Clinical Significance of Serum Vascular Endothelial Growth Factor in Malignant Pleural Mesothelioma

Yasumitsu, Akihiro; Tabata, Chiharu; Tabata, Rie; Hirayama, Noriko; Murakami, Aki; Yamada, Shusai; Terada, Takayuki; Iida, Shinichiro; Tamura, Kazutoshi; Fukuoka, Kazuya; Kuribayashi, Kozo; Nakano, Takashi

doi:10.1097/jto.0b013e3181d2f008

Cited by 71 publications

(40 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In esophageal, pancreatic and colorectal cancer, VEGF overexpression was significantly correlated with poor patient prognosis, in accordance with other malignancies (23,24). In malignant pleural mesothelioma, the serum level of VEGF has been reported to be significantly correlated with poor survival of patients (25). Our study revealed that in patients with stage III NSCLC, overexpression of VEGF-A in NSCLC tumor tissue was significantly correlated with a decreased 5-year survival rate.…”

Section: Discussionsupporting

confidence: 84%

Significance of survivin expression: Prognostic value and survival in stage III non-small cell lung cancer

Wang

Liu

Yang

et al. 2012

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Abstract. This study was designed to determine the levels of survivin expression and identify its clinical significance as a prognostic factor for stage III non-small cell lung cancer (NSCLC). A total of 210 cases of stage III NSCLC were collected and the expression levels of survivin and vascular endothelial growth factor A (VEGF-A) in tumor tissues were investigated using immunohistochemistry (IHC).

show abstract

Section: Discussionsupporting

confidence: 84%

Significance of survivin expression: Prognostic value and survival in stage III non-small cell lung cancer

Wang

Liu

Yang

et al. 2012

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

show abstract

“…IL-8 is a member of the C-X-C chemokine family and has direct growth-potentiating and angiogenic effects on tumors. VEGF is a powerful mitogen for the vascular endothelium, and in patients with MPM, elevated serum levels of VEGF correlate with advanced disease stage and worse survival (45). It is reasonable to surmise that each of these factors has tumor-promoting effects in the tumor microenvironment.…”

Section: Discussionmentioning

confidence: 99%

Expression of Interleukin-4 Receptor Alpha in Human Pleural Mesothelioma Is Associated with Poor Survival and Promotion of Tumor Inflammation

Burt

Báder

Winter

et al. 2012

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: The origin and pathogenesis of malignant pleural mesothelioma (MPM) are closely aligned with inflammation. MPM tumors express interleukin-4 receptor a (IL-4Ra), the principal subunit of the IL-4 receptor. We set out to determine the biologic function and clinical relevance of IL-4Ra in human MPM.Experimental Design: Expression of IL-4Ra by human MPM tumors was determined by quantitative real-time PCR (n ¼ 37) and immunohistochemistry (n ¼ 52). Intracellular cytokine analysis of T-cellderived IL-4 was carried out on matched tumor and blood samples from eight patients with MPM. Four human MPM cell lines were used to determine the direct effects of IL-4 on MPM tumor cells.Results: High tumor mRNA expression of IL-4Ra was an independent predictor of poor survival in patients with epithelial MPM [HR, 3.13, 95% confidence interval (CI), 1.68-7.15; P ¼ <0.0001]. Ninetyseven percent of epithelial MPM tumors and 95% of nonepithelial MPM tumors expressed IL-4Ra protein by immunohistochemistry, and strong IL-4Ra staining correlated with worse survival in patients with epithelial histology (P ¼ 0.04). A greater percentage of tumor-infiltrating T cells produced IL-4 compared with matched blood T cells (21% AE 7% vs. 4% AE 2%, P ¼ 0.0002). In response to IL-4, human MPM cells showed increased STAT-6 phosphorylation and increased production of IL-6, IL-8, and VEGF, without effect on proliferation or apoptosis.Conclusions: Tumor expression of IL-4Ra is inversely correlated with survival in patients undergoing surgical resection for epithelial MPM. Tumor-infiltrating T cells in MPMs are polarized to produce IL-4 and may provide endogenous activation signals to MPM tumor cells in situ. The IL-4/IL-4 receptor axis is a potential therapeutic target in human MPM.

show abstract

“…Overexpression of VEGF is one of the characteristics of MMs (18). We demonstrated that patients with malignant pleural mesothelioma had higher VEGF levels in pleural effusion and serum than a non-malignant population who had been exposed to asbestos (19,20). VEGF-receptor 1 (VEGF-R1), VEGF-R2 and VEGF-R3 are tyrosine kinase receptors for VEGF and are expressed in MM (18,21).…”

Section: Frequent Deletion Of 3p211 Region Carrying Semaphorin 3g Anmentioning

confidence: 97%

Frequent deletion of 3p21.1 region carrying semaphorin 3G and aberrant expression of the genes participating in semaphorin signaling in the epithelioid type of malignant mesothelioma cells

Yoshikawa

Sato²,

Tsujimura

et al. 2011

Int J Oncol

View full text Add to dashboard Cite

Abstract. Array-based comparative genomic hybridization analysis was performed on 21 malignant mesothelioma (MM) samples (16 primary cell cultures and 5 cell lines) and two reactive mesothelial hyperplasia (RM) primary cell cultures. The RM samples did not have any genomic losses or gains. In MM samples, deletions in 1p, 3p21, 4q, 9p21, 16p13 and 22q were detected frequently. We focused on 3p21 because this deletion was specific to the epithelioid type. Especially, a deletion in 3p21.1 region carrying seven genes including SEMA3G was found in 52% of MM samples (11 of 14 epithelioid samples). The allele loss of 3p21.1 might be a good marker for the epithelioid MM. A homozygous deletion in this region was detected in two MM primary cell cultures. A heterozygous deletion detected in nine samples contained the 3p21.1 region and 3p21.31 one carrying the candidate tumor suppressor genes such as semaphorin 3F (SEMA3F), SEMA3B and Ras association (RalGDS/AF-6) domain family member 1 (RASSF1A). SEMA3B, 3F and 3G are class 3 semaphorins and inhibit growth by competing with vascular endothelial growth factor (VEGF) through binding to neuropilin. All MM samples downregulated the expression of more than one gene for SEMA3B, 3F and 3G when compared with Met5a, a normal pleura-derived cell line. Moreover, in 12 of 14 epithelioid MM samples the expression level of SEMA3A was lower than that in Met5a and the two RM samples. An augmented expression of VEGFA was detected in half of the MM samples. The expression ratio of VEGFA/SEMA3A was significantly higher in the epithelioid MMs than in Met5a, RMs and the non-epithelioid MMs. Our data suggest that the downregulated expression of SEMA3A and several SEMA3s results in a loss of inhibitory activities in tumor angiogenesis and tumor growth of VEGFA; therefore, it may play an important role on the pathogenesis of the epithelioid type of MM.

show abstract

Clinical Significance of Serum Vascular Endothelial Growth Factor in Malignant Pleural Mesothelioma

Abstract: Our data suggest that the VEGF serum concentration could be a useful marker for screening MPM among asbestos-exposed individuals and as a prognostic factor.

Cited by 71 publications

References 27 publications

Significance of survivin expression: Prognostic value and survival in stage III non-small cell lung cancer

Significance of survivin expression: Prognostic value and survival in stage III non-small cell lung cancer

Expression of Interleukin-4 Receptor Alpha in Human Pleural Mesothelioma Is Associated with Poor Survival and Promotion of Tumor Inflammation

Frequent deletion of 3p21.1 region carrying semaphorin 3G and aberrant expression of the genes participating in semaphorin signaling in the epithelioid type of malignant mesothelioma cells

Contact Info

Product

Resources

About