Pairing a newly developed gel with immunotherapy that was delivered to post-surgical mouse brains with glioblastoma, a highly malignant and deadly cancer, improved the immunotherapy’s effectiveness, report researchers from the University of North Carolina Lineberger Comprehensive Cancer Center and colleagues.
“We have shown here that in combination, LAU-0901/Avastin, ELV/LAU-0901, or ELV/Avastin had a synergistic effect in decreasing tumor growth by 69, 79, and 89%, respectively,” says Bazan. “We concluded that LAU-0901 and ELV combined with Avastin exert a more potent inhibition of glioblastoma multiforme progression than monotherapy. To our knowledge, this is the first study that demonstrates the efficacy of these novel therapeutic regimens in a model of glioblastoma multiforme and may provide the basis for future therapeutics in patients with GBM.”
Researchers from NUS Yong Loo Lin School of Medicine have discovered that the FDA-approved anti-fungal drug, sulconazole, exhibits anti-cancer properties towards glioblastoma cells. This was published in the latest issue of Science Advances. An in-depth investigation of this compound revealed that it competes with biotin (Vitamin H), an important co-factor for metabolic enzymes and modifier of histones, allowing it to inhibit the normal function of biotin-dependent metabolic enzymes and specific histone modification-associated gene expression. This compromises glioblastoma metabolism and epigenetics, thereby impairing the tumour growth and invasiveness of glioblastoma cells.
Gliomas are the most common type of brain tumor that occur in adults and children. Glioblastoma multiforme (GBM) is the most common, aggressive form of brain cancer in adults and is universally fatal. The current standard-of-care options for GBM include surgical resection, radiotherapy, and concomitant and/or adjuvant chemotherapy. One of the major challenges that impedes success of chemotherapy is the presence of the blood–brain barrier (BBB). Because of the tightly regulated BBB, immune surveillance in the central nervous system (CNS) is poor, contributing to unregulated glioma cell growth.
Glioblastoma multiforme (GBM) is an extremely aggressive primary human brain tumor. The median survival of GBM patients is 15 months in case of completing the modern complex treatment protocol. Chemotherapy can help to extend the life expectancy of patients. GBM treatment resistance is associated with cancer stem cells (CSCs). The present paper analyses the main reasons for ineffectiveness of the existing GBM treatment methods and suggests treating CSCs as a complex phenomenon, resulting from the coordinated interaction of normal stem cells and cancer cells (CCs) in immunosuppressive microsurroundings.
Gliomas are the most common type of brain tumor that occur in adults and children. Glioblastoma multiforme (GBM) is the most common, aggressive form of brain cancer in adults and is universally fatal. The current standard-of-care options for GBM include surgical resection, radiotherapy, and concomitant and/or adjuvant chemotherapy. One of the major challenges that impedes success of chemotherapy is the presence of the blood–brain barrier (BBB). Because of the tightly regulated BBB, immune surveillance in the central nervous system (CNS) is poor, contributing to unregulated glioma cell growth. This review gives a comprehensive overview of the latest advances in treatment of GBM with emphasis on the significant advances in immunotherapy and novel therapeutic delivery strategies to enhance treatment for GBM. View Full-Text
The researchers found that each of the neural transcription factors induced cell conversion to a different neuronal type. Neurog2 expression yielded the fastest and most efficient cell conversion. Based on the neurotransmitter released, majority of the cells expressing Neurog2 and NeuroD1 became glutamatergic neurons, while those expressing Ascl1 became GABAergic neurons, underscoring specific signaling influences of each factor.
Inhibition of miR-21 by the nanoparticles induced the expression of pro-apoptotic genes, such as PTEN and PDCD4, which enhanced tumor cell apoptosis. In addition, the expression of RAGE was suppressed by the nanoparticles, resulting in decreased levels of vascular endothelial growth factor in the tumor. The reduction of CD31-positive endothelial cells confirmed the anti-angiogenic effects of the nanoparticles. The results indicate that the intranasal delivery of the self-assembled nanoparticles of antagomir-21 and RAP is an efficient treatment of glioblastoma.
Diffuse intrinsic pontine glioma is one of the deadliest central nervous system tumours of childhood, with a median overall survival of less than 12 months. Convection-enhanced delivery has been proposed as a means to efficiently deliver therapeutic agents directly into the brainstem while minimising systemic exposure and associated toxic effects. We did this study to evaluate the safety of convection-enhanced delivery of a radioimmunotherapy agent targeting the glioma-associated B7-H3 antigen in children with diffuse intrinsic pontine glioma.
Implantation of biodegradable wafers near the brain surgery site to deliver anti-cancer agents which target residual tumor cells by bypassing the blood-brain barrier has been a promising method for brain tumor treatment. However, further improvement in the prognosis is still necessary. We herein present novel materials and device technologies for drug delivery to brain tumors, i.e., a flexible, sticky, and biodegradable drug-loaded patch integrated with wireless electronics for controlled intracranial drug delivery through mild-thermic actuation. The flexible and bifacially-designed sticky/hydrophobic device allows conformal adhesion on the brain surgery site and provides spatially-controlled and temporarily-extended drug delivery to brain tumors while minimizing unintended drug leakage to the cerebrospinal fluid. Biodegradation of the entire device minimizes potential neurological side-effects. Application of the device to the mouse model confirms tumor volume suppression and improved survival rate. Demonstration in a large animal model (canine model) exhibited its potential for human application.
The blood-brain barrier (BBB) is a critical biological structure that prevents damage to the brain and maintains its bathing microenvironment. However, this barrier is also the obstacle to deliver beneficial drugs to treat CNS (central nervous system) diseases. Many efforts have been made for improvement of delivering drugs across the BBB in recent years to treat CNS diseases. In this review, the anatomical and functional structure of the BBB is comprehensively discussed. The mechanisms of BBB penetration are summarized, and the methods and effects on increasing BBB permeability are investigated in detail. It also elaborates on the physical, chemical, biological and nanocarrier aspects to improve drug delivery penetration to the brain and introduces some specific drug delivery effects on BBB permeability.
An Ommaya reservoir is a quarter-sized, soft, plastic, dome-shaped device that is placed under your scalp. It’s connected to a catheter (thin, flexible tube) that’s placed in one of the ventricles in your brain (see Figures 1 and 2). Your ventricles are hollow spaces that make cerebrospinal fluid (CSF), which surrounds your brain and spinal cord.
The new experimental therapy significantly slowed down the growth of solid cancerous tumors in mice. The team, led by the labs of UC San Diego bioengineering professor Peter Yingxiao Wang and bioengineering professor emeritus Shu Chien, detailed their work in a paper published Aug. 12 in Nature Biomedical Engineering.
The treatment of GBM is a difficult and challenging task. In the past decade, although treatment of GBM has not shown significant improvements, discoveries and new strategies are emerging. The success of immunotherapy in other cancers, together with studies on the formation and mechanisms of cancer stem cells, and more explorations in overcoming the problem of crossing the BBB, may eventually bring new hope to the treatment of GBM.
In this week’s episode of the “First Opinion Podcast,” writer and philosopher Adam Hayden opens up about his experience as one of a minority of people with glioblastoma who live longer than 15 to 18 months. Just 7% of people diagnosed with this aggressive brain cancer are still alive five years after their diagnosis, a milestone Hayden hit in June.
Of all potential therapeutic strategies to date, virotherapy offers the greatest chance of counteracting each of the obstacles mounted by GBM. Virotherapy can xenogenize a tumor that is deft at behaving like “self”, triggering adaptive immune recognition in an otherwise immunologically quiet compartment. Viruses can also directly lyse tumor cells, creating damage and further stimulating secondary immune reactions that are detrimental to tumor growth. In this review, we summarize the basic immune mechanisms underpinning GBM immune evasion and the recent successes achieved using virotherapies.
Preclinical research from The University of Texas MD Anderson Cancer Center finds that although glioblastoma stem cells (GSCs) can be targeted by natural killer (NK) cells, they are able to evade immune attack by releasing the TFG-β signaling protein, which blocks NK cell activity. Deleting the TFG-β receptor in NK cells, however, rendered them resistant to this immune suppression and enabled their anti-tumor activity.
CAR-T-mediated immunotherapy for glioblastoma multiforme. The broad categories of immunotherapy include cancer vaccines, checkpoint inhibitors, oncolytic virus therapies, and chimeric antigen receptor (CAR) functionalized immune cell therapies. In this short chapter, we provide a brief view of the cell-based immunotherapy developed for GBM, with a focus on CAR-T cells.
The Company has received approval from the Israeli Ministry of Health to begin the Phase 1/2 portion of its study of its lead asset, EV101, designed to investigate the safety and efficacy of synthetic cannabidiol (CBD) when administered alone or in combination with clomiphene, concurrently with temozolomide, to treat patients suffering from recurrent or progressive glioblastoma (GBM). The study will be conducted at the Davidoff Institute of Oncology, Rabin Medical Center, in Israel under Principal Investigator Dr. Tali Siegal.
Glioblastoma multiforme (GBM) is the most fatal malignancy, and despite extensive treatment, tumors inevitably recur. This study aimed to identify recurrence-associated molecules in GBM. The gene expression profile GSE139533, containing 70 primary and 47 recurrent GBM tissues and their corresponding clinical traits, was downloaded from the Gene Expression Omnibus (GEO) database and used for weighted gene co-expression network analysis (WGCNA) and differentially expressed gene (DEG) analysis.
As Glioblastoma (GBM) Awareness Day approaches, we recognize that glioblastoma multiforme (GBM) is a challenging indication that has not received any new approved therapies in well over a decade. New innovations are creating opportunities for therapeutic research, and Worldwide Clinical Trials is poised to support development in GBM treatments. In this short video, Alaeddin Homsi, MS, BS, Executive Director for Oncology Project Management, discusses Worldwide’s increasing commitment to oncology research and its recent work supporting GBM studies, in particular.
In this review, we explore the mechanisms by which cancer cells, and especially GBM, can acquire resistance to treatment. We describe and discuss the concept of persister/tolerant cells that precede and/or accompany the acquisition of resistance. Persister/tolerant cells are cancer cells that are not eliminated by treatment(s) because of different mechanisms ranging from dormancy/quiescence to senescence. We discuss the possibility of targeting these mechanisms in new therapeutic regimen.
Early symptoms of brain tumours in adults are non-specific, and patients may present multiple times to primary care services before they are referred for investigation. Look for symptoms of raised intracranial pressure (such as headaches exacerbated by lying down, triggered by the Valsalva manoeuvre, or associated with vomiting or visual disturbance), combinations of symptoms (such as headache plus cognitive impairment, headache plus weakness, headache plus personality change), and symptoms that progress over time. New onset focal or generalised seizures in adulthood also warrant investigation for a brain tumour.
Twenty Nine Years ago, Yacobus Fitriyadi Kusdinata was diagnosed with a Glioblastoma Multiforme. He feels strongly that the best medication for him was not chemotherapy nor radiotherapy but exercise. “It has been over 19 years since my diagnosis. I feel great, I am healthy, I don’t take any medication, I just jog 15 km three times weekly”. – Yacobus Fitriyadi Kusdinata
Unlike other brain tumors that start in the body and spread to the brain, glioblastoma starts in the brain or spinal cord. Primary brain tumors are relatively rare, with fewer than 25,000 Americans diagnosed with them each year. Metastasized tumors, however, are more prevalent and an estimated 400,000 are diagnosed in the United States each year.
Houston Methodist Neurological Institute researchers from the department of neurosurgery shrunk a deadly glioblastoma tumor by more than a third using a helmet generating a noninvasive oscillating magnetic field that the patient wore on his head while administering the therapy in his own home. The 53-year-old patient died from an unrelated injury about a month into the treatment, but during that short time, 31% of the tumor mass disappeared. The autopsy of his brain confirmed the rapid response to the treatment.
Reactive oxygen and nitrogenous sources include endogenous (physiological processes), and exogenous sources contain reactive oxygen and nitrogen (xenobiotic interaction). The cellular oxidation/reduction shifts to oxidative stress when the regulation mechanisms of antioxidants are surpassed, and this raises the ability to damage cellular lipids, proteins, and nucleic acids.
Nanomaterials found in consumer and health-care products can pass from the bloodstream to the brain side of a blood-brain barrier model with varying ease depending on their shape - creating potential neurological impacts that could be both positive and negative, a new study reveals.
The Ivy Brain Tumor Center at Barrow Neurological Institute, a nonprofit translational research program, is conducting a Phase 0, first-in-human clinical trial of sonodynamic therapy (SDT) in ascending energy doses to assess safety and efficacy in patients with recurrent high-grade glioma. In this study, sonodynamic therapy is the combination of the drug SONALA-001 (5-ALA, aminolevulinic acid HCl, or ALA) and a Magnetic Resonance-Guided Focused Ultrasound device called the Exablate 4000 Type-2 Device. The goal of this study is to assess biological changes (tumor cell death) associated with the sonodynamic therapy.
Decisions in glioblastoma surgery are often guided by presumed eloquence of the tumor location. The authors introduce the “expected residual tumor volume” (eRV) and the “expected resectability index” (eRI) based on previous decisions aggregated in resection probability maps. The diagnostic accuracy of eRV and eRI to predict biopsy decisions, resectability, functional outcome, and survival was determined.