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Biomedicines
Special Issues
Early Diagnosis and Targeted Therapy of Pancreatic Cancer
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Early Diagnosis and Targeted Therapy of Pancreatic Cancer

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: 30 September 2024 | Viewed by 1610

Special Issue Editor

Dr. Nelson Yee

E-Mail Website
Guest Editor
Penn State Cancer Institute, 500 University Drive, Hershey, PA 17033-0850, USA
Interests: cancer clinical investigation; translational cancer research; machine learning in oncology

Special Issue Information

Dear Colleagues,

Steady progress has been made in understanding the biology of pancreatic cancer, yet further improvement in the treatment and early diagnosis of pancreatic cancer is still required to address unmet needs. Cytotoxic chemotherapy of pancreatic carcinoma has remained a mainstay of treatment though with modest benefit, and targeted- and immuno-therapies have been focuses of intensive investigation. The application of stereotactic body radiation, radiosensitizers, and MRI-guided radiation therapy have shown the good potential of improving the therapeutic response of pancreatic cancer. New technologies involving tumor molecular profiling and blood-based biopsy for circulating tumor cells/DNA and extracellular vesicles have demonstrated strong potential for the early detection and diagnosis of pancreatic cancer. Machine and deep learning for analytics of big data have emerged as powerful predictive tools in pancreatic cancer. The aims of this Special Issue are to generate a collection of articles that focus on recent advances of diagnosis and treatment in pancreatic cancer, with the goal of advancing our understanding of and treatments for this challenging oncological disease. 

Dr. Nelson Yee
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • targeted therapy
  • molecular profiling
  • liquid biopsy
  • radiation therapy
  • immunotherapy
  • machine learning
  • early detection
  • extracellular vesicles
  • exosomes
  • circulating tumor cells
  • circulating tumor DNA
  • pancreatic cancer

Published Papers (2 papers)

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Research

15 pages, 3923 KiB  
Article
CCK Receptor Inhibition Reduces Pancreatic Tumor Fibrosis and Promotes Nanoparticle Delivery
by Thomas Abraham, Michael Armold, Christopher McGovern, John F. Harms, Matthew C. Darok, Christopher Gigliotti, Bernadette Adair, Jennifer L. Gray, Deborah F. Kelly, James H. Adair and Gail L. Matters
Biomedicines 2024, 12(5), 1024; https://doi.org/10.3390/biomedicines12051024 - 7 May 2024
Viewed by 353
Abstract
The poor prognosis for pancreatic ductal adenocarcinoma (PDAC) patients is due in part to the highly fibrotic nature of the tumors that impedes delivery of therapeutics, including nanoparticles (NPs). Our prior studies demonstrated that proglumide, a cholecystokinin receptor (CCKR) antagonist, reduced fibrosis pervading [...] Read more.
The poor prognosis for pancreatic ductal adenocarcinoma (PDAC) patients is due in part to the highly fibrotic nature of the tumors that impedes delivery of therapeutics, including nanoparticles (NPs). Our prior studies demonstrated that proglumide, a cholecystokinin receptor (CCKR) antagonist, reduced fibrosis pervading PanIN lesions in mice. Here, we further detail how the reduced fibrosis elicited by proglumide achieves the normalization of the desmoplastic tumor microenvironment (TME) and improves nanoparticle uptake. One week following the orthotopic injection of PDAC cells, mice were randomized to normal or proglumide-treated water for 3–6 weeks. Tumors were analyzed ex vivo for fibrosis, vascularity, stellate cell activation, vascular patency, and nanoparticle distribution. The histological staining and three-dimensional imaging of tumors each indicated a reduction in stromal collagen in proglumide-treated mice. Proglumide treatment increased tumor vascularity and decreased the activation of cancer-associated fibroblasts (CAFs). Additionally, PANC-1 cells with the shRNA-mediated knockdown of the CCK2 receptor showed an even greater reduction in collagen, indicating the CCK2 receptors on tumor cells contribute to the desmoplastic TME. Proglumide-mediated reduction in fibrosis also led to functional changes in the TME as evidenced by the enhanced intra-tumoral distribution of small (<12 nm) Rhodamine-loaded nanoparticles. The documented in vivo, tumor cell-intrinsic anti-fibrotic effects of CCK2R blockade in both an immunocompetent syngeneic murine PDAC model as well as a human PDAC xenograft model demonstrates that CCK2R antagonists, such as proglumide, can improve the delivery of nano-encapsulated therapeutics or imaging agents to pancreatic tumors. Full article
(This article belongs to the Special Issue Early Diagnosis and Targeted Therapy of Pancreatic Cancer)
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17 pages, 3052 KiB  
Article
The Assessment of a Novel Endoscopic Ultrasound-Compatible Cryocatheter to Ablate Pancreatic Cancer
by John M. Baust, Anthony Robilotto, Isaac Raijman, Kimberly L. Santucci, Robert G. Van Buskirk, John G. Baust and Kristi K. Snyder
Biomedicines 2024, 12(3), 507; https://doi.org/10.3390/biomedicines12030507 - 23 Feb 2024
Viewed by 998
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease that may be treated utilizing thermal therapies. Cryoablation is an effective, minimally invasive therapy that has been utilized for the treatment of various cancers, offering patients a quicker recovery and reduced side effects. Cryoablation [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease that may be treated utilizing thermal therapies. Cryoablation is an effective, minimally invasive therapy that has been utilized for the treatment of various cancers, offering patients a quicker recovery and reduced side effects. Cryoablation has been utilized on a limited basis for the treatment of PDAC. With the recent reports on the success of cryoablation, there is a growing interest in the use of cryoablation as a standalone, minimally invasive procedure to treat PDAC. While offering a promising path, the application of cryoablation to PDAC is limited by current technologies. As such, there is a need for the development of new devices to support advanced treatment strategies for PDAC. To this end, this study investigated the performance of a new endoscopic ultrasound-compatible cryoablation catheter technology, FrostBite. We hypothesized that FrostBite would enable the rapid, effective, minimally invasive delivery of ultra-cold temperatures to target tissues, resulting in effective ablation via an endoscopic approach. Thermal properties and ablative efficacy were evaluated using a heat-loaded gel model, tissue-engineered models (TEMs), and an initial in vivo porcine study. Freeze protocols evaluated included single and repeat 3 and 5 min applications. Isotherm assessment revealed the generation of a 2.2 cm diameter frozen mass with the −20 °C isotherm reaching a diameter of 1.5 cm following a single 5 min freeze. TEM studies revealed the achievement of temperatures ≤ −20 °C at a diameter of 1.9 cm after a 5 min freeze. Fluorescent imaging conducted 24 h post-thaw demonstrated a uniformly shaped ellipsoidal ablative zone with a midline diameter of 2.5 cm, resulting in a total ablative volume of 6.9 cm3 after a single 5 min freeze. In vivo findings consistently demonstrated the generation of ablative areas measuring 2.03 cm × 3.2 cm. These studies demonstrate the potential of the FrostBite cryocatheter as an endoscopic ultrasound-based treatment option. The data suggest that FrostBite may provide for the rapid, effective, controllable freezing of cancerous pancreatic and liver tissues. This ablative power also offers the potential of improved safety margins via the minimally invasive nature of an endoscopic ultrasound-based approach or natural orifice transluminal endoscopic surgery (NOTES)-based approach. The results of this pre-clinical feasibility study show promise, affirming the need for further investigation into the potential of the FrostBite cryocatheter as an advanced, minimally invasive cryoablative technology. Full article
(This article belongs to the Special Issue Early Diagnosis and Targeted Therapy of Pancreatic Cancer)
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