1. 第一部分（40分）
The tumor-associated microenvironment, which consists of extracellular matrix (ECM), cancer-associated fibroblasts (CAFs), inflammatory immune cells, and tumor-associated vasculature, plays a critical role during tumorigenesis. CAFs, which are abundant in tumor-associated stroma, secrete several factors, including HGF and SDF1, to promote epithelial cell neoplastic transformation and cancer cell proliferation. In addition, CAFs interact with other stromal components to stimulate tumor-enhancing inflammation and angiogenesis. Moreover, ECM remodeling by CAFs is essential for tumor cell invasion and metastasis. Although CAFs are important constituents of the tumor stroma, the paracrine signals that mediate direct crosstalk between CAFs and tumor cells in metastasis are poorly understood.
Exosomes are membrane vesicles that originate in large multivesicular bodies (MVBs) and are released in the extracellular milieu upon fusion of MVBs with the plasma membrane. Exosomes have the same topology as a cell and contain a broad array of biologically active material. Several cellular components of the tumor microenvironment and cancer cells secrete exosomes that function in an autocrine or paracrine manner to promote tumor-induced immune suppression, angiogenesis, and premetastatic niche formation. Currently, it is unknown whether CAFs secrete exosomes and whether these microvesicles support cancer cell metastasis.
2. 第二部分（20分）
Because the spectrum of cancer care includes screening as well as treatment, a comprehensive understanding of breast cancer cost must incorporate the cost of screening and associated workup. While the body of evidence concerning Medicare expenditures for cancer treatment has grown, relatively little is known about cost associated with screening Medicare beneficiaries for breast cancer. This is especially important among older women because recent guidelines have concluded that there is insufficient evidence to assess the benefits and harms of screening mammography in women 75 years or older.
It is particularly timely to consider the cost implications of breast cancer screening because newer breast cancer screening technologies, such as digital mammography and computer-aided detection (CAD), have expanded the options available to clinicians and are diffusing into clinical practice. The adoption of these new technologies can increase costs directly through reimbursement for the tests and also lead to higher rates of supplementary imaging, biopsy, or cancer detection. It is critical to assess the relation between screening expenditures and population outcomes since newer modalities can increase cancer detection rates but may not improve patient outcomes, particularly among older women.
Ideally, higher breast cancer screening expenditures at the population level should correspond to earlier stage at diagnosis, lower treatment cost, or both. This can be evaluated by comparing differences in screening cost and cancer outcomes across geographic regions, hypothesizing that women living in regions that
“invest” more in screening services may be less likely to be diagnosed at a later stage. However, in actual practice, it is unclear whether higher screening costs are associated with earlier stage at diagnosis or lower cancer treatment costs at the population level. To address these knowledge gaps, we estimated national breast cancer screening and treatment costs in the Medicare fee-for-service program. Our second objective was to assess regional variation in breast cancer screening cost, while our third objective was to determine the association between regional screening cost and breast cancer incidence and treatment costs. These data will inform clinicians and policy makers in a context of debate about Medicare reimbursement for various cancer screening modalities and concerns about growth in cancer expenditures.
3. 第三部分（20分）
The Nobel Assembly at Karolinska Institutet has today decided to award: The Nobel Prize in Physiology or Medicine 2012 jointly to-John B. Gurdon and Shinya Yamanaka(山中伸弥) for the discovery that mature cells can be reprogrammed to become pluripotent.
Summary
The Nobel Prize recognizes two scientists who discovered that mature, specialised cells can be reprogrammed to become immature cells capable of developing into all tissues of the body. Their findings have revolutionised our understanding of how cells and organisms develop. John B. Gurdon discovered in
1962 that the specialisation of cells is reversible. In a classic experiment, he replaced the immature cell nucleus in an egg cell of a frog with the nucleus from a mature intestinal cell. This modified egg cell developed into a normal tadpole. The DNA of the mature cell still had all the information needed to develop all cells in the frog.
Shinya Yamanaka discovered more than 40 years later, in 2006, how intact mature cells in mice could be reprogrammed to become immature stem cells. Surprisingly, by introducing only a few genes, he could reprogram mature cells to become pluripotent stem cells, i.e. immature cells that are able to develop into all types of cells in the body. These groundbreaking discoveries have completely changed our view of the development and cellular specialisation. We now understand that the mature cell does not have to be confined forever to its specialised state. Textbooks have been rewritten and new research fields have been established. By reprogramming human cells, scientists have created new opportunities to study diseases and develop methods for diagnosis and therapy.
Life, a journey towards increasing specialization. All of us developed from fertilized egg cells. During the first days after conception, the embryo consists of immature cells, each of which is capable of developing into all the cell types that form the adult organism. Such cells are called pluripotent stem cells. With further development of the embryo, these cells give rise to nerve cells, muscle cells, liver cells and all other cell types - each of them specialised to carry out a specific task in the adult body. This journey from immature to specialized cell was previously considered to be unidirectional. It was thought that the cell changes in such a way
during maturation that it would no longer be possible for it to return to an immature, pluripotent stage. Frogs jump backwards in development John B. Gurdon challenged the dogma that the specialised cell is irreversibly committed to its fate. He hypothesized that its genome might still contain all the information needed to drive its development into all the different cell types of an organism. In 1962, he tested this hypothesis by replacing the cell nucleus of a frog's egg cell with a nucleus from a mature, specialized cell derived from the intestine of a tadpole. The egg developed into a fully functional, cloned tadpole and subsequent repeats of the experiment yielded adult frogs. The nucleus of the mature cell had not lost its capacity to drive development to a fully functional organism.
Gurdon's landmark discovery was initially met with skepticism but became accepted when it had been confirmed by other scientists. It initiated intense research and the technique was further developed, leading eventually to the cloning of mammals. Gurdon's research taught us that the nucleus of a mature, specialized cell can be returned to an immature, pluripotent state. But his experiment involved the removal of cell nuclei with pipettes followed by their introduction into other cells. Would it ever be possible to turn an intact cell back into a pluripotent stem cell? A roundtrip journey–mature cells return to a stem cell state. Shinya Yamanaka was able to answer this question in a scientific breakthrough more than 40 years after Gurdon´s discovery. His research concerned embryonal stem cells, i.e. pluripotent stem cells that are isolated from the embryo and cultured in the laboratory. Such stem cells were initially isolated from mice by Martin Evans (Nobel Prize 2007) and Yamanaka tried to find the genes that kept them immature. When several of these genes had been identified,
he tested whether any of them could reprogram mature cells to become pluripotent stem cells. Yamanaka and his co-workers introduced these genes, in different combinations, into mature cells from connective tissue, fibroblasts, and examined the results under the microscope. They finally found a combination that worked, and the recipe was surprisingly simple. By introducing four genes together, they could reprogram their fibroblasts into immature stem cells!
The resulting induced pluripotent stem cells (iPS cells) could develop into mature cell types such as fibroblasts, nerve cells and gut cells. The discovery that intact, mature cells could be reprogrammed into pluripotent stem cells was published in 2006 and was immediately considered a major breakthrough. From surprising discovery to medical use The discoveries of Gurdon and Yamanaka have shown that specialized cells can turn back the developmental clock under certain circumstances. Although their genome undergoes modifications during development, these modifications are not irreversible. We have obtained a new view of the development of cells and organisms. Research during recent years has shown that iPS cells can give rise to all the different cell types of the body. These discoveries have also provided new tools for scientists around the world and led to remarkable progress in many areas of medicine. iPS cells can also be prepared from human cells. For instance, skin cells can be obtained from patients with various diseases, reprogrammed, and examined in the laboratory to determine how they differ from cells of healthy individuals. Such cells constitute invaluable tools for understanding disease mechanisms and so provide new opportunities to develop medical therapies.
Sir John B. Gurdon was born in 1933 in Dippenhall, UK. He received his Doctorate from the University of Oxford in 1960 and was a postdoctoral fellow at California Institute of Technology. He joined Cambridge University, UK, in 1972 and has served as Professor of Cell Biology and Master of Magdalene College. Gurdon is currently at the Gurdon Institute in Cambridge. Shinya Yamanaka was born in Osaka, Japan in 1962. He obtained his MD in 1987 at Kobe University and trained as an orthopaedic surgeon before switching to basic research. Yamanaka received his PhD at Osaka City University in 1993, after which he worked at the Gladstone Institutes in San Francisco, USA and Nara Institute of Science and Technology in Japan. Yamanaka is currently Professor at Kyoto University, where he directs its Center for iPS Research and Application. He is also a senior investigator at the Gladstone Institutes.
二、汉译英（20分，要求精准翻译）
1．Toru Aoyama博士最终认为，对2/3期接受D2胃切除术的胃癌患者，体重减轻为通过S-1辅助化疗依从性最重要的风险因素。该项研究同时强调，对于因晚期胃癌并接受胃切除术的患者，需要针对围手术期营养干预进行更加深入的研究。（5分）
2．流感已进入高峰期，未来一段时期内将维持在较高的活动水平。现阶段主要是甲型Ｈ１Ｎ１流感病毒和甲型Ｈ３Ｎ２亚型流感病毒共同流行，且甲型Ｈ１Ｎ１流感病毒逐渐转变为主导毒株。（5分）
3. 约有700,000名患者接受原发性肿瘤切除术后，其中近一半会在某个时间点出现复发，并且很多这类患者最终因为原发病而死亡。与传统观点不同的是，宾夕法尼亚大学佩
雷尔曼（Perelman）医学院的研究人员在动物模型上证实，复发肿瘤侵袭性的增强或许是由于机体免疫系统的改变而导致的。（5分）
4. 心脏骤停后常常使用低温疗法进行脑保护，不少患者也会出现抽搐的表现。该研究旨在探索脑电图（EEG）分级评分的预后价值以及在心脏骤停后低温治疗（TH）和复温（NT）治疗中根据持续脑电图（cEEG）的发现治疗抽搐的临床转归。然而研究发现治疗抽搐并不能改善临床转归。（5分）
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