Protective or pathogenic effects of vascular endothelial growth factor (VEGF) as potential biomarker in cerebral malaria

Canavese, Miriam; Spaccapelo, Roberta

doi:10.1179/2047773214y.0000000130

Cited by 24 publications

(18 citation statements)

References 67 publications

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“…VEGF plays a significant role in controlling the neoplastic angiogenic process. Recent studies have confirmed that VEGF promotes the growth of arterial, venous and lymphatic endothelial cells both in vitro and in vivo and promotes the survival and migration of endothelial cells (35,36). In our study, we demonstrated that Ad.RGD-ING4-PTEN inhibits CD34 and VEGF expression and reduces MVD in s.c. xenografted CNE human NPC tumors.…”

Section: Discussionsupporting

confidence: 76%

Adenovirus-mediated ING4/PTEN double tumor suppressor gene co-transfer modified by RGD enhances antitumor activity in human nasopharyngeal carcinoma cells

Wang

Yang

Sheng

et al. 2015

International Journal of Oncology

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Inhibitor of growth-4 (ING4) is a member of the inhibitor of growth (ING) family and acts as a tumor suppressor protein. PTEN is a phosphatase and shows potent and extensive antitumor activity. In this study, we constructed an RGD-modified bicistronic ING4/PTEN adenovirus (Ad.RGD-ING4-PTEN) and comprehensively investigated its effects following modification of the CNE human nasopharyngeal carcinoma cell line both in vitro and in vivo. We demonstrated that Ad.RGD-ING4-PTEN enhanced growth inhibition and apoptosis. Furthermore, expression of P21, Bax and cleaved caspase-3 was upregulated, while that of Bcl-2 and survivin was downregulated in CNE cells and CNE xenografted tumors. Moreover, Ad.RGD-ING4-PTEN treatment additively downregulated CD34, VEGF and microvessel density in subcutaneously (s.c.) xenografted CNE cell tumors. The enhanced antitumor activity generated by Ad.RGD-ING4-PTEN was closely associated with activation of the intrinsic and extrinsic apoptotic pathways and additive inhibition of tumor angiogenesis both in vitro and in vivo. On the basis of this evidence, it is believed that cancer gene therapy combining two tumor suppressors such as ING4 and PTEN can be used to establish an effective and novel therapeutic strategy for nasopharyngeal carcinoma and other cancers.

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Section: Discussionsupporting

confidence: 76%

Adenovirus-mediated ING4/PTEN double tumor suppressor gene co-transfer modified by RGD enhances antitumor activity in human nasopharyngeal carcinoma cells

Wang

Yang

Sheng

et al. 2015

International Journal of Oncology

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“…have demonstrated the ability of intracerebral antigen-specific CD8 + T to initiate central nervous system vascular leakage through a perforin-dependent mechanism involving VEGF, that down-regulates tight junction proteins 12–24 hours before activation of the apoptotic caspase cascade [ 64 ]. Notably, VEGF is increased in the brains of mice with ECM [ 65 ] and humans with CM [ 66 , 67 ] and has been shown to inhibit endothelial cell apoptosis [ 68 – 70 ]. This scenario provides a potential explanation for the rapid recovery from ECM and reestablishment of the vascular integrity that can occurs after administration of anti-malarial drugs, which would not be possible if vascular dysfunction was mediated through extensive loss of endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

Perivascular Arrest of CD8+ T Cells Is a Signature of Experimental Cerebral Malaria

et al. 2015

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There is significant evidence that brain-infiltrating CD8+ T cells play a central role in the development of experimental cerebral malaria (ECM) during Plasmodium berghei ANKA infection of C57BL/6 mice. However, the mechanisms through which they mediate their pathogenic activity during malaria infection remain poorly understood. Utilizing intravital two-photon microscopy combined with detailed ex vivo flow cytometric analysis, we show that brain-infiltrating T cells accumulate within the perivascular spaces of brains of mice infected with both ECM-inducing (P. berghei ANKA) and non-inducing (P. berghei NK65) infections. However, perivascular T cells displayed an arrested behavior specifically during P. berghei ANKA infection, despite the brain-accumulating CD8+ T cells exhibiting comparable activation phenotypes during both infections. We observed T cells forming long-term cognate interactions with CX3CR1-bearing antigen presenting cells within the brains during P. berghei ANKA infection, but abrogation of this interaction by targeted depletion of the APC cells failed to prevent ECM development. Pathogenic CD8+ T cells were found to colocalize with rare apoptotic cells expressing CD31, a marker of endothelial cells, within the brain during ECM. However, cellular apoptosis was a rare event and did not result in loss of cerebral vasculature or correspond with the extensive disruption to its integrity observed during ECM. In summary, our data show that the arrest of T cells in the perivascular compartments of the brain is a unique signature of ECM-inducing malaria infection and implies an important role for this event in the development of the ECM-syndrome.

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“…CM is diagnosed by the existence of P. falciparum and functional changes. There is no biological test available to confirm human CM 45 .…”

Section: Discussionmentioning

confidence: 99%

Indocyanine Green Liposomes for Diagnosis and Therapeutic Monitoring of Cerebral Malaria

et al. 2016

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Cerebral malaria (CM) is a major cause of death of Plasmodium falciparum infection. Misdiagnosis of CM often leads to treatment delay and mortality. Conventional brain imaging technologies are rarely applicable in endemic areas. Here we address the unmet need for a simple, non-invasive imaging methodology for early diagnosis of CM. This study presents the diagnostic and therapeutic monitoring using liposomes containing the FDA-approved fluorescent dye indocyanine green (ICG) in a CM murine model. Increased emission intensity of liposomal ICG was demonstrated in comparison with free ICG. The Liposomal ICG's emission was greater in the brains of the infected mice compared to naïve mice and drug treated mice (where CM was prevented). Histological analyses suggest that the accumulation of liposomal ICG in the cerebral vasculature is due to extensive uptake mediated by activated phagocytes. Overall, liposomal ICG offers a valuable diagnostic tool and a biomarker for effectiveness of CM treatment, as well as other diseases that involve inflammation and blood vessel occlusion.

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Protective or pathogenic effects of vascular endothelial growth factor (VEGF) as potential biomarker in cerebral malaria

Cited by 24 publications

References 67 publications

Adenovirus-mediated ING4/PTEN double tumor suppressor gene co-transfer modified by RGD enhances antitumor activity in human nasopharyngeal carcinoma cells

Adenovirus-mediated ING4/PTEN double tumor suppressor gene co-transfer modified by RGD enhances antitumor activity in human nasopharyngeal carcinoma cells

Perivascular Arrest of CD8+ T Cells Is a Signature of Experimental Cerebral Malaria

Indocyanine Green Liposomes for Diagnosis and Therapeutic Monitoring of Cerebral Malaria

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