New way to kill lymphoma without chemotherapy

虚心

New way to kill lymphoma without chemotherapy
22.01.2013

Golden nanoparticle starves cancer cell to death



How do you annihilate lymphoma without using any drugs?


...more about:
> B-cell > B-cell lymphoma > Cancer > cancer drug > gold nanoparticle > heart disease > Hodgkin lymphoma > human cell > lymphoma cells > lymphoma research > Thaxton > tumor growthStarve it to death by depriving it of what appears to be a favorite food: HDL cholesterol.

Northwestern Medicine(r) researchers discovered this with a new nanoparticle that acts like a secret double agent. It appears to the cancerous lymphoma cell like a preferred meal -- natural HDL. But when the particle engages the cell, it actually plugs it up and blocks cholesterol from entering. Deprived of an essential nutrient, the cell eventually dies.

A new study by C. Shad Thaxton, M.D., and Leo I. Gordon, M.D. shows that synthetic HDL nanoparticles killed B-cell lymphoma, the most common form of the disease, in cultured human cells, and inhibited human B-cell lymphoma tumor growth in mice.

The paper will be published Jan. 21 in the journal Proceedings of the National Academy of Sciences.

"This has the potential to eventually become a nontoxic treatment for B-cell lymphoma which does not involve chemotherapy," said Gordon, a co-corresponding author with Thaxton on the paper. "It's an exciting preliminary finding."

Gordon is a professor of medicine in hematology/oncology and Thaxton is an assistant professor of urology, both at Northwestern University Feinberg School of Medicine.

Gordon also is co-director of the hematologic malignancy program at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University and a physician at Northwestern Memorial Hospital. Thaxton is also a member of the Lurie Cancer Center.

Lymphoma Gobbles HDL Cholesterol

Recent studies have shown that B-cell lymphoma is dependent on the uptake of natural HDL -- short for high-density lipoprotein -- from which it derives fat content, such as cholesterol.

The nanoparticle -- originally developed by Thaxton as a possible therapy for heart disease -- closely mimics the size, shape and surface chemistry of natural HDL particles. But it has one key
difference: a five nanometer gold particle at its core. Thus, when the nanoparticle is incubated with human B-cell lymphoma cells or used to treat a mouse with the human tumor, it socks lymphoma with a double whammy. After it attaches to the lymphoma cell, the gold particle's spongy surface sucks out its cholesterol while the gold core prevents the cell from absorbing more cholesterol typically carried in the core of natural HDL particles.

The lymphoma research showed Thaxton that the HDL nanoparticle had more than one trick up its golden sleeve.

"At first I was heavily focused on developing nanoparticles that could remove cholesterol from cells, especially those involved in heart disease," Thaxton said. "The lymphoma work has broadened this focus to how the HDL nanoparticles impact both the removal and uptake of cholesterol by cells. We discovered the particles are multi-taskers."

The Northwestern study also showed that natural HDL did not kill the cells or inhibit tumor growth. The nanoparticle was essential to starve the lymphoma cell.

Detour From Heart Disease to Cancer Killer

After developing the HDL nanoparticle, Thaxton gave a lecture in 2010 to Feinberg faculty. Gordon was in the audience. He knew that patients with advanced forms of B-cell lymphoma sometimes have dropping levels of cholesterol. A long-time lymphoma researcher and oncologist, Gordon was looking for new methods to deliver drugs to patients. He contacted Thaxton and they began to collaborate.

They tested the HDL nanoparticle alone and the HDL nanoparticle transporting cancer drugs. Surprisingly, the nanoparticle without drugs was just as effective at killing the B-cell lymphoma cells.

"We thought, 'That's odd. Why don't we need the drug?'" Gordon recalled.

That's when the scientists began delving into the mechanism by which the HDL nanoparticles were sticking to the HDL receptors on the lymphoma cell and manipulating cholesterol transport. In addition, patient samples analyzed by collaborators at Duke University for the study showed that lymphoma cells in patients had an overproduction of these HDL receptors compared to normal lymphocytes.

B-cell Lymphoma Most Common Lymphoma

The National Cancer Institutes reports that in 2012 there were about
70,000 new cases of non-Hodgkin lymphoma in the U.S. with nearly
19,000 deaths. About 90 percent of those new cases were B-cell lymphoma. Non-Hodgkin lymphoma is a cancer that starts in cells called lymphocytes, which are part of the body's immune system.

Why a Heart of Gold?

"Gold has a good track record of being compatible with biologic systems," Thaxton said.

Thaxton and Gordon are encouraged by their early data showing that the HDL nanoparticles do not appear toxic to other human cells normally targeted by HDLs, normal human lymphocytes or to mice. Also, because gold nanoparticles can be made in a discreet size and shape, they are excellent scaffolds for creating synthetic HDLs that closely mimic those found in nature.

"Like every new drug candidate, the HDL nanoparticle will need to undergo further testing," Thaxton noted.

The co-first authors of the paper are Shuo Yang and Marina Damiano.
Shuo is a research associate in medicine in Gordon's laboratory in the division of hematology/oncology at the Feinberg School and Marina is a graduate student in the department of chemistry at Weinberg College of Arts and Sciences.

The research was supported by The Howard Hughes Medical Institute and the Schwartz Foundation. Thaxton is a co-founder of AuraSense, LLC a start-up biotech company that holds the license to the HDL nanoparticles used in the study.

NORTHWESTERN NEWS: www.northwestern.edu/newscenter/.

虚心

不知道是不是应该放在这个版块?如果不对,版主可以任意移动,希望对大家有帮助,毕竟这是好消息.

挑战霍奇金

和前天发的帖子是一样的内容。

知足常乐

能不能翻译过来

冬去春来

Kan bu dong.{:soso_e112:}

勇者

在不使用任何药物的情况下，你如何能够消除淋巴瘤？最好的方法莫过于夺去它最喜欢的食物——高密度脂蛋白胆固醇，让其饿死。



来自西北大学医学院的研究人员发现了一种新的纳米颗粒，它能够像双重秘密间谍那样发挥作用。其看起很像癌性淋巴瘤细胞喜欢的一种首选食物——天然HDL。然而一旦这种颗粒进入细胞，它实际上会堵塞细胞，阻止胆固醇进入。丧失这种必需的营养物质，细胞会最终死亡。



新研究由西北大学Feinberg医学院C. Shad Thaxton博士和Leo I. Gordon博士领导，他们在培养的人类细胞中证实合成的HDL纳米颗粒能够杀死B细胞淋巴瘤，并抑制了小鼠体内人类B细胞淋巴瘤的生长。该研究论文发表在1月21日的《美国科学院院刊》（PNAS）上。



“这有可能最终成为一种不涉及化疗的无毒性B细胞淋巴瘤疗法。这是一个令人兴奋的初步研究结果，” Gordon说。



淋巴瘤贪食HDL胆固醇



近期的研究表明，B细胞淋巴瘤依赖摄取天然的HDL，从中获得如胆固醇等脂肪物质。



Thaxton最初开发这种纳米颗粒是作为心脏病的一种潜在治疗。新纳米粒子大小、形状及表面化学性质与天然HDL颗粒接近相似，但其具有的一个关键性的差异就是：它的核心是一个5纳米的金颗粒。因此，当将纳米颗粒与人类B细胞淋巴瘤细胞共孵育，或是用于治疗人类肿瘤小鼠之时，它能够给予淋巴瘤双重打击。当它附着到淋巴瘤细胞上之时，金颗粒的多孔表面将它的胆固醇吸出，并同时阻止细胞吸收更多的胆固醇。



淋巴瘤研究向Thaxton表明，这种HDL纳米颗粒不只会耍一套把戏。



Thaxton说：“起初，我侧重于开发能够清除细胞，尤其是那些与心脏病相关的细胞中胆固醇的纳米颗粒。淋巴瘤的研究工作将焦点扩展到了HDL纳米颗粒影响细胞胆固醇去除与摄取的机制。我们发现这些颗粒执行了多重任务。”



西北大学的研究还表明，天然HDL无法杀死细胞或是抑制肿瘤生长。纳米颗粒是饿死这种淋巴瘤细胞的必要条件。



从心脏病绕道到癌症杀手



在开发出HDL纳米颗粒后，2010年haxton给Feinberg学院的全体教员做了一次演讲。当时Gordon在听众席就坐。Gordon知道一些晚期B细胞淋巴瘤的患者有时胆固醇水平会下降。作为长期的淋巴瘤研究人员和肿瘤专家，Gordon一直在寻找传递药物的新方法。他联系了Thaxton，开始了两人之间的合作。



他们对HDL纳米颗粒以及HDL纳米颗粒转运抗癌药物进行了测试。令人惊讶的是，他们发现没有药物的纳米颗粒一样能有效杀伤B细胞淋巴瘤细胞。



“我们认为‘这很奇怪’。为什么我们不需要药物？”Gordon回忆说。



这时，科学家们开始探究HDL纳米颗粒附着到淋巴瘤细胞HDL受体，操控胆固醇传送的机制。此外，杜克大学的合作者们分析了患者的样本，证实相比正常淋巴细胞，患者的淋巴瘤细胞HDL受体过表达。



B细胞淋巴瘤是最常见的淋巴瘤



美国国家癌症研究所报告，在2012年美国有7万非霍奇金淋巴瘤新增病例，导致近1.9万人死亡。大约90%的新增病例是B细胞淋巴瘤。



为什么以黄金做核心？



“因为过往的记录表明黄金与生物系统兼容良好，”Thaxton说。



早期的研究数据表明HDL纳米颗粒似乎对于HDLs通常靶向的其他人类细胞、正常人淋巴瘤细胞和小鼠无毒，这是因为研究人员谨慎地控制了这些黄金纳米颗粒的大小及形状，它们为生成近似于自然中HDLs的合成HDLs提供了极好的支架。



“就像所有的新候选药物一样，HDL纳米颗粒还需要开展进一步的测试，” Thaxton说。

勇者

翻译来源：http://www.biosou.com/index_newshow.php?newsid=83924