Navigation Links
U of M researchers develop model for better testing, targeting of MPNST

MINNEAPOLIS/ST. PAUL (MAY 20, 2013) University of Minnesota Medical School researchers from the Masonic Cancer Center, University of Minnesota, in partnership with the University's Brain Tumor Program, have developed a new mouse model of malignant peripheral nerve sheath tumors (MPNST) that allow them to discover new genes and gene pathways driving this type of cancer.

The research was published this week in the journal Nature Genetics.

Utilizing the Sleeping Beauty transposon method, researchers in the lab of David Largaespada, Ph.D., professor in the Medical School and College of Biological Sciences, were able to use an unbiased approach to generate mouse models of MPNST development that lead to the identification of genes related to this tumor's development.

MPNST is a genetically diverse, aggressive form of sarcoma impacting connective tissue surrounding nerves that occurs sporadically or in association with Neurofibromatosis Type 1 (NF1) syndrome. The exact cause of MPNST is not known, but symptoms include swelling in the arms and legs, soreness and stiffness at the site of the tumor. MPNSTs are the most common malignancy in adults with NF1 syndrome and leading cause of NF1-related mortality.

Due to the invasive nature and high incidence of metastasis of MPNSTs, surgical resection, radiotherapy and chemotherapeutic treatments have proven to be ineffective for long-term treatment, resulting in 5-year survival rates of less than 25 percent with metastatic disease.

One of the most surprising findings in this research showed the gene FOXR2 is intrinsically linked to the growth of MPNSTs. This gene has not been heavily studied as researchers had not identified a clear function of this gene.

"By using an unbiased approach, it helped us identify FOXR2 as an important gene in MPNST development and develop experiments to pinpoint the role FOXR2 plays in maintaining the aggressive nature of these tumors," said Eric Rahrmann, Ph.D., the paper's lead author and a postdoctoral fellow in the Largaespada lab. "When we turn off FOXR2, the growth ability of these MPNSTs drastically decreases."

Other findings showed interesting evidence of pathways that could be viable targets for therapeutics. The activation of the Wnt signaling pathway was shown to drive MPNSTs. This pathway has been highly implicated in colon cancer but not previously linked to MPNSTs.

Researchers also found many of the MPNSTs have dual loss of the genes called NF1 and PTEN. This pairing of lost genes causes MPNST formation. Both of these genes have previously been shown as pathways related to MPNSTs but it wasn't clear the extent to which they work together.

Now, researchers are applying these findings to the testing of therapeutics currently on the market for other drugs. This research is continuing both in the mouse model and within primary tumor settings of human cell lines.

"We want to know if these drugs, which are not currently directed at MPNSTs, could be repurposed to provide alternate therapies for patients," said Largaespada.

Researchers are also looking into more direct ways to target tumors through the Wnt pathway and paired NF1 and PTEN pathways, utilizing mouse models and human cell lines in the lab setting.


Contact: Caroline Marin
University of Minnesota Academic Health Center

Related biology news :

1. Study by UC Santa Barbara researchers suggests that bacteria communicate by touch
2. UC Santa Barbara researchers discover genetic link between visual pathways of hydras and humans
3. Researchers attempt to solve problems of antibiotic resistance and bee deaths in one
4. UNH researchers find African farmers need better climate change data to improve farming practices
5. Ottawa researchers to lead world-first clinical trial of stem cell therapy for septic shock
6. Researchers uncover molecular pathway through which common yeast becomes fungal pathogen
7. Researchers print live cells with a standard inkjet printer
8. Columbia Engineering and Penn researchers increase speed of single-molecule measurements
9. Researchers reveal how a single gene mutation leads to uncontrolled obesity
10. Researchers discover novel therapy for Crohns disease
11. New paper by Notre Dame researchers describes method for cleaning up nuclear waste
Post Your Comments:
(Date:6/20/2016)... Securus Technologies, a leading provider of ... safety, investigation, corrections and monitoring announced that after ... secured the final acceptance by all three (3) ... Systems (MAS) installed. Furthermore, Securus will have contracts ... by October, 2016. MAS distinguishes between legitimate wireless ...
(Date:6/7/2016)... 7, 2016  Syngrafii Inc. and San Antonio ... that includes integrating Syngrafii,s patented LongPen™ eSignature "Wet" ... collaboration will result in greater convenience for SACU ... while maintaining existing document workflow and compliance requirements. ... Highlights: ...
(Date:6/1/2016)... -- Favorable Government Initiatives Coupled With Implementation ... to Boost Global Biometrics System Market Through 2021  ... " Global Biometrics Market By Type, By End ... - 2021", the global biometrics market is projected to ... growing security concerns across various end use sectors such ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... ... June 27, 2016 , ... Parallel 6 , the ... today the Clinical Reach Virtual Patient Encounter CONSULT module which enables both ... physician and clinical trial team. , Using the CONSULT module, patients and physicians can ...
(Date:6/27/2016)... 27, 2016  Liquid Biotech USA ... of a Sponsored Research Agreement with The University ... (CTCs) from cancer patients.  The funding will be ... correlate with clinical outcomes in cancer patients undergoing ... then be employed to support the design of ...
(Date:6/24/2016)... , June 24, 2016 Epic Sciences ... detects cancers susceptible to PARP inhibitors by targeting ... cells (CTCs). The new test has already been ... in multiple cancer types. Over 230 ... damage response pathways, including PARP, ATM, ATR, DNA-PK ...
(Date:6/23/2016)... ... 23, 2016 , ... Mosio, a leader in clinical research ... Recruitment and Retention Tips.” Partnering with experienced clinical research professionals, Mosio revisits the ... tools, and strategies for clinical researchers. , “The landscape of how patients receive ...
Breaking Biology Technology: