Angiogenesis is an independent prognostic factor in malignant mesothelioma

Edwards, John; Cox, G.; Andi, A.; Jones, J. Louise; Walker, Rosemary A.; Waller, David; O’Byrne, Kenneth J.

doi:10.1054/bjoc.2001.1997

Cited by 108 publications

(83 citation statements)

References 53 publications

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“…35,39,42,65 In our study, we also showed that survival time and relapse time were significantly shorter in NSCLC patients with tumors with high total COX-2 mRNA expression in cancer cells and stromal cells. Several studies have investigated the prognostic significance of COX-2 expression in NSCLC but with different results.…”

Section: Discussionsupporting

confidence: 65%

Total cyclooxygenase‐2 mRNA levels correlate with vascular endothelial growth factor mRNA levels, tumor angiogenesis and prognosis in non‐small cell lung cancer patients

Yuan

Shun

et al. 2005

Intl Journal of Cancer

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Interaction between cancer cells and adjacent stromal cells is important to promote tumor development. Our aim was to study total COX‐2 mRNA expression in both cancer cells and surrounding stromal cells and its association with angiogenic factor VEGF mRNA expression, tumor angiogenesis and prognosis in patients with NSCLC. COX‐2 mRNA expression in both cancer cells and stromal tissue was analyzed using real‐time quantitative (RTQ) RT‐PCR in 60 NSCLC surgical specimens. Immunohistochemistry (IHC) was used to localize COX‐2 protein in tumor specimens. Correlations between tumoral total COX‐2 mRNA expression and VEGF mRNA expression (measured by RTQ RT‐PCR), intratumoral microvessel counts (evaluated by IHC), other clinicopathologic variables, survival and relapse were tested. COX‐2 protein expression was found in cancer as well as the surrounding stromal cells (including infiltrating inflammatory cells and endothelial cells of tumor‐associated microvessels). VEGF protein expression was mainly located in cancer cells. There was a significant association between high tumoral total COX‐2 mRNA expression and high VEGF mRNA expression (p = 0.01) or high intratumoral MVC (p < 0.001) but not other clinicopathologic variables, including tumor status and lymph node metastasis. Patients with higher tumoral total COX‐2 mRNA expression had a statistically shorter survival time (median 15.0 ± 2.61 months) and relapse time (median 5.0 ± 1.37 months) than those with lower tumoral total COX‐2 mRNA expression (median 40.0 ± 3.12 and 34.0 ± 3.11 months; p < 0.0001 and p < 0.0001, respectively, log‐rank test). A significant difference in survival and relapse time was also seen between patients with high and low tumoral VEGF mRNA expression and between those with high and low intratumoral MVC (p = 0.0046 and p = 0.0038, respectively). After stratification by disease stage or histologic subtype, the prognostic significance of high total COX‐2 mRNA expression was still apparent in both stage I and stage II–IV and in both squamous cell carcinoma and adenocarcinoma (p ≤ 0.01 for all). Multivariate analysis using the Cox regression model with backward elimination showed that tumoral total COX‐2 mRNA expression and lymph node status were the 2 most important independent prognostic predictors for survival and disease relapse. We report that total COX‐2 mRNA expression in cancer cells and surrounding stromal cells correlates strongly and positively with VEGF mRNA expression, intratumoral MVC and adverse prognosis in NSCLC patients. This implies that COX‐2 expression in both cancer cells and stromal cells within the tumor microenvironment may play an important role in upregulating the expression of the angiogenic factor VEGF and tumor angiogenesis in NSCLC and explains, in part, the adverse prognostic effect of COX‐2 overexpression in patients with NSCLC. © 2005 Wiley‐Liss, Inc.

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Section: Discussionsupporting

confidence: 65%

Total cyclooxygenase‐2 mRNA levels correlate with vascular endothelial growth factor mRNA levels, tumor angiogenesis and prognosis in non‐small cell lung cancer patients

Yuan

Shun

et al. 2005

Intl Journal of Cancer

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“…High MVD is associated with a poor outcome in this disease (Kumar-Singh et al, 1997;Edwards et al, 2001), in keeping with the results from similar studies in other solid tumours (Dickinson et al, 1994;Fox et al, 1994;Cox et al, 2000c). Furthermore, in other solid tumours, such as nonsmall cell lung cancer, novel biological staging systems are being developed, which contribute independently to TNM stage (Cox et al, 2000a;O'Byrne et al, 2001).…”

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confidence: 74%

Matrix metalloproteinases 2 and 9 (gelatinases A and B) expression in malignant mesothelioma and benign pleura

et al. 2003

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Matrix metalloproteinases (MMPs), in particular the gelatinases (MMP-2 and -9), play a significant role in tumour invasion and angiogenesis. The expression and activities of MMPs have not been characterised in malignant mesothelioma (MM) tumour samples. In a prospective study, gelatinase activity was evaluated in homogenised supernatants of snap frozen MM (n ¼ 35), inflamed pleura (IP, n ¼ 12) and uninflammed pleura (UP, n ¼ 14) tissue specimens by semiquantitative gelatin zymography. Matrix metalloproteinases were correlated with clinicopathological factors and with survival using Kaplan -Meier and Cox proportional hazard models. In MM, pro-and active MMP-2 levels were significantly greater than for MMP-9 (P ¼ 0.006, Po0.001). Active MMP-2 was significantly greater in MM than in UP (P ¼ 0.04). MMP-2 activity was equivalent between IP and MM, but both pro-and active MMP-9 activities were greater in IP (P ¼ 0.02, P ¼ 0.009). While there were trends towards poor survival with increasing total and pro-MMP-2 activity (P ¼ 0.08) in univariate analysis, they were both independent poor prognostic factors in multivariate analysis in conjunction with weight loss (pro-MMP-2 P ¼ 0.03, total MMP-2 P ¼ 0.04). Total and pro-MMP-2 also contributed to the Cancer and Leukemia Group B prognostic groups. MMP-9 activities were not prognostic. Matrix metalloproteinases, and in particular MMP-2, the most abundant gelatinase, may play an important role in MM tumour growth and metastasis. Agents that reduce MMP synthesis and/or activity may have a role to play in the management of MM.

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“…As expected, prolonged inflammation causes the level of COX-2 to increase, which is actually recognized as an important malignant mesothelioma prognostic factor (30,31). A recent study has clearly shown that COX-2 expression is a strong prognostic factor in human mesothelioma, which contributes independently to other clinical and histopathologic factors in determining short survival (31).Although the regulation of mRNA stability seems to be the most important regulatory step for COX-2 expression, several studies have reported that other mechanisms, such as transcriptional control or hypermethylation (32), are also involved in regulating COX-2 expression.…”

Section: Cyclooxygenasessupporting

confidence: 63%

Cyclooxygenase-2, Epidermal Growth Factor Receptor, and Aromatase Signaling in Inflammation and Mesothelioma

Nuvoli¹,

Galati²

2013

Molecular Cancer Therapeutics

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Malignant mesothelioma or mesothelioma is a rare form of cancer that develops from transformed cells originating in the mesothelium, the protective lining that covers many of the internal organs of the body. It is directly linked to asbestos exposure, which acts as a carcinogen by initiating the carcinogenic process. Because of their shape, asbestos fibers can cross the membrane barriers inside the body and cause inflammatory and fibrotic reactions. Such reactions are believed to be the mechanism by which asbestos fibers may trigger malignant mesothelioma in the pleural membrane around the lungs. Carcinogens are known to modulate the transcription factors, antiapoptotic proteins, proapoptotic proteins, protein kinases, cell-cycle proteins, cell adhesion molecules, COX-2, and growth factor signaling pathways. This article reviews recent studies regarding some malignant mesothelioma molecular targets not only for cancer prevention but also for cancer therapy.

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Angiogenesis is an independent prognostic factor in malignant mesothelioma

Cited by 108 publications

References 53 publications

Total cyclooxygenase‐2 mRNA levels correlate with vascular endothelial growth factor mRNA levels, tumor angiogenesis and prognosis in non‐small cell lung cancer patients

Total cyclooxygenase‐2 mRNA levels correlate with vascular endothelial growth factor mRNA levels, tumor angiogenesis and prognosis in non‐small cell lung cancer patients

Matrix metalloproteinases 2 and 9 (gelatinases A and B) expression in malignant mesothelioma and benign pleura

Cyclooxygenase-2, Epidermal Growth Factor Receptor, and Aromatase Signaling in Inflammation and Mesothelioma

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