【Abstract】 Objective To explore the features of Ki-ras mutations at codon 12 in Chinese patients of pancreatic cancer and to compare these features with those in Western countries. Methods Fifty-nine samples were collected during operations for pancreatic adenocarcinoma in our hospital from December 1989 to November 1997. The patients, age ranged from 30 to 73 years 〔(55.5±10.4) years〕,with 38 males and 21 female. TNM staging of the patients: stage Ⅰ(n=4); stage Ⅱ(n=8), stage Ⅲ(n=42),stage Ⅳ(n=5). PCR was used to amplify target gene and Dot blot hybridization for detecting Ki-ras mutations at codon 12 was performed in fifty-nine specimens of Chinese pancreatic cancer. The data of Ki-ras mutations at codon 12 from Western countries were gotten by Medline system. Results Ki-ras mutation at codon 12 was detected in 76.3% of the patients in this group. The frequency of double mutation of Ki-ras at codon 12 in this group (15.6%) was highest than that in western countries. Our results were compared with those reported in Western countries. The results suggested that there were the significant differences in the substitution of Ki-ras mutations at codon 12 and in the ratio of transition to transversion in pancreatic cancer among various countries. Conclusion Ki-ras mutations at codon 12 is frequent in Chinese pancreatic cancer, and a gene component to pancreatic cancer may be different among various countries. In addition, the effect of Ki-ras mutations at codon 12 on prognosis of patients with pancreatic cancer is different in various countries.
Objective To investigate the effect of common iliac vein allograft replacing the portal vein-superior mesenteric vein transition area invaded by pancreatic cancer. Methods The clinical data of a patient with pancreatic cancer admitted to the Beijing Tsinghua Changgung Hospital in December 2021 who underwent pancreaticoduodenectomy combined with common iliac vein allograft replacing the junction of portal vein, superior mesenteric vein and splenic vein were analyzed retrospectively. The patient was a 77-year-old man who complained of “epigastric pain for 1 month and pancreatic mass was found for 1 week”. After admission, the patient was diagnosed with pancreatic cancer through inspection, and then the surgery was required. Preoperative examination and intraoperative exploration confirmed that the junction of portal vein, superior mesenteric vein, and spleen vein was invaded by tumor. In addition, the length of the invaded vessels measured by preoperative 3D reconstruction image was 5.5 cm, and the distance between the broken end of portal vein and the broken end of superior mesenteric vein measured was 4.5 cm during the operation. After tumor and vessels were resected, vascular anastomosis could not be performed directly. After accurate evaluation, pancreaticoduodenectomy combined with common iliac vein allograft replacing the junction of portal vein, superior mesenteric vein and splenic vein was performed. The operative time was 11 h, and the intraoperative blood loss was 400 mL. After the operation, the routine treatment was performed in ICU and was transferred to the general ward on the 7th day. Postoperative laboratory tests were performed to monitor liver function changes routinely, and imaging examination were was performed to monitor portal venous system blood flow. Results Postoperative complications such as biliary fistula, pancreatic fistula, hemorrhage, infection and thrombosis were not occurred. Postoperative pathological diagnosis: pancreatic ductal adenocarcinoma, medium-low differentiation. Enhanced CT reexamination on the 2nd and 13th day after the operation showed that the blood flow at the junction of portal vein, superior mesenteric vein and splenic vein of the common iliac vein allograft was unobstructed, and there was no stenosis or thrombosis at each anastomosis. Conclusions The application of common iliac vein allograft replacing the portal vein-superior mesenteric vein transition area invaded by pancreatic cancer is safe and feasible. The short-term efficacy is satisfactory, and long-term prognosis remains to be further observed.
Objective To investigate the mechanism of the resistance of pancreatic cancer cells to tumor necrosis factor related apoptosis inducing ligand (TRAIL)mediated apoptosis. MethodsThe expression of TRAIL receptor-4 (TRAIL-R4) in normal pancreas tissue and pancreatic cancer was analyzed by using Northern blotting, Western blotting and immunohistochemistry.ResultsTRAIL-R4 mRNA and protein were expressed at moderate to high levels in human pancreatic cancer, but demonstrated weak to negative in the normal pancreas. Moreover, pancreatic cancer cells showed b TRAIL-R4 immunostaining throughout the tumor mass. Conclusion TRAIL-R4 levels are significantly different in pancreatic cancer in comparison to the normal pancreas. These findings give new insights into the resistance mechanisms of pancreatic cancer cells towards TRAILmediated apoptosis.
ObjectiveTo review the recent advances in the pancreatic cancer stem cells field and identify the research trend in future. MethodsCurrent literatures on pancreatic cancer stem cells were collected and reviewed. ResultsPancreatic cancer was a highly lethal disease and was usually diagnosed at a late stage, for which there were few effective therapies. Emerging evidence had suggested that pancreatic cancer cells proposed a heterogeneous organization. A subpopulation of stem celllike cells sustains tumor growth, propagation, metastasis, and resistance to standard chemotherapy. Cancer stem cells were identified based on their expression of different sets of cell surface markers and functional characteristics. Some important signaling pathways which maintain self-renewal and metastasis were upregulated in pancreatic cancer stem cells. ConclusionsCurrent findings clearly suggest that specific elimination of cancer stem cells is possible and therapeutically relevant. An improved understanding of the biological behavior of such cells may lead to the development of novel diagnosis and treatment regimens for pancreatic cancer.
ObjectiveTo systematically review the intestinal flora diversity profile of pancreatic cancer patients. MethodsThe Cochrane Library, PubMed, Web of Science, EMbase, CNKI, CBM, WanFang Data and VIP databases were electronically searched to collect cross-sectional studies on the intestinal flora diversity profile of pancreatic cancer patients from inception to December 31, 2021. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies; then, meta-analysis was performed by using RevMan 5.3 software. ResultsA total of 7 cross-sectional studies involving 250 pancreatic cancer patients and 166 healthy controls were included. The results of meta-analysis showed that: compared with the healthy control group, the intestinal flora of patients with pancreatic cancer α reduced diversity with the Shannon index. High-throughput sequencing found that Proteobacteria and Prevotella were more abundant in pancreatic cancer patients, Firmicutes, Faecalbacterium, Bifidobacterium and Clostridium in pancreatic cancer patients was lower. ConclusionCurrent evidence shows that the intestinal flora of pancreatic cancer patients has certain characteristics. Proteobacteria and Prevotella are relatively abundant in pancreatic cancer patients. Due to limited quality and quantity of the included studies, more high-quality studies are needed to verify above conclusion.
ObjectiveTo explore the prognostic factors of pancreatic cancer. MethodsClinical data of 71 patients of pancreatic cancer who treated in The First Hospital of Lanzhou University from January 2010 to December 2014 were retrospectively collected to analyze the prognostic factors of pancreatic cancer. ResultsSixty patients of the 71 patients were followed up for 5-36 months, with the median time of 16 months, and the 1, 2, and 3-year cumulative survival rates were 60.6%, 23.9%, and 1.4% respectively. Univariate analysis results showed that, gender (P=0.043), lymph node metastasis (P=0.002), distant metastasis (P=0.000), TNM staging (P=0.000), and peripancreatic invasion (P=0.000) were correlated with the prognosis of pancreatic cancer, that female patients, patients with the presence of lymph node metastasis, distant metastasis, later TNM staging, and peripancreatic invasion had worse prognosis. Cox proportional hazard model results showed that, distant metastasis (P=0.047), TNM staging (P=0.002), and peripancreatic invasion (P=0.016) were prognostic factors of pancreatic cancer, patients with the presence of distant metastasis, later TNM staging, and peripancreatic invasion had poor prognosis. ConclusionDistant metastasis, TNM staging, and peripancreatic invasion were independent prognostic factors of pancreatic cancer.
Objective To summarize the diagnosis and surgical treatment experience of pancreatic ductal stones combined with pancreatic cancer. Methods Nine cases of pancreatic ductal stones combined with pancreatic cancer who treated in our hospital from January 2005 to December 2015 were collected to make a retrospective analysis, summarizing the clinical features, imaging diagnosis, and surgical treatment. Results Four of 9 cases received ultrasound combined with CT angiography, and all of them were diagnosed as pancreatic ductal stones combined with pancreatic cancer; 4 cases received magnetic resonance cholangiopancreatography (MRCP)/magnetic resonance angiography (MRA), and 3 cases were considered as pancreatic ductal stones combined with pancreatic cancer; 3 cases received endoscopic retrograde cholangiopancreatography (ERCP), and all of them were diagnosed as pancreatic cancer. All of the 9 cases underwent surgery, including 4 cases of pancreaticoduodenectomy, 3 cases of distal pancreatectomy with splenectomy, 1 case of pancreatolithotomy plus distal pancreaticojejunostomy, and 1 case of laparoscopic exploration with biopsy. No one died after surgery, but gastric stress ulcer bleeding happened in 1 case, and class B pancreatic fistula happened in 1 case. All of the 9 cases were followed-up for 5-36 months, with the median were 13 months. Seven cases died during follow up period, 5 cases survived longer than 1 year, and 2 cases survived longer than 3 years. Conclusions For patients with recurrent pancreatic stones, we should be wary of the possibility of combining pancreatic cancer, CT and MRCP can be used as further examination of this disease, a variety of imaging methods combination can improve the diagnosis. If imaging examination reveals swollen pancreas without surgical contraindications, surgery is necessary, and standard pancreaticoduodenectomy or pancreas body and tail resection is recommended.
ObjectiveTo investigate the growth characteristics of pancreatic cancer cells in the twodimensional culture system (monolayer) and threedimensional culture system (type Ⅰ collagen and extracellular matrix gel). MethodsThree pancreatic cancer cell lines (SW1990, PCT, and ASPC1) were cultured in monolayer, type Ⅰ collagen, and extracellular matrix gel, respectively. The growth patterns were observed, growth curves were detected by CCK8 test, and the cell cycle distributions were analyzed by propidium iodide staining. Results In the twodimensional culture system, cells grew in monolayer. In the type Ⅰ collagen and the ECM gel threedimensional culture system, cells formed multicellular spheroids (MCS), of which the growth rates were slower than those of the cells in monolayer. The proportions of S phase of SW1990, PCT, and ASPC1 cells in twodimensional culture system were significantly more than those in the type Ⅰ collagen on 4 d and 8 d 〔(29.6±3.0)% vs. (18.2±5.1)%, (33.6±2.1)% vs. (14.5±3.2)%, (33.1±1.8)% vs. (24.7±2.6)%; Plt;0.05〕, while the difference of proportion of three cell lines in G2/M phase was not different between twodimensional culture system and type Ⅰ collagen (Pgt;0.05). The proportions of G0/G1 phase of SW1990 and PCT cells cultured in the type Ⅰ collagen on 4 d and 8 d and ASPC1 cells cultured in the type Ⅰ collagen on 4 d were significant more than those cultured in twodimensional culture system (Plt;0.05). The proportions of S phase of ASPC1 cells and SW1990 cells cultured in the type Ⅰ collagen on 4 d were significant more than those cultured in the type Ⅰ collagen on 8 d (Plt;0.05). ConclusionsThe characteristics of pancreatic cancer cells in twodimensional and threedimensional culture systems are different. MCS culture system can better mimic the in vivo growth environment of cells in tumors.
【 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.
【Abstract】Objective To investigate the relationship between the development of pancreatic cancer and inflammation, and the therapy strategy.Methods Related articles were reviewed.Results The pathogenesis of inflammation in pancreatic cancer development involves cytokines, NF-κB, COX-2, PPAR-γ, DNA damage, gene changes，etc. Based on these mechanisms some medications are under developing. Conclusion Accumulative effects of pancreatic inflammation may lead to DNA changes, and even pancreatic cancer development. Medications aimed at suppressing pancreatic inflammation may help with prevention and treatment of pancreatic cancer.