The expression of nitric oxide synthases in human brain tumours and peritumoral areas

Bakshi, A.; Nag, Tapas Chandra; Wadhwa, Sanjay; Mahapatra, Ashoka; Sarkar, Chitra

doi:10.1016/s0022-510x(97)00315-8

Cited by 43 publications

(25 citation statements)

References 17 publications

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“…The area adjacent to the tumor margin, where the angiogenic response has been observed, represents the invasion front into the neighboring tissue. In this area, differences in the level of various molecules involved in enhanced cell proliferation, edema and invasiveness have been observed (7)(8)(9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

Assessment of angiogenesis by CD105 and nestin expression in peritumor tissue of glioblastoma

et al. 2010

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Abstract. Angiogenesis in the peritumor tissue of glioblastoma (GBM) is still an open field of research. This study investigates neovascularization in the tumor surrounding areas by examining CD105 and nestin expression along with microvessel density (MVD) with the aim of establishing their possible prognostic significance. Angiogenesis was also confirmed by investigating, in vessel walls, the presence of pericytes, which are multipotent stem cells, expressing ·-smooth muscle actin (·-SMA). In our study, including 40 GBM patients, tissue samples were obtained from tumors (first area) and white matter at a distance <1 cm (second area) and between 1 and 3.5 cm (third area) from the tumor margin. CD105 and nestin were detected by immunohistochemistry in hyperplastic endothelium of GBM and peritumor tissue, and occasionally coexpressed or colocalized. Pericytes encircling hyperplastic endothelium were evident in all three areas. Univariate analysis revealed that patients with a CD105-MVD value ≥8 in the third area have a significantly shorter survival time and Cox analysis indicated an about 3.5-fold increase in death risk in the same patients. These results demonstrate that a tumor neoangiogenesis occurs in GBM peritumor tissue with intimate involvement of pericytes. CD105-MVD in the area located at a greater distance from the tumor margin carries prognostic significance.

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Section: Introductionmentioning

confidence: 99%

Assessment of angiogenesis by CD105 and nestin expression in peritumor tissue of glioblastoma

et al. 2010

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“…The expression of nNOS occurs in both the tumor and peritumoral areas of brain tumors (16). Indeed, tumors with high histological grades also present increased levels of nNOS expression (18,60).…”

Section: Discussionmentioning

confidence: 99%

“…However, nNOS and NO are also involved in brain diseases and cancer pathogenesis (14,15). In general, brain tumors and peritumoral areas express NOS, which improves the blood supply required for cancer development (16,17). NO formed by nNOS contributes to angiogenesis, vasodilation and vascular permeability, thus serving a role in tumor growing and malignancy (18).…”

Section: Introductionmentioning

confidence: 99%

Function of neuronal nitric oxide synthase enzyme in temozolomide-induced damage of astrocytic tumor cells

Resende

Titze‐de‐Almeida

2018

Oncol Lett

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Abstract. Astrocytic tumors, including astrocytomas and glioblastomas, are the most common type of primary brain tumors. Treatment for glioblastomas includes radiotherapy, chemotherapy with temozolomide (TMZ) and surgical ablation. Despite certain therapeutic advances, the survival time of patients is no longer than 12-14 months. Cancer cells overexpress the neuronal isoform of nitric oxide synthase (nNOS). In the present study, it was examined whether the nNOS enzyme serves a role in the damage of astrocytoma (U251MG and U138MG) and glioblastoma (U87MG) cells caused by TMZ. First, TMZ (250 µM) triggered an increase in oxidative stress at 2, 48 and 72 h in the U87MG, U251MG and U138MG cell lines, as revealed by 2',7'-dichlorofluorescin-diacetate assay. The drug also reduced cell viability, as measured by MTT assay. U87MG cells presented a more linear decline in cell viability at time-points 2, 48 and 72 h, compared with the U251MG and U138MG cell lines. The peak of oxidative stress occurred at 48 h. To examine the role of NOS enzymes in the cell damage caused by TMZ, N(ω)-nitro-L-arginine methyl ester (L-NAME) and 7-nitroindazole (7-NI) were used. L-NAME increased the cell damage caused by TMZ while reducing the oxidative stress at 48 h. The preferential nNOS inhibitor 7-NI also improved the TMZ effects. It caused a 12.8% decrease in the viability of TMZ-injured cells. Indeed, 7-NI was more effective than L-NAME in restraining the increase in oxidative stress triggered by TMZ. Silencing nNOS with a synthetic small interfering (si)RNA (siRNAnNOShum_4400) increased by 20% the effects of 250 µM of TMZ on cell viability (P<0.05). Hoechst 33342 nuclear staining confirmed that nNOS knock-down enhanced TMZ injury. In conclusion, our data reveal that nNOS enzymes serve a role in the damage produced by TMZ on astrocytoma and glioblastoma cells. RNA interference with nNOS merits further studies in animal models to disclose its potential use in brain tumor anticancer therapy.

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“…nNOS was significantly dominant in glial cells of gliomas. However, that NOS dense status becomes sparse in the peritumoral tissues [73]. NOSs of tumour cells, opposite to the healthy cells, synthesize predominantly superoxide and peroxynitrite, which generate oxidative stress [74].…”

Section: Roles Of Noss In Brain Cancersmentioning

confidence: 99%

Role of Nitric Oxide Synthase in Normal Brain Function and Pathophysiology of Neural Diseases

Dagdeviren¹

2017

Nitric Oxide Synthase - Simple Enzyme-Complex Roles

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Nitric oxide synthase has three isoforms; according to their roles and tissues or cells they are involved. Neuronal NOS (nNOS) takes place in neuronal signalling, endothelial NOS (eNOS) takes place in vasodilation and inducible NOS (iNOS) takes place in immune responses. nNOS and eNOS are dominant but all isoforms have various roles in the central nervous system. nNOS and eNOS separately or together works in healthy brain during cognitive processes and in unhealthy brain during the pathology of related diseases. These roles were shown by inhibitor applied or by transgenic animal model studies and also by investigating the diseases at the molecular level. Besides, it is possible to say that iNOS has roles in some neurological pathologies creating immune responses. Three different isoforms mainly serve in different systems so there are lots of researchers from various disciplines working collaterally not knowing the others related works about NOSs. Because of this, a comprehensive chapter will be valuable for neuroscientists working with either healthy or unhealthy brains. The purpose of this chapter is to gather an overview of NOSs duties during the normal processes of the brain like learning and memory formation and abnormal processes such as depression, schizophrenia and brain cancers.

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The expression of nitric oxide synthases in human brain tumours and peritumoral areas

Cited by 43 publications

References 17 publications

Assessment of angiogenesis by CD105 and nestin expression in peritumor tissue of glioblastoma

Assessment of angiogenesis by CD105 and nestin expression in peritumor tissue of glioblastoma

Function of neuronal nitric oxide synthase enzyme in temozolomide-induced damage of astrocytic tumor cells

Role of Nitric Oxide Synthase in Normal Brain Function and Pathophysiology of Neural Diseases

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