Cyclooxygenase-2 and Hypoxia-Inducible Factor-1α protein expression is related to inflammation, and up-regulated since the early steps of colorectal carcinogenesis

Mariani, Francesco; Sena, Paola; Marzona, Laura; Riccio, Massimo; Fano, Rita Adriana; Manni, Paola; Gregorio, Carmela Di; Pezzi, Annalisa; Leòn, Maurizio Ponz de; Monni, S; Pol, Anto De; Roncucci, Luca

doi:10.1016/j.canlet.2009.02.001

Cited by 56 publications

(41 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The fluorescence intensity at the selected areas, linearly correlated with the number of pixels, was quantitatively analyzed using the standard imaging analysis software of an NIS-Elements system. To each sample was assigned a code number and the score, called immunofluorescence intensity score (IFIS), was determined by an observer who was blind to tissue groups during analysis (25).…”

Section: Evaluation Of Caspase-3 Active and Bcl-2 Immunofluorescencementioning

confidence: 99%

Altered Expression of Apoptosis Biomarkers in Human Colorectal Microadenomas

Sena

Roncucci

Marzona

et al. 2010

Cancer Epidemiology, Biomarkers &Amp; Prevention

Self Cite

View full text Add to dashboard Cite

Human colorectal microadenomas are considered the earliest detectable premalignant lesions in the colon. They can be identified as aggregates of enlarged crypts with thicker epithelial linings and elongated luminal openings on the colonic mucosal surface after methylene blue staining and observation under a dissecting microscope. Multiple lines of evidence suggest that a central role in neoplastic development is played by the inhibition of apoptosis, followed by disruption of DNA repair. Understanding the early mechanisms of colorectal carcinogenesis may help develop new approaches of colorectal cancer prevention and treatment. The aim of the present study was to quantify poly-ADP ribose polymerase 1 (PARP-1)-positive cells and to evaluate apoptotic control mechanisms through Caspase-3 active and Bcl-2 protein expression in human microadenomas and in normal colorectal mucosa using immunofluorescence techniques coupled with confocal microscopy and immunoblot experiments. The mean percentage of PARP-1-positive epithelial cells was 3.0 ± 0.37% (SD) and 15.67 ± 0.40% in microadenoma and in normal mucosa, respectively. Proteins involved in programmed cell death were differently expressed in microadenoma and in normal mucosa. Indeed, by semiquantitative immunoflourescence analysis, confirmed by Western blot, microadenoma showed high levels of Caspase-3 active and low levels of Bcl-2 expression, whereas the opposite was true for normal colorectal mucosa. In the stroma of normal colorectal mucosa, fibroblast-like cells and neutrophils were the cells that underwent apoptosis to a greater extent. In conclusion, malfunction of the control mechanisms of programmed cell death seems present in the early stages of colorectal cancer development. Cancer Epidemiol Biomarkers Prev; 19(2); 351-7. ©2010 AACR.

show abstract

Section: Evaluation Of Caspase-3 Active and Bcl-2 Immunofluorescencementioning

confidence: 99%

Altered Expression of Apoptosis Biomarkers in Human Colorectal Microadenomas

Sena

Roncucci

Marzona

et al. 2010

Cancer Epidemiology, Biomarkers &Amp; Prevention

Self Cite

View full text Add to dashboard Cite

show abstract

“…IL-6 overexpression is a well-known risk factor for CAC and the role of HIF-1α during CAC progression is well documented (22,27). However, whether IL-6 contributes to CAC progression through the regulation of HIF-1α remains unclear.…”

Section: Discussionmentioning

confidence: 99%

“…In clinical studies, HIF-1α was shown to be overexpressed in multiple types of cancer, including colorectal (20,21). In addition, HIF-1α was identified to be overexpressed in patients with IBD and in the early stages of colorectal cancer (22). Furthermore, patients carrying one or both of the common HIF-1α polymorphisms, C1772T and G1790A, displayed a significantly higher risk for the development of CAC (23).…”

Section: Introductionmentioning

confidence: 99%

Interleukin-6 promotes tumor progression in colitis-associated colorectal cancer through HIF-1α regulation

Han

Meng

et al. 2016

Oncology Letters

View full text Add to dashboard Cite

Abstract. Interleukin-6 (IL-6) is a well-known etiological factor of colitis-associated colorectal cancer (CAC) and has a significant role in CAC progression. In addition, hypoxia-inducible factor 1α (HIF-1α) serves a primary role in the progression of CAC. However, the association between IL-6 and HIF-1α during the progression of CAC remains unclear. To investigate this association, the present study induced CAC in a mouse model using azoxymethane and dextran sulfate sodium. In addition, an anti-IL-6 receptor antibody was used to inhibit IL-6. In this model, anti-IL-6 receptor antibody treatment significantly inhibited the development of CAC and the expression of HIF-1α, in colorectal adenomas and adenocarcinomas. In patients with CAC, the HIF-1α gene was demonstrated to be overexpressed in tumor tissue compared with adjacent non-malignant tissue. Furthermore, HIF-1α mRNA expression was positively correlated with serum IL-6 concentration. The results of the present study suggest that IL-6 promotes CAC progression, in the early stage of the disease, through HIF-1α regulation.

show abstract

“…84 Expression level of HIF-1α is upregulated in inflammatory conditions and malignant lesions. 86 In vitro systems, it was reported that HIF-1α activated NFκB. With the use of mice lacking IKK-β in different cell types, Rius et al showed that NFκB was a critical transcriptional activator of HIF-1α, indicating an interrelationship between NFκB and HIF-1α.…”

confidence: 99%

“…85 Due to the pivotal role of hypoxia in tumor progression, the expression of HIF-1α is expected as a prognosis biomarker and potential therapeutic target. 86 It is generally accepted that hypoxia plays an important role in tumor cell chemoresistance and the inhibition of HIF-1α is likely to be an efficient strategy to improve the treatment outcomes of conventional cytotoxic drugs. Treatment of subcutaneous xenografts in immunodeficient mice with an agent which inhibited HIF-1 activity in vitro led to smaller and less vascularized tumors, regardless of tumor type.…”

confidence: 99%