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While people who eat a lot of red meat are known to be at higher risk for certain cancers, other carnivores are not, prompting researchers at the University of California, San Diego School of Medicine to investigate the possible tumor-forming role of a sugar called Neu5Gc, which is naturally found in most mammals but not in humans.
In a study published in the Dec. 29 online early edition of the Proceedings of the National Academy of Sciences, the scientists found that feeding Neu5Gc to mice engineered to be deficient in the sugar (like humans) significantly promoted spontaneous cancers. The study did not involve exposure to carcinogens or artificially inducing cancers, further implicating Neu5Gc as a key link between red meat consumption and cancer.
"Until now, all of our evidence linking Neu5Gc to cancer was circumstantial or indirectly predicted from somewhat artificial experimental setups," said principal investigator Ajit Varki, MD, Distinguished Professor of Medicine and Cellular and Molecular Medicine and member of the UC San Diego Moores Cancer Center. "This is the first time we have directly shown that mimicking the exact situation in humans -- feeding non-human Neu5Gc and inducing anti-Neu5Gc antibodies -- increases spontaneous cancers in mice."
Varki's team first conducted a systematic survey of common foods. They found that red meats (beef, pork and lamb) are rich in Neu5Gc, affirming that foods of mammalian origin such as these are the primary sources of Neu5Gc in the human diet. The molecule was found to be bio-available, too, meaning it can be distributed to tissues throughout the body via the bloodstream.
The researchers had previously discovered that animal Neu5Gc can be absorbed into human tissues. In this study, they hypothesized that eating red meat could lead to inflammation if the body's immune system is constantly generating antibodies against consumed animal Neu5Gc, a foreign molecule. Chronic inflammation is known to promote tumor formation.
To test this hypothesis, the team engineered mice to mimic humans in that they lacked their own Neu5Gc and produced antibodies against it. When these mice were fed Neu5Gc, they developed systemic inflammation. Spontaneous tumor formation increased fivefold and Neu5Gc accumulated in the tumors.
"The final proof in humans will be much harder to come by," Varki said. "But on a more general note, this work may also help explain potential connections of red meat consumption to other diseases exacerbated by chronic inflammation, such as atherosclerosis and type 2 diabetes.
"Of course, moderate amounts of red meat can be a source of good nutrition for young people. We hope that our work will eventually lead the way to practical solutions for this catch-22."
參考譯文：
長期以來，大量可重復的流行病學資料顯示，人類長期食用哺乳動物源“紅肉”（牛肉、豬肉和羊肉等）增加癌癥發生風險。雖然，迄今已經有多種理論被提出試圖用來解釋這種現象，但是都沒有被最終證實。
12月29日發表在美國國家科學院院刊網絡版上的一項研究中，科學家發現，給經過基因工程改造象人類一樣存在Neu5Gc缺陷的小鼠喂食非人類唾液酸N-羥乙酰神經氨酸（Neu5Gc）顯著促進癌癥發生。該研究中由于實驗小鼠沒有涉及致癌物質暴露或人工誘導腫瘤，進一步提示Neu5Gc可能是紅肉消費和癌癥之間關聯的一個關鍵因素。
加州大學圣迭戈穆爾斯癌癥研究中心首席研究員阿吉特•瓦爾基博士領導的研究團隊首先對人類常見食物系統進行篩查。他們發現，哺乳動物源性紅肉含有豐富的Neu5Gc，而這種糖分子物質容易被人體吸收，口服后生物利用度高，可以通過血液分布到整個身體組織。
因此，研究人員推測，由于人類缺乏Neu5Gc，那么被人踢吸收后可能坐位一種外源性抗原激發人體免疫反應而引發炎癥反應。而慢性炎癥是已知的一種致癌因素。
為了驗證這一假設，研究團隊利用基因工程技術改造出模擬人體的Neu5Gc缺陷小鼠。由于這些小鼠缺乏Neu5Gc，喂食它們Neu5Gc后激發了全身炎癥反應，自發性腫瘤的發生增加了五倍，而且腫瘤組織內富集Neu5Gc存在。
“雖然難以在人類獲得最終的證實，但是在更廣泛的意義上，這項工作也有助于解釋紅肉消費與其他可以由慢性炎癥加重的其他疾病，如動脈粥樣硬化和2型糖尿病等之間潛在的聯系。”瓦爾基博士說。
原始來源：http://www.sciencedaily.com/releases/2014/12/141229152226.htm
In a study published in the Dec. 29 online early edition of the Proceedings of the National Academy of Sciences, the scientists found that feeding Neu5Gc to mice engineered to be deficient in the sugar (like humans) significantly promoted spontaneous cancers. The study did not involve exposure to carcinogens or artificially inducing cancers, further implicating Neu5Gc as a key link between red meat consumption and cancer.
"Until now, all of our evidence linking Neu5Gc to cancer was circumstantial or indirectly predicted from somewhat artificial experimental setups," said principal investigator Ajit Varki, MD, Distinguished Professor of Medicine and Cellular and Molecular Medicine and member of the UC San Diego Moores Cancer Center. "This is the first time we have directly shown that mimicking the exact situation in humans -- feeding non-human Neu5Gc and inducing anti-Neu5Gc antibodies -- increases spontaneous cancers in mice."
Varki's team first conducted a systematic survey of common foods. They found that red meats (beef, pork and lamb) are rich in Neu5Gc, affirming that foods of mammalian origin such as these are the primary sources of Neu5Gc in the human diet. The molecule was found to be bio-available, too, meaning it can be distributed to tissues throughout the body via the bloodstream.
The researchers had previously discovered that animal Neu5Gc can be absorbed into human tissues. In this study, they hypothesized that eating red meat could lead to inflammation if the body's immune system is constantly generating antibodies against consumed animal Neu5Gc, a foreign molecule. Chronic inflammation is known to promote tumor formation.
To test this hypothesis, the team engineered mice to mimic humans in that they lacked their own Neu5Gc and produced antibodies against it. When these mice were fed Neu5Gc, they developed systemic inflammation. Spontaneous tumor formation increased fivefold and Neu5Gc accumulated in the tumors.
"The final proof in humans will be much harder to come by," Varki said. "But on a more general note, this work may also help explain potential connections of red meat consumption to other diseases exacerbated by chronic inflammation, such as atherosclerosis and type 2 diabetes.
"Of course, moderate amounts of red meat can be a source of good nutrition for young people. We hope that our work will eventually lead the way to practical solutions for this catch-22."
參考譯文：
長期以來，大量可重復的流行病學資料顯示，人類長期食用哺乳動物源“紅肉”（牛肉、豬肉和羊肉等）增加癌癥發生風險。雖然，迄今已經有多種理論被提出試圖用來解釋這種現象，但是都沒有被最終證實。
12月29日發表在美國國家科學院院刊網絡版上的一項研究中，科學家發現，給經過基因工程改造象人類一樣存在Neu5Gc缺陷的小鼠喂食非人類唾液酸N-羥乙酰神經氨酸（Neu5Gc）顯著促進癌癥發生。該研究中由于實驗小鼠沒有涉及致癌物質暴露或人工誘導腫瘤，進一步提示Neu5Gc可能是紅肉消費和癌癥之間關聯的一個關鍵因素。
加州大學圣迭戈穆爾斯癌癥研究中心首席研究員阿吉特•瓦爾基博士領導的研究團隊首先對人類常見食物系統進行篩查。他們發現，哺乳動物源性紅肉含有豐富的Neu5Gc，而這種糖分子物質容易被人體吸收，口服后生物利用度高，可以通過血液分布到整個身體組織。
因此，研究人員推測，由于人類缺乏Neu5Gc，那么被人踢吸收后可能坐位一種外源性抗原激發人體免疫反應而引發炎癥反應。而慢性炎癥是已知的一種致癌因素。
為了驗證這一假設，研究團隊利用基因工程技術改造出模擬人體的Neu5Gc缺陷小鼠。由于這些小鼠缺乏Neu5Gc，喂食它們Neu5Gc后激發了全身炎癥反應，自發性腫瘤的發生增加了五倍，而且腫瘤組織內富集Neu5Gc存在。
“雖然難以在人類獲得最終的證實，但是在更廣泛的意義上，這項工作也有助于解釋紅肉消費與其他可以由慢性炎癥加重的其他疾病，如動脈粥樣硬化和2型糖尿病等之間潛在的聯系。”瓦爾基博士說。
原始來源：http://www.sciencedaily.com/releases/2014/12/141229152226.htm
