2016年9月24日星期六

中国重大突破 癌细胞用这种方法弄死了

他和研究团队一起发现了“饿死”癌细胞的新疗法,并发表在国际生物和医学领域权威杂志elife上,得到了国际著名肿瘤学者的肯定。

  “癌细胞也需要‘吃’东西才能生存,剥夺它的食物,癌细胞就会死亡。”浙江大学肿瘤研究所教授胡汛说,就是循着这个看似简单的原理,他和研究团队一起发现了“饿死”癌细胞的新疗法,并发表在国际生物和医学领域权威杂志elife上,得到了国际著名肿瘤学者的肯定。

  经过多年基础研究,胡汛发现葡萄糖是癌细胞必需“吃”的东西,照理看剥夺葡萄糖癌细胞就会死亡。但实际上葡萄糖供应不足时,肿瘤没有饿死还不断生长。

  胡汛教授道出了其中奥秘:肿瘤中有大量的乳酸,乳酸解离成乳酸阴离子和氢离子,成为癌细胞的两位“帮手”,让其自身能够根据“食物”的多少决定“消耗”多少。
两位“帮手”协同作用,使得癌细胞在葡萄糖含量很少时,非常节约地利用葡萄糖;在没有葡萄糖的情况下进入“休眠”状态;当有葡萄糖供应时即刻恢复生长状态。
因此,若想有效“饿死”癌细胞,不仅要剥夺葡萄糖,还需同时破坏乳酸阴离子和氢离子的协同作用。在葡萄糖饥饿或缺乏的前提下,只要去除这两个因子中的任何一个,癌细胞就会快速死亡。
  研究人员用碱如碳酸氢钠(小苏打)来去除肿瘤内的氢离子,就可破坏乳酸根和氢离子的协同作用,从而快速有效地杀死处于葡萄糖饥饿或缺乏的肿瘤细胞。

  将基础科研成果快速转化成肿瘤临床治疗,让更多患者受益是关键。

  2012年起,拥有30年临床经验的浙江大学医学院附属第二医院放射介入科医生晁明和胡汛团队一拍即合,投入到对原发性肝细胞肝癌新型疗法研究中,并将这种方法命名为“靶向肿瘤内乳酸阴离子和氢离子的动脉插管化疗栓塞术”,简称“TILA-TACE”。
临床上,晁明给出解释:“常规动脉插管化疗栓塞术(cTACE)切断了肿瘤的‘食物通道’,然后我们再用碳酸氢钠去除肿瘤内的氢离子,相当于不仅不给肿瘤‘吃饭’,还让它去健身房快速消耗,迅速‘饿死’。”

  令人欣喜地是,他们进行的临床研究结果显示:用cTACE治疗了37例病人,18例有效;用TILA-TACE治疗了40例病人,40例有效。

  而且在这个临床研究中用TILA-TACE治疗的肝癌都是难治型肝癌。

  而国际上综合报道,cTACE治疗的平均客观有效率位35%。35%到100%,这样巨大的对比,不仅让国际同行在接受这篇文章时,非常慎重,就连两位教授也一直是带着怀疑在进行这项研究。

  “目前初步统计,病人的中位生存期,已超过三年半;后续还需要大样本的随机对照研究,如果证实有效,对肝癌治疗来说,确实是一个飞跃。”两位专家表示。

2016年9月8日星期四

Fasting Diets Are Gaining Acceptance

Mark Mattson, a neuroscientist at the National Institute on Aging in Maryland, has not had breakfast in 35 years. Most days he practices a form of fasting — skipping lunch, taking a midafternoon run, and then eating all of his daily calories (about 2,000) in a six-hour window starting in the afternoon.

“Once you get used to it, it’s not a big deal,” said Dr. Mattson, chief of the institute’s laboratory of neurosciences. “I’m not hungry at all in the morning, and this is other people’s experience as well. It’s just a matter of getting adapted to it.”

In a culture in which it’s customary to eat three large meals a day while snacking from morning to midnight, the idea of regularly skipping meals may sound extreme. But in recent years intermittent fasting has been gaining popular attention and scientific endorsement.

It has been promoted in best-selling books and endorsed by celebrities like the actors Hugh Jackman and Benedict Cumberbatch. The late-night talk show host Jimmy Kimmel claims that for the past two years he has followed an intermittent fasting program known as the 5:2 diet, which entails normal eating for five days and fasting for two — a practice Mr. Kimmel credits for his significant weight loss.
Fasting to improve health dates back thousands of years, with Hippocrates and Plato among its earliest proponents. Dr. Mattson argues that humans are well suited for it: For much of human history, sporadic access to food was likely the norm, especially for hunter-gatherers. As a result, we’ve evolved with livers and muscles that store quickly accessible carbohydrates in the form of glycogen, and our fat tissue holds long-lasting energy reserves that can sustain the body for weeks when food is not available.

“From an evolutionary perspective, it’s pretty clear that our ancestors did not eat three meals a day plus snacks,” Dr. Mattson said.

Across the world, millions of people fast periodically for religious and spiritual reasons. But some are now looking at the practice as a source of health and longevity.

Valter Longo, the director of the Longevity Institute at the University of Southern California, initially studied fasting in mice that showed that two to five days of fasting each month reduced biomarkers for diabetes, cancer and heart disease. The research has since been expanded to people, and scientists saw a similar reduction in disease risk factors.

Dr. Longo said the health benefits of fasting might result from the fact that fasting lowers insulin and another hormone called insulinlike growth factor, or IGF-1, which is linked to cancer and diabetes. Lowering these hormones may slow cell growth and development, which in turn helps slow the aging process and reduces risk factors for disease.

“When you have low insulin and low IGF-1, the body goes into a state of maintenance, a state of standby,” Dr. Longo said. “There is not a lot of push for cells to grow, and in general the cells enter a protected mode.”

Critics say that health benefits or not, various forms of intermittent fasting are too impractical for most people.

The 5:2 diet, for example, advocates eating without restrictions for five days and then consuming just 500 calories — roughly the equivalent of a light meal — on each of the other two days of the week. Another regimen, called alternate-day fasting, involves eating no more than 500 calories every other day.

A third regimen, which Dr. Mattson follows, is known as time-restricted feeding. The idea is to consume all of the day’s calories in a narrow window, typically six to eight hours, and fasting for the remaining 16 to 18 hours in a day. Studies of time-restricted feeding practices in both animals and humans have suggested that the practice may lower cancer risk and help people maintain their weight.

The scientific community remains divided about the value of intermittent fasting. Critics say that the science is not yet strong enough to justify widespread recommendations for fasting as a way to lose weight or boost health, and that most of the evidence supporting it comes from animal research. Advocates say the body of research on intermittent fasting is growing rapidly and indicates that the health benefits are striking.

The 5:2 diet, in particular, is backed by “promising” studies that show that it lowers weight and improves blood sugar, inflammation and other aspects of metabolic health, said Joy Dubost, a registered dietitian and a spokeswoman for the Academy of Nutrition and Dietetics, the country’s largest organization of dietitians. She noted that fasting isn’t appropriate for pregnant women, people with diabetes and people on medications.

“Most people who do this understand that it’s not about binge eating,” Dr. Dubost said. “But they like that it gives them the freedom not to worry about calories, carbs and other restrictions on days when they’re not fasting.”

Krista Varady, an associate professor of nutrition at the University of Illinois at Chicago, has studied the effects of alternate-day fasting on hundreds of obese adults. In trials lasting eight to 10 weeks, she has found that people lose on average about 13 pounds and experience marked reductions in LDL cholesterol, blood pressure, triglycerides and insulin, the fat-storage hormone.

Dr. Varady found in her research that intermittent fasting was easiest when people ate a moderately high-fat diet and were allowed to consume up to 500 calories on their fasting days. In her studies, 10 percent to 20 percent of people usually find the diet too difficult and quickly stop. Those who stick with it typically adjust after a rocky first few weeks.

“We’ve run close to 700 people through various trials,” Dr. Varady said. “We thought people would overeat on their feast days to compensate. But people for some reason, regardless of their body weight, can only eat about 10 or 15 percent more than usual. They don’t really overeat, and I think that’s why this works.”

In 2011, Dr. Mattson and his colleagues reported a study of the 5:2 program that followed 107 overweight and obese women. Half of the subjects were assigned to eat no more than 500 calories each on two consecutive days each week. A control group was assigned to follow a low-calorie diet.

After six months, both groups had lost weight. But the intermittent fasting group lost slightly more — about 14 pounds on average — and had greater reductions in belly fat. They also retained more muscle and had greater improvements in blood sugar regulation.

Dr. Mattson’s interest in intermittent fasting grew out of work on animals that showed that alternate-day fasting protected mice from strokes, Alzheimer’s and Parkinson’s disease, and consistently extended their life spans by 30 percent. Dr. Mattson and his colleagues found that alternate-day fasting increased the production of proteins that protect brain cells, enhancing their ability to repair damaged DNA. Fasting, he said, acts as a mild stress that makes cells throughout the body stronger, shoring up their ability to adapt to later insults.

In this way, intermittent fasting is like exercise, which causes immediate stress and inflammation, but protects against chronic disease in the long run. Eating fruits and vegetables may have a similar effect. While very large doses of antioxidants can cause cancer in humans, moderate amounts of exposure can make cells more resilient, Dr. Mattson said.

“There is overlap between the way cells respond to exercise, to fasting, and even to exposure to some of the chemicals in fruits and vegetables,” he added.

Dr. Mattson is now starting a rigorous clinical trial of people 55 to 70 years old who are prediabetic and at high risk for developing Alzheimer’s disease. He plans to study whether intermittent fasting may slow cognitive decline.

Dr. David Ludwig, a professor of nutrition at the Harvard T. H. Chan School of Public Health, said one benefit of fasting is that it forces the body to shift from using glucose for fuel to using fat. During this process, the fat is converted to compounds known as ketones, a “clean” energy source that burns more efficiently than glucose, like high-octane gasoline, Dr. Ludwig said.

The same process, known as ketosis, occurs when people go on extremely low-carb, high-fat diets. Dr. Ludwig said ketones seem to have unique effects on the brain. High-fat diets, for example, have been used for years to treat people who suffer from epileptic seizures.

“There are extensive reports of children who had debilitating seizures who were cured on ketogenic diets,” Dr. Ludwig said. “If it benefits the brain to prevent seizures, then maybe it benefits the brain in other ways.”

Dr. Ludwig noted that the long-term effectiveness of fasting had not been well studied. He cautioned that for many people, fasting is simply too difficult and may slow metabolism. A potentially more practical approach is to limit sugar and other processed carbohydrates, replacing them with natural fats, protein and unrefined carbohydrates, he said.

“It takes a very disciplined person to skip a couple meals every day,” he added.

But Dr. Mattson, who has been skipping meals for decades, said the adjustment to skipping breakfast and lunch was a lot like the change that occurs when a couch potato starts exercising.

“If you’ve been sedentary for years and then you go out and try to run five miles, you’re not going to feel very good until you get in shape,” he said. “ It’s not going to be a smooth transition right away. It takes two weeks to a month to adapt.”

2016年9月4日星期日

LOW-CALORIE DIET FOR TYPE 2 DIABETES

In 2013, we awarded our largest ever research grant of £2.4 million to understand the impact of a low calorie diet on Type 2 diabetes.

Professor Roy Taylor at Newcastle University and Professor Mike Lean at the University of Glasgow are comparing the long-term effects of a new weight management approach to the best diabetes care currently available.

The aim is to find out if an intensive weight management plan can help people put their Type 2 diabetes into remission for the long term.

The DiRECT study

What is the background to this research?

Not everyone with Type 2 diabetes is overweight, but weight gain and obesity are the most important risk factors for Type 2 diabetes and the reason why Type 2 has become a global epidemic that affects overweight people of all ages.

Surgical operations, such as gastric banding and gastric bypass, are potential solutions because they lead to dramatic weight loss, which can put Type 2 diabetes into remission for up to 80% of patients. But these treatments are expensive, invasive and carry a risk of surgical complications, which mean they can only be offered as a last resort.

What do we know already about low-calorie diets?

In 2011, a Diabetes UK research trial at Newcastle University tested a low-calorie diet in 11 people with Type 2 diabetes, which helped us to understand how Type 2 diabetes can be put into remission.

After the 8-week diet, volunteers had reduced the amount of fat in their liver and pancreas. This helped to restore their insulin production and put their Type 2 diabetes into remission. Three months later, some had put weight back on, but most still had normal blood glucose control.
This study was only a first step. It was designed to tell us about the underlying biology of Type 2 diabetes, and it followed the participants for only three months.

Another study, published in 2016, confirmed these findings and showed (in 30 people) that Type 2 diabetes could be kept in remission 6 months after the low-calorie diet was completed. It also suggested that the diet was effective in people that had had Type 2 diabetes for up to 10 years.

Both of these studies were very small, and were carried out in a research environment. We don't yet understand the long-term effects of these diets, or how a low-calorie diet might be used to bring about and maintain Type 2 diabetes remission in a real-life setting, as part of routine GP care.

What is the aim of the current research?

The DiRECT (Diabetes Remission Clinical Trial) study aims to find out if intensive weight control can bring about the remission of Type 2 diabetes and be maintained long-term through routine NHS care.

The trial will compare the long-term effects of a low-calorie diet and weight management programme to bsst available care for Type 2 diabetes.

What will the research involve?

A number of GP practices across Scotland and Tyneside are recruiting people aged 20-65 who are overweight and have been diagnosed with Type 2 diabetes in the last six years. Participants at half of the practices will receive the current best-available Type 2 diabetes care, while those at the other half will receive a low-calorie diet for between 8 and 20 weeks.

Afterwards, those on the low-calorie diet will be gradually re-introduced to normal food over a period of two to eight weeks and will receive expert support to help them maintain their weight loss in the long term.

Participants receiving best-available care will get weight loss support in accordance with the latest clinical guidelines, but won't receive the low-calorie diet.

The researchers will test metabolisms and measure fat deposits inside the body, to reveal exactly how major weight loss can put Type 2 diabetes into remission. They'll also carry out psychological assessments with  the participants and healthcare professionals taking part in the study, to work out how this approach to weight management might form part of routine GP care.

Where is the research taking place?

This study will take place at around 30 GP practices in Scotland and Tyneside. The research will be carried out and the data analysed by researchers at the University of Glasgow and at Newcastle University.

Who can take part?

Only people invited to take part by their GP practice can get involved in this study. Recruitment is only taking place at selected GP practices in Scotland and Tyneside. Individual patients are not being recruited.

How will it benefit people with diabetes?

If this study shows that a low-calorie diet can safely put Type 2 diabetes into remission for the long-term, it could completely transform the way this condition is viewed and treated.

If the diet can be used practically and effectively, it could lead to significant changes in the way that Type 2 diabetes is managed by the NHS. It could also help people with this condition live for longer, improving quality of life and reducing the risk of serious health complications, without the need for invasive weight loss surgery.

If a low-calorie diet can be used within routine GP care , it could ultimately be of enormous benefit to millions of people living with Type 2 diabetes in the UK.

When will results be available?

This study will last until October 2018, and the overall results will be released once all of the data has been analysed. We'll report the results in Diabetes UK publications and on the website.

The low-calorie diet

What will the diet used consist of?

The diet used in DiRECT will last for between 8 and 20 weeks and provide around 800 calories a day. It will consist of four diet soups or shakes per day, providing all essential vitamins and minerals and lots of fluids.

Will the diet cure Type 2 diabetes?

The diet being studied isn't a 'quick fix' for Type 2 diabetes. It should help people taking part in the study to lose weight – specifically, the fat in and around their liver and pancreas. This should, in turn, help to put their Type 2 diabetes into remission.

It's likely that some people who take part in the research will find the diet challenging, and every participant will have to work hard to keep weight off in the long-term to maintain Type 2 diabetes remission.

Is the diet used in this research available now?

Low-calorie diet foods are not available on prescription from the NHS. They're marketed by a range of private companies, but can be expensive and come with limited evidence of long-term benefit.

This research is the only way to tell if weight management using a low-calorie diet is practical and more effective than the current best-available treatments for Type 2 diabetes.

Should people with Type 2 diabetes follow the diet used in this research?

Until we have evidence that a low-calorie diet is more effective than the current best-available treatment, Diabetes UK recommend that people with Type 2 diabetes only attempt to lose weight in this way after they have spoken to their GP.

We're confident that DiRECT will answer important questions and give the NHS enough evidence to decide whether low-calorie diets should be offered as a routine treatment option. People with diabetes should always consult their GP before making changes to the way that they manage their condition.

What diet does Diabetes UK recommend for people with Type 2?

Diabetes UK recommends that people with Type 2 diabetes eat a healthy, balanced diet that is low in sugar, salt and fat and includes plenty of fruits and vegetables. For information on living a healthy lifestyle and eating well with Type 2 diabetes please see our guide to diabetes.