Can Zika Be Used To Fight Glioblastoma Brain Tumors?

MedicalResearch.com Interview with:

Milan G. Chheda, MD Assistant Professor  Department of Medicine  Oncology Division  Molecular Oncology  Department of Neurology Washington University School of Medicine in St. Louis

Dr. Chheda

Milan G. Chheda, MD
Assistant Professor
Department of Medicine
Oncology Division
Molecular Oncology
Department of Neurology
Washington University School of Medicine in St. Louis

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Glioblastoma is an extremely aggressive brain tumor. Most patients die in less than two years. A longstanding challenge has been killing tumor cells that are inherently resistant to our current therapies (radiation and chemotherapy). These cells, called cancer stem cells, are extremely hardy. A longstanding dream of oncologists has been to devise a way to find them and kill them. The public health epidemic in 2015 made Zhe Zhu, post-doctoral fellow in Jeremy Rich’s lab, wonder whether Zika virus could work on cancer stem cells, that share properties with stem cells in fetal brain. Zika virus doesn’t cause significant problems in adults.

We took a lesson from nature and tested Zika virus.

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Study Identifies CD70 as a Novel Glioblastoma Target

MedicalResearch.com Interview with:

Jianping Huang, MD, PhD Associate Professor Director of Clinical Laboratory Operations UF Brain Tumor Immunotherapy Program Department of Neurosurgery, University of Florida

Dr. Huang

Jianping Huang, MD, PhD
Associate Professor
Director of Clinical Laboratory Operations
UF Brain Tumor Immunotherapy Program
Department of Neurosurgery, University of Florida

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Identification and validation of molecules that are involved in tumor progression and reduced survival in glioma patients is the starting point for developing active, safe and effective therapy. Unfortunately, very few target molecules have been identified for the deadly disease of glioma up until recently. Our studies have identified that the molecule CD70 is ectopically expressed on gliomas and involved in promoting glioma progression. Our research shows that CD70 leads to a “double jeopardy” scenario in Glioblastoma (GBM) patients by promoting tumor aggressiveness and inhibiting our immune response to cancer. These results provide a strong scientific rationale to target CD70 using state-of-the-art therapeutic approaches, such as chimeric antigen receptor (CAR) T cell therapy.

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Stereotactic Radiation Therapy Achieves Superior Results in Some Brain Tumors

MedicalResearch.com Interview with:

Professor Rakesh Jalali, MD Professor of Radiation Oncology President, Indian Society of Neuro-Oncology Tata Memorial Parel, Mumbai India

Dr. Jalali

Professor Rakesh Jalali, MD
Professor of Radiation Oncology
President, Indian Society of Neuro-Oncology
Tata Memorial
Parel, Mumbai India 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Randomized controlled trials to test the efficacy of radiotherapy techniques are challenging to perform. High-precision conformal techniques such as stereotactic radiosurgery/radiotherapy, intensity modulated radiotherapy (IMRT) and particle therapy, etc have been incorporated into routine clinical practice including for brain tumors without always being supported by level-1 evidence.

We therefore conducted a prospective, randomized, controlled trial of stereotactic conformal radiotherapy compared to conventional radiotherapy in young patients with residual/progressive bening and low grade brain tumors requiring radiotherapy for optimal disease control.

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Computer Bests Neuroradiologists in Distinguishing Tumor Recurrence From Radiation Necrosis

MedicalResearch.com Interview with:

Dr. Pallavi Tiwari PhD Assistant Professor biomedical engineering Case Western Reserve University

Dr. Pallavi Tiwari

Dr. Pallavi Tiwari PhD
Assistant Professor biomedical engineering
Case Western Reserve University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: One of the biggest challenges in neuro-oncology currently is distinguishing radionecrosis, a side-effect of aggressive radiation, from tumor recurrence on imaging. Surgical intervention is the only means of definitive diagnosis, but suffers from considerable morbidity and mortality. The treatments for radionecrosis and cancer recurrence are very different. Early identification of the two conditions can help speed prognosis, therapy, and improve patient outcomes.

The purpose of this feasibility study was to evaluate the role of machine learning algorithms along with computer extracted texture features, also known as radiomic features, in distinguishing radionecrosis and tumor recurrence on routine MRI scans (T1w, T2w, FLAIR). The radiomic algorithms were trained on 43 studies from our local collaborating institution – University Hospitals Case Medical Center, and tested on 15 studies at a collaborating institution, University of Texas Southwest Medical Center. We further compared the performance of the radiomic techniques with two expert readers.

Our results demonstrated that radiomic features can identify subtle differences in quantitative measurements of tumor heterogeneity on routine MRIs, that are not visually appreciable to human readers. Of the 15 test studies, the radiomics algorithm could identify 12 of 15 correctly, while expert 1 could identify 7 of 15, and expert 2, 8 of 15.

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Insurance Status Affects Glioblastoma Survival

MedicalResearch.com Interview with:

Wuyang Yang, M.D., M.S. Research Fellow Department of Neurosurgery Johns Hopkins Hospital Baltimore, MD 21287

Dr. Wuyang Yang

Wuyang Yang, M.D., M.S.
Research Fellow
Department of Neurosurgery
Johns Hopkins Hospital
Baltimore, MD 21287

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The treatment for glioblastoma (GBM) patients involves a combined approach of surgery, radiation therapy and chemotherapy. Despite advancement in the therapeutic approaches for GBM, differing socioeconomic status result in disparities in health-care access, and may superimpose a significant impact on survival of glioblastoma patients. Insurance status is an indirect indicator of overall socioeconomic status of a patient, and has been shown to correlate with survival of patients with malignant tumor in other parts of the body. We conducted the first study to determine a relationship between different types of insurance and survival of GBM patients.

In our study of 13,665 cases of GBM patients, we found that non-Medicaid insured patients have a significant survival benefit over uninsured and even Medicaid insured patients. This is the first time a study describes this relationship in glioblastoma patients, and also the first to compare and quantify the likelihood of poor prognosis between different insurance categories. A difference in insurance coverage was also uncovered, and patients with insurance were more likely to be older, female, white, and married. In addition, we found that younger, female, married patients with smaller tumor size survive longer than other patients, which confirmed findings in existing literature.

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Soluble Aspirin May Be Able To Cross Blood-Brain Barrier To Attack Glioblastomas

MedicalResearch.com Interview with:

Dr Kieran Breen PhD Director of Research, Brain Tumour Research University of Portsmouth, UK

Dr. Kieran Breen

Dr Kieran Breen PhD
Director of Research, Brain Tumour Research
University of Portsmouth, UK

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: There is evidence that aspirin (acetyl salicylic acid) can be toxic to brain tumour cells. However, its existing preparations cannot readily enter the brain because the drug is a suspension rather than being completely soluble. Furthermore, there can be significant side effects associated with the existing form of the drug including gastric bleeding. The object of this research was to develop a new formulation of aspirin which is truly soluble. When combined with two other compounds, the drug enters the brain and can therefore target the tumour cells. This study also showed that aspirin can kill tumour cells without causing any damage to the normal nerve cells. Continue reading

Meningioma Risk Lower In Patients With High Blood Sugar and Diabetes

MedicalResearch.com Interview with:

Dr. Judith Schwartzbaum PhD Associate professor of epidemiology Ohio State's Comprehensive Cancer Center

Dr. Judith Schwartzbaum

Dr. Judith Schwartzbaum PhD
Associate professor of epidemiology
Ohio State’s Comprehensive Cancer Center

MedicalResearch.com: What is the background for this study?

Response: Meningioma is a slow-growing brain tumor that is associated with obesity. To further understand this risk we examined records of blood sugar levels within approximately 15 years before tumor diagnosis comparing blood sugar levels of people who developed meningioma to those in people who did not.

MedicalResearch.com:What are the main findings?

Response: To our surprise we found that risk of this tumor was lower in people with high levels of blood sugar and diabetes.

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Dog Genome Can Be Used To Identify Human Brain Tumor Genes

MedicalResearch.com Interview with:

Katarina Truvé PhD Swedish University of Agricultural Sciences and  Kerstin Lindblad-Toh Uppsala University

Dr. Katarina Truvé

Katarina Truvé PhD
Swedish University of Agricultural Sciences and
Kerstin Lindblad-Toh
Uppsala University

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Truvé: Gliomas are malignant brain tumors that are rarely curable. These tumors occur with similar frequencies in both dogs and humans. Gliomas in dogs are strikingly similar at the biological and imaging level to human tumor counterparts. Some dog breeds such as Boxer and Bulldog are at considerably higher risk of developing glioma. Since these breeds at high risk are recently related, they are most likely carrying shared genetic risk factors. Our goal was therefore to use the dog genome to locate genes that may be involved in the development of glioma in both dogs and humans. We found a strongly associated locus and identified three candidate genes, DENR, P2RX7 and CAMKK2 in the genomic region. We have shown that CAMKK2 is lower expressed in glioma tumors than normal tissue in both dogs and human, and it has been reported that the associated canine mutation in P2RX7 results in a decrease in receptor function.

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Anti-Hypertension Drug Prazosin May Inhibit Glioblastoma Brain Tumor Cells

MedicalResearch.com Interview with:

Hervé Chneiweiss MD PhD Bâtiment A3 pièce 336 Case courrier 2 Plasticité Gliale et Tumeurs cérébrales Neuroscience Paris Seine (directeur) Inserm/Université Pierre et Marie Curie

Dr. Herve Chneiweiss

Hervé Chneiweiss MD PhD
Bâtiment A3 pièce 336 Case courrier 2 Plasticité Gliale et Tumeurs cérébrales Neuroscience Paris Seine (directeur) Inserm/Université Pierre et Marie Curie

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Chneiweiss: Treatments available for glioblastoma — malignant brain tumors — have little effect. An international collaboration[1] led by the Laboratoire Neurosciences Paris-Seine (CNRS/ INSERM/UPMC)[2] tested active ingredients from existing medications and eventually identified one compound of interest, prazosin, on these tumors.

We chose to study the most common malignant tumors that develop from brain cells, glioblastomas, which represent the fourth most frequent cause of cancer deaths among adults and the second in children. This is due to the inefficacy of current treatments. Indeed, a glioblastoma can resist treatment and reawaken from a very small number of tumor cells called glioblastoma-initiating cells (GIC). It is these cells — whose characteristics and properties resemble those of stem cells — that were targeted in the study.

Rather than trying to discover new compounds, the team opted for repositioning existing drugs. In other words, we tested a collection of substances used for so long to treat other conditions that their patents have now fallen into the public domain[3]. This method makes it possible to develop new active ingredients cheaply and very rapidly. Twelve hundred compounds were thus tested on normal human neural stem cells and on glioblastoma-initiating cells from different aggressive tumors. Twelve of these compounds showed a toxic effect on GIC — and none on the normal neural stem cells. The most effective was prazosin. Tested in mice carrying glioblastoma-initiating cells, prazosin significantly reduced the size of tumors and prolonged survival of the mice by more than 50%.

[1] Including scientists from the Laboratoire d’Innovation Thérapeutique (CNRS/Université de Strasbourg), the Stanford University Institute for Stem Cell Biology and Regenerative Medicine (USA) and the Instituto Estadual do Cérebro Paulo Niemeyer in Rio de Janeiro (Brazil).

[2] This laboratory forms part of the Institut de Biologie Paris-Seine.

[3] Pharmaceutical compounds are protected by a patent for 20 years after their discovery. Because of the length of the clinical trials that are necessary before a drug can be put on the market, the duration of their patent protection does not normally exceed 10-15 years after a Marketing Authorization (MA) is granted.

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Dual Treatment Strategies Can Slow Glioblastoma Tumor Growth

MedicalResearch.com Interview with:

Rakesh K. Jain, Ph.D. A.W.Cook Professor of Radiation Oncology (Tumor Biology) Director, E.L. Steele Laboratory Department of Radiation Oncology Harvard Medical School and Massachusetts General Hospital Boston, MA 02114

Dr. Rakesh Jain

Rakesh K. Jain, Ph.D.
A.W.Cook Professor of Radiation Oncology (Tumor Biology)
Director, E.L. Steele Laboratory
Department of Radiation Oncology
Harvard Medical School and
Massachusetts General Hospital
Boston, MA    02114

MedicalResearch.com: What is glioblastoma and why is it difficult to treat?

Dr. Jain: Glioblastoma (GBM) is the most common malignant tumor of the brain, and remains highly lethal. The standard treatment consists of surgical removal followed by chemo-radiation and anti-angiogenic therapy with anti-vascular endothelial growth factor (VEGF) antibody. Unfortunately, glioblastoma cells invade the brain far from the original tumor mass. Hence, even with the best surgical techniques it is not possible to remove all tumor cells, as they are embedded in vital parts of the brain at the time of the surgery. As a result, even after multimodal therapies, most  glioblastoma patients succumb to their disease within 2 years. New approaches are desperately needed.

MedicalResearch.com: What is anti-angiogenic therapy and why is it used for glioblastoma?

Dr. Jain: One key feature ofglioblastomas is their highly abnormal, leaky and ineffective vasculature. This leads to brain swelling around the tumor and poor tumor blood perfusion, which in turn can render the tumors more aggressive. These vascular abnormalities are due to the uncontrolled overproduction in GBMs of angiogenic factors such as VEGF. Anti-angiogenic therapies using anti-VEGF agents can transiently “normalize” the GBM vasculature structure and function and reduce brain swelling, increase blood perfusion, and impact morbidity and survival. Unfortunately, even when this therapy is added to the standard therapy with surgery and chemo-radiation, GBM patients typically do not survive on average more than 1.5 years.

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