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Nitrosylcobalamin acts as "Trojan horse" to target cancer cells
Karla Gale
Last Updated: 2009-03-25 10:10:28 -0400 (Reuters Health)
NEW YORK (Reuters Health) - Nitric oxide attached to a vitamin B12 analog is a promising cytotoxic agent that targets tumor cells overexpressing B12 receptors, researchers report.
Long-term treatment with this chemotherapeutic agent -- nitrosylcobalamin (NO-Cbl) -- has so far resulted in up to 77% tumor volume reduction in three dogs that had spontaneous carcinoma, with no signs of toxicity, according to a presentation at this week's national meeting of the American Chemical Society in Salt Lake City.
"We call NO-Cbl a 'Trojan horse' because cancer cells require abnormally high levels of vitamin B12 to divide and proliferate," and thus have B-12 receptor density many times higher than normal cells, presenter Dr. Joseph A Bauer told Reuters Health. "Cancer cells cannot distinguish NO-Cbl from regular B12, so NO-Cbl is readily ingested by the cancer cells and the nitric oxide is released and kills the cell from within by causing apoptosis."
The treated tumors in the dogs were a thyroid carcinoma, a malignant peripheral nerve sheath tumor, and an anal sac adenocarcinoma. After twice-daily injections of NO-Cbl 28 mg/kg for up to 15 months, tumor regression ranged from 43% to 77%, and an iliac lymph node metastasis was reduced by 90%.
One of the original three dogs has now been off treatment and cancer-free for 2 years.
"Most cancers that respond well are adenocarcinomas," noted Dr. Bauer, director of scientific research at the Bauer Research Foundation in Port St. Lucie, Florida. "The most sensitive to NO-Cbl are leukemias and cancers of the breast, ovary, colon, and the CNS."
In meeting materials, the researchers note that "NO-Cbl sensitizes multidrug-resistant cancer cells to the antitumor effects of several different drugs, so it may be valuable when utilized in combination regimens."
Dr. Bauer and his associates plan to monitor the 10 dogs they currently have on study for one year. "At that time, we will compile the data and submit it to the FDA to file an IND (investigational new drug) application to initiate a human clinical trial," he added.
Nitrosylcobalamin acts as "Trojan horse" to target cancer cells
Karla Gale
Last Updated: 2009-03-25 10:10:28 -0400 (Reuters Health)
NEW YORK (Reuters Health) - Nitric oxide attached to a vitamin B12 analog is a promising cytotoxic agent that targets tumor cells overexpressing B12 receptors, researchers report.
Long-term treatment with this chemotherapeutic agent -- nitrosylcobalamin (NO-Cbl) -- has so far resulted in up to 77% tumor volume reduction in three dogs that had spontaneous carcinoma, with no signs of toxicity, according to a presentation at this week's national meeting of the American Chemical Society in Salt Lake City.
"We call NO-Cbl a 'Trojan horse' because cancer cells require abnormally high levels of vitamin B12 to divide and proliferate," and thus have B-12 receptor density many times higher than normal cells, presenter Dr. Joseph A Bauer told Reuters Health. "Cancer cells cannot distinguish NO-Cbl from regular B12, so NO-Cbl is readily ingested by the cancer cells and the nitric oxide is released and kills the cell from within by causing apoptosis."
The treated tumors in the dogs were a thyroid carcinoma, a malignant peripheral nerve sheath tumor, and an anal sac adenocarcinoma. After twice-daily injections of NO-Cbl 28 mg/kg for up to 15 months, tumor regression ranged from 43% to 77%, and an iliac lymph node metastasis was reduced by 90%.
One of the original three dogs has now been off treatment and cancer-free for 2 years.
"Most cancers that respond well are adenocarcinomas," noted Dr. Bauer, director of scientific research at the Bauer Research Foundation in Port St. Lucie, Florida. "The most sensitive to NO-Cbl are leukemias and cancers of the breast, ovary, colon, and the CNS."
In meeting materials, the researchers note that "NO-Cbl sensitizes multidrug-resistant cancer cells to the antitumor effects of several different drugs, so it may be valuable when utilized in combination regimens."
Dr. Bauer and his associates plan to monitor the 10 dogs they currently have on study for one year. "At that time, we will compile the data and submit it to the FDA to file an IND (investigational new drug) application to initiate a human clinical trial," he added.
Nitrosylcobalamin充当“特洛伊木马”的目标癌细胞
卡拉烈风
最后更新：2009年3月25日10时10分28秒-0400（路透社）
纽约（路透社） - 一氧化氮附着在维生素B12的模拟是一种很有前途的代理目标细胞肿瘤细胞过度表达B12的受体,研究人员的报告.
长期与此化疗药物治疗 - nitrosylcobalamin（无边界层） - 至今在多达77％,导致肿瘤的三只狗的自发表达了与毒性的迹象,量减少,据介绍在这本周的全国会议的美国化学协会在盐湖城.
“我们称之为无边界层一'特洛伊木马',因为癌细胞需要异常高的维生素B12水平的分裂和增殖”,从而有B - 12受体密度比正常细胞高出许多倍,主持人李约瑟博士阿鲍尔告诉路透社健康.“癌症细胞不能区分无边界层经常维生素B12,所以没有很容易摄取边界层的癌细胞和一氧化氮的释放,从内杀死导致细胞凋亡的细胞.”
在狗的肿瘤治疗甲状腺癌,恶性神经鞘瘤,及肛门囊腺癌.之后,每天两次注射的NO -边界层28毫克/长达15个月,肿瘤缩小介乎43％至77％,和髂淋巴结转移是由90％降低公斤.
原来的三只狗之一,现已关闭和癌症治疗无2年.
“大多数癌症的反应良好的腺癌,博士指出：”鲍尔,科研主任鲍尔研究基金会在圣露西港,佛罗里达州.“最敏感的无边界层是白血病和乳腺癌,卵巢癌,结肠癌和中枢神经系统.”
在会议材料,研究人员指出,“无边界层敏感性的多药耐药性癌细胞中的几个不同药物的抗肿瘤作用,因此它可能是有价值的治疗方案时,结合使用.”
Bauer博士和他的同事计划监察10只狗,他们目前的研究已经一年.“当时,我们将汇编的数据,并提交给FDA的文件一实业（研究性新药）的申请发起的人体临床试验,”他补充说.
卡拉烈风
最后更新：2009年3月25日10时10分28秒-0400（路透社）
纽约（路透社） - 一氧化氮附着在维生素B12的模拟是一种很有前途的代理目标细胞肿瘤细胞过度表达B12的受体,研究人员的报告.
长期与此化疗药物治疗 - nitrosylcobalamin（无边界层） - 至今在多达77％,导致肿瘤的三只狗的自发表达了与毒性的迹象,量减少,据介绍在这本周的全国会议的美国化学协会在盐湖城.
“我们称之为无边界层一'特洛伊木马',因为癌细胞需要异常高的维生素B12水平的分裂和增殖”,从而有B - 12受体密度比正常细胞高出许多倍,主持人李约瑟博士阿鲍尔告诉路透社健康.“癌症细胞不能区分无边界层经常维生素B12,所以没有很容易摄取边界层的癌细胞和一氧化氮的释放,从内杀死导致细胞凋亡的细胞.”
在狗的肿瘤治疗甲状腺癌,恶性神经鞘瘤,及肛门囊腺癌.之后,每天两次注射的NO -边界层28毫克/长达15个月,肿瘤缩小介乎43％至77％,和髂淋巴结转移是由90％降低公斤.
原来的三只狗之一,现已关闭和癌症治疗无2年.
“大多数癌症的反应良好的腺癌,博士指出：”鲍尔,科研主任鲍尔研究基金会在圣露西港,佛罗里达州.“最敏感的无边界层是白血病和乳腺癌,卵巢癌,结肠癌和中枢神经系统.”
在会议材料,研究人员指出,“无边界层敏感性的多药耐药性癌细胞中的几个不同药物的抗肿瘤作用,因此它可能是有价值的治疗方案时,结合使用.”
Bauer博士和他的同事计划监察10只狗,他们目前的研究已经一年.“当时,我们将汇编的数据,并提交给FDA的文件一实业（研究性新药）的申请发起的人体临床试验,”他补充说.