Skip to main content

Advertisement

SpringerLink
Log in

Opioid growth factor (OGF) for hepatoblastoma: a novel non-toxic treatment

  • SHORT REPORT
  • Published:
Investigational New Drugs Aims and scope Submit manuscript

Summary

Hepatoblastoma is the most common liver malignancy in children, typically diagnosed before age 2. The survival rate for hepatoblastoma has increased dramatically in the last 30 years, but the typical chemotherapeutic agents used for treatment are associated with significant toxicity. In this report, the authors present two cases of hepatoblastoma treated with surgical resection and a novel biotherapeutic regimen that included opioid growth factor (OGF). Case #1 is an infant diagnosed with a large mass on prenatal ultrasound. After subsequent diagnosis of hepatoblastoma, she was treated with one course of neoadjuvant chemotherapy at approximately 1 week of age. Following significant complications from the chemotherapy (neutropenic fever, pneumonia and sepsis), the patient’s parents declined further chemotherapy, and the infant was treated with surgical resection and opioid growth factor (OGF)/low dose naltrexone (LDN). She is currently at close to 10 years disease–free survival. Case #2 is a child diagnosed with a liver mass on ultrasound at 20 months of age, later biopsy-proven to represent hepatoblastoma. Due to existing co-morbidities including autosomal recessive polycystic kidney disease and hypertension, and indications from the biopsy that the tumor might be insensitive to chemotherapy, the parents elected not to proceed with neoadjuvant chemotherapy. The patient was treated with surgical resection and OGF/LDN, and is currently at more than 5 years disease-free survival. This case series highlights the need for less toxic treatment options than conventional chemotherapy. Modulation of the OGF-OGF receptor axis represents a promising safe and therapeutic avenue for effective treatment of hepatoblastoma.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Institutional subscriptions

References

  1. Litten JB, Tomlinson GE (2008) Liver tumors in children. Oncologist 13(7):812–820

    Article  PubMed  Google Scholar 

  2. Davenport KP, Blanco FC, Sandler AD (2012) Pediatric malignancies: neuroblastoma, Wilm’s tumor, hepatoblastoma, rhabdomyosarcoma, and sacroccygeal teratoma. Surg Clin N Am 92(3):745–767

    Article  PubMed  Google Scholar 

  3. Birch JM (2011) Epidemiology of pediatric liver tumors. In: Zimmermann A, Perilongo G, Malogolowkin M, von Schweinitz D (eds) Pediatric liver tumors. Springer, Heidelberg, pp 15–26

    Chapter  Google Scholar 

  4. Moon SB, Shin HB, Seo JM, Lee SK (2011) Hepatoblastoma: 15-year experience and role of surgical treatment. J Korean Surg Soc 81(2):134–140

    Article  PubMed  Google Scholar 

  5. Hadzic N, Finegold MJ (2011) Liver neoplasia in children. Clin Liver Dis 15(2):443–462

    Article  PubMed  Google Scholar 

  6. von Schweinitz D (2012) Hepatoblastoma: recent developments in research and treatment. Semin Pediatr Surg 21(1):21–30

    Article  Google Scholar 

  7. Grewal S, Merchant T, Reymond R et al (2010) Auditory late effects of childhood cancer therapy: a report from the Children’s Oncology Group. Pediatrics 125:e938–e950

    Article  PubMed  Google Scholar 

  8. Skinner R, Parry A, Price L, Cole M, Craft AW, Pearson AD (2009) Persistent nephrotoxicity during 10-year follow-up after cisplatin or carboplatin treatment in childhood: relevance of age and dose as risk factors. Eur J Cancer 45(18):3213–3219

    Article  CAS  PubMed  Google Scholar 

  9. Langholz B, Skolnik JM, Barrett JS, Renbarger J, Seibel NL, Zajicek A, Arndt CA (2011) Dactinomycin and vincristine toxicity in the treatment of childhood cancer: a retrospective study from the Children’s Oncology Group. Pediatr Blood Cancer 57(2):252–257

    Article  PubMed  Google Scholar 

  10. Lennon AS, Norales G, Armstrong MB (2012) Cardiac arrest and possible seizure activity after vincristine injection. Am J Health Syst Pharm 69(16):1394–1397

    Article  CAS  PubMed  Google Scholar 

  11. Harake D, Franco VI, Henkel JM, Miller TL, Lipshultz SE (2012) Cardiotoxicity in childhood cancer survivors: strategies for prevention and management. Futur Cardiol 8(4):647–670

    Article  CAS  Google Scholar 

  12. Aviram R, Cohen IJ, Kornreich L, Braslavski D, Meizner I (2005) Prenatal imaging of fetal hepatoblastoma. J Matern Fetal Neonatal Med 17(2):157–159

    Article  PubMed  Google Scholar 

  13. Malogolowkin MH, Katzenstein HM, Meyers RL, Krailo MD, Rowland JM, Haas J, Finegold MJ (2011) Complete surgical resection is curative for children with hepatoblastoma with pure fetal histology: a report from the Children’s Oncology Group. J Clin Oncol 29(24):3301–3306

    Article  PubMed  Google Scholar 

  14. Zagon IS, Donahue RN, McLaughlin PJ (2009) Opioid growth factor-opioid growth factor receptor axis is a physiological determinant of cell proliferation in diverse human cancers. Am J Physiol Regul Integr Comp Physiol 297(4):R1154–R1161

    Article  CAS  PubMed  Google Scholar 

  15. McLaughlin PJ, Levin RJ, Zagon IS (2003) Opioid growth factor (OGF) inhibits the progression of human squamous cell carcinoma of the head and neck transplanted into nude mice. Cancer Lett 199:209–217

    Article  CAS  PubMed  Google Scholar 

  16. Zagon IS, Kreiner S, Heslop JJ, Conway AB, Morgan CR, McLaughlin PJ (2008) Prevention and delay in progression of human pancreatic cancer by stable overexpression of the opioid growth factor receptor. Int J Oncol 33:317–323

    PubMed  Google Scholar 

  17. Zagon IS, Hytrek SD, Lang CM, Smith JP, McGarrity TJ, Wu Y, McLaughlin PJ (1996) Opioid growth factor ([Met5]-enkephalin) prevents the incidence and retards the growth of human colon cancer. Am J Physiol Regul Integr Comp Physiol 271:R780–R786

    CAS  Google Scholar 

  18. Cheng F, Zagon IS, Verderame MF, McLaughlin PJ (2007) The opioid growth factor (OGF)-OGF receptor axis uses the p16 pathway to inhibit head and neck cancer. Cancer Res 67:10511–10518

    Article  CAS  PubMed  Google Scholar 

  19. Zagon IS, McLaughlin PJ, Goodman SR, Rhodes RE (1987) Opioid receptors and endogenous opioids in diverse human and animal cancers. J Natl Cancer Inst 79:1059–1065

    CAS  PubMed  Google Scholar 

  20. Avella DM, Kimchi ET, Donahue RN, Tagaram HR, McLaughlin PJ, Zagon IS, Staveley-O'Carroll KF (2010) The opioid growth factor-opioid growth factor receptor axis regulates cell proliferation of human hepatocellular cancer. Am J Physiol Regul Integr Comp Physiol 298(2):R459–R466

    Article  CAS  PubMed  Google Scholar 

  21. McLaughlin PJ, Zagon IS, Skitzki J (1999) Human neuroblastoma cell growth in tissue culture is regulated by opioid growth factor. Int J Oncol 14(2):373–380

    CAS  PubMed  Google Scholar 

  22. Jaglowski JR, Zagon IS, Stack BC, Verderame MF, Leure-duPree AE, Manning JD, McLaughlin PJ (2005) Opioid growth factor enhances tumor growth inhibition and increases the survival of paclitaxel-treated mice with squamous cell carcinoma of the head and neck. Cancer Chemother Pharmacol 56:97–104

    Article  CAS  PubMed  Google Scholar 

  23. Zagon IS, Jaglowski JR, Verderame MF, Leure-duPree AE, Smith JP, McLaughlin PJ (2005) Combination chemotherapy with gemcitabine and biotherapy with opioid growth factor (OGF) enhances the growth inhibition of pancreatic adenocarcinoma. Cancer Chemother Pharmacol 56:510–520

    Article  CAS  PubMed  Google Scholar 

  24. Donahue RN, Zagon IS, McLaughlin PJ (2011) The opioid growth factor inhibits established ovarian cancer in nude mice and can be combined with taxol or cisplatin to enhance growth inhibition. J Cancer Ther 2:110–124

    Article  CAS  Google Scholar 

  25. Stambuk N et al (1997) Peptid-M (LUPEX) immunotherapy in multiple sclerosis, optic neuritis and uveitis. Int J Thymol 5(9):448–464

    CAS  Google Scholar 

  26. Wybran J, Plotnikoff NP (1991) Methionine-enkephalin, a new lymphokine for the treatment of ARC patients. In: Plotnikoff NJ, Murgo AJ, Faith R, Wybran J (eds) Stress and immunity. CRC Press, Boca Raton

    Google Scholar 

  27. Bihari B, Plotnikoff NP (1999) Methionine enkephalin in the treatment of AIDS-related complex. In: Plotnikoff NP, Murgo A, Faith RE, Good RA (eds) Cytokines stress & immunity. CRC Press, Boca Raton

    Google Scholar 

  28. Plotnikoff N, Wybran J (1989) Methionine-enkephalin shows promise in reducing HIV in blood. Am Fam Physician 40(3):234

    CAS  PubMed  Google Scholar 

  29. Plotnikoff NP, Miller GC, Nimeh N, Faith RE, Murgo AJ, Wybran J (1987) Enkephalins and T-cell enhancement in normal volunteers and cancer patients. Ann N Y Acad Sci 496:608–619

    Article  CAS  PubMed  Google Scholar 

  30. Wybran J, Schandene L, Van Vooren JP, Vandermoten G, Latinne D, Sonnet J, De Bruyere M, Taelman H, Plotnikoff NP (1987) Imunologic properties of methionine-enkephalin, and therapeutic implications in AIDS, ARC, and cancer. Ann N Y Acad Sci 496:108–114

    Article  CAS  PubMed  Google Scholar 

  31. Plotnikoff NP (1988) Opioids: immunomodulators. A proposed role in cancer and aging. Ann N Y Acad Sci 521:312–322

    Article  CAS  PubMed  Google Scholar 

  32. Blebea J, Mazo JE, Kihara TK, Vu JH, McLaughlin PJ, Atnip RG, Zagon IS (2000) Opioid growth factor modulates angiogenesis. J Vasc Surg 32:364–373

    Article  CAS  PubMed  Google Scholar 

  33. Blebea J, Vu JH, Assadnia S, McLaughlin PJ, Atnip RG, Zagon IS (2002) Differential effects of vascular growth factors on arterial and venous angiogenesis. J Vasc Surg 35:532–538

    Article  PubMed  Google Scholar 

  34. Smith JP, Bingaman SI, Mauger DT, Harvey HH, Demers LM, Zagon IS (2010) Opioid growth factor improves clinical benefit and survival in patients with advanced pancreatic cancer. Open Access J Clin Trials 2:37–48

    Google Scholar 

  35. Smith JP, Conter RL, Bingaman SI, Harvey HA, Mauger DT, Ahmad M, Demers LM, Stanley WB, McLaughlin PJ, Zagon IS (2004) Treatment of advanced pancreatic cancer with opioid growth factor: phase I. Anticancer Drugs 15(3):203–209

    Article  CAS  PubMed  Google Scholar 

  36. Donahue RN, McLaughlin PJ, Zagon IS (2011) Low-dose naltrexone suppresses ovarian cancer and exhibits enhanced inhibition in combination with cisplatin. Exp Biol Med (Maywood) 236(7):883–895

    Article  CAS  Google Scholar 

  37. Smith JP, Stock H, Bingaman S, Mauger D, Rogosnitzky M, Zagon IS (2007) Low-dose naltrexone therapy improves active Crohn’s disease. Am J Gastroenterol 102:820–828

    Article  CAS  PubMed  Google Scholar 

  38. Gironi M, Martinelli-Boneschi F, Sacerdote P, Solaro C, Zaffaroni M, Cavarretta R, Moiola L, Bucello S, Radaelli M, Pilato V, Rodegher M, Cursi M, Franchi S, Martinelli V, Nemni R, Comi G, Martino G (2008) A pilot trial of low dose naltrexone in primary progressive multiple sclerosis. Mult Scler 14:1076–1083

    Article  CAS  PubMed  Google Scholar 

  39. McLaughlin PJ, Zagon IS (1987) Modulation of human neuroblastoma transplanted into nude mice by endogenous opioid systems. Life Sci 41(12):1465–1472

    Article  CAS  PubMed  Google Scholar 

  40. Zagon IS, McLaughlin PJ (1989) Opioid antagonist modulation of murine neuroblastoma: a profile of cell proliferation and opioid peptides and receptors. Brain Res 480(1–2):16–28

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to thank Margaret McKernan, MD for assistance in manuscript preparation.

Conflicts of interest

I.S. Zagon and P.J. McLaughlin hold a patent on the use of OGF in gastrointestinal cancer treatment.

Ethical standards

All treatments described in the report complied with the current laws of Israel and the United States.

Author information

Authors and Affiliations

  1. MedInsight Research Institute, P.O. Box 386, Telz Stone, 90840, Israel

    Moshe Rogosnitzky

  2. Department of Pathology, Texas Children’s Cancer Center at Baylor College, Houston, TX, 77030, USA

    Milton J. Finegold

  3. Department of Neural & Behavioral Science, The Pennsylvania State University, College of Medicine, Hershey, PA, 17033, USA

    Patricia J. McLaughlin & Ian S. Zagon

Authors
  1. Moshe Rogosnitzky
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Milton J. Finegold
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Patricia J. McLaughlin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ian S. Zagon
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Moshe Rogosnitzky.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rogosnitzky, M., Finegold, M.J., McLaughlin, P.J. et al. Opioid growth factor (OGF) for hepatoblastoma: a novel non-toxic treatment. Invest New Drugs 31, 1066–1070 (2013). https://doi.org/10.1007/s10637-012-9918-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10637-012-9918-3

Keywords

Search

Navigation