The PD-1 is encoded by the PDCD1 ge

The PD-1 is encoded by the PDCD1 gene. It is primarily expressed by activated T-cells as negative costimulatory receptor; binding of PD-1 to its ligands, PD-L1 and PD-L2, downregulates T-cells and the immune system[55,56]. Many tumor cells express PD-L1 and PD-L2 which is a mechanism which allows escape from immune destruction of the tumor cells. Pembrolizumab is an antiPD-1 antibody that is approved for use in metastatic melanoma and metastatic non-small cell lung cancer and is currently under study for other malignancies, and PD-L1 expression may be a potential marker for efficacy of anti-PD-1 studies for pancreatic cancer. Elevated CRP levels in the plasma, a well-established marker of inflammation, at diagnosis correlate with higher tumor stage and grading and poorer clinical outcome in pancreatic cancer[57]. Patients with CRP greater than 13 mg/L had improved survival with ruxolitinib and capecitabine compared to capecitabine and placebo in a randomized phase Ⅱ study also known as the RECAP study enrolling 127 patients with metastatic pancreatic cancer (median overall survival of 83 d vs 55 d, P = 0.01)[58]. The CRP level could be a useful marker for patient stratification in the management of pancreatic cancer, and the JAK inhibitor ruxolitinib may improve clinical outcome in patients with elevated CRP. An ongoing phase Ⅲ study, known as JANUS 2, is examining these promising leads as a second-line setting in patients with advanced pancreatic cancer[59]. There is high prevalence of BRCA1/2 mutations in Ashkenazi Jewish with pancreatic cancer[60]. The BRCA1 and BRCA2 gene encodes large proteins that coordinate the homologous recombination repair double strand breaks (DSBs) pathway. Poly ADP-ribose polymerases (PARP) are a family of nuclear enzymes that regulates the repair of DNA single-strand breaks through the baseexcision repair (BER) pathway. Since BRCA1/2-mutated tumors cannot utilize homologous recombination to repair DSBs, exposing these cells to PARP inhibitor, which shuts down BER rescue pathway, will lead to accumulation of DNA damage, genomic instability and cell death, also known as synthetic lethality[61]. Investigators from Memorial Sloan-Kettering Cancer Center have reported high response rate with combination of gemcitabine, cisplatin and veliparib, a PARP inhibitor, as firstline treatment in patients with andvanced pancreatic cancer and mutant BRCA[62]. Ongoing phase Ⅱ randomized study comparing gemcitabine and cisplatin with and without veliparib is currently underway (NCT01585805). This study will most likely provide us the information on using BRAC mutation as a biomarker for personalized treatment.

結果 (中文) 1:

PD-1 是由 PDCD1 基因编码的。它主要是由活化的 T 细胞表示为消极刺激的受体;PD 1 绑定到其配体、 PD L1 和 PD L2、 下调 T 细胞和免疫系统 [55,56]。许多肿瘤细胞表达 pd-l1 和 pd-l2 是一种允许逃避免疫破坏肿瘤细胞的机制。Pembrolizumab 是 antiPD-1 抗体，批准用于转移性黑色素瘤转移性非小细胞肺癌，目前正在研究其他恶性肿瘤和 pd-l1 表达可能是一个潜在标记抗 PD 1 研究胰腺癌的疗效。等离子，既定的炎症标志物，在诊断与较高的肿瘤分期和分级与胰腺癌 [57] 穷临床结局的 CRP 水平升高。患者 CRP 大于 13 毫克/升改善了生存与 ruxolitinib 和卡培他滨与卡培他滨和安慰剂的 ⅱ 期临床研究也被称为相比概括研究招生 127 例转移性胰腺癌 (中位总生存期的 83 d vs 55 d，P = 0.01) [58]。CRP 水平可能是一个有用标志物在胰腺癌，管理对病人进行分层和 JAK 抑制剂 ruxolitinib 可以提高反应蛋白升高患者的临床疗效。正在进行的阶段 ⅲ，称为 JANUS 2，正在研究这些有价值的线索作为第二线的设置，在患者晚期胰腺癌 [59]。还有高患病率的 BRCA1/2 突变的德系犹太人犹太与胰腺癌 [60]。BRCA1 和 BRCA2 基因编码协调同源重组修复双链断裂 （双链断裂） 通路的大型蛋白质。聚 ADP-核糖聚合酶 (PARP) 是一个家庭的核酶调节通过 baseexcision (BER) 修复通路的 DNA 单链断裂的修复。由于 BRCA1/2 突变的肿瘤不能利用同源重组修复双链断裂，揭露 PARP 抑制剂，它关闭 BER 救援通路，这些细胞将导致积累 DNA 损伤、 基因组不稳定性和细胞死亡，也被称为合成杀伤力 [61]。纪念斯隆-凯特琳癌症中心的研究人员报告说高响应率结合吉西他滨联合顺铂和 veliparib，PARP 抑制剂，作为一道防线 [62] BRCA 突变与赶超先进胰腺癌患者的治疗。正在进行二期随机研究比较吉西他滨与顺铂与无 veliparib 目前正在 (NCT01585805)。这项研究将最有可能提供我们信息 BRAC 突变作为生物标志物用于个性化治疗。

結果 (中文) 3:

PD-1是由PDCD1基因编码。它主要是由活化的T细胞共刺激受体表达阴性；PD-1及其配体结合，PD-L1和PD-L2，下调T细胞和免疫系统[对于]。许多肿瘤细胞表达PD-L1和PD-L2是一种机制，允许逃避免疫杀伤肿瘤细胞。Pembrolizumab是antipd-1抗体被批准用于转移性黑色素瘤和转移性非小细胞肺癌和其他恶性肿瘤是目前研究下，和PD-L1的表达可能为抗PD-1研究胰腺癌疗效的潜在标志物。在血浆中的C-反应蛋白水平升高，一个完善的炎症标志物，在诊断与更高的肿瘤分期和分级和较差的胰腺癌的临床结果[ 57 ]。CRP大于13 mg/L的患者改善与ruxolitinib与卡培他滨与卡培他滨和安慰剂的随机相位Ⅱ研究也称为RECAP研究纳入127例转移性胰腺癌的生存期（83 d和55 d，P = 0.01，中位生存期）[ 58 ]。CRP水平可作为胰腺癌的管理病人分层的有用标记，和JAK抑制剂ruxolitinib可提高CRP升高患者的临床结果。正在进行的一期Ⅲ研究，称为Janus 2，检查这些有希望的线索作为二线治疗晚期胰腺癌[ 59 ]。有胰腺癌[ 60 ]在德系犹太人BRCA1 / 2基因突变的发生率高。BRCA1和BRCA2基因编码的蛋白质大协调同源重组修复双链断裂（DSBs）通路。多聚ADP核糖聚合酶（PARP）是一个家庭的核的酶，调节DNA单链断裂修复通过baseexcision修复（BER）通路。由于BRCA1 / 2-mutated肿瘤不能利用同源重组修复DNA双链断裂，使这些细胞PARP抑制剂，即关闭BER救援通路，会导致DNA损伤的积累，基因组不稳定和细胞死亡，也被称为合成致死[ 61 ]。从纪念斯隆-凯特琳癌症中心的研究者报道的高响应率联合吉西他滨，顺铂和Veliparib，PARP抑制剂，与晚期胰腺癌和突变的BRCA [ 62 ]患者的一线治疗。持续的阶段Ⅱ随机对照研究比较吉西他滨联合顺铂与无veliparib-正在进行中（nct01585805）。本研究将最有可能为我们提供使用BRAC突变作为个体化治疗的生物标志物的信息。