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癌症弱化与起源的假说。

Hypotheses of cancer weakening and origin.

作者信息

Chan John Cheung Yuen

机构信息

33 Magnus St, Nelson Bay NSW 2315 Australia.

出版信息

J Cancer. 2015 Mar 9;6(5):457-63. doi: 10.7150/jca.10911. eCollection 2015.

DOI:10.7150/jca.10911
PMID:25874009
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4392054/
Abstract

Approximately 2.7 billion years ago, cyanobacteria began producing oxygen by photosynthesis. Any free oxygen they produced was chemically captured by dissolved iron or organic matter. There was no ozone layer to protect living species against the radiation from space. Eukaryotic cells lived in water, under hypoxic environments, and metabolized glucose by fermentation. The Great Oxygenation Event (GOE) describes the point when oxygen sinks became saturated. This massive oxygenation of the Earth occurred approximately half a billion years ago. Species that evolved after the GOE are characterized by aerobic metabolism. Mammals evolved approximately a few hundred million years ago, with the ancient eukaryotic genes deeply embedded in their genome. Many genes have been exchanged by horizontal gene transfer (HGT) throughout the history of cellular evolution. Mammals have been invaded by viruses, and while viral genetic relics are embedded in mammalian junk genes, not all junk genes are genetic relics of viruses. These viral relics have been inactivated through evolution and have little impact on mammalian life. However, there is evidence to suggest that these viral genetic relics are linked to cancer. This hypothesis states that cancer develops when cell reproduction becomes defective because of the active involvement of viral genes, in a process similar to genetic engineering. Cancer cells are amalgamations of genetically modified organisms (GMOs). There are two main groups in cancer development. One group of cells arises by genetic engineering of a viral genetic relic, such as endogenous retroviruses (ERVs), which evolved after oxygenation of the atmosphere. This group is referred to here as genetically modified organisms from viral genes (GMOV). GMOVs may be inhibited by anticancer drugs. The second group arises by engineering of the genes of ancient eukaryotes, which existed prior to the oxygenation of the Earth. This second group is referred to as genetically modified organisms from ancient eukaryotic genes (GMOE). The GMOE group lives in hypoxic environments and metabolizes glucose by fermentation. GMOEs represent advanced cancer, which proliferate aggressively and are resistant to DNA damage. It has been demonstrated that as an ERV becomes more prevalent in a mammalian genome, the possibility that the mammal will develop cancer increases. The hypothesis also states that most cancers have their origins in GMOV by the incorporation of viral genes from junk genes. As the cancer progresses, further subgroups of cancer GMOs will develop. If the cancer advances even further, the GMOE could eventually develop prior to late-stage cancer. Because the genes of ancient eukaryotes have enhanced innate immunity, GMOE will eventually prevail over the weaker GMOV during cancer subgroup competition. Hence, cancer development is mainly determined by genes in the mammalian genome. An inherent weakness of cancer cells is their dependence on glucose and iron. Furthermore, they cannot tolerate physical disturbance. Ancient gene GMOs can be treated with a combination of mechanical vibration using glucose-coated magnetic nanoparticles and strengthening of the immune system. Herein, I suggest trials for verifying this hypothesis.

摘要

大约27亿年前,蓝细菌开始通过光合作用产生氧气。它们产生的任何游离氧都会被溶解的铁或有机物化学捕获。当时没有臭氧层来保护生物免受来自太空的辐射。真核细胞生活在水中,处于缺氧环境中,并通过发酵代谢葡萄糖。大氧化事件(GOE)描述了氧汇饱和的那个时间点。地球的这种大规模氧化大约发生在5亿年前。在大氧化事件之后进化的物种以有氧代谢为特征。哺乳动物大约在几亿年前进化而来,古老的真核基因深深嵌入它们的基因组中。在细胞进化的整个历史中,许多基因通过水平基因转移(HGT)进行了交换。哺乳动物受到病毒的侵袭,虽然病毒遗传遗迹嵌入在哺乳动物的垃圾基因中,但并非所有垃圾基因都是病毒的遗传遗迹。这些病毒遗迹通过进化已经失活,对哺乳动物的生命影响很小。然而,有证据表明这些病毒遗传遗迹与癌症有关。这个假说指出,当细胞繁殖由于病毒基因的积极参与而出现缺陷时,就会发生癌症,这一过程类似于基因工程。癌细胞是转基因生物(GMO)的融合体。癌症发展主要有两个群体。一组细胞是由病毒遗传遗迹的基因工程产生的,比如内源性逆转录病毒(ERVs),它们是在大气氧化之后进化而来的。这一组在这里被称为来自病毒基因的转基因生物(GMOV)。GMOV可能会被抗癌药物抑制。第二组是由地球氧化之前就存在的古代真核生物的基因工程产生的。这第二组被称为来自古代真核基因的转基因生物(GMOE)。GMOE群体生活在缺氧环境中,并通过发酵代谢葡萄糖。GMOE代表晚期癌症,它们增殖迅速且对DNA损伤具有抗性。已经证明,随着ERV在哺乳动物基因组中变得更加普遍,该哺乳动物患癌症的可能性就会增加。该假说还指出,大多数癌症起源于GMOV,是通过从垃圾基因中整合病毒基因产生的。随着癌症的发展,癌症转基因生物的进一步亚群将会出现。如果癌症进一步发展,GMOE最终可能在晚期癌症之前出现。因为古代真核生物的基因增强了先天免疫力,在癌症亚群竞争中,GMOE最终将战胜较弱的GMOV。因此,癌症的发展主要由哺乳动物基因组中的基因决定。癌细胞的一个固有弱点是它们对葡萄糖和铁的依赖。此外,它们无法耐受物理干扰。古代基因转基因生物可以通过使用葡萄糖包被的磁性纳米颗粒进行机械振动和增强免疫系统的联合治疗。在此,我建议进行试验以验证这一假说。

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本文引用的文献

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An ancient defense system eliminates unfit cells from developing tissues during cell competition.在细胞竞争过程中,一种古老的防御系统会从发育组织中清除功能失调的细胞。
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