(Press-News.org) (SACRAMENTO, Calif.) -- Researchers at UC Davis, in collaboration with colleagues at Jackson Laboratory, have developed a new way to personalize treatments for aggressive bladder cancer. In early proof-of-concept research, the team took bladder tumors from individual patients, identified actionable mutations and grafted the tumors into mice. From there, the researchers simultaneously tested multiple therapies in the tumor models. Treatments that were effective in the models could then be given to patients. The research was published today in the journal PLoS One.
"By prescreening, we can determine which medication works, providing a much higher chance the patient will benefit," said first author Chong-Xian Pan, a genitourinary oncologist. "This can reduce toxicity, increase efficiency and lower costs."
In theory, finding a tumor's mutations should outline a clear treatment plan, as targeted drugs are matched with genetic anomalies. However, although genomic tools can find mutations, they don't always identify which ones drive a patient's cancer.
"Look at how many mutations a cancer can have -- from only a few in pediatric cancers to dozens or hundreds in adult cancers," said Pan. "Lung cancer probably has hundreds of mutations and only a few of those are important. But at this point we can't always figure out which mutations are important and which are unimportant."
Without knowing which mutations are crucial to cancer growth, oncologists must opt for one therapy over another. If the choice is wrong, time and toxicity can make it difficult to backtrack and try a different treatment.
"The patient gets a biopsy and we send the tissue off for genomic analysis, which will show us abnormalities that can be treated," said Ralph de Vere White, distinguished professor of urology and director of the UC Davis Comprehensive Cancer Center. "Let's say there are four of them. Now we have to guess which one is driving the cancer, and the success rate is about 12 percent. That's putting the patient through a lot for just 12 percent."
Though Pan's study was small, the grafts showed remarkable genetic fidelity to the original patient tumors -- between 92 and 97 percent -- even after several months. This outcome proved vastly more effective than growing cell lines in a dish, which deviate from the mother tumor in just a few days.
The new model also provided information that would be impossible to obtain in patients, the researchers said. Because tumors develop more rapidly in mice, they could quickly determine which therapies were effective. They could also conduct multiple biopsies to follow tumor evolution, identify escape mutations and test therapeutic countermoves. Most importantly, the grafts provided insights into which drugs could help patients.
"In one case, the drug cisplatin didn't work and gemcitabine barely worked, but the combination really knocked the tumor out in the mouse," said Pan. "And that's exactly what happened in the patient."
The researchers said that while grafting patient tumors for further study holds a great deal of promise, the ultimate goal is to use computers to help select effective treatments.
"We're not saying the mouse model is the answer," said de Vere White, "but we have a high failure rate with the standard of care, and we're trying to figure out if the mouse can helps us do better. In time, we'd like to be able to biopsy the patient, sequence the tumor, feed that information into the computer and have the computer tell us which therapy will work."
INFORMATION:
Other authors were Hongyong Zhang, Clifford G. Tepper, Tzu-yin Lin, Ryan R. Davis Paramita M. Ghosh and David R. Gandara at UC Davis; James Keck, Carol Bult, Susan Airhart and Edison Liu at The Jackson Laboratory; and Parkash Gill at the University of Southern California.
This research was supported by the Veteran Administration (1I01BX001784), the National Cancer Institute (P30 CA093373) and The Laney Foundation.
To learn more about the UC Davis Comprehensive Cancer Center, go to http://cancer.ucdavis.edu.
About 500,000 babies are born premature in the United States each year, according to the U.S. National Library of Medicine. Those infants, born before 37 weeks of gestation, will likely deal with the threat of numerous complications or even death.
Accurate data on how those infants fare is important as doctors and parents face difficult decisions. Dr. Michael Malloy, a neonatologist and professor at the University of Texas Medical Branch at Galveston, recently took a closer look at the infant mortality rates of extremely preterm infants.
What Malloy found and described ...
New research has found that people with high levels of autistic traits are more likely to produce unusually creative ideas.
Psychologists from the University of East Anglia (UEA) and University of Stirling examined the relationship between autistic-like traits and creativity. While they found that people with high autistic traits produced fewer responses when generating alternative solutions to a problem - known as 'divergent thinking' - the responses they did produce were more original and creative. It is the first study to find a link between autistic traits and the ...
Every hospital should have access to regional multidisciplinary teams that can provide expert advice for children and adolescents with concerns about sex development, and provide them and their parents with psychological support, according to a revised Society for Endocrinology guideline on disorders of sex development (DSD) published today in Clinical Endocrinology.
Recommendations include:
Expert input should be provided in all cases where sex assignment is delayed at birth
In adolescents, DSD should be considered in boys and girls with abnormal pubertal progress
...
The death rate among pre-school children in the UK is almost double that of Sweden, with prematurity, congenital abnormalities, and infections all taking a significant toll, finds research published online in Archives of Disease in Childhood.
The findings prompt the researchers to call for a stronger focus on prevention to improve the UK's position on the European child mortality league table.
The researchers compared causes of death among children under the age of 5 in the UK and Sweden, using nationally collated data spanning the period 2006-2008 to tease out the ...
Rings made of titanium--an increasingly popular alternative to gold and silver--are giving emergency doctors a headache because they are so difficult to prize off swollen fingers, reveals a case study published online in Emergency Medicine Journal.
But now help is at hand, thanks to the ingenuity of plastic surgeons.
The popularity of titanium rings is growing because the metal is light yet strong, extremely durable, and doesn't cause skin allergies.
But a swollen finger caused by ring constriction is a relatively common problem in emergency care. And if not dealt ...
Highlights
Most donors and recipients support swapping health information before kidney transplantation, but there was low interest in sharing social information.
Both donors and recipients wanted the transplant team involved in information disclosure.
Most donors and recipients did not think the recipient had a right to know why a donor was excluded from donating.
Approximately 6,000 living donor kidney transplants are performed annually in the United States.
Washington, DC (August 13, 2015) -- Both donors and recipients want more information about each ...
Camden and Newark, New Jersey, are perceived as two of the most violent cities in the nation, yet New Jersey's police officers are among the least likely to get shot on the job. Montana, with its serene landscapes and national parks, has among the highest homicide rates for law enforcement officers. Why?
Across all 50 states and the District of Columbia, homicides of police officers are linked to the statewide level of gun ownership, according to a new study published in the American Journal of Public Health. The study found that police officers serving in states with ...
DALLAS, August 13, 2015 -- Smartphone applications and wearable sensors have the potential to help people make healthier lifestyle choices, but scientific evidence of mobile health technologies' effectiveness for reducing risk factors for heart disease and stroke is limited, according to a scientific statement from the American Heart Association, published in the association's journal Circulation.
The new statement reviewed the small body of published, peer-reviewed studies about the effectiveness of mobile health technologies (mHealth) for managing weight, increasing ...
At home on the sofa, in a hospital bed, or in a care home: where a death takes place is always recorded on the death certificate. Until now, however, this information has never been collated and evaluated. In an Original Article in the current issue of Deutsches Ärzteblatt International (Dtsch Arztbl Int 112:496-504), Burkhard Dasch and his co-authors analyze for the first time the place of death records for Germany. What they found was that every second person died in a hospital; only one in four died at home.
The study evaluated more than 24 000 death certificates ...
Marks on two 3.4 million-year-old animal bones found at the site of Dikika, Ethiopia, were not caused by trampling, an extensive statistical analysis confirms. The Journal of Human Evolution is publishing the results of the study, which developed new methods of fieldwork and analysis for researchers exploring the origins of tool making and meat eating in our ancestors.
"Our analysis clearly shows that the marks on these bones are not characteristic of trampling," says Jessica Thompson, an assistant professor of anthropology at Emory University and lead author of the study. ...
