Two-thirds of cancers are due to "bad luck"

(CBS) - Although about one-third of cancers can be linked to environmental factors or inherited genes, new research suggests the remaining two-thirds may be caused by random mutations.

These mutations take place when stem cells divide, according to the study by researchers at Johns Hopkins Kimmel Cancer Center. Stem cells regenerate and replace cells that die off. If stem cells make random mistakes and mutate during this cell division, cancer can develop. The more of these mistakes that happen, the greater a person's risk that cells will grow out of control and develop into cancer, the study authors explained in a Hopkins news release.

Although unhealthy lifestyle choices, such as smoking, are a contributing factor, the researchers concluded that the "bad luck" of random mutations plays a key role in the development of many forms of cancer.

"All cancers are caused by a combination of bad luck, the environment and heredity, and we've created a model that may help quantify how much of these three factors contribute to cancer development," said Dr. Bert Vogelstein, professor of oncology at the Johns Hopkins University School of Medicine.

"Cancer-free longevity in people exposed to cancer-causing agents, such as tobacco, is often attributed to their 'good genes,' but the truth is that most of them simply had good luck," added Vogelstein, who is also co-director of the Ludwig Center at Johns Hopkins and an investigator at the Howard Hughes Medical Institute.

The researchers said their findings might not only change the way people perceive their risk for cancer, but also funding for cancer research.

Cristian Tomasetti is a biomathematician and assistant professor of oncology at the Johns Hopkins University School of Medicine and Bloomberg School of Public Health. "If two-thirds of cancer incidence across tissues is explained by random DNA mutations that occur when stem cells divide, then changing our lifestyle and habits will be a huge help in preventing certain cancers, but this may not be as effective for a variety of others," Tomasetti said in the news release.

"We should focus more resources on finding ways to detect such cancers at early, curable stages," Tomasetti suggested.

For the study, the investigators looked at previous studies for the number of stem cell divisions in 31 different body tissue types and compared those rates to the lifetime risk of cancer in those areas.

The researchers said they weren't able to include some major forms of cancer, such as breast and prostate cancer, due to a lack of reliable research on the rate of stem cell division in those areas.

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Two-thirds of cancers are due to "bad luck"

Random Mutations Responsible for About Two-Thirds of Cancer Risk: Study

THURSDAY, Jan. 1, 2015 (HealthDay News) -- Although about one-third of cancers can be linked to environmental factors or inherited genes, new research suggests the remaining two-thirds may be caused by random mutations.

These mutations take place when stem cells divide, according to the study by researchers at Johns Hopkins Kimmel Cancer Center. Stem cells regenerate and replace cells that die off. If stem cells make random mistakes and mutate during this cell division, cancer can develop. The more of these mistakes that happen, the greater a person's risk that cells will grow out of control and develop into cancer, the study authors explained in a Hopkins news release.

Although unhealthy lifestyle choices, such as smoking, are a contributing factor, the researchers concluded that the "bad luck" of random mutations plays a key role in the development of many forms of cancer.

"All cancers are caused by a combination of bad luck, the environment and heredity, and we've created a model that may help quantify how much of these three factors contribute to cancer development," said Dr. Bert Vogelstein, professor of oncology at the Johns Hopkins University School of Medicine.

"Cancer-free longevity in people exposed to cancer-causing agents, such as tobacco, is often attributed to their 'good genes,' but the truth is that most of them simply had good luck," added Vogelstein, who is also co-director of the Ludwig Center at Johns Hopkins and an investigator at the Howard Hughes Medical Institute.

The researchers said their findings might not only change the way people perceive their risk for cancer, but also funding for cancer research.

Cristian Tomasetti is a biomathematician and assistant professor of oncology at the Johns Hopkins University School of Medicine and Bloomberg School of Public Health. "If two-thirds of cancer incidence across tissues is explained by random DNA mutations that occur when stem cells divide, then changing our lifestyle and habits will be a huge help in preventing certain cancers, but this may not be as effective for a variety of others," Tomasetti said in the news release.

"We should focus more resources on finding ways to detect such cancers at early, curable stages," Tomasetti suggested.

For the study, the investigators looked at previous studies for the number of stem cell divisions in 31 different body tissue types and compared those rates to the lifetime risk of cancer in those areas.

The researchers said they weren't able to include some major forms of cancer, such as breast and prostate cancer, due to a lack of reliable research on the rate of stem cell division in those areas.

Original post:
Random Mutations Responsible for About Two-Thirds of Cancer Risk: Study

Two-thirds of cancers are due to "bad luck," study finds

16 hours 58 minutes ago by Mary Elizabeth Dallas - CBS News

Although about one-third of cancers can be linked to environmental factors or inherited genes, new research suggests the remaining two-thirds may be caused by random mutations.

These mutations take place when stem cells divide, according to the study by researchers at Johns Hopkins Kimmel Cancer Center. Stem cells regenerate and replace cells that die off. If stem cells make random mistakes and mutate during this cell division, cancer can develop. The more of these mistakes that happen, the greater a person's risk that cells will grow out of control and develop into cancer, the study authors explained in a Hopkins news release.

Although unhealthy lifestyle choices, such as smoking, are a contributing factor, the researchers concluded that the "bad luck" of random mutations plays a key role in the development of many forms of cancer.

"All cancers are caused by a combination of bad luck, the environment and heredity, and we've created a model that may help quantify how much of these three factors contribute to cancer development," said Dr. Bert Vogelstein, professor of oncology at the Johns Hopkins University School of Medicine.

"Cancer-free longevity in people exposed to cancer-causing agents, such as tobacco, is often attributed to their 'good genes,' but the truth is that most of them simply had good luck," added Vogelstein, who is also co-director of the Ludwig Center at Johns Hopkins and an investigator at the Howard Hughes Medical Institute.

The researchers said their findings might not only change the way people perceive their risk for cancer, but also funding for cancer research.

Cristian Tomasetti is a biomathematician and assistant professor of oncology at the Johns Hopkins University School of Medicine and Bloomberg School of Public Health. "If two-thirds of cancer incidence across tissues is explained by random DNA mutations that occur when stem cells divide, then changing our lifestyle and habits will be a huge help in preventing certain cancers, but this may not be as effective for a variety of others," Tomasetti said in the news release.

"We should focus more resources on finding ways to detect such cancers at early, curable stages," Tomasetti suggested.

For the study, the investigators looked at previous studies for the number of stem cell divisions in 31 different body tissue types and compared those rates to the lifetime risk of cancer in those areas.

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Two-thirds of cancers are due to "bad luck," study finds

Aggie grad happy to put off retiring to advance stem cell science

David Eller could have retired a long time ago.

At the age of 76, he could spend his days on permanent vacation fly-fishing in Idaho, golfing in San Antonio or skiing on the Italian-Austrian border like he has done to get away from work for many years.

He isn't working because he is desperate for money and accolades. He's had those for many years.

During the '80s, Eller oversaw revolutionary cattle cloning practices as CEO of Granada BioSciences, a company he founded. He served as chairman of the Texas A&M System Board of Regents from 1983 to 1989. The Oceanography & Meteorology Building on A&M's campus was named in his honor in 1988.In 2000, he was namedexecutive vice president and president of DuPont's European operations.He is president of Eller Holding Company, a privately-held family investment company.

Instead of settling down after a life of amassing great wealth and personal achievement, he co-founded Houston-based Celltex Therapeutics Corporation in 2011 and put himself at the forefront of the contentious issue of autologous stem cell therapy in the name of fighting for ill people to harness the healing properties of their own bodies.

These days it is Celltex that drives Eller's passion, enabling him to combine his humanitarian and entrepreneurial impulses and perhaps one day leave a lasting mark on health care. It is the culmination of the journey he began on the A&M campus in the late 1950s.

"When I started this company I really didn't need another job," Eller said. "I certainly didn't need one with so many rules and regulations we had to adhere to that gives us a lot of headaches. All in all, the biggest reward out of it is seeing people improve their quality of life."

Since 2011, the company has helped treat approximately 600 patients between the ages of 6 and 96 by injecting stem cells taken from their own bodies into a troubled area with no complications, according to Eller. He believes Celltex's reach could expand tenfold if the entire operation could be conducted out of the United States, where the practice was banned in 2012, but that could take years of fighting a two-front war.

The daily war is educating as many doctors and potential patients as possible on the benefits of being treated with a one's own stem cells. The second, long-term war is maneuvering through the FDA's web of red tape that currently bans the practice from being performed on U.S. soil.

Eller spent four years in the Texas A&M Corps of Cadets until his 1959 graduation, which he says plays a major role in his character.

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Aggie grad happy to put off retiring to advance stem cell science

Official lured big-dollar donor into giving $100 million for flashy stem cell center.

A high-dollar fundraiser for the so-called health sciences branch of UCSD is heading off to the City of Hope in Duarte to become chief rainmaker there.

Kristin Jean Bertell, who was named associate vice chancellor for Health Sciences Development at UCSD two years ago in October, received gross pay of $247,800 in 2013, according to the University of California's salary website.

Set to report in February as "chief philanthropy officer, Bartell will "provide executive and strategic oversight for all aspects of City of Hopes philanthropic efforts, as the cancer treatment center and biomedical research institution enters a new era of growth and development," according to the nonprofit's announcement of the move.

A year before being named associate vice chancellor, Bertell became "executive director of development for principal gifts" for UCSD's health sciences operation.

Prior to that the UCLA graduate had variously served as vice president for Institute Relations at the Salk Institute for Biological Studies, and as a senior vice president of the Greenwood Company in San Francisco, which "is particularly well-known for the development of successful fundraising strategies for health care institutions grappling with the fundraising challenges caused by health systems, tightening institutional budgets, [and] dramatic changes in the delivery of health care and managed care," the firm's website says.

Luring elderly high-rollers into funding flashy medical centers named after themselves has grown into a multibillion-dollar national business, and Bertell is no slacker, credited in the City of Hope's December 15 news release with having been "the primary development lead in securing a landmark $100 million donation" for UCSD's Sanford Stem Cell Clinical Center.

The cash came from billionaire T. Denny Sanford, who piled up big money at South Dakota's First Premier bank issuing high-interest credit cards to so-called credit-impaired customers.

"First Premier now has 3 million active cardholders," Forbes reported in 2007. "Its cards are to be avoided if possible they have 10% to 20% interest rates but cost $175 in fees to get a card with a $1,000 limit. The typical customer stays only 18 months before graduating to something better. 'We provide a lifeline for credit-impaired people,' Sanford says."

According to UCSD's website, "His gift to create the Sanford Stem Cell Clinical Center is the second largest donation received by UC San Diego in its 53-year history, following only the $110 million gift by Joan and Irwin Jacobs to endow the UC San Diego Jacobs School of Engineering."

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Official lured big-dollar donor into giving $100 million for flashy stem cell center.

Knee meniscus fixed using revolutionary stem cell procedure

Meg Goodale

Lise Fortier checks the meniscus of a sheep that she operated on last summer, using a groundbreaking new procedure to regenerate knee meniscus.

Researchers report on a revolutionary new procedure that uses 3-D printing and the bodys stem cells to regenerate knee meniscus, a tissue lining that acts as a natural cushion between the femur and tibia.

People with damaged menisci develop arthritis and are forced to limit their activity.

The procedure, published online Dec. 10 in the journal Science Translational Medicine, has proved successful in sheep at Cornell University six months after surgery, though the researchers will monitor the sheep for a year to ensure the animals do not develop arthritis. Sheep menisci are structurally similar to those of humans, and clinical trials in humans could begin in two to three years.

Most middle-aged people who end up with a degenerate meniscus have it trimmed up [surgically], but if you lose more than 20 to 30 percent, then you are very prone to arthritis, said Lisa Fortier, professor of large animal surgery at Cornells College of Veterinary Medicine and a co-author of the paper; she led the meniscus surgeries on sheep. If everybody who needed it could replace their meniscus they could slow arthritis and maintain their full function, Fortier added.

The technique was developed by the papers senior author Jeremy Mao, professor of dental medicine at Columbia University Medical Center, and involves taking an MRI of the patients (in this case sheeps) knee. Using a 3-D printer, Mao printed a biodegradable polyester scaffold in the exact shape of a patients meniscus. Through multiple lab experiments, Maos group discovered that two growth factors, when used in specific concentrations and at critical times, recruited the most stem cells for meniscal repair. The growth factors were then laced into the scaffold, allowing the bodys stem cells build a new meniscus four to six weeks after surgery.

Currently, a torn meniscus requires replacement with cadaver tissue, which has a low success rate and can lead to disease and rejection, and synthetic menisci have proved ineffective and hard to fit properly in diversely built patients.

Approximately a million people undergo meniscus surgeries each year in the United States.

Co-authors include Scott Rodeo, orthopedic surgeon at the Hospital for Special Surgery, an affiliate of Weill Cornell Medical College; and Chang H. Lee, Chuanyong Lu and Cevat Erisken, all at Columbia University Medical Center.

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Knee meniscus fixed using revolutionary stem cell procedure

Japan scientist quits as cell research discredited

SUB

FILE - In this Jan. 28, 2014 file photo, researcher Haruko Obokata, the lead author of a widely heralded stem-cell research paper by the Japanese government-funded laboratory Riken Center for Development Biology, speaks about research results during a news conference in Kobe, western Japan. Obokata said in a statement Friday, Dec. 19, 2014 that she was leaving the Riken Center for Developmental Biology after the lab concluded the stem cells she said she had created probably never existed. The center said it had stopped trying to match Obokata's results. (AP Photo/Kyodo News) JAPAN OUT, MANDATORY CREDIT

Posted: Friday, December 19, 2014 6:25 am | Updated: 11:45 am, Fri Dec 19, 2014.

Japan scientist quits as cell research discredited Associated Press |

TOKYO (AP) The Japanese researcher whose claim of a major breakthrough in stem cell research was discredited resigned after the government lab where she worked failed to replicate her results.

Haruko Obokata said in a statement Friday that she was leaving the Riken Center for Developmental Biology after the lab concluded the stem cells she said she had created probably never existed. The center said it had stopped trying to match Obokata's results.

"Now, I am just exhausted. For the results to end this way is just perplexing," she said.

Obokata initially was lauded for leading the research that raised hopes for a discovery of a simple way to grow replacement tissue. But questions about the validity of the research prompted Riken scientists, including Obokata, to retract two scientific papers.

The allegations of research misconduct prompted a shake-up at Riken.

2014 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.

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Japan scientist quits as cell research discredited

'Genome editing' could correct genetic mutations for future generations

Scientists at Indiana University and colleagues at Stanford and the University of Texas have demonstrated a technique for "editing" the genome in sperm-producing adult stem cells, a result with powerful potential for basic research and for gene therapy.

The researchers completed a "proof of concept" experiment in which they created a break in the DNA strands of a mutant gene in mouse cells, then repaired the DNA through a process called homologous recombination, replacing flawed segments with correct ones.

The study involved spermatogonial stem cells, which are the foundation for the production of sperm and are the only adult stem cells that contribute genetic information to the next generation. Repairing flaws in the cells could thus prevent mutations from being passed to future generations.

"We showed a way to introduce genetic material into spermatogonial stem cells that was greatly improved from what had been previously demonstrated," said Christina Dann, associate scientist in the Department of Chemistry at IU Bloomington and a co-author of the study. "This technique corrects the mutation, theoretically leaving no other mark on the genome."

The paper, "Genome Editing in Mouse Spermatogonial Stem/Progenitor Cells Using Engineered Nucleases," was published in the online science journal PLOS-ONE.

The lead author, Danielle Fanslow, carried out the research as an IU research associate and is now a doctoral student at Northwestern University. Additional co-authors are from the Stanford School of Medicine and the University of Texas Southwestern Medical Center.

A challenge to the research was the fact that spermatogonial stem cells, like many types of adult stem cells, are notoriously difficult to isolate, culture and work with. It took years of intensive effort by multiple laboratories before conditions were created a decade ago to maintain and propagate the cells.

For the IU research, a primary hurdle was to find a way to make specific, targeted modifications to the mutant mouse gene without the risk of disease caused by random introduction of genetic material. The researchers used specially designed enzymes, called zinc finger nucleases and transcription activator-like effector nucleases, to create a double strand break in the DNA and bring about the repair of the gene.

Stem cells that had been modified in the lab were then transplanted into the testes of sterile mice. The transplanted cells grew or colonized within the mouse testes, indicating the stem cells were viable. However, attempts to breed the mice were not successful.

"Whether the failure to produce sperm was a result of abnormalities in the transplanted cells or the recipient testes was unclear," the researchers write.

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'Genome editing' could correct genetic mutations for future generations

Baby cells learn to communicate using the lsd1 gene

21 hours ago Fruit fly ovarian follicle progenitor cells, with different colors marking a specific kind of activity (red) specific gene expression (green) and nuclear DNA (blue). Credit: Ming-Chia Lee and Allan Spradling

We would not expect a baby to join a team or participate in social situations that require sophisticated communication. Yet, most developmental biologists have assumed that young cells, only recently born from stem cells and known as "progenitors," are already competent at inter-communication with other cells.

New research from Carnegie's Allan Spradling and postdoctoral fellow Ming-Chia Lee shows that infant cells have to go through a developmental process that involves specific genes before they can take part in the group interactions that underlie normal cellular development and keep our tissues functioning smoothly. The existence of a childhood state where cells cannot communicate fully has potentially important implications for our understanding of how gene activity on chromosomes changes both during normal development and in cancerous cells. The work is published in Genes and Development.

The way that the molecules that package a cell's chromosomes are organized in order to control gene activity is known as the cell's "epigenetic state." The epigenetic state is fundamental to understanding Spradling and Lee's findings. To developmental biologists, changes in this epigenetic state ultimately explain how the cell's properties are altered during tissue maturation.

"In short, acquired epigenetic changes in a developing cell are reminiscent of the learned changes the brain undergoes during childhood," Spradling explained. "Just as it remains difficult to map exactly what happens in a child's brain as it learns, it is still very difficult to accurately measure epigenetic changes during cellular development. Not enough cells can usually be obtained that are at precisely the same stage for scientists to map specific molecules at specific chromosomal locations."

Lee and Spradling took advantage of the unsurpassed genetic tools available in the fruit fly to overcome these obstacles and provide new insight into the epigenetics of cellular development.

Using a variety of tools and techniques, they focused on cells in the fruit fly ovary and were able identify a specific gene called lsd1 that is needed for ovarian follicle progenitor cells to mature at their normal rate. The researchers found that the amount of the protein that is encoded by this gene, Lsd1, which is present in follicle progenitors decreases as the cells approach differentiation. What's more, the onset of differentiation could be shifted by changing the levels of Lsd1 protein that are present. They deduced that differentiation ensues when Lsd1 levels fall below a critical threshold, and that this likely corresponds to when genes can be stably expressed.

"The timing of differentiation is very important for normal development," Lee said. "Differentiation onset determines how many times progenitors divide, and even small perturbations in Lsd1 levels changed the number of follicle cells that were ultimately produced, which reduced ovarian function."

Previously, it was thought that the follicle cell progenitors started to differentiate based on an external signal they received from another kind of ovarian cells known as germ cells. Lee and Spradling found that while this germ cell signal was essential, it was already being regularly sent even before the progenitors responded. Instead, it was the Lsd1-mediated change in their epigenetic state that timed when progenitor cells started to respond to the signal and begun differentiating. Once they become competent, however, differentiating follicle cells communicate extensively with their neighbors, and continued to do so throughout their lives.

As is frequently the case in basic biological research, the molecules and mechanisms studied here are found in most multicellular animals and hence the researchers conclusions are likely to apply broadly throughout the animal kingdom, including in humans.

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Baby cells learn to communicate using the lsd1 gene

Canadian scientists crack stem cell reprogramming code

By Sheryl Ubelacker The Canadian Press

WATCH: Dr. Andras Nagy describes the scientific breakthrough he led in solving the mystery of the stem cell reprogramming code.

TORONTO A Canadian-led international team of researchers has begun solving the mystery of just how a specialized cell taken from a persons skin is reprogrammed into an embryonic-like stem cell, from which virtually any other cell type in the body can be generated.

The research is being touted as a breakthrough in regenerative medicine that will allow scientists to one day harness stem cells to treat or even cure a host of conditions, from blindness and Parkinsons disease to diabetes and spinal cord injuries.

Besides creating the reprogramming roadmap, the scientists also identified a new type of stem cell, called an F-class stem cell due to its fuzzy appearance. Their work is detailed in five papers published Wednesday in the prestigious journals Nature and Nature Communications.

Dr. Andras Nagy, a senior scientist at Mount Sinai Hospital in Toronto, led the team of 50 researchers from Canada, the Netherlands, South Korea and Australia, which spent four years analyzing and cataloguing the day-by-day process that occurs in stem cell reprogramming.

The work builds on the 2006-2007 papers by Shinya Yamanaka, who showed that adult skin cells could be turned into embryonic-like, or pluripotent, stem cells through genetic manipulation, a discovery that garnered the Japanese scientist the Nobel Prize in 2012.

Nagy likened the roughly 21-day process to complete that transformation to a black box, so called because scientists did not know what went on within the cells as they morphed from one cell type into the other.

It was just like a black box, Nagy said Wednesday, following a briefing at the hospital. You start with a skin cell, you arrive at a stem cell but we had no idea what was happening inside the cell.

Nagys team set about cataloguing the changes as they occurred by removing cells from culture dishes at set points during the three-week period, then analyzing such cellular material as DNA and proteins present at that moment.

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Canadian scientists crack stem cell reprogramming code