HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Potential synergistic anti-tumor activity between lenalidomide and sorafenib in hepatocellular carcinoma.

AbstractBACKGROUND AND AIM:
The immune modulatory drug lenalidomide has shown promising anti-tumor activity in a clinical trial of patients with advanced hepatocellular carcinoma (HCC). The present study explored whether lenalidomide can enhance the anti-tumor activity of sorafenib, the standard molecular targeted therapy for HCC.
METHODS:
The anti-tumor efficacy of single-agent or combination treatment was measured by change in tumor volume and animal survival using an orthotopic liver cancer model. Distribution of T-cell subpopulations in tumor-infiltrating lymphocytes (TILs) and splenocytes derived from tumor-implanted mice was measured by flow cytometry. Depletion of relevant T-cell subpopulations or cytokines was done by co-administration of relevant antibodies with study drug treatment. Tumor cell apoptosis and tumor angiogenesis were measured by transferase deoxytidyl uridine end labeling assay and immunohistochemical study, respectively.
RESULTS:
Combination of sorafenib and lenalidomide produced significant synergistic anti-tumor efficacy in terms of tumor growth delay and animal survival. This synergistic effect was associated with a significant increase in interferon-γ expressing CD8(+) lymphocytes in TILs and a significantly higher number of granzyme- or perforin-expressing CD8(+) T cells, compared with vehicle- or single-agent treatment groups. Combination treatment significantly increased apoptotic tumor cells and vascular normalization in tumor tissue. The synergistic anti-tumor effect was abolished after CD8 depletion.
CONCLUSIONS:
Lenalidomide can enhance the anti-tumor effects of sorafenib in HCC through its immune modulatory effects, and CD8(+) TILs play an important role in the anti-tumor synergism.
AuthorsDa-Liang Ou, Chun-Jung Chang, Yung-Ming Jeng, Yi-Jang Lin, Zhong-Zhe Lin, Anita K Gandhi, Sheng-Chieh Liao, Zi-Ming Huang, Chiun Hsu, Ann-Lii Cheng
JournalJournal of gastroenterology and hepatology (J Gastroenterol Hepatol) Vol. 29 Issue 12 Pg. 2021-31 (Dec 2014) ISSN: 1440-1746 [Electronic] Australia
PMID25160036 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.
Chemical References
  • Antineoplastic Agents
  • Immunologic Factors
  • Phenylurea Compounds
  • Niacinamide
  • Thalidomide
  • Interferon-gamma
  • Sorafenib
  • Lenalidomide
Topics
  • Animals
  • Antineoplastic Agents (pharmacology, therapeutic use)
  • CD8-Positive T-Lymphocytes (immunology)
  • Carcinoma, Hepatocellular (drug therapy, immunology, pathology)
  • Disease Models, Animal
  • Drug Synergism
  • Drug Therapy, Combination
  • Humans
  • Immunologic Factors (pharmacology, therapeutic use)
  • Interferon-gamma
  • Lenalidomide
  • Liver Neoplasms (drug therapy, immunology, pathology)
  • Mice
  • Niacinamide (analogs & derivatives, pharmacology, therapeutic use)
  • Phenylurea Compounds (pharmacology, therapeutic use)
  • Sorafenib
  • T-Lymphocyte Subsets
  • Thalidomide (analogs & derivatives, pharmacology, therapeutic use)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: