRb. Finally, the possible prognostic value of immunohistochemical evaluation of pRb and/or pRb2/p130 expression can represent a useful tool for the characterization of the angiogenic phenotype of specific tumor histotypes.

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Section: Correlation Of Retinoblastoma Family Members and Vegf Expresmentioning

confidence: 99%

Involvement of RB gene family in tumor angiogenesis

Gabellini¹,

Bufalo²,

Zupi³

2006

Oncogene

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“…The relative risk J Bras Pneumol. 2005; 32(1): [56][57][58][59][60][61][62][63][64][65] of lung cancer for former smokers, albeit lower than for smokers, is higher than for nonsmokers, reinforcing the need for prevention measures since over 50% of lung cancer cases occur among former smokers. The use of chemoprevention in former smokers relies on the evidence of persistent genetic damage in the airways as well as in the etiological role of tobacco in genetic alterations.…”

Section: Smoking As a Risk Factormentioning

confidence: 99%

“…The vascular endothelial growth factor (VEGF) and the fibroblast growth factor are important angiogenesis inducers. (57) Expression of VEGF in increased in metastatic lung cancer, worsening the prognosis in cases of NSCLC. In squamous cell carcinoma, the VEGF receptor (Flt-1) is constantly expressed, suggesting an autocrine role of VEGF in Flt-1, and the mutant p53 acts synergistically with hypoxia to express VEGF.…”

Section: Apoptosis and Angiogenesismentioning

confidence: 99%

“…(57) Expression of VEGF is a prognostic indicator in patients with lung cancer, participating in tumor progression through two mechanisms: as a growth factor for tumor cells and as a mitotic factor for vascular endothelial cells. (57) Smoking causes the loss of fragile histidine triad (FHIT) gene function, and carcinogens present in tobacco smoke cause a deletion in the FHIT allele. Continuous exposure causes deletion in the second allele, leading to the loss of FHIT expression.…”

Section: Apoptosis and Angiogenesismentioning

confidence: 99%

“…Fibroblast growth factor is expressed in 70% of all NSCLCs, but its importance in prognosis remains undefined. (2,15,57) …”

Section: Apoptosis and Angiogenesismentioning

confidence: 99%

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Marcadores moleculares no câncer de pulmão: papel prognóstico e sua relação com o tabagismo

Duarte

Paschoal

2006

J. bras. pneumol.

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Epidemiological studies have demonstrated a causal relationship between smoking and lung cancer. Although most lung cancer cases are linked to smoking, only a minority of heavy smokers develop lung cancer, leading to the notion that genetic factors affect individual susceptibility. The principal molecular changes in lung cancer are seen in tumor suppressor genes, proto-oncogenes, growth factors, telomerase activity, and methylation status of promoters. Well-known agents include angiogenesis-stimulating factors (such as vascular endothelial growth factor), as well as factors related to tumor cell proliferation and apoptosis (epidermal growth factor receptor, p53, K-ras, retinoblastoma and BCL-2). Several of these genetic factors have already been investigated, but no single parameter has yet presented sufficient selectivity regarding prognostic value or therapeutic efficacy. Treatment strategies to cure lung cancer should focus on these early genetic lesions in order to promote their repair or to eliminate these lung cancer cells.

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Chemotherapy with rituximab followed by high‐dose therapy and autologous stem cell transplantation in patients with mantle cell lymphoma

Thiéblemont

Antal

Lacotte‐Thierry

et al. 2005

Cancer

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A hallmark of neoplasia is dysregulated apoptosis, programmed cell death. Apoptosis is crucial for normal tissue homeostasis. Dysregulation of apoptotic pathways leads to reduced cytocidal responses to chemotherapeutic drugs or radiation and is a frequent contributor to therapeutic resistance in cancer. The literature pertaining to detection of apoptotic pathway constituents in cytologic specimens is reviewed herein. Virtually all methods for detecting apoptosis, including classic cytomorphologic evaluation, TUNEL assay, immunocytochemistry, and gene sequence analysis, may be applied to cytologic samples as well as tissue. Components of both intrinsic and extrinsic apoptotic pathways have been studied, including many reports examining p53 and bcl‐2, as well as studies of caspase inhibitory proteins XIAP and survivin, death receptors and ligands such as Fas, Fas‐ligand, and TRAIL. p53 undergoes oncogenic alteration more than any other protein; its immunocytochemical detection almost always connotes loss of its physiologic role as an inducer of apoptosis in response to a damaged genome. Several reports establish cytologic sampling as being as useful as tissue sampling. In one respect cytologic sampling is superior to tissue sampling in particular, by allowing clinicians to repeat sampling of the same tumor before and after administration of therapy; a number of reports use this approach to attempt to predict tumor response by assaying the effect of chemotherapy on the induction of apoptosis. Diagn. Cytopathol. 2010;38:685–697. © 2010 Wiley‐Liss, Inc.

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Vascular endothelial growth factor, p53, Rb, Bcl-2 expression and response to chemotherapy in advanced non-small cell lung cancer

Cited by 44 publications

References 32 publications

Involvement of RB gene family in tumor angiogenesis

Involvement of RB gene family in tumor angiogenesis

Marcadores moleculares no câncer de pulmão: papel prognóstico e sua relação com o tabagismo

Chemotherapy with rituximab followed by high‐dose therapy and autologous stem cell transplantation in patients with mantle cell lymphoma

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