Category Archives: Transhuman News

Newswise The inflammasomea protein signaling network that is activated to rid the body of virus or bacteria-infected cellsmay play an important role in triggering an immune response to cancer and causing an existing class of drugs to work better against cancers.

A collaborative research study led by experts at the Johns Hopkins Kimmel Cancer Center and University of Maryland Marlene and Stewart Greenebaum Cancer Center, supported by Stand Up To Cancer and the Adelson Medical Research Foundation, found that the inflammasome imparts a DNA repair defect-like state in cancer cells. In laboratory and animal models of ovarian and breast cancer cells, it induced an immune activating signal that directly made the cells susceptible to treatment with drugs called PARP inhibitors, drugs that disable the cancer cells ability to repair DNA damage caused by anticancer therapies. As a result, the cancer cell dies.

The findings published online May 26 in the Proceedings of the National Academy of Sciences, appear to apply across multiple tumor types and create the potential for a wider use of PARP inhibitors.

Newswise In laboratory models, the researchers used the epigenetic drug 5-azacytidine to induce transcriptional BRCAness in two-thirds and one-third of ovarian and triple negative breast cancer cell lines tested. These BRCAness data were correlated with inflammasome activation in two cell lines, which demonstrated the most marked induction of BRCAness, explains Michael Topper, Ph.D., co-corresponding author on the study, Evelyn Grollman Glick Scholar and instructor in oncology at the Johns Hopkins Kimmel Cancer Center. Epigenetics refers to chemical alterations to the DNA of cells that can change gene behavior without mutating the DNA. The drug 5-azacityidine is classified as a demethylating agent because it blocks a chemical process known as DNA methylation and can restore function to some cancer suppressor genes. Ongoing research also studies the ability of this drug, and other epigenetic drugs, to prime cancer cells for a better response to immunotherapies.

We believe we have uncovered a novel relationship in which the drug not only primes the immune response but also causes the breast and ovarian cancer cells to act as if they have a BRCA mutation. We think this reveals a new mechanism that has not previously been linked to immune therapy response, says Topper.

Turning the inflammasome on with epigenetic therapy, makes cancer cells targets of the immune system and responsive to drugs known as PARP inhibitors, the researchers say. Specifically, it makes tumor cells that do not have BRCA mutations act like they do, says Feyruz Rassool, Ph.D., the senior corresponding author, professor of radiation oncology and co-director of Experimental Therapeutics Program at the University of Maryland Marlene and Stewart Greenebaum Cancer Center.

BRCA mutations alter the bodys ability to repair DNA, putting those affected at higher risk of developing breast, ovarian, pancreas and other cancers. However, cancersparticularly breast and ovarian cancersthat contain BRCA mutations often respond to treatment with PARP inhibitors, which disable the cancer cells ability to repair damage caused by anticancer drugs and radiation therapy.

This mutation is present in only a small percentage of patients with breast and ovarian cancers, and this is the only setting where PARP inhibitors have demonstrable clinical efficacy, says co-author Stephen Baylin, M.D., Virginia and D.K. Ludwig Professor for Cancer Research.

Using 5-azacytidine to make cancer cells, which do not have BRCA mutations act like they have the mutationsa situation the researchers refer to as BRCAnesssensitizes cancer cells to treatment with PARP inhibitors and may expand the benefit of the drug to more patients.

The relationships between the inflammasome in the tumor cells and diminished ability of the cells to repair DNA damage may apply to multiple common tumor types, says Baylin. In data obtained from The Cancer Genome Atlas, Topper showed the possibility that activating the inflammasome with 5-azacytidine could produce BRCAness in many common tumor types. Treating with drugs like 5-azacytidine could extend treatment to patients with a broad range of cancers. A clinical trial combining an inhibitor of DNA methylation and a PARP inhibitor in patients with breast cancers, which do not have BRCA mutations, has begun through Stand up to Cancer.

The researchers also explain that a pathway called STING (stimulator of interferon genes) is a key regulator of the inflammasome. STING, shown to convert cold tumors, or tumors that do not attract the attention of the immune system, into hot tumors, ones that are most likely to respond to immunotherapies. STING causes CD8+ T cells to traffic to tumors and, in animal models, made breast cancer cells more responsive to immune checkpoint inhibitors.

In a surprising twist, the work of the investigators could potentially shed light on a severe and deadly inflammatory process, called cytokine storm syndrome (CSS), occurring in SARS-CoV-2 infection, the researchers say. They hypothesize that overactivation of the inflammasome may be a key regulator of CSS, the most severe complication of COVID-19 infection. Topper, Rassool and Baylin are collaborating with an international consortium called COV-IRT (COVID-19 International Research Team), aimed at using an open science model to rapidly advance COVID-19 research and therapies. They hope to use their inflammasome discovery to study and develop a serum test to predict early which patients will develop the most severe COVID-19 infections and to look for existing drugs that could inhibit the inflammasome and stop CSS.

In addition to Topper, Rassool and Baylin, other investigators participating in the research included Lena McLaughlin, Lora Stojanovic, Aksinija Kogan, Julia Rutherford, Eun Yong Choi, Ying Zou and Rena Lapidus, from University of Maryland, and Ray-Whay Chiu Yen, and Limin Xia from the Johns Hopkins Kimmel Cancer Center.

The research was funded by the Van Andel InstituteStand up to Cancer, the Adelson Medical Research Foundation, Evelyn Grollman Glick Scholar, The Hodson Trust, the Leukemia Lymphoma Society, the Maryland Cigarette Restitution Fund Program, the National Cancer InstituteCancer Center Support Grant P30 CA134274 University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, the Molecular Medicine Graduate Program, University of Maryland, the Biochemistry Graduate Program, University of Maryland and the Human Genetics Graduate Program, University of Maryland, the Commonwealth Foundation, the Defense Health Program through the Department of Defense Ovarian Cancer Research Program, and Teal Innovator Award OC130454/ W81XWH-14-1-0385.

Excerpt from:
Activating Inflammasome May Improve Cancer's Response To Immunotherapy And Parp Inhibitors - Newswise

The Alexander Grass Humanities Institute (AGHI), in conjunction with Great Talk, Inc., hosted a panel of scientists to speak about the ethical considerations and implications of stem cell research on Oct. 21.

The event was moderated by Director of AGHI William Egginton. The four panelists included two experts in genomics research, a journalist who specializes in the role of technology in biomedical research and an expert in medical law.

Dr. Anthony Wynshaw-Boris, chair of the Department of Genetics and Genome Sciences at Case Western Reserve University School of Medicine, discussed how cell lines were cultivated as tools in the past for scientists to use to grow cell cultures to study diseases or develop vaccines. However, there wasnt as much debate about the development of these tools in the past as there is now.

These are scientific tools that we use. The political and social aspects... are arising today because of our polarization, Wynshaw-Boris said.

The panel had an in-depth conversation regarding the ethics of the use of scientific tools such as stem cell lines derived from fetal tissue, embryonic cells, abortion-derived cell lines and cells acquired without consent.

Dr. Eric Green, director of the National Human Genome Research Institute at the National Institutes of Health, argued that the investment that has been made in these cell lines to calibrate them for use in biomedical research cannot be ignored.

Should there be a halt on the use of that mature tool because of its origins that were created in a time when there was a different view? Green asked.

Antonio Regalado, senior editor for biomedicine at MIT Technology Review who writes about the impact of technology on medicine and biomedical research, responded to Greens query.

Regalado brought up the fact that makeup companies have been facing a lot of backlash recently for testing their products on animals. Regalado pointed out that makeup companies could then use a similar argument by saying that since they have already invested money in animal testing procedures, they should not have to find new, less harmful methods of testing.

I don't know that we should rule out the possibility of alternatives if the scientific community decides to put their minds to it. Perhaps an equivalent cell line could be developed, Regalado said.

Diane Hoffman, director of the Law and Health Care Program at the University of Maryland Francis King Carey School of Law, described various perspectives in debate over the ethical concerns of stem cell research.

The challenge, according to Hoffman, is striking a balance between implementing a blanket policy through the government and informing consumers to allow them to make ethical decisions.

Industry wanting innovation, and government wanting safety and efficacy, and consumers wanting access. Those three things are... how we consider these ethical issues, Hoffmann said.

The conversation then shifted to eugenics, the practice of editing human DNA to achieve specific, desirable characteristics, such as eliminating diseases, changing eye color or editing IQ.

Green described an initiative funded by the Human Genome Project, the Ethical, Legal and Social Implications Research Program (ELSI), which focuses on the ethical, legal and social implications of biomedical research.

We can meld together what is scientifically possible to what is the body of evidence of what has come out when we have looked at these ELSI issues and then have conversations... and try to come to consensus on what the guardrails should look like, Green said.

Hoffmann echoed Green, describing the need of the scientific community to also consider allocation of these resources.

Weve got a ways to go in terms of thinking about... how we can be more just in our allocation of medical resources and the benefits of the research were doing, Hoffmann said.

She brought up the idea of giving priority in receiving benefits to vulnerable populations that have been previously harmed by the health-care system.

Wynshaw-Boris added that each study that is conducted needs to address the ELSI considerations mentioned by Green.

Studies have to be done... in partnership with diverse populations, and we have to be committed to that, Wynshaw-Boris said. We have to make progress on it all the time, and that's what we have to be committed to.

The discussion concluded with a consensus among the panelists that the scientific community needs to address social and health inequities as advancements in genetics and genomic techniques continue to occur.

We have to bring more trust to science than exists now, Green said.

See the article here:
Panelists debate the implications and ethics of stem cell research - Johns Hopkins News-Letter

More than a century ago, in 1910, President William Howard Taft made what then seemed a bold but reasonable prediction: Within five years, he said, cancer will have been removed from the list of fatal maladies.

So, what happened?

Despite what seem like endless decades of hope, exhaustive research and unyielding effort by the worlds smartest scientists, we still have yet to find a cure or long-term treatments for cancer. But finally, we appear to be edging closer to the finish line, and immunotherapy might prove key.

For decades, the cancer treatment of choice has been chemotherapy. But, while chemotherapy can be incredibly effective at treating cancer, it takes a steep toll on human body. The side-effects of most chemotherapy treatments can be quite severe, and while the end result does often get rid of malignant cells, it also destroys plenty of healthy cells in the process.

Cancer is immensely complicated. Its not just one disease it can actually take over a hundred forms, and attack different parts of our body. Whats worse, what starts as one disease can mutate into something entirely different. Many tumors also contain more than one type of cancer cell.

Another challenge of treating cancer lies in the fact that there are great differences in patients physiologies, lifestyles, attitudes towards treatment, responses to treatment, genetic makeup and even epigenetic factors.

Cancer is as individual as the person who has it, explainsJoyce Ohm, PhD, at the Department of Cancer Genetics and Genomics at Roswell Park Cancer Institute in Buffalo, New York.

Lets say there are identical twin sisters, both with breast cancer. They may have been born with exactly the same genetic mutations, but one responds to therapy and one doesnt. One may live and one may die.

Its exceptionally difficult to find something that will work on everyone. Immunotherapy seeks to resolve this issue by personalizing treatments for each patient.

Immunotherapy isnt a new treatment by any means; scientists have been researching it for many years, and theyve invested a lot of time creating the right procedures and improving chances for all cancer patients.

The talk of immunotherapy started way back in 1890s, when William Coley, a physician, started researching how our immune system responds to viral infections. He hypothesized that scientists could jumpstart our natural immune response to cancer by provoking it with a controlled virus infection. But for years, little practical progress was made, and immunotherapy was viewed as having limited potential.

As crude as this method sounds, its basics eventually led scientists to explore how our own immune system responds to cancer and what can be done to target it without damaging other somatic cells. It also works on many types of cancers, even some that do not respond to chemotherapy or radiation.

Although immunotherapy is not yet as widely used assurgery,chemotherapy, orradiation therapy, immunotherapy drugs have been approved to treat many types of cancer. The one the doctor decides to use depends on the type of cancer they are tackling.

The main aim of immunotherapy today is to help activate dormant T-cells and help the immune system better recognize cancerous cells and get rid of them safely. T-cell transfer therapy basically attempts to re-engineer our immune response. Its a complicated process but so far it has shown great success. Other cancer immunotherapy treatments include immune checkpoint inhibitors that block certain chemicals in our body from stopping immune response to cancer cells; the use of cytokines, laboratory-made versions of a type of natural protein that boosts our immune response; lab-made monoclonal antibodies that bind to specific targets on cancer cells; and treatment vaccines.

The key in developing immunotherapies is finding the right cancer targets. Chow Kwan Ting, a researcher from City University of Hong Kong (CityU), who has won the famous Croucher Innovation Award in recognition of her scientific achievements, focuses on the role of plasmacytoid dendritic cells (pDCs) in cancer treatment.

These cells havent been researched thoroughly before, but theyre known to play an important part of immune systems response to viral infections. Dr. Chows studies have shown that pDCs play a role in other types of infections as well, and that they could potentially do more than simply fight off an infection: they might actually play a role in cancer immunity.

Other scientists are advancing a range of promising immunotherapies that researchers hope will lead to breakthrough cures. A team of researchers at the German Cancer Research Center and the Berlin Institute of Health are targeting the metabolic enzyme IL4I1 (Interleukin-4-Induced-1). The survival probability of patients with gliomas, a type of malignant brain tumor, decreased when the enzyme was present in higher concentrations in these tumors.

In 2004, Sophie Lucas, a researcher at the University of Louvain de Duve Institute, began studying the blocking of immune defenses in tumors in order to understand the functioning of cells that are said to be immunosuppressive (they block the bodys immune responses). The goal was to identify and remove them, thus stimulating antibodies to act against the tumor.Last August, Nature Communications published the results of the first tests carried out by Dr. Lucas and her team on a tool using what are called anti-GARP antibodies that prevent the bodys natural immune response from being blocked. It worked on mice; human studies are next.

Of course, more research is needed to turn immunotherapy research into potential cures, but the very fact that scientists keep learning new things about cancer treatment is encouraging. Scientists are looking into liver and breast cancer as they are more prevalent in Hong Kong than other types of cancer.

Immunotherapy can sometimes have similar side-effects as chemotherapy, such as nausea, vomiting and hair loss, but they are usually less severe. It can also be used in combination with radiation therapy or surgery.

Along with gene therapy and tumor DNA sequencing, immunotherapy is providing new options and helping us edge closer to promises made more than a century ago.

Claire Adams is a content creator and external associate of the City University of Hong Kong. Her goal is to promote CityU young scholars research papers that are closely related to the healthcare industry. She wishes to emphasise the importance of the research paper on rare cells and the innovative immunotherapeutic strategy, which truly brings hope to new cancer immunotherapy and vaccine. By promoting this work among the scientific and healthcare community, Claire is hoping to raise awareness of the City University of Hong Kongs contribution to society. Follow her on Twitter@adamsnclaire

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How immunotherapy is revolutionizing cancer care - Genetic Literacy Project