刘梦奇, 2019年胰腺癌研究及诊疗新进展 SMAD4阴性的胰腺癌患者。 [6 BRUSSELAERS N SADR-AZODI O ENGSTRAND L Long- 3.7光疗 term proton pump inhibitor usage and the association with pancreatic cancer in Sweden [J].J Gastroenterol. 2019. 来自英国的 Garcia-Lopez等(0)先前报道了通 L Epub ahead of print 过紫外光激发的合成分子纳米机器通过单向旋转[7]LUM.Ⅱs.xUW,eta. ABO blood group and the risk of 在活细胞上产生纳米机械作用,以通过其在细胞 pancreatic neoplasms in Chinese Han population: a study at Shanghai Pancreatic Cancer Institute [J]. Pancreas. 2019 膜上钻孔来杀死细胞。近期通过技术改进,他们 48(9:c65-66 研发了新的可以通过波长较长的可见光激发的合[8] BEEGHLY- FADIEL A. LUU HN, DU L. et al. Early onset 成分子纳米机器,并且在基因工程胰腺癌小鼠模 pancreatic malignancies: clinical characteristics and survival 型中取得了良好效果;同时消除了继发性的紫外 associations[J].Int J Cancer, 2016. 139(10):2169-2177. [9 BEN-AHARON I. ELKABETS M. PELOSSOF R et al 线照射引起的损伤。这种通过机械作用杀死 Genomic landscape of pancreatie adenocareinoma in younger 癌细胞的治疗方式不会引起细胞出现抗性,有望 versus older patients: does age matter? Clin Cancer Res 在将来应用于临床实际中,为胰腺癌的治疗提供 019,2507):2185-2193. 10] SOUDER D C, ANDERSON R M. An expanding GSK3 network: 种新的手段。 plications for aging research [J]. Geroscience, 2019. 41(4) 3.8社会经济状况 369-382 既往有研究认为,胰腺癌患者较低的社会 [11 KIM Y M SEO Y H, PARK C B et al. Roles of GSK3 in metabolic shift toward abnormal anabolism in cell 经济状况会导致较为消极的治疗,并进一步导 [J]. Ann y Acad sci,2010,1201:65-71 致更差的预后。而在最新的一项研究中, Powers[12] THOMAS H.I-6 drives niche formation in pancreatic eancer 等321通过对1552例胰腺癌患者进行回顾性分析 liver metastasis [J]. Nat Rev Gastroenterol Hepatol, 2019 165):263 发现,社会经济状况与患者所接受的治疗措施及 [13] LAW H C. LAGUNDZIN D. CLEMENT E et al. The 其预后并无关系,这提示在施行标准化临床路径 proteomic landscape of pancreatic ductal adenocarcinoma liver 的大体量胰腺中心接受治疗可以在一定程度上抵 identifies molecular subtypes and associations with 消患者因社会经济水平造成的治疗和预后差异。 clinical response [J]. Clin Cancer Res, 2019. Epub ahead 4结语 [14 ZHOU J. ZHANG L, ZHENG H. et al. Identifieation of 胰腺癌恶性程度高,病情进展快,预后极 chemoresistance-related mRNAs based on gemcitabine- 差;并且发病率和致死率均呈逐年上升趋势。尽 resistant pancreatic cancer cell lines [J]. Cancer Med. 2019 Epub ahead of print j 管进展缓慢,但随着对胰腺癌分子生物学和临床[15」 JIANG Y,HER.IANG.ea. Transcription factor NFAT 病理学特征研究的不断深人,相信胰腺癌精准 contributes to the glycolytic phenotype rewiring and pancreatic 化、个体化治疗的时代会早日到来 cancer progression via transcription of PGK1 [J].Cell Death Dis,2019.10(12):948 [16] LIANG C, SHIS, QIN Y, et al. Localisation of PGKI determines [参考文献] metabolie phenotype to balance metastasis and proliferation in 1 SIEGEL R L MILLER K D, JEMAL A Cancer statistics, 2019 ts with SMAD4-negative pancreatic eancer [J].Gut [JJ. CA Cancer JClin, 2019, 69(1):7-34 Epub ahead of print] [2] FERLAY J ERVIK M. LAM F et al. Global cancer observatory: Z. LIU Q. wU J. et al. Fibroblast activation protein cancertoday[Eb/oL].http://gco.iare.fr/today,2018. alpha-positive pancreatic stellate cells promote the migration [3 FENG R M. ZONG Y N, CAO S M. et al. Current cancer and invasion of pancreatic cancer by CXCLl-mediated Akt situation in China: good or bad news from the 2018 Global phosphorylation [J].Ann Transl Med,2019.7(20): 532. Cancer Statistics? [J]. Cancer Commun(Lond), 2019, 39(1): [18] FAN CS, CHEN LL, HSU T A, et al. Endothelial-mesenchymal transition harnesses HSP90 alpha-secreting M2-macrophages [4 VINCENT A. HERMAN J SCHULICK R et al.Pancreatic to exacerbate pancreatie ductal adenocareinoma [J].J cancer[J]. Lancet.2011.378(9791):607-620 Hematol OncoL. 2019. 12(1): 138. [5] HUANG B Z PANDOL S J JEON C Y, et al. New-onset [19] ELYADA E, BOLISETTY M LAISE P, et al. Cross-species diabetes, longitudinal trends in metabolic markers, and risk of single-cell analysis of pancreatic ductal adenocarcinoma reveals pancreatie cancer in a heterogeneous population [J].Clin antigen-presenting cancer-associated fibroblasts [J].Cancer Gastroenterol Hepatol, 2019. Epub ahead of print Discov,2019,9(8:1102-1123.8 SMAD4阴性的胰腺癌患者。 3.7 光疗 来自英国的García-López等［50］先前报道了通 过紫外光激发的合成分子纳米机器通过单向旋转 在活细胞上产生纳米机械作用，以通过其在细胞 膜上钻孔来杀死细胞。近期通过技术改进，他们 研发了新的可以通过波长较长的可见光激发的合 成分子纳米机器，并且在基因工程胰腺癌小鼠模 型中取得了良好效果；同时消除了继发性的紫外 线照射引起的损伤［51］。这种通过机械作用杀死 癌细胞的治疗方式不会引起细胞出现抗性，有望 在将来应用于临床实际中，为胰腺癌的治疗提供 一种新的手段。 3.8 社会经济状况 既往有研究认为，胰腺癌患者较低的社会 经济状况会导致较为消极的治疗，并进一步导 致更差的预后。而在最新的一项研究中，Powers 等［52］通过对1 552例胰腺癌患者进行回顾性分析 发现，社会经济状况与患者所接受的治疗措施及 其预后并无关系，这提示在施行标准化临床路径 的大体量胰腺中心接受治疗可以在一定程度上抵 消患者因社会经济水平造成的治疗和预后差异。 4 结语 胰腺癌恶性程度高，病情进展快，预后极 差；并且发病率和致死率均呈逐年上升趋势。尽 管进展缓慢，但随着对胰腺癌分子生物学和临床 病理学特征研究的不断深入，相信胰腺癌精准 化、个体化治疗的时代会早日到来。 ［参 考 文 献］ ［1］ SIEGEL R L, MILLER K D, JEMAL A. Cancer statistics, 2019 ［J］. CA Cancer J Clin, 2019, 69(1): 7-34. ［2］ FERLAY J, ERVIK M, LAM F, et al. Global cancer observatory: cancer today［EB/OL］. http://gco.iarc.fr/today, 2018. ［3］ FENG R M, ZONG Y N, CAO S M, et al. Current cancer situation in China: good or bad news from the 2018 Global Cancer Statistics?［J］. Cancer Commun (Lond), 2019, 39(1): 22. ［4］ VINCENT A, HERMAN J, SCHULICK R, et al. Pancreatic cancer［J］. Lancet, 2011, 378(9791): 607-620. ［5］ HUANG B Z, PANDOL S J, JEON C Y, et al. New-onset diabetes, longitudinal trends in metabolic markers, and risk of pancreatic cancer in a heterogeneous population［J］. Clin Gastroenterol Hepatol, 2019. ［Epub ahead of print］ ［6］ BRUSSELAERS N, SADR-AZODI O, ENGSTRAND L. Long￾term proton pump inhibitor usage and the association with pancreatic cancer in Sweden［J］. J Gastroenterol, 2019. ［Epub ahead of print］ ［7］ LIU M, JI S, XU W, et al. ABO blood group and the risk of pancreatic neoplasms in Chinese Han population: a study at Shanghai Pancreatic Cancer Institute［J］. Pancreas, 2019, 48(9): e65-e66. ［8］ BEEGHLY-FADIEL A, LUU HN, DU L, et al. Early onset pancreatic malignancies: clinical characteristics and survival associations［J］. Int J Cancer, 2016, 139(10): 2169-2177. ［9］ BEN-AHARON I, ELKABETS M, PELOSSOF R, et al. Genomic landscape of pancreatic adenocarcinoma in younger versus older patients: does age matter?［J］. Clin Cancer Res, 2019, 25(7): 2185-2193. ［10］ SOUDER D C, ANDERSON R M. An expanding GSK3 network: implications for aging research［J］. Geroscience, 2019, 41(4): 369-382. ［11］ KIM Y M, SEO Y H, PARK C B, et al. Roles of GSK3 in metabolic shift toward abnormal anabolism in cell senescence ［J］. Ann N Y Acad Sci, 2010, 1201: 65-71. ［12］ THOMAS H. IL-6 drives niche formation in pancreatic cancer liver metastasis［J］. Nat Rev Gastroenterol Hepatol, 2019, 16(5): 263. ［13］ LAW H C, LAGUNDZIN D, CLEMENT E J, et al. The proteomic landscape of pancreatic ductal adenocarcinoma liver metastases identifies molecular subtypes and associations with clinical response［J］. Clin Cancer Res, 2019. ［Epub ahead of print］ ［14］ ZHOU J, ZHANG L, ZHENG H, et al. Identification of chemoresistance-related mRNAs based on gemcitabine￾resistant pancreatic cancer cell lines［J］. Cancer Med, 2019. ［Epub ahead of print］ ［15］ JIANG Y, HE R, JIANG Y, et al. Transcription factor NFAT5 contributes to the glycolytic phenotype rewiring and pancreatic cancer progression via transcription of PGK1［J］. Cell Death Dis, 2019, 10(12): 948. ［16］ LIANG C, SHI S, QIN Y, et al. Localisation of PGK1 determines metabolic phenotype to balance metastasis and proliferation in patients with SMAD4-negative pancreatic cancer［J］. Gut, 2019. ［Epub ahead of print］ ［17］ WEN Z, LIU Q, WU J, et al. Fibroblast activation protein alpha-positive pancreatic stellate cells promote the migration and invasion of pancreatic cancer by CXCL1-mediated Akt phosphorylation［J］. Ann Transl Med, 2019, 7(20): 532. ［18］ FAN C S, CHEN L L, HSU T A, et al. Endothelial-mesenchymal transition harnesses HSP90 alpha-secreting M2-macrophages to exacerbate pancreatic ductal adenocarcinoma［J］. J Hematol Oncol, 2019, 12(1): 138. ［19］ ELYADA E, BOLISETTY M, LAISE P, et al. Cross-species single-cell analysis of pancreatic ductal adenocarcinoma reveals antigen-presenting cancer-associated fibroblasts［J］. Cancer Discov, 2019, 9(8): 1102-1123. 刘梦奇，等  2019年胰腺癌研究及诊疗新进展