Breaking News
January 20, 2019 - Exercise makes even the ‘still overweight’ healthier: study
January 20, 2019 - University of Utah to establish first-of-its-kind dark sky studies minor in the US
January 20, 2019 - School-based nutritional programs reduce student obesity
January 20, 2019 - Improved maternity care practices in the southern U.S. reduce racial inequities in breastfeeding
January 20, 2019 - New enzyme biomarker test indicates diseases and bacterial contamination
January 20, 2019 - Republican and Democratic governors have different visions to transform health care, say researchers
January 20, 2019 - Researchers discover that spin flips happen in only half a picosecond in the course of a chemical reaction
January 20, 2019 - Suicide Risk Up More Than Fourfold for Cancer Patients
January 20, 2019 - Doctors find 122 nails in Ethiopian’s stomach
January 20, 2019 - UV disinfection technology eliminates up to 97.7% of pathogens in operating rooms
January 20, 2019 - Researchers discover mechanism which drives leukemia cell growth
January 20, 2019 - AHA: Infection as a Baby Led to Heart Valve Surgery for Teen
January 20, 2019 - Injection improves vision in a form of childhood blindness
January 20, 2019 - Multiple sclerosis therapies delay progression of disability
January 20, 2019 - New study finds infrequent helmet use among bike share riders
January 20, 2019 - Clearing up information about corneal dystrophies
January 20, 2019 - Researchers describe new behavior in energy metabolism that refutes existing evidence
January 20, 2019 - New study takes first step toward treating endometriosis
January 20, 2019 - Researchers find how GREB1 gene promotes resistance to prostate cancer treatments
January 20, 2019 - Replacing Sitting Time With Activity Lowers Mortality Risk
January 20, 2019 - A simple, inexpensive intervention makes birth safer for moms and babies in parts of Africa
January 19, 2019 - New anti-inflammatory compound acts as ‘surge protector’ to reduce cancer growth
January 19, 2019 - Significant flaws found in recently released forensic software
January 19, 2019 - New Leash on Life? Staying Slim Keeps Pooches Happy, Healthy
January 19, 2019 - Men and women remember pain differently
January 19, 2019 - Rising air pollution linked with increased ER visits for breathing problems
January 19, 2019 - Study uses local data to model food consumption patterns among Seattle residents
January 19, 2019 - The brain’s cerebellum plays role in controlling reward and social behaviors, study shows
January 19, 2019 - Relationship between nurse work environment and patient safety
January 19, 2019 - Pioneering surgery restores movement to children paralyzed by acute flaccid myelitis
January 19, 2019 - Genetic variants linked with risk tolerance and risky behaviors
January 19, 2019 - New research provides better understanding of our early human ancestors
January 19, 2019 - First-ever tailored reporting guidance to improve patient care and outcomes
January 19, 2019 - 4.6 percent of Massachusetts residents have opioid use disorder
January 19, 2019 - New study suggests vital exhaustion as risk factor for dementia
January 19, 2019 - New antibiotic discovery heralds breakthrough in the fight against drug-resistant bacteria
January 19, 2019 - Ural Federal University scientists synthesize a group of multi-purpose fluorophores
January 19, 2019 - Researchers identify new therapeutic target in the fight against chronic liver diseases
January 19, 2019 - Preparation, characterization of Soyasapogenol B loaded onto functionalized MWCNTs
January 19, 2019 - FDA Approves Ontruzant (trastuzumab-dttb), a Biosimilar to Herceptin
January 19, 2019 - Tobacco use linked with higher use of opioids and sedatives
January 19, 2019 - Study delves deeper into developmental dyslexia
January 19, 2019 - Anti-vaccination movement one of the top health threats in 2019 says WHO
January 19, 2019 - Newly developed risk score more effective at identifying type 1 diabetes
January 19, 2019 - Highly effective protocol to prepare cannabis samples for THC/CBD analysis
January 19, 2019 - Prinston Pharmaceutical Inc. Issues Voluntary Nationwide Recall of Irbesartan and Irbesartan HCTZ Tablets Due to Detection of a Trace Amount of Unexpected Impurity, N-Nitrosodiethylamine (NDEA) in the Products
January 19, 2019 - How does solid stress from brain tumors cause neuronal loss, neurologic dysfunction?
January 19, 2019 - $14.7 million partnership to supercharge vaccine development
January 19, 2019 - Ian Fotheringham receives Charles Tennant Memorial Lecture award
January 19, 2019 - Brain vital signs detect neurophysiological impairments in players with concussions
January 19, 2019 - Lack of job and poor housing conditions increased likelihood of people attending A&E
January 19, 2019 - Novel targeted drug delivery system improves conventional cancer treatments
January 19, 2019 - Rutgers study finds gene responsible for spread of prostate cancer
January 19, 2019 - Complications Higher Than Expected for Invasive Lung Tests
January 19, 2019 - 3-D printed implant promotes nerve cell growth to treat spinal cord injury
January 19, 2019 - Automated texts lead to improved outcomes after total knee or hip replacement surgery
January 19, 2019 - Poor cardiorespiratory fitness could increase risk of future heart attack, finds new study
January 19, 2019 - Drinking soft drinks while exercising in hot weather may increase risk of kidney disease
January 19, 2019 - Formlabs 3D prints anatomical models
January 19, 2019 - Heart-Healthy Living Also Wards Off Type 2 Diabetes
January 19, 2019 - Teaching Kids to Be Smart About Social Media (for Parents)
January 19, 2019 - Metabolite produced by gut microbiota from pomegranates reduces inflammatory bowel disease
January 19, 2019 - Researchers examine how spray from showers and toilets expose us to disease causing bacteria
January 19, 2019 - Behavioral experiments confirm that additional neurons improve brain function
January 19, 2019 - New study compares performance of real-time infectious disease forecasting models
January 19, 2019 - Obesity can be risk factor for developing renal cell carcinoma, confirms study
January 19, 2019 - New regulation designs on cigarette packs direct smokers’ attention to health warnings
January 19, 2019 - QIAGEN receives first companion diagnostic approval in Japan
January 19, 2019 - Study explores role of Dunning-Kruger effect in anti-vaccine attitudes
January 19, 2019 - Immune checkpoint inhibitors induce rheumatic and musculoskeletal diseases
January 19, 2019 - Newly identified subset of immune cells may be key to fighting chronic inflammation
January 19, 2019 - New immune response regulators discovered
January 18, 2019 - Poor blood oxygenation during sleep predicts chance of heart-related death
January 18, 2019 - First international consensus on the diagnosis and management of fibromuscular dysplasia
January 18, 2019 - Rapid resistance gene sequencing technology can hasten identification of antibiotic-resistant bacteria
January 18, 2019 - Researchers develop artificial enzymatic pathway for synthesizing isoprenoids in E. coli
January 18, 2019 - Scientists advise caution in immunotherapy research
January 18, 2019 - How children across the world develop language
January 18, 2019 - Columbia Medical Student Receives McDonogh Scholarship
January 18, 2019 - Secretive ‘Rebate Trap’ Keeps Generic Drugs For Diabetes And Other Ills Out Of Reach
Researchers use ‘top-down proteomics’ strategy to get new insights into cancer

Researchers use ‘top-down proteomics’ strategy to get new insights into cancer

image_pdfDownload PDFimage_print

When a RAS gene operates normally, it acts as an on/off switch for cell signaling to control cell proliferation. But when the gene mutates, the switch jams into the “on” position, allowing cells to proliferate uncontrollably.

This unstoppable cascade inevitably leads to cancer.

“The mutation in the gene is very common in pancreatic and colon cancer,” said Neil Kelleher, the Walter and Mary Elizabeth Glass Professor of Chemistry, Molecular Biosciences and Medicine at Northwestern University. “But there are currently no drugs that can target the mutation and fix the broken switch.”

Now Kelleher’s team has gathered insights that could potentially lead to new treatments for this historically “undruggable” target. An expert in proteins and director of Northwestern’s Proteomics Center of Excellence, Kelleher has developed a new technology that can -; in precise detail -; detect and quantify the effect of RAS mutations on RAS proteins.

Responsible for the signaling that controls cell growth and death, these proteins have been directly implicated in promoting tumor formation and cancer progression. Understanding how RAS proteins function in cancer could lead to much-needed avenues for treatment.

The findings from Northwestern’s proteomics team were presented in the paper “Precise characterization of KRAS4b proteoforms in human colorectal cells and tumors reveals mutation/modification cross-talk,” which was published April 2 in the Proceedings of the National Academy of Sciences.

Discovered in 1982, the RAS gene family, which includes KRAS, HRAS and NRAS, are the first cancer genes ever pinpointed in human cancer cells. But despite the passing of 36 years and a motivated effort to understand the gene, researchers have made little progress in developing cancer treatments that target it. According to the National Cancer Institute, the RAS family accounts for 30 percent of all human cancers, including 95 percent of pancreatic and 45 percent of colorectal cancers. Even worse: Cancers related to RAS genes have been notoriously difficult to treat because typical chemotherapy and radiation strategies are largely ineffective.

“Having a mutation in the RAS gene is bad news,” said Caroline DeHart, a research assistant professor in Kelleher’s laboratory, who served as the study’s co-first author with Luca Fornelli and Ioanna Ntai. “Once it fires up the proteins that kick-start proliferation, it’s nearly impossible to stop.”

In the past few years, research institutions have increased efforts to understand this family of genes and the proteins they produce. The National Cancer Institute, for example, established its RAS Initiative in 2013 to explore and develop effective approaches to attack the proteins encoded by mutated RAS genes. Researchers typically have examined RAS proteins by cutting them up and analyzing the pieces. While inexpensive, this approach is not without limitations.

“In order to understand what you’re looking at, you eventually have to stitch the pieces back together,” DeHart said. “This makes highly similar proteins like those in the RAS family exceptionally difficult to characterize with any degree of confidence.”

This is where Kelleher’s novel technique has a profound advantage. His laboratory employs “top-down proteomics,” which uses mass spectrometry to analyze proteins while they are still fully intact. His team applied this method, for the first time, to KRAS’s biology and provided complete molecular specificity for a normal and mutated protein form called KRAS4b, which was isolated from colorectal cancer cell lines and patient tumor samples. Kelleher’s team then measured how much KRAS4b was present in the samples and determined how the protein changed in cancer compared to healthy tissues. During the course of this work, they also discovered 11 protein forms, or “proteoforms,” of KRAS4b and measured them in six patient samples.

“Put simply, we can get more information by examining the intact proteins,” said Kelleher, who coined the now-accepted term “proteoforms” with a collaborator in 2013. “We can understand how the KRAS4b proteoform looks in different cancers and are applying the same ‘top-down’ strategy to other key proteins in cancer. New knowledge often leads to new opportunities in advancing our battle against cancer.”

Source:

https://news.northwestern.edu/stories/2018/april/top-down-approach-gets-to-the-bottom-of-cancer/

Tagged with:

About author

Related Articles