APLN/APLNR Signaling Controls Key Pathological Parameters of Glioblastoma

Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults. GBM-expansion depends on a dense vascular network and, coherently, GBMs are highly angiogenic. However, new intratumoral blood vessels are often aberrant with consequences for blood-flow and vascular barrier function. Hence, the delivery of chemotherapeutics into GBM can be compromised. Furthermore, leaky vessels support edema-formation, which can result in severe neurological deficits. The secreted signaling peptide Apelin (APLN) plays an important role in the formation of GBM blood vessels. Both APLN and the Apelin receptor (APLNR) are upregulated in GBM cells and control tumor cell invasiveness. Here we summarize the current evidence on the role of APLN/APLNR signaling during brain tumor pathology. We show that targeting APLN/APLNR can induce anti-angiogenic effects in GBM and simultaneously blunt GBM cell infiltration. In addition, we discuss how manipulation of APLN/APLNR signaling in GBM leads to the normalization of tumor vessels and thereby supports chemotherapy, reduces edema, and improves anti-tumorigenic immune reactions. Hence, therapeutic targeting of APLN/APLNR signaling offers an interesting option to address different pathological hallmarks of GBM.

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Evidence for a Blood Ganglion Barrier in the Superior Cervical Ganglion of the Rat

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100053681 ◽

1982 ◽

Vol 40 ◽

pp. 204-204

Author(s):

D. M. DePace

Keyword(s):

Blood Vessels ◽

Superior Cervical Ganglion ◽

Peripheral Nerves ◽

Time Schedule ◽

Transmission Electron ◽

Cervical Ganglion ◽

The Central Nervous System ◽

Cervical Ganglia ◽

Capillary Circulation ◽

And Control

The majority of blood vessels in the superior cervical ganglion possess a continuous endothelium with tight junctions. These same features have been associated with the blood brain barrier of the central nervous system and peripheral nerves. These vessels may perform a barrier function between the capillary circulation and the superior cervical ganglion. The permeability of the blood vessels in the superior cervical ganglion of the rat was tested by intravenous injection of horseradish peroxidase (HRP). Three experimental groups of four animals each were given intravenous HRP (Sigma Type II) in a dosage of.08 to.15 mg/gm body weight in.5 ml of.85% saline. The animals were sacrificed at five, ten or 15 minutes following administration of the tracer. Superior cervical ganglia were quickly removed and fixed by immersion in 2.5% glutaraldehyde in Sorenson's.1M phosphate buffer, pH 7.4. Three control animals received,5ml of saline without HRP. These were sacrificed on the same time schedule. Tissues from experimental and control animals were reacted for peroxidase activity and then processed for routine transmission electron microscopy.

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Prevalence, awareness, treatment, and control of hypertension in Nigeria in 1995 and 2020: A systematic analysis of current evidence

Journal of Clinical Hypertension ◽

10.1111/jch.14220 ◽

2021 ◽

Author(s):

Davies Adeloye ◽

Eyitayo O. Owolabi ◽

Dike B. Ojji ◽

Asa Auta ◽

Mary T. Dewan ◽

...

Keyword(s):

Current Evidence ◽

Systematic Analysis ◽

And Control

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The Association of Human Herpesviruses with Malignant Brain Tumor Pathology and Therapy: Two Sides of a Coin

International Journal of Molecular Sciences ◽

10.3390/ijms22052250 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2250

Author(s):

Evita Athanasiou ◽

Antonios N. Gargalionis ◽

Fotini Boufidou ◽

Athanassios Tsakris

Keyword(s):

Brain Tumor ◽

Brain Tumors ◽

Comprehensive Evaluation ◽

Tumor Development ◽

Scientific Data ◽

Malignant Brain Tumor ◽

Direct Role ◽

Tumor Pathology ◽

Human Herpesviruses

The role of certain viruses in malignant brain tumor development remains controversial. Experimental data demonstrate that human herpesviruses (HHVs), particularly cytomegalovirus (CMV), Epstein–Barr virus (EBV) and human herpes virus 6 (HHV-6), are implicated in brain tumor pathology, although their direct role has not yet been proven. CMV is present in most gliomas and medulloblastomas and is known to facilitate oncomodulation and/or immunomodulation, thus promoting cancer cell proliferation, invasion, apoptosis, angiogenesis, and immunosuppression. EBV and HHV-6 have also been detected in brain tumors and high-grade gliomas, showing high rates of expression and an inflammatory potential. On the other hand, due to the neurotropic nature of HHVs, novel studies have highlighted the engagement of such viruses in the development of new immunotherapeutic approaches in the context of oncolytic viral treatment and vaccine-based strategies against brain tumors. This review provides a comprehensive evaluation of recent scientific data concerning the emerging dual role of HHVs in malignant brain pathology, either as potential causative agents or as immunotherapeutic tools in the fight against these devastating diseases.

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Normal cells repel WWOX-negative or -dysfunctional cancer cells via WWOX cell surface epitope 286-299

Communications Biology ◽

10.1038/s42003-021-02271-2 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Yu-An Chen ◽

Yong-Da Sie ◽

Tsung-Yun Liu ◽

Hsiang-Ling Kuo ◽

Pei-Yi Chou ◽

...

Keyword(s):

Cell Surface ◽

Cancer Cells ◽

Room Temperature ◽

Metastatic Cancer ◽

Normal Cells ◽

Tgfβ Receptor ◽

Membrane Type ◽

Cell Invasiveness ◽

And Control ◽

Metastatic Cancer Cells

AbstractMetastatic cancer cells are frequently deficient in WWOX protein or express dysfunctional WWOX (designated WWOXd). Here, we determined that functional WWOX-expressing (WWOXf) cells migrate collectively and expel the individually migrating WWOXd cells. For return, WWOXd cells induces apoptosis of WWOXf cells from a remote distance. Survival of WWOXd from the cell-to-cell encounter is due to activation of the survival IκBα/ERK/WWOX signaling. Mechanistically, cell surface epitope WWOX286-299 (repl) in WWOXf repels the invading WWOXd to undergo retrograde migration. However, when epitope WWOX7-21 (gre) is exposed, WWOXf greets WWOXd to migrate forward for merge. WWOX binds membrane type II TGFβ receptor (TβRII), and TβRII IgG-pretreated WWOXf greet WWOXd to migrate forward and merge with each other. In contrast, TβRII IgG-pretreated WWOXd loses recognition by WWOXf, and WWOXf mediates apoptosis of WWOXd. The observatons suggest that normal cells can be activated to attack metastatic cancer cells. WWOXd cells are less efficient in generating Ca2+ influx and undergo non-apoptotic explosion in response to UV irradiation in room temperature. WWOXf cells exhibit bubbling cell death and Ca2+ influx effectively caused by UV or apoptotic stress. Together, membrane WWOX/TβRII complex is needed for cell-to-cell recognition, maintaining the efficacy of Ca2+ influx, and control of cell invasiveness.

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MS-1 Surgical strategy for brain tumor based on molecular and functional connectomics profiles

Neuro-Oncology Advances ◽

10.1093/noajnl/vdaa143.008 ◽

2020 ◽

Vol 2 (Supplement_3) ◽

pp. ii2-ii2

Author(s):

Tatsuya Abe

Keyword(s):

Overall Survival ◽

Brain Tumor ◽

Standard Procedure ◽

Awake Craniotomy ◽

Surgical Strategy ◽

Neurological Deficits ◽

Cortical Mapping ◽

Photodynamic Diagnosis ◽

Tumor Surgery ◽

Brain Tumor Surgery

Abstract It is reported that the development of new perioperative motor deficits was associated with decreased overall survival despite similar extent of resection and adjuvant therapy. The maximum safe resection without any neurological deficits is required to improve overall survival in patients with brain tumor. Surgery is performed with various modalities, such as neuro-monitoring, photodynamic diagnosis, neuro-navigation, awake craniotomy, intraoperative MRI, and so on. Above all, awake craniotomy technique is now the standard procedure to achieve the maximum safe resection in patients with brain tumor. It is well known that before any treatment, gliomas generate globally (and not only focally) altered functional connectomics profiles, with various patterns of neural reorganization allowing different levels of cognitive compensation. Therefore, perioperative cortical mapping and elucidation of functional network, neuroplasticity and reorganization are important for brain tumor surgery. On the other hand, recent studies have proposed several gene signatures as biomarkers for different grades of gliomas from various perspectives. Then, we aimed to identify these biomarkers in pre-operative and/or intra-operative periods, using liquid biopsy, immunostaining and various PCR methods including rapid genotyping assay. In this presentation, we would like to demonstrate our surgical strategy based on molecular and functional connectomics profiles.

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Friend or Foe: Paradoxical Roles of Autophagy in Gliomagenesis

Cells ◽

10.3390/cells10061411 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1411

Author(s):

Don Carlo Ramos Batara ◽

Moon-Chang Choi ◽

Hyeon-Uk Shin ◽

Hyunggee Kim ◽

Sung-Hak Kim

Keyword(s):

Brain Tumor ◽

Glioblastoma Multiforme ◽

Cancer Biology ◽

Molecular Mechanisms ◽

Primary Brain Tumor ◽

Molecular Target ◽

Therapeutic Strategies ◽

Homeostatic Mechanism ◽

Cellular Context ◽

Cellular Components

Glioblastoma multiforme (GBM) is the most common and aggressive type of primary brain tumor in adults, with a poor median survival of approximately 15 months after diagnosis. Despite several decades of intensive research on its cancer biology, treatment for GBM remains a challenge. Autophagy, a fundamental homeostatic mechanism, is responsible for degrading and recycling damaged or defective cellular components. It plays a paradoxical role in GBM by either promoting or suppressing tumor growth depending on the cellular context. A thorough understanding of autophagy’s pleiotropic roles is needed to develop potential therapeutic strategies for GBM. In this paper, we discussed molecular mechanisms and biphasic functions of autophagy in gliomagenesis. We also provided a summary of treatments for GBM, emphasizing the importance of autophagy as a promising molecular target for treating GBM.

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Molecular Mechanisms of Drug Resistance in Glioblastoma

International Journal of Molecular Sciences ◽

10.3390/ijms22126385 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6385

Author(s):

Maya A. Dymova ◽

Elena V. Kuligina ◽

Vladimir A. Richter

Keyword(s):

Drug Resistance ◽

Brain Tumor ◽

Molecular Mechanisms ◽

Primary Brain Tumor ◽

Therapeutic Resistance ◽

Molecular Characteristics ◽

Blood Brain ◽

Conventional Radiation ◽

The Brain ◽

Made In

Glioblastoma multiforme (GBM) is the most common and fatal primary brain tumor, is highly resistant to conventional radiation and chemotherapy, and is not amenable to effective surgical resection. The present review summarizes recent advances in our understanding of the molecular mechanisms of therapeutic resistance of GBM to already known drugs, the molecular characteristics of glioblastoma cells, and the barriers in the brain that underlie drug resistance. We also discuss the progress that has been made in the development of new targeted drugs for glioblastoma, as well as advances in drug delivery across the blood–brain barrier (BBB) and blood–brain tumor barrier (BBTB).

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5′-AMP-activated protein kinase activity is elevated early during primary brain tumor development in the rat

International Journal of Cancer ◽

10.1002/ijc.25558 ◽

2010 ◽

Vol 128 (9) ◽

pp. 2230-2239 ◽

Cited By ~ 29

Author(s):

Taichang Jang ◽

Joy M. Calaoagan ◽

Eunice Kwon ◽

Steven Samuelsson ◽

Lawrence Recht ◽

...

Keyword(s):

Brain Tumor ◽

Protein Kinase ◽

Kinase Activity ◽

Tumor Development ◽

Primary Brain Tumor ◽

Protein Kinase Activity ◽

Amp Activated Protein Kinase

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Stereotactic Laser Interstitial Thermal Therapy for Recurrent High-Grade Gliomas

Neurosurgery ◽

10.1227/neu.0000000000001443 ◽

2016 ◽

Vol 79 (suppl_1) ◽

pp. S24-S34 ◽

Cited By ~ 25

Author(s):

Ian Lee ◽

Steven Kalkanis ◽

Constantinos G. Hadjipanayis

Keyword(s):

Thermal Therapy ◽

Neurological Deficits ◽

Current Evidence ◽

High Grade ◽

Medline Search ◽

Laser Interstitial Thermal Therapy ◽

Ablation Volume ◽

Treatment Paradigm ◽

High Grade Gliomas

Abstract BACKGROUND: The value of maximal safe cytoreductive surgery in recurrent high-grade gliomas (HGGs) is gaining wider acceptance. However, patients may harbor recurrent tumors that may be difficult to access with open surgery. Laser interstitial thermal therapy (LITT) is emerging as a technique for treating a variety of brain pathologies, including primary and metastatic tumors, radiation necrosis, and epilepsy. OBJECTIVE: To review the role of LITT in the treatment of recurrent HGGs, for which current treatments have limited efficacy, and to discuss the possible role of LITT in the disruption of the blood-brain barrier to increase delivery of chemotherapy locoregionally. METHODS: A MEDLINE search was performed to identify 17 articles potentially appropriate for review. Of these 17, 6 reported currently commercially available systems and as well as magnetic resonance thermometry to monitor the ablation and, thus, were thought to be most appropriate for this review. These studies were then reviewed for complications associated with LITT. Ablation volume, tumor coverage, and treatment times were also reviewed. RESULTS: Sixty-four lesions in 63 patients with recurrent HGGs were treated with LITT. Frontal (n = 34), temporal (n = 14), and parietal (n = 16) were the most common locations. Permanent neurological deficits were seen in 7 patients (12%), vascular injuries occurred in 2 patients (3%), and wound infection was observed in 1 patient (2%). Ablation coverage of the lesions ranged from 78% to 100%. CONCLUSION: Although experience using LITT for recurrent HGGs is growing, current evidence is insufficient to offer a recommendation about its role in the treatment paradigm for recurrent HGGs.

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