Invasion-promoting extracellular matrix composition enhances photodynamic therapy response in 3D pancreatic cancer models

2017 ◽  
Author(s):  
Gwendolyn M. Cramer ◽  
Hamid El-Hamidi ◽  
Jonathan P. Celli
Keyword(s):  
Pancreatic Cancer ◽  
Extracellular Matrix ◽  
Photodynamic Therapy ◽  
Therapy Response ◽  
Matrix Composition ◽  
Cancer Models

Abstract 2676: A secreted tissue engineered extracellular matrix (shECM) prevents recurrence in post-resection pancreatic cancer models

2012 ◽  
Author(s):  
Emmett Pinney ◽  
Rhiana Menen ◽  
Mohamed Hassanein ◽  
Mayra Montes-Camacho ◽  
Gail Naughton ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Extracellular Matrix ◽  
Cancer Models

scholarly journals The Revolutionary Roads to Study Cell–Cell Interactions in 3D In Vitro Pancreatic Cancer Models

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 930
Author(s):  
Donatella Delle Cave ◽  
Riccardo Rizzo ◽  
Bruno Sainz ◽  
Giuseppe Gigli ◽  
Loretta L. del Mercato ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Therapeutic Response ◽  
Three Dimensional ◽  
Cellular Models ◽  
Common Cancer ◽  
Cancer Models ◽  
Anti Cancer ◽  
Tumor Environment

Pancreatic cancer, the fourth most common cancer worldwide, shows a highly unsuccessful therapeutic response. In the last 10 years, neither important advancements nor new therapeutic strategies have significantly impacted patient survival, highlighting the need to pursue new avenues for drug development discovery and design. Advanced cellular models, resembling as much as possible the original in vivo tumor environment, may be more successful in predicting the efficacy of future anti-cancer candidates in clinical trials. In this review, we discuss novel bioengineered platforms for anticancer drug discovery in pancreatic cancer, from traditional two-dimensional models to innovative three-dimensional ones.

scholarly journals Immune Cell Modulation of the Extracellular Matrix Contributes to the Pathogenesis of Pancreatic Cancer

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 901
Author(s):  
Ramiz S. Ahmad ◽  
Timothy D. Eubank ◽  
Slawomir Lukomski ◽  
Brian A. Boone
Keyword(s):  
Pancreatic Cancer ◽  
Extracellular Matrix ◽  
Immune Cells ◽  
Immune Cell ◽  
Treatment Strategies ◽  
Stellate Cells ◽  
Pancreatic Stellate Cells ◽  
Ductal Adenocarcinoma ◽  
Cellular Mechanisms ◽  
Novel Treatment Strategies

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with a five-year survival rate of only 9%. PDAC is characterized by a dense, fibrotic stroma composed of extracellular matrix (ECM) proteins. This desmoplastic stroma is a hallmark of PDAC, representing a significant physical barrier that is immunosuppressive and obstructs penetration of cytotoxic chemotherapy agents into the tumor microenvironment (TME). Additionally, dense ECM promotes hypoxia, making tumor cells refractive to radiation therapy and alters their metabolism, thereby supporting proliferation and survival. In this review, we outline the significant contribution of fibrosis to the pathogenesis of pancreatic cancer, with a focus on the cross talk between immune cells and pancreatic stellate cells that contribute to ECM deposition. We emphasize the cellular mechanisms by which neutrophils and macrophages, specifically, modulate the ECM in favor of PDAC-progression. Furthermore, we investigate how activated stellate cells and ECM influence immune cells and promote immunosuppression in PDAC. Finally, we summarize therapeutic strategies that target the stroma and hinder immune cell promotion of fibrogenesis, which have unfortunately led to mixed results. An enhanced understanding of the complex interactions between the pancreatic tumor ECM and immune cells may uncover novel treatment strategies that are desperately needed for this devastating disease.

scholarly journals Alkynyl N-BODIPYs as Reactive Intermediates for the Development of Dyes for Biophotonics

2020 ◽  
Vol 3 (1) ◽  
pp. 15
Author(s):  
César Ray ◽  
Andrés García-Sampedro ◽  
Christopher Schad ◽  
Edurne Avellanal-Zaballa ◽  
Florencio Moreno ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Photodynamic Therapy ◽  
Click Chemistry ◽  
Cancer Cells ◽  
Reactive Intermediates ◽  
New Approach ◽  
Pancreatic Cancer Cells ◽  
Bio Imaging

A new approach for the rapid multi-functionalization of BODIPY dyes towards biophotonics is reported. It is based on novel N-BODIPYs, through reactive intermediates with alkynyl groups to be further derivatized by click chemistry. This approach has been exemplified by the development of new dyes for cell bio-imaging, which have proven to successfully internalize into pancreatic cancer cells and accumulate in the mitochondria. The in vitro suitability for photodynamic therapy (PDT) was also analyzed and confirmed our compounds to be promising PDT candidates for the treatment of pancreatic cancer.

scholarly journals An Efficient Photodynamic Therapy Treatment for Human Pancreatic Adenocarcinoma

2020 ◽  
Vol 9 (1) ◽  
pp. 192 ◽  
Author(s):  
Alexandre Quilbe ◽  
Olivier Moralès ◽  
Martha Baydoun ◽  
Abhishek Kumar ◽  
Rami Mustapha ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Photodynamic Therapy ◽  
Immune System ◽  
Cancer Cells ◽  
Pancreatic Adenocarcinoma ◽  
Cell Lines ◽  
Folate Receptor ◽  
Mice Model ◽  
Gene And Protein Expression ◽  
The Impact

To date, pancreatic adenocarcinoma (ADKP) is a devastating disease for which the incidence rate is close to the mortality rate. The survival rate has evolved only 2–5% in 45 years, highlighting the failure of current therapies. Otherwise, the use of photodynamic therapy (PDT), based on the use of an adapted photosensitizer (PS) has already proved its worth and has prompted a growing interest in the field of oncology. We have developed a new photosensitizer (PS-FOL/PS2), protected by a recently published patent (WO2019 016397-A1, 24 January 2019). This photosensitizer is associated with an addressing molecule (folic acid) targeting the folate receptor 1 (FOLR1) with a high affinity. Folate binds to FOLR1, in a specific way, expressed in 100% of ADKP or over-expressed in 30% of cases. The first objective of this study is to evaluate the effectiveness of this PS2-PDT in four ADKP cell lines: Capan-1, Capan-2, MiapaCa-2, and Panc-1. For this purpose, we first evaluated the gene and protein expression of FOLR1 on four ADKP cell lines. Subsequently, we evaluated PS2’s efficacy in our cell lines and we assessed the impact of PDT on the secretome of cancer cells and its impact on the immune system. Finally, we evaluate the PDT efficacy on a humanized SCID mouse model of pancreatic cancer. In a very interesting way, we observed a significant increase in the proliferation of activated-human PBMC when cultured with conditioned media of ADKP cancer cells subjected to PDT. Furthermore, to evaluate in vivo the impact of this new PS, we analyzed the tumor growth in a humanized SCID mice model of pancreatic cancer. Four conditions were tested: Untreated, mice (nontreated), mice with PS (PS2), mice subjected to illumination (Light only), and mice subjected to illumination in the presence of PS (PDT). We noticed that the mice subjected to PDT presented a strong decrease in the growth of the tumor over time after illumination. Our investigations have not only suggested that PS2-PDT is an effective therapy in the treatment of PDAC but also that it activates the immune system and could be considered as a real adjuvant for anti-cancer vaccination. Thus, this new study provides new treatment options for patients in a therapeutic impasse and will provide a new arsenal in the fight against PDAC.

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