glioblastoma Archives - Amazing Health Advances

Sleeper Cells: Newly Discovered Stem Cell Resting Phase Could Put Brain Tumors to Sleep

AHA Publisher — Thu, 22 Jul 2021 07:00:18 +0000

Arizona State University via EurekAlert – Christopher Plaisier, an assistant professor of biomedical engineering in the Ira A. Fulton Schools of Engineering at Arizona State University, and Samantha O’Connor, a biomedical engineering doctoral student in the Plaisier Lab, are leading research into a new stage of the stem cell life cycle that could be the key to unlocking new methods of brain cancer treatment. Their work was recently published in the research journal Molecular Systems Biology. “The cell cycle is such a well-studied thing and yet here we are looking at it again for the umpteenth time and a new phase pops out at us,” Plaisier says. “Biology always has new insights to show us, you just have to look.” The spark for this discovery came through a collaboration with Patrick Paddison, an associate professor at the Fred Hutchinson Cancer Research Center in Seattle, and Dr. Anoop Patel, an assistant professor of neurological surgery at the University of Washington who is also involved in the Fred Hutchinson Cancer Research Center. Paddison’s team called upon Plaisier to help analyze their brain stem cell data characterized through a process called single-cell RNA sequencing. “That data turned out to be pretty amazing,” Plaisier says. “It mapped out into this beautiful circular pattern that we identified as all of the different phases of the cell cycle.” O’Connor developed a new cell cycle classifier tool — called ccAF, or cell cycle ASU/Fred Hutchinson to represent the collaboration between the two institutions — that takes a closer, “high-resolution” look at what’s happening within the growth cycles of stem cells and identifies genes that can be used to track progress through the cell cycle. “Our classifier gets deeper into the cell cycle because there could be pieces we’re capturing that have important implications for disease,” O’Connor says. When Plaisier and O’Connor used the ccAF tool to analyze cell data for glioma tumors, they found the tumor cells were often either in the Neural G0 or G1 growth state. And as tumors become more aggressive, fewer and fewer cells remain in the resting Neural G0 state. This means more and more cells are proliferating and growing the tumor. They correlated this data with the prognosis for patients with glioblastoma, a particularly aggressive type of brain tumor. Those with higher Neural G0 levels in tumor cells had less aggressive tumors. They also found that the quiescent Neural G0 state is independent of a tumor’s proliferation rate, or how fast its cells divide and create new cells. “That was an interesting finding from our results, that quiescence itself could be a different biological process,” Plaisier says. “It’s also a potential point where we could look for new drug treatments. If we could push more cells into that quiescent state, the tumors would become less aggressive.” Current cancer drug treatments focus on killing cancer cells. However, when the cancer cells are killed, they release cell debris into the surrounding area of the tumor, which can cause the remaining cells to become more resistant to the drugs. “So, instead of killing the cells, if we put them to sleep it could potentially be a much better situation,” Plaisier says. With their ccAF tool, they were also able to find new states at the beginning and end of the cell cycle that exist between the commonly known states. These are among the topics for their next phase of research. “We’re starting to think about ways to dig into those and learn more about the biology of the entry and exit from the cell cycle because those are potentially really important points where the cells will either go into the G1 state or G0,” Plaisier says. Figuring out what triggers a cell to enter the division cycle or remain in a G0 resting state could help understand the processes behind tumor growth. “The primary feature of any cancer is that the cells are proliferating,” Plaisier says. “If we could get in there and figure out what the mechanisms are, that might be a place to slow them down.” Plaisier and O’Connor are making the ccAF classifier tool open source and available in a variety of formats for anyone studying single-cell RNA sequencing data to ease into the process of studying cell cycles. To read the original article click here.

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Cure for Deadly Brain Cancer May Be on Its Way

AHA Publisher — Thu, 15 Apr 2021 07:00:16 +0000

Brian Blum via Israel21c – Glioblastoma is a particularly aggressive form of brain cancer, accounting for half of all primary brain cancers. It has a 40 percent survival rate after a year and just 5% after five years, even after surgery, radiation and chemotherapy. Researchers at Tel Aviv University have discovered a potential treatment, tested on mice and 3D lab models so far. If it works on humans, glioblastoma could become “chronic but manageable,” says Prof. Ronit Satchi-Fainaro, director of the university’s Cancer Biology Research Center and Cancer Research and Nanomedicine Laboratory. “It could even cure it completely.” What Satchi-Fainaro and her team discovered is that glioblastoma results in part from a failure in the brain’s immune system, which leads to the amplification of cancerous cell division. This immune system misstep is tied to the secretion of a protein called P-Selectin (SELP) which, when bound to the brain’s microglia immune cells, alters their function so that, rather than inhibiting the spread of cancer cells, they do the opposite. Since cells communicate with each other via proteins, the researchers investigated which proteins are secreted when the microglia encounter glioblastoma cells. They found that six proteins were overexpressed. Satchi-Fainaro next blocked each of the six proteins in turn, to see if one in particular was the main culprit in blocking the brain’s immune function. It was SELP that was disrupting the immune system and boosting the tumors. SELP normally helps cells – white blood cells in particular – travel inside the body. The problem is that “the encounter between glioblastoma cells and microglia cells causes them to express SELP in large quantities,” Satchi-Fainaro explains. That allows the cancer cells to travel and penetrate the brain tissue. The tumor “corrupts and reeducates” the microglia so that instead of defending the brain against cancer, it generates more SELP. But when SELP was inhibited, the tumor cells had a slower division rate, stopped migrating to the brain and were less invasive. The positive result (for the mice at least): the cancer’s progression in the brain was dramatically hindered. Dramatic Effects For the study, Satchi-Fainaro and her team modified hundreds of mice to give them glioblastoma. All the mice with tumors died within weeks. However, those given a chemical compound that blocks production of the SELP protein all recovered. The same effect was found on tumor cells taken from human patients and inserted into a 3D model of the human brain in a lab. ISRAEL21c profiled Satchi-Fainaro in our article on bio-convergence. where we looked at her work with 3D-printed tumors that allow cancer physicians to “try out” drugs on a perfect copy of the actual tumor. While addressing brain cancer was Satchi-Fainaro’s main goal in her glioblastoma study, another benefit has been discovered: Inhibiting SELP can ease the pain associated with sickle cell anemia. The next step is proving that inhibiting SELP is safe in humans. If so, Satchi-Fainaro hopes that approval of the treatment will be given quickly. “Glioblastoma patients need new treatments immediately,” she says. “Glioblastoma is the deadliest type of cancer in the central nervous system, accounting for most malignant brain tumors. It is aggressive, invasive, and fast-growing, making it resistant to existing treatments, with patients dying within a year of the cancer’s onset. Moreover, glioblastoma is defined as a ‘cold tumor’, which means that it does not respond to immunotherapeutic attempts to activate the immune system against it.” She adds: “Our treatment may be the needed breakthrough in the battle against the most daunting cancer of all. It is paving the way for a new therapy for a disease that hasn’t had anything new in terms of treatment over the last decade.” The study, published in the journal Nature Communications, was led by PhD student Eilam Yeini in collaboration with neurosurgeons from Tel Aviv Sourasky Medical Center, who supplied glioblastoma tissue samples removed during surgery. Neurosurgeons from Johns Hopkins University and the Lieber Institute in the United States supplied healthy brain tissue from autopsies. Satchi-Fainaro recently won the Youdim, Bruno, Humboldt and Kadar Family Awards for outstanding research in 2020. Her groundbreaking study was funded by the Israel Cancer Research Fund, the European Research Council, the Morris Kahn Foundation, the Israel Cancer Association and the Israel Science Foundation. To read the original article click here. For more articles from Israel21c click here.

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Innovative Genome Editing Treatment Destroys Cancer Cells

AHA Publisher — Tue, 08 Dec 2020 08:00:17 +0000

Abigail Klein Leichman via Israel21c – There’s been a lot of press about upcoming Covid-19 vaccines built with mRNA – genetic messengers that carry instructions to cells to make proteins to treat or prevent disease. This same technology was used to treat cancer in mice in the laboratory of Prof. Dan Peer, VP for R&D and head of the Laboratory of Precision Nanomedicine at the Shmunis School of Biomedicine and Cancer Research at Tel Aviv University. The novel lipid nanoparticle-based delivery system, called CRISPR-LNPs, carries mRNA that encodes for the enzyme Cas9. This enzyme acts as a molecular pair of scissors that snips the cancer cells’ DNA, effectively destroying them. The results of the study, funded by Israel Cancer Research Fund, were published November 18 in the Science Advances journal. “This is the first study in the world to prove that the CRISPR genome editing system can be used to treat cancer in a living animal effectively,” said Peer. “It must be emphasized that this is not chemotherapy. There are no side effects, and a cancer cell treated in this way will never become active again. The molecular scissors of Cas9 cut the cancer cell’s DNA, thereby neutralizing it and permanently preventing replication.” Peer and his team chose to test the technology on two of the deadliest cancers: glioblastoma and metastatic ovarian cancer. Glioblastoma is the most aggressive type of brain cancer, with a five-year survival rate of only 3%. A single treatment with CRISPR-LNPs doubled the average life expectancy of mice with glioblastoma tumors, improving their overall survival rate by about 30%. Ovarian cancer is the most lethal cancer of the female reproductive system; only a third of the patients survive this disease. Treatment with CRISPR-LNPs in a metastatic ovarian cancer mice model increased their overall survival rate by 80%. “The CRISPR genome editing technology, capable of identifying and altering any genetic segment, has revolutionized our ability to disrupt, repair or even replace genes in a personalized manner,” said Peer. “Despite its extensive use in research, clinical implementation is still in its infancy because an effective delivery system is needed to safely and accurately deliver the CRISPR to its target cells. The delivery system we developed targets the DNA responsible for the cancer cells’ survival. This is an innovative treatment for aggressive cancers that have no effective treatments today.” He said the research team now intends “to go on to experiments with blood cancers that are very interesting genetically, as well as genetic diseases such as Duchenne muscular dystrophy. It will probably take some time before the new treatment can be used in humans, but we are optimistic.” The researchers include, among others, Daniel Rosenblum, Anna Gutkin and Dinorah Friedmann-Morvinski from TAU; Dr. Zvi Cohen, head of neurosurgical oncology at Sheba Medical Center, Dr. Mark Behlke, CSO at Integrated DNA Technologies; and Prof. Judy Lieberman of Boston Children’s Hospital and Harvard Medical School. “Through Ramot, the technology transfer company of Tel Aviv University, we are already negotiating with international corporations and foundations, aiming to bring the benefits of genetic editing to human patients,” said Peer. To read the original article click here. For more articles from Israel21c click here.

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Brain Tumor Surgery that Pushes Boundaries Boosts Patients Survival

AHA Publisher — Fri, 28 Feb 2020 08:00:24 +0000

UCSF Helen Diller Family Comprehensive Cancer Center via NewsWise – Survival may more than double for adults with glioblastoma, the most common and deadly type of brain tumor, if neurosurgeons remove the surrounding tissue as aggressively as they remove the cancerous core of the tumor. Newswise — Survival may more than double for adults with glioblastoma, the most common and deadly type of brain tumor, if neurosurgeons remove the surrounding tissue as aggressively as they remove the cancerous core of the tumor. This discovery, reported in a retrospective study headed by researchers at UC San Francisco, is welcome news for those in the glioblastoma community, which celebrated its last breakthrough in 2005 with the introduction of the chemotherapy drug temozolomide. Removing the “non-contrast enhancing tumor” – so called because it does not light up on MRI when a contrast agent is injected into the vein – represents a paradigm shift for neurosurgeons, according to senior author and neurosurgeon Mitchel Berger, MD, director of the UCSF Brain Tumor Center. “Traditionally, the goal of neurosurgeons has been to achieve total resection, the complete removal of contrast-enhancing tumor,” said Berger, who is also affiliated with the UCSF Weill Institute for Neurosciences. “This study shows that we have to recalibrate the way we have been doing things and, when safe, include non-contrast-enhancing tumor to achieve maximal resection.” Some 22,850 Americans are diagnosed each year with glioblastoma – one of the most relentless adult cancers and one that may be best known for claiming the lives of senators John McCain and Edward Kennedy, and the son of Vice President Joe Biden. The average survival for the 91 percent of glioblastoma patients whose tumor is characterized by IDH-wild-type mutations is 1.2 years, according to a 2019 study. However, the remaining 9 percent have a type of glioblastoma classified as IDH mutant, with average survival of 3.6 years. In their study, which publishes in JAMA Oncology on Feb. 6, 2020, the researchers tracked the outcomes of 761 newly diagnosed patients at UCSF who had been treated from 1997 through 2017. The patients, whose average age was 60, were divided into four groups with varying risk based on age, treatment protocols, and extent of resections of both contrast-enhancing and non-contrast-enhancing tumor. This article has been modified. To read the original article click here.

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Scientists Breach Brain Barriers to Attack Tumors

AHA Publisher — Wed, 22 Jan 2020 05:38:18 +0000

Yale University via Science Daily – The brain is equipped with barriers designed to keep out dangerous pathogens. Researchers have now found a novel way to circumvent the brain’s natural defenses when they’re counterproductive. To read the original article click here.

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Neurons Promote Growth of Brain Tumor Cells

AHA Publisher — Sat, 28 Sep 2019 02:48:35 +0000

German Cancer Research Center via EurekAlert – Glioblastomas invade the healthy brain in a diffuse pattern like a fungal network. As a result, they cannot be completely removed by surgery, and they also survive intensive chemotherapy and radiotherapy. Glioblastomas are thus among the most dangerous tumors in humans; the average survival time is 15 months following the initial diagnosis. Joint press release by Heidelberg University Hospital and the German Cancer Research Center In a current paper published in the journal “Nature”, Heidelberg-based researchers and physicians describe how neurons in the brain establish contact with aggressive glioblastomas and thus promote tumor growth / New tumor activation mechanism provides starting points for clinical trials. Neurons transmit their signals to each other via synapses, fine cell projections with terminals that contact another neuron. Researchers and physicians at Heidelberg University Hospital, Heidelberg Medical Faculty, and the German Cancer Research Center (DKFZ) have now discovered that neurons in the brain form these kinds of direct cell-to-cell contacts with tumor cells of aggressive glioblastomas too, thus transmitting impulses to the cancer cells. The tumor benefits from this “input”: The activation signals are probably a driving force behind the tumor growth and the invasion of healthy brain tissue by tumor cells, as Frank Winkler, Thomas Kuner, and their teams discovered using special imaging methods. But there is also some good news: Certain substances can block the signal transmission in animal experiments. The results have just been published online in the journal “Nature”. Networks of Neurons and Tumor Cells Glioblastomas invade the healthy brain in a diffuse pattern like a fungal network. As a result, they cannot be completely removed by surgery, and they also survive intensive chemotherapy and radiotherapy. Glioblastomas are thus among the most dangerous tumors in humans; the average survival time is 15 months following the initial diagnosis. In 2015, the team led by Frank Winkler, head of the Research Group Experimental Neurooncology in the Clinical Cooperation Unit Neurooncology, discovered a cause of this resistance to treatment: The glioblastoma cells are connected to one another through long cell protrusions. They communicate through these connections, exchange substances that are relevant for their survival, and thus protect themselves from treatment-related damage. The current findings add a further piece of the puzzle to our understanding of this type of cancer: “The tumor cells are not only interconnected in the brain like neurons; they also receive direct signals from them,” explained Winkler, whose research group is affiliated with the University Hospital and the DKFZ. The researchers observed the growth of human glioblastomas that they had transferred to mice, and studied cell cultures with human neurons and tumor cells, and tissue samples from patients. To do so, they used a wide range of modern microscopy methods, which provide detailed three-dimensional images of the connections – only micrometers large – between neurons and tumor cells as well as showing their molecular structure and signals within the cells. Electrical recordings from tumor cells revealed electrical currents generating from the synaptic connections, which form the starting point for further processing of these signals in the tumor cells. “We were able to show that signal transmission from neurons to tumor cells does in fact work like stimulating synapses between the neurons themselves,” added Thomas Kuner, Director of the Department of Functional Neuroanatomy at the Institute for Anatomy and Cell Biology, where the synaptic connections were first discovered by Varun Venkataramani. “This project began with an observation in basic research. In close cooperation with our clinical partners, it has led to conceptually new insights which will allow new treatment approaches to be developed using targeted translational research.” A Fatal Mechanism – But One That Opens Up New Avenues for Treatment How exactly activation of the tumor cell ultimately leads to increased tumor growth and invasion of healthy areas of the brain by the glioma cells has yet to be clarified. It is clear that this mechanism can be blocked in animals, however. Possible methods include a significant reduction of brain activity (for example under general anesthesia), pharmacological interventions that interrupt binding of the neurotransmitters on the AMPA receptor, or blocking the AMPA receptor using genetic engineering. In all these cases, tumor spread became slower in animal experiments. “This mechanism is therefore an extremely interesting approach for drug development and future drug treatments,” neurooncologist Winkler emphasized. “Suitable substances have in fact already been approved that block the AMPA receptor and are used to treat other neurological diseases. These substances are promising candidates for clinical trials.” “The new results not only show what makes glioblastomas so aggressive, but also how they could be stopped. That is highly relevant from a translational point of view and paves the way for clinical studies,” commented Wolfgang Wick, Medical Director of the Neurology Department at Heidelberg University Hospital and head of the Clinical Cooperation Unit Neurooncology at DKFZ. “We are also extremely pleased that the work of our junior researcher Varun Venkataramani, who also works in clinical practice, has been acknowledged by a publication in such a prestigious journal as, Nature’.” The relevance of the results from Heidelberg has been confirmed by a paper from Stanford University, California, USA: Michelle Monje and her research team also found synaptic connections between neurons and tumor cells in currently untreatable pediatric brain tumors and also observed the treatment effects reported by the Heidelberg-based researchers. Both papers are being published in “Nature” simultaneously. To read the original article click here.

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