Recent Advances in Pancreatic Cancer (Closed)

A topical collection in Biomolecules (ISSN 2218-273X). This collection belongs to the section "Molecular Medicine".

Viewed by 34992

Editor

Gastroenterology Unit IRCCS “Casa Sollievo della Sofferenza” Hospital, San Giovanni Rotondo (FG), Italy
Interests: microbiota; gene expression; gastroenterology; pancreatic diseases; liver diseases
Special Issues, Collections and Topics in MDPI journals

Topical Collection Information

Dear Colleagues,

Pancreatic cancer (PC) is one of the most aggressive malignancies in industrialized countries, characterized by early metastasis and aggressive behavior. To date, it is the fourth leading cause of cancer death in men and women, with projections foreseeing it becoming the second leading cause of cancer death in the next decade in Western countries.

Since the overall survival is unacceptably low, novel therapeutic approaches to overcoming the resistance of PC to conventional anticancer therapies are urgently needed. In recent years, the crucial genetic changes leading to pancreatic cancer have been identified, and different complementary strategies have been studied in in vitro and in vivo models of pancreatic cancer.

This Topical Collection will focus on the latest research and new strategies for improving the prevention, diagnosis and therapy of pancreatic cancer, encompassing the genomics, transcriptomics, proteomics, metabolomics, dietary, nutraceutical and microbiota points of view.

Dr. Valerio Pazienza
Collection Editor

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Keywords

  • pancreatic cancer
  • system biology
  • miRNAs
  • microbiota
  • chemoresistance
  • targeted drugs
  • nutraceuticals
  • diet
  • metabolomic
  • survival prediction

Published Papers (12 papers)

2023

Jump to: 2022, 2021, 2020

10 pages, 1776 KiB  
Communication
Near-Infrared Fluorescence Imaging of Pancreatic Cancer Using a Fluorescently Labelled Anti-CEA Nanobody Probe: A Preclinical Study
by Labrinus van Manen, Lizzie D. A. N. de Muynck, Victor M. Baart, Shadhvi Bhairosingh, Pieterjan Debie, Alexander L. Vahrmeijer, Sophie Hernot and J. Sven D. Mieog
Biomolecules 2023, 13(4), 618; https://0-doi-org.brum.beds.ac.uk/10.3390/biom13040618 - 30 Mar 2023
Cited by 3 | Viewed by 1581
Abstract
Molecular fluorescence-guided surgery using near-infrared light has the potential to improve the rate of complete resection of cancer. Typically, monoclonal antibodies are being used as targeting moieties, however smaller fragments, such as single-domain antibodies (i.e., Nanobodies®) improve tumor specificity and enable [...] Read more.
Molecular fluorescence-guided surgery using near-infrared light has the potential to improve the rate of complete resection of cancer. Typically, monoclonal antibodies are being used as targeting moieties, however smaller fragments, such as single-domain antibodies (i.e., Nanobodies®) improve tumor specificity and enable tracer injection on the same day as surgery. In this study, the feasibility of a carcinoembryonic antigen-targeting Nanobody (NbCEA5) conjugated to two zwitterionic dyes (ZW800-1 Forte [ZW800F] and ZW800-1) for visualization of pancreatic ductal adenocarcinoma (PDAC) was investigated. After site-specific conjugation of NbCEA5 to the zwitterionic dyes, binding specificity was evaluated on human PDAC cell lines with flow cytometry. A dose escalation study was performed for both NbCEA5-ZW800F and NbCEA5-ZW800-1 in mice with subcutaneously implanted pancreatic tumors. Fluorescence imaging was performed up to 24 h after intravenous injection. Furthermore, the optimal dose for NbCEA5-ZW800-1 was injected in mice with orthotopically implanted pancreatic tumors. A dose-escalation study showed superior mean fluorescence intensities for NbCEA5-ZW800-1 compared to NbCEA5-ZW800F. In the orthotopic tumor models, NbCEA5-ZW800-1 accumulated specifically in pancreatic tumors with a mean in vivo tumor-to-background ratio of 2.4 (SD = 0.23). This study demonstrated the feasibility and potential advantages of using a CEA-targeted Nanobody conjugated to ZW800-1 for intraoperative PDAC imaging. Full article
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2022

Jump to: 2023, 2021, 2020

17 pages, 1137 KiB  
Review
STAT3 Inhibitors: A Novel Insight for Anticancer Therapy of Pancreatic Cancer
by Xin Li, Wenkai Jiang, Shi Dong, Wancheng Li, Weixiong Zhu and Wence Zhou
Biomolecules 2022, 12(10), 1450; https://0-doi-org.brum.beds.ac.uk/10.3390/biom12101450 - 09 Oct 2022
Cited by 7 | Viewed by 2892
Abstract
The signal transducer and activator of transcription (STAT) is a family of intracellular cytoplasmic transcription factors involved in many biological functions in mammalian signal transduction. Among them, STAT3 is involved in cell proliferation, differentiation, apoptosis, and inflammatory responses. Despite the advances in the [...] Read more.
The signal transducer and activator of transcription (STAT) is a family of intracellular cytoplasmic transcription factors involved in many biological functions in mammalian signal transduction. Among them, STAT3 is involved in cell proliferation, differentiation, apoptosis, and inflammatory responses. Despite the advances in the treatment of pancreatic cancer in the past decade, the prognosis for patients with pancreatic cancer remains poor. STAT3 has been shown to play a pro-cancer role in a variety of cancers, and inhibitors of STAT3 are used in pre-clinical and clinical studies. We reviewed the relationship between STAT3 and pancreatic cancer and the latest results on the use of STAT3 inhibitors in pancreatic cancer, with the aim of providing insights and ideas around STAT3 inhibitors for a new generation of chemotherapeutic modalities for pancreatic cancer. Full article
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15 pages, 4988 KiB  
Article
COL11A1-Driven Epithelial–Mesenchymal Transition and Stemness of Pancreatic Cancer Cells Induce Cell Migration and Invasion by Modulating the AKT/GSK-3β/Snail Pathway
by Hui Wang, Huichao Zhou, Hong Ni and Xiaohong Shen
Biomolecules 2022, 12(3), 391; https://0-doi-org.brum.beds.ac.uk/10.3390/biom12030391 - 02 Mar 2022
Cited by 11 | Viewed by 2938
Abstract
Background: Collagen type XI α1 (COL11A1) is associated with tumorigenesis and development in many human malignancies. Previous reports indicate that COL11A1 may be a significant diagnostic marker for pancreatic ductal adenocarcinoma (PDAC); however, its biological role in PDAC progression remains unclear. In this [...] Read more.
Background: Collagen type XI α1 (COL11A1) is associated with tumorigenesis and development in many human malignancies. Previous reports indicate that COL11A1 may be a significant diagnostic marker for pancreatic ductal adenocarcinoma (PDAC); however, its biological role in PDAC progression remains unclear. In this study, we investigated the influence of COL11A1 on the invasion and migration abilities of pancreatic cancer cells and explored its potential molecular mechanisms. Methods: Cell migration and invasion were assessed using Transwell assays in pancreatic cancer cells transfected with siCOL11A1 and pCNV3-COL11A1 plasmids. The protein and mRNA expression levels of N-cadherin, E-cadherin, Vimentin, cluster of differentiation (CD)-24, CD44, serine–threonine kinase (AKT), glycogen synthase kinase (GSK)-3β, phospho (p)-AKTSer473, p-GSK-3βSer9, and Snail were analyzed using Western blotting and real-time polymerase chain reaction (PCR). The effect of COL11A1 on cell stemness was tested using flow cytometry and clone formation assays. Results: These results demonstrated that COL11A1 significantly promoted the invasion and migration abilities of PDAC cells. Furthermore, COL11A1 facilitated the occurrence of epithelial–mesenchymal transition (EMT) and cell stemness by upregulating the expression levels of p-AKTSer473, p-GSK-3βSer9, and Snail. Conclusions: This study suggests that the activation of the AKT/GSK-3β/Snail signaling pathway induced by COL11A1 plays a major role in the progression of PDAC. Therefore, COL11A1 could serve as a potential target for PDAC treatment. Full article
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16 pages, 1162 KiB  
Review
Targeting the Endocannabinoidome in Pancreatic Cancer
by Valerio Falasca and Marco Falasca
Biomolecules 2022, 12(2), 320; https://0-doi-org.brum.beds.ac.uk/10.3390/biom12020320 - 17 Feb 2022
Cited by 5 | Viewed by 3666
Abstract
Pancreatic Ductal adenocarcinoma (PDAC), the most common malignancy of the pancreas, is an aggressive and lethal form of cancer with a very high mortality rate. High heterogeneity, asymptomatic initial stages and a lack of specific diagnostic markers result in an end-stage diagnosis when [...] Read more.
Pancreatic Ductal adenocarcinoma (PDAC), the most common malignancy of the pancreas, is an aggressive and lethal form of cancer with a very high mortality rate. High heterogeneity, asymptomatic initial stages and a lack of specific diagnostic markers result in an end-stage diagnosis when the tumour has locally advanced or metastasised. PDAC is resistant to most of the available chemotherapy and radiation therapy treatments, making surgery the most potent curative treatment. The desmoplastic tumour microenvironment contributes to determining PDAC pathophysiology, immune response and therapeutic efficacy. The existing therapeutic approaches such as FDA-approved chemotherapeutics, gemcitabine, abraxane and folfirinox, prolong survival marginally and are accompanied by adverse effects. Several studies suggest the role of cannabinoids as anti-cancer agents. Cannabinoid receptors are known to be expressed in pancreatic cells, with a higher expression reported in pancreatic cancer patients. Therefore, pharmacological targeting of the endocannabinoid system might offer therapeutic benefits in pancreatic cancer. In addition, emerging data suggest that cannabinoids in combination with chemotherapy can increase survival in transgenic pancreatic cancer murine models. This review provides an overview of the regulation of the expanded endocannabinoid system, or endocannabinoidome, in PDAC and will explore the potential of targeting this system for novel anticancer approaches. Full article
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2021

Jump to: 2023, 2022, 2020

13 pages, 603 KiB  
Review
Recent Advances in Pancreatic Cancer: Novel Prognostic Biomarkers and Targeted Therapy—A Review of the Literature
by Konstantin Schlick, Dominik Kiem and Richard Greil
Biomolecules 2021, 11(10), 1469; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11101469 - 06 Oct 2021
Cited by 7 | Viewed by 2627
Abstract
Pancreatic adenocarcinoma carries a devastating prognosis. For locally advanced and metastatic disease, several chemotherapeutic regimens are currently being used. Over the past years, novel approaches have included targeting EGFR, NTRK, PARP, K-Ras as well as stroma and fibrosis, leading to approval of NTRK [...] Read more.
Pancreatic adenocarcinoma carries a devastating prognosis. For locally advanced and metastatic disease, several chemotherapeutic regimens are currently being used. Over the past years, novel approaches have included targeting EGFR, NTRK, PARP, K-Ras as well as stroma and fibrosis, leading to approval of NTRK and PARP inhibitors. Moreover, immune check point inhibitors and different combinational approaches involving immunotherapeutic agents are being investigated in many clinical trials. MiRNAs represent a novel tool and are thought to greatly improve management by allowing for earlier diagnosis and for more precise guidance of treatment. Full article
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15 pages, 3638 KiB  
Article
Multimodal Treatment with GEMOX Plus Helical Tomotherapy in Unresectable Locally Advanced Pancreatic Cancer: A Pooled Analysis of Two Phase 2 Studies
by Alessandro Passardi, Ilario Giovanni Rapposelli, Emanuela Scarpi, Francesco Giulio Sullo, Giulia Bartolini, Elisa Neri, Giulia Ghigi, Luca Tontini, Giorgio Ercolani, Manlio Monti, Silvia Ruscelli, Laura Matteucci, Martina Valgiusti, Giovanni Luca Frassineti and Antonino Romeo
Biomolecules 2021, 11(8), 1200; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11081200 - 12 Aug 2021
Cited by 2 | Viewed by 2135
Abstract
In locally advanced pancreatic cancer (LAPC), the combination of chemotherapy and radiotherapy is a widely used treatment option. We performed a pooled analysis, including an exploratory analysis for prognostic and predictive factors, of two phase 2 trials including 73 patients with LAPC, treated [...] Read more.
In locally advanced pancreatic cancer (LAPC), the combination of chemotherapy and radiotherapy is a widely used treatment option. We performed a pooled analysis, including an exploratory analysis for prognostic and predictive factors, of two phase 2 trials including 73 patients with LAPC, treated with gemcitabine and oxaliplatin (GEMOX) and hypofractionated tomotherapy. With a median follow-up of 36 months (range 1–65), median progression-free (PFS) and overall survival (OS) were 10.2 (95% confidence interval [CI] 7.8–13.2) and 14.3 (95% CI 12.0–18.1) months, respectively. The overall resectability rate was 23.3% (95% CI 13.6–33.0), and the R0 resection rate was 13.7% (95% CI 5.8–21.6). In the multivariate analysis, ECOG performance status (PS) 0 and low levels of CA 19–9 were associated with improved OS and PFS. Concerning OS, log(CA19–9) resulted in a hazard ratio (HR) of 1.20 (95% CI 1.02–1.42), p = 0.027. For ECOG PS 0, HR was 1.00; for PS 1, HR was 2.69 (95% CI 1.46–4.96); for PS 2, HR was 4.18 (95% CI 0.90–19.46); p = 0.003. Low CA19–9 levels were also predictive for resection, with an odds ratio of 0.71 (95% CI 0.52–0.97), p = 0.034. In conclusion, GEMOX and hypofractionated radiotherapy is a treatment option in LAPC. Further studies are needed to identify differences in tumor biology, which may help to predict resectability and prognosis. Full article
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12 pages, 692 KiB  
Review
Neutrophil in the Pancreatic Tumor Microenvironment
by Lin Jin, Hong Sun Kim and Jiaqi Shi
Biomolecules 2021, 11(8), 1170; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11081170 - 07 Aug 2021
Cited by 25 | Viewed by 5143
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a malignancy with a poor prognosis and low survival rates. PDAC is characterized by a fibroinflammatory tumor microenvironment enriched by abundant fibroblasts and a variety of immune cells, contributing to its aggressiveness. Neutrophils are essential infiltrating immune cells [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) is a malignancy with a poor prognosis and low survival rates. PDAC is characterized by a fibroinflammatory tumor microenvironment enriched by abundant fibroblasts and a variety of immune cells, contributing to its aggressiveness. Neutrophils are essential infiltrating immune cells in the PDAC microenvironment. Recent studies have identified several cellular mechanisms by which neutrophils are recruited to tumor lesion and promote tumorigenesis. This review summarizes the current understanding of the interplay between neutrophils, tumor cells, and other components in the PDAC tumor microenvironment. The prognosis and therapeutic implications of neutrophils in PDAC are also discussed. Full article
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11 pages, 1610 KiB  
Article
Non-Tumor CCAAT/Enhancer-Binding Protein Delta Potentiates Tumor Cell Extravasation and Pancreatic Cancer Metastasis Formation
by JanWillem Duitman, Leonie Hartl, Joris J. T. H. Roelofs, Maarten F. Bijlsma and C. Arnold Spek
Biomolecules 2021, 11(8), 1079; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11081079 - 22 Jul 2021
Cited by 4 | Viewed by 1699
Abstract
CCAAT/enhancer-binding protein delta (C/EBPδ) is a transcription factor involved in apoptosis and proliferation, which is downregulated in pancreatic ductal adenocarcinoma (PDAC) cells. Loss of nuclear C/EBPδ in PDAC cells is associated with decreased patient survival and pro-tumorigenic properties in vitro. Interestingly however, next [...] Read more.
CCAAT/enhancer-binding protein delta (C/EBPδ) is a transcription factor involved in apoptosis and proliferation, which is downregulated in pancreatic ductal adenocarcinoma (PDAC) cells. Loss of nuclear C/EBPδ in PDAC cells is associated with decreased patient survival and pro-tumorigenic properties in vitro. Interestingly however, next to C/EBPδ expression in tumor cells, C/EBPδ is also expressed by cells constituting the tumor microenvironment and by cells comprising the organs and parenchyma. However, the functional relevance of systemic C/EBPδ in carcinogenesis remains elusive. Here, we consequently assessed the potential importance of C/EBPδ in somatic tissues by utilizing an orthotopic pancreatic cancer model. In doing so, we show that genetic ablation of C/EBPδ does not significantly affect primary tumor growth but has a strong impact on metastases; wildtype mice developed metastases at multiple sites, whilst this was not the case in C/EBPδ-/- mice. In line with reduced metastasis formation in C/EBPδ-/- mice, C/EBPδ-deficiency also limited tumor cell dissemination in a specific extravasation model. Tumor cell extravasation was dependent on the platelet-activating factor receptor (PAFR) as a PAFR antagonist inhibited tumor cell extravasation in wildtype mice but not in C/EBPδ-/- mice. Overall, we show that systemic C/EBPδ facilitates pancreatic cancer metastasis, and we suggest this is due to C/EBPδ-PAFR-dependent tumor cell extravasation. Full article
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10 pages, 589 KiB  
Article
Equivalent Efficacy but Different Safety Profiles of Gemcitabine Plus Nab-Paclitaxel and FOLFIRINOX in Metastatic Pancreatic Cancer
by Ilario Giovanni Rapposelli, Andrea Casadei-Gardini, Caterina Vivaldi, Giulia Bartolini, Laura Bernardini, Alessandro Passardi, Giovanni Luca Frassineti, Valentina Massa and Alessandro Cucchetti
Biomolecules 2021, 11(6), 780; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11060780 - 22 May 2021
Cited by 2 | Viewed by 2294
Abstract
FOLFIRINOX (FFX) and gemcitabine + nab-paclitaxel (GN) are the most common chemotherapy regimens in first-line treatment of metastatic pancreatic cancer (PC). They have not been compared each other in a prospective trial, but only in retrospective studies, which can thus be affected by [...] Read more.
FOLFIRINOX (FFX) and gemcitabine + nab-paclitaxel (GN) are the most common chemotherapy regimens in first-line treatment of metastatic pancreatic cancer (PC). They have not been compared each other in a prospective trial, but only in retrospective studies, which can thus be affected by several biases. In order to overcome these biases, we took advantage of matching-adjusted indirect comparison (MAIC), that allows an indirect comparison by reducing cross-trial differences, and compared data from 268 patients treated with GN in a real-world setting with data from the 171 patients included in the FFX arm of the PRODIGE trial. Survival outcomes did not differ between the two populations. Overall survival was 11.1 months for both treatments (hazard ratio (HR) of FFX 1.10, 95% confidence interval (CI) 0.81–1.49; p = 0.527). Progression-free survival was 6.0 months with GN and 6.4 months with FFX (HR of FFX 1.11, 95% CI 0.82–1.50; p = 0.520). On the other hand, we observed a difference in the toxicity profiles: grade 3/4 anemia was more frequent with GN, whereas a higher occurrence of grade 3/4 vomiting and diarrhea was reported with FFX. FFX and GN show an equivalent efficacy but different safety profiles in the first-line therapy of metastatic pancreatic cancer. Searching for reliable predictive biomarkers is advised in order to improve therapeutic strategy in metastatic PC. Full article
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18 pages, 7640 KiB  
Article
Improving Gemcitabine Sensitivity in Pancreatic Cancer Cells by Restoring miRNA-217 Levels
by Concetta Panebianco, Nadia Trivieri, Annacandida Villani, Fulvia Terracciano, Tiziana Pia Latiano, Adele Potenza, Francesco Perri, Elena Binda and Valerio Pazienza
Biomolecules 2021, 11(5), 639; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11050639 - 26 Apr 2021
Cited by 12 | Viewed by 2906
Abstract
Chemoresistance is a major problem in the therapeutic management of pancreatic cancer, concurring to poor clinical outcome. A number of mechanisms have been proposed to explain resistance to gemcitabine, a standard of care for this malignancy, among which is included aberrant miRNA expression. [...] Read more.
Chemoresistance is a major problem in the therapeutic management of pancreatic cancer, concurring to poor clinical outcome. A number of mechanisms have been proposed to explain resistance to gemcitabine, a standard of care for this malignancy, among which is included aberrant miRNA expression. In the current study, we investigated the role of miR-217, which is strongly down-regulated in cancerous, compared to normal, pancreatic tissues or cells, in sensitizing human pancreatic cancer cell lines to this drug. The low expression of miR-217 in pancreatic cancer patients was confirmed in two gene expression datasets (GSE41372 and GSE60980), and the prognostic value of two target genes (ANLN and TRPS1), was estimated on clinical data from the Tumor Cancer Genome Atlas (TCGA). Transfecting miR-217 mimic in pancreatic cancer cells reduced viability, enhanced apoptosis, and affected cell cycle by promoting a S phase arrest in gemcitabine-treated cells. Moreover, in drug-exposed cells subjected to miR-217 forced expression, a down-regulation for several genes involved in cancer drug resistance was observed, many of which are cell cycle regulators, such as CCND1, CCNE1, CDK2, CDKN1A, CDKN1B, while others, such as ARNT, BRCA1, BRCA2, ELK1, EGFR, ERBB4, and RARA are involved in proliferation and cell cycle progression. Our results support the notion that miR-217 enhances pancreatic cancer sensitivity to gemcitabine, mainly impairing cell cycle progression. Full article
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18 pages, 4109 KiB  
Article
Inhibition of the Receptor for Advanced Glycation End Products Enhances the Cytotoxic Effect of Gemcitabine in Murine Pancreatic Tumors
by Priyanka Swami, Kelly A. O’Connell, Swetha Thiyagarajan, Ayrianne Crawford, Prathamesh Patil, Prakash Radhakrishnan, Simon Shin, Thomas C. Caffrey, James Grunkemeyer, Tammi Neville, Stefan W. Vetter, Michael A. Hollingsworth and Estelle Leclerc
Biomolecules 2021, 11(4), 526; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11040526 - 01 Apr 2021
Cited by 6 | Viewed by 2730
Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains a very difficult cancer to treat. Recent in vitro and in vivo studies suggest that the activation of the receptor for advanced glycation end products (RAGE) by its ligands stimulates pancreatic cancer cell proliferation and tumor growth. Additional [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) remains a very difficult cancer to treat. Recent in vitro and in vivo studies suggest that the activation of the receptor for advanced glycation end products (RAGE) by its ligands stimulates pancreatic cancer cell proliferation and tumor growth. Additional studies show that, in the RAGE ligand, the high mobility group box 1 (HMGB1) protein plays an important role in chemoresistance against the cytotoxic agent gemcitabine by promoting cell survival through increased autophagy. We hypothesized that blocking the RAGE/HMGB1 interaction would enhance the cytotoxic effect of gemcitabine by reducing cell survival and autophagy. Using a preclinical mouse model of PDAC and a monoclonal antibody (IgG 2A11) as a RAGE inhibitor, we demonstrate that RAGE inhibition concurrent with gemcitabine treatment enhanced the cytotoxic effect of gemcitabine. The combination of IgG 2A11 and gemcitabine resulted in decreased autophagy compared to treatment with gemcitabine combined with control antibodies. Notably, we also observed that RAGE inhibition protected against excessive weight loss during treatment with gemcitabine. Our data suggest that the combination of gemcitabine with a RAGE inhibitor could be a promising therapeutic approach for the treatment of pancreatic cancer and needs to be further investigated. Full article
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2020

Jump to: 2023, 2022, 2021

13 pages, 2854 KiB  
Article
High Levels of Prebiotic Resistant Starch in Diet Modulate a Specific Pattern of miRNAs Expression Profile Associated to a Better Overall Survival in Pancreatic Cancer
by Nadia Trivieri, Concetta Panebianco, Annacandida Villani, Riccardo Pracella, Tiziana Pia Latiano, Francesco Perri, Elena Binda and Valerio Pazienza
Biomolecules 2021, 11(1), 26; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11010026 - 29 Dec 2020
Cited by 12 | Viewed by 2763
Abstract
Dietary patterns are well known risk factors involved in cancer initiation, progression, and in cancer protection. Previous in vitro and in vivo studies underline the link between a diet rich in resistant starch (RS) and slowing of tumor growth and gene expression in [...] Read more.
Dietary patterns are well known risk factors involved in cancer initiation, progression, and in cancer protection. Previous in vitro and in vivo studies underline the link between a diet rich in resistant starch (RS) and slowing of tumor growth and gene expression in pancreatic cancer xenograft mice. The aim of this study was to investigate the impact of a diet rich in resistant starch on miRNAs and miRNAs-target genes expression profile and on biological processes and pathways, that play a critical role in pancreatic tumors of xenografted mice. miRNA expression profiles on tumor tissues displayed 19 miRNAs as dysregulated in mice fed with RS diet as compared to those fed with control diet and differentially expressed miRNA-target genes were predicted by integrating (our data) with a public human pancreatic cancer gene expression dataset (GSE16515). Functional and pathway enrichment analyses unveiled that miRNAs involved in RS diet are critical regulators of genes that control tumor growth and cell migration and metastasis, inflammatory response, and, as expected, synthesis of carbohydrate and glucose metabolism disorder. Mostly, overall survival analysis with clinical data from TCGA (n = 175) displayed that almost four miRNAs (miRNA-375, miRNA-148a-3p, miRNA-125a-5p, and miRNA-200a-3p) upregulated in tumors from mice fed with RS were a predictor of good prognosis for pancreatic cancer patients. These findings contribute to the understanding of the potential mechanisms through which resistant starch may affect cancer progression, suggesting also a possible integrative approach for enhancing the efficacy of existing cancer treatments. Full article
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