目的:通过生物信息学分析以及细胞生物学实验研究角蛋白6A(KRT6A)对胰腺导管腺癌(PDAC)诊断、预后判断、免疫微环境以及PDAC细胞PANC1增殖、凋亡等生物学行为的影响。方法:通过GEPIA平台整合TCGA(The Cancer Genome Atlas)数据库与GTEx(...目的:通过生物信息学分析以及细胞生物学实验研究角蛋白6A(KRT6A)对胰腺导管腺癌(PDAC)诊断、预后判断、免疫微环境以及PDAC细胞PANC1增殖、凋亡等生物学行为的影响。方法:通过GEPIA平台整合TCGA(The Cancer Genome Atlas)数据库与GTEx(Genotype-Tissue)数据库中的数据,分析KTRT6A在PDAC组织中的表达情况,并通过CIBERSORT工具分析KRT6A表达与PDAC组织中免疫细胞浸润的关系,然后通过GSEA方法研究与KRT6A基因表达相关的肿瘤信号通路。选取长海医院病理科保存的60例PDAC组织与癌旁组织标本进行免疫组化分析,验证KRT6A在肿瘤组织中表达情况;通过干扰RNA敲减PANC1细胞中KRT6A的表达,采用CCK-8实验以及流式细胞术检测敲减KRT6A对细胞的增殖、凋亡的影响。结果:利用TCGA与GTEx数据库数据分析发现,KRT6A在人PDAC组织中呈高表达,且与患者较差的生存期存在关联(P=0.015)。利用CIBERSORT软件以及GSEA分析发现,KRT6A高表达的PDAC组织中M2型巨噬细胞浸润性升高(P=0.034),且与Wnt通路(NES:1.7359272,P<0.05)、磷酸戊糖途径(PPP)(NES:1.5613053,P<0.05)等信号通路上调有关联(P<0.05或P<0.01);免疫组化结果进一步验证了KRT6A在PDAC组织中呈高表达(P<0.001)。增殖和凋亡实验发现,干扰KRT6A能够显著抑制PANC1细胞的增殖(P<0.05)以及凋亡(P<0.001)。结论:KRT6A在人PDAC组织中呈高表达,敲减其表达能够抑制PANC1细胞的增殖和凋亡,具有作为PDAC诊断与预后判断新靶标的潜力。展开更多
Authors introduction： Qian Zhan, female, who was born in Sept, 1979. She studied in the Shanghai Second Medical University during 1998 to 2005. She majored in Clinical Medicine, and earned her master degree in 2005. ...Authors introduction： Qian Zhan, female, who was born in Sept, 1979. She studied in the Shanghai Second Medical University during 1998 to 2005. She majored in Clinical Medicine, and earned her master degree in 2005. In 2005, she went to the Beaujon Hospital of Paris 7th Universit3. in France, as a foreign intern. Later, she came to postgraduate work and residencies in the general surgery department of Shanghai Ruijin Hospital. Her clinical work is focused on multidisciplinary especially postoperative management for the patients with pancreatic cancer. In addition, she is a lead researcher in the pancreatic cancer group for nano based drug delivery, systems. Chenghong Peng, male, who was born in Apr, 1957. He worked in the 2nd Affiliated Hospital of Zhejiang University School of Medicine during 1989 to 2002. In 2002, Chenghong Peng came m Shanghai Ruiiin Hospital and began to take charge of general surgery department. As a pioneer in the hepatobifiopancreatic field, Chenghong Peng devoted himself in the basic and clinical research of pancreatic tmnors. He brings forth new ideas by creating ＂Pancreatic multiple treatment collaborating groups＂, which integrate the advantages of gasn＇oenterology, department, endoscopy department, radiology department, pathology deparnnent and SICU. He constantly strives for excellence in pancreatic surgery. In the previous five years, he performed more than 300 cases of pancreatectomy each year, and has accomplished more than 2,000 cases of pancreatectomy altogether, among which the resectable rate is 74%. Besides, he is also committed to laparoscopic surgery and robotic surgeD,. He has achieved more than 200 laparoscopic hepatectomies, 150 laparoscopic pancreatectomies and 500 robotic hepatobiliopancreatic surgeries （350 robotic pancreatic surgeries included）, which keeps leading position in China. In 2011, Chenghong Peng has won the first prize in 3rd international congress of CRSA, which marked that our achievement in robotic surgery was recognized by oversea peers.Background： To explore the effectiveness, safety, and efficacy of the robot-assisted surgery in the radical resection of pancreatic ductal adenocarcinoma （PDAC）. Methods： The clinical data of 72 patients with PDAC who underwent radical resection using the da Vinci Surgical System from April 2010 to December 2014 were retrospectively analyzed. Results： Among these 72 patients, three were converted to conventional laparotomy due to the vascular invasion or due to the difficulties in tissue isolation from the surrounding organs. Among 39 patients who underwent the pancreatoduodenectomy, the average operative time was 395.3±118.8 min, and the mean intra-operative blood loss was 447.3±269.9 mL. Among 31 patients who underwent the distal pancreatectomy （DP）, the average operative time was 185.5±74.1 min, and the mean intra-operative blood loss was 267.1±305.3 mL. In two patients who received the middle pancreatectomy （NIP）, the average operative time was 225 rain and mean intra-operative blood loss was 100 mL. Among all the 72 patients, an average of 4.2±2.6 lymph nodes were dissected, with an average hospital stay of 22.6±10.7 days. Complications were observed in 18 patients, which included pancreatic fistula （n=11）, bile leak （n=5）, anastomotic bleeding （n：2）, pancreatic fistula complicated with portal vein thrombosis （n=1）, and anastomotic bleeding complicated with acute renal failure （n=l）. Except that one patient died due to post-operative bleeding and acute renal failure, all the other patients were cured after conservative treatment. These 72 patients were followed for 1-45 （15.6±5.8） months, during which 10 patients died. Eleven patients suffered from recurrence or metastasis, among which 6 had local recurrence, 4 had liver metastasis, and 1 had ascites accompnaied with incision site tumor metastasis. Conclusions- Radical resection of PDAC by robotic surgical system is safe and feasible. It has less surgical trauma and enables faster post-operative recovery, and therefore can achieve the lymph node dissection scope and tumor resection margin required by the standards of radical resection for pancreatic cancer. Nevertheless, its long-term efficacy requires further validation.展开更多
The history of pancreatic cancer surgery, though fraught with failure and setbacks, is punctuated by periods of incremental progress dependent upon the state of the art and the mettle of the surgeons daring enough to ...The history of pancreatic cancer surgery, though fraught with failure and setbacks, is punctuated by periods of incremental progress dependent upon the state of the art and the mettle of the surgeons daring enough to attempt it. Surgical anesthesia and the aseptic techniques developed during the latter half of the 19 th century were instrumental in establishing a viable setting for pancreatic surgery to develop. Together, they allowed for bolder interventions and improved survival through the postoperative period. Surgical management began with palliative procedures to address biliary obstruction in advanced disease. By the turn of the century, surgical pioneers such as Alessandro Codivilla and Walther Kausch were demonstrating the technical feasibility of pancreatic head resections and applying principles learned from palliation to perform complicated anatomical reconstructions. Allen O. Whipple, the namesake of the pancreaticoduodenectomy（PD）, was the first to take a systematic approach to refining the procedure. Perhaps his greatest contribution was sparking a renewed interest in the surgical management of periampullary cancers and engendering a community of surgeons who advanced the field through their collective efforts. Though the work of Whipple and his contemporaries legitimized PD as an accepted surgical option, it was the establishment of high-volume centers of excellence and a multidisciplinary approach in the later decades of the 20^th century that made it a viable surgical option. Today, pancreatic surgeons are experimenting with minimally invasive surgical techniques, expanding indications for resection, and investigating new methods for screening and early detection. In the future, the effective management of pancreatic cancer will depend upon our ability to reliably detect the earliest cancers and precursor lesions to allow for truly curative resections.展开更多
目的探讨全胰切除术(TP)在胰腺肿瘤患者中的近远期疗效。方法回顾性纳入2005年6月至2018年3月复旦大学附属中山医院43例TP患者,分析其临床病理特征、手术情况、术后并发症及总生存期。结果本组共43例,其中胰腺导管腺癌(PDAC)25例,胰腺...目的探讨全胰切除术(TP)在胰腺肿瘤患者中的近远期疗效。方法回顾性纳入2005年6月至2018年3月复旦大学附属中山医院43例TP患者,分析其临床病理特征、手术情况、术后并发症及总生存期。结果本组共43例,其中胰腺导管腺癌(PDAC)25例,胰腺导管内乳头状黏液瘤(IPMN)14例,实性假乳头状瘤2例,腺鳞癌1例,神经内分泌肿瘤(NET)1例。并发症发生率为76.7%,30 d病死率为7.0%,中位生存期为20.0个月。与PDAC组比较,IPMN组患者输血率(21.4%vs 60.0%,P=0.043)、联合血管切除率(21.4%vs 64.0%,P=0.019)和腹腔感染率(0 vs 32.0%,P=0.034)均较低,且术后住院时间较短(11.5 d vs23.0 d,P=0.004)。进一步分析表明,浸润性IPMN患者在TP术后获得了更长的远期生存(35.8个月vs 15.0个月,P=0.033)。结论TP术式安全可行且在部分病例中能获得良好的肿瘤学效果,IPMN可能是较PDAC更优选的手术适应证。展开更多
Pancreatic cancer has a poor prognosis. Current therapies for pancreatic cancer have limited effects. In the past decade, precision medicine has shown great potential for clinical applications. In this review, differe...Pancreatic cancer has a poor prognosis. Current therapies for pancreatic cancer have limited effects. In the past decade, precision medicine has shown great potential for clinical applications. In this review, different strategies for applying precision medicine to the treatment of pancreatic cancer are described.展开更多
Background: Pancreatic ductal adenocarcinoma(PDAC) is the most deadly type of tumor, and its pathogenesis remains unknown. Circular RNAs(circRNAs) may be functional and bind to micro RNAs and consequently, influence t...Background: Pancreatic ductal adenocarcinoma(PDAC) is the most deadly type of tumor, and its pathogenesis remains unknown. Circular RNAs(circRNAs) may be functional and bind to micro RNAs and consequently, influence the activity of targeted mRNAs. Recent researches indicate that one circRNA, ciRS-7, acts as a sponge of miR-7 and thus, inhibits its activity. It is well known that miR-7 is a cancer suppressor in many cancers. However, the relationship between ciRS-7 and miR-7, and the role of ciRS-7 in PDAC, remains to be elucidated. Methods: miR-7 and ciRS-7 expression in 41 pairs of PDAC tumors and their paracancerous tissues were detected by quantitative reverse transcription polymerase chain reaction(qRT-PCR). The relationships between their expression levels and clinicopathological features in PDAC tissues were assessed. The relationship between miR-7 and ciRS-7 was also assessed by Spearman’s correlation. We also used cell lines to evaluate the role of ciRS-7 in cell line behavior. The ciRS-7 interfere RNA(si RNA) and its empty vector were transfected into PDAC cells. PDAC cells proliferation and invasion abilities were detected by MTT assay and invasion analysis. The expression of proteins was assessed by Western blotting. Results: ciRS-7 expression was significantly higher in PDAC tissues than paracancerous tissues( P = 0.002). However, miR-7 expression showed the opposite trend( P = 0.048). Moreover, ciRS-7 expression was inversely correlated with miR-7 in PDAC( r s =-0.353, P = 0.023). ciRS-7 expression was also significantly elevated in venous invasion(3.72 ± 2.93 vs. 2.14 ± 1.26;P = 0.028) and lymph node metastasis(4.19 ± 2.75 vs. 2.32 ± 1.90;P = 0.016) in PDAC patients. Furthermore, ciRS-7 knockdown suppressed cell proliferation and invasion of PDAC cells( P < 0.05), and the downregulation of ciRS-7 resulted in miR-7 overexpression and subsequent inhibition of epidermal growth factor receptor(EGFR) and signal transducer and activator of transcription 3(STAT3). Conclusions: Circular RNA ciRS-7 plays an oncogene role in PDAC, partly by targeting miR-7 and regulating the EGFR/STAT3 signaling pathway.展开更多
文摘目的:通过生物信息学分析以及细胞生物学实验研究角蛋白6A(KRT6A)对胰腺导管腺癌(PDAC)诊断、预后判断、免疫微环境以及PDAC细胞PANC1增殖、凋亡等生物学行为的影响。方法:通过GEPIA平台整合TCGA(The Cancer Genome Atlas)数据库与GTEx(Genotype-Tissue)数据库中的数据,分析KTRT6A在PDAC组织中的表达情况,并通过CIBERSORT工具分析KRT6A表达与PDAC组织中免疫细胞浸润的关系,然后通过GSEA方法研究与KRT6A基因表达相关的肿瘤信号通路。选取长海医院病理科保存的60例PDAC组织与癌旁组织标本进行免疫组化分析,验证KRT6A在肿瘤组织中表达情况;通过干扰RNA敲减PANC1细胞中KRT6A的表达,采用CCK-8实验以及流式细胞术检测敲减KRT6A对细胞的增殖、凋亡的影响。结果:利用TCGA与GTEx数据库数据分析发现,KRT6A在人PDAC组织中呈高表达,且与患者较差的生存期存在关联(P=0.015)。利用CIBERSORT软件以及GSEA分析发现,KRT6A高表达的PDAC组织中M2型巨噬细胞浸润性升高(P=0.034),且与Wnt通路(NES:1.7359272,P<0.05)、磷酸戊糖途径(PPP)(NES:1.5613053,P<0.05)等信号通路上调有关联(P<0.05或P<0.01);免疫组化结果进一步验证了KRT6A在PDAC组织中呈高表达(P<0.001)。增殖和凋亡实验发现,干扰KRT6A能够显著抑制PANC1细胞的增殖(P<0.05)以及凋亡(P<0.001)。结论:KRT6A在人PDAC组织中呈高表达,敲减其表达能够抑制PANC1细胞的增殖和凋亡,具有作为PDAC诊断与预后判断新靶标的潜力。
文摘Authors introduction： Qian Zhan, female, who was born in Sept, 1979. She studied in the Shanghai Second Medical University during 1998 to 2005. She majored in Clinical Medicine, and earned her master degree in 2005. In 2005, she went to the Beaujon Hospital of Paris 7th Universit3. in France, as a foreign intern. Later, she came to postgraduate work and residencies in the general surgery department of Shanghai Ruijin Hospital. Her clinical work is focused on multidisciplinary especially postoperative management for the patients with pancreatic cancer. In addition, she is a lead researcher in the pancreatic cancer group for nano based drug delivery, systems. Chenghong Peng, male, who was born in Apr, 1957. He worked in the 2nd Affiliated Hospital of Zhejiang University School of Medicine during 1989 to 2002. In 2002, Chenghong Peng came m Shanghai Ruiiin Hospital and began to take charge of general surgery department. As a pioneer in the hepatobifiopancreatic field, Chenghong Peng devoted himself in the basic and clinical research of pancreatic tmnors. He brings forth new ideas by creating ＂Pancreatic multiple treatment collaborating groups＂, which integrate the advantages of gasn＇oenterology, department, endoscopy department, radiology department, pathology deparnnent and SICU. He constantly strives for excellence in pancreatic surgery. In the previous five years, he performed more than 300 cases of pancreatectomy each year, and has accomplished more than 2,000 cases of pancreatectomy altogether, among which the resectable rate is 74%. Besides, he is also committed to laparoscopic surgery and robotic surgeD,. He has achieved more than 200 laparoscopic hepatectomies, 150 laparoscopic pancreatectomies and 500 robotic hepatobiliopancreatic surgeries （350 robotic pancreatic surgeries included）, which keeps leading position in China. In 2011, Chenghong Peng has won the first prize in 3rd international congress of CRSA, which marked that our achievement in robotic surgery was recognized by oversea peers.Background： To explore the effectiveness, safety, and efficacy of the robot-assisted surgery in the radical resection of pancreatic ductal adenocarcinoma （PDAC）. Methods： The clinical data of 72 patients with PDAC who underwent radical resection using the da Vinci Surgical System from April 2010 to December 2014 were retrospectively analyzed. Results： Among these 72 patients, three were converted to conventional laparotomy due to the vascular invasion or due to the difficulties in tissue isolation from the surrounding organs. Among 39 patients who underwent the pancreatoduodenectomy, the average operative time was 395.3±118.8 min, and the mean intra-operative blood loss was 447.3±269.9 mL. Among 31 patients who underwent the distal pancreatectomy （DP）, the average operative time was 185.5±74.1 min, and the mean intra-operative blood loss was 267.1±305.3 mL. In two patients who received the middle pancreatectomy （NIP）, the average operative time was 225 rain and mean intra-operative blood loss was 100 mL. Among all the 72 patients, an average of 4.2±2.6 lymph nodes were dissected, with an average hospital stay of 22.6±10.7 days. Complications were observed in 18 patients, which included pancreatic fistula （n=11）, bile leak （n=5）, anastomotic bleeding （n：2）, pancreatic fistula complicated with portal vein thrombosis （n=1）, and anastomotic bleeding complicated with acute renal failure （n=l）. Except that one patient died due to post-operative bleeding and acute renal failure, all the other patients were cured after conservative treatment. These 72 patients were followed for 1-45 （15.6±5.8） months, during which 10 patients died. Eleven patients suffered from recurrence or metastasis, among which 6 had local recurrence, 4 had liver metastasis, and 1 had ascites accompnaied with incision site tumor metastasis. Conclusions- Radical resection of PDAC by robotic surgical system is safe and feasible. It has less surgical trauma and enables faster post-operative recovery, and therefore can achieve the lymph node dissection scope and tumor resection margin required by the standards of radical resection for pancreatic cancer. Nevertheless, its long-term efficacy requires further validation.
文摘The history of pancreatic cancer surgery, though fraught with failure and setbacks, is punctuated by periods of incremental progress dependent upon the state of the art and the mettle of the surgeons daring enough to attempt it. Surgical anesthesia and the aseptic techniques developed during the latter half of the 19 th century were instrumental in establishing a viable setting for pancreatic surgery to develop. Together, they allowed for bolder interventions and improved survival through the postoperative period. Surgical management began with palliative procedures to address biliary obstruction in advanced disease. By the turn of the century, surgical pioneers such as Alessandro Codivilla and Walther Kausch were demonstrating the technical feasibility of pancreatic head resections and applying principles learned from palliation to perform complicated anatomical reconstructions. Allen O. Whipple, the namesake of the pancreaticoduodenectomy（PD）, was the first to take a systematic approach to refining the procedure. Perhaps his greatest contribution was sparking a renewed interest in the surgical management of periampullary cancers and engendering a community of surgeons who advanced the field through their collective efforts. Though the work of Whipple and his contemporaries legitimized PD as an accepted surgical option, it was the establishment of high-volume centers of excellence and a multidisciplinary approach in the later decades of the 20^th century that made it a viable surgical option. Today, pancreatic surgeons are experimenting with minimally invasive surgical techniques, expanding indications for resection, and investigating new methods for screening and early detection. In the future, the effective management of pancreatic cancer will depend upon our ability to reliably detect the earliest cancers and precursor lesions to allow for truly curative resections.
文摘目的探讨全胰切除术(TP)在胰腺肿瘤患者中的近远期疗效。方法回顾性纳入2005年6月至2018年3月复旦大学附属中山医院43例TP患者,分析其临床病理特征、手术情况、术后并发症及总生存期。结果本组共43例,其中胰腺导管腺癌(PDAC)25例,胰腺导管内乳头状黏液瘤(IPMN)14例,实性假乳头状瘤2例,腺鳞癌1例,神经内分泌肿瘤(NET)1例。并发症发生率为76.7%,30 d病死率为7.0%,中位生存期为20.0个月。与PDAC组比较,IPMN组患者输血率(21.4%vs 60.0%,P=0.043)、联合血管切除率(21.4%vs 64.0%,P=0.019)和腹腔感染率(0 vs 32.0%,P=0.034)均较低,且术后住院时间较短(11.5 d vs23.0 d,P=0.004)。进一步分析表明,浸润性IPMN患者在TP术后获得了更长的远期生存(35.8个月vs 15.0个月,P=0.033)。结论TP术式安全可行且在部分病例中能获得良好的肿瘤学效果,IPMN可能是较PDAC更优选的手术适应证。
文摘Pancreatic cancer has a poor prognosis. Current therapies for pancreatic cancer have limited effects. In the past decade, precision medicine has shown great potential for clinical applications. In this review, different strategies for applying precision medicine to the treatment of pancreatic cancer are described.
基金supported by grants from the Key Research and Development Program Projects in Anhui Province(1804h08020277)the Programs for Science and Technology Development of An-hui Province(1606c08234)
文摘Background: Pancreatic ductal adenocarcinoma(PDAC) is the most deadly type of tumor, and its pathogenesis remains unknown. Circular RNAs(circRNAs) may be functional and bind to micro RNAs and consequently, influence the activity of targeted mRNAs. Recent researches indicate that one circRNA, ciRS-7, acts as a sponge of miR-7 and thus, inhibits its activity. It is well known that miR-7 is a cancer suppressor in many cancers. However, the relationship between ciRS-7 and miR-7, and the role of ciRS-7 in PDAC, remains to be elucidated. Methods: miR-7 and ciRS-7 expression in 41 pairs of PDAC tumors and their paracancerous tissues were detected by quantitative reverse transcription polymerase chain reaction(qRT-PCR). The relationships between their expression levels and clinicopathological features in PDAC tissues were assessed. The relationship between miR-7 and ciRS-7 was also assessed by Spearman’s correlation. We also used cell lines to evaluate the role of ciRS-7 in cell line behavior. The ciRS-7 interfere RNA(si RNA) and its empty vector were transfected into PDAC cells. PDAC cells proliferation and invasion abilities were detected by MTT assay and invasion analysis. The expression of proteins was assessed by Western blotting. Results: ciRS-7 expression was significantly higher in PDAC tissues than paracancerous tissues( P = 0.002). However, miR-7 expression showed the opposite trend( P = 0.048). Moreover, ciRS-7 expression was inversely correlated with miR-7 in PDAC( r s =-0.353, P = 0.023). ciRS-7 expression was also significantly elevated in venous invasion(3.72 ± 2.93 vs. 2.14 ± 1.26;P = 0.028) and lymph node metastasis(4.19 ± 2.75 vs. 2.32 ± 1.90;P = 0.016) in PDAC patients. Furthermore, ciRS-7 knockdown suppressed cell proliferation and invasion of PDAC cells( P < 0.05), and the downregulation of ciRS-7 resulted in miR-7 overexpression and subsequent inhibition of epidermal growth factor receptor(EGFR) and signal transducer and activator of transcription 3(STAT3). Conclusions: Circular RNA ciRS-7 plays an oncogene role in PDAC, partly by targeting miR-7 and regulating the EGFR/STAT3 signaling pathway.
