124 results match your criteria pdac reducing

Co-delivery of autophagy inhibitor and gemcitabine using a pH-activatable core-shell nanobomb inhibits pancreatic cancer progression and metastasis.

Theranostics 2021 4;11(18):8692-8705. Epub 2021 Aug 4.

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, People's Republic of China.

Metastasis is one of the main reasons for the high mortality associated with pancreatic ductal adenocarcinoma (PDAC), and autophagy regulates the metastatic migration of tumor cells, their invasion of tissues, and their formation of focal adhesions. Inhibiting autophagy may suppress tumor growth and metastasis, but the abundant extracellular matrix hinders the deep penetration of therapeutic agents. To enhance the penetration of drugs that can inhibit metastasis of pancreatic cancer, a pH-responsive drug delivery system was formulated. Read More

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Cyclin Dependent Kinase-1 (CDK-1) Inhibition as a Novel Therapeutic Strategy against Pancreatic Ductal Adenocarcinoma (PDAC).

Cancers (Basel) 2021 Aug 30;13(17). Epub 2021 Aug 30.

Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Università degli Studi di Palermo, 90123 Palermo, Italy.

The role of CDK1 in PDAC onset and development is two-fold. Firstly, since CDK1 activity regulates the G2/M cell cycle checkpoint, overexpression of CDK1 can lead to progression into mitosis even in cells with DNA damage, a potentially tumorigenic process. Secondly, CDK1 overexpression leads to the stimulation of a range of proteins that induce stem cell properties, which can contribute to the development of cancer stem cells (CSCs). Read More

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Therapy-naïve and radioresistant 3D pancreatic cancer cell cultures are effectively radiosensitized by β1 integrin targeting.

Int J Radiat Oncol Biol Phys 2021 Sep 2. Epub 2021 Sep 2.

OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany; Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiooncology-OncoRay, 01328 Dresden, Germany; German Cancer Consortium, Partner Site Dresden: German Cancer Research Center, 69120 Heidelberg, Germany; Department of Radiotherapy and Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany. Electronic address:

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is one of the cancers with unmet needs. The role of highly conformal radiotherapy is still under debate for PDAC. Owing to its desmoplastic nature, integrin-mediated interactions between PDAC cells and extracellular matrix (ECM) profoundly contribute to PDAC therapy resistance. Read More

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September 2021

Targeted transcriptome and mutation analysis improve the diagnostic performance of EUS-FNA biopsies in pancreatic cancer.

Clin Cancer Res 2021 Aug 16. Epub 2021 Aug 16.

Department of Upper Gastrointestinal and Hepatopancreaticobiliary Surgery, Monash Health

Background: Pancreatic ductal adenocarcinoma (PDAC) carries a poor prognosis, and current diagnostic tests have suboptimal sensitivity. Incorporating standard cytology with targeted transcriptomic and mutation analysis may improve the accuracy of diagnostic biopsies, thus reducing the burden of repeat procedures and delays to treatment initiation.

Methods: We reviewed the accuracy of 308 EUS-FNA PDAC biopsies using a large multicenter clinical and biospecimen database, then performed RNA sequencing on 134 EUS-FNA biopsies spanning all stages of disease. Read More

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Downregulated expression of IL‑28RA is involved in the pathogenesis of pancreatic ductal adenocarcinoma.

Int J Oncol 2021 Aug 1;59(2). Epub 2021 Jul 1.

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230022, P.R. China.

Pancreatic cancer ranks seventh in terms of cancer‑related mortality in men and women worldwide, where the most common subtype is pancreatic ductal adenocarcinoma (PDAC). To date, the pathogenesis of PDAC remains incompletely understood and the prognosis of PDAC is poor. In the present study, the expression of interleukin‑28 receptor α subunit (IL‑28RA) in PDAC tissues was detected using immunofluorescence staining and western blotting. Read More

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A Tumor-Penetrating Nanomedicine Improves the Chemoimmunotherapy of Pancreatic Cancer.

Small 2021 07 18;17(29):e2101208. Epub 2021 Jun 18.

School of Biomedical Sciences and Engineering, Guangzhou International Campus, South China University of Technology, Guangzhou, 511442, China.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors with a low survival rate. The therapeutic effect of chemotherapy and immunotherapy for PDAC is disappointing due to the presence of dense tumor stroma and immunosuppressive cells in the tumor microenvironment (TME). Herein, a tumor-penetrating nanoparticle is reported to modulate the deep microenvironment of PDAC for improved chemoimmunotherapy. Read More

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FGFBP1-mediated crosstalk between fibroblasts and pancreatic cancer cells via FGF22/FGFR2 promotes invasion and metastasis of pancreatic cancer.

Acta Biochim Biophys Sin (Shanghai) 2021 Jul;53(8):997-1008

Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200031, China.

Fibroblast growth factor-binding protein 1 (FGFBP1) promotes fibroblast growth factor (FGF) activity by releasing FGFs from extracellular matrix storage. We previously reported that the tumor suppressor F-box and WD repeat domain-containing 7 suppresses FGFBP1 by reducing expression of c-Myc, which inhibits the proliferation and migration of pancreatic cancer cells. However, the potential mechanism by which FGFBP1 facilitates pancreatic ductal adenocarcinoma (PDAC) remains unexplored. Read More

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Neoadjuvant immunotherapy is reshaping cancer management across multiple tumour types: The future is now!

Eur J Cancer 2021 Jul 6;152:155-164. Epub 2021 Jun 6.

Princess Máxima Center, University Medical Center Utrecht, Heidelberglaan 25, 3584 Utrecht, the Netherlands. Electronic address:

The Italian Network for Tumor Biotherapy (Network Italiano per la Bioterapia dei Tumori [NIBIT]) Foundation hosted its annual 2020 Think Tank meeting virtually, at which representatives from academic, clinical, industry, philanthropic, and regulatory organisations discussed the role of neoadjuvant immunotherapy for the treatment of cancer. Although the number of neoadjuvant immunotherapeutic trials is increasing across all malignancies, the Think Tank focused its discussion on the status of neoadjuvant trials in cutaneous melanoma (CM), muscle-invasive urothelial bladder cancer (MIBC), head and neck squamous cell carcinoma (HNSCC), and pancreatic adenocarcinoma (PDAC). Neoadjuvant developments in CM are nothing short of trailblazing. Read More

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Heme Oxygenase-1 Inhibition Potentiates the Effects of Nab-Paclitaxel-Gemcitabine and Modulates the Tumor Microenvironment in Pancreatic Ductal Adenocarcinoma.

Cancers (Basel) 2021 May 8;13(9). Epub 2021 May 8.

Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a poor prognosis. Tumor hypoxia plays an active role in promoting tumor progression, malignancy, and resistance to therapy in PDAC. We present evidence that nab-paclitaxel-gemcitabine (NPG) and/or a hypoxic tumor microenvironment (TME) up-regulate heme oxygenase-1 (HO-1), providing a survival advantage for tumors. Read More

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NOX4 links metabolic regulation in pancreatic cancer to endoplasmic reticulum redox vulnerability and dependence on PRDX4.

Sci Adv 2021 May 7;7(19). Epub 2021 May 7.

Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.

There is an urgent need to identify vulnerabilities in pancreatic ductal adenocarcinoma (PDAC). PDAC cells acquire metabolic changes that augment NADPH production and cytosolic redox homeostasis. Here, we show that high NADPH levels drive activity of NADPH oxidase 4 (NOX4) expressed in the endoplasmic reticulum (ER) membrane. Read More

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Fzd7/Wnt7b signaling contributes to stemness and chemoresistance in pancreatic cancer.

Cancer Med 2021 05 2;10(10):3332-3345. Epub 2021 May 2.

Department of Pathophysiology, Basic Medical College, China Medical University, Shenyang, P.R. China.

Mining databases and data obtained from assays on human specimens had shown that Fzd7 is closely associated with Wnt7b, that Fzd7/Wnt7b expression is upregulated in pancreatic cancer tissues compared with normal tissues, and its expression is negatively correlated with survival. Fzd7/Wnt7b knockdown in Capan-2 and Panc-1 cells reduced the proliferative capacity of pancreatic cancer stem cells (PCSCs), reduced drug resistance, decreased the percentage of CD24 CD44 subset of cells and the levels of ABCG2, inhibited cell-sphere formation, and reduced gemcitabine (GEM) resistance. In contrast, Fzd7/Wnt7b overexpression increased the percentage of the CD24 CD44 subset of cells, and increased the levels of ABCG2 detected in cell spheroids. Read More

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Targeting the Stromal Pro-Tumoral Hyaluronan-CD44 Pathway in Pancreatic Cancer.

Int J Mol Sci 2021 Apr 12;22(8). Epub 2021 Apr 12.

Department of Bioscience, Biotechnology and Biopharmaceutics, University of Bari, 70126 Bari, Italy.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies. Present-day treatments have not shown real improvements in reducing the high mortality rate and the short survival of the disease. The average survival is less than 5% after 5 years. Read More

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Inhibition of the Receptor for Advanced Glycation End Products Enhances the Cytotoxic Effect of Gemcitabine in Murine Pancreatic Tumors.

Biomolecules 2021 04 1;11(4). Epub 2021 Apr 1.

Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58015, USA.

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. Read More

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Bcl3 Couples Cancer Stem Cell Enrichment With Pancreatic Cancer Molecular Subtypes.

Gastroenterology 2021 Jul 2;161(1):318-332.e9. Epub 2021 Apr 2.

Comprehensive Cancer Center Munich at Klinikum rechts der Isar, Technische Universität München, Munich, Germany.

Background & Aims: The existence of different subtypes of pancreatic ductal adenocarcinoma (PDAC) and their correlation with patient outcome have shifted the emphasis on patient classification for better decision-making algorithms and personalized therapy. The contribution of mechanisms regulating the cancer stem cell (CSC) population in different subtypes remains unknown.

Methods: Using RNA-seq, we identified B-cell CLL/lymphoma 3 (BCL3), an atypical nf-κb signaling member, as differing in pancreatic CSCs. Read More

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Peptidylarginine Deiminase Inhibitor Application, Using Cl-Amidine, PAD2, PAD3 and PAD4 Isozyme-Specific Inhibitors in Pancreatic Cancer Cells, Reveals Roles for PAD2 and PAD3 in Cancer Invasion and Modulation of Extracellular Vesicle Signatures.

Int J Mol Sci 2021 Jan 30;22(3). Epub 2021 Jan 30.

Tissue Architecture and Regeneration Research Group, School of Life Sciences, University of Westminster, London W1W 6 UW, UK.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies with limited survival rate. Roles for peptidylarginine deiminases (PADs) have been studied in relation to a range of cancers with roles in epigenetic regulation (including histone modification and microRNA regulation), cancer invasion, and extracellular vesicle (EV) release. Hitherto though, knowledge on PADs in PDAC is limited. Read More

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January 2021

The role of non-coding RNAs in ABC transporters regulation and their clinical implications of multidrug resistance in cancer.

Expert Opin Drug Metab Toxicol 2021 Mar 22;17(3):291-306. Epub 2021 Feb 22.

Institution of Drug Metabolism and Pharmaceutical Analysis, Cancer Center of Zhejiang University,Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.

Introduction: Multi-drug resistance (MDR) is a hindrance toward the successful treatment of cancers. The primary mechanism that gives rise to acquired chemoresistance is the overexpression of adenosine triphosphate-binding cassette (ABC) transporters. The dysregulation of non-coding RNAs (ncRNAs) is a widely concerned reason contributing to this phenotype. Read More

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Research Progress of Pancreas-Related Microorganisms and Pancreatic Cancer.

Front Oncol 2020 14;10:604531. Epub 2021 Jan 14.

Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, China.

Pancreatic cancer is one of the most common digestive system cancers. Early diagnosis is difficult owing to the lack of specific symptoms and reliable biomarkers. The cause of pancreatic cancer remains ambiguous. Read More

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January 2021

Role of primary cilium in pancreatic ductal adenocarcinoma (Review).

Int J Oncol 2020 11 14;57(5):1095-1102. Epub 2020 Sep 14.

Department of Specialistic Clinical and Odontostomatological Sciences, Polytechnic University of Marche, I‑60131 Ancona, Italy.

The primary cilium is a non‑motile cellular structure extending from the apical membrane of epithelial cells that is involved in several processes due to its ability to receive and elaborate different signals. Ciliogenesis and its obliteration are essential for proliferating cells, and several signalling pathways are responsible for their regulation. In fact, the primary cilium is a central hub for numerous signalling pathways implicated in a variety of biological processes, such as the Hedgehog, mammalian target of rapamycin and Wnt pathways. Read More

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November 2020

FOLFIRINOX regulated tumor immune microenvironment to extend the survival of patients with resectable pancreatic ductal adenocarcinoma.

Gland Surg 2020 Dec;9(6):2125-2135

Department of Oncology, First Affiliated Hospital of Soochow University, Suzhou, China.

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly malignant tumors worldwide due to its ineffective diagnosis and poor prognosis. The longest median overall survival (OS) to PDAC patients has been provided by FOLFIRINOX. It is essential to identify the mechanisms of FOLFIRINOX to gain new insights for the treatment of PDAC. Read More

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December 2020

New Onset of DiabetEs in aSsociation with pancreatic ductal adenocarcinoma (NODES Trial): protocol of a prospective, multicentre observational trial.

BMJ Open 2020 11 19;10(11):e037267. Epub 2020 Nov 19.

First Department of Medicine, University of Szeged, Szeged, Hungary

Introduction: Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis with an overall 5-year survival of approximately 8%. The success in reducing the mortality rate of PDAC is related to the discovery of new therapeutic agents, and to a significant extent to the development of early detection and prevention programmes. Patients with new-onset diabetes mellitus (DM) represent a high-risk group for PDAC as they have an eightfold higher risk of PDAC than the general population. Read More

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November 2020

Upregulation of amplified in breast cancer 1 contributes to pancreatic ductal adenocarcinoma progression and vulnerability to blockage of hedgehog activation.

Theranostics 2021 1;11(4):1672-1689. Epub 2021 Jan 1.

Cancer Centre, Faculty of Health Sciences, University of Macau, Macau SAR, China.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and devastating cancers without effective treatments. Amplified in breast cancer 1 (AIB1) is a member of the steroid receptor coactivator family that mediates the transcriptional activities of nuclear receptors. While AIB1 is associated with the initiation and progression of multiple cancers, the mechanism by which AIB1 contributes to PDAC progression remains unknown. Read More

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Risk factors and socio-economic burden in pancreatic ductal adenocarcinoma operation: a machine learning based analysis.

BMC Cancer 2020 Nov 27;20(1):1161. Epub 2020 Nov 27.

Department of Anesthesiology, South Campus, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

Background: Surgical resection is the major way to cure pancreatic ductal adenocarcinoma (PDAC). However, this operation is complex, and the peri-operative risk is high, making patients more likely to be admitted to the intensive care unit (ICU). Therefore, establishing a risk model that predicts admission to ICU is meaningful in preventing patients from post-operation deterioration and potentially reducing socio-economic burden. Read More

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November 2020

Three-Dimensional Cell Culture Systems in Radiopharmaceutical Cancer Research.

Cancers (Basel) 2020 Sep 25;12(10). Epub 2020 Sep 25.

Department of Radiopharmaceutical and Chemical Biology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, 01328 Dresden, Germany.

In preclinical cancer research, three-dimensional (3D) cell culture systems such as multicellular spheroids and organoids are becoming increasingly important. They provide valuable information before studies on animal models begin and, in some cases, are even suitable for reducing or replacing animal experiments. Furthermore, they recapitulate microtumors, metastases, and the tumor microenvironment much better than monolayer culture systems could. Read More

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September 2020

Pancreatic cancer resistance conferred by stellate cells: looking for new preclinical models.

Exp Hematol Oncol 2020 3;9:18. Epub 2020 Aug 3.

Department of Medical Oncology, Amsterdam University Medical Centers, Location VUMC, Cancer Center Amsterdam, CCA Room 1.52 De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.

Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor response to chemo- and (modest-dose conventionally fractionated) radio-therapy. Emerging evidence suggests that pancreatic stellate cells (PSCs) secrete deoxycytidine, which confers resistance to gemcitabine. In particular, deoxycytidine was detected by analysis of metabolites in fractionated media from different mouse PSCs, showing that it caused PDAC cells chemoresistance by reducing the capacity of deoxycytidine kinase (dCK) for gemcitabine phosphorylation. Read More

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A generalizable data-driven multicellular model of pancreatic ductal adenocarcinoma.

Gigascience 2020 07;9(7)

Institute for Systems Biology, 401 Terry Avenue North, Seattle, WA 98109, USA.

Background: Mechanistic models, when combined with pertinent data, can improve our knowledge regarding important molecular and cellular mechanisms found in cancer. These models make the prediction of tissue-level response to drug treatment possible, which can lead to new therapies and improved patient outcomes. Here we present a data-driven multiscale modeling framework to study molecular interactions between cancer, stromal, and immune cells found in the tumor microenvironment. Read More

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Vitamin D Prevents Pancreatic Cancer-Induced Apoptosis Signaling of Inflammatory Cells.

Biomolecules 2020 07 15;10(7). Epub 2020 Jul 15.

Department of Medicine-DIMED, Laboratory Medicine, University of Padova, Via Giustiniani 2, 35128 Padova, Italy.

Combined approaches based on immunotherapy and drugs supporting immune effector cell function might increase treatment options for pancreatic ductal adenocarcinoma (PDAC), vitamin D being a suitable drug candidate. In this study, we evaluated whether treatment with the vitamin D analogue, calcipotriol, counterbalances PDAC induced and SMAD4-associated intracellular calcium [Ca] alterations, cytokines release, immune effector function, and the intracellular signaling of peripheral blood mononuclear cells (PBMCs). Calcipotriol counteracted the [Ca] depletion of PBMCs induced by SMAD4-expressing PDAC cells, which conditioned media augmented the number of calcium flows while reducing whole [Ca]. Read More

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Improvement of biodistribution profile of a radiogallium-labeled, αvβ6 integrin-targeting peptide probe by incorporation of negatively charged amino acids.

Ann Nucl Med 2020 Aug 8;34(8):575-582. Epub 2020 Jun 8.

Department of Biofunction Imaging Analysis, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Kita-ku, Okayama, 700-8530, Japan.

Objective: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers. Since αvβ6 integrin has been reported as a promising target for PDAC diagnosis, we previously developed H-Cys(mal-NOTA-Ga)-(Gly)6-A20FMDV2-NH ([Ga]CG6) as an αvβ6 integrin-targeting probe. Although [Ga]CG6 specifically binds to αvβ6 integrin-positive xenografts, the uptake of [Ga]CG6 in the organs surrounding the pancreas, such as the liver and spleen, was comparable to that in the αvβ6 integrin-positive xenografts. Read More

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Oxidative stress induces monocyte-to-myofibroblast transdifferentiation through p38 in pancreatic ductal adenocarcinoma.

Clin Transl Med 2020 Jun 4;10(2):e41. Epub 2020 Jun 4.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.

Background: Cancer-associated fibroblasts (CAFs) are among the most prominent cells during the desmoplastic reaction in pancreatic ductal adenocarcinoma (PDAC). However, CAFs are heterogeneous and the precise origins are not fully elucidated. This study aimed to explore whether monocytes can transdifferentiate into fibroblasts in PDAC and evaluate the clinical significance of this event. Read More

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Construction of a novel bispecific fusion protein to enhance targeting for pancreatic cancer imaging.

Biomaterials 2020 10 30;255:120161. Epub 2020 May 30.

Department of Diagnostic Imaging, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China. Electronic address:

Early detection and diagnosis are the most important endeavors for reducing associated morbidity and mortality of pancreatic ductal adenocarcinoma (PDAC). Developing molecular imaging probes that can specifically and effectively target cancer-associated biological pathways is one of the key points for sensitive and accurate diagnosis for PDAC. Herein, a small-sized, bispecific fusion protein constructed by genetic fusion of different binding domains of antibodies, termed Bi50, with enhanced targeting effect for PDAC is reported. Read More

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October 2020

Autophagy promotes immune evasion of pancreatic cancer by degrading MHC-I.

Nature 2020 05 22;581(7806):100-105. Epub 2020 Apr 22.

Department of Radiation Oncology, Perlmutter Cancer Center, New York University School of Medicine, New York, NY, USA.

Immune evasion is a major obstacle for cancer treatment. Common mechanisms of evasion include impaired antigen presentation caused by mutations or loss of heterozygosity of the major histocompatibility complex class I (MHC-I), which has been implicated in resistance to immune checkpoint blockade (ICB) therapy. However, in pancreatic ductal adenocarcinoma (PDAC), which is resistant to most therapies including ICB, mutations that cause loss of MHC-I are rarely found despite the frequent downregulation of MHC-I expression. Read More

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