大麻提取物可阻断脑瘤生长
http://www.100md.com
2004年8月18日
生物谷报道 日前西班牙科学家的一项新研究结果表明，一种大麻提取物有望使脑瘤和其他类型的肿瘤缩小。
在以前的研究中，科学家已经通过在老鼠身上的实验证明，大麻中含有的一种活性物质可以对脑瘤有所改善。这一次西班牙Complutense大学的科学家准确地演示了这一生化过程，大麻提取物是通过阻断肿瘤血管生成所需的一种关键化学物质来实现疗效的。而且该研究小组首次通过人体实验证明，在患有最具威胁性的脑瘤——多形性成胶质细胞瘤的病人身上，大麻提取物阻止了该化学物质的形成。虽然目前此项研究还只是处于初级阶段，但是研究者认为这是一个好的开始：“大麻提取物阻止了血管生成，而一个肿瘤如果不能实现血管生成，它就不会再生长。要是我们一方面阻止其血管生成，另一方面想办法杀死肿瘤细胞，我们就能找到治疗癌症的一种新方法。”
该研究小组在30只老鼠身上测试了delta-9-四氢大麻醇的效果。他们发现这种大麻提取物抑制了好几种基因的表达，而这几种基因与一种名为脉管内皮生长因子(VEGF)的化学物的生成有关，VEGF对于血管生成来说非常关键。大麻提取物显著降低了老鼠体内VEGF的活性，在两个人类脑瘤患者身上也显示了同样的效果。西班牙学者的研究表明，这种药是通过提高一种名为神经酰胺的脂肪分子的活性来实现这一效果的。研究者说：“我们发现老鼠脑部的肿瘤变小了，还有一点苍白。”肿瘤的苍白表明其血供应缺乏，该药物在人类患者身上也有同样效果，不过“效果还是很初步的”。
, 百拇医药
英国研究肿瘤的医学专家Richard Sullivan认为，这一研究为以肿瘤血供应为攻击目标的抗癌药物提供了一种重要的新的前驱化合物。他强调，因为目前其他科学家已经在研制一些VEGF抑制剂，对于大麻提取物就应该进行更详细深入的研究。
相关研究成果刊登在8月115日的《肿瘤研究》杂志上。
ORIGINAL TEXT：
Marijuana ingredient inhibits VEGF pathway required for brain tumor blood vessels
Cannabinoids, the active ingredients in marijuana, restrict the sprouting of blood vessels to brain tumors by inhibiting the expression of genes needed for the production of vascular endothelial growth factor (VEGF).
, 百拇医药
According to a new study published in the August 15, 2004 issue of the journal Cancer Research, administration of cannabinoids significantly lowered VEGF activity in laboratory mice and two patients with late-stage glioblastoma.
"Blockade of the VEGF pathway constitutes one of the most promising antitumoral approaches currently available," said Manuel Guzmᮬ professor of biochemistry and molecular biology, with the Complutense University in Madrid, Spain, and the study's principal investigator.
, 百拇医药
"The present findings provide a novel pharmacological target for cannabinoid-based therapies."
Glioblastoma multiforme, the most aggressive form of glioma, strikes more than 7,000 Americans each year and is considered one of the most malignant and deadliest forms of cancer, generally resulting in death within one to two years following diagnosis.
The disease is usually treated with surgery, followed by conventional radiation alone or in combination with chemotherapy. However, the main tumor often evades total destruction, surviving and growing again, eventually killing the patient. For this reason, researchers are actively seeking other therapeutic strategies, some of which might be considered novel.
, 百拇医药
In this study, the investigators chose to work with cannabinoids which, in previous studies, have been shown to inhibit the growth of blood vessels, or angiogenesis, in laboratory mice. However, little was known about the specific mechanisms by which cannabinoids impair angiogenesis, or whether the chemical might do the same in human tumors.
To answer the first part of the question, the scientists induced gliomas in mice, which were subsequently inoculated with cannabinoids. Using DNA array analysis, the team examined 267 genes associated with the growth of blood vessels in tumors and found that cannabinoids lowered the expression of several genes related to the VEGF pathway, critical for angiogenesis.
, 百拇医药
The researchers also discovered that cannabinoids apparently worked by increasing the activity of ceramide, a lipid mediator of apoptosis, resulting in the functional inhibition of cells needed for VEGF production. The ability of cannabinoids to alter VEGF production was significantly stifled following the introduction of a ceramide inhibitor.
"As far as we know, this is the first report showing that ceramide depresses VEGF pathway by interfering with VEGF production," according to Guzmᮮ
, 百拇医药
To answer the second part of the question relating to clinical tests, the scientists obtained tumor biopsies from two patients with glioblastomas who had failed standard therapy, including surgery, radiotherapy and chemotherapy. The biopsied tissue was analyzed before and after local injection of a cannabinoid.
"In both patients, VEGF levels in tumor extracts were lower after cannabinoid inoculation," said Guzmᮮ
The results, he added, suggest a potential new approach toward the treatment of these otherwise intractable brain tumors.
, 百拇医药
"It is essential to develop new therapeutic strategies for the management of glioblastoma multiforme," the scientists wrote, "which will most likely require a combination of therapies to obtain significant clinical results."
Also participating in the study were Cristina Blằuez and Amador Haro, from Complutense University; Luis Gonzᬥz-Feria, from University Hospital, Tenerife, Spain; Luis ?varez, from La Paz University Hospital in Madrid; and M. Llanos Casanova, from the Project on Cellular and Molecular Biology and Gene Therapy, CIEMAT, also in Madrid.
, http://www.100md.com
###
Founded in 1907, the American Association for Cancer Research is a professional society of more than 22,000 laboratory, translational, and clinical scientists engaged in all areas of cancer research in the United States and in more than 60 countries. AACR's mission is to accelerate the prevention and cure of cancer through research, education, communication, and advocacy. Its principal activities include the publication of five major peer-reviewed scientific journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. AACR's Annual Meetings attract more than 15,000 participants who share new and significant discoveries in the cancer field. Specialty meetings, held throughout the year, focus on the latest developments in all areas of cancer research., 百拇医药
在以前的研究中，科学家已经通过在老鼠身上的实验证明，大麻中含有的一种活性物质可以对脑瘤有所改善。这一次西班牙Complutense大学的科学家准确地演示了这一生化过程，大麻提取物是通过阻断肿瘤血管生成所需的一种关键化学物质来实现疗效的。而且该研究小组首次通过人体实验证明，在患有最具威胁性的脑瘤——多形性成胶质细胞瘤的病人身上，大麻提取物阻止了该化学物质的形成。虽然目前此项研究还只是处于初级阶段，但是研究者认为这是一个好的开始：“大麻提取物阻止了血管生成，而一个肿瘤如果不能实现血管生成，它就不会再生长。要是我们一方面阻止其血管生成，另一方面想办法杀死肿瘤细胞，我们就能找到治疗癌症的一种新方法。”
该研究小组在30只老鼠身上测试了delta-9-四氢大麻醇的效果。他们发现这种大麻提取物抑制了好几种基因的表达，而这几种基因与一种名为脉管内皮生长因子(VEGF)的化学物的生成有关，VEGF对于血管生成来说非常关键。大麻提取物显著降低了老鼠体内VEGF的活性，在两个人类脑瘤患者身上也显示了同样的效果。西班牙学者的研究表明，这种药是通过提高一种名为神经酰胺的脂肪分子的活性来实现这一效果的。研究者说：“我们发现老鼠脑部的肿瘤变小了，还有一点苍白。”肿瘤的苍白表明其血供应缺乏，该药物在人类患者身上也有同样效果，不过“效果还是很初步的”。
, 百拇医药
英国研究肿瘤的医学专家Richard Sullivan认为，这一研究为以肿瘤血供应为攻击目标的抗癌药物提供了一种重要的新的前驱化合物。他强调，因为目前其他科学家已经在研制一些VEGF抑制剂，对于大麻提取物就应该进行更详细深入的研究。
相关研究成果刊登在8月115日的《肿瘤研究》杂志上。
ORIGINAL TEXT：
Marijuana ingredient inhibits VEGF pathway required for brain tumor blood vessels
Cannabinoids, the active ingredients in marijuana, restrict the sprouting of blood vessels to brain tumors by inhibiting the expression of genes needed for the production of vascular endothelial growth factor (VEGF).
, 百拇医药
According to a new study published in the August 15, 2004 issue of the journal Cancer Research, administration of cannabinoids significantly lowered VEGF activity in laboratory mice and two patients with late-stage glioblastoma.
"Blockade of the VEGF pathway constitutes one of the most promising antitumoral approaches currently available," said Manuel Guzmᮬ professor of biochemistry and molecular biology, with the Complutense University in Madrid, Spain, and the study's principal investigator.
, 百拇医药
"The present findings provide a novel pharmacological target for cannabinoid-based therapies."
Glioblastoma multiforme, the most aggressive form of glioma, strikes more than 7,000 Americans each year and is considered one of the most malignant and deadliest forms of cancer, generally resulting in death within one to two years following diagnosis.
The disease is usually treated with surgery, followed by conventional radiation alone or in combination with chemotherapy. However, the main tumor often evades total destruction, surviving and growing again, eventually killing the patient. For this reason, researchers are actively seeking other therapeutic strategies, some of which might be considered novel.
, 百拇医药
In this study, the investigators chose to work with cannabinoids which, in previous studies, have been shown to inhibit the growth of blood vessels, or angiogenesis, in laboratory mice. However, little was known about the specific mechanisms by which cannabinoids impair angiogenesis, or whether the chemical might do the same in human tumors.
To answer the first part of the question, the scientists induced gliomas in mice, which were subsequently inoculated with cannabinoids. Using DNA array analysis, the team examined 267 genes associated with the growth of blood vessels in tumors and found that cannabinoids lowered the expression of several genes related to the VEGF pathway, critical for angiogenesis.
, 百拇医药
The researchers also discovered that cannabinoids apparently worked by increasing the activity of ceramide, a lipid mediator of apoptosis, resulting in the functional inhibition of cells needed for VEGF production. The ability of cannabinoids to alter VEGF production was significantly stifled following the introduction of a ceramide inhibitor.
"As far as we know, this is the first report showing that ceramide depresses VEGF pathway by interfering with VEGF production," according to Guzmᮮ
, 百拇医药
To answer the second part of the question relating to clinical tests, the scientists obtained tumor biopsies from two patients with glioblastomas who had failed standard therapy, including surgery, radiotherapy and chemotherapy. The biopsied tissue was analyzed before and after local injection of a cannabinoid.
"In both patients, VEGF levels in tumor extracts were lower after cannabinoid inoculation," said Guzmᮮ
The results, he added, suggest a potential new approach toward the treatment of these otherwise intractable brain tumors.
, 百拇医药
"It is essential to develop new therapeutic strategies for the management of glioblastoma multiforme," the scientists wrote, "which will most likely require a combination of therapies to obtain significant clinical results."
Also participating in the study were Cristina Blằuez and Amador Haro, from Complutense University; Luis Gonzᬥz-Feria, from University Hospital, Tenerife, Spain; Luis ?varez, from La Paz University Hospital in Madrid; and M. Llanos Casanova, from the Project on Cellular and Molecular Biology and Gene Therapy, CIEMAT, also in Madrid.
, http://www.100md.com
###
Founded in 1907, the American Association for Cancer Research is a professional society of more than 22,000 laboratory, translational, and clinical scientists engaged in all areas of cancer research in the United States and in more than 60 countries. AACR's mission is to accelerate the prevention and cure of cancer through research, education, communication, and advocacy. Its principal activities include the publication of five major peer-reviewed scientific journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. AACR's Annual Meetings attract more than 15,000 participants who share new and significant discoveries in the cancer field. Specialty meetings, held throughout the year, focus on the latest developments in all areas of cancer research., 百拇医药