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World Journal of Surgical Oncology Sep 2019Pancreatic carcinoma (PC) is one of the most lethal malignancies, and its poor prognosis is strongly associated with invasion and metastasis. CA19.9 is considered to be...
BACKGROUND
Pancreatic carcinoma (PC) is one of the most lethal malignancies, and its poor prognosis is strongly associated with invasion and metastasis. CA19.9 is considered to be the most sensitive serum marker for PC in clinical practice; however, the detection of CA19.9 in PC has a certain false positive and false negative rate. The expression of the calcium-binding protein S100A4 has been reported to be associated with poor prognosis in various cancers. This study aimed to investigate the relationship between S100A4 and CA19.9 and its prognostic significance in PC.
METHODS
We performed immunohistochemical staining for S100A4 in formalin-fixed, paraffin-embedded blocks of 128 PC tissues. The levels of S100A4 expression and pre-operative serum CA19.9 were correlated with clinicopathological parameters. The possible correlation between S100A4 protein expression and pre-operative serum CA19.9 levels were evaluated using the chi-square test and Spearman correlation. Survival was assessed by Kaplan-Meier analysis together with a single variable or multivariate Cox analysis.
RESULTS
A significant positive correlation between S100A4 expression and pre-operative serum CA19.9 level was observed in PC tissues (ρ = 0.202, P = 0.022). The co-expression of both proteins correlated significantly with tumor differentiation (ρ = - 0.280, P = 0.001), TNM stage (ρ = - 0.389, P = 0.000), and lymph node metastasis (ρ = 0.254, P = 0.008). Upregulation of S100A4 was identified as a significant, independent predictor of poor overall survival (P = 0.000). Moreover, higher serum CA19.9 levels (≥ 35 U/mL) were also recognized as an independent predictor of inferior overall survival (P = 0.001). Additionally, upregulation of S100A4 and higher pre-operative serum CA19.9 levels (≥ 35 U/mL) in patients with PC contributed to a significant decrease in overall survival (P = 0.000).
CONCLUSIONS
The expression levels of S100A4 in PC tissues were positively correlated with pre-operative serum CA19.9 levels. S100A4 expression and pre-operative serum CA19.9 levels were significant, independent prognostic factors for the overall survival of patients with PC. S100A4 expression/pre-operative serum CA19.9 levels may prove useful as dual prognostic biomarkers for PC. Analysis of CA19.9 in combination with S100A4 can better predict the prognosis of PC.
Topics: Biomarkers, Tumor; CA-19-9 Antigen; Female; Follow-Up Studies; Humans; Lymphatic Metastasis; Male; Middle Aged; Pancreatectomy; Pancreatic Neoplasms; Preoperative Care; Prognosis; Retrospective Studies; S100 Calcium-Binding Protein A4; Survival Rate
PubMed: 31526392
DOI: 10.1186/s12957-019-1707-4 -
Current Pharmaceutical Design 2012Recent studies have demonstrated that the interaction between the cancer and the stroma, play a key role in the development of pancreatic cancer. The desmoplasia, which... (Review)
Review
Recent studies have demonstrated that the interaction between the cancer and the stroma, play a key role in the development of pancreatic cancer. The desmoplasia, which consists of fibroblasts, pancreatic stellate cells, lymphatic and vascular endothelial cells, immune cells, pathologic increased nerves, and the extracellular matrix (ECM), creates a complex tumor microenvironment that promotes pancreatic cancer development, invasion, metastasis, and resistance to chemotherapy. Thus, the potential approach for targeting the components of this desmoplastic reaction or the pancreatic tumor microenvironment might represent a novel therapeutic approach to advanced pancreatic carcinoma. Novel therapies that target on the pancreatic tumor microenvironment should become one of the more effective treatments for pancreatic cancer.
Topics: Animals; Antineoplastic Agents; Cell Communication; Humans; Molecular Targeted Therapy; Neoplasm Proteins; Pancreatic Neoplasms; Stromal Cells; Tumor Microenvironment
PubMed: 22372501
DOI: 10.2174/13816128112092404 -
Oncotarget Feb 2017Ellagic aicd (EA), a dietary polyphenolic compound found in plants and fruits, possesses various pharmacological activities. This study investigated the effect of EA on...
Ellagic aicd (EA), a dietary polyphenolic compound found in plants and fruits, possesses various pharmacological activities. This study investigated the effect of EA on human pancreatic carcinoma PANC-1 cells both in vitro and in vivo; and defined the associated molecular mechanisms. In vitro, the cell growth and repairing ability were assessed by CCK-8 assay and wound healing assay. The cell migration and invasion activity was evaluated by Tanswell assay. In vivo, PANC-1 cell tumor-bearing mice were treated with different concentrations of EA. We found that EA significantly inhibited cell growth, cell repairing activity, and cell migration and invasion in a dose-dependent manner. Treatment of PANC-1 xenografted mice with EA resulted in significant inhibition in tumor growth and prolong mice survival rate. Furthermore, flow cytometric analysis showed that EA increased the percentage of cells in the G1 phase of cell cycle. Western blot analysis revealed that EA inhibited the expression of COX-2 and NF-κB. In addition, EA reversed epithelial to mesenchymal transition by up-regulating E-cadherin and down-regulating Vimentin. In summary, the present study demonstrated that EA inhibited cell growth, cell repairing activity, cell migration and invasion in a dose-dependent manner. EA also effectively inhibit human pancreatic cancer growth in mice. The anti-tumor effect of EA might be related to cell cycle arrest, down-regulating the expression of COX-2 and NF-κB, reversing epithelial to mesenchymal transition by up-regulating E-cadherin and down-regulating Vimentin. Our findings suggest that the use of EA would be beneficial for the management of pancreatic cancer.
Topics: Animals; Antigens, CD; Blotting, Western; Cadherins; Cell Cycle; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cyclooxygenase 2; Dose-Response Relationship, Drug; Ellagic Acid; Epithelial-Mesenchymal Transition; Humans; Mice, Inbred BALB C; Mice, Nude; NF-kappa B; Pancreatic Neoplasms; Survival Analysis; Tumor Burden; Vimentin; Xenograft Model Antitumor Assays
PubMed: 28135203
DOI: 10.18632/oncotarget.14811 -
International Journal of Biological... 2018Since the five-year survival rate is less than 5%, pancreatic ductal adenocarcinoma (PDAC) remains the 4th cause of cancer-related death. Although PDAC has been...
Since the five-year survival rate is less than 5%, pancreatic ductal adenocarcinoma (PDAC) remains the 4th cause of cancer-related death. Although PDAC has been repeatedly researched in recent years, it is still predicted to be the second leading cause of cancer death by year 2030. In our study, the differentially expressed genes in dataset GSE62452 were used to construct a co-expression network by WGCNA. The yellow module related to grade of PDAC was screened. Combined with co-expression network and PPI network, 36 candidates were screened. After survival and regression analysis by using GSE62452 and TCGA dataset, we identified 10 real hub genes ( and ) tightly related to progression of PDAC. According to Oncomine database and The Human Protein Atlas (HPA), we found that all real hub genes were overexpressed in pancreatic carcinoma compared with normal tissues on transcriptional and translational level. ROC curve was plotted and AUC was calculated to distinguish recurrent and non-recurrent PDAC and every AUC of the real hub gene was greater than 0.5. Finally, functional enrichment analysis and gene set enrichment (GSEA) was performed and both of them showed the cell cycle played a vital role in PDAC.
Topics: Disease Progression; Gene Expression Regulation, Neoplastic; Humans; Pancreatic Neoplasms; Prognosis; ROC Curve; Regression Analysis; Transcriptome
PubMed: 29483831
DOI: 10.7150/ijbs.22619 -
Gut Jun 2022We aimed to determine the long-term yield of pancreatic cancer surveillance in hereditary predisposed high-risk individuals.
OBJECTIVE
We aimed to determine the long-term yield of pancreatic cancer surveillance in hereditary predisposed high-risk individuals.
DESIGN
From 2006 to 2019, we prospectively enrolled asymptomatic individuals with an estimated 10% or greater lifetime risk of pancreatic ductal adenocarcinoma (PDAC) after obligatory evaluation by a clinical geneticist and genetic testing, and subjected them to annual surveillance with both endoscopic ultrasonography (EUS) and MRI/cholangiopancreatography (MRI/MRCP) at each visit.
RESULTS
366 individuals (201 mutation-negative familial pancreatic cancer (FPC) kindreds and 165 PDAC susceptibility gene mutation carriers; mean age 54 years, SD 9.9) were followed for 63 months on average (SD 43.2). Ten individuals developed PDAC, of which four presented with a symptomatic interval carcinoma and six underwent resection. The cumulative PDAC incidence was 9.3% in the mutation carriers and 0% in the FPC kindreds (p<0.001). Median PDAC survival was 18 months (range 1-32). Surgery was performed in 17 individuals (4.6%), whose pathology revealed 6 PDACs (3 T1N0M0), 7 low-grade precursor lesions, 2 neuroendocrine tumours <2 cm, 1 autoimmune pancreatitis and in 1 individual no abnormality. There was no surgery-related mortality. EUS detected more solid lesions than MRI/MRCP (100% vs 22%, p<0.001), but less cystic lesions (42% vs 83%, p<0.001).
CONCLUSION
The diagnostic yield of PDAC was substantial in established high-risk mutation carriers, but non-existent in the mutation-negative proven FPC kindreds. Nevertheless, timely identification of resectable lesions proved challenging despite the concurrent use of two imaging modalities, with EUS outperforming MRI/MRCP. Overall, surveillance by imaging yields suboptimal results with a clear need for more sensitive diagnostic markers, including biomarkers.
Topics: Carcinoma; Carcinoma, Pancreatic Ductal; Early Detection of Cancer; Humans; Middle Aged; Pancreatic Neoplasms
PubMed: 33820756
DOI: 10.1136/gutjnl-2020-323611 -
Gastrointestinal Endoscopy Dec 1996The aim of the study was to update our previously published data on the clinical TNM staging of ampullary and pancreatic carcinoma by endosonography. (Comparative Study)
Comparative Study
BACKGROUND
The aim of the study was to update our previously published data on the clinical TNM staging of ampullary and pancreatic carcinoma by endosonography.
METHODS
Endosonography was performed in 70 patients with pancreatic cancer and in 32 patients with ampullary carcinoma. TNM staging was carried out before surgery and compared with findings of histology and/or surgery.
RESULTS
Endosonography was accurate in staging the depth of tumor invasion. Early-stage carcinomas could be distinguished from advanced cancers. Nonresectability was accurately assessed on the basis of vascular involvement using real-time ultrasound. Tumor compression due to peritumoral pancreatitis and direct tumor invasion into the base of the mesocolon could not be diagnosed by endosonography. The overall accuracy in tumor staging for pancreatic and ampullary carcinomas was 83.6% and 84.4%, respectively. Endosonography was accurate in diagnosing regional lymph node metastases but not accurate in defining nonmetastatic lymphadenopathy and distant metastases.
CONCLUSION
Endosonography was accurate in staging tumor stage and lymph node metastases. Minimally invasive methods of resection for superficial ampullary cancers should be based on endosonography staging.
Topics: Ampulla of Vater; Cholangiopancreatography, Endoscopic Retrograde; Common Bile Duct Neoplasms; Endosonography; Female; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Pancreas; Pancreatic Neoplasms; Predictive Value of Tests
PubMed: 8979062
DOI: 10.1016/s0016-5107(96)70056-1 -
Medical Science Monitor : International... May 2017BACKGROUND We assessed the role of adjuvant intensity-modulated radiotherapy (IMRT) in combination with chemotherapy for pancreatic carcinomas after curative resection...
BACKGROUND We assessed the role of adjuvant intensity-modulated radiotherapy (IMRT) in combination with chemotherapy for pancreatic carcinomas after curative resection and identified prognostic factors related to pancreatic carcinoma after multidisciplinary treatment strategies. MATERIAL AND METHODS Pancreatic carcinoma patients (n=61) who received adjuvant radiotherapy after resection (median dose, 50.4 Gy) between 2010 and 2016 were retrospectively identified. Sixty patients received chemotherapy, including concurrent chemoradiotherapy (CCRT), systemic chemotherapy, and regional intra-arterial infusion chemotherapy (RIAC). The Kaplan-Meier method was used to measure the 3-year overall survival (OS) and disease-free survival (DFS) rates. Log-rank univariate analysis and multivariate Cox regression model analysis were used to identify prognostic factors. RESULTS Median follow-up time was 25.5 (range, 4.9-59.7) months. The 3-year OS and DFS rates were 31.0% and 16.1%, respectively. The median OS and DFS were 27.4 and 16.7 months, respectively. Multivariate analysis indicated that independent favorable predictors for OS were CCRT (p=0.039) and postoperative RIAC (p=0.044). Moreover, postoperative RIAC (p=0.027), and pre-radiotherapy CA19-9 ≤37 U/mL (p=0.0080) were independent favorable predictors for DFS. The combination of radiotherapy and chemotherapy was tolerated well by the patients, and no treatment-related death occurred. CONCLUSIONS Combined IMRT and adjuvant chemotherapy appeared safe and effective for pancreatic carcinoma. CCRT was associated with improved survival with acceptable toxicity. We propose that radiotherapy could be a part of postoperative treatment, but it should be administered concurrently with chemotherapy. Adding RIAC was associated with improved OS and DFS and it could be integrated into the postoperative treatment regimen.
Topics: Adenocarcinoma; Adult; Aged; Chemoradiotherapy; Chemotherapy, Adjuvant; Disease-Free Survival; Female; Humans; Infusions, Intra-Arterial; Kaplan-Meier Estimate; Male; Middle Aged; Pancreatic Neoplasms; Postoperative Period; Radiotherapy Dosage; Radiotherapy, Intensity-Modulated; Retrospective Studies
PubMed: 28512284
DOI: 10.12659/msm.904393 -
The growth pattern and microvasculature of pancreatic tumours induced with cultured carcinoma cells.British Journal of Cancer Feb 2000Pancreatic cancer is one of the most frustrating problems in gastroenterological surgery, since there is little we can do to improve the survival of patients with...
Pancreatic cancer is one of the most frustrating problems in gastroenterological surgery, since there is little we can do to improve the survival of patients with current treatment strategies. If one is to elucidate factors related to carcinogenesis, tumour biology, diagnostics and new treatment modalities of this malignant disease, then it is essential to develop a suitable animal model. In the present study we investigated rat pancreatic tumour growth after intrapancreatic injection of cultured pancreatic carcinoma cells (DSL-6A/C1), originally derived from an azaserine-induced tumour, as well as the features of tumour microcirculation using the microangiography technique. After intrapancreatic inoculation, tumours were detected in 64% of animals. A 1 cm3 tumour volume was reached within 20 weeks after inoculation. The tumours were ductal adenocarcinomas. Larger tumours showed invasive growth and spreading into the surrounding tissues, mainly into spleen and peritoneum. Microangiography revealed that the pancreatic tumours had an irregular and scanty vessel network and there were avascular areas in the center of the tumour. The area between normal pancreas and the induced tumour had dense vascularization. Intrapancreatic tumour induction with cultured pancreatic carcinoma cells produced a solid and uniformly growing tumour in Lewis rats and it thus provides a possible model for pancreatic cancer studies.
Topics: Animals; Cell Division; Male; Neoplasm Transplantation; Pancreatic Neoplasms; Rats; Rats, Inbred Lew; Tumor Cells, Cultured
PubMed: 10732764
DOI: 10.1054/bjoc.1999.1017 -
The Kurume Medical Journal 2014Comparative study of contrast-enhanced ultrasonography (CE-US) and histopathology of surgically resected specimens in 13 patients with pancreatic carcinoma. A time... (Comparative Study)
Comparative Study
Comparative study of contrast-enhanced ultrasonography (CE-US) and histopathology of surgically resected specimens in 13 patients with pancreatic carcinoma. A time intensity curve was used to determine the percentage brightness increase in cancerous and normal regions and the patients were divided into two groups, hyperperfusion, with a percentage brightness increase over 80% (n=6) and hypoperfusion, with an increase of less than 80% (n=7) on CE-US. The hyperperfusion group included well-differentiated tubular adenocarcinoma, adenosquamous cell carcinoma and acinar cell carcinoma, while all 7 patients in the hypoperfusion group had moderately differentiated tubular adenocarcinoma. Immunological staining (α-SMA and anti-CD34) of the resected specimens showed significantly higher microartery count (MAC) in the hyperperfusion group (p<0.005) than in the hypoperfusion group or normal pancreas. In the normal pancreas, the mean vessel diameter was significantly higher (over 100 μm) than in the hyperperfusion group (30 μm; p<0.005). It was concluded that a muscular arterial vessel density of less than 30 μm is an important factor in determining staining degree and carcinoma progression by CE-US in pancreatic carcinoma.
Topics: Actins; Adenocarcinoma; Aged; Antigens, CD34; Arteries; Biomarkers, Tumor; Carcinoma; Carcinoma, Acinar Cell; Carcinoma, Adenosquamous; Contrast Media; Female; Humans; Immunohistochemistry; Male; Middle Aged; Muscle, Smooth, Vascular; Pancreatic Neoplasms; Polysaccharides; Predictive Value of Tests; Staining and Labeling; Ultrasonography
PubMed: 24531182
DOI: 10.2739/kurumemedj.ms63006 -
Cancer Medicine Feb 2023Pancreatic carcinoma (PC) is a highly lethal cancer with an increasing mortality rate, its five-year survival rate is only approximately 4%. N6-methyladenosine (m6A)...
BACKGROUND
Pancreatic carcinoma (PC) is a highly lethal cancer with an increasing mortality rate, its five-year survival rate is only approximately 4%. N6-methyladenosine (m6A) modification is the most common posttranscriptional modification of RNA, it could affect tumor formation by regulating m6A modifications in the mRNA of key oncogenes or tumor suppressor genes. However, its role in PC remains unclear.
METHODS
We combined bioinformatic analysis with in vitro and in vivo experiments to investigate the expression profile of methylation modulators and identify key m6A regulators in the progression of PC. Further study focused on exploring the target genes binding to the regulators through RIP and immunofluorescence staining experiment.
RESULTS
TCGA and Gene Expression Omnibus (GEO) analyses revealed an overall increasing trend in the expression of m6A regulators in PC, and consensus clustering analysis of m6A modification showed that the expression of regulators was negatively correlated with the survival rate. LASSO-Cox regression analysis revealed that IGF2BP2, METTL3, ALKBH5 and KIAA1429 were associated with hazard ratios (HR), but only IGF2BP2 was sufficiently appropriate for the m6A survival prognosis model. The IHC and WB results verified high protein expression of IGF2BP2 in PC, and IGF2BP2 knockdown inhibited the proliferation and migration of PC cells. We predicted and verified B3GNT6 was observably regulated by IGF2BP2 via RIP assays. In addition, IF staining confirmed the co-expression of IGF2BP2 and B3GNT6. The tumor-promoting effect of IGF2BP2 and its co-expression with B3GNT6 were verified in an animal model.
CONCLUSIONS
Elevated m6A levels promote PC progression. IGF2BP2 is a credible marker and modulates B3GNT6 mRNA stability, indicating that IGF2BP2 is a potential prognostic marker and therapeutic target in PC progression.
Topics: Animals; Methylation; RNA, Messenger; Pancreatic Neoplasms; RNA
PubMed: 35908253
DOI: 10.1002/cam4.5096