Navigation Links
UT Southwestern scientists make mouse model of human cancer, demonstrate cure
Date:3/5/2013

DALLAS March 5, 2013 UT Southwestern Medical Center scientists report the first successful blocking of tumor development in a genetic mouse model of an incurable human cancer.

"To my knowledge, this is the first time that a mouse model of a genetically defined malignant human cancer has been generated in which the formation of the tumor from beginning to end can be monitored and in which blocking the pathway cures the mouse of the tumor," said Dr. Luis Parada, chair of the department of developmental biology at UT Southwestern and senior author of the study published in Cell and online. The study's first author is Dr. Wei Mo, a postdoctoral researcher in the department.

"We showed that blocking the activity of a receptor molecule named CXCR4 in these tumors through genetic manipulation or by chemical blockade inhibited tumor development. Together, these data reveal a potential target for therapy of these uncommon but currently untreatable malignant peripheral nerve sheath tumors (MPNSTs)," Dr. Parada added.

The study is a collaboration between Dr. Parada's laboratory and that of Dr. Lu Q. Le, co-senior author of the study and assistant professor of dermatology. Dr. Le also is co-director of the adult Comprehensive Neurofibromatosis Clinic at UT Southwestern, the first such clinic in North Texas, which is part of the Simmons Comprehensive Cancer Center. The researchers noted that co-authors at The University of Texas MD Anderson Cancer Center and Baylor College of Medicine, Houston, greatly accelerated the research effort.

MPNSTs are rare but highly aggressive tumors that are resistant to therapy and are typically fatal. The malignancies can occur sporadically or in a subset of patients with a condition called neurofibromatosis 1 (NF1) one of the most commonly inherited disorders of the nervous system, which affects an estimated 1 in 3,500 people.

The severity of NF1 can vary widely, even among family members, from mild dermatological symptoms to benign tumors that wrap around nerves and can be disfiguring, debilitating, and even life-threatening, depending on where they form, Dr. Le said. In addition, individuals with an improperly-functioning NF1 gene have an increased risk of developing cancerous tumors such as MPNSTs, he said.

The researchers generated a mouse model that spontaneously develops MPNSTs and compared gene expression activity in cancerous tumors and in the precursor cells that give rise to the tumors, which are the kind of cells in which MPNSTs develop.

They found that a protein (CXCR4), which is essential for tumor growth, is more abundant in cancerous cells than in precursor cells. In addition, they found that a molecule produced by the cancer cells themselves (CXCL12) works with CXCR4 to further the growth of cancer by stimulating the expression of the cyclin D1 protein, which promotes cell division via a signaling pathway outlined in the study.

When they examined human MPNSTs, the scientists found increased expression of CXCR4 accompanied by activity in the same pathway as the one identified in the mice, the researchers said.

Next, they blocked the activity of CXCR4 in the MPNST mice using either genetic manipulation or an FDA-approved antagonist drug for CXCR4 called AMD3100. Both strategies inhibited cancer development in mice whose tumors expressed increased levels of CXCR4, and were less effective in tumors without increased CXCR4 expression. They identified the same situation in the human cancer cells, the researchers report.

"We are very encouraged by these findings because they provide us with new directions and therapeutic windows to combat this deadly cancer, where none exist today," said Dr. Le, who added that the researchers are currently planning human trials.


'/>"/>

Contact: Deborah Wormser
deborah.wormser@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center
Source:Eurekalert  

Related biology news :

1. Mesquite trees displacing Southwestern grasslands
2. Sea lamprey genome mapped with help from scientists at OU
3. Sequestration will be a devastating blow to the nations research institutions and scientists
4. Scientists explore topical health issues at meeting in Texas
5. Stanford scientists help shed light on key component of Chinas pollution problem
6. Fat worms inch scientists toward better biofuel production
7. Scientists create new maps depicting potential worldwide coral bleaching by 2056
8. Scientists find surprising new influence on cancer genes
9. Scientists find bone-marrow environment that helps produce infection-fighting T and B cells
10. MBL scientists find genes linked to human neurological disorders in sea lamprey genome
11. Scientists identify molecular system that could help develop treatments for Alzheimers disease
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
UT Southwestern scientists make mouse model of human cancer, demonstrate cure
(Date:5/9/2016)... UAE, May 9, 2016 Elevay ... comes to expanding freedom for high net worth professionals ... in today,s globally connected world, there is still no ... could ever duplicate sealing your deal with a firm ... passports by taking advantage of citizenship via investment programs ...
(Date:4/28/2016)... 28, 2016 First quarter 2016:   ... compared with the first quarter of 2015 The gross ... M (loss: 18.8) and the operating margin was 40% (-13) ... Cash flow from operations was SEK 249.9 M (21.2) , ... is unchanged, SEK 7,000-8,500 M. The operating margin for ...
(Date:4/19/2016)... The new GEZE SecuLogic access ... "all-in-one" system solution for all door components. It can ... door interface with integration authorization management system, and thus ... minimal dimensions of the access control and the optimum ... offer considerable freedom of design with regard to the ...
Breaking Biology News(10 mins):
(Date:5/19/2016)... ... May 19, 2016 , ... KCAS Bioanalytical and Biomarker Services, ... Director, Large Molecule & Biomarker Bioanalysis. , Dr. Siddiqui has more than 15 ... for preclinical and clinical safety programs. “We’ve seen significant demand for, and we ...
(Date:5/18/2016)... 2016 The Biotech industry continues to ... that there are no opportunities ahead. Today, ActiveWallSt.com has on ... THLD ), Seattle Genetics Inc. (NASDAQ: SGEN ... Corp. (NASDAQ: OPHT ). Sign up now to ... http://www.activewallst.com/ Threshold Pharmaceuticals Inc.,s shares gained ...
(Date:5/17/2016)... -- Haselmeier announces the launch by Merck ... EMA, the European Medicines Agency. Originally launched in 2011 ... new pen version includes enhancements to further improve the ... patients during use. Its enhanced design has ... with a larger display window that improves the readability ...
(Date:5/17/2016)... BASEL, Switzerland , May 17, 2016 /PRNewswire/ ... sciences company located in Basel, Switzerland ... an investigational oral inhibitor of P38 mitogen-activated protein ... ) , Strekin will build the ... Pamapimod in indications in which MAP Kinases play ...
Breaking Biology Technology: