胰腺癌早期症状隐匿,缺乏特异性,易被忽视,患者就诊时多为进展期,手术切除率特别是根治性手术切除率较低,远期疗效不佳。近20年来,尽管新的影像诊断技术及综合治疗手段不断问世,给许多恶性肿瘤的治疗开创了崭新的局面,但却未从根本上改变胰腺癌诊治的窘境。胰腺癌总体疗效较差,但早期病例根治术后仍可使其生存率明显延长。据美国对1989~1995年1340家医院的100313例胰腺癌的统计,Ⅰ期胰腺癌的5年生存率为32.8%。日本的全国统计资料显示,Ⅰ期胰腺导管癌的术后5年生存率达61%。可见,提高胰腺癌远期疗效的关键仍在于早期诊断。目前,影像学检查是胰腺癌最常用的检查手段,对影像学检查呈现出一些细微变化而难以定性的患者,下述方法可成为早期诊断的佐证。
【Abstract】ObjectiveTo investigate the relationship between tumor suppressor gene DPC4 and the development and prognosis of pancreatic carcinoma. MethodsRelevant literatures of recent years were reviewed. ResultsDPC4 was located on chromosome 18. Its product was Smad 4 protein. Smad 4 protein was the central component of the transforming growth factor-beta signaling pathway, and all the biological effect was the results of interaction of Smad 4 and different Smads. The gene was deleted or inactive in about 50% of pancreatic carcinomas. The deletion of DPC4 had a great relation to the development and prognosis of pancreatic carcinoma. ConclusionThe alteration of tumor suppressor gene DPC4 is connected with the development and prognosis of pancreatic carcinoma. However, this research should be further studied.
ObjectiveTo study the expression of lipid associated with neutrophil gelatinase associated lipocalin (NGAL) in nude mice orthotopic pancreatic cancer tissues and the relationship between the occurred and development of pancreatic cancer. MethodsThe expressions of NGAL mRNA and protein of pancreatic cancer tissues and their adjacent tissues, and normal pancreatic tissues in nude mice were detected by using RT-PCR and immunohistochemical methods. ResultsThe expressions of NGAL mRNA in pancreatic cancer tissues and adjacent tissues were significantly higher than that in normal pancreatic tissues (P < 0.05), and the expression of NGAL mRNA in pancreatic carcinoma tissues was significantly higher than that in para carcinoma tissues (P < 0.05). The strong positive expression rate of NGAL protein in pancreatic carcinoma tissues was significantly higher than thoes in para carcinoma tissues and normal pancreatic tissues (P < 0.05). ConclusionsNGAL is highly expressed in pancreatic cancer tissues, and NGAL may be an important regulatory factor in the development of pancreatic cancer.
【 Abstract 】 Objective Overexpressions of epidermal growth factor (EGF) and EGF receptor have been associated with progression and invasive phenotype of pancreatic cancer. However, the underlying molecular mechanism by which EGF worked in pancreatic cancer cells has not been completely understood. In this study, effect of EGF on the invasion and metastasis of pancreatic cancer cells and its regulatory mechanism were investigated. Methods The effects of EGF on the proliferation, adhesion and invasion of pancreatic cancer cells were detected by WST-1 proliferation assay, adhesion assay and invasive assay, respectively. The activity and expression of MMP-2 and MMP-9 were examined by zymography, Western blot and RT-PCR, respectively. The activity of NF- κ B was examined by EMSA. Results EGF could significantly promote the invasiveness of pancreatic cancer cells but did not affect cell proliferation or adhesion. The expressions of NF- κ B and MMP-9 were significantly increased by EGF, but EGF did not affect the activity and expression of MMP-2. Furthermore, EGF stimulated the NF- κ B binding activity. Pretreatment with NF- κ B inhibitors, pyrrolidine dithiocarbamate (PDTC), could significantly inhibit the activity of NF- κ B induced by EGF. Meanwhile, the EGF-induced expression and activity of MMP-9, as well as cell invasiveness were also inhibited by NF- κ B inhibitor. Conclusion EGF could increase the expression and promote the invasiveness of MMP-9 via the activation of NF- κ B in pancreatic cancer cells, which implies that NF- κ B inhibitant, such as PDTC, may diminish the invasiveness of pancreatic cancer cells.
Objective To observe the effect of epidermal growth factor (EGF) on the proliferation, adhesion, invasiveness and the activation of nuclear factor-κB (NF-κB), matrix metalloproteinases (MMPs) expression and explore related mechanisms in pancreatic cancer cells. Methods Cell invasion assay, proliferation assay and adhesion assay were used to examine the proliferation, adhesion and invasiveness of pancreatic cancer cells, respectively. NF-κB activity was detected by electrophoretic mobility shift assay (EMSA), and MMPs protein and mRNA expressions were investigated by gelatin zymography, Western blot and reverse transcriptase-polymerase chain reaction (RT-PCR). Results EGF increased the invasiveness of pancreatic cancer cell in a dose-dependent manner (P<0.05), but did not affect cell proliferation or adhesion. The expressions of MMP-9 mRNA and protein significantly increased after induction by EGF and were highest when EGF concentration was 50 ng/ml, while there was no effect on the expressions of MMP-2 mRNA and protein. Furthermore, NF-κB activity increased with increased concentration of EGF in a concentration-dependent manner (P<0.05). In addition, NF-κB activity and the expressions of MMP-9 mRNA and protein by pretreatment with both pyrrolidine dithiocarbamate (PDTC) and EGF decreased when compared that by pretreatment with EGF alone. The invasiveness of pancreatic cancer cell by pretreatment with both PDTC and EGF decreased when compared that by pretreatment with EGF alone and nothing (P<0.05).Conclusion The findings indicate that the NF-κB-mediated MMP-9 induction is essential for EGF-induced invasiveness in pancreatic cancer cells, which can be inhibited by PDTC.
ObjectiveTo summarize current patient-derived organoids as preclinical cancer models, and its potential clinical application prospects. MethodsCurrent patient-derived organoids as preclinical cancer models were reviewed according to the results searched from PubMed database. In addition, how cancer-derived human tumor organoids of pancreatic cancer could facilitate the precision cancer medicine were discussed. ResultsThe cancer-derived human tumor organoids show great promise as a tool for precision medicine of pancreatic cancer, with potential applications for oncogene modeling, gene discovery and chemosensitivity studies. ConclusionThe cancer-derived human tumor organoids can be used as a tool for precision medicine of pancreatic cancer.
Objective To investigate the effect of angiostatin gene combined with somastatin on inhibiting proliferation of human pancreatic cancer cell BXPC-3 and endothelial cell of vascular ECV-304 and on inducing their apoptosis in vitro. Methods The pcDNA3/angio was transfected BXPC-3 by liposome-mediated gene transfer method. RT-PCR and Western blot were used to detect the expression of angiostatin gene. In vitro, MTT and flow cytometry (FCM) were used to detect whether angiostatin gene combined with somastatin could effect the growth inhibition of BXPC-3 and ECV-304 cells. Results Angiostatin was expressed and secreted by transfected BXPC-3. The growth of BXPC-3 was inhibited by certain concentration of somatostatin (≥10 μg/ml, P<0.01), which was dependent on the dose of somatostatin in a concentration extent; Simultaneity apoptosis was induced (P<0.01). But the growth of ECV-304 was not inhibited with somatostation (Pgt;0.05). Angiostatin could inhibit the growth of ECV-304 and induced apoptosis (P<0.01), but it had no effect on the growth of BXPC-3 (Pgt;0.05). Angiostation gene combined with somatostation could inhibit the growth both of BXPC-3 and ECV-304 (P<0.01), and induce apoptosis of them (P<0.01); but the effect couldn’t be additived. Conclusions ①Somatostatin directly inhibits the proliferation of human pancreatic cancer cells and induces apoptosis, but it doesn’t directly inhibit angiogenesiso of human pancreatic cancer. ②Angiostatin specially inhibits the proliferation of endothelial cell of vascular and induces apoptosis. Angiostatin could inhibit angiogenesis of human pancreatic cancer to induce necrosis of cancer cell.
【摘要】 目的 探讨125I粒子植入治疗中晚期胰腺癌的临床并发症及相关护理措施。 方法 回顾分析2006年10月-2010年4月121例行125I粒子植入治疗的胰腺癌患者的临床治疗及护理,采取积极有效的护理措施,预防及处理并发症,促进患者康复。 结果 121例患者接受放射性125I粒子植入治疗后,7例出现胰瘘,13例出现胃肠道反应,经对症处理和精心护理后均治愈。 结论 125I粒子组织间植入近距离治疗中晚期胰腺癌近期疗效好、安全、副反应少,良好的护理对改善中晚期胰腺癌患者预后具有重要意义。【Abstract】 Objective To observe the complications in patients with middle and advanced pancreatic carcinoma due to treatment of 125I particle implantation, and the investigate the proper nursing methods. Methods The clinical data including the therapy and nursing methods for the complications in 121 patients with middle and advanced pancreatic carcinoma due to treatment of 125I particle implantation from October 2006 to October 2010 were retrospectively analyzed. The treatment and care for complication were analyzed. Results In the 121 patients who had been treated by 125I particle, pancreatic fistula occurred in seven, and severe gastrointestinal upset was found in 13. The patients with the complications recovered after postoperative treatment and nursing. Conclusion 125I particle implantation for patients with middle and advanced pancreatic carcinoma is effective and safe with a few side reactions; proper nursing is important to improve the prognosis.
ObjectiveTo retrospectively investigate the correlation between tumor immune nutritional indexes and the resectability in patients with pancreatic cancer.MethodsWe selected pancreatic patients with pathological diagnosis who admitted to Xuanwu Hospital of Capital Medical University from January 2015 to December 2018. The clinical data of patients were retrospectively analyzed. Nutritional and inflammatory hematological parameters at one week before operation were carefully collected, the parameters including: the neutrophil count, lymphocyte count, monocyte count, hemoglobin (Hb), platelet count, albumin (Alb), prealbumin (PA), cholesterol, and serum tumor markers (CEA and CA19-9). The ratio of neutrophil count to lymphocyte count (NLR), ratio of platelet count to lymphocyte count (PLR), ratio of lymphocyte count to monocyte count (LMR), prognostic nutrition index (PNI), nutritional risk score (GNIR), and controlled nutritional status score (COUNT) were calculated. The receiver working characteristic curve (ROC curve) was used to evaluate the predictive value of various indexes in radical resection of pancreatic cancer.ResultsOf the 55 patients with pancreatic cancer, 22 received radical surgery and 33 did not. There was no significant difference in gender, BMI, neutrophil count, monocyte count, platelet count, hemoglobin, albumin, prealbumin, cholesterol, and tumor location between the radical operation group and the non-radical operation group (P>0.05), but there were significant differences in age, lymphocyte count, CEA, and CA19-9 between the two groups (P<0.05). There was no significant difference in the area under the curve (AUC) of neutrophil count, lymphocyte count, monocyte count, hemoglobin, platelet count, albumin, prealbumin, cholesterol, NLR, PLR, LMR, PNI, and GNIR to predict the resectability of pancreatic cancer (P>0.05), but there was statistical significance in COUNT score, CEA, and CA19-9 (P<0.05). The AUC values of COUNT, CEA, and CA19-9 were 0.700, 0.705, and 0.739 respectively, the sensitivity corresponding to the best critical point cutoff value were 59.09%, 80.00%, and 100%, as well as the specificity were 87.88%, 66.67%, and 42.42%, respectively. The specificity of COUNT was high, but the sensitivity was poor. The sensitivity of CEA and CA19-9 were high and the specificity were poor.ConclusionsThe COUNT is a simple and useful predictor to predict the resectability of pancreatic cancer. The combination of COUNT and serum tumor markers of CEA and CA19-9 can help to better predict the surgical indications of pancreatic cancer.