事件记录
播音员: Examining the latest research and telling you about the latest breakthroughs. 科学研究节目在电视上播出.
主持人: Only 15% of patients with squamous cell lung cancer survive to five years past their diagnosis. 这是一种很难治疗的癌症. 我的客人，博士. Trudy Oliver has developed a new tool for understanding the disease and developing targeted therapies.
Dr. 奥利弗，你开发了一种肺鳞状细胞癌的小鼠模型. 为什么这很重要？?
Dr. 特鲁迪奥利弗: This is really important because, up until now, we've known very little about this disease. Most patients with squamous cell carcinoma are treated with chemotherapy and when that doesn't work, 病人真的没有任何二线治疗. 而对于其他类型的肺肿瘤, 在过去的10到20年里, there've been tremendous advancements in developing targeted therapies and we really lack these targeted therapies for squamous cell carcinoma of the lung and one of the reasons why our understanding of this disease has lagged behind is because we don't have good model systems.
主持人: And in the process of making this model for lung squamous cell carcinoma you've made some important discoveries about what triggers formations of these tumors.
Dr. 特鲁迪奥利弗: 这是正确的. So in 2011 a group called the Cancer Genome Atlas sequenced about 200 human squamous tumors and in that process they discovered the genes that are most frequently altered in the disease, 其中一种叫做SOX2 . So SOX2 is frequently overexpressed or highly expressed in the human squamous tumors and so we took a unique approach to use viruses to deliver genes to the mouse lung that we think are important drivers of the disease. And so we put SOX2 in viruses and delivered them to the mouse lung by having the mice inhale the viruses and the viruses then allow the expression of SOX2 in the mouse lung. This in combination with other - specific other hits in the lung that we engineered - led to the exclusive development of squamous lung tumors.
主持人: 当你在老鼠身上做实验时, 我的意思是, did you think it would work or did you think it would work as well as it did? 我的意思是我不知道. 这对我来说很神奇.
Dr. 特鲁迪奥利弗: 感觉就像... and that's probably why it was so exciting is it definitely felt 就像 this is a longshot and part of the reason why it was a longshot was our approach. So we knew that these genes were important and we knew that if we made genetically engineered mice, 这需要花费成千上万美元，并且需要数年的时间来开发, we believed we'd ultimately have a model but we didn't know what combination to use.
主持人: 哦，我明白了.
Dr. 特鲁迪奥利弗: 所以实际, to test every important combination would take millions of dollars and five, 十年了，我知道我负担不起. 所以大发娱乐说的是长远目标, let's take advantage of these viruses that will allow us to develop - to deliver many genes in a short amount of time with a lot less money but, 从技术上讲, 传递这些基因不是一件容易的事. So we infected a lot of mice with a lot of genes in different combinations and then we monitored the mice by micro-CT imaging.
So we actually have a device where you put a mouse on a little bed that rotates in a machine and then we get 3-D images of what's going on in the lung. 他们是小. 如果你看看你的拇指, the mouse lung is really no bigger than the end of your thumb and the first time we saw a big mass in the lung was thrilling.
主持人: 是的.
Dr. 特鲁迪奥利弗: The whole lab was excited and screaming and running around high-fiving each other. 看看肺里的这个斑点. And once we started seeing the second tumor and the third tumor, we knew we were on to something.
主持人: 那么老鼠身上的肿瘤和人类的有多相似呢?
Dr. 特鲁迪奥利弗: 它们非常相似. 事实上, 我会说病理学家, 在显微镜下观察大发娱乐的肿瘤, 不知道是老鼠的吗. 他们会认为他们在研究人类疾病. So they visually look 就像 human tumors and then when we stain them for biomarkers of the human disease, 用什么来诊断这是人类鳞状肿瘤, 大发娱乐的小鼠肿瘤会因为这些标记而亮起来.
主持人: 在你的模型中，你实际上结合了基因表达的两种变化? 这是SOX2的变化，然后是另一个基因的变化...
Dr. 特鲁迪奥利弗: 这是正确的.
主持人: Lkb1.
Dr. 特鲁迪奥利弗: So SOX2 expression alone in the mouse lung doesn't really do anything in terms of cancer. But what we found is that when we combine that with loss of this gene called Lkb1, 这也被称为肿瘤抑制因子, 大发娱乐发现这导致了肺鳞状细胞瘤.
主持人: So help me understand how, 就像, if someone were to develop this kind of cancer, how it might happen. 他们会先遗传其中一个突变还是你不知道, 的, 导致这些变化和肿瘤形成的一系列事件?
Dr. 特鲁迪奥利弗: 所以大发娱乐知道在很多癌症病例中, 仅仅有一个基因变化并不足以产生肿瘤. It usually requires two or three or seven hits, as we call it, to - for cancer to develop. 大发娱乐知道在大发娱乐的环境中有很多东西容易导致癌症. Smoking is definitely one of the biggest risk factors for lung cancer but there're other things, 就像, 石棉暴露, 氡接触, 这在犹他州很常见吗. 不良的饮食习惯, 缺乏锻炼, any of these things can lead to cell stress in the body and when we undergo any kind of cell stress, which could be from our environment but could be just the internal workings of our cells, 这可能导致突变.
主持人: 你现在打算怎么处理这个模型?
Dr. 特鲁迪奥利弗: 好吧, this model is really the first step now to begin to understand the disease 就像 we've wanted to do and so there are so many exciting things that we can use this model for. One of which is to really understand what is the cell of origin of this tumor. 这些攻击是什么类型的肺细胞, SOX2和Lkb损失, 导致了这种特殊肿瘤类型的发展?
The second thing that we can ask, that I'm really excited about, is what therapies work. 大发娱乐可以用老鼠来测试新的疗法, novel combinations of therapies and we can do this in a way that would be impossible to do in humans. 这是大发娱乐做过的最激动人心的事. Now that we have a model it just unleashes so many questions that we can ask to gain a better understanding of the disease.
播音员: 有趣的. 信息丰富的. 而这一切都是为了更好的健康. 大发娱乐是Scope健康科学广播.