Skip to main content

Advertisement

SpringerLink
Log in

Local Delivery System of Immune Modulating Drug for Unresectable Adenocarcinoma: In Vitro Experimental Study and In Vivo Animal Study

  • Published:
CardioVascular and Interventional Radiology Aims and scope Submit manuscript

Abstract

The purpose of the study was to evaluate the efficacy and safety of a developed drug delivery system containing OK-432 through in vitro and animal study. An OK-432-impregnated polycarbonate/polyurethane stent membrane was used to develop a drug delivery system (DDS) enabling the locoregional release of OK-432. Polyethyleneglycol was used as a detergent and porosity generator. The stability of OK-432 in solvent, releasing kinetics of drug, and cytotoxicity of the DDS were evaluated. OK-432-impregnated DDS was implanted in mice in which a human adenocarcinoma cell line was injected and grown in their back. Flow cytometry and enzyme-linked immunosorbent assay were used for quantifying the amount of drug. OK-432 exposed to phosphate-buffered saline and OK-432 exposed to N,N-dimethylacetamide showed similar results on dot graphs and histograms. However, OK-432 exposed to tetrahydrofurane showed different dot graphs and histograms, which means that the antigenicity of the drug was changed. The release rate of OK-432 was maintained at a constant level for 6 weeks. The local delivery of OK-432 was found to have an antitumor effect on a human adenocarcinoma cell line in an animal study, but no effect on this cell line in in vitro cell culture. Histologic examination showed minimal inflammatory reaction in surrounding tissue. Our study shows that local treatment using this OK-432 release system is safe and effective in reducing adenocarcinoma in a mouse model.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

References

  1. Mezawa S, Homma H, Sato T, et al. (2000) A study of carboplatin-coated tube for the unresectable cholangiocarcinoma. Hepatology 32:916–923

    Article  CAS  PubMed  Google Scholar 

  2. Uehara K, Ichida T, Sugahara S, et al. (2002) Systemic administration of liposome-encapsulated OK-432 prolongs the survival of rats with hepatocellular carcinoma through the induction of IFN-gamma-producing hepatic lymphocytes. J Gastroenterol Hepatol 17:81–90

    Article  CAS  PubMed  Google Scholar 

  3. Okamoto M, Oshikawa T, Tano T, et al. (2003) Involvement of Toll-like receptor 4 signaling in interferon-gamma production and antitumor effect by streptococcal agent OK-432. J Natl Cancer Inst 95:316–326

    Article  CAS  PubMed  Google Scholar 

  4. Nose M, Uzawa A, Ogyu T, et al. (2001) OK-432 reduces mortality and bacterial translocation in irradiated and granulocyte-colony stimulating factor (G-CSF)-treated mice. J Radiat Res (Tokyo) 42:191–200

    Article  CAS  Google Scholar 

  5. Nakahara S, Tsunoda T, Baba T, et al. (2003) Dendritic cells stimulated with a bacterial product, OK-432, efficiently induce cytotoxic T lymphocytes specific to tumor rejection peptide. Cancer Res 63:4112–4118

    CAS  PubMed  Google Scholar 

  6. Takahashi K, Harauchi D, Kimura S, et al. (1998) OK-432 develops CTL and LAK activity in mononuclear cells from regional lymph nodes of lung cancer patients. Int J Immunopharmacol 20:375–388

    Article  CAS  PubMed  Google Scholar 

  7. Oshikawa T, Okamoto M, Ohe G, et al. (2003) Anti-tumor immune response induced by the fractions derived from OK-432, a streptococcal preparation, by using a monoclonal antibody TS-2 that neutralizes the interferon-gamma-inducing activity of OK-432: comparison between the TS-2-binding and TS-2-unbinding fraction. Int Immunopharmacol 3:643–655

    Article  CAS  PubMed  Google Scholar 

  8. Nishikido M, Kiyohara T, Koga S, et al. (2001) OK432-induced killer cell activity: potential method for monitoring immunological complications after renal transplantation. Nephrol Dial Transplant 16:2067–2071

    Article  CAS  PubMed  Google Scholar 

  9. Itoh T, Ueda Y, Okugawa K, Fujiwara H, et al. (2003) Streptococcal preparation OK432 promotes functional maturation of human monocyte-derived dendritic cells. Cancer Immunol Immunother 52:207–214

    CAS  PubMed  Google Scholar 

  10. Shih CM, Shih CC, Su YY, et al. (2005) In vitro study of drug loading on polymer-free oxide films of metallic implants. J Biomed Mater Res A 75(3): 519–529

    Article  PubMed  Google Scholar 

  11. Gershlick AH (2005) Drug eluting stents in 2005. Heart 91(Suppl 3):iii24–iii31

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Machan L, Burt HM, Hunter WL (1997) Local delivery of chemotherapy: a supplement to existing cancer treatments. A case for surgical pastes and coated stents. Adv Drug Deliv Rev 26:199–207

    Article  PubMed  Google Scholar 

  13. Jung GS, Song HY, Kang SG, et al. (2000) Malignant gastroduodenal obstructions: treatment by means of a covered expandable metallic stent-initial experience. Radiology 216:758–763

    Article  CAS  PubMed  Google Scholar 

  14. Monson JR, Donohue JH, McIlrath DC, et al. (1991) Total gastrectomy for advanced cancer. A worthwhile palliative procedure. Cancer 68:1863–1868

    Article  CAS  PubMed  Google Scholar 

  15. Meijer S, De Bakker OJ, Hoitsma HF (1983) Palliative resection in gastric cancer. J Surg Oncol 23:77–80

    Article  CAS  PubMed  Google Scholar 

  16. Kikuchi S, Tsutsumi O, Kobayashi N, et al. (1999) Does gastrojejunostomy for unresectable cancer of the gastric antrum offer satisfactory palliation? Hepatogastroenterology 46:584–587

    CAS  PubMed  Google Scholar 

  17. Baron TH (2001) Expandable metal stents for the treatment of cancerous obstruction of the gastrointestinal tract. N Engl J Med 344:1681–1687

    Article  CAS  PubMed  Google Scholar 

  18. Pinto IT (1997) Malignant gastric and duodenal stenosis: palliation by peroral implantation of a self-expanding metallic stent. Cardiovasc Intervent Radiol 20:431–434

    Article  CAS  PubMed  Google Scholar 

  19. Feretis C, Benakis P, Dimopoulos C, et al. (1997) Duodenal obstruction caused by pancreatic head carcinoma: Palliation with self-expandable endoprostheses. Gastrointest Endosc 46:161–165

    Article  CAS  PubMed  Google Scholar 

  20. Song HY, Choi KC, Kwon HC, et al. (1992) Esophageal strictures: treatment with a new design of modified Gianturco stent. Work in progress. Radiology 184:729–734

    Article  CAS  PubMed  Google Scholar 

  21. Song HY, Yang DH, Kuh JH, et al. (1993) Obstructing cancer of the gastric antrum: palliative treatment with covered metallic stents. Radiology 187:357–358

    Article  CAS  PubMed  Google Scholar 

  22. Tatsugami K, Tamada K, Abe K, et al. (2000) Local injections of OK432 can help the infiltration of adoptively transferred CD8+ T cells into the tumor sites and synergistically induce the local production of Th1-type cytokines and CXC3 chemokines. Cancer Immunol Immunother 49:361–368

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgment

This study was supported by Korea Science and Engineering foundation (KOSEF), through its 2000 basic science support program (R01-2000-000-00121-0).

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Inha University, College of Medicine, Inchon, Korea

    Don Haeng Lee & Seok Jeong

  2. Department of Diagnostic Radiology, Seoul National University Bundang Hospital, 300, Gumi-dong, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-707, Korea

    Sung-Gwon Kang, Chang Jin Yoon, Jung-Ah Choi & Jae Hyung Park

  3. Department of Radiology, Chosun University, College of Medicine, Gwangju, Korea

    Ju Nam Byun

  4. Department of Biomedical Engineering, Korea University, College of Medicine, Seoul, Korea

    Kyu Back Lee

Authors
  1. Don Haeng Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sung-Gwon Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Seok Jeong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chang Jin Yoon
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jung-Ah Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ju Nam Byun
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jae Hyung Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kyu Back Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sung-Gwon Kang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lee, D.H., Kang, SG., Jeong, S. et al. Local Delivery System of Immune Modulating Drug for Unresectable Adenocarcinoma: In Vitro Experimental Study and In Vivo Animal Study. Cardiovasc Intervent Radiol 29, 832–837 (2006). https://doi.org/10.1007/s00270-005-0194-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00270-005-0194-x

Keywords

Search

Navigation