Download presentation
Presentation is loading. Please wait.
1
Volume 3, Issue 4, Pages 536-542 (April 2001)
Enhanced Therapeutic Effect of HSV-tk+GCV Gene Therapy and Ionizing Radiation for Prostate Cancer Madhu Chhikara, Hanxian Huang, Maria T. Vlachaki, Xiaohong Zhu, Bin Teh, Kam J. Chiu, Shiao Woo, Barry Berner, E.O'Brian Smith, Kerby C. Oberg, Laura K. Aguilar, Timothy C. Thompson, E.Brian Butler, Estuardo Aguilar-Cordova Molecular Therapy Volume 3, Issue 4, Pages (April 2001) DOI: /mthe Copyright © 2001 American Society for Gene Therapy Terms and Conditions
2
FIG. 1 Single-therapy dose escalation analyses. Subcutaneous RM-1 tumors of 50–60 mm3 were used to determine effective but noncurative single-therapy doses to be used in the combination-therapy studies. (A) Vector doses were analyzed by single AdV-tk intratumoral injections at doses ranging from 1 × 109 to 1 × 1011 vp per tumor in half-log increments followed by 6 days of GCV at 20 mg/kg bid. (B) Radiation doses were analyzed by single-fraction delivery of 5, 10, and 15 Gy as described in text. Molecular Therapy 2001 3, DOI: ( /mthe ) Copyright © 2001 American Society for Gene Therapy Terms and Conditions
3
FIG. 2 Combination-therapy effects on tumor growth and animal survival. Tumorsthat received adenoviral vectorswere injected with 3 × 1010 AdV-tk or AdV-β-gal vp. Irradiated tumors received a single dose of 5 Gy. (A) Relative tumor growth after treatment. (B) Survival of animals in each treatment group. Molecular Therapy 2001 3, DOI: ( /mthe ) Copyright © 2001 American Society for Gene Therapy Terms and Conditions
4
FIG. 3 Histology of treated primary tumors showing ischemic necrosis and lymphocytic infiltrates. (A) Focal ischemic necrosis (outlined by arrows) was present in all tumors (tumor from XRT group, original magnification 10×). (B) Occasionally focal ischemic necrosis was extensive leaving only a rind of tumor surrounding vessels present (*vessel lumen, tumor from AdV-tk group, original magnification 10×). (C and D) From the AdV-tk+GCV combined with XRT group. (C) A band of infiltrating lymphocytes at the tumor perimeter (arrows). The lymphocytes have small condensed nuclei and a scant rim of cytoplasm in contrast to tumor cells with the large granular nuclei and abundant eosinophilic cytoplasm. Smooth muscle fibers are present on the left, demarcating the boundary of tumor invasion (larger cells to the right and upper right). (D) Deep within the tumor, lymphocytes percolate through the tumor, focally forming clusters (arrow). Molecular Therapy 2001 3, DOI: ( /mthe ) Copyright © 2001 American Society for Gene Therapy Terms and Conditions
5
FIG. 4 Quantitation of CD4 and CD8 T lymphocyte infiltration in tumors from different treatment groups. Immunohistochemistry was performed on tissue sections and number of positive cells per mm2 of tumor tissue determined by counting under the microscope. Molecular Therapy 2001 3, DOI: ( /mthe ) Copyright © 2001 American Society for Gene Therapy Terms and Conditions
6
FIG. 5 Systemic effect on lung metastases of combination therapy delivered to the primary tumor. (A) Number of visible lung nodules 12 days after primary tumors were treated with single or combination therapy. (B) Two representative examples each of lungs from treated and control animals. Molecular Therapy 2001 3, DOI: ( /mthe ) Copyright © 2001 American Society for Gene Therapy Terms and Conditions
Similar presentations
© 2025 SlidePlayer.com. Inc.
All rights reserved.