TY - JOUR
T1 - Transfer of the AQP1 cDNA for the correction of radiation-induced salivary hypofunction
AU - Baum, Bruce J.
AU - Zheng, Changyu
AU - Cotrim, Ana P.
AU - Goldsmith, Corinne M.
AU - Atkinson, Jane C.
AU - Brahim, Jaime S.
AU - Chiorini, John A.
AU - Voutetakis, Antonis
AU - Leakan, Rose Anne
AU - Van Waes, Carter
AU - Mitchell, James B.
AU - Delporte, Christine
AU - Wang, Songlin
AU - Kaminsky, Stephen M.
AU - Illei, Gabor G.
PY - 2006/8
Y1 - 2006/8
N2 - The treatment of most patients with head and neck cancer includes ionizing radiation (IR). Salivary glands in the IR field suffer significant and irreversible damage, leading to considerable morbidity. Previously, we reported that adenoviral (Ad)-mediated transfer of the human aquaporin-1 (hAQP1) cDNA to rat [C. Delporte, B.C. O'Connell, X. He, H.E. Lancaster, A.C. O'Connell, P. Agre, B.J. Baum, Increased fluid secretion after adenoviral-mediated transfer of the aquaporin-1 cDNA to irradiated rat salivary glands. Proc. Natl. Acad. Sci. U S A. 94 (1997) 3268-3273] and miniature pig [Z. Shan, J. Li, C. Zheng, X. Liu, Z. Fan, C. Zhang, C.M. Goldsmith, R.B. Wellner, B.J Baum, S. Wang. Increased fluid secretion after adenoviral-mediated transfer of the human aquaporin-1 cDNA to irradiated miniature pig parotid glands. Mol. Ther. 11 (2005) 444-451] salivary glands ∼16 weeks following IR resulted in a dose-dependent increase in salivary flow to ≥80% control levels on day 3. A control Ad vector was without any significant effect on salivary flow. Additionally, after administration of Ad vectors to salivary glands, no significant lasting effects were observed in multiple measured clinical chemistry and hematology values. Taken together, the findings show that localized delivery of AdhAQP1 to IR-damaged salivary glands is useful in transiently increasing salivary secretion in both small and large animal models, without significant general adverse events. Based on these results, we are developing a clinical trial to test if the hAQP1 cDNA transfer strategy will be clinically effective in restoring salivary flow in patients with IR-induced parotid hypofunction.
AB - The treatment of most patients with head and neck cancer includes ionizing radiation (IR). Salivary glands in the IR field suffer significant and irreversible damage, leading to considerable morbidity. Previously, we reported that adenoviral (Ad)-mediated transfer of the human aquaporin-1 (hAQP1) cDNA to rat [C. Delporte, B.C. O'Connell, X. He, H.E. Lancaster, A.C. O'Connell, P. Agre, B.J. Baum, Increased fluid secretion after adenoviral-mediated transfer of the aquaporin-1 cDNA to irradiated rat salivary glands. Proc. Natl. Acad. Sci. U S A. 94 (1997) 3268-3273] and miniature pig [Z. Shan, J. Li, C. Zheng, X. Liu, Z. Fan, C. Zhang, C.M. Goldsmith, R.B. Wellner, B.J Baum, S. Wang. Increased fluid secretion after adenoviral-mediated transfer of the human aquaporin-1 cDNA to irradiated miniature pig parotid glands. Mol. Ther. 11 (2005) 444-451] salivary glands ∼16 weeks following IR resulted in a dose-dependent increase in salivary flow to ≥80% control levels on day 3. A control Ad vector was without any significant effect on salivary flow. Additionally, after administration of Ad vectors to salivary glands, no significant lasting effects were observed in multiple measured clinical chemistry and hematology values. Taken together, the findings show that localized delivery of AdhAQP1 to IR-damaged salivary glands is useful in transiently increasing salivary secretion in both small and large animal models, without significant general adverse events. Based on these results, we are developing a clinical trial to test if the hAQP1 cDNA transfer strategy will be clinically effective in restoring salivary flow in patients with IR-induced parotid hypofunction.
KW - Adenoviral vector
KW - Animal model
KW - Aquaporin-1
KW - Clinical trial
KW - Gene therapy
KW - Radiation damage
KW - Salivary gland
UR - https://www.scopus.com/pages/publications/33748568793
U2 - 10.1016/j.bbamem.2005.11.006
DO - 10.1016/j.bbamem.2005.11.006
M3 - 文献综述
C2 - 16368071
AN - SCOPUS:33748568793
SN - 0005-2736
VL - 1758
SP - 1071
EP - 1077
JO - Biochimica et Biophysica Acta - Biomembranes
JF - Biochimica et Biophysica Acta - Biomembranes
IS - 8
ER -
