Monthly Archives: June 2017

MONDAY, June 5, 2017 (HealthDay News) -- Genetically tuning a person's own immune cells to target cancer appears to provide long-lasting protection against a blood cancer called multiple myeloma, an early trial from China shows.

The treatment, called CAR T-cell therapy, caused 33 out of 35 patients with recurring multiple myeloma to either enter full remission or experience a significant reduction in their cancer.

The results are "impressive," said Dr. Len Lichtenfeld, deputy chief medical officer for the American Cancer Society.

"These are patients who have had prior treatment and had their disease return, and 100 percent of the patients are reported to have had some form of meaningful response to these cells that were administered," Lichtenfeld said.

The new therapy is custom-made for each patient. Doctors collect the patient's own T-cells -- one of the immune system's main cell types -- and genetically reprogram them to target and attack abnormal multiple myeloma cells.

Lead researcher Dr. Wanhong Zhao likened the process to fitting immune cells with a GPS that steers them to cancer cells -- making them into professional killers that never miss their target.

Zhao is associate director of hematology at the Second Affiliated Hospital of Xi'an Jiaotong University in Xi'an, China.

CAR T-cell therapy is promising because the genetically altered T-cells are expected to roost in a person's body, multiplying and providing long-term protection, Lichtenfeld said.

"The theory is they should attack the tumor and continue to grow to become a long-term monitoring and treatment system," Lichtenfeld said. "It's not a one-shot deal."

The technology represents the next step forward in immunotherapy for cancer, said Dr. Michael Sabel, chief of surgical oncology at the University of Michigan.

"Immunotherapy is now really providing hope to a lot of patients with cancers that were not really responding to our standard chemotherapies," Sabel said.

CAR T-cell therapy previously has been used to treat lymphoma and lymphocytic leukemia, Lichtenfeld said.

Zhao and his colleagues decided to try the therapy to treat multiple myeloma. They re-engineered the patients' T-cells and then reintroduced them to the body in three infusions performed within one week.

Multiple myeloma is a cancer that occurs in plasma cells, which are mainly found in bone marrow and produce antibodies to fight infections. About 30,300 people will likely be diagnosed with multiple myeloma this year in the United States, researchers said in background notes.

"Multiple myeloma is a disease that historically was fatal in the course of a couple of years," Lichtenfeld said. During the past two decades, new breakthroughs have extended survival out 10 to 15 years in some patients, he noted.

To date, 19 of the first 35 Chinese patients have been followed for more than four months, researchers report.

Fourteen of those 19 patients have reached the highest level of remission, researchers report. There hasn't been a relapse among any of these patients, including five followed for more than a year.

"That's as far as you can go in terms of driving down the amount of tumor that's in the body," Lichtenfeld said.

Out of the remaining five patients, one experienced a partial response and four a very good response, researchers said.

However, about 85 percent of the patients experienced cytokine release syndrome (CRS), a potentially dangerous side effect of CAR T-cell therapy.

Symptoms of cytokine release syndrome can include fever, low blood pressure, difficulty breathing, and impaired organ function, the researchers said. However, most of the patients experienced only transient symptoms, and "now we have drugs to treat it," Lichtenfeld said.

History suggests the therapy will cost a lot if it receives approval, Lichtenfeld said. However, prior to approval, much more research will be needed, he added.

The Chinese research team plans to enroll a total of 100 patients in this clinical trial at four hospitals in China. They also plan a similar clinical trial in the United States by 2018, Zhao said.

The study was funded by Nanjing Legend Biotech Co., the Chinese firm developing the technology.

The findings were presented Monday at the American Society of Clinical Oncology annual meeting, in Chicago. Data and conclusions presented at meetings are usually considered preliminary until published in a peer-reviewed medical journal.

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Gene-Based Therapy May Thwart a Tough Blood Cancer - Sioux City Journal

Liver fibrosis is the excessive accumulation of scar tissue in the liver. It occurs when chronic damage to the liver causes inflammation and cell death, resulting in an accumulation of extracellular matrix proteins and a hardening of the liver. Diagnosis of the condition can be difficult, and treatment for advanced cases is often limited to liver transplantation. Previous work has identified that there is some genetic variation in response to liver damage and the development of liver fibrosis. Therefore, it is hoped that improvements in diagnostics and a better ability to predict prognosis could help to both identify those most at risk of fibrosis and prevent progression of the disease. A recently published study in Nature Genetics set out to identify the protein responsible for the genetic variations associated with liver inflammation and scarring. We spoke to Dr Mohammed Eslam, from the Westmead Institute, to learn more about the study and how this finding could help pave the future of diagnosis and treatment for patients.

Credit: Westmead Institute

ME: In 2015, we identified that common genetic variations associated with liver inflammation and fibrosis (scarring) were located on chromosome 19 between the IFNL3 and IFNL4 genes. However, the causative protein of this genetic area association with inflammation and fibrosis was obscure. This information was critical for any further trials to translate this finding into a potential therapeutic option. In our latest work, we discovered that IFN-3 is the causative protein of hepatic inflammation and fibrosis.

Full details of the study can be found here.

AM: What implications does this study have for the future treatment of liver fibrosis?

ME: Now that weve identified IFNL3 as the cause of liver scarring, we can work towards developing novel treatments specifically targeting this gene. This could be medicine targeting IFNL3 that is tailored to an individuals genetic makeup, but could also include modifying usual treatment depending on whether a patient has IFNL3 risk genes. Furthermore, this could be possibly even helpful in scarring in other organs such as the heart, lung and kidneys. Overall, these outcomes fulfil several promises in the modern era of precision medicine.

AM: What are some of the current challenges of detecting liver fibrosis in patients?

ME: A liver biopsy, which is a procedure in which a small needle is inserted into the liver to collect a tissue sample, is still the golden standard of assessment of liver biopsies. However, due to the limitations of this method, an active area of research is to find a non-invasive method which can predict liver fibrosis with a high degree of accuracy, with some options is currently available. Also, another challenge is the ability to predict the patients fibrosis progression rates (i.e. slow or fast) rather than just the fibrosis level at particular time point. AM: Can you tell us about the diagnostic tool you have developed, and how this will help clinicians?

ME: To translate these findings and using machine learning techniques, we have designed a diagnostic tool that incorporates IFNL3 genotyping with other simple clinical variables, which is freely available (www.fibrogene.com) for all doctors to use, to aid in predicting liver fibrosis risk.

AM: What future work do you have planned?

ME: Our team is working to extend this work to further understand the fundamental mechanisms of how IFNL3 contributes to liver disease progression and hopefully we could translate these findings into new therapeutic treatments. Mohammed Eslam was speaking to Anna MacDonald, Editor for Technology Networks.

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A Step Closer to Personalised Medicine for Liver Fibrosis - Technology Networks

Dr. Nigma Talib Four Seasons Los AngelesWhile Dr. Nigma Talib is a newcomer to the United States, her London skin-care clinic has a several-months-long waiting list. We expect it wont take long for a similar queue to form at the Four Seasons Los Angeles at Beverly Hills, where she started practicing in September. Her face treatments get under way with a consultation (she is a naturopathic physician), during which she inquires about any underlying skin woes and recommends nutritional solutions for a healthier visage. Nearly all of her treatments incorporate high-tech elementssuch as LED paddles for pushing vitamins, peptides, and hyaluronic acid deeper into the skinand are backed by proprietary research. Talibs signature platelet-rich-plasma microneedling procedure adds plant stem cells and activates the skins own collagen synthesis to repair damage and boost elasticity ($550-$1,200).

Craig Venter Health Nucleus Many of the best hospitals in the country offer top-notch executive health programs, where clients spend a day undergoing a battery of health diagnostic tests, but Craig Venters Health Nucleus in San Diego adds a full genetic workup to the typical roster of state-of-the-art MRIs, 3-D heart imaging, and other tests. Venter, who launched the Health Nucleus physical in early 2016, is one of the premier genetic scientists in the world, and his team of physicians can help interpret the results of the testing in a way that is accessible for the layperson. Have a deletion on your RECQL gene? Venters team will tell you if there is any recent or known research on that anomaly and how it might impact your future health, if at all. They will even reach out in subsequent months and years to update you on any new studies that relate to something in your genetic makeup. Test results are presented in an analog binder as well as a digital document ($25,000).

Dr. John Lombard LifeSpan MedicineLifeSpan Medicine neurologist John Lombard hears constantly from his patients that their memories arent as sharp as they used to be. So last January, he and Dr. Chris Rennafounder of the concierge practice, which has offices in Dallas, Los Angeles, and New York Citylaunched a dedicated brain-health track for LifeSpans members. The service can be effective for everything from improving memory and productivity to treating mood and sleep conditions, migraines, and early dementiaeven managing brain injuries, tumors, and degenerative disorders. After a comprehensive neurological assessment, treatment plans typically run from 3 to 6 months with the goals of a return to wellness and prevention of disease. Lombard is an expert at determining the precise scan to order for a specific concern, and he often drills down to the cellular or genetic level to connect defects there to the brains biology and chemistry. He is a firm believer in evidential science but isnt afraid to take avant-garde (but still scientifically sound) approaches to brain healthsuch as improving blood flow to the brain or reducing high cortisol levels as interventions in early cognitive decline ($750$25,000).

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Beauty, Wellness, and Your Brain: 3 Best of the Best Healthcare Heroes - Robb Report

In science and medicine the terminology applied can be the difference between life and death, success and failure. Words have precise meanings, and a productive dialogue in the sciences requires adherence to a common set of mutually recognized terms. Shared meaning is like a verbal handshake that ensures a positive connection where information can flow.

Genetic engineering, familiarly known by the slippery colloquialism GMO, has been central to the production of drugs like insulin, enzymes used in cheese making, and laboratory-produced fibers. The widest-recognized successes have been the adoption of the technology by 20 million farmers onto almost half a billion acres of farmland, most of those in the developing world. Some 70 percent of grocery store products now contain ingredients from genetically engineered plants. And while scientists and farmers acknowledge concerns arising from the overuse of the technology, such as weed and insect resistance, there remains zero credible evidence of health-related concerns.

Still the most beautiful and altruistic applications of this technology remain to be deployed. The innovations geared to solve specific issues in hunger, environment or consumer health have not left university laboratories or government greenhouses.

This cutting edge has not been dulled due to technical problems or clandestine dangers. Instead, technology has been stalled because of high deregulation costs and negative public perception founded on misinformation.

Could part of the problem simply be the bad branding of a good technology? Our social psyche has been saturated with fear-based manufactured risk and misinformation. Could cleaning up our vocabulary advance the publics understanding of the science and help illuminate its actual risks and benefits, while curing the tales of fear mongering?

Goodbye, GMO

Take for instance the abbreviation GMO. The term appears to have been first used thirty-three years ago this week, appropriately in the New York Times, a venue that regularly uses language to blur scientific reality in food space. Over the last decades the term has been adopted as nomenclature of derision; after all, who would want to feed their child an alien organism?

GMO is not a scientific term. Scientifically speaking, genetic modification is ambiguous, applying to many situations. Genetic modification is what happens upon a sexual crossing, mutation, multiplication of chromosomes (like in a seedless watermelon or banana), introduction of a single new gene from an unrelated species or the tweaking a genome with new gene editing techniques. These are all examples of genetic modification, but not all offer the predictability and precision of the process of genetic engineering.

This is why actual scientists rarely (if ever) use the GMO designation in technical parlance. It first regularly was highlighted in rhetoric opposing the technology, and since has sadly been adopted by mainstream media. Works that apply the term tend to disparage the technology, and opt for GMO rather than a scientifically precise term to stoke the negative perception.

For instance, the term GMO is prominently presented in the 2012 publication (retracted) by French biologist Gilles-Erich Seralini and colleagues, juxtaposed with tumor-ridden suffering animals. Their intent was to label the sad and grotesque figures of suffering animals with the three letters, G-M-O. A valid scientific effort would have labeled a figure with the gene installed that made the plant unique, not a catch-all term for an engineered plant. Seralinis work met tremendous outcry from a scientific community that saw this as being a political and manipulative use of the scientific literature to advance an agenda.

The use of the term GMO in the figures is consistent with that interpretation.

In order to help advance the public discussion, we should agree to abandon the meaningless term GMO. This is especially important for academics, scientists, farmers, dietitians and physiciansprofessionals the public relies upon to answer questions about food and farming. It is time for the science-minded community to adopt a common vocabulary to enhance effective discussion and enjoy more meaningful dialogue.

Toward a new phrasebook

Here are my suggestions for how we can adopt a common vocabulary to make sure were all speaking the same language about these technologies.

1. Stop using GMO. It is imprecise. Everything not arising as a clone is genetically modified from previous forms, as is anything changed by mutation. You are a unique genetic modification of your parents combined genes. A dachshund is a genetic modification of an ancestral gray wolf. Instead we should replace GMO with Genetic Engineering. Genetic engineering is adding, subtracting, or adjusting genes in the lab that change a trait in the resulting plant, animal or microbe. It satisfies the very definition of engineering the application of science and mathematics to affect properties of matter or the sources of energy in nature to be made useful to people.

However, the term GMO is something people recognize. Effective communication depends on shared meaning, so scientists or journalists should use the term once in a presentation or article parenthetically, then switch to genetic engineering. Experts should make it clear that GMO is not an acceptable term when discussing science.

The flawed GMO must also still be included in keywords, image tags, or in any online content. If it is not present, someone searching the internet for credible information with this non-scientific term may encounter a higher proportion of scientifically questionable information. Providing a parenthetical mention or brief reference ensures that those seeking science-based answers can find them.

2. An All-Encompassing Term. A better term for the scientific processes used to produce new varieties or breeds, or the intermediate steps, would be best referred to as crop or animal genetic improvement. In other words, when we use traditional breeding methods to make plants or animals better, it takes many steps and lots of selection. Thats genetic improvement, whether it is done by sexual exchange, breaking DNA strands with radiation or doubling chromosomes with chemistry.

3. The Newest Technologies. New technologies are now being used that allow scientists to make incredibly specific changes to DNA sequence, without leaving foreign DNA sequences (that some find objectionable) behind. These techniques should be collectively referred to as gene editing. Especially avoid referring to the technology by its technical name like CRISPR/Cas 9 or TALEN, which are specific types of gene editing. It is important because the list of gene editing methods is inevitably growing. Gene editing is also more precise than the often-used genome editing.

The purpose of this brief new glossary is not to provide a mandate based on my narrow experience and observations. Instead, my goal is to offer a proposal so a scientific community eager to precisely engage the public can challenge the pros and cons of these terms to hone an optimal vocabulary. My hope is to ultimately derive an agreed-upon terminology that can be adopted and consistently applied by experts in science, medicine and agriculture. Journalists and science communications may then adopt the precise wording of the discipline for improved precision in communication.

Concrete, unambiguous terms can help curious and concerned people understand the realities of genetic engineering. Certainly medicine has benefited from precise language, such as how childhood cognitive disabilities are now characterized with greater sensitivity and improved medical precision. This change improved social stigma of various developmental disorders, brought compassionate understanding to the conditions, and enhanced treatment for those affected.

Better scientific literacy and precision in terminology around genetic engineering would lead to a more productive discourse that ultimately could enable more rapid deployment of safe technologies that can help people and the planet. The individuals that insist on adhering to antiquated, divisive and imprecise terms will be automatically characterized as antiquated, divisive and imprecise.

The first step is to stop using the archaic, imprecise term GMO.

Kevin Folta is a land-grant scientist exploring ways to make better food with less input, and how to communicate science. This article was published with his permission. All of Dr. Foltas funding can be found at kevinfolta.com/transparency.

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Kevin Folta: Please say no to the term 'GMO' - AGDAILY

Some bodily activities, sleeping, for instance, mostly occur once every 24 hours; they follow a circadian rhythm. Other bodily functions, such as body temperature, cognitive performance and blood pressure, present an additional 12-hour cycle, but little is known about the biological basis of their rhythm. A team of scientists from various institutions, including Baylor College of Medicine, has revealed that, in addition to 24-hour clocks, mammals and other organisms have 12-hour clocks that are autonomous, work independently from 24-hour clocks and can be modified by external factors. Studying 12-hour clocks is important because altered 12-hour cycles have been linked to human disease. The study appears in Cell Metabolism.

Our lab has been working on how the 24-hour cycles are regulated, and we and others have shown that disturbing these clocks may lead to diseases of metabolism, said senior author Dr. Bert OMalley, chair and professor of molecular and cellular biology and Thomas C. Thompson Chair in Cell Biology at Baylor College of Medicine. For instance, experimental evidence shows that night-shift workers who periodically change their night and day shifts or people who travel overseas often alter their sleep cycles, and this seems to make them prone to gain weight and develop diabetes and other alterations of metabolism that may lead to disease. Its not a good idea to disturb the circadian rhythm on a regular basis.

In addition to physiological activities that cycle every 24 hours, mammals and other organisms have activities that repeat every 12 hours. For example, it has been reported that blood pressure, body temperature, hormone levels and response to therapy fluctuate in 12-hour cycles. In addition, altered 12-hour cycles have been associated with human diseases. Other researchers had identified about 200 genes that are activated in 12-hour cycles. In this study, OMalley and his colleagues set out to determine whether there was a larger number of 12-hour genes and whether their cycles followed the definition of a biological clock, that is whether they worked autonomously and their oscillation could be adjusted by the environment.

Math meets biology to indentify the bodys internal clocks

Dr. Bokai Zhu, first author of this study and a postdoctoral fellow in the OMalley lab, carried out biological analyses to determine the activity of thousands of mice genes in time. Then, co-author Dr. Clifford Dacso, professor of molecular and cellular biology at Baylor College of Medicine, and co-author and mathematician Dr. Athanasios Antoulas, professor of electrical and computer engineering at Rice University, applied mathematical analyses to these biological data.

We were surprised to identify more than 3,000 genes that were expressed following 12-hour rhythms. A large portion of these genes was superimposed on the already known 24-hour gene activities, Zhu said.

The 12-hour clock is autonomous and can be synchronized by external cues

Further work showed that the 12-hour rhythms of genetic activity work as biological clocks. They occur regularly and autonomously in the cells, and their oscillation can be synchronized by certain external stimuli. OMalley and colleagues discovered that 12-hour clocks are independent from 24-hour clocks. When they experimentally eliminated a 24-hour clock, 12-hour clocks continued ticking. Furthermore, the external cues that can synchronize 24-hour clocks, such as sunlight, do not affect 12-hour clocks.

Of all the genes we analyzed, two sets with 12-hour cycles stood out; those involved with protein quality control and processing, which mainly occur in a cellular structure called endoplasmic reticulum, and those related to the energy supply of the cell, which involves the mitochondria, Zhu said. The activities of the endoplasmic reticulum and mitochondria depend on each other, and we have shown here that the 12-hour genes in the endoplasmic reticulum are synchronized with the 12-hour genes in the mitochondria, which provide the energy needed for protein processing.

In addition, we found that certain liver conditions are associated with disturbed 12-hour gene expression in mice. We anticipate that further study of 12-hour cycles might lead to opportunities to improve prevention of or treatments for diseases of the liver and other organs in the future, OMalley said.

Other contributors to this work include Qiang Zhang, Yinghong Pan, Emily M. Mace and Brian York. The authors are affiliated with one or more of the following institutions: Baylor College of Medicine, Rice University, the University of Houston and the Max Planck Institute.

This research was supported by grants from the NationaI Institutes of Health (U24 DK097748 and R01 HD07857), the Brockman Foundation, the Center for Advancement of Science in Space, Peter J. Fluor Family Fund, Philip J. Carroll, Jr. Professorship, Joyce Family Foundation, the National Science Foundation Grant CCF-1320866 and the German Science Foundation Grant AN-693/1-1.

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12-hour biological clock coordinates essential bodily functions - Baylor College of Medicine News (press release)

A consultant studies a mammogram. The drug olaparib could slow cancer growth by three months, researchers have found. Photograph: Rui Vieira/PA

A type of inherited and incurable breast cancer that tends to affect younger women could be targeted by a new therapy, researchers have found.

A small study presented at the worlds largest cancer conference found treating patients with the drug olaparib could slow cancer growth by three months and be less toxic for patients with inherited BRCA-related breast cancer.

Researchers said there was not enough data to say whether patients survived longer as a result of the treatment.

We are in our infancy, said Dr Daniel Hayes, president of the American Society of Clinical Oncology and professor of breast cancer research at the University of Michigan. This is clearly an advance; this is clearly proof of concept these can work with breast cancer.

Does it look like its going to extend life? We dont know yet, he said.

The drug is part of the developing field of precision medicine, which targets patients genes to tailor treatment.

It is a perfect example of how understanding a patients genetics and the biology of their tumor can be used to target its weaknesses and personalize treatment, said Andrew Tutt, director of the Breast Cancer Now Research Centre at The Institute of Cancer Research.

Olaparib is already available for women with BRCA-mutant advanced ovarian cancer, and is the first drug to be approved that is directed against an inherited genetic mutation. The study was the first to show olaparib can slow growth of inherited BRCA-related breast cancer. The drug is not yet approved for that use.

People with inherited mutations in the BRCA gene make up about 3% of all breast cancer patients, and tend to be younger. The median age of women in the olaparib trial was 44 years old.

BRCA genes are part of a pathway to keep cells reproducing normally. An inherited defect can fail to stop abnormal growth, thus increasing the risk of cancer. The study examined the effectiveness of olaparib against a class of BRCA-related cancers called triple negative. Olaparib is part of a class of four drugs called PARP-inhibitors that work by shutting down a pathway cancer cells use to reproduce.

The study from Memorial Sloan Kettering Cancer Center in New York randomly treated 300 women with advanced, BRCA-mutated cancer with olaparib or chemotherapy. All the participants had already received two rounds of chemotherapy.

About 60% of patients who received olaparib saw tumors shrink, compared with 29% of patients who received chemotherapy. That meant patients who received olaparib saw cancer advance in seven months, versus four months for only chemotherapy.

Researchers cautioned it is unclear whether olaparib extended life for these patients, and that more research was needed to find out which subset of patients benefit most from olaparib.

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New therapy offers hope against incurable form of breast cancer - The Guardian