Borderline or locally advanced pancreatic adenocarcinoma: A single center experience on the FOLFIRINOX induction regimen

IntroductionThis study aimed to determine the impact of FOLFIRINOX neoadjuvant therapy on patients with non-metastatic borderline/locally advanced (BL/LA) pancreatic ductal adenocarcinoma (PDAC), in current practice.Material and methodsFrom 2010 to 2017, 258 patients with BL/LA PDAC from a single high-volume institution received FOLFIRINOX neoadjuvant treatment.ResultsThe 258 patients received a median number of 6 cycles of FOLFIRINOX (range, 3–16); 98 (38%) patients underwent curative surgery, and 160 (62%) continued medical treatment. A venous resection was performed in 57 patients (58%), and an arterial resection in 12 (12%). The postoperative 30- and 90-day mortality rates were 6.1% and 8.2%, respectively. Adjuvant chemotherapy was performed in 57 patients (59%). The median overall survival (OS) in patients who did (n = 98) or did not (n = 160) undergo surgical resection were 39 months and 19 months, respectively (P < 0.001). In resected patients, the ASA 3 score (P < 0.01), venous resection (P < 0.01), hemorrhage (P < 0.01), and R1 margin status (P = 0.03) were found to negatively influence the OS. The median OS was significantly higher in patients who did not require a venous resection (not reached vs. 26.5 months, P < 0.001).ConclusionsNeoadjuvant FOLFIRINOX provided a survival benefit in BL/LA PDAC patients, particularly in those who did not ultimately require venous resection.     

The role of lncRNA MSC-AS1/miR-29b-3p axis-mediated CDK14 modulation in pancreatic cancer proliferation and Gemcitabine-induced apoptosis

Pancreatic ductal adenocarcinoma (PDAC) remains a leading cause of cancer-related death due to the failure of traditional therapies. In the present study, we attempted to construct a lncRNA-miRNA-mRNA network which may modulate PDAC cell proliferation and Gemcitabine-induced cell apoptosis starting from CDK14, a new member of the CDK family and an oncogene in many cancers. Based on TCGA data, a significant positive correlation was observed between lncRNA MSC-AS1 and CDK14. Moreover, MSC-AS1 expression was upregulated in PDAC tissues. Higher MSC-AS1 expression was correlated with poorer prognosis in patients with PDAC. MSC-AS1 knockdown in Panc-1 and BxPC-3 cells significantly inhibited the cell proliferation. Moreover, miR-29b-3p, which has been reported to act as a tumor suppressor, was predicted to bind to both MSC-AS1 and CDK14. Contrary to MSC-AS1, higher miR-29b-3p expression was correlated to better prognosis in patients with PDAC. In both PDAC cell lines, miR-29b-3p negatively regulated MSC-AS1 and CDK14. As confirmed using luciferase reporter gene and RIP assays, MSC-AS1 served as a ceRNA for miR-29b-3p to counteract miR-29b-mediated CDK14 repression. MSC-AS1 knockdown inhibited CDK14 protein levels and PDAC proliferation and enhanced gemcitabine-induced cell death and apoptosis while miR-29b-3p inhibition exerted an opposing effect; the effect of MSC-AS1 knockdown was partially attenuated by miR-29b-3p inhibition. Taken together, we demonstrated that MSC-AS1/miR-29b-3p axis modulates the cell proliferation and GEM-induced cell apoptosis in PDAC cell lines through CDK14. We provided a novel experimental basis for PDAC treatment from the perspective of lncRNA-miRNA-mRNA network.     

LINC00205 promotes proliferation,migration and invasion of HCC cells by targeting miR-122-5p

Long non-coding RNAs (lncRNAs) have been identified as crucial regulators in the tumorigenesis and progression of hepatocellular carcinoma (HCC). Recently, long intergenic non-protein coding RNA 205 (LINC00205) has been identified as a prognostic biomarker in HCC. However, the biological role of LINC0205 and its potential molecular mechanism are poorly investigated. Here, we found that the expression of LINC00205 was dramatically up-regulated in HCC tissues compared to adjacent nontumor tissues. Furthermore, the level of LINC00205 in both Hep3B and Huh7 cells was prominently higher than that in normal hepatic cell line LO2. Notably, the high expression of LINC00205 was strongly correlated with tumor size ≥5 cm, venous infiltration and advanced tumor stages. Functionally, LINC00205 knockdown obviously repressed the proliferation, migration and invasion of Hep3B and Huh7 cells in vitro. An inverse correlation between LINC00205 and miR-122-5p was detected in HCC tissues. Interestingly, LINC00205 knockdown increased the level of miR-122-5p in both Hep3B and Huh7 cells. Mechanistically, luciferase reporter assay demonstrated LINC00205 acted as a competing endogenous RNA (ceRNA) by directly interacting with miR-122-5p. More importantly, miR-122-5p overexpression significantly restrained the proliferation, migration and invasion of HCC cells. Collectively, our study provides solid evidence to support the oncogenic role of LINC00205 in HCC, which may be benefit for the improvement of HCC therapy.     

Fungal mycobiome drives IL-33 secretion and type 2 immunity in pancreatic cancer

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Indocyanine green loaded hyaluronan-derived nanoparticles for fluorescence-enhanced surgical imaging of pancreatic cancer

Pancreatic ductal adenocarcinoma is highly lethal and surgical resection is the only potential curative treatment for the disease. In this study, hyaluronic acid derived nanoparticles with physico-chemically entrapped indocyanine green, termed NanoICG, were utilized for intraoperative near infrared fluorescence detection of pancreatic cancer. NanoICG was not cytotoxic to healthy pancreatic epithelial cells and did not induce chemotaxis or phagocytosis, it accumulated significantly within the pancreas in an orthotopic pancreatic ductal adenocarcinoma model, and demonstrated contrast-enhancement for pancreatic lesions relative to non-diseased portions of the pancreas. Fluorescence microscopy showed higher fluorescence intensity in pancreatic lesions and splenic metastases due to NanoICG compared to ICG alone. The in vivo safety profile of NanoICG, including, biochemical, hematological, and pathological analysis of NanoICG-treated healthy mice, indicates negligible toxicity. These results suggest that NanoICG is a promising contrast agent for intraoperative detection of pancreatic tumors.     

93例胰腺导管腺癌患者的临床预后分析

目的探讨影响胰腺癌患者预后的相关因素。方法回顾性分析93例胰腺患者的临床分期、病理分化、手术情况、CA199指标、是否化疗等情况,分析其对患者预后的影响。结果93例胰腺癌患者中位无瘤生存期(median disease free survival,mDFS)为14个月,中位总生存期(median overall survival,mOS)为16.5个月。将肿瘤分期、肿瘤分化程度、术前CA199水平、治疗后CA199是否下降、是否达到R0切除、是否进行淋巴结清扫、是否新辅助化疗进行COX回归多因素分析,均可作为独立因素影响患者DFS和OS(P<0.05)。结论肿瘤分期、分化程度、术前CA199水平、治疗后CA199是否下降可作为判断胰腺癌患者预后的指标,手术中R0切除、淋巴结清扫和新辅助化疗可提高患者预后。     

Combinatorial Approaches to Enhance DNA Damage following Enzyme-Mediated Depletion of L-Cys for Treatment of Pancreatic Cancer

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Proteins of the retinoblastoma pathway,FEN1 and MGMT are novel potential prognostic biomarkers in pancreatic adenocarcinoma

Background

We studied the expression of some major proteins involved in cell-cycle regulation and DNA repair, the roles of which are not well known in pancreatic ductal adenocarcinoma (PDAC), but which have a significant impact on carcinogenesis of many other cancers.