Abstract:Over the last seven decades, a significant scientific contribution took place in the delineation of the implications of vascular endothelial-derived growth factor (VEGF) in the processes of angiogenesis. Under pathological conditions, mainly in response to hypoxia or ischemia, elevated VEGF levels promote vascular damage and the growth of abnormal blood vessels. Indeed, the development of VEGF biology has revolutionized our understanding of its role in pathological conditions. Hence, targeting VEGF or VEGFmedi… Show more
“…VEGFR: GBM is a highly vascularized tumor and anti-angiogenic therapies have been widely investigated for its treatment [ 39 ]. VEGF is implicated in the process of angiogenesis [ 40 ]. It is activated in hypoxic conditions by translocation of hypoxia-inducible transcription factors (HIF1α and HIF1β) to the nucleus.…”
Section: Pathophysiology Of Gbm and Role Of Tksmentioning
Glioblastoma multiforme (GBM) is an aggressive brain tumor with high mortality rates. Due to its invasiveness, heterogeneity, and incomplete resection, the treatment is very challenging. Targeted therapies such as tyrosine kinase inhibitors (TKIs) have great potential for GBM treatment, however, their efficacy is primarily limited by poor brain distribution due to the presence of the blood–brain barrier (BBB). This review focuses on the potential of TKIs in GBM therapy and provides an insight into the reasons behind unsuccessful clinical trials of TKIs in GBM despite the success in treating other cancer types. The main section is dedicated to the use of promising drug delivery strategies for targeted delivery to brain tumors. Use of brain targeted delivery strategies can help enhance the efficacy of TKIs in GBM. Among various drug delivery approaches used to bypass or cross BBB, utilizing nanocarriers is a promising strategy to augment the pharmacokinetic properties of TKIs and overcome their limitations. This is because of their advantages such as the ability to cross BBB, chemical stabilization of drug in circulation, passive or active targeting of tumor, modulation of drug release from the carrier, and the possibility to be delivered via non-invasive intranasal route.
“…VEGFR: GBM is a highly vascularized tumor and anti-angiogenic therapies have been widely investigated for its treatment [ 39 ]. VEGF is implicated in the process of angiogenesis [ 40 ]. It is activated in hypoxic conditions by translocation of hypoxia-inducible transcription factors (HIF1α and HIF1β) to the nucleus.…”
Section: Pathophysiology Of Gbm and Role Of Tksmentioning
Glioblastoma multiforme (GBM) is an aggressive brain tumor with high mortality rates. Due to its invasiveness, heterogeneity, and incomplete resection, the treatment is very challenging. Targeted therapies such as tyrosine kinase inhibitors (TKIs) have great potential for GBM treatment, however, their efficacy is primarily limited by poor brain distribution due to the presence of the blood–brain barrier (BBB). This review focuses on the potential of TKIs in GBM therapy and provides an insight into the reasons behind unsuccessful clinical trials of TKIs in GBM despite the success in treating other cancer types. The main section is dedicated to the use of promising drug delivery strategies for targeted delivery to brain tumors. Use of brain targeted delivery strategies can help enhance the efficacy of TKIs in GBM. Among various drug delivery approaches used to bypass or cross BBB, utilizing nanocarriers is a promising strategy to augment the pharmacokinetic properties of TKIs and overcome their limitations. This is because of their advantages such as the ability to cross BBB, chemical stabilization of drug in circulation, passive or active targeting of tumor, modulation of drug release from the carrier, and the possibility to be delivered via non-invasive intranasal route.
“…We also applied VEGF from October 6, 2020, to February 26, 2021; in this interval, the patient exhibited improvements in verbal memory, executive function, and cognitive flexibility associated with the regeneration of MCA branches. Angiogenesis may be induced by VEGF in pathological conditions such as brain ischemia, as shown previously [12]. Progranulin may also play an important role in the recovery of memory and frontal lobe functions by enhancing the neurogenesis of the frontal and temporal lobes, as shown in a mouse model of ischemia [6,13].…”
Vascular dementia (VaD) is the second most prevalent cause of dementia in the world after Alzheimer’s disease (AD), but no curative treatment has yet been established. We treated a 70-year-old male Japanese VaD patient with Hashimoto’s thyroiditis using cytokine-induced neurogenesis and angiogenesis to regenerate residual neuronal stem cells and degenerated middle cerebral artery (MCA) branches. This treatment successfully regenerated the atrophied cerebral cortex, hippocampus, and degenerated MCA branches and was associated with improved cognitive function and the resolution of electrophysiological abnormalities. To the best of our knowledge, this is the first case report to demonstrate that cytokine-induced neurogenesis and angiogenesis reversed cognitive decline due to VaD.
“…Angiogenesis and abnormal microvessels are important links in the pathogenesis of PSO, particularly vascular changes that precede epidermal hyperplasia in PSO . Angiogenesis is closely related to the VEGF signaling pathway, especially the key target VEGFA . It has been reported that VEGFA could promote the aggravation of PSO, and targeting VEGFA signaling in the epidermis could prevent the continued development of PSO …”
Baicalin (BAI), the main active component of Scutellaria
baicalensis, has significant anti-inflammatory and
antibacterial effects. Echinacoside (ECH), an active component from Echinacea purpurea, has significant antiangiogenesis
and antioxidant effects. In previous studies, BAI or ECH has been
used for some skin inflammation problems by topical treatment. Psoriasis
(PSO) is a common inflammatory skin disease with typical features
such as excessive inflammatory response and vascular proliferation
in skin lesions. Because of the anti-inflammatory effect of BAI and
the antiangiogenic activity of ECH, it is proposed that the combination
of BAI and ECH can ameliorate psoriatic skin lesions better than a
single component. This study aims to explore the effects and potential
mechanisms of BAI combined with ECH on imiquimod (IMQ)-induced psoriatic
skin lesions by topical treatment. Transcriptome analysis first showed
that the TNF signaling pathway and the VEGF signaling pathway were
significantly enriched in IMQ-induced psoriatic skin lesions. Topical
application of BAI combined with ECH could ameliorate IMQ-induced
skin lesions in mice, especially the better effects of B2-E1 (BAI/ECH
= 2:1). Network pharmacology analysis and molecular docking indicated
that BAI-treated PSO on the skin by regulating the TNF signaling pathway,
and ECH treated PSO on the skin by regulating the VEGF signaling pathway.
Meanwhile, the ELISA test and the qPCR assay showed that BAI combined
with ECH could inhibit the expression of key cytokines and genes related
to the TNF signaling pathway and the VEGF signaling pathway. Zebrafish
experiments demonstrated the anti-inflammatory and antiangiogenic
effects of BAI combined with ECH and revealed the potential mechanisms
associated with regulating the inflammation-related TNF signaling
pathway and the angiogenesis-related VEGF signaling pathway. This
suggested that BAI combined with ECH may be a promising topical agent
to ameliorate psoriatic skin lesions in the future.
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