Department of Clinical Sciences, Animal Cancer Center, Colorado State University, Fort Collins, CO 80523, USA.
J Vet Intern Med. 2011 Jul-Aug;25(4):920-6. doi: 10.1111/j.1939-1676.2011.0753.x. Epub 2011 Jul 7.
Low-dose, continuous (metronomic) chemotherapy improves tumor control by inhibiting tumor angiogenesis and suppressing regulatory T cells (Treg) in mice and humans. The effects of metronomic chemotherapy on Treg and tumor angiogenesis in dogs has not been investigated previously.
To determine whether metronomic cyclophosphamide (CYC) therapy decreases Treg or exhibits antiangiogenic activity or both in dogs with soft tissue sarcoma (STS). We hypothesized that Treg numbers would be increased in dogs with STS and that continuous dosing of CYC would decrease Treg in a dose-dependent manner, as well as exhibit antiangiogenic activity.
Eleven client-owned dogs with grade I or II STS. Twenty-one healthy dogs were used as controls.
Prospective, open, clinical trial. Dogs with STS were enrolled in 2 dose cohorts and administered CYC at 12.5 or 15 mg/m(2) p.o. once daily for 28 days. Whole blood and tumor biopsy specimens were obtained on days 0, 14, and 28 to assess changes in T lymphocyte subsets by flow cytometry and tumor microvessel density (MVD), respectively.
Administration of CYC at 12.5 mg/m(2)/d significantly decreased the number of Treg from days 0 to 28, but there was no change in the percentage of Treg or tumor MVD. In dogs that received CYC at 15.0 mg/m(2)/d, both the number and percent of Treg as well as tumor MVD were significantly decreased over 28 days.
CYC administered at 15 mg/m(2)/d should be used in further studies examining the antitumor properties of low-dose CYC in dogs.
低剂量、连续（节拍）化疗通过抑制肿瘤血管生成和抑制调节性 T 细胞（Treg）在小鼠和人类中改善肿瘤控制。节拍化疗对犬的 Treg 和肿瘤血管生成的影响以前尚未研究过。
确定节拍环磷酰胺（CYC）治疗是否会减少软组织肉瘤（STS）犬的 Treg 或表现出抗血管生成活性或两者兼有。我们假设 STS 犬的 Treg 数量会增加，并且 CYC 的连续给药会以剂量依赖性方式减少 Treg，并且表现出抗血管生成活性。
11 只患有 I 级或 II 级 STS 的患犬。21 只健康犬作为对照。
前瞻性、开放性、临床试验。患有 STS 的犬被纳入 2 个剂量组，并以 12.5 或 15 mg/m2 口服每天一次给药 28 天。在第 0、14 和 28 天采集全血和肿瘤活检标本，通过流式细胞术评估 T 淋巴细胞亚群的变化，通过肿瘤微血管密度（MVD）评估肿瘤 MVD 的变化。
以 12.5 mg/m2/d 给予 CYC 可显著降低 Treg 的数量，从第 0 天到第 28 天，但 Treg 的百分比或肿瘤 MVD 没有变化。在接受 CYC 15.0 mg/m2/d 的犬中，Treg 的数量和百分比以及肿瘤 MVD 在 28 天内均显著降低。
在进一步研究低剂量 CYC 在犬中的抗肿瘤特性时，应使用 15 mg/m2/d 的 CYC 进行治疗。
