Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
July-2017 Volume 14 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
July-2017 Volume 14 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Therapy with transcutaneous administration of imiquimod combined with oral administration of sorafenib suppresses renal cell carcinoma growing in an orthotopic mouse model

  • Authors:
    • Takashi Karashima
    • Keiko Udaka
    • Mayumi Niimura
    • Katsuhide Suzuki
    • Hiroto Osakabe
    • Tsutomu Shimamoto
    • Satoshi Fukata
    • Keiji Inoue
    • Naoto Kuroda
    • Motoharu Seiki
    • Taro Shuin
  • View Affiliations / Copyright

    Affiliations: Department of Urology, Kōchi Medical School, Nankoku, Kōchi 783‑8505, Japan, Department of Immunology, Kōchi Medical School, Nankoku, Kōchi 783‑8505, Japan, Department of Diagnostic Pathology, Kōchi Red Cross Hospital, Kōchi, Kōchi 780‑0062, Japan, Medical Innovation Center, Kōchi Medical School, Nankoku, Kōchi 783‑8505, Japan
  • Pages: 1162-1166
    |
    Published online on: May 24, 2017
       https://doi.org/10.3892/ol.2017.6235
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Imiquimod is an imidazoquinoline immune response modifier that is used in antiviral and antiallergic creams. Combination therapy using transcutaneous imiquimod and oral sorafenib was previously demonstrated to reduce the tumor burden of renal cell carcinoma growing cutaneously in a mouse model. In the present study, an orthotopic mouse model was used to investigate whether combined treatment with oral sorafenib and transcutaneous imiquimod inhibited renal cell carcinoma growing in the kidney. Kidneys of female BALB/c mice were orthotopically implanted with RENCA mouse kidney cancer cells, and the mice were transcutaneously treated with cream containing imiquimod and/or with orally administered sorafenib 5 days following cell implantation. Tumor burden and incidence were determined 28 days following the start of therapy. Splenocyte activity was quantified using the 51Cr release assay and the fluorescence‑activated cell sorting assay with cluster of differentiation (CD) 4 and CD8 antibodies. Imiquimod, sorafenib and combination therapy were tolerated well. A combination of transcutaneous imiquimod and oral sorafenib inhibited the growth of RENCA tumors in the kidney significantly compared with the control. The 51Cr release assay demonstrated that transcutaneous imiquimod therapy significantly induced the release of 51Cr from RENCA cells compared with the control. The fluorescence‑activated cell sorting assay demonstrated that transcutaneous imiquimod therapy induced CD8+ and CD4‑ splenocytes compared with the control. In summary, the results of the present study demonstrated that combined treatment with transcutaneous imiquimod and oral sorafenib may be a promising strategy for the treatment of patients with renal cell carcinoma.
View Figures

Figure 1

Figure 2

Figure 3

View References

1 

Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, et al: Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 366:2443–2454. 2012. View Article : Google Scholar : PubMed/NCBI

2 

Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, Drake CG, Camacho LH, Kauh J, Odunsi K, et al: Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 366:2455–2465. 2012. View Article : Google Scholar : PubMed/NCBI

3 

Royal RE, Levy C, Turner K, Mathur A, Hughes M, Kammula US, Sherry RM, Topalian SL, Yang JC, Lowy I and Rosenberg SA: Phase 2 trial of single agent Ipilimumab (anti-CTLA-4) for locally advanced or metastatic pancreatic adenocarcinoma. J Immunother. 33:828–833. 2010. View Article : Google Scholar : PubMed/NCBI

4 

Hemmi H, Kaisho T, Takeuchi O, Sato S, Sanjo H, Hoshino K, Horiuchi T, Tomizawa H, Takeda K and Akira S: Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway. Nat Immunol. 3:196–200. 2002. View Article : Google Scholar : PubMed/NCBI

5 

Peet NP, Baugh LE, Sunder S and Lewis JE: Synthesis and antiallergic activity of some quinolinones and imidazoquinolinones. J Med Chem. 28:298–302. 1985. View Article : Google Scholar : PubMed/NCBI

6 

Lebwohl M, Dinehart S, Whiting D, Lee PK, Tawfik N, Jorizzo J, Lee JH and Fox TL: Imiquimod 5% cream for the treatment of actinic keratosis: Results from two phase III, randomized, double-blind, parallel group, vehicle-controlled trials. J Am Acad Dermatol. 50:714–721. 2004. View Article : Google Scholar : PubMed/NCBI

7 

Geisse JK, Rich P, Pandya A, Gross K, Andres K, Ginkel A and Owens M: Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: A double-blind, randomized, vehicle-controlled study. J Am Acad Dermatol. 47:390–398. 2002. View Article : Google Scholar : PubMed/NCBI

8 

Naylor MF, Crowson N, Kuwahara R, Teague K, Garcia C, Mackinnis C, Haque R, Odom C, Jankey C and Cornelison RL: Treatment of lentigo maligna with topical imiquimod. Br J Dermatol. 149 Suppl 66:S66–S70. 2003. View Article : Google Scholar

9 

Lyons JF, Wilhelm S, Hibner B and Bollag G: Discovery of a novel Raf kinase inhibitor. Endocr Relat Cancer. 8:219–225. 2001. View Article : Google Scholar : PubMed/NCBI

10 

Karashima T, Komatsu T, Niimura M, Kawada C, Kamada M, Inoue K, Udaka K, Kuroda N and Shuin T: Novel combination therapy with imiquimod and sorafenib for renal cell carcinoma. Int J Urol. 21:702–706. 2014. View Article : Google Scholar : PubMed/NCBI

11 

Vines T and Faunce T: Freedom of information applications as an ‘evergreening’ tactic: Secretary, department of health and ageing v iNOVA pharmaceuticals (Australia) Pty Ltd (2010) 191 FCR 573; [2010]FCA 1442. J Law Med. 19:43–52. 2011.PubMed/NCBI

12 

Karashima T, Inoue K, Fukata S, Iiyama T, Kurabayashi A, Kawada C and Shuin T: Blockade of the vascular endothelial growth factor-receptor 2 pathway inhibits the growth of human renal cell carcinoma, RBM1-IT4, in the kidney but not in the bone of nude mice. Int J Oncol. 30:937–945. 2007.PubMed/NCBI

13 

Visseren MJ, van Elsas A, van er Voort EI, Ressing ME, Kast WM, Schrier PI and Melief CJ: CTL specific for the tyrosinase autoantigen can be induced from healthy donor blood to lyse melanoma cells. J Immunol. 154:3991–3998. 1995.PubMed/NCBI

14 

Li Z, Oka Y, Tsuboi A, Fujiki F, Harada Y, Nakajima H, Masuda T, Fukuda Y, Kawakatsu M, Morimoto S, et al: Identification of a WT1 protein-derived peptide, WT1, as a HLA-A 0206-restricted, WT1-specific CTL epitope. Microbiol Immunol. 52:551–558. 2008. View Article : Google Scholar : PubMed/NCBI

15 

Majewski S, Marczak M, Mlynarczyk B, Benninghoff B and Jablonska S: Imiquimod is a strong inhibitor of tumor cell-induced angiogenesis. Int J Dermatol. 44:14–19. 2005. View Article : Google Scholar : PubMed/NCBI

16 

Vidal D, Matías-Guiu X and Alomar A: Efficacy of imiquimod for the expression of Bcl-2, Ki67, p53 and basal cell carcinoma apoptosis. Br J Dermatol. 151:656–662. 2004. View Article : Google Scholar : PubMed/NCBI

17 

Kim CH, Ahn JH, Kang SU, Hwang HS, Lee MH, Pyun JH and Kang HY: Imiquimod induces apoptosis of human melanocytes. Arch Dermatol Res. 302:301–306. 2010. View Article : Google Scholar : PubMed/NCBI

18 

Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, Negrier S, Chevreau C, Solska E, Desai AA, et al: Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 356:125–134. 2007. View Article : Google Scholar : PubMed/NCBI

19 

Santoni M, Berardi R, Amantini C, Burattini L, Santini D, Santoni G and Cascinu S: Role of natural and adaptive immunity in renal cell carcinoma response to VEGFR-TKIs and mTOR inhibitor. Int J Cancer. 134:2772–2777. 2014. View Article : Google Scholar : PubMed/NCBI

20 

Cabrera R, Ararat M, Xu Y, Brusko T, Wasserfall C, Atkinson MA, Chang LJ, Liu C and Nelson DR: Immune modulation of effector CD4+ and regulatory T cell function by sorafenib in patients with hepatocellular carcinoma. Cancer Immunol Immunother. 62:737–746. 2013. View Article : Google Scholar : PubMed/NCBI

21 

Delgado-Charro MB and Guy RH: Transdermal Drug DeliveryHillary AM, Lloyd AW and Swarbrick J: Drug Delivery and Targeting: For Pharmacists and Pharmaceutical Scientists. Taylor & Francis; London and New York: pp. 189–214. 2001

22 

Mathias NR and Hussain MA: Non-invasive systemic drug delivery: Developability considerations for alternate routes of administration. J Pharm Sci. 99:1–20. 2010. View Article : Google Scholar : PubMed/NCBI

23 

Oertel W, Ross JS, Eggert K and Adler G: Rationale for transdermal drug administration in Alzheimer disease. Neurology. 69 4 Suppl 1:S4–S9. 2007. View Article : Google Scholar : PubMed/NCBI

24 

Seeberger LC and Hauser RA: Optimizing bioavailability in the treatment of Parkinson's disease. Neuropharmacol. 53:791–800. 2007. View Article : Google Scholar

25 

Santini B, Zanoni I, Marzi R, Cigni C, Bedoni M, Gramatica F, Palugan L, Corsi F, Granucci F and Colombo M: Cream formulation impact on topical administration of engineered colloidal nanoparticles. PLoS One. 10:e01263662015. View Article : Google Scholar : PubMed/NCBI

26 

Soria I, Myhre P, Horton V, Ellefson P, McCarville S, Schmitt K and Owens M: Effect of food on the pharmacokinetics and bioavailability of oral imiquimod relative to a subcutaneous dose. Int J Clin Pharmacol Ther. 38:476–481. 2000. View Article : Google Scholar : PubMed/NCBI

27 

Stein P, Gogoll K, Tenzer S, Schild H, Stevanovic S, Langguth P and Radsak MP: Efficacy of imiquimod-based transcutaneous immunization using a nano-dispersed emulsion gel formulation. PLoS One. 9:e1026642014. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Karashima T, Udaka K, Niimura M, Suzuki K, Osakabe H, Shimamoto T, Fukata S, Inoue K, Kuroda N, Seiki M, Seiki M, et al: Therapy with transcutaneous administration of imiquimod combined with oral administration of sorafenib suppresses renal cell carcinoma growing in an orthotopic mouse model. Oncol Lett 14: 1162-1166, 2017.
APA
Karashima, T., Udaka, K., Niimura, M., Suzuki, K., Osakabe, H., Shimamoto, T. ... Shuin, T. (2017). Therapy with transcutaneous administration of imiquimod combined with oral administration of sorafenib suppresses renal cell carcinoma growing in an orthotopic mouse model. Oncology Letters, 14, 1162-1166. https://doi.org/10.3892/ol.2017.6235
MLA
Karashima, T., Udaka, K., Niimura, M., Suzuki, K., Osakabe, H., Shimamoto, T., Fukata, S., Inoue, K., Kuroda, N., Seiki, M., Shuin, T."Therapy with transcutaneous administration of imiquimod combined with oral administration of sorafenib suppresses renal cell carcinoma growing in an orthotopic mouse model". Oncology Letters 14.1 (2017): 1162-1166.
Chicago
Karashima, T., Udaka, K., Niimura, M., Suzuki, K., Osakabe, H., Shimamoto, T., Fukata, S., Inoue, K., Kuroda, N., Seiki, M., Shuin, T."Therapy with transcutaneous administration of imiquimod combined with oral administration of sorafenib suppresses renal cell carcinoma growing in an orthotopic mouse model". Oncology Letters 14, no. 1 (2017): 1162-1166. https://doi.org/10.3892/ol.2017.6235
Copy and paste a formatted citation
x
Spandidos Publications style
Karashima T, Udaka K, Niimura M, Suzuki K, Osakabe H, Shimamoto T, Fukata S, Inoue K, Kuroda N, Seiki M, Seiki M, et al: Therapy with transcutaneous administration of imiquimod combined with oral administration of sorafenib suppresses renal cell carcinoma growing in an orthotopic mouse model. Oncol Lett 14: 1162-1166, 2017.
APA
Karashima, T., Udaka, K., Niimura, M., Suzuki, K., Osakabe, H., Shimamoto, T. ... Shuin, T. (2017). Therapy with transcutaneous administration of imiquimod combined with oral administration of sorafenib suppresses renal cell carcinoma growing in an orthotopic mouse model. Oncology Letters, 14, 1162-1166. https://doi.org/10.3892/ol.2017.6235
MLA
Karashima, T., Udaka, K., Niimura, M., Suzuki, K., Osakabe, H., Shimamoto, T., Fukata, S., Inoue, K., Kuroda, N., Seiki, M., Shuin, T."Therapy with transcutaneous administration of imiquimod combined with oral administration of sorafenib suppresses renal cell carcinoma growing in an orthotopic mouse model". Oncology Letters 14.1 (2017): 1162-1166.
Chicago
Karashima, T., Udaka, K., Niimura, M., Suzuki, K., Osakabe, H., Shimamoto, T., Fukata, S., Inoue, K., Kuroda, N., Seiki, M., Shuin, T."Therapy with transcutaneous administration of imiquimod combined with oral administration of sorafenib suppresses renal cell carcinoma growing in an orthotopic mouse model". Oncology Letters 14, no. 1 (2017): 1162-1166. https://doi.org/10.3892/ol.2017.6235
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team