Background: The typical pathological feature of pancreatic ductal adenocarcinoma (PDAC) is a significant increase in stromal reaction, leading to a hypoxic and poorly vascularized tumor microenvironment. Tumor cells undergo metabolic reprogramming, such as the Warburg effect, yet the underlying mechanisms are not fully understood.
Methods: Interference and overexpression experiments were conducted to analyze the in vivo and in vitro effects of USP7 on the growth and glycolysis of tumor cells.
Pancreatic cancer is characterized by severe metabolic stress due to its prominent desmoplasia and poor vascularization. Integrin subunit alpha 3 (ITGA3) is a cell surface adhesion protein involved in tumor progression. However, the role of ITGA3 in pancreatic cancer progression, especially in metabolic reprogramming, remains largely unknown.
View Article and Find Full Text PDFBackground: Deciphering the role of plasma proteins in pancreatic cancer (PC) susceptibility can aid in identifying novel targets for diagnosis and treatment.
Methods: We examined the relationship between genetically determined levels of plasma proteins and PC through a systemic proteome-wide Mendelian randomization (MR) analysis utilizing cis-pQTLs from multiple centers. Rigorous sensitivity analyses, colocalization, reverse MR, replications with varying instrumental variable selections and additional datasets, as well as subsequent meta-analysis, were utilized to confirm the robustness of significant findings.
(1) Background: Recently, cell division cycle associated 8 (CDCA8) was found to be overexpressed in pancreatic ductal adenocarcinoma (PDAC). Here, we aimed to explore the specific mechanism of action of CDCA8 in PDAC progression. (2) Methods: All human PDAC samples and clinical data were collected from Huashan Hospital, Fudan University.
View Article and Find Full Text PDFPancreatic ductal adenocarcinoma (PDA) is often concomitant with diabetes mellitus, which mainly manifests as an increased blood glucose level. Previous studies revealed that diabetic status reduced the survival and blunted gemcitabine sensitivity in PDA patients. This study is aimed at analyzing the mechanism of elevated gemcitabine resistance and cancer invasion ability under high glucose environment.
View Article and Find Full Text PDFPurpose: Pancreatic cyst neoplasm (PCN) is a precursor of pancreatic cancer. Previous studies reported PCN was often concurrent with diabetes. We aim to examine the association between diabetes with PCN malignancy and to detect the potential role of diabetes in PCN management and treatment.
View Article and Find Full Text PDFPurpose: Gemcitabine (GEM) is the first-line chemotherapeutic drug for pancreatic cancer treatment in clinical practice. However, many reasons can reduce the efficacy of GEM, among which the high expression of ATP-binding cassette (ABC) transporters is a significant factor. In this study, we aimed to investigate the antitumor effect of gemcitabine-loaded human serum albumin nanoparticle (GEM-HSA-NP) on GEM-resistant pancreatic cancer cells induced by the high expression of ABC transporters, namely multidrug resistance protein 1/P-gp/ABCB1 (MDR1) and multidrug resistance-associated protein 1/ ABCC1 (MRP1).
View Article and Find Full Text PDFIncreased insulin level (or "hyperinsulinemia") is a common phenomenon in pancreatic ductal adenocarcinoma (PDA) patients and signals poor clinical outcomes. Insulin is safe in low PDA risk population, while insulin significantly promotes PDA risk in high PDA risk population. The correlation between insulin and PDA is a reciprocal self-reinforcing relationship.
View Article and Find Full Text PDFBackground: Sodium glucose transporters (SGLTs) play vital roles in glucose uptake in many solid cancers, including pancreatic cancer (PC). However, their expression profile in pancreatic cancer and correlation with prognosis are not clear. Thus, we aimed to analyse the expression profile and prognostic significance of SGLT-1 and SGLT-2 in PC.
View Article and Find Full Text PDFTo explore the expression profile and prognostic relevance of GLUT-1 in pancreatic cancer, a meta-analysis, bioinformatics analysis based on Gene Expression Omnibus (GEO), Oncomine dataset and The Cancer Genome Atlas (TCGA) database, and immunohistochemistry in tumor and normal tissue from 88 pancreatic ductal adenocarcinoma (PDAC) patients were performed. GLUT-1 was significantly overexpressed in pancreatic cancer but it could not be a significant biomarker for prognosis. TNM stage and pathological grade could be biomarker of poor prognosis of patients with pancreatic cancer.
View Article and Find Full Text PDFApical microvilli of polarized epithelial cells govern the absorption of metabolites and the transport of fluid in tissues. Previously, we reported that tall and dense basal microvilli present on the endothelial cells of pancreatic cancers, a lethal malignancy with a high metabolism and unusual hypomicrovascularity, contain nutrient trafficking vesicles and glucose; their length and density were related to the glucose uptake of pancreatic cancers in a small-scale analysis. However, the implications of basal microvilli on pancreatic cancers are unknown.
View Article and Find Full Text PDFPancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death worldwide, and the mortality of patients with PDAC has not significantly decreased over the last few decades. Novel strategies exhibiting promising effects in preclinical or phase I/II clinical trials are often situated in an embarrassing condition owing to the disappointing results in phase III trials. The efficacy of the current therapeutic regimens is consistently compromised by the mechanisms of drug resistance at different levels, distinctly more intractable than several other solid tumours.
View Article and Find Full Text PDFBackground: The molecular signature underlying pancreatic ductal adenocarcinoma (PDAC) progression may include key proteins affecting the malignant phenotypes. Here, we aimed to identify the proteins implicated in PDAC with different tumour-node-metastasis (TNM) stages.
Methods: Eight-plex isobaric tags coupled with two-dimensional liquid chromatography-tandem mass spectrometry were used to analyse the proteome of PDAC tissues with different TNM stages.
: Pancreatic cancer (PC) is a malignant tumor with limited therapeutic choices and extremely poor prognosis. Personalized therapy based on gene alternations is a promising choice. Considering tumor heterogeneity, the practice of ctDNA analysis has drawn the attention.
View Article and Find Full Text PDFPancreatic cancer (PC) is a highly lethal tumor with controversial high glucose uptake and hypomicrovascularity, and the hypomicrovasculature, which is considered to have poor perfusion, blocks the delivery of drugs to tumors. The preferential existence of a novel endothelial projection with trafficking vesicles in PCs, referring to basal microvilli, was described previously. However, the perfusion and nutrients delivering status of the basal microvilli microvessels are unknown.
View Article and Find Full Text PDFPortal vein (PV) involvement is common in patients with pancreatic ductal adenocarcinoma (PDAC). To the best of our knowledge, pancreatectomy combined with PV resection (PVR) is the only radical therapy for patients with PV involvement. However, there remains a debate on whether patients with PV involvement could benefit from PVR or not.
View Article and Find Full Text PDFPurpose: Nonsurgical therapies, including biotherapy, chemotherapy, and liver-directed therapy, provided a limit survival benefit for PNET patients with hepatic metastases. With the development of liver resection technique, there was a controversy on whether to perform a liver resection for these patients.
Methods: A computerized search was made of the Medline/PubMed, EMbase, Cochrane Library, and SinoMed (CBM) before March 2018.
The main focus of the present study was to evaluate whether ABC transporter family promoter methylation predicted multidrug resistance in gemcitabine-resistant cancer cell lines (BxPC-3/Gem and PANC-1/Gem). Using low concentrations of gemcitabine, the cell lines acquired drug resistance with different initial gemcitabine concentrations. A novel technology, methylation-sensitive high-resolution melting, was used to monitor the dynamic changes of ABC transporter family promoter methylation, including ATP binding cassette subfamily B member 1 (ABCB1), ATP binding cassette subfamily C (ABCC) and ATP binding cassette subfamily G member 2 (ABCG2) mRNA expression.
View Article and Find Full Text PDFPancreatic cancer is a uniformly lethal malignancy with an abundant dense desmoplastic stroma. Because of its dense stroma, conventional drugs were considered to not penetrate this physical barrier, and this caused a systemic drug resistance. Thus, abolishing this barrier with targeted agents is considered to improve the efficiency of chemotherapeutic treatment.
View Article and Find Full Text PDFEvidence shows that portal vein resection (PVR) increase the resectability but does little benefit to overall survival in all pancreatic ductal adenocarcinoma (PDAC) patients. But for patients with portal vein involvement, PVR is the only radical choice. But whether the PDAC patients with portal vein involvement would benefit from radical pancreaticoduodenectomy with PVR or not is controversial.
View Article and Find Full Text PDFObjective: The objectives of this systematic review and meta-analysis were to examine morbidity, mortality, and long-term survival after surgical resection of hepatic metastases from pancreatic ductal adenocarcinoma (PDAC) patients.
Background: Patients with hepatic metastases from pancreatic ductal adenocarcinoma are facing a dilemma of whether to make hepatic resection.
Methods: A systematic literature research was undertaken through computerized databases as well as manually research from unpublished data.
Lymphatic metastasis is the major metastatic pattern of pancreatic cancer and considered as an independent risk factor of survival. However, there is still no effective way for the diagnosis and treatment for lymphatic metastases of pancreatic cancer. In this study, using albumin as a carrier of gemcitabine (Gem), further modified by pyropheophorbide-a, we have designed and synthesized a nanoparticle (NP) compound named "pheophorbide-a (P@)-Gem-human serum albumin (HSA)-NPs".
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