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Pancreatic cancer (PC) is one of the deadliest gastrointestinal cancers, accounting for the fourth highest number of cancer-related fatalities. Increasing data suggests that mesenchymal stem cells (MSCs) might influence the drug resistance of GC cells in the tumor microenvironment and play essential roles in drug resistance development. However, the precise underlying process remains a mystery. The purpose of this study was to look at the control of MSC-induced SNHG7 in pancreatic cancer. In vitro and in vivo sphere formation, colony formation, and flow cytometry investigations revealed the stemness and Folfirinox resistance in pancreatic cancer cells. To confirm the direct connections between SNHG7 and other related targets, RNA pulldown and immunoprecipitation tests were performed. MSC co-culture enhanced the stemness and Folfirinox resistance in pancreatic cancer cells according to the findings. MSC co-culture increased SNHG7 expression in pancreatic cancer cells, contributing to the stemness and Folfirinox resistance. We demonstrated that Notch1 interacted with SNHG7 and could reverse the facilitative effect of SNHG7 on the stemness and Folfirinox resistance in pancreatic cancer cells. Finally, our findings showed that MSCs increased SNHG7 expression in pancreatic cancer cells, promoting the stemness and Folfirinox resistance via the Notch1/Jagged1/Hes-1 signaling pathway. These findings could provide a novel approach and therapeutic target for pancreatic cancer patients. [ABSTRACT FROM AUTHOR]

Objectives: There are few reports about the survival rate of patients with pancreatic adenosquamous cancer (PASC). This study evaluated and analyzed prognostic factors of patients with resectable pancreatic adenosquamous cancer (rPASC), which might fulfill the blank in the research of PASC. Methods: In this study, we identified and analyzed 55 patients who were diagnosed with rPASC from January 2013 to May 2019 at the Pancreatic Disease Center of the Shanghai Ruijin Hospital affiliated with Shanghai Jiaotong University School of Medicine. Age, sex, BMI, tumor position, and other important demographic data were collected and analyzed. The follow-up was updated by December 31th, 2019 with a median follow-up of nine months. Results: Among the 55 patients, 23 (41.8%) patients were female, and the mean age was 62.0 ± 10.3 years. The median overall survival (OS) time was 10 ± 2.1 months, and the median disease-free survival (DFS) time was 4 ± 0.9 months. The 1-year, 3-year, and 5-year survival rates were 40.9, 17.5, and 11.6%, respectively. The multivariate analysis showed that normal serum level of Ca199 (HR = 0.464, 95% CI = 0.222–0.970, P = 0.041) and Ca125 (HR = 0.441, 95% CI = 0.233–0.835, P = 0.012) were independent favorable prognostic factors. Conclusion: Patients with rPASC had poor survival. The 5-year survival rate was only 11.6%. Normal serum levels of Ca199 and Ca125 were independent favorable prognostic factors that predicted prognosis. [ABSTRACT FROM AUTHOR]

The tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC) involves a significant accumulation of cancer-associated fibroblasts (CAFs) as part of the host response to tumor cells. The origins and functions of transcriptionally diverse CAF populations in PDAC remain poorly understood. Tumor cell-intrinsic genetic mutations and epigenetic dysregulation may reshape the TME; however, their impacts on CAF heterogeneity remain elusive. SETD2, a histone H3K36 trimethyl-transferase, functions as a tumor suppressor. Through single-cell RNA sequencing, we identify a lipid-laden CAF subpopulation marked by ABCA8a in Setd2 -deficient pancreatic tumors. Our findings reveal that tumor-intrinsic SETD2 loss unleashes BMP2 signaling via ectopic gain of H3K27Ac, leading to CAFs differentiation toward lipid-rich phenotype. Lipid-laden CAFs then enhance tumor progression by providing lipids for mitochondrial oxidative phosphorylation via ABCA8a transporter. Together, our study links CAF heterogeneity to epigenetic dysregulation in tumor cells, highlighting a previously unappreciated metabolic interaction between CAFs and pancreatic tumor cells. [Display omitted] • Enhanced OXPHOS in SETD2 -deficient human and mouse pancreatic tumors • Identification of lipid-laden CAF marked by ABCA8a in Setd2 -deficient pancreatic tumors • ABCA8a facilitates lipid transfer from lipid-laden CAFs to tumor cells for fueling OXPHOS • Tumor SETD2 loss unleashes BMP signaling to promote lipid-laden CAF differentiation Niu et al. identify a lipid-laden CAF subset marked by ABCA8a in Setd2 -deficient pancreatic tumors, which transports lipids and metabolically sustains tumor growth via OXPHOS. Both in vivo and ex vivo experiments reveal that tumor-intrinsic SETD2 loss induces epigenetic reprogramming and unleashes BMP signaling to foster the differentiation of lipid-laden CAFs. [ABSTRACT FROM AUTHOR]

CCL17 is well known for its ability to engage CCR4 + CD8 + T cells, which have been shown to play a critical role in preventing tumorigenesis. In this study, we attempted to inhibit in vivo pancreatic tumorigenesis by engaging murine CCR4 + CD8 + T cells through a drug-eluting scaffold with a payload of CCL17. The drug-eluting scaffold was fabricated by electrospinning polyglyconate and porcine gelatin. The electrospun scaffold featured randomly distributed non-woven fibers with diameters ranging from 1 μm to 4 μm. The in vitro study confirmed that scaffolding materials were non-cytotoxic to pancreatic cancer cells. The in vivo study showed an increased presence of murine CCR4 + CD8 + T cells into the tumor mass treated with drug-eluting scaffold compared to those with non-eluting scaffold or the control groups. The weights of tumor masses were 132.04 mg ± 12.25 mg in the control group, 158.12 mg ± 18.98 mg in the NES group and 96.22 mg ± 14.56 mg in the DES group, respectively. The volumes of tumor masses were 1035.21 mm 3 ± 128.97 mm 3 in the control group, 978.56 mm 3 ± 110.19 mm 3 in the NES group and 634.35 mm 3 ± 87.12 mm 3 in the DES group, respectively. Further study showed that the increased presence of CCR4 + CD8 + T cells also inhibited the hepatic metastasis of pancreatic cancer cells. Our study shed a new light on the post-operative treatment of pancreatic cancer to prevent the recurrence. [ABSTRACT FROM AUTHOR]