Dai Chung, MD, Pritha Paul, PhD candidate, Sora Lee, PhD, Carmelle Romain, MD, Natasha Volny, Kwang Kim, PhD and Jingbo Qiao, PhD
Gastrin-releasing peptide (GRP), the mammalian equivalent of bombesin (BBS), is a gut/neuropeptide that stimulates the growth of a number of normal and neoplastic tissues through an autocrine, paracrine or endocrine mechanisms, including normal gastrointestinal tract mucosa as well as various neoplastic tissues such as pancreatic cancer, colon cancer and small cell lung cancer. We have previously shown that GRPR expression was increased in undifferentiated neuroblastomas, and GRP, acting through GRPR, triggers cell division in an autocrine/paracrine manner. In addition, we have identified the phosphatidylinositol 3-kinase (PI3K) pathway as an emergent critical signaling mechanism of GRPR-mediated neuroblastoma growth.
The major focus of our laboratory is to determine GRP/GRPR as an important novel therapeutic target in the treatment of neuroblastoma. Our published studies have shown important roles for the GRP-mediated PI3K/Akt pathway in the process of neuroblastoma growth and metastasis. The ongoing studies are logical extensions of previous findings and are designed to discern molecular mechanisms and signaling events regulating the process of GRP-induced neuroblastoma progression. We will also identify a novel importance of determining GRPR expression in clinically significant ‘high-risk' patients, as defined by the COG criteria, for designing clinical treatment protocols. Finally, our studies will enhance the knowledge of hormone-responsive cancer pathogenesis and help clarify the complex signaling pathways involved.
To date, there have been several pre-clinical new investigational drug trials using GRPR antagonists for a few select adult cancers. Therefore, our promising data could allow us to introduce a pre-clinical trial to target GRPR in ‘high-risk' patients with metastatic, refractory neuroblastomas and potentially lead to the development of novel therapy as adjuvant treatment for this devastating disease with high mortality rate in infants and children.
Surgical management of complications of burn injury. Colon N, Schlegel C, Chung DH. In Herndon (Ed). Total Burn Care, 4th edition, Elsevier, Philadelphia, pp. 421-431, 2012
Congenital lung anomalies: Can we postpone resection? Colon N, Schlegel C, Pietsch J, Chung DH, Jackson GP. J Pediatr Surg 2012 Jan;47(1):87-92.Effects of oxidative stress on intestinal type 1 insulin-like growth factor receptor expression. Baregamian N, Song J, Chung DH. Eur J Pediatr Surg 2012 Feb;22(1):97-104.
PI3K/AKT and ERK regulate retinoic acid-induced neuroblastoma cellular differentiation. Qiao J, Paul P, Lee S, Qiao L, Josifi E, Tiao JR, Chung, DH. Biochem Biophys Res Commun 2012 Aug 3;424(3):421-426.Protein kinase C mediates bombesin-induced rapid VEGF secretion in neuroblastoma cells. Schlegel C, Paul P, Lee S, Kim K, Colon N, Qiao J, Chung DH. Anticancer Res. 2012 Nov;32(11):4691-6.
Focal adhesion kinase is a critical regulator of neuroblastoma liver metastasis. Lee S, Qiao J, Paul P, O’Connor KL, Evers BM, Chung DH Oncotarget. 2012 Nov 16. Epub ahead of print.Pediatric Surgery. Chung DH. In Townsend, Beauchamp, Evers, Mattox, Textbook of Surgery, 19th edition, Elsevier, Philadelphia 2012.
Care of the Child with Burns. Nursing Care of the Critically Ill Child, 3rd edition. Pietsch J, Chung DH. In Hazinski (Ed), Elsevier, Philadelphia 2012.