Potential New Treatment for Liver Cancer Discovered

StephenW

http://www.emaxhealth.com/1275/potential-new-treatment-liver-cancer-discovered
Potential New Treatment for Liver Cancer Discovered
By Deborah Mitchell on December 13, 2011 - 6:54am

BOSTON, MA--For the first time, researchers have discovered a special type of molecular regulator called a micro-RNA (miR-124) that could be used someday as a treatment for liver cancer. The same team also found a mechanism in mice that ultimately causes normal liver cells to transform into cancerous ones.
Liver cancer remains difficult to treat

Liver cancer will be diagnosed in an estimated 26,000 people in the United States in 2011, and nearly 20,000 individuals will die of the disease. Worldwide, liver cancer is the third cause of death caused by cancer, falling in behind lung (1.4 million deaths) and stomach cancer (740,000 deaths) at around 700,000 deaths.

Among the most common causes of and risk factors for liver cancer are chronic hepatitis B infection, which is common in Asia (where it is a childhood disease), hepatitis C (more common in Japan, Europe, and North America), alcohol abuse, and exposure to environmental toxins (including aflatoxin B1, which is the most potent liver cancer-causing chemical known), all of which can damage the liver and thus lead to cancer. Other factors include cirrhosis, hemochromatosis (disorder characterized by excess iron in the body), and non-alcoholic steatohepatitis.

In the new study, which was conducted by researchers at the Dana-Farber Cancer Institute, mice were exposed to a cancer-causing chemical called DEN, which triggered a circuit of inflammation in the liver that ultimately led to cancer. The investigators identified one element of the circuit called miR-124. Molecules in this class have been associated with different types of cancer.

Another key player in the circuit is HNF4α, a substance that has an important role in the formation of liver cells and their function. If HNF4α is suppressed, the result can be inflammation, which can then lead to cancer.

According to Dimitrios Iliopoulos, PhD, of Dana-Farber’s Department of Cancer Immunology and AIDS, he and the team decided to enhance the activity of miR-124 in hopes it would restore normal activity in HNF4α, which in turn would stop the inflammatory cycle and stop liver cancer from growing.

When they administered miR-124 to mice with liver cancer once a week for four weeks, they discovered that miR-124 halted more than 80 percent of liver tumor growth by causing the cancer cells to self-destruct. Another benefit of miR-124 was that it prevented the development of liver tumors.

Current treatments for liver cancer are limited. The only proven cure is a liver transplant. Individuals who have a small tumor may undergo a partial hepatic (liver) resection, although most people with liver cancer also have cirrhosis and cannot tolerate liver resection. Other treatments include chemotherapy, proton beam therapy, chemoembolization (delivery of chemotherapy directly to the tumor), radioembolization (a type of radiotherapy), and ablation, but the results are not promising at this point.

Iliopoulos and his team expressed the hope that “miR-124 potentially could be used as a preventive in patients at high risk of liver cancer because they have chronic hepatitis C or as a therapeutic agent in patients with liver cancer.” The authors plan to begin a phase I clinical trial to explore this possible new liver cancer treatment in 2012.

SOURCE:
Dana-Farber Cancer Institute

StephenW

潜在治疗肝癌的新发现
德博拉米切尔2011年12月13日 - 6:54

马萨诸塞州的波士顿 - 这是第一次，研究人员已经发现了一个特殊类型的分子调节称为微RNA（MIR - 124），可作为治疗肝癌有一天。同样的团队还发现，在小鼠的机制，最终导致正常肝细胞转化为癌细胞的。
仍然难以治疗肝癌

在2011年，估计有26000人在美国被诊断肝癌和近20000人将死于这种疾病。在世界范围内，肝癌是由癌症导致死亡的第三个原因，在后面的肺（140万例死亡）和胃癌（74万死亡）约700,000人死亡。

其中最常见的原因及肝癌的危险因素是慢性乙肝病毒感染，这是在亚洲的共同（它是一种儿童疾病），丙型肝炎（在日本，欧洲和北美更常见​​），酗酒，和接触环境毒素（包括黄曲霉毒素B1，这是最有力的肝癌引起化学已知），所有这些都可以损害肝脏，从而导致癌症。其他因素包括肝硬化，血色病（在体内多余的铁的障碍），和非酒精性脂肪性肝炎。

在新的研究，这是由达纳 - 法伯癌症研究所的研究人员进行的，老鼠被暴露在一种致癌化学物质称为书房，从而引发炎症的电路在肝脏，最终导致癌症。研究者发现一种名为miR - 124的电路元素。在这个类中的分子已经与不同类型的癌症。

另一个电路中的关键球员是HNF4α，一种物质，在肝细胞的形成及其功能的重要作用。如果HNF4α被抑制，结果可能是炎症，它可以导致癌症。

据迪米特里奥斯Iliopoulos，博士，达纳 - 法伯的癌症免疫学和艾滋病系，他和球队决定，以加强在MIR - 124，希望活动，将恢复HNF4α，这反过来会停止的炎症周期的正常活动和肝癌生长停止。

当他们管理的miR - 124对小鼠肝癌的四个星期，每周一次，他们发现，miR - 124的停止超过80％的肝肿瘤的生长，导致癌细胞自我毁灭。 miR - 124的另一个好处是，它阻止肝肿瘤的发展。

目前肝癌的治疗方法是有限的。唯一证明治疗是肝移植。有一个小肿瘤的个体可能接受了部分肝切除（肝），虽然大多数癌症患者的人也有肝硬化及不能耐受肝切除术。其他治疗方法包括质子束疗法，化疗，栓塞化疗（化疗提供直接作用于肿瘤），radioembolization（A型放疗），和消融，但结果并不在这一点上有前途。

Iliopoulos和他的团队表示，希望“的miR - 124可能被用来作为在肝癌的高风险患者的预防，因为他们有慢性丙型肝炎或作为肝癌患者的治疗剂。”计划开始I期临床试验，以探讨在2012年这个可能的新治疗肝癌。