tumor cells Archives - Amazing Health Advances

New Study Offers Possible Immunotherapy Breakthrough for Cancer

AHA Publisher — Mon, 25 Oct 2021 07:00:40 +0000

Jon Schiller via Israel21c – For cancer immunotherapy to be most effective, a patient’s immune system must be able to “see” the tumor in question. “Hotspots” on cancer cells’ outer membranes can provide this service. These molecular structures contain mutated peptides called neoantigens that the immune system’s T cells recognize as foreign – the first step in binding to the neoantigens and killing the cancerous cells. But only a handful of neoantigens qualify as hotspots. And they are hard to find because they are presented to the immune system by protein complexes that come in thousands of versions. The Weizmann Institute of Science’s Prof. Yardena Samuels and her PhD student Aviyah Peri led a team using bioinformatics to develop a method for identifying features common to many tumors. This can help develop effective immunotherapy for entire groups of patients. Their findings were published in the Journal of Clinical Investigation. The scientists applied algorithms to search through international databases of the genomes of thousands of cancer patients. Focusing on melanoma, the main cancer type studied by the Samuels lab, they looked for common mutations presented by common protein complexes. The search produced several neoantigens that could potentially be considered hotspots. Next, the scientists subjected these candidate molecules to laboratory analysis and investigated their interactions with T cells. Using this approach, the scientists identified a hotspot neoantigen derived from an oncogene known as RAS, which is involved in a third of all human cancers and 20% of melanoma cases. They and their colleagues isolated the T cell receptor that can recognize this hotspot neoantigen in melanoma tumors. They then engineered T cells from healthy individuals to express this receptor and incubated them with tumor samples from patients whose tumors displayed this hotspot. The T cells killed only those cells that displayed the neoantigen. “We’ve uncovered a neoantigen that is expressed in thousands of new melanoma cases every year, and we’ve shown that it can be used in these patients to mark tumor cells for immune destruction,” Peri said. “Our study suggests that our newly developed platform can lead to ‘off-the-shelf’ immunotherapies in which T cell receptors that recognize cancer hotspots can be prepared in advance, ready to be applied in groups of patients whose tumors have been shown to harbor these hotspots,” said Samuels. Also participating in the study were the late Prof. Nir Friedman of Weizmann’s Immunology Department, Prof. Masha Y. Niv of the Hebrew University of Jerusalem, Prof. Steven A. Rosenberg of the US National Cancer Institute, Prof. Cyrille J. Cohen of Bar-Ilan University, Dr. Ansuman T. Satpathy of Stanford University School of Medicine and other researchers. To read the original article click here.

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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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Breakthrough Discovery Could Turn Cancer into a Treatable Disease

AHA Publisher — Tue, 22 Sep 2020 07:00:45 +0000

University of Salford via News-Medical Net – Professor Michael Lisanti and Professor Federica Sotgia have made a discovery that could turn cancer into a treatable disease and remove the fear from a cancer diagnosis. Despite years of research and billions of pounds of investment, there are no MHRA/FDA-approved drugs for the prevention of metastasis. As a consequence, cancer metastasis remains a mysterious, untreatable, lethal disease. What is cancer metastasis? Metastasis is what happens when cancer cells spread throughout the body, most often to other organs, like the brain, bone tissue, the lungs and the liver. Metastasis, more often than not, turns cancer into an untreatable, terminal disease. No effective therapies are available. After surgical removal of the primary tumor, most cancer patients are treated with chemo-therapy and radiation to eradicate the remaining tumor cells that have been left behind, by incomplete surgical removal of cancerous lesions. Unfortunately, many cancer patients ultimately undergo tumour recurrence, resulting in distant metastasis (cancer spread). As a result, more than 90% of these patients that undergo treatment failure, die from metastatic disease. Therefore, the discovery of inhibitors of metastasis could turn cancer into a chronic treatable disease and remove the fear from a cancer diagnosis. In order to fill this knowledge gap and meet clinical needs, researchers at the University of Salford have identified that the Achilles’ heel of metastasis is ATP-depletion, which can be achieved by simply removing the cancer cell’s ability to make new energy. Professor Michael Lisanti and Professor Federica Sotgia, who both work in Translational Medicine at The University of Salford, have designed and tested new inhibitors of cancer metastasis that are based on an existing FDA-approved antibiotic, namely Doxycycline, first approved in 1967. They have now chemically modified Doxycycline, making it 5 times more potent for the targeting of metastatic cancer cells. Fortunately, this modification also renders Doxycycline ineffective as an antibiotic, effectively removing the risk for the development of antibiotic resistant bacteria and infections. In addition, they show that this new drug, which is named Doxy-Myr, to reflect that addition of a fatty acid, is also non-toxic in pre-clinical studies. “While this new family of drugs must now undergo clinical trials the work directly shows proof of concept that it is feasible to successfully design drugs that can prevent metastasis, by targeting the process of cellular energy production. Hence, cutting off the fuel supply, prevents metastasis. This breakthrough could ultimately change clinical practice, by adding metastasis prevention, as a new, more effective, weapon in the war on cancer. ” (Professor Michael Lisanti, University of Salford) To read the original article click here.

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Scientists Discover a Way to Stop the Spread of Devastating Childhood Cancer

AHA Publisher — Thu, 16 Jul 2020 07:00:55 +0000

University of East Anglia via EurekAlert – Researchers at the University of East Anglia and University of Manchester have made an important breakthrough that could lead to ‘kinder’ treatments for children with bone cancer, and save lives. Current treatment is gruelling, with outdated chemotherapy cocktails and limb amputation. But despite all of this, the five-year survival rate is poor at just 42 per cent – largely because of how rapidly bone cancer spreads to the lungs. New research published today identifies a set of key genes that drive bone cancer spread to the lungs in patients. In further experiments in mice with engineered human bone cancer cells that lack these key genes, the cancer cannot spread to the lungs. The research was led by Dr Darrell Green, from UEA’s Norwich Medical School and Dr Katie Finegan from the University of Manchester. Darrell was inspired to study childhood bone cancer after his best friend died from the disease as a teenager. Now, the team has made what could be the most important discovery in the field for more than 40 years. Dr Green said: “Primary bone cancer is a type of cancer that begins in the bones. It’s the third most common solid childhood cancer, after brain and kidney, with around 52,000 new cases every year worldwide. “It can rapidly spread to other parts of the body, and this is the most problematic aspect of this type of cancer. Once the cancer has spread it is very difficult to treat. “Around a quarter of patients have cancer that has already spread by the time they are diagnosed. Around half of patients with apparent localised disease relapse, with cancer spread detected later on. These figures have remained stagnant, with no significant breakthroughs in treatment, for more than four decades. “In high school, my best friend Ben Morley became ill with primary bone cancer. His illness inspired me to do something about it myself because during my studies I realised that this cancer has been all but left behind others in terms of research and treatment progress. So I studied and went through university and obtained my PhD to eventually work in primary bone cancer. “I want to understand the underlying biology of cancer spread so that we can intervene at the clinical level and develop new treatments so that patients won’t have to go through the things my friend Ben went through. Ultimately we want to save lives and reduce the amount of disability caused by surgery.” The research team investigated the most common type of primary bone cancer called osteosarcoma. The genetic drivers that cause osteosarcoma are well known (TP53 and RB1 structural variants) but much less is known about what drives its spread to other parts of the body. Dr Green said: “Because primary bone cancer spreads so fast to other parts of the body, it’s very important to solve exactly why this happens. “We developed new technology to isolate circulating tumour cells in the blood of patients. These cells are critical for scientific study because they effectively carry out the metastatic process. This was extremely challenging because there is only one such cell per billion normal blood cells – it took over a year to develop but we cracked it. “It was also challenging because most studies investigating circulating tumour cells are performed in common adult cancers where the methods significantly differ because the cancer biology is so different. “Osteosarcoma is a less common sarcoma cancer so we had to start from scratch to not only find these cells in the first place, but to keep them alive so we could profile their gene expression.” After profiling tumours, circulating tumour cells (CTCs) and metastatic tumours from patient donors, they were able to identify a potential driver for metastasis – known as MMP9. Dr Green said: “This driver that we identified is well known in cancer, but it is also considered ‘un-druggable’ because the cancer quickly becomes resistant to treatment, or it finds a way to escape being targeted. “So we thought we would try something a bit clever and find the ‘master regulator’ of MMP9 so that we could ‘action’ the ‘un-actionable’.” The team began collaborating with researchers at the University of Manchester who were working on the proposed master regulator of MMP9 – MAPK7 – in several cancers using mouse models including osteosarcoma. Together, they engineered human osteosarcoma cells to contain a silenced version of MAPK7. They found that when these cells were put into mice, the primary tumour grew much more slowly. Importantly, it didn’t spread to the lungs – even when the tumours were left to grow for a long time. “Getting even deeper, our study shows that silencing MAPK7 stopped metastasis because that gene pathway was hijacking a particular part of the immune system that caused the spread,” said Dr Green. “This is really important because not only do we now have a gene pathway associated with metastasis, we know that removing this gene pathway actually stops cancer spread in a live animal. And we also know how and why this is happening – through hijacking the immune system. “The next step already gearing up to take place is to silence this pathway in treatment form, now that we have shown how critical this pathway is. “If these findings are effective in clinical trials, it would no doubt save lives and improve quality of life because the treatment should be much kinder, compared to the gruelling chemotherapy and life changing limb amputation that patients receive today.” Senior author Dr Katherine Finegan from the University of Manchester said: “It has been great to work together with Darrell and the team at UEA. This is the first output from a new co-operative we have set up to tackle the significant unmet need that is finding an effective treatment once osteosarcoma has spread. This co-operative called OMeNet brings together researchers from across the UK to cohesively study the spread of osteosarcoma and expedite the discovery of new treatments. “Using Darrell’s genetic insights from patient material, we were able to validate their work in models of primary bone cancer. As a result, we have highlighted a potential new way to treat metastatic bone cancer by targeting a key protein that promotes metastases: MAPK7. This work has uncovered a novel treatment option for osteosarcoma, something we have not had for the last 40 years. “In the Finegan lab we are already in the process of developing new drugs against MAPK7, which we hope to implement for the benefit of primary bone cancer patients in the future. “We would also like to thank the charity Friends of Rosie who funded the work in the Manchester lab and support childhood cancer research here in the North West.” Super Strong Sophie One of the patients who donated tissue to the study was five-year-old ‘Super Strong’ Sophie Taylor from Norwich. She was first diagnosed with osteosarcoma in January 2018, and underwent surgery to amputate part of her leg, as well as chemotherapy. Sadly Sophie was taken to hospital with breathing difficulties a year after diagnosis at the beginning of January 2019, where her family were told there was extensive cancer in her lungs. She passed away on January 18, 2019. Sophie’s dad Alex Taylor said: “Sophie was diagnosed with Osteosarcoma in January 2018. Unfortunately it was in her lungs at the time it was found. “When we were informed necrosis from chemotherapy was low we embarked on finding additional options and were fortunate to come into contact with Dr Darrell Green. “We did not hesitate in offering Sophie’s tumour for research and to also have her DNA and RNA analysed to link it to additional drugs to pursue. It gave us hope and it was amazing to have Darrell fighting in our corner. “Unfortunately the way Sophie’s journey panned out we didn’t get to try the options we put on the table but we are extremely pleased that Sophie has been able to help in the way she did. “We will continue to support Darrell and the work he does and Sophie’s future charity will aim to support the continuation of bone cancer research so future Sophies get a better outcome. “We are delighted Darrell’s work is being recognised, he is a remarkable man and we are really grateful for his support during treatment, after treatment and since Sophie’s passing. He truly deserves the credit and recognition he receives. “Sophie was simply a child from out of this world, she demonstrated strength and courage beyond comprehension and deserved a much better outcome. She had her leg amputated, months of hard chemotherapy, nursed an awful wound from surgery and just got on with it, fulfilling a range of achievements including going to the top of Snowdon, playing football with and becoming close friends Leicester City’s James Maddison, and she inspired many people around the world. We are so proud of how she fought and even more so that she has contributed to research which will be lifesaving for future children. “We will add this to her legacy and share it with pride and will continue to ‘takeasophie’ and stick our tongue out at cancer just like Sophie did. Thank you Darrell and well done that your immense hard work is paying off, we are very proud of you.” To read the original article click here.

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Scientists Discover Molecule That Destroys Pancreatic Cancer Cells

AHA Publisher — Wed, 04 Dec 2019 08:00:15 +0000

Abigail Klein Leichman via Israel21c – Israeli breakthrough study shows 90% reduction of pancreatic cancer cells in mice after treatment with a molecule named PJ34. A little molecule named PJ34 can cause cancer cells to self-destruct, according to an Israeli study published recently in the biomedical journal Oncotarget. Prof. Malka Cohen-Armon and her team at Tel Aviv University’s Sackler Faculty of Medicine did their experiment using xenografts — transplantations of human pancreatic cancer into mice. The mice’s immune systems were compromised so that their bodies wouldn’t reject the transplanted cells. In collaboration with Dr. Talia Golan’s team at the Cancer Research Center at Sheba Medical Center, the scientists injected PJ34 into the mice for 14 days in a row. PJ34 originally was developed to treat stroke. But it has been found to have a powerful effect on human cancer cells. The molecule causes something to go wrong during cell duplication, leading to rapid cell death. “In research published in 2017, we discovered a mechanism that causes the self-destruction of human cancer cells during their duplication (mitosis) without affecting normal cells,” explained Cohen-Armon. “We have now harnessed this information to efficiently eradicate human pancreatic cancer cells in xenografts.” Tumors Practically Disappeared A month after the molecule was administered, the number of cancer cells in the mice’s tumors were found to be reduced by 80 to 90 percent. One mouse’s tumor completely disappeared. Cohen-Armon noted that the treated mice suffered no adverse effects from the PJ34 molecule regimen, nor did they experience changes in their weight or behavior. Also significant is that the PJ34 molecule exclusively interrupts the duplication of human cancer cells, leaving normal cells alone. Although PJ34 could work on other types of cancer cells, pancreatic cancer presents a pressing need. It’s the 12th most common cancer worldwide and the fourth leading cause of cancer death. This type of cancer is often resistant to existing treatments. Early diagnosis of pancreatic cancer is difficult, as often there are no symptoms. As a result, around 80 percent of patients are diagnosed at the metastatic stage and fewer than 3% of patients at the metastatic stage survive more than five years after diagnosis. Therefore, the Israeli research holds great potential for the development of a new effective therapy to treat this aggressive cancer in humans. It could also prove effective against aggressive forms of breast, lung, brain and ovarian cancer. The molecule PJ34 now is being tested in pre-clinical trials according to FDA regulations before larger animal trials and then human clinical trials can begin. Last June, ISRAEL21c reported on a multinational research study led by Golan demonstrating the effectiveness of new drug regimen for pancreatic cancer in people with BRCA mutations. To read the original article click here. For more articles from Israel21c click here.

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