Inducible nitric oxide synthase expression correlates with angiogenesis, lymphangiogenesis, and poor prognosis in gastric cancer patients

Zhang, Wei; He, Xu; Ma, Yingyu; Wang, Hui-Ju; Xia, Yingjie; Zhao, Zhenze; Ye, Zai-yuan; Tao, Hou‐Quan

doi:10.1016/j.humpath.2010.09.020

Cited by 36 publications

(32 citation statements)

References 32 publications

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“…Since then, a few studies have demonstrated that HIF-1α expression was associated with not only poor clinical features but also patient survival 11, 21. In our study, we found that normal gastric tissues did not express HIF-1α, GLUT-1, and iNOS, although CA-9 was expressed in normal gastric mucosa, while HIF-1α, GLUT-1, and iNOS were overexpressed in GAs, which were all consistent with the findings of previous reports 12-15, 22. We also found that HIF-1α expression was well correlated with the expression of GLUT-1, CA-9 and iNOS.…”

Section: Discussionsupporting

confidence: 92%

“…We also found that HIF-1α expression was well correlated with the expression of GLUT-1, CA-9 and iNOS. Moreover, in accordance with earlier studies 11, 14, 15, 22, we clearly demonstrated that the expression of HIF-1α and GLUT-1 were significantly correlated with lymph node metastasis, and the expression of GLUT-1 and iNOS were significantly correlated with advanced stage. Our data suggest that HIF-1α activation induces GLUT-1, CA-9, and iNOS 3, 5, and that HIF-1α, GLUT-1, and iNOS may play an important role in promoting tumor development and dissemination.…”

Section: Discussionsupporting

confidence: 92%

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Clinicopathological Implications of the Expression of Hypoxia-related Proteins in Gastric Cancer

Jung¹,

Im²,

Jung³

et al. 2013

Int. J. Med. Sci.

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Objectives: Tumor hypoxia confers poor prognosis of a wide range of solid tumors due to increased malignancy, increased likelihood of metastasis and treatment resistance. The aim of this study was to assess the significance of the expression of HIF-1α and HIF-1α-inducible proteins in gastric cancer and their impact on prognosis. Materials and Methods: The expression of HIF-1α, GLUT-1, CA-9, and iNOS proteins was analyzed by immunohistochemistry in 193 gastric adenocarcinomas (GAs) and 20 normal gastric mucosa. Results: HIF-1α, GLUT-1, CA-9 and iNOS were expressed in 52.3%, 43.0%, 57.0%, and 43.0% of GAs, respectively, which are higher than the normal counterparts except for CA-9. HIF-1α expression was positively correlated with the expression of GLUT-1, CA-9 and iNOS. GLUT-1 expression was higher in the intestinal type (p = 0.012); however, iNOS expression was higher in the less-differentiated type and the diffuse type (p = 0.006, p = 0.032, respectively). The expression of HIF-1α and GLUT-1 was significantly correlated with lymph node metastasis (p = 0.009, p = 0.008, respectively), while the expression of GLUT-1 and iNOS was significantly correlated with the depth of invasion and advanced stage (p = 0.044, p = 0.004; p = 0.009, p = 0.008, respectively). Overall survival was shorter in patients with GLUT-1 expression than in those without GLUT-1 expression, which was statistically significant by univariate analysis (p = 0.042). On multivariate analysis, however, stage was determined as the only independent prognostic marker (p < 0.001). Conclusions: Our data suggest that overexpression of HIF-1α, GLUT-1, and iNOS may play an important role in gastric cancer progression. GLUT-1 is a potential candidate for predicting patient survival.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 92%

Clinicopathological Implications of the Expression of Hypoxia-related Proteins in Gastric Cancer

Jung¹,

Im²,

Jung³

et al. 2013

Int. J. Med. Sci.

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“…As mentioned earlier, Glynn has shown that NOS2 expression predicted poor survival of ER- breast cancer patients [12,147]. Zhang and Wang added that NOS2 expression also correlated with poor prognosis in gastric cancer patients and salivary gland adenoid cystic carcinoma [95,148]. Evidence supports the strategic combination of NOS2 with other relevant biomarkers, which could greatly improve the prognostic accuracy of various malignancies.…”

Section: Future For Diagnosismentioning

confidence: 91%

Gene expression profiles of NO- and HNO-donor treated breast cancer cells: insights into tumor response and resistance pathways

et al. 2014

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Nitric oxide (NO) synthase 2 (NOS2), a major inflammatory protein, modulates disease progression via NO in a number of pathologies, including cancer. The role of NOS2-derived NO is not only flux-dependent, which is higher in mouse vs. human cells, but also varies based on spatial and temporal distribution both within tumor cells and in the tumor microenvironment. NO donors have been utilized to mimic NO flux conditions and to investigate the effects of varied NO concentrations. As a wide range of effects mediated by NO and other nitrogen oxides such as nitroxyl (HNO) have been elucidated, multiple NO- and HNO-releasing compounds have been developed as potential therapeutics, including as tumor modulators. One of the challenges is to determine differences in biomarker expression from extracellular vs. intracellular generation of NO or HNO. Taking advantage of new NO and HNO releasing agents, we have characterized the gene expression profile of estrogen receptor-negative human breast cancer (MDA-MB-231) cells following exposure to aspirin, the NO donor DEA/NO, the HNO donor IPA/NO and their intracellularly-activated prodrug conjugates DEA/NO-aspirin and IPA/NO-aspirin. Comparison of the gene expression profiles demonstrated that several genes were uniquely expressed with respect to NO or HNO, such as miR-21, HSP70, cystathionine γ-lyase and IL24. These findings provide insight into targets and pathways that could be therapeutically exploited by the redox related species NO and HNO.

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“…7 The primary goal of this research is the early diagnosis of GC-related EMT by engineered nanoparticle molecular imaging. CD146 is found to be overexpressed in most of the gastric or gastroesophageal tumors, and in 50%-70% of esophageal cancers, it has been extensively used as a useful marker to evaluate the stage of GC.…”

Section: Introductionmentioning

confidence: 99%

Bio-functionalized dense-silica nanoparticles for MR/NIRF imaging of CD146 in gastric cancer

Wang¹,

Qu²,

Li³

et al. 2015

IJN

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Purpose Nano dense-silica ( d SiO 2 ) has many advantages such as adjustable core–shell structure, multiple drug delivery, and controllable release behavior. Improving the gastric tumor-specific targeting efficiency based on the development of various strategies is crucial for anti-cancer drug delivery systems. Methods Superparamagnetic iron oxide nanoparticles (SPION) were coated with d SiO 2 as core–shell nanoparticles, and labeled with near infra-red fluorescence (NIRF) dye 800ZW (excitation wavelength: 778 nm/emission wavelength: 806 nm) and anti-CD146 monoclonal antibody YY146 for magnetic resonance (MR)/NIRF imaging study in xenograft gastric cancer model. The morphology and the size of pre- and postlabeling SPION@ d SiO 2 core–shell nanoparticles were characterized using transmission electron microscopy. Iron content in SPION@ d SiO 2 nanoparticles was measured by inductively coupled plasma optical emission spectrometry. Fluorescence microscopy and fluorescence-activated cell sorter studies were carried out to confirm the binding specificity of YY146 and 800ZW–SPION@ d SiO 2 –YY146 on MKN45 cells. In vivo and in vitro NIRF imaging, control (nanoparticles only) and blocking studies, and histology were executed on MKN45 tumor-bearing nude mice to estimate the affinity of 800ZW–SPION@ d SiO 2 –YY146 to target tumor CD146. Results 800ZW–SPION@ d SiO 2 –YY146 nanoparticles were uniformly spherical in shape and dispersed evenly in a cell culture medium. The diameter of the nanoparticle was 20–30 nm with 15 nm SPION core and ~10 nm SiO 2 shell, and the final concentration was 1.7 nmol/mL. Transverse relaxivity of SPION@ d SiO 2 dispersed in water was measured to be 110.57 mM −1 ·s −1 . Fluorescence activated cell sorter analysis of the nanoparticles in MKN45 cells showed 14-fold binding of 800ZW–SPION@ d SiO 2 –YY146 more than the control group 800ZW–SPION@ d SiO 2 . Series of NIRF imaging post intravenous injection of 800ZW–SPION@ d SiO 2 –YY146 demonstrated that the MKN45 xenograft tumor model could be clearly identified as early as a time point of 30 minutes postinjection. Quantitative analysis revealed that the tumor uptake peaked at 24 hours postinjection. Conclusion This is the first successful study of functional nanoparticles for MR/NIRF im...

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Inducible nitric oxide synthase expression correlates with angiogenesis, lymphangiogenesis, and poor prognosis in gastric cancer patients

Cited by 36 publications

References 32 publications

Clinicopathological Implications of the Expression of Hypoxia-related Proteins in Gastric Cancer

Clinicopathological Implications of the Expression of Hypoxia-related Proteins in Gastric Cancer

Gene expression profiles of NO- and HNO-donor treated breast cancer cells: insights into tumor response and resistance pathways

Bio-functionalized dense-silica nanoparticles for MR/NIRF imaging of CD146 in gastric cancer

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