Glioblastoma

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For the Brain, Timing Is Everything

For decades the dominant approach to understanding the brain has been to measure how many times individual neurons activate during particular behaviors. In contrast to this “rate code,” a more recent hypothesis proposes that neurons signal information by changing the precise timing when they activate.

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Glioblastoma multiforme – an overview

Although the biology of glioblastoma multiforme has recently been widely investigated, the studies summarizing the knowledge of its development and treatment are still not sufficient in terms of comprehensive brain tumor analysis.

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Nomograms for predicting progression-free survival and overall survival after surgery and concurrent chemoradiotherapy for glioblastoma: a retrospective cohort study

Glioblastoma (GBM) is the most common malignant brain tumor in adults. The prognosis of GBM patients is poor. Even with active standard treatment, the median overall survival is only 14.6 months. It is therefore critical to ascertain recurrence and search for factors that influence the prognosis of GBM. This study aimed to screen the variables related to the progression-free survival (PFS) and overall survival (OS) of GBM patients undergoing surgery and concurrent chemoradiotherapy, as well as propose a nomogram for individual risk prediction based on preoperative imaging parameters and clinicopathological variables readily available in clinical practice.

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At the Frontiers of Human Glioblastoma: Challenges in Introducing New Therapeutic Strategies

Adult Glioblastoma is a highly aggressive malignant brain tumor. Although numerous mechanistic studies have revealed and underlined the unique behavior of Glioblastoma, still, only a few chemotherapeutics are used for its treatment. The standard procedure, which has not been modified in the last two decades, includes surgical resection followed by radiotherapy with concomitant temozolomide chemotherapy. Unfortunately, glioblastoma recurrence is extremely frequent, and the median patient survival remains 15 to 18 months from diagnosis. Problems with the introduction of new therapies, even as adjuvants, include the low penetration of anticancer drugs in the brain due to the blood–brain barrier, the high inter- and intra-tumor heterogeneity of glioblastoma cells, as well as their invasiveness and resistance to therapy. Many promising targeted therapies based on preclinical studies failed to prolong glioblastoma patient survival and the stagnation implementing new therapeutic strategies is evident. Therefore, new glioblastoma models that will improve our knowledge and allow investigation of new therapeutic strategies under conditions that mimic the situation in patients with high fidelity are demanded.

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Dose Escalated Radiotherapy for Glioblastoma Multiforme: An International Systematic Review and Meta-Analysis of 22 Prospective Trials

DE-RT alone resulted in superior PFS and OS vs. SoC-RT alone. DE-RT+TMZ did not lead to improved outcomes vs. SoC-RT+TMZ. No differential benefit based on MGMT status was found. Future studies are warranted to define which subgroups benefit most from DE-RT.

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Multiple strategies to improve the therapeutic efficacy of oncolytic herpes simplex virus in the treatment of glioblastoma

Oncolytic viruses have attracted widespread attention as biological anticancer agents that can selectively kill tumor cells without affecting normal cells. Although progress has been made in therapeutic strategies, the prognosis of patients with glioblastoma (GBM) remains poor and no ideal treatment approach has been developed. Recently, oncolytic herpes simplex virus (oHSV) has been considered a promising novel treatment approach for GBM.

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Is combined recognition the solution for CAR-T therapy against glioblastoma, other solid tumors?

CAR-T therapies that use engineered versions of patients' own immune cells to recognize cancer antigens have shown great efficacy in certain blood cancers. But they’ve been largely ineffective against solid tumors because of a lack of tumor-specific antigens and the tendency of CAR-Ts to wither in an immunosuppressive tumor microenvironment.

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The global race for a T cell receptor that zeros in on—and annihilates—solid tumors

So far, the Beijing-based research has been conducted only in animal models, but the research is a tantalizing step toward a new form of CAR T cell therapy for solid tumors, the subject of a worldwide race in recent years. The current form of treatment is composed of specially endowed cells that are engineered to destroy cancers of the blood. The emerging form of therapy promises the same powerful action—killing cancer cells, but this time from solid tumors while leaving healthy tissue unscathed.

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MGMT-Positive vs MGMT-Negative PatientsWith Glioblastoma: Identification of Prognostic Factors and Resection Threshold

The importance of the O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status as a predictive factor for the response to chemotherapy with temozolomide is well established. Its significance though at stratifying glioblastoma (GBM) patients in regard to their prognostic factors and the impact of surgical approach on them has not been identified.

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Researchers decipher the molecular underpinning of exceptional responses in glioblastoma patients

Despite access to some of the best possible medical care in the world, Senators John McCain and Edward Kennedy both died within 18 months of their diagnosis of glioblastoma, an aggressive form of brain cancer. While this deadly outcome typifies the nature of this disease, some glioblastoma patients see exceptional benefits from chemotherapy and survive beyond expectations. Why this happens has been revealed by researchers at the University of Minnesota in a new study published in the Proceedings of the National Academy of Sciences.

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Activating the brain’s immune system against the deadly cancer Glioblastoma prevents it from spreading

Groundbreaking research from Tel Aviv University may lead to a significant breakthrough in the battle against deadly brain cancer.

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Study: Chemotherapy to Treat Glioblastoma May Be More Effective During Morning

Patients with glioblastoma receiving temozolomide in the morning had an average overall survival of about 17 months, compared to an average overall survival of approximately 13.5 months for those taking the drug in the evening.

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Stem cell-based therapy treating glioblastoma multiforme

Due to their ability to preserve healthy tissues and to provide an effective and long-lasting response, stem cells (SCs) with tropism for tumour cells have attracted considerable attention in the scientific community. As is the case here, SCs can be used to target brain tumour cancer cells, especially high-grade malignant gliomas like GB, by overcoming the resistance and exerting benefits for patients affected with such lethal disease. Herein, we will discuss the research knowledge regarding SC-based therapy for the treatment of GB, focalising our attention on SCs and SC-released extracellular vesicles modified to express/load different antitumour payloads, as well as on SCs exploited as a diagnostic tool. Advantages and unresolved issues of anticancer SC-based therapy will also be considered.

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Optune + TMZ provided an unprecedented long-term survival benefit

Survival with Optune + TMZ vs TMZ alone was significantly higher at the 2-year landmark analysis and remained higher at 5 years

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“Zooming in” on Glioblastoma: Understanding Tumor Heterogeneity and its Clinical Implications in the Era of Single-Cell Ribonucleic Acid Sequencing

Glioblastoma (GBM) is the most common primary brain malignancy in adults and one of the most aggressive of all human cancers. It is highly recurrent and treatment-resistant, in large part due to its infiltrative nature and inter- and intratumoral heterogeneity. This heterogeneity entails varying genomic landscapes and cell types within and between tumors and the tumor microenvironment (TME). In GBM, heterogeneity is a driver of treatment resistance, recurrence, and poor prognosis, representing a substantial impediment to personalized medicine.

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Exploring Nanotech In Treating Glioblastoma

MGC Pharmaceuticals (MXC) has expanded its pre-clinical research program to explore the use of nanotechnology for treating glioblastoma multiforme (GBM). GBM is an aggressive type of brain tumor that spreads rapidly and has a low survival rate of just 6 percent four years on from a patient’s diagnosis.
The original in-vitro program was completed in November last year and tested two cannabinoid formulations on GBM tissues. The research showed that cannabidiol (CBD) slowed the tumor’s viability, while cannabigerol (CBG) impairs the tumor’s progression. Moreover, CBG can destroy glioblastoma stem cells, which are the root of cancer development and currently resistant to various treatments.

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Convection-enhanced drug delivery for glioblastoma: a review

Convection-enhanced delivery (CED) is a method of targeted, local drug delivery to the central nervous system (CNS) that bypasses the blood-brain barrier (BBB) and permits the delivery of high-dose therapeutics to large volumes of interest while limiting associated systemic toxicities. Since its inception, CED has undergone considerable preclinical and clinical study as a safe method for treating glioblastoma (GBM). However, the heterogeneity of both, the surgical procedure and the mechanisms of action of the agents studied-combined with the additional costs of performing a trial evaluating CED-has limited the field's ability to adequately assess the durability of any potential anti-tumor responses. As a result, the long-term efficacy of the agents studied to date remains difficult to assess.

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Blocking Cell Division in Glioblastoma

The findings suggest that a drug blocking this pathway could be combined with other brain tumor treatments to increase their effectiveness, according to Shi-Yuan Cheng, PhD, professor in the Ken and Ruth Davee Department of Neurology Division of Neuro-Oncology and senior author of the study.

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Glioblastoma multiforme: a review of where we have been and where we are going

Malignant gliomas such as glioblastoma multiforme (GBM) present some of the greatest challenges in the management of cancer patients worldwide, despite notable recent achievements in oncology. Even with aggressive surgical resections using state-of-the-art preoperative and intraoperative neuroimaging, along with recent advances in radiotherapy and chemotherapy, the prognosis for GBM patients remains dismal: median survival after diagnosis is about 14 months.

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New spherical nucleic acid ‘drug’ kills tumor cells in humans with glioblastoma

Early clinical trial shows experimental drug crosses blood-brain barrier to trigger death of brain tumor cells

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Nanotherapeutic penetrates blood-brain barrier, shows promise in glioblastoma

In a first-in-human trial, a nanotherapeutic, NU-0129, penetrated the blood-brain barrier after infusion into eight patients with recurrent glioblastoma, showing some efficacy and no severe side effects.

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Advances in drug delivery technology for the treatment of glioblastoma multiforme

Glioblastoma multiforme (GBM) is a particularly aggressive and malignant type of brain tumor, notorious for its high recurrence rate and low survival rate. The treatment of GBM is challenging mainly because several issues associated with the GBM microenvironment have not yet been resolved. These obstacles originate from a variety of factors such as genetics, anatomy, and cytology, all of which collectively hinder the treatment of GBM. Recent advances in materials and device engineering have presented new perspectives with regard to unconventional drug administration methods for GBM treatment.

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Systems approach to therapeutic combinations for glioblastoma

Delivering drugs to brain tumours is challenging due to the presence of the blood brain barrier – tightly packed cells that line the walls of the blood vessels in the brain. These cells allow only some substances such as water, oxygen and essential nutrients to pass through in order to protect the brain. However, it can have a negative affect when trying to treat a brain tumour as it will stop the treatment reaching the brain and, therefore, the tumour.

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Creating a safe CAR T-Cell therapy to fight solid tumors in children

Chimeric Antigen Receptor T-cell therapy -- CAR T -- has revolutionized leukemia treatment. Unfortunately, the therapy has not been effective for treating solid tumors including childhood cancers such as neuroblastoma. Preclinical studies using certain CAR T against neuroblastoma revealed toxic effects. Now, a group of scientists at Children's Hospital Los Angeles have developed a modified version of CAR T that shows promise in targeting neuroblastoma, spares healthy brain tissue and more effectively kills cancer cells. Their study was published today in Nature Communications. While this work is in the preclinical phase, it reveals potential for lifesaving treatment in children and adults with solid tumors.

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Creating a safe CAR T-Cell therapy to fight solid tumors in children

Chimeric Antigen Receptor T-cell therapy -- CAR T -- has revolutionized leukemia treatment. Unfortunately, the therapy has not been effective for treating solid tumors including childhood cancers such as neuroblastoma. Preclinical studies using certain CAR T against neuroblastoma revealed toxic effects. Now, a group of scientists at Children's Hospital Los Angeles have developed a modified version of CAR T that shows promise in targeting neuroblastoma, spares healthy brain tissue and more effectively kills cancer cells. Their study was published today in Nature Communications. While this work is in the preclinical phase, it reveals potential for lifesaving treatment in children and adults with solid tumors.

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