Volume 3, Issue 4, Pages (April 2001)

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Volume 3, Issue 4, Pages 500-506 (April 2001) In Vivo Surgical Resection Plus Adjuvant Gene Therapy in the Treatment of Mammary and Prostate Cancer Steven W. Sukin, Madhu Chhikara, Xiaohong Zhu, Gustavo Ayala, Laura K. Aguilar, E. O'Brian Smith, Brian J. Miles, Timothy C. Thompson, Dov Kadmon, Estuardo Aguilar-Cordova Molecular Therapy Volume 3, Issue 4, Pages 500-506 (April 2001) DOI: 10.1006/mthe.2001.0285 Copyright © 2001 American Society for Gene Therapy Terms and Conditions

FIG. 1 Effect of combination therapy in female BALB/C mice with TM40-D mammary tumors following surgical resection of subcutaneous tumors and irrigation of the wounds with PBS or Ad-tk (3 × 1010 vp/100 μl). (A) Kaplan-Meier recurrence curve (P = 0.0005) and (B) survival curve (P = 0.0001) over time. (Solid line) Controls, (dashed line) Ad-tk-treated group. Molecular Therapy 2001 3, 500-506DOI: (10.1006/mthe.2001.0285) Copyright © 2001 American Society for Gene Therapy Terms and Conditions

FIG. 2 Effect of combination therapy in male C57BL/6 mice with RM-9 prostate tumors: (A) Kaplan–Meier recurrence curve (P = 0.1031) and (B) survival curve (P = 0.1628) over time. (Solid line) Controls, (dashed line) Ad-tk-treated group. Molecular Therapy 2001 3, 500-506DOI: (10.1006/mthe.2001.0285) Copyright © 2001 American Society for Gene Therapy Terms and Conditions

FIG. 3 (A) Photographs of six representative lung samples from mice treated with surgery plus adjuvant therapy using either Ad-tk (left) or saline (right), demonstrating the systemic effect of combined treatment in a metastatic model. (B) At sacrifice, lungs were removed from animals and the numbers of lung nodules counted. The mean number of lung nodules in the group treated with gene therapy was 3.5 (range 0–18); the mean number in the control group was 17 (range 9–31). Each data point represents the number of lung nodules from each animal, and the bars represent the mean of each treatment group. Molecular Therapy 2001 3, 500-506DOI: (10.1006/mthe.2001.0285) Copyright © 2001 American Society for Gene Therapy Terms and Conditions

FIG. 4 Histologic analysis of treatment sites following combination therapy. Animals were euthanized 4 days following surgical resection of sc tumors with placement of either PBS or Ad-tk into the wounds. Specimens were fixed in formalin, sectioned, and stained with hematoxylin and eosin. (A) Slides from a control mouse show grade 3 tumor (see arrow); (B) higher power of same specimen; (C) high magnification reveals multiple mitotic figures (see arrows). (D) A slide from a mouse treated with Ad-tk shows minimal tumor at surgical resection site on low power (arrow points to site of surgical resection). (E) Another specimen from the treatment group reveals grade 3 tumor but (F) no mitotic figures seen at higher magnification. Molecular Therapy 2001 3, 500-506DOI: (10.1006/mthe.2001.0285) Copyright © 2001 American Society for Gene Therapy Terms and Conditions