Category Archives: Gene Medicine

MONDAY, April 3, 2017 (HealthDay News) -- Many survivors of childhood cancer have mutations in cancer-associated genes, possibly increasing their risk for cancers later in life, researchers report.

The new study included more than 3,000 people who survived childhood cancer for five years or more. More than 12 percent had changes in one of 156 genes linked to increased risk of cancer, the findings showed.

By age 45, more than one-quarter of the people had developed another cancer, most commonly meningioma (brain tumor), thyroid cancer, breast cancer and non-melanoma skin cancer, according to the study.

The report was scheduled for presentation Monday at an American Association for Cancer Research (AACR) meeting in Washington, D.C. Research presented at medical meetings should be considered preliminary until it is published in a peer-reviewed journal.

"The remarkable advances realized over the past four decades in the treatment and survival of pediatric cancer patients is one of the most notable success stories within the cancer field," co-senior study author Les Robison said in an AACR news release. Robison is chairman of St. Jude Children's Research Hospital's department of epidemiology and cancer control in Memphis, Tenn.

"However, childhood cancer survivors are at increased risk of [additional cancers], largely considered to be therapy-related," he added.

Many types of childhood cancer have cure rates of more than 80 percent, and there are now more than 400,000 long-term survivors of childhood cancer in the United States, Robison noted.

While radiation therapy puts them at risk of developing cancers in such areas as the brain, skin, breast, thyroid and connective tissue, this study shows that genetics independently increase the risk for breast cancer, thyroid cancer and sarcomas, Robison said. Sarcomas are tumors that commonly grow in connective tissue, such as the bones, muscles and tendons.

"Our findings have immediate implications for the growing population of long-term survivors of childhood cancer," he said.

The study authors recommend that people who develop specific types of abnormal tissue growth receive genetic counseling.

Robison said the researchers believe the study findings will lead to personalized treatment recommendations based on genetic profiles for children who are newly diagnosed with cancer.

Study co-lead author Zhaoming Wang said more research is needed to understand the possible links between genetic factors and exposure to cancer treatments. In addition, Wang, also with St. Jude's department of epidemiology and cancer control, suggested that further study is needed to replicate the new findings.

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Gene Changes May Put Childhood Cancer Survivors at Risk - Montana Standard

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2017 Global Gene Medicine Therapy Market in North America ... - Edition Time

April 3, 2017 The growth of Neisseria meningitidis colonies on New York City Medium Agar. Credit: Wikipedia

Neisseria meningitidis, a bacterium usually associated with meningitis and sepsis, is the cause of a recent cluster of sexually transmitted infections in Columbus, Ohio and in other US cities. The bacterium appears to be adapting to a urogenital environment, an analysis of the organism's DNA shows.

The DNA analysis helps doctors track the spread of this type of bacteria, distinguish it from others, anticipate which vaccines might be protective, and understand how it has evolved.

The findings are scheduled for publication in PNAS.

Genetic changes make this "clade" of N. meningitidis look more like relatives that are known to cause gonorrhea, says lead author Yih-Ling Tzeng, PhD, assistant professor of medicine (infectious diseases) at Emory University School of Medicine.

In particular, the bacteria have lost their outer coat-capsules, potentially enhancing their ability to stick to mucosal surfaces in the body, and have gained enzymes that promote growth in a low-oxygen environment.

Some good news is that the capsule-less organism is less likely to cause invasive diseases such as meningitis, because the capsule protects the bacteria against components of the immune system found in the blood, Tzeng says.

N. meningitidis is carried at the back of the nose and throat, without symptoms, in 5 to 10 percent of people. As its name suggests, when N. meningitidis invades other parts of the body, it can cause meningitis, an infection of the lining of the brain and spinal cord, as well as deadly bloodstream infections.

In 2015, N. meningitidis began to appear in heterosexual men coming to the Sexual Health Clinic in Columbus as the cause of urethritis: inflammation leading to painful urination. These infections were initially presumed to be gonorrhea, caused by N. gonorrhoeae. More than 100 cases have been reported in Columbus, and the same type of N. meningitidis infection has appeared in Michigan, Indiana and Georgia.

Jose Bazan, DO, the Clinic's medical director and assistant professor of medicine (infectious diseases) at Ohio State University and Abby Norris Turner PhD, assistant professor of medicine (infectious diseases) teamed up with Tzeng and David Stephens, MD, professor of medicine of Emory University School of Medicine, and colleagues from Indiana University School of Medicine and the Centers for Disease Control and Prevention (CDC) to investigate.

The Columbus clinic is part of the CDC's nationwide Gonococcal Isolate Surveillance Project (GISP), which monitors antibiotic resistance. Emory co-authors include Carlos del Rio, MD, professor of medicine and global health and director of the Atlanta GISP laboratory, and Timothy Read, PhD, associate professor of medicine and human genetics.

The scientists looked at the genomes of 52 N. meningitidis samples from Columbus, and two from Indianapolis and two from Atlanta. All 56 genomes had many common features, so they're closely related, but they are continuing to evolve.

N. meningitidis is usually classified by serogroups, based on the structure of the capsule. . Vaccines against the A, C, Y, and W serogroups have been available in the US for years, and vaccines against serogroup B were introduced in 2014.

Outbreaks of N. meningitidis serogroup C meningitis and sepsis have been observed in several countries among men who have sex with men. In contrast, the bacteria described in the PNAS paper could not be assigned to any serogroup based on initial screening tests.

The loss of several genes for synthesizing components of the capsule explains the blank result, Tzeng says. However, clues in the DNA of the capsule-less bacteria make them look like they were originally derived from a serogroup C ancestor.

It is possible that vaccines that were approved in the last few years against the B serogroup might still be effective against this meningococcal clade, because the capsule-less bacteria continue to produce other proteins targeted by those vaccines, the scientists found. A vaccine against gonorrhea has been a challenge, because repeat infections are common.

N. meningitidis doesn't usually encounter low-oxygen conditions, but this clade, linked to urethritis, has picked up genes that help them to grow in the environment of the urogenital tract. Based on their sequences, the genes appear to have come directly from N. gonorrhoeae, suggesting that on at least one occasion, the two types of bacteria were in the same place and exchanged DNA.

"All the urethritis patients responded to standard treatments for gonorrhea and there were no alarming resistance markers," Tzeng says. "However, as the gene conversion demonstrates, this clade can readily take up DNA from gonococci and it is not unthinkable that gonococcal antibiotic resistance genes could jump into this clade by gene transfer, if it is to its advantage."

Explore further: Harmless bacteria may be helpful against meningococcal outbreaks

More information: Emergence of a new Neisseria meningitidis clonal complex 11 lineage 11.2 clade as an effective urogenital pathogen, PNAS, http://www.pnas.org/cgi/doi/10.1073/pnas.1620971114

Nasal drops of harmless bacteria can inhibit a related bug that sometimes causes meningococcal disease, according to new findings published online in Clinical Infectious Diseases. The studyconducted among college students, ...

University of York scientists have shed new light on why teenagers and young adults are particularly susceptible to meningitis and septicaemia.

Scientists at Oxford University have identified the key groups of bacteria responsible for the majority of meningococcal disease cases in England and Wales over the past 20 years.

A study conducted by UCSF Benioff Children's Hospital Oakland Research Institute (CHORI) scientists shows greatly improved protective antibody responses to a new mutant vaccine antigen for prevention of disease caused by ...

Simon Fraser University researcher Lisa Craig is part of an international team that has uncovered new details about a microbe that invades the brain, sometimes with fatal results. The information is a critical piece of the ...

A team of international researchers has moved a step closer to developing a vaccine to protect against middle ear infection, currently the most common infection in children under the age of five. The vaccine could also be ...

Neisseria meningitidis, a bacterium usually associated with meningitis and sepsis, is the cause of a recent cluster of sexually transmitted infections in Columbus, Ohio and in other US cities. The bacterium appears to be ...

Flare-ups in chronic obstructive pulmonary disease, the UK's fourth leading cause of death, can be reduced by 20% by a combined triple inhaler, according to the results of a trial of more than 2,000 people conducted by The ...

In the first study of its kind, researchers found real-world massage therapy to be an effective treatment for chronic low back pain.

A study, published in the American Journal of Respiratory and Critical Care Medicine, describes a new treatment pathway for antibiotic resistant bacteria and infectious diseases with benefits for patients and health care ...

(Medical Xpress)A team of researchers with the Icahn School of Medicine at Mount Sinai in New York City has found that mice who have survived a dengue or West Nile viral infection fare worse when subsequently infected ...

About half of all women will experience urinary tract infections in their lifetimes, and despite treatment, about a quarter will develop recurrent infections within six months of initial infection.

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Meningitis bacteria adapting to STI niche, genetic analysis shows - Medical Xpress

April 3, 2017 by Garth Sundem Tamara Terzian, Ph.D., and colleagues detail the genes that regulate p53. Credit: University of Colorado Cancer Center

The gene p53 is the most commonly mutated gene in cancer - it is p53's job to monitor cells for DNA damage and to mark damaged cells for destruction and so cancer cells with mutated DNA must disable p53 before it disables them. However, there is a second, darker side to p53. While intact or "wild type" p53 is a tumor suppressor, mutated p53 can itself become an oncogene, driving the progression of the disease. A University of Colorado Cancer Center study presented today at the American Association for Cancer Research (AACR) Annual Meeting 2017 picks apart the dark side of this gene, the mutated, oncogenic form of p53, to show that other genes, Mdm2 and now for the first time Mdm4, keep mutated p53 in check.

"Because p53 is the most frequently mutated gene in cancer, it has a tremendous impact on tumorigenesis. Anything that regulates the p53 pathway has an importance in tumor development - and potentially for therapy," says senior author Tamara Terzian, PhD, investigator at the CU Cancer Center and assistant professor at the Gates Center for Regenerative Medicine on the University of Colorado Anschutz Medical Campus.

In healthy cells, Mdm2 and Mdm4 keep p53 at low levels; studies have shown that nixing these proteins results in a spike in p53 and the destruction of the cell. Commonly, DNA damage - either oncogenic mutations or other non-cancer stressors - results in high p53 and cell death. And, also commonly, cancer evades this blockade by mutating p53, keeping its levels artificially low despite high DNA damage.

But there is another storyline to p53 and cancer. In this second story, cancer mutates p53 and uses this new form to drive its growth directly. Now cancer would like to turn up this mutated form of p53. And now doctors, instead of wishing that healthy p53 would spike in response to oncogenic DNA, wish that mutated p53 would go away.

"When you take out either of these two genes, Mdm2 or Mdm4, mutated p53 is elevated and mice die earlier of mutant-p53-driven cancers," Terzian says. However, Terzian's study also shows cooperation between 2 and 4. "When you knock down either, you boost the level of mutant p53, and when you take them both out, it kind of goes through the roof," she says.

Therapies now in clinical trials attempt to force cancer-causing mutant p53 back into the mold of cancer-killing healthy p53, for example, because many cells hold both mutant and wild type p53, "by activating the wild type or depleting the mutant or making the mutant into the wild type," Terzian says.

"We want to know both what regulates p53 and what are its target genes," Terzian says. "And in the case of mutant p53 we are not talking about a homogenous actor - we have multiple mutations and each one makes a protein of its own; each has a mind of its own. Wild type is just one form, but mutant proteins have endless possibilities. Asking questions about these possibilities expands the horizon."

The horizon is becoming clearer - wild type p53 kills cancer and mutant p53 causes cancer. Both types are suppressed by Mdm2 and Mdm4. The challenge is to manipulate these proteins or other actors in the chain of signaling that extends from these proteins, at the right time in the right patients.

"By understanding how mutant p53 proteins are regulated, we increase the likelihood of developing a successful therapeutic strategy to treat tumors," says Terzian.

Explore further: Cancer drug trial success

The one-size-fits-all approach to early stage breast cancer creates a paradox: Millions of dollars are spent on unnecessary surgeries and radiation to treat women with low-risk 'in situ' lesions, an estimated 85% of which ...

(HealthDay)Millions of Americans take low-dose aspirin every day for heart health. In doing so, they may also slightly lower their risk of dying from several cancers, a large new study suggests.

On the list of dreaded medical tests, a prostate biopsy probably ranks fairly high. The common procedure requires sticking a needle into the prostate gland to remove tissue for assessment. Thousands of men who undergo the ...

A team of researchers report a significant genetic association linked to an aggressive form of melanoma in a study published today in the journal Genome Research. Acral lentiginous melanoma, or ALM, is an uncommon type of ...

There's a reason why melanoma, the most serious type of skin cancer, is so aggressive. You just need to watch the cells in action.

A University of Queensland researcher has found patients with non-hodgkins lymphoma are most likely to survive if they have a rich variety of T-cells.

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Study sheds light on dark side of tumor suppressor gene, p53 - Medical Xpress

Genetic errors associated with heart health may guide drug development Science Daily A new study of such "beneficial" genetic mutations, led by Washington University School of Medicine in St. Louis, may provide guidance on the design of new therapies intended to reduce the risk of heart attacks. The study is published March 29 in the ... Gene mutation could help develop drug to reduce heart attacksCardiovascular Business all 3 news articles »

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Genetic errors associated with heart health may guide drug development - Science Daily

Durham Herald Sun

Screening genome's 'dark matter' for risks Durham Herald Sun Researchers have developed a method to swiftly screen the non-coding DNA of the human genome for links to diseases that are driven by changes in gene regulation. The technique could revolutionize modern medicine's understanding of the genetically ... and more »

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Screening genome's 'dark matter' for risks - Durham Herald Sun