大家好，本期文献翻译带练专栏主题都是癌症治疗相关，是当前科研热点之一呢，21年也考察过癌症相关主题，可以留意一下。
文献翻译带练21 Cancer & Molecular targeted therapy
As a major branch of the protein kinase family, protein tyrosine kinases, transfer the γ-phosphate group on adenosine triphosphate(ATP) to the tyrosine residues of many key proteins, and subsequently completes the transmission of information between cells through the phosphorylation of phenolic hydroxy groups, which play a vital role in cell growth, regulation, and differentiation, migration, and apoptosis of tumor cells. As a crucial node of cell information transmission, the abnormal expression of protein tyrosine kinases can affect the correct activation of its downstream signaling pathway, which, in turn, causes the dysregulation of cell proliferation, thereby leading to a series of diseases.
参考答案：作为蛋白激酶家族的一个主要分支，蛋白酪氨酸激酶将三磷酸腺苷（ATP）上的γ-磷酸基团转移到许多关键蛋白质的酪氨酸残基，然后通过酚羟基的磷酸化完成细胞间的信息传递，在肿瘤细胞的生长、调节、分化、迁移和凋亡中起着至关重要的作用。作为细胞信息传递的关键节点，蛋白酪氨酸激酶的异常表达会影响其下游信号通路的正确激活，进而导致细胞增殖失调，从而导致一系列疾病。
The introduction of tyrosine kinase inhibitors (TKIs) substantially modified the treatment of patients with Chronic myeloid leukemia (CML). Imatinib mesylate, the first tyrosine kinase inhibitor approved by the Food and Drug Administration (FDA), is the first line of treatment for CML. Imatinib mesylate acts through competition for the ATP-binding site in the tyrosine kinase domain of ABL, inhibiting the ability of this protein to transfer ATP phosphate groups to tyrosine residues of target proteins, which is necessary for signal transduction for cell proliferation and apoptosis. Despite the therapeutic success of target therapy, the occurrence of resistance to imatinib mesylate has led to the development of second- and third-generation TKIs. Several studies are investigating resistance to imatinib, however no specific mechanism has been identified.
参考答案：酪氨酸激酶抑制剂（TKIs）的引入极大地改变了慢性粒细胞白血病（CML）患者的治疗。甲磺酸伊马替尼是美国食品和药物管理局（FDA）批准的第一种酪氨酸激酶抑制剂，是治疗慢性粒细胞白血病的一线药物。甲磺酸伊马替尼通过竞争ABL(注：ABL是一种原癌基因表达的蛋白)酪氨酸激酶结构域中的ATP结合位点发挥作用，抑制该蛋白将ATP磷酸基团转移到靶蛋白酪氨酸残基的能力，这是细胞增殖和凋亡信号转导所必需的。尽管靶向治疗取得了成功，但甲磺酸伊马替尼耐药性的出现促使了第二代和第三代TKI的发展。一些研究正在调查伊马替尼的耐药性，但尚未确定具体机制。
文献翻译带练22 Cancer & Immune checkpoint blockade immunotherapy
The programmed death (PD)-1/PD-ligand (PD-L) pathway and regulatory T cells(Tregs) are essential for the maintenance of immune tolerance. Their activation in the tumour microenvironment contributes to the evasion of the transformed cells from the immune surveillance and the suppression of an antitumour immune response. Therefore, PD-1/PD-L1 and Tregs are important targets for cancer immunotherapy.Immune checkpoint blockade immunotherapy is a promising strategy in cancer treatment. At present, the most intensively studied area in onco-immunology is therapy targeting programmed cell death protein1 (PD-1) and its ligand PD-L1. Therapy with these immune checkpoints has higher efficacy in treating inoperable, progressive or recurrent cancers than conventional therapies.
参考答案：程序性死亡受体-1/程序性死亡受体-配体通路(注：这里虽然没有受体receptor，但后有配体ligand，为了前后意思连贯，所以加个受体)与调节性T细胞(treg)是维持免疫耐受所必需的。在肿瘤微环境中，PD-1/PD-L通路和调节性T细胞有助于转化细胞逃避免疫监视和抑制抗肿瘤免疫反应。因此，PD-1/PD-L1和treg是癌症免疫治疗的重要靶点。免疫检查点阻断免疫疗法是一种很有前途的癌症治疗策略。目前，肿瘤免疫学研究最集中的领域是靶向PD-1及其治疗配体PD-L1。与传统疗法相比，使用这些免疫检查点疗法治疗无法手术的、进展性或复发性癌症的疗效更高。
The programmed death (PD)-1 is a type I transmembrane receptor of the immunoglobulin superfamily. PD-1 is responsible for the downregulation of T cell receptor (TCR) signalling.PD-1 expression appears on the surface of T cells during their thymic development and in the periphery after TCR stimulation and cytokine production. CD4-CD8- thymocytes, peripheral CD4+ and CD8+ T cells, B cells, monocytes, natural killer (NK) cells and dendritic cells (DCs) can express PD-1.PD-1 has two ligands: PD-L1 and PD-L2, of which PD-L1 is better studied and perceived as a potential target for immune response regulation.PD-L1 is expressed after antigenic stimulation on immune and non-immune cells,such as T cells, B cells, antigen-presenting cells (APCs),endothelial and epithelial cells.
参考答案：程序性死亡(PD)-1是免疫球蛋白超家族的I型跨膜受体。PD-1负责下调T细胞受体(TCR)信号转导。PD-1在T细胞胸腺发育过程中出现在T细胞表面，在TCR刺激和细胞因子产生后出现在T细胞外周。CD4-CD8-胸腺细胞、外周血CD4+和CD8+ T细胞、B细胞、单核细胞、自然杀伤细胞和树突状细胞均可表达PD-1。PD-1有两个配体PD-L1和PD-L2，其中PD-L1得到了较好的研究，被认为是调节免疫反应的潜在靶点。PD-L1在免疫细胞和非免疫细胞(如T细胞、B细胞、抗原提呈细胞、内皮细胞和上皮细胞)上经抗原刺激后表达。