Featured Research

from universities, journals, and other organizations

Finnish Scientists Discover New Approach To Treat Virus-induced Lymphomas

Date:
March 16, 2007
Source:
University of Helsinki
Summary:
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.

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. Pδivi Ojala (University of Helsinki) in collaboration with the groups of Professor Marikki Laiho (University of Helsinki), Dr. Pirjo Laakkonen (University of Helsinki), and Dr. Jόrgen 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.

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).

Reference: Sarek G., Kurki S., Enbδck J., Iotzova G., Haas J., Laakkonen P., Laiho M., and Ojala P.M.: Reactivation of the p53 Pathway as a Novel Treatment Modality for KSHV-induced Lymphomas, J. Clin. Invest., March 15, 2007.


Story Source:

The above story is based on materials provided by University of Helsinki. Note: Materials may be edited for content and length.


Cite This Page:

University of Helsinki. "Finnish Scientists Discover New Approach To Treat Virus-induced Lymphomas." ScienceDaily. ScienceDaily, 16 March 2007. <www.sciencedaily.com/releases/2007/03/070315210112.htm>.
University of Helsinki. (2007, March 16). Finnish Scientists Discover New Approach To Treat Virus-induced Lymphomas. ScienceDaily. Retrieved July 25, 2014 from www.sciencedaily.com/releases/2007/03/070315210112.htm
University of Helsinki. "Finnish Scientists Discover New Approach To Treat Virus-induced Lymphomas." ScienceDaily. www.sciencedaily.com/releases/2007/03/070315210112.htm (accessed July 25, 2014).

Share This




More Health & Medicine News

Friday, July 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Beatings and Addiction: Pakistan Drug 'clinic' Tortures Patients

Beatings and Addiction: Pakistan Drug 'clinic' Tortures Patients

AFP (July 24, 2014) — A so-called drugs rehab 'clinic' is closed down in Pakistan after police find scores of ‘patients’ chained up alleging serial abuse. Duration 03:05 Video provided by AFP
Powered by NewsLook.com
Too Few Teens Receiving HPV Vaccination, CDC Says

Too Few Teens Receiving HPV Vaccination, CDC Says

Newsy (July 24, 2014) — The Centers for Disease Control and Prevention is blaming doctors for the low number of children being vaccinated for HPV. Video provided by Newsy
Powered by NewsLook.com
New Painkiller Designed To Discourage Abuse: Will It Work?

New Painkiller Designed To Discourage Abuse: Will It Work?

Newsy (July 24, 2014) — The FDA approved Targiniq ER on Wednesday, a painkiller designed to keep users from abusing it. Like any new medication, however, it has doubters. Video provided by Newsy
Powered by NewsLook.com
Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Newsy (July 24, 2014) — Sheik Umar Khan has treated many of the people infected in the Ebola outbreak, and now he's become one of them. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins