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癌也许永远不能被彻底根除? 精选

已有 14817 次阅读 2014-6-26 06:18 |个人分类:期刊论文|系统分类:论文交流| 癌症

尽管从个体发育的角度探索癌的起源蹒跚而行,但从系统演化的角度认识癌的发生却初现端倪。6月24日,德国科学家在《自然——通讯》(Nature Communications)上宣布,他们在基础后生动物水螅的两个种中首次发现自然发生的肿瘤,并由此得出一个令人沮丧的结论:“癌像地球上所有多细胞生物一样古老,它也许永远不能被彻底根除”(cancer... ...will probably never be completely eradicated)!

言下之意,只要是多细胞生物,就一定会有癌,而且是无法彻底消失的。那么,他们得出这样的结论有何依据呢?首先,他们认为癌基因是古老的,已从一些古老的动物中找到癌基因,其中大多数都能引起人类癌症。其次,他们揭示癌起源于细胞死亡的编程错误,而水螅中的癌是由于为性分化编程的干细胞大量积累而未被程序性死亡(细胞凋亡)自然移除所致。再次,他们发现癌的浸润性也是古已有之,意味着把它移植给正常细胞后也会诱生癌。

这篇文章从癌基因、致癌机制和癌细胞特征等方面显示出新意,但似乎仍有证据不充足,分析太简单之嫌,难道癌的发生和发展真的如此简单?完全没有想象的那么复杂?以本人的知识层次,我觉得它至少还缺乏以下几个方面的论证:

首先,抗癌基因或肿瘤抑制基因(tumor suppressor)的分析。对于癌的发生,仅分析癌基因是远远不够的,因为那样无法解释为什么大多数生物不生癌。换句话说,不是有了癌基因,就一定会致癌。很多抗癌基因的本质是DNA损伤修复蛋白,只有当抗癌基因突变失活后,DNA的氧化损伤无法修复,癌才会发生。该文似乎忽略了以往有关“癌可以预防”的共识,这样如何解释饮食、环境污染、生活习惯等因素在致癌中的作用?这类参考资料不计其数,仅举一例,参见Applying What We Know to Accelerate Cancer Prevention(cancer prevention.pdf

其次,表观遗传因素的分析。癌的发生并非仅仅取决于癌基因与抗癌基因之间的相互作用,还可因表观遗传变异而出现。比如,DNA甲基转移酶(DNMT)基因突变将导致DNA甲基化模式改变,使得某些本该表达的基因不能表达,而不该表达的基因却表达。该文只考虑遗传因素的致癌作用,不考虑表观遗传因素的致癌作用,显然有失偏颇,难以服人。参见Cancer Epigenetics: From Mechanism to Therapy(epigenetic cancer.pdf)。

再次,慢性炎症的成因过程、后果分析。无论是感染性或非感染性,慢性炎症都是癌的重要诱因,因为炎症可以导致促炎细胞因子基因活化,为癌的发生、发展和转移创造有利的微环境。本文虽然提出致癌的原因在于细胞凋亡受阻,但那显然不是最初的原因,甚至只是结果。参见Dietary and Genetic Obesity Promote Liver Inflammation and Tumorigenesis by Enhancing IL-6 and TNF Expression(IL-6 TNFa.pdf

因此,尽管该文有新意,但缺陷也很明显,只可视为开创研究,不能作出最终评判。这就意味着“癌也许永远不能被彻底根除”的断言并不一定成立,好在这句话并没写在文章中,而可能只是作者面对记者采访时的一种说法(有待证实)。



附:


文章首页标题及摘要截图(来源于Nature Communications网页的Preview)


Science Daily新闻报道内容


Cancer 'as old as multi-cellular life on Earth': Researchers discover a primordial cancer in a primitive animal

Date:
June 24, 2014
Source:
Kiel University
Summary:
Can cancer ever be completely defeated? Researchers have now reached a sobering conclusion: "cancer is as old as multi-cellular life on Earth and will probably never be completely eradicated," says one expert, following his latest research results. The researchers have now achieved an impressive understanding of the roots of cancer, providing proof that tumors indeed exist in primitive and evolutionary old animals.


Tumour-bearing Hydra-Polyp (right) next to a healthy animal (left).
Credit: Photo/copyright: Klimovich/ CAU

Every year millions of people around the world are diagnosed with cancer. Each one of them dreams of a victory in the battle against it. But can cancer ever be completely defeated? Researchers at Kiel University (CAU) in Germany have now reached a sobering conclusion: "cancer is as old as multi-cellular life on earth and will probably never be completely eradicated," says Professor Thomas Bosch in his latest research results.

The study by an international team led by Bosch was published in the scientific journal Nature Communications.

The so-called cancer genes are ancient

The causes of tumors are the so-called cancer genes. As from when evolution started producing tumors is an issue that the scientists Tomislav Domazet-Lošo and Diethard Tautz from the Max Planck Institute for Evolutionary Biology in Plön have been investigating for several years, using bio-informational methods and databases that they have developed in-house. "During the search for the origin of the cancer gene, we unexpectedly made a discovery in the ancient group of animals," explains Domazet-Lošo. He is one of the authors of the present study and is currently working at the Ruder Bošković Institute and the Catholic University of Croatia in Zagreb. "Our data predicted that the first multi-cellular animals already had most of the genes which can cause cancer in humans." What was missing until now was, on the one hand, evidence that these animals can actually suffer from tumors and, on the other, the molecular understanding of the mechanisms of tumor formation in these simple animals.

Cause of tumors: error in the programming of cell death

The research team led by the evolutionary biologist Professor Thomas Bosch from the Zoological Institute of Kiel University have now achieved an impressive understanding of the roots of cancer. Bosch has been investigating stem cells and the regulation of tissue growth in Hydra, a phylogenetic old polyp, for many years. "Now we have discovered tumor-bearing polyps in two different species of Hydra, an organism very similar to corals," emphasises Bosch regarding the first result of the new study. This provides proof that tumors indeed exist in primitive and evolutionary old animals.

The team also tracked down the cellular cause of the tumors along the entire body axis. For the first time they were able to show that the stem cells, which are programmed for sex differentiation, accumulate in large quantities and are not removed naturally by programmed cell death. Interestingly, these tumors affect only female Hydra polyps and resemble ovarian cancers in humans.

"When undertaking more detailed molecular analyses of the tumors we found a gene that becomes active dramatically in tumor tissue and that normally prevents the programmed cell death," explains Alexander Klimovich, a scholarship student at the Alexander-von-Humboldt Foundation at the Zoological Institute of Kiel University and co-lead author of the current study regarding the second finding of the study. "As a non-functioning cell death mechanism is also made responsible for the growth and spread of tumors in many types of human cancer, striking similarities appear here to cancer in humans," continues Klimovich.

The third finding of the scientists was to show that tumor cells are invasive. This means that if tumor cells are introduced into a healthy organism, they can trigger tumor growth there. Therefore Bosch reaches the following conclusion from his research into Hydra species: "The invasive characteristic of cancer cells is also an evolutionary old feature."

Tumors have deep roots in evolution

The funds that are being deployed throughout the world in the campaign against cancer are enormous. It was estimated that in the US alone, more than 500 billion dollars were invested in cancer research by 2012. The worldwide research has led to improved preventative, diagnostic and treatment methods, which can definitely record successes. However it is precisely as far as some frequent tumors are concerned where only slow progress has been achieved. Every second person affected by cancer still succumbs to the disease today. In Germany alone every fourth person dies of cancer and this trend is rising. (World Cancer Report 2014) These figures were an incentive for the National Institute of Health in the US to launch a network of Physical Science-Oncology Centers, a new initiative that seeks to bridge intellectual barriers between diverse scientific disciplines. Paul Davies, a well-known theoretical physicist and popular science writer who now leads one such center in Phoenix, Arizona, recently concluded: "Clearly, we will fully understand cancer only in the context of biological history." (The Guardian, 2012)

According to the research team led by Bosch, the findings of primordial tumors in Hydra are a breakthrough step in that direction: "Our research reconfirms that primordial animals such as Hydra polyps provide an enormous amount of information to help us understand such complex problems as 'cancer'. Our study also makes it unlikely that the 'War on Cancer' proclaimed in the 1970s can ever be won. However, knowing your enemy from it origins is the best way to fight it, and win many battles," says Bosch.

Story Source:

The above story is based on materials provided by Kiel University. Note: Materials may be edited for content and length.

Journal Reference:

  1. Tomislav Domazet-Lošo, Alexander Klimovich, Boris Anokhin, Friederike Anton-Erxleben, Mailin J. Hamm, Christina Lange, Thomas C.G. Bosch. Naturally occurring tumours in the basal metazoan Hydra. Nature Communications, 2014; 5 DOI: 10.1038/ncomms5222







































































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