Category Archives: Cell Medicine

June 27, 2017 by Heather Lindsay Irradiated cancer cell with a small amount of DNA (green) in the cytoplasm. Credit: Dr. Claire Vanpouille-Box/Weill Cornell Medicine

An enzyme implicated in autoimmune diseases and viral infections also regulates radiation therapy's ability to trigger an immune response against cancer, Weill Cornell Medicine scientists found in a new study. Their discovery can help to better tailor treatment for patients.

Immunotherapy is an innovative approach to cancer treatment that unleashes the power of the immune system to fight the disease. The method has revolutionized treatment for several cancers. However, only a minority of patients responds to the treatment. Radiation therapy may boost patients' responses to immunotherapy, but the best way to achieve this effect has remained unclear.

In a study published June 9 in Nature Communications, investigators discovered that radiation in mice elicits the accumulation of DNA in a cellular compartment where it mimics the presence of a virus, generating molecular signals that are normally triggered by infection. The most important signal, known as interferon-beta, is required to activate immune cells that can kill virally infected cells. Thus, radiation therapy tricks the immune system to see the cancer cells as if they were infected by a virus, and by doing so, it activates the immune system against the tumor.

However, not all ways used to irradiate the tumor achieve this effect, due to the induction of an enzyme that clears the DNA, called TREX1.

"We found that the induction of interferon-beta by radiotherapy is under the control of TREX1," said senior study author Dr. Sandra Demaria, professor of radiation oncology and of pathology and laboratory medicine at Weill Cornell Medicine and member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine.

"When the radiation dose used is increased above a certain threshold, TREX1 levels increase in the cancer cells, blocking the production of interferon. Intriguingly, this mechanism of escape from immune detection by cancer cells irradiated with certain doses mimics one of the ways HIV evades the immune system."

For their study, the researchers treated mice with breast or colorectal cancer with different doses of radiation therapy, and also studied these treatments in human lung and breast cancer cells. They then evaluated mouse tumors and human cells in the laboratory to determine what cellular changes occurred. Importantly, they demonstrated in the mice that blocking the induction of TREX1 restored radiation's ability to induce effective anti-tumor immune responses when used with immunotherapy.

"The findings that TREX1 is a regulator of radiation therapy ability to activate the immune system and that its induction depends on the radiation dose used is potentially practice-changing, if these results are verified in patients," said study co-author Dr. Silvia Formenti, chairman of the Department of Radiation Oncology, the Sandra and Edward Meyer Professor of Cancer Research and associate director of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, and radiation oncologist-in-chief at NewYork-Presbyterian/Weill Cornell Medical Center.

The team is now studying whether the doses of radiation that induce TREX1 in carcinomas are similar in other types of cancers.

"This is important to help guide the choice of radiation to be used in clinical trials that test combinations of radiotherapy with immunotherapy in different cancers," Demaria said.

Formenti is leading several studies testing these combinations in patients with lung and other cancers.

As research and treatment progresses, "we need to be mindful when we use radiation to elicit an immune response," Formenti said. "It's important to use the dose per fraction that is likely to work the best to elicit an immune response, and we have now a way to determine what it is by measuring the levels of interferon-beta and TREX1 in each individual patient."

Explore further: New targeted molecular therapy takes aim at incurable prostate cancer

An enzyme implicated in autoimmune diseases and viral infections also regulates radiation therapy's ability to trigger an immune response against cancer, Weill Cornell Medicine scientists found in a new study. Their discovery ...

Researchers at the University of Pittsburgh School of Medicine and the University of Toronto have uncovered the first molecular steps that lead to immune system activation and eventual rejection of a transplanted organ. The ...

A new study by scientists at UCLA found that when mice eat a high-fat diet, the cells in their small intestines respond the same way they do to a viral infection, turning up production of certain immune molecules and causing ...

The mammalian immune system consists of millions of individual cells that are produced daily from precursor cells in the bone marrow. During their development, immune cells undergo a rapid expansion, which is interrupted ...

Researchers at the Biocomplexity Institute of Virginia Tech have discovered a new therapeutic target for inflammatory bowel diseaseand it's right inside our immune cells.

Scientists from St. Jude Children's Research Hospital and Fred Hutchinson Cancer Research Center have developed an algorithm that functions like a Rosetta Stone to help decipher how the immune system recognizes and binds ...

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Original post:
Enzyme key to triggering anti-cancer immune response - Medical Xpress

The mum of missing airman Corrie McKeague has revealed how close police are to finding her son.

Police have been searching for the 23-year-old at a landfill site in Milton, Cambridgeshire, since March, after he went missing on a night out in Bury St Edmunds on September 24 last year.

Officers believe that the 23-year-old was dumped by a bin lorry into the landfill site.

Nicola Urquhart, 48, believes that Corrie could be found 'literally tomorrow' if he is in the landfill.

On the Find Corrie Facebook page, she wrote: "The police will continue to search this area [the cell] of the landfill until they either find Corrie or the rubbish starts clearly and consistently showing it has gone back too far in date ranges.

"This is why no completion date can be given as this is reviewed daily/weekly."

She added: "Rubbish is still being found with dates and locations to show they are still in the correct area so they are slowly working their way back to the edges of the entire cell.

"Due to the rubbish that is being found, if Corrie is in this landfill he could literally be found tomorrow."

Nicola also wanted to clarify what the 'cell' actually represented, as previously she said that there was a smaller area left to search.

The mother uses the analogy of a football cut in half and filled with rubbish.

"This is what I understand to be the cell, however the reality is if you were to get a medicine ball and cut that in half and place the football inside it, it is actually the edges of the medicine ball that's the edges of the entire cell.

"The police have searched through the rubbish in the football. To empty the football shaped area they were able to say this may take about 10 weeks (which it roughly did).

"And as they got to the edges they could see the dates of the rubbish was going back far too early, prior to when Corrie disappeared.

"On one side however, the rubbish is still being found with dates and locations to show that they are still in the correct area, so they are slowly working their way back to the edges of the entire cell (the edges of the medicine ball).

"So the area they are searching is still the same depth as the middle of the cell as they are no where near the edges yet which means this will take far longer to search than I first understood."

Corrie was last seen on CCTV at 3.24am walking into a refuse area behind a Greggs in Bury St Edmunds.

Police believe the only way that the 23-year-old could have left that area without being spotted by CCTV is through a bin lorry that entered the refuse area to take rubbish from a Biffa bin only hours later.

The airman's mobile was tracked travelling in a similar direction to a bin lorry's route.

The bin lorry's weight was also found to have carried rubbish heavy enough to have contained Corrie's body.

Police and the family are confident that the airman is in the landfill.

Specialists have sifted through more than 5000 tonnes of rubbish so far.

Read the original post:
Mum of Corrie McKeague reveals how close police are to finding her son - Cambridge News

When Shannon DeAndrea saw a knot on her 18-month-old sons head last July, she thought he had just fallen.

But more popped up and wouldnt go away. He also began feeling sick.

I finally decided he needed to see a pediatrician, said DeAndrea, who lives in Blairs.

She was told he had ear infections and her son, Nathan, was put on rounds of antibiotics. The knots were normal, she was told.

Another medical provider said he looked anemic. Blood work revealed his hemoglobin was dangerously low.

We ended up in the ER, DeAndrea said. They couldnt figure out why he was anemic.

Shannon and Nathan were sent to Roanoke, where he was diagnosed with a stage 4 neuroblastoma on Aug. 23. He had a tumor in his abdomen that spread to his bone marrow. He had spots on his skull, ribs and spine.

Neuroblastomas are cancers that begin in early nerve cells of the sympathetic nervous system, according to the American Cancer Society.

Since his diagnosis, her son now 2 has had several rounds of chemotherapy and two stem cell transplants and is doing well.

Now hes just like a normal 2-year-old, DeAndrea said. Hes running around with his sister. Hes eating well.

Dr. William Clark is associate professor of medicine and attending physician at Virginia Commonwealth University Massey Cancer Center Stem Cell Transplantation Program. Clark said the procedure is used for conditions including multiple myeloma, lymphoma, sickle cell anemia and leukemia.

Stem cell transplants are used to replace bone marrow that has been destroyed by cancer or destroyed by the chemo and/or radiation used to treat the cancer, according to the American Cancer Society.

High doses of chemo (sometimes along with radiation), work better than standard doses to kill cancer cells. However, high doses can also kill the stem cells and cause the bone marrow to stop making blood cells, which are needed for life. The transplanted stem cells replace the bodys stem cells after the bone marrow and its stem cells have been destroyed by treatment, according to the American Cancer Society.

Two types of stem cell transplants include autologous, which uses stem cells from the patients own body, and allogeneic using stem cells from another person, Clark said.

For leukemia patients, most of the time, we give them stem cells from someone else, Clark said. Chemotherapy helps lower the leukemia disease burden, but the new immune system provided by the new stem cells can fight against the cancer cells and get rid of them, he said.

Virginia Commonwealth Universitys cancer center performs an average of about 160-195 stem cell transplants per year, Clark said. Slightly more than half are autologous procedures, and the rest are allogeneic, he said.

Whitt Clement, former delegate who represented the Danville area in the General Assembly, underwent a stem cell transplant for acute myeloid leukemia in September 2015.

The most important aspect for patients is being self-aware and their own best advocates, Clement said.

My experience was that the patient has to ask a lot of questions throughout the process, he said.

He suspected something was wrong when he noticed his platelet count declining over seven years. He went to a hematologist and had a bone marrow biopsy that revealed his condition.

If I had not taken the initiative myself and gone to see a hematologist, matters would have progressed to the point where I would have been symptomatic, Clement said.

Finding the perfect match in a donor is also important, Clement said. Fortunately, he had a sibling who met all the criteria and donated stem cells.

A person can get great matches from unrelated donors, but its preferable for a donor to be a sibling, said Clement, partner at Hunton & Williams law firm in Richmond.

Your body has an easier time tolerating the new stem cells, he said.

Clement served in the Virginia House of Delegates from 1988-2002, and as Virginias secretary of transportation from 2002-2005 under Gov. Mark Warner.

For someone with multiple myeloma, the transplant does not cure the disease but delays the time it returns by up to seven and a half years, Clark said.

Lymphoma, leukemia and sickle cell anemia can be cured with the procedure, Clark said. Lymphoma can be cured in about 50 to 80 percent of cases, depending on the lymphoma, Clark said.

The first 30 days after the transplant are the most critical, Clement said. During that time, different organs can have varying reactions to the new cells. It can affect the kidneys, liver, gastrointestinal tract, skin, and cause other side effects.

The idea is that the closer the match, the less likely youll have those adverse reactions, he said.

The process includes being put on an immunosuppressant to prevent the immune system from attacking the new cells, Clement said.

He credits the quality of his recovery to asking lots of questions and being his own advocate tape recording conversations with medical providers, coming in with written questions.

Ive been able to recover better because of that, he said.

Its a long journey and so a person confronted with the transplant situation has got to prepare himself for a long journey that requires a lot of questions along the way, Clement said.

There are about 20 million potential stem cell/bone marrow donors in the BeTheMatch Registry in the United States, Clark said.

Stem cell transplants began in the late 50s/early 60s with the first successful procedure done in an identical twin, Clark said. However, stem cell transplants were limited until medicines that prevent rejections became available.

The number of procedures increased in the 1980s, Clark said.

Danville resident Susan Mathena, cancer patient navigator at Danville Regional Medical Center, became a donor about 20 years ago because she wanted to help people. Mathena has also been an organ donor since she got her drivers license.

I see patients all the time that need stem cell transplants, Mathena said. We always need a source of bone marrow donation.

Though she will age out of the stem cell donor list soon, she could still be contacted if she is the only match for someone in need, she said.

Clark will speak next month on stem cell/bone marrow transplants at Ballou Recreation Center at an event held by the Cancer Research and Resource Center of Southern Virginia in Danville.

Thousands of patients with blood cancers like leukemia or other diseases like sickle cell anemia need a bone marrow/stem cell transplant to survive, including some of our own community members, said Kate Stokely Powell, coordinator at the center.

Clarks presentation offers an opportunity in Southside for people battling illness, medical students and professionals and the public to learn from an expert in the field of stem cell transplants, Powell said.

Doctors, hospitals and families affected by a blood cancer disease have done a great job of building a massive database of blood types for potential donor matches, Clement said.

For DeAndrea and her son, Nathan, the first transplant included four or five days of chemo. The new stem cells following the chemo that killed off his old stem cells from the transplant were like a rescue, she said.

Its wiping you out and then giving you your cells back to restart your immune system, DeAndrea said.

A second round of heavy chemo was to try to kill what was left of the cancer and replenish cells, she said.

It was rough, it was a nightmare, DeAndrea said. It was by far the worst phase of his treatment, but I believe, in the long run, its worth it.

She said the procedures should increase Nathans chances for survival and prevent a relapse.

Nathan just finished radiation Tuesday and will go in for a biopsy of his bone marrow this week, DeAndrea said.

Well find out next week where we stand as far as the cancer goes, she said.

Follow this link:
After two stem cell transplants and several rounds of chemo, 'now he's just like a normal 2-year-old' - GoDanRiver.com

June 23, 2017

Imagine being able to take cells from your skin, transform them into other types of cells, such as lung, brain, heart or muscle cells, and use those to cure your ailments, from diabetes to heart disease or macular degeneration. To realise this, however, challenges still remain, Professor Janet Rossant, a pioneer in the field, says.

All across the world, scientists have begun clinical trials to try and do just that, by making use of the incredible power and versatility of stem cells, which are special cells that can make endless copies of themselves and transform into every other type of cell.

While human embryos contain embryonic stem cells, which help them to develop, the use of those cells has been controversial. The scientists are using induced pluripotent stem cells instead, which are other cells that have been reprogrammed to behave like stem cells.

"There are still significant challenges that we need to overcome, but in the long run we might even be able to create organs from stem cells taken from patients. That would enable rejection-free transplants," said Professor Janet Rossant, a pioneer in the field.

The mouse that changed everything

A speaker at the recent Commonwealth Science Conference 2017 held in Singapore and organised by Britain's Royal Society and Singapore's National Research Foundation, Prof Rossant gave an overview of stem cells' origins, history, uses and potential.

Now a senior scientist at The Hospital for Sick Children (also known as Sick Kids) in Toronto, Canada, after a decade as its chief of research, she was the first scientist to demonstrate the full power of stem cells in mice.

In the early 1990s, scientists believed that stem cells could only become certain types of cells and carry out limited functions. Based on her own research and that of others, however, Prof Rossant believed that they were capable of far more.

Working with other scientists, she created an entire mouse out of stem cells in 1992, upending the conventional wisdom. "We went on to create many baby mice that were completely normal, and completely derived from stem cells grown in a petri dish," she said.

"That was an amazing experiment, and it was instrumental in making people believe that human embryonic stem cells could have the full potential to make every cell type in the body," she added.

When scientists learned how to remove stem cells from human embryos in 1998, however, controversy ensued. Many lobbied against the cells' use in medical research and treatment due to the moral implications of destroying even unwanted embryos to gain the cells.

In Canada, Prof Rossant chaired the working group of the Canadian Institutes of Health Research on Stem Cell Research, establishing guidelines for the field. These guidelines helped to keep the field alive in Canada, and were influential well beyond the country's borders.

In 2006, Japanese researchers succeeded in taking skin cells from adult mice and reprogramming them to behave like embryonic stem cells. These revolutionary, induced pluripotent stem (IPS) cells allowed scientists to sidestep the ongoing controversy.

The challenges in the way

While stem cells have been used for medical treatment in some cases bone marrow transplants, for example, are a form of stem cell therapy there are several challenges that need to be overcome before they can be used more widely to treat diseases and injuries.

"We need to get better at turning stem cells into the fully mature cells that you need for therapy. That's going to take more work. Another issue is that of scale-up. If you're going to treat a patient, you need to be able to grow millions of cells," said Prof Rossant.

She added: "Safety is another concern. One of the most exciting things about pluripotent stem cells is that they can divide indefinitely in the culture dish. But that's also one of the most scary things about them, because that's also how cancer works.

"Furthermore, because we need to genetically manipulate cells to get IPS cells, it's very hard to know whether we've got completely normal cells at the end of the day. These are all issues that need to be resolved."

She noted that some scientists are working on making "failsafe" IPS cells, which have a built-in self-destruct option if they become dangerous. "Bringing stem cells into regenerative medicine is going to require interdisciplinary, international collaboration," she said.

In the meantime, stem cells have been a boon to medical research, as scientists can use them to create an endless supply of different cells to study diseases and injuries, and test drugs. "That's the biggest use of IPS cells right now," Prof Rossant said.

Sick kids and how to help them

At SickKids, which is Canada's largest paediatric research hospital, she has been using stem cells to study cystic fibrosis, a frequently fatal genetic disorder that causes mucus to build up and clog some organs such as the lungs. It affects primarily children and young adults.

SickKids discovered the CFTR gene that, when mutated, causes the disease. It was also the first to produce mature lung cells, from stem cells, that can be used to study the disease and test drugs against it.

Even better, Prof Rossant and her team were able to turn skin cells from cystic fibrosis patients into IPS cells and then into lung cells with the genetic mutation specific to each of them. This is critical to personalising treatment for each patient.

"Drugs for cystic fibrosis are extraordinarily expensive, and patients can have the same mutation and yet respond differently to the same drug," Prof Rossant explained. "With our work, we can make sure that each patient gets the right drug at the right time."

In 1998, Prof Rossant also discovered a new type of stem cell in mice, now called the trophoblast stem cell. These surround an embryo and attach it to the uterine wall, eventually becoming the placenta. She is using such cells to study placenta defects and pregnancy problems.

By using IPS cells to create heart cells and other cells, pharmaceutical companies can also test their new drugs' effectiveness and uncover potential side effects, as well as develop personalised medicines.

"There are still huge amounts of opportunities in pluripotent stem cells," said Prof Rossant, who has won numerous awards for her research, including the Companion of the Order of Canada and the 2016 Friesen International Prize in Health Research.

She is also president and scientific director of the Toronto-based Gairdner Foundation, which recognises outstanding biomedical research worldwide, and a professor at the University of Toronto's molecular genetics, obstetrics and gynaecology departments.

"Meetings like the Commonwealth Science Conference are a fantastic opportunity for scientists to come together, learn about each other's work and establish new relationships, which will help to push science forward, including in stem cell research," she said.

She noted: "The world of science is becoming increasingly interdisciplinary, so this kind of meeting of minds across nations, cultures and scientific fields is really the way of the future."

Explore further: Cardiac stem cells from heart disease patients may be harmful

Discovered more than two decades ago, the hormone leptin has been widely hailed as the key regulator of leanness. Yet, the pivotal experiments that probe the function of this protein and unravel the precise mechanism of its ...

New research overturns long-held views on a basic messaging system within living cells. Key cellular communication machinery is more regionally constrained within the cell than previously thought. The findings suggest new ...

Scientists used human pluripotent stem cells to generate human embryonic colons in a laboratory that function much like natural human tissues when transplanted into mice, according to research published June 22 in Cell Stem ...

The leading cause of acute gastroenteritis linked to eating raw seafood disarms a key host defense system in a novel way: It paralyzes a cell's skeleton, or cytoskeleton.

It's a tiny marine invertebrate, no more than 3 millimeters in size. But closely related to humans, Botryllus schlosseri might hold the key to new treatments for cancer and a host of vascular diseases.

Paracetamol is popular for relieving pain. But if you are pregnant, you should think twice before popping these pills according to the researchers in a new study. In an animal model, Paracetamol, which is the pain-relieving ...

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

See the article here:
Stem cells: the future of medicine - Medical Xpress

Duke researchers have discovered a unique repair mechanism in the developing backbone of zebrafish that could give insight into why spinal discs of longer-lived organisms like humans degenerate with age.

The repair mechanism apparently protects the fluid-filled cells of the notochord, the precursor of the spine, from mechanical stress as a young fish begins swimming. Notochord cells go on to form the gelatinous center of intervertebral discs, the flat, round cushions wedged between each vertebrae that act as shock absorbers for the spine.

The disappearance of these cells over time is associated with degenerative disc disease, a major cause of human pain and disability worldwide.

It is not difficult to speculate that these same mechanisms of repair and regeneration are present in humans at very early stages, but are lost over time," said Michel Bagnat, Ph.D., senior author of the study and assistant professor of cell biology at Duke University School of Medicine. If we are going to think about techniques that foster intervertebral disc regeneration, this is the basic biology we need to understand.

The study appears June 22, 2017, in Current Biology.

Bagnat likens the notochord to a garden hose filled with water. The hardy structure consists of a sheath of epithelial cells surrounding a collection of giant fluid-filled or vacuolated cells. During development, these vacuolated cells rarely pop, despite being under constant mechanical stress. Recent research has suggested that tiny pouches known as caveolae (Latin for little caves) that form in the plasma membrane of these cells can provide a buffer against stretching or swelling.

To see whether the caveolae protected vacuoles from bursting, his team and collaborators from Germany generated mutants of three caveolar genes in their model organism, the zebrafish. Because these small aquarium fish are transparent as embryos, the scientists could easily visualize any spinal defects triggered by the loss of caveolae.

The researchers found that when the mutant embryos hatched and started swimming, exerting pressure on their underdeveloped backbones, their vacuolated cells started to break up. While the finding confirmed their suspicions, it turned up a puzzling discovery. In the caveolar mutants, you see these serial lesions up and down the notochord, and yet the mature spine formed normally, said Bagnat. That was very puzzling to us.

To figure out how that was possible, lead authors Jamie Garcia and Jennifer Bagwell took a closer look at the notochord of mutant fish. They marked the vacuolated cells green and the surrounding epithelial sheath cells red and then filmed the fish shortly after they hatched and started swimming. First, they could see an occasional vacuolated cell break and spill its contents like a water balloon. Then, over the course of fifteen hours, a nearby epithelial sheath cell would move in, crawl over the detritus of the collapsed cell, and morph into a new vacuolated cell.

They performed a few more experiments and found that the repair response was triggered by the release of the cell contents, specifically the basic molecular building blocks known as nucleotides. The researchers then isolated live epithelial sheath cells and treated them with nucleotide analogs to show that they turned into vacuolated cells.

These cells, which reside in the discs of both zebrafish and man, seem capable of controlling their own repair and regeneration, said Bagnat. Perhaps it is a continuous release of nucleotides that is important for keeping the disc in good shape.

The study may offer insight not only into the development of back and neck pain, but also into the origins of cancer. Their data suggests that chordomas, rare and aggressive notochord cell tumors, may begin when epithelial sheath cells leave the notochord and invade the skull and other tissues.

The research was supported by National Institutes of Health (AR065439, AR065439-04S1, T32DK007568-26, and CA193256), a Capes-Humboldt Fellowship, the Max Planck Society, and a Faculty Scholar grant from the Howard Hughes Medical Institute.

CITATION: "Sheath cell invasion and trans-differentiation repair mechanical damage caused by loss of caveolae in the zebrafish notochord," Jamie Garcia, Jennifer Bagwell, Brian Njaine, James Norman, Daniel S. Levic, Susan Wopat, Sara E. Miller, Xiaojing Liu, Jason W. Locasale, Didier Y.R. Stainier and Michel Bagnat. Current Biology, June 22, 2017. DOI# 10.1016/j.cub.2017.05.035

Read more from the original source:
Cells In Fish's Spinal Discs Repair Themselves - Duke Today

June 22, 2017

New research overturns long-held views on a basic messaging system within living cells. Key cellular communication machinery is more regionally constrained within the cell than previously thought. The findings suggest new approaches to designing precision drugs. Localizing drug action at a specific 'address' within the cell could mean fewer side effects in treating cancer, diabetes, heart disease and other serious conditions.

Research results reported this week in the journal Science overturn long-held views on a basic messaging system within living cells.

The findings suggest new approaches to designing precisely targeted drugs for cancer and other serious diseases.

Dr. John D. Scott, professor and chair of pharmacology at the University of Washington School of Medicine and a Howard Hughes Medical Institute Investigator, along with Dr. F. Donelson Smith of the UW and HHMI, led this study, which also involved Drs. Claire and Patrick Eyers and their group at the University of Liverpool.

The researchers explained that key cellular communication machinery is more regionally constrained inside the cell than was previously thought. Communication via this vital system is akin to social networking on your Snapchat account.

Within a cell, the precise positioning of such messaging components allows hormones, the body's chief chemical communicators, to transmit information to exact places inside the cell. Accurate and very local activation of the enzyme that Scott and his group study helps assure a correct response occurs in the right place and at the right time.

The video will load shortly

"The inside of a cell is like a crowded city," said Scott, "It is a place of construction and tearing down, goods being transported and trash being recycled, countless messages, (such as the ones we have discovered), assembly lines flowing, and packages moving. Strategically switching on signaling enzyme islands allows these biochemical activities to keep the cell alive and is important to protect against the onset of chronic diseases such as diabetes, heart disease and certain cancers."

Advances in electron microscopy and native mass spectrometry enabled the researchers to determine that a critical component of the signaling system, anchored protein kinase A, remains intact during activation. Parts of the molecule are flexible, allowing it to both contract and stretch, with floppy arms that can reach out to find appropriate targets.

Still, where the molecule performs its act, space is tight. The distance is, in fact, about the width of two proteins inside the cell.

The video will load shortly

"We realize that in designing drugs to reach such targets that they will have to work within very narrow confines, " Scott said.

One of his group's collective goals is figuring out how to deliver precision drugs to the right address within this teeming cytoplasmic metropolis.

"Insulating the signal so that the drug effect can't happen elsewhere in the cell is an equally important aspect of drug development because it could greatly reduce side effects," Scott said.

An effort to take this idea of precision medicine a step further is part of the Institute for Targeted Therapeutics at UW Medicine in Seattle. The institute is being set up by Scott and his colleagues in the UW Department of Pharmacology.

The scientists are collaborating with cancer researchers to better understand the molecular causesand possible future treatmentsfor a certain liver malignancy. This particular liver cancer arises from a mutation that produces an abnormal form of the enzyme that is the topic of this current work, protein kinase A, and alters the enzyme's role in cell signaling.

The video will load shortly

Other advances that gave the researchers a clearer view of the signaling mechanisms reported in Science include CRISPR gene editing, live-cell imaging techniques, and more powerful ways to look at all components of a protein complex.

Explore further: Study unveils T cell signaling process central to immune response

More information: "Local protein kinase A action proceeds through intact holoenzymes" Science (2017). science.sciencemag.org/cgi/doi/10.1126/science.aaj1669

Journal reference: Science

Provided by: University of Washington

New research overturns long-held views on a basic messaging system within living cells. Key cellular communication machinery is more regionally constrained within the cell than previously thought. The findings suggest new ...

The leading cause of acute gastroenteritis linked to eating raw seafood disarms a key host defense system in a novel way: It paralyzes a cell's skeleton, or cytoskeleton.

It's a tiny marine invertebrate, no more than 3 millimeters in size. But closely related to humans, Botryllus schlosseri might hold the key to new treatments for cancer and a host of vascular diseases.

Scientists used human pluripotent stem cells to generate human embryonic colons in a laboratory that function much like natural human tissues when transplanted into mice, according to research published June 22 in Cell Stem ...

Paracetamol is popular for relieving pain. But if you are pregnant, you should think twice before popping these pills according to the researchers in a new study. In an animal model, Paracetamol, which is the pain-relieving ...

Fathers-to-be, take note: You may be more useful in the labor and delivery room than you realize.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Read more:
Localized signaling islands in cells: New targets for precision drug design - Medical Xpress

Ask Dr. Kevin: Understanding Sickle Cell Disease

Dr. Kevin Williams

Ask Dr. Kevin is a new feature brought to you by Pfizer Rare Disease in collaboration with the National Newspaper Publishers Association (NNPA) to increase understanding of sickle cell disease.

Dr. Kevin is currently the Chief Medical Officer for Rare Disease at Pfizer. He pursued medicine after being inspired by his fathers work as a general practitioner in his hometown of Baton Rouge. Dr. Kevin is passionate about raising awareness and increasing understanding of sickle cell disease in the African-American community.

What is sickle cell disease?

Sickle cell disease (SCD) is an inherited genetic disease that affects hemoglobin, the oxygen-carrying protein within red blood cells (RBC). While normal RBCs are flexible and oval-shaped, individuals with SCD have sharp, crescent-shaped RBCs that have trouble passing through the bodys blood vessels, irritating the vessels lining. This irritation leads to the production of sticky proteins that cause RBCs to clump together, along with other cells in the blood, and creates blockages in blood flow. The reduced blood flow leads to severe pain and organ damage, like the heart, brain, eyes, liver, lungs, and spleen (causing the inability to fight certain infections).

How does someone get sickle cell disease?

SCD is passed from parent to child. Everyone has two hemoglobin genes, one from each parent, and both parents must carry and pass the sickle cell gene to their child. With each pregnancy, the child has a 25% chance of having SCD if both parents have the trait.

Is sickle cell disease contagious?

No. You can only inherit it if your parents carry the sickle cell gene and pass it to you. SCD is a serious, lifelong condition that a person has from birth. You do not lose or outgrow it over time.

Are African-Americans more likely to have sickle cell disease?

SCD is more common in certain ethnic groups, especially those of African descent. It is estimated that nearly one in 14 African-American individuals carries the sickle trait and SCD occurs in one out of every 500.

What is the most common symptom for people with sickle cell disease?

Pain is the most common and difficult symptom of SCD, as it can be sudden and so severe that people need to go to the emergency room (ER) or be admitted to the hospital. This type of pain is referred to as a sickle pain crisis or vaso-occlusive crisis (as it is due to blood vessel blockage). Pain can occur anywhere blood flows, but common sites are lower back, arms, chest, stomach, and legs. Certain triggers are known to cause a pain crisis, such as dehydration, extremely hot or cold temperatures, and stress.

How can patients with sickle cell disease prevent pain?

Although you may not prevent every pain episode, avoiding triggers may reduce the occurrence and/or severity of pain crises. Its important to:

Stay hydrated to prevent dehydration. Drinking water is best.

Exercise regularly, but dont overdo it.

Avoid very hot or cold temperatures.

Manage stress to your body and mind.

Get plenty of rest.

Its also important to go for regular health checkups and talk to your doctor about managing pain episodes.

Is it possible to die from sickle cell disease?

SCD can cause a lifetime of health issues and complications that may lead to early death. In developed countries, like the United States, people with SCD often live between 40 and 60 years of age. However, in developing countries, like some countries in Africa, 90% of babies born with SCD will die before age 5.

What is the impact of sickle cell disease on the African-American community?

Severe pain crises lead to frequent ER visits and hospitalizations, which stress the patient and family, as well as the health care system. Also, those living with SCD often face disease misperceptions. For example, people with SCD are frequently believed to be drug abusers, because they have a high tolerance for pain killers. Missed days at school and work interfere with productivity and may lead to the perception that people with SCD are lazy. Studies have also shown that school-age children have a lower IQ due to effects of SCD on their developing brains.

Are there support groups for sickle cell disease?

Yes. National support groups and advocacy organizations are a great way to connect with others living with the disease. There may also be local groups in your area.

What can someone with a friend or family member who has sickle cell disease do to help?

It is important to understand and support those individuals living with SCD. As a friend, be considerate and help direct their focus away from the pain. As a family member, encourage regular checkups and help them communicate their feelings and avoid triggers that lead to a pain crisis. A knowledgeable, compassionate community can help reduce the stigma related to SCD. Stand up for those living with SCD and, now that you know more about the disease, educate others!

Stay tuned for the next Ask Dr. Kevin article, which will appear in September. Meanwhile, here are resources to find more information about sickle cell disease or the collaboration between the NNPA and Pfizer Rare Disease.

About Dr. Kevin Williams

Dr. Kevin Williams is the Chief Medical Officer (CMO) for Pfizer Rare Disease. In this role, he leads a Medical Affairs organization of approximately 150 medical colleagues around the globe supporting Pfizers efforts and portfolio in Rare Disease. Dr. Kevin joined Pfizer in January 2004 as a Director, Regional Medical & Research Specialists working in the HIV disease area.

After moving into a Team Leader position in July 2005, he has served in various leadership roles during his career at Pfizer, most recently as the Global Medical Affairs Vice President for Rare Disease in Pfizers Global Innovative Pharma business unit where he supervised a group of global colleagues providing medical leadership and strategic support for inline and pipeline assets in Endocrinology, Hematology, TTR-Amyloidosis, Gauchers Disease, and other rare diseases. Dr. Kevin moved into his current Rare Disease CMO position in May 2016.

Dr. Kevin received his medical degree from the UCLA School of Medicine and is board certified in Internal Medicine. Following a 2-year fellowship in Health Services Research at UCLA and a brief academic career as an Instructor of Medicine at the UCLA School of Medicine, he spent 8 years in private practice caring for HIV-positive patients while maintaining an academic appointment at the UCLA School of Medicine as an Assistant Clinical Professor of Medicine. In addition to his medical degree, Dr. Kevin has a Masters in Public Health from the UCLA School of Public Health and a Juris Doctorate from Harvard Law School.

See the rest here:
Ask Dr. Kevin: Understanding Sickle Cell Disease - Lasentinel

June 22, 2017 by Sarah Bates NSF-funded researchers have developed a technique that is based on the physical principles of light scattering to non-invasively determine the properties of subcellular structures (such as cell nuclei) in organs, providing physicians with more diagnostic information. Credit: Lev T. Perelman, Beth Israel Deaconess Medical Center and Harvard University

Pancreatic cancer is difficult to detect early because the pancreas is deep inside the abdomen, making potentially cancerous cells hard to reach and identify without surgery.

Researchers funded by the National Science Foundation (NSF) developed a new light-based technique that can identify precancerous and cancerous cystssmall, fluid-filled cavities in the bodyby piggybacking on a standard diagnostic procedure.

"This approach can be called a virtual biopsy, as it does not collect any tissue," said Lev Perelman, professor at Harvard University and director of the Center for Advanced Biomedical Imaging and Photonics at Beth Israel Deaconess Medical Center, whose team developed the tool with the support of the NSF Directorate for Engineering Biophotonics program.

One-fifth of pancreatic cancers come from cysts. While magnetic resonance imaging and other non-invasive imaging techniques in use today can scan for cysts, they have limited accuracy in determining which cysts are malignant and which are benign.

The best available diagnostic approach involves inserting a thin tube called an endoscopic ultrasound through a person's mouth into the stomach and the first part of the small intestine. There, a small needle is inserted through stomach wall or intestine into the pancreas, where it can puncture a cyst. Medical personnel then collect and analyze cyst tissue. But lab results take time and are often inconclusive.

Perelman, who explores the ways in which light interacts with biological tissue, thought that a technique based on the physical principles of light scattering would be able to non-invasively determine the properties of subcellular structures (such as cell nuclei) in organs, providing physicians with diagnostic information.

Imagine a cell or a cellular nucleus, a small ball with a diameter of a fraction of the width of a hair, Perelman explains. If you shine white light on that ball, only part of that light will be reflected back at you and it will come back changed. Certain wavelengths will also be absorbed depending on the ball's composition. The vast majority of cells in the human body only reflect visible light, though some, such as red blood cells, also absorb it.

His team applied light-scattering spectroscopy to several organs before discovering its potential to help overcome the unique challenges posed by the pancreas.

"Pancreatic cysts are a major clinical problem for gastroenterologists," said Douglas Pleskow, clinical chief in the division of gastroenterology at Beth Israel Deaconess Medical Center and associate professor of medicine at Harvard Medical School, who collaborates with Perelman. "We need better tools, and that's where the spectroscopy comes into play. The question is: Can this be used as a reliable tool to tell us whether a cyst is cancerous or not?"

Applying the basic premise about light scattering, the researchers inserted a tiny fiber optic probe connected to a broadband light source into the needle used to collect fluid samples in pancreatic cysts. They gathered the photons reflected from a cyst's surface and then used an algorithm to process the data, providing an immediate result.

"The goal is to make this a real-time diagnosis, and eventually avoid having to puncture the cyst at all," Pleskow said, emphasizing that the tool is still in the research stage. "We anticipate this could replace everything, but medicine takes a long time to change."

In a study published in the journal Nature Biomedical Engineering, the team reported they accurately identified 95 percent of cysts in 25 patients.

"What makes NSF grants so valuable," Perelman said, "is that they provide seed money to figure out basic principles about how stuff works before applying for larger funding needed to advance technology toward making it clinically available. The NSF Biophotonics program, directed by Leon Esterowitz, played an especially critical role in its long-term support for the light-scattering spectroscopy research."

Explore further: Light scattering spectroscopy helps doctors identify early pancreatic cancer

More information: Lei Zhang et al. Light scattering spectroscopy identifies the malignant potential of pancreatic cysts during endoscopy, Nature Biomedical Engineering (2017). DOI: 10.1038/s41551-017-0040

Pancreatic cancer has the lowest survival rate among all major cancers, largely because physicians lack diagnostic tools to detect the disease in its early, treatable stages. Now, a team of investigators led by Lev T. Perelman, ...

A look back at more than half a million patient records has established that patients with pancreatic cysts have a significantly higher overall risk of pancreatic cancer compared to those without such cysts, according to ...

Researchers at the Indiana University School of Medicine have discovered a highly accurate, noninvasive test to identify benign pancreatic cysts, which could spare patients years of nerve-racking trips to the doctor or potentially ...

In a "look-back" analysis of data stored on 130 patients with pancreatic cysts, scientists at Johns Hopkins have used gene-based tests and a fixed set of clinical criteria to more accurately distinguish precancerous cysts ...

Pancreatic cancer is often detected at a late stage, which results in poor prognosis and limited treatment options. Researchers at The Sahlgrenska Academy have now developed a method which identifies the cancer's visible ...

Johns Hopkins scientists have developed a gene-based test to distinguish harmless from precancerous pancreatic cysts. The test may eventually help some patients avoid needless surgery to remove the harmless variety. A report ...

A telecom company in the Netherlands has teamed up with the country's traffic safety authority to develop a bicycle lock that also blocks its mobile network, in a move aimed at protecting young riders who regularly pedal ...

A data analytics firm that worked on the Republican campaign of Donald Trump exposed personal information belonging to some 198 million Americans, or nearly every eligible registered voter, security researchers said Monday.

From "The Jetsons" to "Chitty Chitty Bang Bang", flying cars have long captured the imagination.

Researchers at UC Santa Barbara professor Yasamin Mostofi's lab have given the first demonstration of three-dimensional imaging of objects through walls using ordinary wireless signal. The technique, which involves two drones ...

Your next doctor could very well be a bot. And bots, or automated programs, are likely to play a key role in finding cures for some of the most difficult-to-treat diseases and conditions.

The long range of airborne drones helps them perform critical tasks in the skies. Now MIT spinout Open Water Power (OWP) aims to greatly improve the range of unpiloted underwater vehicles (UUVs), helping them better perform ...

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

See the original post:
Light-scattering tool peers into pancreas to find cancer - Phys.Org

June 22, 2017 Credit : Susanna M. Hamilton, Broad Communications

Scientists at the Broad Institute of MIT and Harvard have found that a set of genetic mutations in blood cells that arises during aging may be a major new risk factor for cardiovascular disease. In contrast to inherited genetic predispositions and traditional lifestyle risk factors, such as smoking or an unhealthy diet, the new mutations are "somatic mutations" that originate in stem cells in the bone marrow as people age.

Because the mutations are relatively common in older people (over 10% of people over the age of 70 harbor at least one of these mutations), potential future efforts to screen for the mutations in blood cells, identify people at increased risk for coronary heart disease, and reduce risk in those individuals through lifestyle changes or therapeutic interventions could have a significant clinical impact, according to the researchers.

"There is more work to be done, but these results demonstrate that pre-malignant mutations in blood cells are a major cause of cardiovascular disease that in the future may be treatable either with standard therapies or new therapeutic strategies based on these findings," said Benjamin Ebert, a co-senior author of the new study, an institute member at the Broad, a professor of medicine at Harvard Medical School, and a hematologist at Brigham and Women's Hospital.

Featured in the New England Journal of Medicine, the work also contributes to the broader understanding of pathogenesis in coronary heart disease by supporting the hypothesis that inflammation, in addition to elevated cholesterol levels, plays an important role in this illness and potentially other diseases of aging.

"A key finding from this study is that somatic mutations are actually modulating risk for a common disease, something we haven't seen other than in cancer," said first author Siddhartha Jaiswal, a pathologist at Massachusetts General Hospital and researcher in the Ebert lab. "It opens up interesting questions about other diseases of aging in which acquired mutations, in addition to lifestyle and inherited factors, could modulate disease risk."

Previous research led by Ebert and Jaiswal revealed that some somatic mutations that are able to confer a selective advantage to blood stem cells become much more frequent with aging. They named this condition "clonal hematopoiesis of indeterminate potential," (CHIP), and found that it increases the risk of developing a blood cancer more than 10-fold and it appeared to increase mortality from heart attacks or stroke. In the new study, the researchers analyzed data from four case-control studies on more than 8,000 people and found that having one of the CHIP-related mutations nearly doubled the risk for coronary heart disease, with the mutations conferring an even greater risk in people who have previously had a heart attack before age 50.

While the human genetics data showed a strong association between CHIP and coronary heart disease, the team hoped to uncover the underlying biology. Using a mouse model prone to developing atherosclerosis, the scientists showed that loss of one of the CHIP-mutated genes, Tet2, in bone marrow cells leads to larger atherosclerotic plaques in blood vessels, evidence that this mutation can accelerate atherosclerosis in mice.

Atherosclerosis is believed to be a disease of chronic inflammation that can arise in response to excess cholesterol in the vessel wall. To examine this on a cellular level the team turned to the macrophage, an immune cell found in atherosclerotic plaques that can develop from CHIP stem cells and carry the same mutations. Because Tet2 and other CHIP-related mutations are known to be so-called "epigenetic regulators" that can alter the activity of other genes, the team examined gene expression levels in the Tet2-mutated macrophages from mice. They found that the mutated cells appear to be "hyper-inflammatory" with increased expression of inflammatory molecules that contribute to atherosclerosis. In support of this finding, humans with TET2 mutations also had higher levels of one of these molecules, IL-8, in their blood.

The work demonstrates that CHIP associates with coronary heart disease in humans, that mutation of the CHIP-related gene Tet2 causes atherosclerosis in mice, and that an inflammatory mechanism likely underlies the process. More work is needed to show whether other genes that are mutated in CHIP also lead to increased inflammation. The team is also exploring whether interventions such as cholesterol lowering therapy or anti-inflammatory drugs might have benefit in people with CHIP.

Inflammation is also thought to modulate several other diseases of aging besides cardiovascular disease, such as autoimmune disorders and neurodegenerative disease. Because CHIP also increases in frequency with age, somatic mutations that alter inflammatory processes could influence several diseases of aging, though more work is needed to test this possibility.

"By combining genetic analysis on large cohorts with disease model and gene expression studies, we've been able to confirm the earlier hints of CHIP's surprising role in cardiovascular disease," said co-senior author Sekar Kathiresan, director of the Broad's Cardiovascular Disease Initiative, associate professor of medicine at Harvard Medical School, and director of the Center for Genomic Medicine at Massachusetts General Hospital. "Beyond the mutations that you inherit from your parents, this work reveals a new genetic mechanism for atherosclerosismutations in blood stem cells that arise with aging."

Explore further: A role for mutated blood cells in heart disease?

More information: Siddhartha Jaiswal et al. Clonal Hematopoiesis and Risk of Atherosclerotic Cardiovascular Disease, New England Journal of Medicine (2017). DOI: 10.1056/NEJMoa1701719

A new study provides some of the first links between relatively common mutations in the blood cells of elderly humans and atherosclerosis.

A significant percentage of lymphoma patients undergoing transplants with their own blood stem cells carry acquired genetic mutations that increase their risks of developing second hematologic cancers and dying from other ...

Imagine this scenario on a highway: A driver starts to make a sudden lane change but realizes his mistake and quickly veers back, too late. Other motorists have already reacted and, in some cases, collide. Meanwhile, the ...

Gene mutations accumulating in cells are typical of the development of cancer. Finnish researchers have found that a similar accumulation of mutations occurs also in some patients with rheumatoid arthritis.

A new strategy - an injectable antibody - for lowering blood lipids and thereby potentially preventing coronary artery disease and other conditions caused by the build-up of fats, cholesterol, and other substances on the ...

Natural genetic changes can put some people at high risk of certain conditions, such as breast cancer, Alzheimer's disease or high blood pressure. But in rare cases, genetic errors also can have the opposite effect, protecting ...

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Originally posted here:
Aging-related mutations in blood cells represent major new risk factor for cardiovascular disease - Medical Xpress

June 20, 2017 05:00 ET | Source: BCC Research

Wellesley, Mass., June 20, 2017 (GLOBE NEWSWIRE) --

Fast-moving developments in 3D cell culture tools and technology are accelerating cancer research and clinical applications, along with other medical research and safety applications. A new report by BCC Research forecasts that some segments could see CAGR as high as 44% in products for pharmaceuticals development through 2021. In another example, neurological safety testing could grow from a $5 million segment in 2015 to $95 million by 2021, according to 3D Cell Cultures: Technologies and Global Markets.

New cell culture products and applications are proliferating even faster than a prior BCC Research report predicted in 2015. Companies such as ThermoFisher, GEHealthcare, MerckMillipore and a range of start-ups and spinouts are pursuing diverse market segments, from cosmetics and skin care to cardiac toxicology and metabolic reactions to new drugs. The new 3D technology allows for groundbreaking visibility into tissue and cancer behaviors in the body, compared with animal testing or more general, 2D in vitro technologies.

Bioreactors with microcarriers are another 3D application seeing rapid market growth. Skin and artificial skin substitutes have been in use for years. Now some of the knowledge behind those advancements are being applied to internal medicine from liver function and metabolic disease and other adjacent fields. These new applications promise not only improved medical safety in determining dosages and tailoring treatments to a patients condition and situation, but also breakthroughs in basic research, drug discovery and development.

Research Highlights

"The standards and best practices emerging in precision cancer care, and the new findings in CNS research could certainly speed up patient-centric care. Some call it personalized medicine, or precision medicine, and it really is a revolution compared with developing mass-market drugs. We are already seeing stem cells and other tools having an impact thanks to 3D Cell Culture technology, says Robert G. Hunter, senior healthcare editor at BCC Research.

About BCC Research

BCC Research is a publisher of market research reports that provide organizations with intelligence to drive smart business decisions. By partnering with industry experts worldwide, BCC Research provides unbiased measurements and assessments of global markets covering major industrial and technology sectors, including emerging markets. For more information, please visit bccresearch.com. Follow BCC Research on Twitter at @BCCResearch.

Related Articles

Wellesley Hills, Massachusetts, UNITED STATES

BCC Research Logo

LOGO URL | Copy the link below

Formats available:

Visit link:
3D Cell Culture Tech Advances Medical Research and Treatments - GlobeNewswire (press release)