Bauer Research Foundation, Akron Innovation Campus, 411 Wolf Ledges Pkwy, Akron, OH 44311, USA.
Invest New Drugs. 2010 Oct;28(5):694-702. doi: 10.1007/s10637-009-9282-0. Epub 2009 Jun 27.
Given the limited options available to treat canine cancers, the use of companion animals for evaluating new drugs may identify better therapies for veterinary and human oncology. The anti-tumor effects of nitrosylcobalamin (NO-Cbl), an apoptosis-inducing, vitamin B12-based carrier of nitric oxide (NO), was evaluated in four dogs with spontaneous cancer.
(1) A 13 year-old female spayed Giant Schnauzer with inoperable thyroid carcinoma and hypercalcemia. (2) A 6 year-old male neutered Golden Retriever with a malignant peripheral nerve sheath tumor (MPNST). (3) A ten yr-old neutered male Bichon Frise with apocrine gland anal sac adenocarcinoma (AGACA). (4) A 7 year-old female spayed Labrador mix with spinal meningioma following partial surgical resection. Tumor regression was measured by physical exam and verified using ultrasound (case 1) and MRI (case 2-4). Serum chemistries and hematologic parameters were monitored throughout the studies.
(1) The Giant Schnauzer demonstrated a 77% reduction in tumor volume after ten weeks of daily NO-Cbl treatment. (2) The Golden Retriever demonstrated a 53% reduction in tumor volume after 15 months of daily NO-Cbl therapy. (3) The Bichon Frise demonstrated a 43% regression of the primary tumor and a 90% regression of an iliac lymph node measured by MRI after 15 months of treatment. After 61 months, the dog currently has stable disease, normal liver enzymes, CBC analysis, and no evidence of toxicity. (4) The Labrador demonstrated complete regression of the residual tumor after 6 months of treatment.
We have shown previously that NO-Cbl is endocytosed by malignant cells, resulting in intra-tumoral NO release. In this study, we have shown that daily long-term use of NO-Cbl induced responses in all dogs without any signs of toxicity. The use of NO-Cbl capitalizes on the tumor-specific properties of the vitamin B12 receptor and represents a promising anti-cancer therapy.
鉴于治疗犬类癌症的方法有限，利用伴侣动物来评估新药可能会为兽医和人类肿瘤学找到更好的治疗方法。本研究评估了亚硝酰钴胺素（NO-Cbl）对四种患有自发性癌症犬的抗肿瘤作用。NO-Cbl 是一种诱导细胞凋亡的、基于维生素 B12 的一氧化氮（NO）载体。
（1）一只 13 岁的雌性去势巨型雪纳瑞，患有无法手术的甲状腺癌和高钙血症。（2）一只 6 岁的雄性去势金毛猎犬，患有恶性外周神经鞘肿瘤（MPNST）。（3）一只 10 岁的雄性去势比熊犬，患有大汗腺肛门囊腺癌（AGACA）。（4）一只 7 岁的雌性已去势拉布拉多犬，在接受部分手术切除后患有脊柱脑膜瘤。通过体格检查和超声（病例 1）和 MRI（病例 2-4）测量肿瘤消退情况。在整个研究过程中监测血清化学和血液学参数。
（1）巨型雪纳瑞在接受 10 周的每日 NO-Cbl 治疗后，肿瘤体积减少了 77%。（2）金毛猎犬在接受 15 个月的每日 NO-Cbl 治疗后，肿瘤体积减少了 53%。（3）比熊犬在接受 15 个月的治疗后，通过 MRI 测量，原发肿瘤缩小了 43%，髂淋巴结缩小了 90%。61 个月后，该犬目前疾病稳定，肝酶正常，CBC 分析正常，无毒性迹象。（4）拉布拉多犬在接受 6 个月的治疗后，残留肿瘤完全消退。
我们之前已经表明，NO-Cbl 被恶性细胞内吞，导致肿瘤内 NO 的释放。在这项研究中，我们表明，长期每天使用 NO-Cbl 诱导所有犬的反应，而没有任何毒性迹象。NO-Cbl 的使用利用了维生素 B12 受体的肿瘤特异性特性，代表了一种有前途的抗癌疗法。
