Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Finnish scientists discovered a new approach to treat virus-induced lymphomas

16.03.2007
Kaposi’s sarcoma herpesvirus (KSHV) is a human tumor virus and an etiological agent for Kaposi’s sarcoma and primary effusion lymphoma (PEL). PELs are aggressive lymphomas with reported median survival time shorter than six months after diagnosis. Researchers at the University of Helsinki have discovered that activation of the p53 pathway offers a novel effective treatment modality for KSHV-infected lymphomas.

The findings by the research group of Dr. Päivi Ojala (University of Helsinki) in collaboration with the groups of Professor Marikki Laiho (University of Helsinki), Dr. Pirjo Laakkonen (University of Helsinki), and Dr. Jürgen Haas (Max von Pettenkofer Institute, Munich & University of Edinburgh) open new options for exploiting reactivation of p53 as a novel and highly selective treatment modality for this virally-induced lymphoma. The project involves scientists from two Academy of Finland National Centre of Excellence Programs, the Translational Genome-Scale Biology and Cancer Biology.

The study will be published 15.3.2007 in the Journal of Clinical Investigation.

TP53 gene encodes a transcription factor (p53) that plays a central role in protecting cells from tumor development by inducing cell-cycle arrest or apoptosis via a complex signal transduction network referred to as the p53 pathway. TP53 gene is mutated or deleted in 50% of all malignant tumors. A recently discovered strategy for p53 activation targets the interaction of p53 with its negative regulator MDM2. This is based on a potent and selective small-molecule inhibitor of the p53–MDM2 interaction, the Nutlin-3a, originally discovered by Dr Lyubomir T Vassilev (Roche Research Center, Nutley, NJ., USA). Nutlin-3a has been suggested to be a potential treatment option for cancers with wt p53.

... more about:
»KSHV »Nutlin-3a »PEL »apoptosis »lymphoma »p53

PEL is a non-Hodgkin type lymphoma latently infected with KSHV, and it manifests as an effusion malignancy in Kaposi’s sarcoma patients. There are no current therapies effective against the aggressive KSHV-induced PEL. KSHV displays two patterns of infection: latent and lytic phase. During latency, only a restricted set of viral genes is expressed. The KSHV genome encodes several homologues of cellular proteins, which engage cellular signaling pathways, govern cell proliferation and modulate apoptosis.

Majority of the PELs appear to have an intact TP53 gene suggesting that genetic alterations are not selected for during PEL tumorigenesis. The results of this study demonstrate binding of the KSHV latency associated antigen LANA to both p53 and MDM2, and that the MDM2 inhibitor Nutlin-3a disrupts the p53-MDM2-LANA complex and selectively induces massive apoptosis in PEL cells. The cytotoxic effect of Nutlin-3a was specific for the KSHV-infected cells since Nutlin-3a did not induce apoptosis in lymphoblastoid cell lines transformed with another human tumor virus, the Epstein-Barr virus, despite of their wt p53 status.

Moreover, the researchers show that Nutlin-3a has striking anti-tumor activity in vivo in a mouse xenograft model for the PEL. Nutlin-3a treatment resulted in a marked regression of all tumors in the treated animals in two weeks. These results demonstrate that p53 reactivation via Nutlin-3a is an efficient treatment for KSHV-lymphomas in mice and suggest a novel therapeutic strategy for treatment of these fatal virus-induced malignancies also in humans.

This work was supported by grants from the Academy of Finland including also Centres of Excellence in Translational Genome-Scale Biology and Cancer Biology, and additional funds have been obtained from the University of Helsinki, Academy of Finland research program for Systems Biology and Bioinformatics, Finnish Cancer Foundations, Sigrid Juselius Foundation, and from the European Union (FP6 INCA project LSHC-CT-2005-018704).

Paivi Lehtinen | alfa
Further information:
http://www.helsinki.fi

Further reports about: KSHV Nutlin-3a PEL apoptosis lymphoma p53

More articles from Life Sciences:

nachricht Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory

nachricht Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Electron highway inside crystal

Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.

Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Researchers identify potentially druggable mutant p53 proteins that promote cancer growth

09.12.2016 | Life Sciences

Scientists produce a new roadmap for guiding development & conservation in the Amazon

09.12.2016 | Ecology, The Environment and Conservation

Satellites, airport visibility readings shed light on troops' exposure to air pollution

09.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>