Posts Tagged ‘physician’

New gene mutations for Wilms tumor found

Wilms tumor is the most common childhood genitourinary tract cancer and the third most common solid tumor of childhood.

“While most children with Wilms tumor are thankfully cured, those with more aggressive tumors do poorly, and we are increasingly concerned about the long-term adverse side effects of chemotherapy in Wilms tumor patients. We wanted to know — what are the genetic causes of Wilms tumor in children and what are the opportunities for targeted therapies? To answer these questions, you have to identify genes that are mutated in the cancer,” said Dr. James Amatruda, Associate Professor of Pediatrics, Molecular Biology, and Internal Medicine at UT Southwestern and senior author for the study.

The new findings appear in Nature Communications. Collaborating with Dr. Amatruda on the study were UT Southwestern faculty members Dr. Dinesh Rakheja, Associate Professor of Pathology and Pediatrics; Dr. Kenneth S. Chen, Assistant Instructor in Pediatrics; and Dr. Joshua T. Mendell, Professor of Molecular Biology. Dr. Jonathan Wickiser, Associate Professor in Pediatrics, and Dr. James Malter, Chair of Pathology, are also co-authors.

Previous research has identified one or two mutant genes in Wilms tumors, but only about one-third of Wilms tumors had these mutations.

“We wanted to know what genes were mutated in the other two-thirds. To accomplish this goal, we sequenced the DNA of 44 tumors and identified several new mutated genes,” said Dr. Amatruda, who holds the Nearburg Family Professorship in Pediatric Oncology Research and is an Attending Physician in the Pauline Allen Gill Center for Cancer and Blood Disorders at Children’s Medical Center. “The new genes had not been identified before. The most common, and in some ways the most biologically interesting, mutations were found in genes called DROSHA and DICER1. We found that these mutations affected the cell’s production of microRNAs, which are tiny RNA molecules that play big roles in controlling the growth of cells, and the primary effect was on a family of microRNAs called let-7.”

“Let-7 is an important microRNA that slows cell growth and in Wilms tumors in which DROSHA or DICER1 were mutated, let-7 RNA is missing, which causes the cells to grow abnormally fast,” Dr. Amatruda said.

These findings have implications for future treatment of Wilms tumor and several other childhood cancers, including neuroblastoma, germ cell tumor, and rhabdomyosarcoma.

“What’s exciting about these results is that we can begin to understand what drives the growth of different types of Wilms tumors. This is a critical first step in trying to treat the cancer based on its true molecular defect, rather than just what a tumor looks like under a microscope,” Dr. Amatruda said. “Most importantly, we begin to think in concrete terms about a therapy, which is an exciting translational goal of our work in the next few years. This study also is a gratifying example of great teamwork. As oncologists, Dr. Chen and I were able to make rapid progress by teaming up with Dr. Rakheja, an expert pathologist, and with Dr. Mendell, a leading expert on microRNA biology.”

According to the American Cancer Society, an estimated 510 cases of Wilms tumor will be diagnosed among children in 2014. Also called nephroblastoma, Wilms tumor is an embryonal tumor of the kidney that usually occurs in children under age 5, and 92 percent of kidney tumors in this age group are Wilms tumor. Survival rates for Wilms tumor have increased from 75 percent in 1975-1979 to 90 percent in 2003-2009.

source : http://www.sciencedaily.com/releases/2014/09/140905113651.htm

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NSAIDs may lower breast cancer recurrence rate in overweight, obese women

“Our studies suggest that limiting inflammatory signaling may be an effective, less toxic approach to altering the cancer-promoting effects of obesity and improving patient response to hormone therapy,” said Linda A. deGraffenried, PhD, associate professor of nutritional sciences at The University of Texas in Austin.

The study found that women whose body mass index (BMI) was greater than 30 and had estrogen receptor alpha (ERα)-positive breast cancer had a 52 percent lower rate of recurrence and a 28-month delay in time to recurrence if they were taking aspirin or other NSAIDs.

“These results suggest that NSAIDs may improve response to hormone therapy, thereby allowing more women to remain on hormone therapy rather than needing to change to chemotherapy and deal with the associated side effects and complications,” said deGraffenried. “However, these results are preliminary and patients should never undertake any treatment without consulting with their physician.”

Using blood from obese patients, deGraffenried and colleagues conducted experiments in the laboratory to recreate a tumor environment containing cancer cells, fat cells, and the immune cells that promote inflammation. They found that the factors associated with obesity initiate a network of signaling within the tumor environment to promote growth and resistance to therapy.

“These studies show that the greatest benefit from aspirin [and other NSAIDs] will be in those with a disease driven by inflammation, and not just obesity,” explained DeGraffenried.

Researchers used data from 440 women diagnosed with invasive, ERα-positive breast cancer and treated at The University of Texas Health Science Center and the START Center for Cancer Care clinic, both in San Antonio, Texas, between 1987 and 2011.

Of the women studied, 58.5 percent were obese and 25.8 percent were overweight. About 81 percent took aspirin, and the rest took another NSAID. About 42 percent and 25 percent took statins and omega-3 fatty acid, respectively.

There was an indication of protection from aspirin and other NSAIDs even after controlling for statins and omega-3 fatty acid use, which also have anti-inflammatory effects.

source : http://www.sciencedaily.com/releases/2014/08/140814124457.htm

Lung cancer diagnosis tool shown to be safe and effective for older patients

Half of all lung cancer patients are over 70 years old when first diagnosed, but studies have shown that these older patients are less likely to receive an accurate diagnosis.

A correct assessment of the stage of a patient’s disease — how much their tumor has grown and spread — is key to ensuring they receive the right treatment.

Non-invasive methods of checking whether a patient’s cancer has spread to their lymph nodes have limited sensitivity and until recently the only way to obtain a tissue sample was under general anaesthetic — limiting its use in elderly patients who often present with other conditions that may restrict the use of general anaesthesia.

Now researchers at University Hospital of South Manchester NHS Foundation Trust and The University of Manchester — part of the Manchester Cancer Research Centre — have looked at a newer technique: endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). This method is carried out under sedation while the patient is still conscious and uses ultrasound to guide a sampling needle down and through the airways of the lungs.

Dr Richard Booton, Consultant Respiratory Physician at the North West Lung Centre and senior lecturer at the University’s Institute of Inflammation and Repair who led the study, said: “We wanted to see if there were any differences between patients aged less than 70 years old and those older than 70, in terms of both the safety of the technique and how useful it was for diagnosis.

“The team recently published their results in the Journal of Thoracic Oncology and found that the procedure was well tolerated at all ages — even in those patients aged over 80 years old. They also showed that EBUS-TBNA is effective for assessing whether a patient’s tumor had spread to the lymph nodes.

“Being able to safely take tissue samples will also allow us to test for specific tumor sub-types and better decide the most appropriate treatment for each individual patient,” added Dr Booton.

source : http://www.sciencedaily.com/releases/2014/08/140804065948.htm