Mutation and Expression of Gene YY1 in Pancreatic Neuroendocrine Tumors and Its Clinical Significance.

OBJECTIVE: The clinical significance of the YY1 gene mutation and expression in pancreatic neuroendocrine tumors (PNETs) remains unknown. Therefore, this study aimed to comprehensively analyze the somatic mutation of YY1 in the different subtypes of PNETs. METHODS: A total of 143 PNETs were assessed by Sanger sequencing to identify the somatic mutation of YY1 gene in various subtypes of PNETs. YY1 protein expression was examined in 103 PNETs by immunohistochemical staining and western blot. Gene mutation and its protein expression were correlated with clinicopathologic features. RESULTS: A recurrent mutation (chr14:100743807C>G) in the YY1 gene was identified in 15 of 83 insulinomas (18%) and in only 1 of 60 noninsulinoma PNETs (1.7%) (P = .0045). The YY1 mutation was not found in MEN1-associated insulinomas. The YY1 mutation in insulinomas was correlated with older age and lower serum glucose levels (age, 57 vs 42.5 years, P = .006; blood glucose, 25.2 vs 33.6 mg/dL, P = .008). YY1 protein expression was found in 100 of 103 PNETs, although expression was weaker in metastases than in localized tumors (P = .036). The stronger expression of YY1 protein was associated with favorable disease-free survival of patients with PNETs (log-rank, P = .011; n = 70). Multivariable statistical analysis showed that YY1 protein expression could be an independent predictor of prognosis. CONCLUSION: The hotspot YY1 mutation mostly occurred in insulinomas and rarely in noninsulinoma PNETs. The stronger YY1 protein expression was correlated with the better prognosis of PNETs patients.

Dynamic hematological changes in patients undergoing distal pancreatectomy with or without splenectomy: a population-based cohort study.

BACKGROUND: The clinical outcomes of patients who received distal pancreatectomy with splenectomy (DPS) and spleen-preserving distal pancreatectomy (SPDP) have been generally investigated. However, postoperative hematological changes after distal pancreatectomy with or without splenectomy are poorly understood. METHODS: Information from patients undergoing distal pancreatectomy (DP) between January 2014 and June 2019 at a single institution was reviewed. A linear mixed-effects model was used to compare dynamic hematological changes between different groups. RESULTS: A total of 302 patients who underwent DP were enrolled. In the long term, most postoperative hematological parameters remained significantly higher than preoperative levels in the DPS group, while postoperative lymphocyte, monocyte, basophil, and platelet levels returned to preoperative levels in the SPDP group. All postoperative hematological parameters except for red blood cell count and serum hemoglobulin level were significantly higher in the DPS group than in the SPDP group. There were no significant differences in hematological changes between the splenic vessel preservation (SVP) and Warshaw technique (WT) groups. CONCLUSIONS: Postoperative hematological changes were significantly different between the DPS and SPDP groups. Compared to DPS, SPDP reduced abnormal hematological changes caused by splenectomy. SVP and WT were comparable in terms of postoperative hematological changes.

Prognostic and predictive value of a five-molecule panel in resected pancreatic ductal adenocarcinoma: A multicentre study.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has a devastating prognosis. The performance of clinicopathologic parameters and molecules as prognostic factors remains limited and inconsistent. The present study aimed to construct a multi-molecule biomarker panel to more accurately predict post-resectional prognosis of PDAC patients. METHODS: Firstly, a novel computational strategy integrating prognostic evidence from omics and literature on the basis of bioinformatics prediction (CIPHER) to generate the network, was designed to systematically identify potential high-confidence PDAC-related prognostic candidates. After specimens from 605 resected PDAC patients were retrospectively collected, 23 candidates were detected immunohistochemically in tissue-microarrays for the development cohort to construct a multi-molecule panel. Lastly, the panel was validated in two independent cohorts. FINDINGS: According to the constructed five-molecule panel, disease-specific survival (DSS) was significantly poorer in high-risk patients than in low-risk ones in development cohort (HR 2.15, 95%CI 1.51-3.05, P<0.0001; AUC 0.67). In two validation cohorts, similar significant differences between the two groups were also observed (HR 3.18 and 3.31, 95%CI 1.89-5.37 and 1.78-6.16, All P<0.0001; AUC 0.72 and 0.73). In multivariate analyses, this panel was the sole prognosticator that was significant in each cohort. Furthermore, its predictive power for long-term survival, higher than its individual constituents, could be largely enhanced by combination with traditional clinicopathological variables. Finally, adjuvant chemotherapy (ACT) correlated with better DSS only in high-risk patients, uni- and multi-variately, in all the cohorts. INTERPRETATION: The novel prognostic panel developed by a systematically network-based strategy presents strong ability in prediction of post-resectional survival of PDAC patients. Furthermore, panel-defined high-risk patients might benefit more from ACT.

Effect of Blumgart anastomosis in reducing the incidence rate of pancreatic fistula after pancreatoduodenectomy.

BACKGROUND: Pancreatic fistula is one of the most serious complications after pancreatoduodenectomy for treating any lesions at the pancreatic head. For years, surgeons have tried various methods to reduce its incidence. AIM: To investigate and emphasize the clinical outcomes of Blumgart anastomosis compared with traditional anastomosis in reducing postoperative pancreatic fistula. METHODS: In this observational study, a retrospective analysis of 291 patients who underwent pancreatoduodenectomy, including Blumgart anastomosis (201 patients) and traditional embedded pancreaticojejunostomy (90 patients), was performed in our hospital. The preoperative and perioperative courses and long-term follow-up status were analyzed to compare the advantages and disadvantages of the two methods. Moreover, 291 patients were then separated by the severity of postoperative pancreatic fistula, and two methods of pancreaticojejunostomy were compared to detect the features of different anastomosis. Six experienced surgeons were involved and all of them were proficient in both surgical techniques. RESULTS: The characteristics of the patients in the two groups showed no significant differences, nor the preoperative information and pathological diagnoses. The operative time was significantly shorter in the Blumgart group (343.5 ± 23.0 vs 450.0 ± 40.1 min, P = 0.028), as well as the duration of pancreaticojejunostomy drainage tube placement and postoperative hospital stay (12.7 ± 0.9 d vs 17.4 ± 1.8 d, P = 0.031; and 21.9 ± 1.3 d vs 28.9 ± 1.3 d, P = 0.020, respectively). The overall complications after surgery were much less in the Blumgart group than in the embedded group (11.9% vs 26.7%, P = 0.002). Patients who underwent Blumgart anastomosis would suffer less from severe pancreatic fistula (71.9% vs 50.0%, P = 0.006), and this pancreaticojejunostomy procedure did not have worse influences on long-term complications and life quality. Thus, Blumgart anastomosis is a feasible pancreaticojejunostomy procedure in pancreatoduodenectomy surgery. It is safe in causing less postoperative complications, especially pancreatic fistula, and thus shortens the hospitalization duration. CONCLUSION: Surgical method should be a key factor in reducing pancreatic fistula, and Blumgart anastomosis needs further promotion.

[Preparation of Two Kinds of Biochar and the Factors Influencing Tetracycline Removal from Aqueous Solution].

In this research, Chinese medicine residue of Evodia lepta and corn stalks were chosen as raw materials to prepare biochar (EIBC and CSBC) at 400, 600, and 800℃, for the removal of tetracycline from solution. The biochar was characterized by elemental analysis, Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), and scanning electron microscopy (SEM). The effects of pyrolytic temperature, biochar dosages, initial concentration, adsorption time, solution pH, ionic strength, and ambient temperature on the removal of tetracycline from solutions by biochar were investigated. The adsorption behavior of tetracycline by biochar was investigated using adsorption kinetics and adsorption isotherms. The results showed that the adsorption capacity of biochar for tetracycline was elevated with increase in the pyrolysis temperature. The biochar prepared from Chinese medicine residue Evodia lepta at under 800℃ (EIBC800) had the best adsorption properties. Biochar dosages, solution pH, ionic strength, and adsorption time had significant effects on the adsorption of tetracycline by EIBC800 and CSBC800. In contrast, the effect of ambient temperature on tetracycline adsorption was a concentration-dependent process. The adsorption kinetics and isotherms of tetracycline onto EIBC800 and CSBC800 were all fitted to pseudo-second order models (R2 0.9540 and 0.8355) and to a Freundlich equation (R2 between 0.8991-0.9579 and 0.9736-0.9946), respectively. The adsorption process was mainly controlled by chemical reaction, and the tetracycline adsorption process was spontaneous and endothermic. Compared with the corn-stalk derived biochar, EIBC800 had better adsorption capacity for antibiotics than CSBC800 did, which indicated that Chinese medicine residue derived biochar had wider prospects for application in the treatment of wastewater containing antibiotic residues.

WT1 associated protein promotes metastasis and chemo-resistance to gemcitabine by stabilizing Fak mRNA in pancreatic cancer.

WT1 associated protein (WTAP), playing an important role in several malignancies owing to its complex function in transcriptional and post-transcriptional regulation, is an independent prognostic indicator for pancreatic cancer (PC). However, its specific role and underlying mechanism in PC remain unclear. In the present study, we found that WTAP could promote migration/invasion and suppress chemo-sensitivity to gemcitabine in PC. Further mechanical investigation revealed that WTAP could bind to and stabilize Fak mRNA which in turn activated the Fak-PI3K-AKT and Fak-Src-GRB2-Erk1/2 signaling pathways. In addition, GSK2256098, a specific Fak inhibitor, could reverse WTAP-mediated chemo-resistance to gemcitabine and metastasis in PC. Taken together, Fak inhibitor might be a promising therapeutic option for PC patients with WTAP overexpression.

Plasminogen Activator Inhibitor 1 as a Poor Prognostic Indicator in Resectable Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Plasminogen activator inhibitor 1 (PAI-1) was previously established to impact several phenotypes in many kinds of cancer, including pancreatic cancer. However, its prognostic significance in pancreatic ductal adenocarcinoma (PDAC) needs support of further evidence. This study was designed to address the issue. METHODS: PAI-1 expression was detected by tissue microarray-based immunohistochemical staining in formalin-fixed paraffin-embedded specimens from 93 PDAC patients with surgical resection from September 2004 to December 2008. Its relationships with clinicopathologic variables and tumor-specific survival (TSS) were further evaluated using Chi-square, Kaplan-Meier, log-rank, as well as Cox regression analyses. RESULTS: Expression of PAI-1 was much higher in tumor than that in nontumor tissues, based on comparison of all samples and 74 matched ones (95 [47.5, 180] vs. 80 [45, 95], Z = -2.439, P = 0.015 and 100 [46.9, 182.5] vs. 80 [45, 95], Z = -2.594, P = 0.009, respectively). In addition, tumoral PAI-1 expression was positively associated with N stage (22/35 for N1 vs. 21/51 for N0, χ2 = 3.903, P = 0.048). Univariate analyses showed that TSS of patients with high PAI-1 tumors was significantly poorer than that of those with low PAI-1 tumors (log rank value = 19.00, P < 0.0001). In multivariate Cox regression test, PAI-1 expression was identified as an independent predictor for long-term prognosis of resectable PDAC (hazard ratio = 2.559, 95% confidence interval = 1.499-4.367, P = 0.001). CONCLUSION: These results suggest that expression of PAI-1 is upregulated in PDAC and might serve as a poor prognostic indicator.

High expression of GRK3 is associated with favorable prognosis in pancreatic ductal adenocarcinoma.

BACKGROUND: It was found that G-protein-coupled receptor kinase 3 (GRK3) played key biological roles in some cancers. However, its associations with clinicopathologic features and prognosis in pancreatic ductal adenocarcinoma (PDAC) remain unknown. METHODS AND METHODS: Expression of GRK3 was detected, using tissue microarray-based immunohistochemistry, in paired formalin-fixed paraffin-embedded tumor and non-tumor samples from 165 patients with PDAC after curative resection, and was further correlated with clinicopathologic parameters and cancer-specific survival (CSS). RESULTS: It was shown that GRK3 expression was much lower in tumor than in non-tumor tissues. Moreover, expression of GRK3 in tumor tissues was significantly associated with gender and T stage. Univariately, high GRK3 expression was predictive for favorable CSS, along with some conventional clinicopathologic variables. In multivariate Cox regression test, GRK3 expression remained to be a significant prognostic marker for PDAC. Finally, combination of GRK3 with some clinicopathologic variables, especially N stage, obtained more precise prediction for CSS. CONCLUSIONS: Our data suggested that expression of GRK3 was down-regulated in PDAC and was an independent prognostic factor.

Surgeons' knowledge regarding the diagnosis and management of pancreatic cancer in China: a cross-sectional study.

BACKGROUND: Pancreatic cancer is rare but highly malignant. Studies have shown that surgeons' knowledge closely links to the correct diagnosis and treatment outcomes of pancreatic cancer. The purpose of this study was to survey current surgeons' knowledge regarding pancreatic cancer. METHODS: A cross-sectional study was conducted among 705 surgeons who attended the 2011 China Surgical Week's meeting in Beijing. A questionnaire regarding the risk factors, clinical manifestations, diagnosis, and treatment of pancreatic cancer was used. Surgeons' answers were analyzed and compared among different regions, levels of hospital, and professional ranks. RESULTS: Most surgeons had a correct knowledge toward the risk factors, diagnosis, and management of pancreatic cancer. However, several knowledge gaps were identified. They include "The association between type 2 diabetes and pancreatic cancer", "The most common histologic type of pancreatic neoplasm", "the typical clinical symptoms of pancreatic cancer", "The accuracy of ultrasound in screening pancreatic cancer", "Enhanced CT in the diagnosis of pancreatic cancer", and "Which is more superior between MRI and CT in the diagnosis of pancreatic cancer". We also found that overall surgeons' responses did not depend on their geographic locations, but on hospital levels and professional ranks. Surgeons working at level three hospitals had better knowledge than others in certain areas and resident surgeons had fewer correct answers in some areas. CONCLUSIONS: Although most surgeons have a good knowledge in most areas related to the diagnosis and treatment of pancreatic cancer in China, certain knowledge gaps exist, particularly among trainees and those from low level hospitals. Continuing medical education programs to improve these knowledge gaps should be implemented.

Prognostic relevance of UCH-L1 and α-internexin in pancreatic neuroendocrine tumors.

Prognostic biomarkers for the pancreatic neuroendocrine tumors are needed. Proteomic study on insulinoma has been rarely reported. We identified the differential expression of proteins between insulinoma and their paired tissues by proteomic analysis, and evaluated the prognostic significance of specific proteins in pancreatic neuroendocrine tumors including insulinoma. The differential expression of select proteins was validated in more than 300 tumors using immunohistochemical staining and western blot. Methylation of UCH-L1 promoter in tumors was examined by methylation specific PCR and validated by sequencing. The concurrent expression of UCH-L1 and α-internexin was correlated with the prognosis in 2 independent collectives of patients with tumors. Sixty-two and 219 proteins were significantly down-regulated and up-regulated in insulinomas, respectively. Demethylation of UCH-L1 promoter was associated with UCH-L1 expression in tumors (p = 0.002). The concurrent expression of UCH-L1 and α-internexin in pancreatic neuroendocrine tumors was significantly associated with better overall survival and disease-free survival in the combination of both cohorts (log rank p = 3.90 × 10-4 and p = 3.75 × 10-5, respectively) and in each of cohorts. The prognostic value of both proteins was also validated in patients with stage II and III tumors (p = 0.017 and p = 0.006, respectively). The proteins UCH-L1 and α-internexin could be independent prognostic biomarkers of pancreatic neuroendocrine tumors.

WT1-associated protein is a novel prognostic factor in pancreatic ductal adenocarcinoma.

Although Wilms tumor 1 (WT1)-associated protein (WTAP) was initially found to be a specific WT1-binding protein, it has increasingly attracted attention because of its oncogenic role in various types of malignancies, including cholangiocarcinoma, glioblastoma and acute myeloid leukemia. However, the clinical impact of WTAP on pancreatic ductal adenocarcinoma (PDAC) is still unknown. A total of 145 patients who underwent surgical treatment from 2004 to 2008 were enrolled in the present study. The cytoplasmic and nuclear expression of WTAP in tumor and adjacent normal tissues was examined by immunohistochemical analysis in order to investigate the relationship between WTAP and the clinicopathological factors and prognosis of patients with PDAC. The nuclear and cytoplasmic expression of WTAP in tumor tissues was significantly higher compared with non-tumor tissues (P<0.001). High expression of WTAP in the nucleus was significantly associated with gender (P=0.010) and tumor stage (P=0.020), while high expression of WTAP in the cytoplasm was significantly associated with gender (P=0.018), histological grade (P=0.047) and perineural invasion (P=0.028). In addition, a univariate analysis revealed that high nuclear expression of WTAP in tumor tissues was significantly associated with poor overall survival (P<0.001), as well as several clinicopathological variables, including gender and N stage. In a multivariate Cox regression analysis, nuclear WTAP expression was identified as an independent prognostic indicator for PDAC (relative risk, 1.855; 95% confidence interval, 1.033-3.333; P=0.039). The results of the present study indicated that high nuclear expression of WTAP is a valuable molecular biomarker of a poor prognosis among patients with PDAC.

Expression of key mTOR pathway components in pancreatic ductal adenocarcinoma: A multicenter study for clinicopathologic and prognostic significance.

Thus far, clinicopathologic and prognostic significance of mTOR signaling pathway in pancreatic ductal adenocarcinoma (PDAC) remains unclear, although it is involved in PDAC. In this study, total (t-) and phosphorylated (p-) mTOR, 4EBP1 and P70S6K, were investigated. It was found that most aforementioned proteins were related to malignant and progressive phenotypes, especially histological grade, in independent development and validation cohorts of PDAC. In the development cohort, high expression and/or phosphorylation of mTOR, 4EBP1 and P70S6K were all univariately associated with poor tumor-specific survival, whereas p-mTOR, p-4EBP1 and p-P70S6K, adjusted for clinicopathologic variables, unlike t-mTOR, t-4EBP1 and t-P70S6K, were shown to be independent prognostic factors in multivariate analysis. Interestingly and importantly, the independently significant impacts of p-mTOR and p-4EBP1 on tumor-specific survival were confirmed in the validation cohort. Contrarily, t-mTOR and t-4EBP1 were only univariately significant, while t-P70S6K and p-P70S6K were not prognostic. Finally, mTOR and EIF4EBP1, genes encoding mTOR and 4EBP1, also serve as prognostic indicators in the publicly available TCGA RNA-sequencing database. Our data indicate that expression and activation, especially the latter, of mTOR and 4EBP1, might have clinicopathologic and prognostic significance in PDAC.

CXCL12-CXCR7 axis contributes to the invasive phenotype of pancreatic cancer.

Chemokine (C-X-C motif) receptor 7 (CXCR7) and its ligand, chemokine (C-X-C motif) ligand 12 (CXCL12), were established to be involved in biological behaviors and associated with prognosis in many cancers. However, effects, underlying mechanisms of CXCL12-CXCR7 axis in invasive phenotype of pancreatic cancer (PC) and its clinicopathologic significances have not been comprehensively explored. In the present study, it was first found by tissue microarray-based immunohistochemistry that CXCL12 and CXCR7 staining scores were significantly associated with vessel invasion and overall survival in two independent cohorts of PC. Besides, co-expression of these proteins was an independent prognosticator in multivariate analysis in both cohorts. Then, migration and invasion, but not proliferation, were decreased in CXCR7-stably silenced PC cells, whereas opposite changes were observed in CXCR7-stably overexpressed cells, accompanied by alterations of mTOR and Rho/ROCK pathways. CXCL12 stimulated migration, invasion, CXCR7 expression and phosphorylation of key mTOR proteins. AMD3100 did not influence effects of CXCL12. Two mTOR inhibitors, rapamycin and Torin1, reversed enhanced invasive phenotypes and mTOR phosphorylation in CXCR7-overexpressed cells. Moreover, CXCR7 directly interacts with mTOR. Finally, liver metastasis, but not growth, was affected by CXCR7 status in orthotopically-implanted PC models in nude mice. Collectively, CXCL12-CXCR7 axis accelerates migration and invasion of PC cells through mTOR and Rho/ROCK pathways, and predicts poor prognosis of PC.

Pancreatic metastasis of renal cell carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) is a common cancer, but pancreatic metastasis of RCC is unusual. Because of the rarity and peculiarity, pancreatic lesions from RCC metastasis were described mostly in case reports which highlight the importance of a systematic analysis of this clinical condition. DATA SOURCES: Data of 7 patients with pancreatic metastasis of RCC treated in the Peking Union Medical College Hospital were extracted and 193 similar patients reported in the past 10 years from the literature were analyzed. Epidemiological, pathological and follow-up information were investigated. Potential prognostic factors were compared with corresponding data reported 10 years ago. RESULTS: Multivariate Cox regression showed that asymptomatic metastasis and surgical procedure were independent factors associated with better survival. Compared with the data reported 10 years ago, follow-up of RCC patients has been emphasized in recent years, and atypical surgery is frequently used since it has similar effect as typical surgery on tumor resection while it is able to preserve more pancreatic function. CONCLUSION: Surgical treatment should be an option as long as the pancreatic metastasis of RCC is resectable.

Filamin A: Insights into its Exact Role in Cancers.

Filamin A (FlnA) is a well-known actin cross-linking protein. It serves as a scaffold for over 90 binding partners and involves in multiple cell functions, of which cell migration and adhesion is especially critical. Recently, its role in the cell has come under scrutiny for FlnA's involvement in cancer development. Originally revealed as a cancer-promoting protein, FlnA actually plays a dual role in cancers. When localized to the cytoplasm, FlnA has a tumor-promoting effect by interacting with signaling molecules. While once localized to the nucleus, it may act to suppress tumor growth and inhibit metastasis by interacting with transcription factors. Thus drugs that can cause FlnA to transpose from cytoplasm to nucleus could be a promising treatment for cancers. Study to this end is on the way in prostate cancer and the results are encouraging. FlnA has been studied in large categories of cancers, such as prostate cancer, breast cancer, melanoma, lung cancer, etc. However, most studies did not evaluate the differences that arise from the localization of the protein, which was a great pity! What's more, although FlnA's is undoubtedly important in cancer invasion and metastasis, both preclinical and clinical researches are very rare in some highly metastatic cancers, such as pancreatic cancer. In this mini-review, we give a comprehensive summary of FlnA' s expression in cancers. Where available, we also indicate the correlation of FlnA with cancer stages and patient prognosis, and clarify its localization (nucleus/cytoplasm) and its dual role (promote/suppress) in different cancers.

Expression and Significances of MTSS1 in Pancreatic Cancer.

Thus far, expression of metastasis suppressor 1 (MTSS1), its clinicopathologic and prognostic significances in pancreatic cancer (PC) remain unknown. Expression of MTSS1 was detected by Western blotting in PC cell lines, and by tissue microarray-based immunohistochemical staining in paired tumor and non-tumor samples from 242 patients with PC. Furthermore, the correlations between MTSS1 expression and clinicopathologic variables as well as overall survival were evaluated. In PC cell lines, MTSS1 was differentially expressed. In addition, MTSS1 expression was significantly lower in tumor than in non-tumor tissues (P < 0.001 in both McNemar and Mann-Whitney U tests). High tumoral expression of MTSS1 was closely associated with absence of lymph node metastasis (P = 0.023). Univariate analysis found that high MTSS1 expression in tumor tissues was a strong predictor of favorable overall survival in the whole cohort (P < 0.001). Besides, its impacts on prognosis were also observed in nine out of fourteen subgroups. Finally, MTSS1 expression was identified as an independent prognostic marker in the whole cohort (P = 0.031) as well as in six subgroups (P < 0.05), as shown by multivariate Cox regression test. Down-regulation of MTSS1 expression is evident in PC, and is associated with lymph node metastasis and poor prognosis.

Expression of c-fos was associated with clinicopathologic characteristics and prognosis in pancreatic cancer.

It has long been regarded that pancreatic cancer (PC) is a life-threatening malignant tumor. Thus, much attention has been paid for factors, especially relative molecules, predictive for prognosis of PC. However, c-fos expression in PC was less investigated. In addition, its association with clinicopathologic variables and prognosis remains unknown. In the present study, expression of c-fos was detected by tissue microarray-based immunohistochemical staining in cancer and adjacent tissues from 333 patients with PC. The staining results were correlated with clinicopathologic parameters and overall survival. Furthermore, prognostic significance of c-fos in subsets of PC was also evaluated. It was shown that low expression of c-fos was more often in cancer than in adjacent tissues of PC (P<0.001). Besides, high cancerous c-fos expression was significantly associated with tumor site and T stage, whereas peri-neural invasion was of a borderline significant relevance. Log-rank test revealed that high expression of c-fos in cancer tissues was a significant marker of poor overall survival, accompanied by some conventional clinicopathologic variables, such as sex, grade, peri-neural invasion, T and N stages. More importantly, cancerous c-fos expression was identified as an independent prognosticator in multivariate analysis. Finally, the prognostic implication of c-fos expression was proven in four subsets of patients with PC. These data suggested that c-fos expression was of relationships with progression and dismal prognosis of PC.

Pancreatic cancer stem cells: new insight into a stubborn disease.

Resistance to conventional therapy and early distant metastasis contribute to the unsatisfactory prognosis of patients with pancreatic cancer. The concept of cancer stem cells (CSCs) brings new insights into cancer biology and therapy. Many studies have confirmed the important role of these stem cells in carcinogenesis and the development of hematopoietic and solid cancers. Recent studies have shown that CSCs regulate aggressive behavior, recurrence, and drug resistance in pancreatic cancer. Here, we review recent advances in pancreatic cancer stem cells (PCSCs) research. Particular attention is paid to the regulation mechanisms of pancreatic cancer stem cell functions, such as stemness-related signaling pathways, microRNAs, the epithelial-mesenchymal transition (EMT), and the tumor microenvironment, and the development of novel PCSCs targeted therapy. We seek to further understand PCSCs and explore potential therapeutic targets for pancreatic cancer.

Recent studies of 5-fluorouracil resistance in pancreatic cancer.

Resistance to 5-fluorouracil (5-FU), an important anticancer drug, is a serious challenge in the treatment of pancreatic cancer. Equilibrative nucleoside transporter 1 and multidrug-resistance protein (MRP) 5 and MRP8, rather than P-glycoprotein, play important roles in 5-FU transport. Thymidylate synthase, dihydropyrimidine dehydrogenase, methylenetetrahydrofolate reductase and thymidine phosphorylase are four key enzymes involved in 5-FU metabolism. Other metabolic enzymes, including uridine monophosphate synthetase, also contribute to chemoresistance. Intracellular signaling pathways are an integrated network, and nuclear factor kappa-light-chain-enhancer of activated B cells, AKT and extracellular signal-regulated kinases are signaling pathways that are particularly relevant to 5-FU resistance. In addition, recent reports indicate that STAT-3 is a crucial survival protein. Proteomic assays provide a powerful tool for identifying target proteins and understanding the role of microRNAs and stromal factors to facilitate the development of strategies to combat 5-FU resistance.