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Therapeutic Efficacy of G207, a Conditionally Replicating Herpes Simplex Virus Type 1 Mutant, for Gallbladder Carcinoma in Immunocompetent Hamsters  Kenji.

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Presentation on theme: "Therapeutic Efficacy of G207, a Conditionally Replicating Herpes Simplex Virus Type 1 Mutant, for Gallbladder Carcinoma in Immunocompetent Hamsters  Kenji."— Presentation transcript:

1 Therapeutic Efficacy of G207, a Conditionally Replicating Herpes Simplex Virus Type 1 Mutant, for Gallbladder Carcinoma in Immunocompetent Hamsters  Kenji Nakano, Tomoki Todo, Kazuo Chijiiwa, Masao Tanaka  Molecular Therapy  Volume 3, Issue 4, Pages (April 2001) DOI: /mthe Copyright © 2001 American Society for Gene Therapy Terms and Conditions

2 FIG. 1 X-Gal staining of gallbladder cancer cells. In vitro expression of β-galactosidase (lacZ), a marker of G207 infection, was detected in approximately 40% of TGBC2TKB cells at 24 h after G207 administration at an m.o.i. of 0.25 (A) and in more than 90% of TGBC2TKB cells at an m.o.i. of 1.0 (B). X-Gal histochemistry of G207-inoculated subcutaneous KIGB-5 tumors at 2 days after intraneoplastic inoculation of G207 (1 × 107 pfu) revealed lacZ expression in tumor cells (C). No histochemical staining was detected in nonneoplastic cells. The section was counterstained with hematoxylin and eosin. Molecular Therapy 2001 3, DOI: ( /mthe ) Copyright © 2001 American Society for Gene Therapy Terms and Conditions

3 FIG. 2 Cytolytic efficacy of G207 on gallbladder cancer cells in vitro. Monolayer cultures of four human (GB-d15, HAG-1, TGBC1TKB, and TGBC2TKB) and a hamster (KIGB-5) gallbladder cancer cell line were inoculated with G207 at an m.o.i. of 0.25, 1.0, or 2.5. Viable cells at time points indicated were counted and expressed as percentages of uninfected controls. The results represent the means of triplicates ± SEM. Molecular Therapy 2001 3, DOI: ( /mthe ) Copyright © 2001 American Society for Gene Therapy Terms and Conditions

4 FIG. 3 The effect of intratumoral inoculation of G207 on the growth of subcutaneous KIGB-5 tumors in hamsters. (A) G207 (1 × 107 pfu) was inoculated into tumors (approximately 100 mm3) either once (Tx+ group) or three times with 4-day intervals (Tx group). While both G207 treatment groups showed a reduction in tumor growth compared with the control group (*P < 0.05, **P < 0.01), repeated G207 inoculations were significantly more efficacious than a single inoculation, resulting in significantly smaller tumor size (§P < 0.05, §§P < 0.01 vs the single G207-inoculated group). Data represent the mean tumor volumes ± SEM. (B) Kaplan–Meier survival curve. Repeated intratumoral inoculations of G207 (Tx+ + + group) significantly prolonged the survival of hamsters bearing KIGB-5 subcutaneous tumors compared with controls (No Tx group) (P < 0.05, log-rank test). Molecular Therapy 2001 3, DOI: ( /mthe ) Copyright © 2001 American Society for Gene Therapy Terms and Conditions

5 FIG. 4 The anti-tumor effect of G207 in immunocompetent hamsters and athymic mice bearing bilateral subcutaneous KIGB-5 tumors. (A) A single intratumoral inoculation of G207 (1 × 107 pfu) was given to the left tumor alone (approximately 10 mm3) in immunocompetent hamsters bearing bilateral tumors. G207 treatment (Tx+ group) inhibited the growth of not only the inoculated but also the uninoculated tumors compared with respective controls (No Tx group). (B) G207 (1 × 107 pfu) was inoculated into the left tumor alone (approximately 50 mm3) either once (Tx+ group) or three times with 4-day intervals (total 3 × 107 pfu; Tx+ + + group) in immunocompetent hamsters bearing bilateral tumors. Both single and repeated G207 treatment caused a significant growth inhibition of inoculated tumors as well as uninoculated tumors compared with respective controls. Repeated treatment was significantly more efficacious than a single inoculation in both inoculated and uninoculated tumors. (C) A single intratumoral inoculation of G207 (1 × 107 pfu) was given to the left tumor alone (approximately 10 mm3) in athymic mice bearing bilateral tumors. G207 treatment caused a temporary growth delay of the inoculated tumors. No anti-tumor effect was observed in the contralateral, uninoculated tumors. *P < 0.05, **P < 0.01 versus controls; §P< 0.05, §§P < 0.01 versus a single inoculation. Molecular Therapy 2001 3, DOI: ( /mthe ) Copyright © 2001 American Society for Gene Therapy Terms and Conditions


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