Breaking News
July 20, 2018 - Immediate Monitoring With ECG Patch Ups A-Fib Diagnosis Rate
July 20, 2018 - Scientists seek to better protect the eye from glaucoma
July 20, 2018 - Football training could improve bone mineral density in prostate cancer patients
July 20, 2018 - Single genetic change in gut bacteria can lead to obesity
July 20, 2018 - Research uncovers new target for therapeutic intervention in breast cancer
July 20, 2018 - WFN to highlight clean air for brain health on World Brain Day 2018
July 20, 2018 - Health Highlights: July 17, 2018
July 20, 2018 - Mom’s marijuana winds up in breast milk
July 20, 2018 - Black men could be healthier if seen by black physicians, new research suggests
July 20, 2018 - Alcoholics have persistent difficulties with emotional communication after long-term abstinence
July 19, 2018 - Researchers unravel how ALL invades the central nervous system
July 19, 2018 - Mother’s microbiome determines offspring’s risk of developing autism
July 19, 2018 - Refining standards of maternal-fetal care
July 19, 2018 - Stitching single cells together any which way you want to
July 19, 2018 - Study identifies RNA molecules that regulate male hormones in prostate cancer
July 19, 2018 - New machine-learning model shows promise in predicting undiagnosed dementia
July 19, 2018 - Sleep supports antioxidant processes, study suggests
July 19, 2018 - MiRagen Therapeutics Announces Initiation of Phase 2 Clinical Trial of MRG-201
July 19, 2018 - Unique brain ‘fingerprint’ can predict drug effectiveness
July 19, 2018 - Life on the border: Struggling to survive in Jordan
July 19, 2018 - CT scans may raise brain tumor risk
July 19, 2018 - Moderate alcohol intake linked with improved male fertility
July 19, 2018 - Alcohol-related cirrhosis mortality on the rise among young adults
July 19, 2018 - Study uncovers new protein complex that shields broken DNA ends
July 19, 2018 - Regular sunscreen use protects young people from melanoma
July 19, 2018 - Using non-invasive brain recordings to characterize activity in deep structures
July 19, 2018 - Mediterranean diet could influence academic performance through effects on sleep quality
July 19, 2018 - Woman’s pregnancy history may be linked to Alzheimer’s disease risk
July 19, 2018 - Study calls for new gold standard in research to treat non-alcoholic steatohepatitis
July 19, 2018 - Cancer patients receiving anti-PD-1 therapies may experience delayed skin reactions
July 19, 2018 - Scientists study adverse effects of carbon, silicon nanotubes and carbon nanofibers
July 19, 2018 - Keck Hospital of USC receives Magnet recognition for excellence in nursing
July 19, 2018 - Scientists identify hidden signals in RNAs that control protein synthesis
July 19, 2018 - Quadrivalent HPV Vaccine Not Tied to Spontaneous Abortion
July 19, 2018 - FDA OKs first drug made to reduce excessive sweating
July 19, 2018 - New Finnish study compares surgical treatment of shoulder impingement syndrome to placebo surgery
July 19, 2018 - New findings do no support caffeine as effective appetite suppressant or weight-loss aid
July 19, 2018 - Kite collaborates with Gadeta to develop novel gamma delta TCR therapies for various cancers
July 19, 2018 - Study evaluates Neoteryx’s VAMS technology for monitoring HbA1c levels of diabetic children
July 19, 2018 - New clinical trial examines use of adrenaline to treat cardiac arrests
July 19, 2018 - Early surgical intervention may improve outcomes for patients with mitral valve disease
July 19, 2018 - Prolonged preoperative opioid use linked to adverse outcomes after total knee and hip arthroplasty
July 19, 2018 - Biophysicists use infrared sensor as new method for drug discovery
July 19, 2018 - Rat study shows negative effects of perinatal exposure to phthalates
July 19, 2018 - Children with disabilities endure long waits for life-changing medical equipment
July 19, 2018 - Ways to stay safe while camping and hiking
July 19, 2018 - People with HIV twice as likely to suffer from heart disease
July 19, 2018 - On-the-Job Stress Relief – Drugs.com MedNews
July 19, 2018 - Compounds found in green tea and wine may block formation of toxic metabolites
July 19, 2018 - Gene regulator associated with protein pileup in exfoliation glaucoma
July 19, 2018 - Trump administration summons immigrant infants
July 19, 2018 - FDA grants approval for first breast cancer drug through ‘Real-Time Oncology Review’
July 19, 2018 - Five tips for men seeking plastic surgery
July 19, 2018 - Researchers discover the reasons why some people get dizzy when hearing certain sounds
July 19, 2018 - Research project investigates snake venom treatment as antibiotic alternative for eye infections
July 19, 2018 - Melanoma could soon be detected using a blood test
July 19, 2018 - Exposure to bright light may have big impact on sleep-related behavior in children
July 19, 2018 - Deleting single gene in gut bacteria affects metabolism, reduces weight gain in mice
July 19, 2018 - New proteomics studies help gain more insights into Alzheimer’s, cancer and listeriosis
July 19, 2018 - Study finds major discrepancies in prescription drug labeling pregnancy information across four countries
July 19, 2018 - Cellectar’s CLR 131 Receives FDA Orphan Drug Designation for Treatment of Ewing’s Sarcoma
July 19, 2018 - Watching the immune system in action reveals what happens when things goes wrong
July 19, 2018 - Increasing blood sugar levels improves memory and performance in older adults
July 19, 2018 - Connection between self-regulation and obesity appears to be different for girls and boys
July 19, 2018 - Researchers develop new, less destructive method for whitening teeth
July 19, 2018 - Revving up innate control of viral infection requires a three-cell ignition
July 19, 2018 - Inaccurate direct-to-consumer raw genetic data can harm patients, new research suggests
July 19, 2018 - Weight loss surgery is effective under the right situations
July 19, 2018 - BioTek awarded patent for autofocus feature on microplate reader
July 19, 2018 - Low-carb diets reduce stiffness of arteries in women and promote weight loss in men
July 19, 2018 - New review examines cannabinoids’ potential for direct treatment of cancer
July 19, 2018 - Allergic responses may help protect the skin against cancer, research suggests
July 19, 2018 - Inappropriate Prescribing of Abx High in Urgent Care Centers
July 19, 2018 - Many at risk for HIV despite lifesaving pill
July 19, 2018 - Tips for doctors and parents on the harms of marijuana use for teens
July 18, 2018 - Researchers detect presence of IgE antibodies after kidney transplantation
July 18, 2018 - New technique allows researchers to create large scale, personalized bone grafts
July 18, 2018 - Smoking May Boost Atrial Fibrillation Risk
July 18, 2018 - Genome editing method targets AIDS virus
July 18, 2018 - These things matter: Medical complications are not inevitable, a physician writes
Study uncovers genomic targets in refractory neuroblastoma

Study uncovers genomic targets in refractory neuroblastoma

image_pdfDownload PDFimage_print

Study led by Tokyo Medical and Dental University (TMDU) elucidates genomic targets in refractory neuroblastoma

Neuroblastoma (NB) is the most common solid tumor found in children. It starts in some very early forms of nerve cells found in the embryo or fetus. Amplification of the gene MYCN is a well-characterized genetic alteration in NB and is directly associated with advanced disease and poor prognosis. Besides MYCN amplification, several other genome alterations in NB have been reported. Notably, deletion of the long arm of chromosome 11 (11q deletion) is one of the most frequent events in aggressive neuroblastoma.

In the past two decades, despite extensive efforts to identify the genes associated with11q aberrations in NB, definitive answers are still unclear. This distinct gap in the field has spurred a team of Tokyo Medical and Dental University (TMDU)-centered researchers to investigate the role of the gene ATM and DNA damage response (DDR)-associated molecules located in 11q. A report of the results was recently published.

“The protein ATM, encoded by the ATM gene, is a master regulator of DDR crucial for maintenance of genome integrity. When DNA damage occurs in genes that play a crucial role in the DDR itself, the checkpoint pathway is compromised, contributing to the formation of cancer,” explains Masatoshi Takagi, lead author of the study. “Among 237 fresh tumor samples from the patients, we found ATM, MRE11A, H2AFX, and/or CHEK1 gene loss or imbalance in 11q in 20.7% of NB, 89.8% of which were stage 3 or 4 cancer.”

Furthermore, nearly half of the samples had a single nucleotide variant and/or copy number alterations in those genes. ATM-defective cells are known to exhibit dysfunctions in DNA repair, suggesting a potential for PARP inhibitor, a commonly used targeted therapy for patients with BRCA mutated ovarian cancer, to arrest NB growth. Indeed, the team found 83.3% NB-derived cell lines exhibited sensitivity to PARP inhibition.

“There is much more to uncover, such as how and when the mutation of DDR-associated molecules, or loss of 11q, occurs during tumor development and progression. Additionally, it will be important to compare the frequency of mutations in DDR-associated molecules or 11q loss between initial samples and relapsed or metastatic region. “Nonetheless, our present results further support the possibility of PARP inhibitor as a promising therapeutic approach for specifically targeting NB due to defects in the series of interrelated pathways that function in the repair of DNA breakage.” Based on those finding, Tokyo Medical and Dental University has launched phase I clinical trial using olaparib for refractory pediatric solid tumors.

Source:

http://www.tmd.ac.jp/english/press-release/20171227_1/index.html

Tagged with:

About author

Related Articles