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Table 3 Results from experiments conducted in human DCIS xenografts

From: Effect of a farnesyl transferase inhibitor (R115777) on ductal carcinoma in situ of the breast in a human xenograft model and on breast and ovarian cancer cell growth in vitro and in vivo

Index

Day 0

Day 14

Day 21

Day 28

  

Control

R115777

Control

R115777

Control

R115777

Overall effect

   Ki67 (%)

27.1 (19.3–32.9)

9.4 (7.2–12.2)

10.3 (7.7–13.9)

13.2 (9.2–18.9)

7.5* (5.4–10.6)

11.8 (7.7–18.2)

8.4 (7.2–8.2)

   Apoptosis (%)

3.7 (3.5–4.2)

2.8 (1.5–5.2)

3.3 (2.1–5.1)

2.7 (1.8–4.1)

3.2 (2.0–5.4)

2.5 (1.5–3.9)

3.8** (2.7–5.2)

   CTI

6.2 (5.2–9.1)

2.8 (1.5–5.1)

3.5 (2.0–6.3)

6.2 (3.8–10.3)

2.6** (1.4–5.0)

3.9 (2.6–6.1)

2.4 (1.8–3.1)

R115777 100 mg/kg

   Ki67 (%)

27.1 (19.3–32.9)

8.4 (5.8–12.3)

8.7 (6.1–12.3)

12.8 (7.6–21.5)

6.2*** (4.5–8.7)

12.1 (6.5–22.4)

8.7 (7.2–10.5)

   Apoptosis (%)

3.7 (3.5–4.2)

3.3 (1.2–9.1)

3.7 (1.8–7.5)

3.0 (1.8–5.2)

3.9 (2.1–7.4)

2.9 (1.4–6.0)

4.1 (2.5–6.7)

   CTI

6.2 (5.2–9.1)

1.8 (1.2–2.7)

2.5 (1.8–3.6)

4.8 (3.8–6.0)

1.9*** (1.4–2.5)

3.2 (2.5–4.1)

2.3 (1.5–3.6)

R115777 50 mg/kg

   Ki67 (%)

27.1 (19.3–32.9)

11.8 (7.0–19.7)

13.9 (10.1–18.9)

14.0 (4.3–45.6)

11.1 (7.2–17.1)

11.1 (3.3–37.3)

7.9 (5.2–12.1)

   Apoptosis (%)

3.7 (3.5–4.2)

2.1 (0.8–5.9)

2.6 (1.1–6.1)

2.3 (0.8–6.7)

2.3 (0.6–8.8)

1.9 (0.8–4.3)

3.2* (1.5–6.8)

   CTI

6.2 (5.2–9.1)

5.9 (3.1–11.2)

6.1 (2.2–16.7)

9.2 (3.7–23.1)

6.2 (2.1–18.5)

6.3 (2.2–18.6)

2.4 (1.4–4.1)

  1. The overall effect of the farnesyl transferase inhibitor R115777 on proliferation and apoptosis of ducatal carcinoma in situ (DCIS) of the breast. Xenografts were implanted into athymic mice on day 0 and left untreated for 14 days. Xenografts were removed on day 14, day 21, and day 28. The mice were gavaged twice daily with either R115777 or control vehicle starting on day 14 after removal of the first pair of xenografts. Proliferation was measured by immunohistochemistry (Ki67) and apoptosis by morphology on haematoxylin and eosin stained slides. Data shown represent the overall effect of R115777 and for both doses separately. Data only include mice for which data were available from day 14 and day 21 or day 28. Data are expressed as geometric means with 95% confidence intervals. Statistical significance was tested for the change between day 14 and day 21 and between day 14 and day 28. *P < 0.05, **P < 0.01, ***P = 0.001. CTI, cell turnover index.