Navigation Links
Cancer drugs may help stop major parasite
Date:7/16/2010

A parasite estimated to afflict as many as 12 million people worldwide relies on a family of genes that should make it vulnerable to compounds developed to treat cancer and other disorders, researchers at Washington University School of Medicine in St. Louis have found.

Scientists searched the genome of the parasite Leishmania to determine that it has three kinds of TOR kinases, proteins that are linked to cell growth and cancer and have been longstanding targets for drug development. When they removed the proteins individually, they found that all three were critical either to the parasite's ability to survive or its ability to cause infections.

"If we can hit any of these proteins with a drug that will inhibit them, we should be able to strike a significant blow against Leishmania," says senior author Stephen Beverley, PhD, the Marvin A. Brennecke Professor and head of Molecular Microbiology. "Given the numerous inhibitors already available, I think there's a pretty good chance that we'll be able to identify a compound that specifically inhibits one of Leishmania's TOR kinases."

The finding appears online in The Proceedings of the National Academy of Sciences.

Infection with the Leishmania parasite, or leishmaniasis, is mainly spread by sand fly bites and is a major public health problem in Asia, Africa, the Middle East and other parts of the developing world. Symptoms include large skin lesions, fever, swelling of the spleen and liver, and, in more serious forms of the disease, disfigurement. The most severe form of leishmaniasis, a condition sometimes called black fever, is fatal if left untreated and is estimated to kill more humans than any other parasite except Plasmodium falciparum, the malaria parasite.

Mammals have only one TOR kinase protein, and drug developers have targeted it to block immune system rejection of transplanted organs, to treat certain forms of cancer and, more recently, to prevent some age-related illnesses.

When Beverley's lab separately deleted each of the first two TOR kinases from Leishmania's genome, the parasite could not survive. Deleting the third TOR kinase led to a parasite that survived the initial stage of its lifecycle, which normally occurs in sand flies. But the modified parasite died when it tried to infect animals or cell cultures.

Closer study of how loss of TOR kinase 3 affected Leishmania revealed that structures inside the parasite known as acidocalcisomes were defective. They were unusual in size and shape and did not carry their usual cargo, high-energy molecules known as polyphosphates.

The study provides the first proof that acidocalcisomes are essential for infection. The properties of the parasite with mutated TOR kinase 3 confirmed prior research that suggested the acidocalcisome may help cells regulate the flow of fluids across the cell membrane or cope with stress and loss of access to the sugar glucose.

"Entry into the host is one of the most stressful times in a parasite's lifecycle," says first author Luciana Madeira da Silva, PhD, a former postdoctoral researcher. "Having fewer ways to cope with stress at that point could be a real problem for Leishmania."

Beverley has begun working with another group that repurposes human TOR kinase inhibitors, adapting them for other uses. They plan to see if existing drugs might disable or kill the Leishmania parasite by inhibiting one of its three TOR kinases.


'/>"/>

Contact: Michael C. Purdy
purdym@wustl.edu
314-286-0122
Washington University School of Medicine
Source:Eurekalert  

Related biology news :

1. WSU researchers find way to make cancer cells more mortal
2. New arsenic nanoparticle blocks aggressive breast cancer
3. Mechanism for link between high fat diet and risk of prostate cancer and disorders unveiled
4. Divide and conquer: Genes decide who wins in the bodys battle against cancer
5. Mahjong gene is key player when cancer, normal cells compete
6. CWRU dental researchers discover human beta defensins-3 ignite in oral cancer growth
7. The Samuel Waxman Cancer Research Foundation awards $1.54 million in research grants for 2010-2011
8. A*STAR scientists score hat-trick against cancer
9. Innovation and current status of prostate cancer gene therapy featured in Human Gene Therapy
10. Damon Runyon Cancer Research Foundation awards prestigious fellowships to 18 top young scientists
11. DNA discovery opens new door to develop tools, therapies for hereditary cancers
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Cancer drugs may help stop major parasite
(Date:4/13/2017)... 2017 According to a new market research report ... Identity Administration, and Authorization), Service, Authentication Type, Deployment Mode, Vertical, and Region ... expected to grow from USD 14.30 Billion in 2017 to USD 31.75 ... ... MarketsandMarkets Logo ...
(Date:4/11/2017)... 2017 No two people are believed ... New York University Tandon School of Engineering and ... that partial similarities between prints are common enough ... phones and other electronic devices can be more ... lies in the fact that fingerprint-based authentication systems ...
(Date:4/5/2017)... , April 5, 2017  The Allen Institute ... Allen Cell Explorer: a one-of-a-kind portal and dynamic digital ... 3D imaging data, the first application of deep learning ... human stem cell lines and a growing suite of ... platform for these and future publicly available resources created ...
Breaking Biology News(10 mins):
(Date:10/12/2017)... ... October 12, 2017 , ... BioMedGPS announces expanded coverage ... its newest module, US Hemostats & Sealants. , SmartTRAK’s US Market for Hemostats ... sealants, synthetic sealants and biologic sealants used in surgical applications. BioMedGPS estimates the ...
(Date:10/11/2017)... (PRWEB) , ... October 11, 2017 , ... ... Foundation President Andi Purple announced Dr. Suneel I. Sheikh, the co-founder, CEO ... ASTER Labs ), Inc. has been selected for membership in ARCS Alumni ...
(Date:10/11/2017)... ... October 11, 2017 , ... ComplianceOnline’s Medical Device Summit ... 7th and 8th June 2018 in San Francisco, CA. The Summit brings together current ... several distinguished CEOs, board directors and government officials from around the world to address ...
(Date:10/11/2017)... and LAGUNA HILLS, Calif. , Oct. ... Cancer Research, London (ICR) and University ... SKY92, SkylineDx,s prognostic tool to risk-stratify patients with multiple myeloma ... MUK nine . The University of Leeds ... partly funded by Myeloma UK, and ICR will perform the ...
Breaking Biology Technology: