Inhibition of angiotensin II activity enhanced the anti-tumor effect of cyclooxygenase-2 inhibitors Via insulin-like growth factor I receptor pathway

Yasumaru, Masakazu; Tsuji, S.; Tsujii, Masahiko; Irie, Takanobu; Komori, Masato; Nishida, Tsutomu; Kakiuchi, Yohei; Kawai, Naoki; Iijima, Hideki; Murata, Hiroaki; Sasaki, Yutaka; Hayashi, Norio

doi:10.1016/s0016-5085(03)80280-9

Cited by 31 publications

(37 citation statements)

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“…Epidemiologic studies found a significant inverse correlation between cancer mortality and the treatment with and the duration of administration of ACE inhibitors (24). Experimental studies have shown that the angiotensin II/angiotensin II receptor system can influence tumor biology by promoting neoangiogenesis and by enhancing microvessel density in solid tumors (17,23,25), by promoting tumor cell proliferation (26,27), by promoting the remodeling of the interstitial matrix (28), and by modulating the local, peritumorous inflammatory reaction (29). Recently, we have shown that ACE is expressed locally in gastric cancer (4), and that the insertion/deletion gene polymorphism of the ACE gene influences tumor development (30), as well as metastatic behavior (5).…”

Section: Discussionmentioning

confidence: 99%

The Angiotensin II/Angiotensin II Receptor System Correlates with Nodal Spread in Intestinal Type Gastric Cancer

Röcken

Röhl

Diebler³

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

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We aimed to substantiate the putative significance of angiotensin II receptor type 1 (AT1R) and type 2 (AT2R) for gastric cancer biology by investigating the correlation of their expression with various clinicopathologic variables and patient survival. Local expression of AT1R, AT2R, and angiotensin-converting enzyme (ACE) was investigated by immunohistochemistry in tumor and corresponding nontumor specimens obtained from 100 patients with gastric cancer, and compared with the ACE insertion/deletion gene polymorphism. AT1R and AT2R were found in the tumor epithelial cells of 26 (26%) and 95 (95%) patients, respectively. AT1R was significantly more prevalent (P < 0.001) in intestinal type gastric cancer than in diffuse type gastric cancer. In intestinal type gastric cancer, its expression correlated with the N category (P = 0.009) and the International Union Against Cancer tumor stage (P = 0.024). AT1R + intestinal type gastric cancers had a larger number of lymph node metastases (P = 0.026), a higher International Union Against Cancer tumor stage (P = 0.032), and a shorter survival time (P = 0.009) than AT1RÀ tumors. Multivariate analysis with lymph nodes as a dependent variable showed that AT1R status and ACE-I/D gene polymorphism are independent risk factors. Irrespective of the genotype, AT1R+ gastric cancers had a relative risk of lymph node metastases of 4.40 (95% confidence interval, 1.30-14.86). When the ACE genotype was included, the relative risk of having lymph node metastases increased considerably in AT1R + tumors being heterozygous or homozygous for the ACE D allele (odds ratio, 19.00; 95% confidence interval, 1.45-248.24). Our study shows that AT1R and AT2R are expressed locally in gastric cancer and that the combination of AT1R expression and ACE I/D gene polymorphism correlates with nodal spread in intestinal type gastric cancer. (Cancer Epidemiol Biomarkers Prev 2007;16(6):1206 -12)

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Section: Discussionmentioning

confidence: 99%

The Angiotensin II/Angiotensin II Receptor System Correlates with Nodal Spread in Intestinal Type Gastric Cancer

Röcken

Röhl

Diebler³

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…The experimental studies have shown that the local reninangiotensin system can influence tumor biology in different ways: (a) by promoting neoangiogenesis and by enhancing microvessel density in solid tumors, which is critical for tumor growth and is mediated in part by the vascular endothelial growth factors (3 -5, 8, 9); (b) by promoting tumor cell proliferation (7,28); and (c) by promoting the remodeling of the interstitial matrix (i.e., the mould in which tumor cells grow; ref. 29).…”

Section: Discussionmentioning

confidence: 99%

“…Recently, it was shown experimentally that a combination therapy including ACE inhibitors may prove useful in cancer treatment (7). A large number of ACE inhibitors are available, which are inexpensive, well tolerated, and seem to reduce the risk of side effects of other chemotherapeutics (32).…”

Section: Discussionmentioning

confidence: 99%

The Number of Lymph Node Metastases in Gastric Cancer Correlates with the Angiotensin I–Converting Enzyme Gene Insertion/Deletion Polymorphism

Röcken

Lendeckel²,

Dierkes³

et al. 2005

Clinical Cancer Research

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Purpose: In the present study, we aimed to substantiate the putative significance of angiotensin I^converting enzyme (ACE) on gastric cancer biology by investigating the influence of its gene polymorphism on gastric cancer progression. Experimental Design: Genomic DNA was purified from peripheral blood mononuclear cells or tissue specimens. Amplified ACE gene fragments were separated on agarose gels. D or I alleles were identified by the presence of 190-or 490-bp fragments, respectively. Local expression of ACE was investigated by immunohistochemistry. Results: Twenty-four of 113 (21%) gastric cancer patients had the II, 57 (51%) the ID, and 32 (28%) the DD genotype. The distribution of the ACE genotypes did not differ significantly from the control group of 189 patients without gastric cancer. However, the ACE genotypes correlated with the number of lymph node metastases and the Unio Internationale Contra Cancrum (UICC) tumor stage. Patients with the II genotype had a highly significantly smaller number of lymph node metastases (P < 0.001) and a significantly lower UICC tumor stage (P = 0.01) than patients with the DD genotype. No correlation was found between tumor type, tumor location, local tumor growth, distant metastases, and the ACE genotype. The expression of ACE in gastric cancer was investigated by immunohistochemistry in 100 of 113 patients. ACE was expressed by endothelial cells in all (100%) specimens and by tumor cells in 56 (56%) specimens. Conclusions: Our study shows that ACE is expressed locally in gastric cancer and that the gene polymorphism influences metastatic behavior.

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“…Reduced prostaglandin biosynthesis through inhibition of COX-2 activity is thought to be the molecular basis for the chemopreventive effects of nonsteroidal anti-inflammatory drugs (NSAID) on colorectal carcinogenesis in both humans and rodents (21,22). Moreover, NSAIDs reportedly reduce IGF-IR expression in vitro and also inhibit IGF-II-stimulated growth and invasion in a dose-dependent manner (24).…”

Section: Introductionmentioning

confidence: 99%

Interplay of Insulin-Like Growth Factor-II, Insulin-Like Growth Factor-I, Insulin-Like Growth Factor-I Receptor, COX-2, and Matrix Metalloproteinase-7, Play Key Roles in the Early Stage of Colorectal Carcinogenesis

Nosho

Yamamoto

Taniguchi

et al. 2004

Clinical Cancer Research

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Inhibition of angiotensin II activity enhanced the anti-tumor effect of cyclooxygenase-2 inhibitors Via insulin-like growth factor I receptor pathway

Cited by 31 publications

References 0 publications

The Angiotensin II/Angiotensin II Receptor System Correlates with Nodal Spread in Intestinal Type Gastric Cancer

The Angiotensin II/Angiotensin II Receptor System Correlates with Nodal Spread in Intestinal Type Gastric Cancer

The Number of Lymph Node Metastases in Gastric Cancer Correlates with the Angiotensin I–Converting Enzyme Gene Insertion/Deletion Polymorphism

Interplay of Insulin-Like Growth Factor-II, Insulin-Like Growth Factor-I, Insulin-Like Growth Factor-I Receptor, COX-2, and Matrix Metalloproteinase-7, Play Key Roles in the Early Stage of Colorectal Carcinogenesis

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