Multi-targeted therapy of everolimus in Kaposi’s sarcoma associated herpes virus infected primary effusion lymphoma

Multi-targeted therapy of everolimus in Kaposi’s sarcoma associated herpes virus infected... Kaposi’s sarcoma associated herpes virus (KSHV) infected primary effusion lymphoma (PEL) is a rare aggressive form of non-Hodgkin’s lymphoma of B cells. KSHV latent and lytic antigens modulate several host cellular signalling pathways especially mammalian target of rapamycin (mTOR), STAT-3 and nuclear factor-kappa B (NF-κB) for rapid tumor progression and immune evasion. Current chemotherapeutic strategies are becoming ineffective as they kill only dividing cells and inefficient to target molecular pathways crucial for active virus replication and its survival. In this study, we evaluated the efficacy of everolimus, an mTOR inhibitor in inducing apoptosis of PEL cells. Dose-dependent treatment of everolimus triggered mitochondria-mediated caspase-dependent apoptosis in PEL cells. Everolimus downregulated KSHV latent antigen expression with concurrent blocking of lytic reactivation for active virus replication. Everolimus also inhibited latent antigen mediated constitutively active STAT-3 and NF-κB signalling. We co-cultured everolimus treated PEL cells with immature dendritic cells and found activation of dendritic cells with increase in surface expression of CD86 and HLA-DR. As everolimus targets and disrupts KSHV antigens as well as antigen facilitated multiple signalling pathways necessary for KSHV survival and maintenance of infection with synchronised boosting of immune system against viral infection, it can be a better therapeutic approach towards treatment of PEL. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Apoptosis Springer Journals

Multi-targeted therapy of everolimus in Kaposi’s sarcoma associated herpes virus infected primary effusion lymphoma

Loading next page...
 
/lp/springer_journal/multi-targeted-therapy-of-everolimus-in-kaposi-s-sarcoma-associated-jeMY1t9Ov3
Publisher
Springer US
Copyright
Copyright © 2017 by Springer Science+Business Media, LLC
Subject
Biomedicine; Cancer Research; Cell Biology; Oncology; Biochemistry, general; Virology
ISSN
1360-8185
eISSN
1573-675X
D.O.I.
10.1007/s10495-017-1391-1
Publisher site
See Article on Publisher Site

References

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 12 million articles from more than
10,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Unlimited reading

Read as many articles as you need. Full articles with original layout, charts and figures. Read online, from anywhere.

Stay up to date

Keep up with your field with Personalized Recommendations and Follow Journals to get automatic updates.

Organize your research

It’s easy to organize your research with our built-in tools.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

Monthly Plan

  • Read unlimited articles
  • Personalized recommendations
  • No expiration
  • Print 20 pages per month
  • 20% off on PDF purchases
  • Organize your research
  • Get updates on your journals and topic searches

$49/month

Start Free Trial

14-day Free Trial

Best Deal — 39% off

Annual Plan

  • All the features of the Professional Plan, but for 39% off!
  • Billed annually
  • No expiration
  • For the normal price of 10 articles elsewhere, you get one full year of unlimited access to articles.

$588

$360/year

billed annually
Start Free Trial

14-day Free Trial