Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
7.8
5.6
Journals
IJMS
Special Issues
Therapeutic Targets in Pancreatic Cancer
ijms-logo
Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

Therapeutic Targets in Pancreatic Cancer

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (20 April 2024) | Viewed by 15857

Special Issue Editors

Dr. Dorota Lubgan

E-Mail
Guest Editor
Translational Radiobiology, Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstr. 27, 91054 Erlangen, Germany
Interests: radiooncology; translational research; clinical trials; pancreatic cancer; supportive therapy
Special Issues, Collections and Topics in MDPI journals
Dr. Nathalie Britzen-Laurent

E-Mail
Guest Editor
Division of Surgical Research, Department of Surgery, Translational Research Center, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany
Interests: pancreatic cancer; translational research; therapeutic targets and novel interventional strategies; mechanisms of anti-tumor reactions; biomarkers
Special Issues, Collections and Topics in MDPI journals
Dr. Benjamin Frey

E-Mail
Guest Editor
Translational Radiobiology, Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstr. 27, 91054 Erlangen, Germany
Interests: radiotherapy; immunotherapy; vaccination; immune checkpoints; hyperthermia; tumor immunology; immunogenic cancer cell death; immunomonitoring; inflammatory and degenerative diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The International Journal of Molecular Sciences is currently running a Special Issue entitled “Therapeutic Targets in Pancreatic Cancer”. As we are acting as guest editors for this Issue, we would like to welcome contributions from various topics and different viewpoints on this research area.

In this Special Issue, we aim to cover all aspects of the current landscape of translational research in pancreatic cancer: prognostic and predictive biomarkers, molecular targeting, DNA damage and repair, targeted and immune therapies, and mechanisms of tumor defense.

Translational and basic approaches are welcome; immunological aspects in the pre-clinic as well as in the patient are desirable. Genetic approaches in prospective patient cohorts (e.g., within the ongoing clinical trials), which are translationally obtained and molecular characterization of tumor tissue for better treatment selection, are also of interest.

We would like to take a look at new preclinical strategies for the treatment of pancreatic cancer, especially new targets for therapy or for the avoidance of resistance to radiation and/or chemotherapy. Pure evaluations of existing cohorts are only accepted in exceptional cases. A translational approach should always be recognizable.

We are very much looking forward to receiving your submission.

Dr. Dorota Lubgan
Dr. Nathalie Britzen-Laurent
Dr. Benjamin Frey
Guest Editors

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • pancreatic cancer
  • translational research
  • therapeutic targets and novel interventional strategies
  • mechanisms of anti-tumor reactions
  • biomarkers

Related Special Issue

Published Papers (12 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review, Other

19 pages, 4617 KiB  
Article
Nuclear MAST4 Suppresses FOXO3 through Interaction with AKT3 and Induces Chemoresistance in Pancreatic Ductal Carcinoma
by Rina Fujiwara-Tani, Takamitsu Sasaki, Ujjal Kumar Bhawal, Shiori Mori, Ruiko Ogata, Rika Sasaki, Ayaka Ikemoto, Shingo Kishi, Kiyomu Fujii, Hitoshi Ohmori, Masayuki Sho and Hiroki Kuniyasu
Int. J. Mol. Sci. 2024, 25(7), 4056; https://doi.org/10.3390/ijms25074056 - 05 Apr 2024
Viewed by 661
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is highly malignant, with a 5-year survival rate of less than 10%. Furthermore, the acquisition of anticancer drug resistance makes PDAC treatment difficult. We established MIA-GEM cells, a PDAC cell line resistant to gemcitabine (GEM), a first-line anticancer drug, [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) is highly malignant, with a 5-year survival rate of less than 10%. Furthermore, the acquisition of anticancer drug resistance makes PDAC treatment difficult. We established MIA-GEM cells, a PDAC cell line resistant to gemcitabine (GEM), a first-line anticancer drug, using the human PDAC cell line—MIA-PaCa-2. Microtubule-associated serine/threonine kinase-4 (MAST4) expression was increased in MIA-GEM cells compared with the parent cell line. Through inhibitor screening, dysregulated AKT signaling was identified in MIA-GEM cells with overexpression of AKT3. MAST4 knockdown effectively suppressed AKT3 overexpression, and both MAST4 and AKT3 translocation into the nucleus, phosphorylating forkhead box O3a (FOXO3) in MIA-GEM cells. Modulating FOXO3 target gene expression in these cells inhibited apoptosis while promoting stemness and proliferation. Notably, nuclear MAST4 demonstrated higher expression in GEM-resistant PDAC cases compared with that in the GEM-sensitive cases. Elevated MAST4 expression correlated with a poorer prognosis in PDAC. Consequently, nuclear MAST4 emerges as a potential marker for GEM resistance and poor prognosis, representing a novel therapeutic target for PDAC. Full article
(This article belongs to the Special Issue Therapeutic Targets in Pancreatic Cancer)
►▼ Show Figures

Figure 1

26 pages, 3573 KiB  
Article
Gemcitabine Modulates HLA-I Regulation to Improve Tumor Antigen Presentation by Pancreatic Cancer Cells
by Alaina C. Larson, Shelby M. Knoche, Gabrielle L. Brumfield, Kenadie R. Doty, Benjamin D. Gephart, Promise R. Moore-Saufley and Joyce C. Solheim
Int. J. Mol. Sci. 2024, 25(6), 3211; https://doi.org/10.3390/ijms25063211 - 11 Mar 2024
Viewed by 931
Abstract
Pancreatic cancer is a lethal disease, harboring a five-year overall survival rate of only 13%. Current treatment approaches thus require modulation, with attention shifting towards liberating the stalled efficacy of immunotherapies. Select chemotherapy drugs which possess inherent immune-modifying behaviors could revitalize immune activity [...] Read more.
Pancreatic cancer is a lethal disease, harboring a five-year overall survival rate of only 13%. Current treatment approaches thus require modulation, with attention shifting towards liberating the stalled efficacy of immunotherapies. Select chemotherapy drugs which possess inherent immune-modifying behaviors could revitalize immune activity against pancreatic tumors and potentiate immunotherapeutic success. In this study, we characterized the influence of gemcitabine, a chemotherapy drug approved for the treatment of pancreatic cancer, on tumor antigen presentation by human leukocyte antigen class I (HLA-I). Gemcitabine increased pancreatic cancer cells’ HLA-I mRNA transcripts, total protein, surface expression, and surface stability. Temperature-dependent assay results indicated that the increased HLA-I stability may be due to reduced binding of low affinity peptides. Mass spectrometry analysis confirmed changes in the HLA-I-presented peptide pool post-treatment, and computational predictions suggested improved affinity and immunogenicity of peptides displayed solely by gemcitabine-treated cells. Most of the gemcitabine-exclusive peptides were derived from unique source proteins, with a notable overrepresentation of translation-related proteins. Gemcitabine also increased expression of select immunoproteasome subunits, providing a plausible mechanism for its modulation of the HLA-I-bound peptidome. Our work supports continued investigation of immunotherapies, including peptide-based vaccines, to be used with gemcitabine as new combination treatment modalities for pancreatic cancer. Full article
(This article belongs to the Special Issue Therapeutic Targets in Pancreatic Cancer)
►▼ Show Figures

Figure 1

16 pages, 4414 KiB  
Article
A Cancer-Specific Monoclonal Antibody against Podocalyxin Exerted Antitumor Activities in Pancreatic Cancer Xenografts
by Hiroyuki Suzuki, Tomokazu Ohishi, Tomohiro Tanaka, Mika K. Kaneko and Yukinari Kato
Int. J. Mol. Sci. 2024, 25(1), 161; https://doi.org/10.3390/ijms25010161 - 21 Dec 2023
Cited by 1 | Viewed by 828
Abstract
Podocalyxin (PODXL) overexpression is associated with poor clinical outcomes in various tumors. PODXL is involved in tumor malignant progression through the promotion of invasiveness and metastasis. Therefore, PODXL is considered a promising target of monoclonal antibody (mAb)-based therapy. However, PODXL also plays an [...] Read more.
Podocalyxin (PODXL) overexpression is associated with poor clinical outcomes in various tumors. PODXL is involved in tumor malignant progression through the promotion of invasiveness and metastasis. Therefore, PODXL is considered a promising target of monoclonal antibody (mAb)-based therapy. However, PODXL also plays an essential role in normal cells, such as vascular and lymphatic endothelial cells. Therefore, cancer specificity or selectivity is required to reduce adverse effects on normal cells. Here, we developed an anti-PODXL cancer-specific mAb (CasMab), PcMab-6 (IgG1, kappa), by immunizing mice with a soluble PODXL ectodomain derived from a glioblastoma LN229 cell. PcMab-6 reacted with the PODXL-positive LN229 cells but not with PODXL-knockout LN229 cells in flow cytometry. Importantly, PcMab-6 recognized pancreatic ductal adenocarcinoma (PDAC) cell lines (MIA PaCa-2, Capan-2, and PK-45H) but did not react with normal lymphatic endothelial cells (LECs). In contrast, one of the non-CasMabs, PcMab-47, showed high reactivity to both the PDAC cell lines and LECs. Next, we engineered PcMab-6 into a mouse IgG2a-type (PcMab-6-mG2a) and a humanized IgG1-type (humPcMab-6) mAb and further produced the core fucose-deficient types (PcMab-6-mG2a-f and humPcMab-6-f, respectively) to potentiate the antibody-dependent cellular cytotoxicity (ADCC). Both PcMab-6-mG2a-f and humPcMab-6-f exerted ADCC and complement-dependent cellular cytotoxicity in the presence of effector cells and complements, respectively. In the PDAC xenograft model, both PcMab-6-mG2a-f and humPcMab-6-f exhibited potent antitumor effects. These results indicated that humPcMab-6-f could apply to antibody-based therapy against PODXL-expressing pancreatic cancers. Full article
(This article belongs to the Special Issue Therapeutic Targets in Pancreatic Cancer)
►▼ Show Figures

Figure 1

19 pages, 21722 KiB  
Article
Integration of Single-Cell RNA Sequencing and Bulk RNA Sequencing Reveals That TAM2-Driven Genes Affect Immunotherapeutic Response and Prognosis in Pancreatic Cancer
by Yan Du, Shi Dong, Wenkai Jiang, Mengyao Li, Wancheng Li, Xin Li and Wence Zhou
Int. J. Mol. Sci. 2023, 24(16), 12787; https://doi.org/10.3390/ijms241612787 - 14 Aug 2023
Cited by 3 | Viewed by 1673
Abstract
Tumor-associated macrophages M2 (TAM2), which are highly prevalent infiltrating immune cells in the stroma of pancreatic cancer (PC), have been found to induce an immunosuppressive tumor microenvironment, thus enhancing tumor initiation and progression. However, the immune therapy response and prognostic significance of regulatory [...] Read more.
Tumor-associated macrophages M2 (TAM2), which are highly prevalent infiltrating immune cells in the stroma of pancreatic cancer (PC), have been found to induce an immunosuppressive tumor microenvironment, thus enhancing tumor initiation and progression. However, the immune therapy response and prognostic significance of regulatory genes associated with TAM2 in PC are currently unknown. Based on TCGA transcriptomic data and single-cell sequencing data from the GEO database, we identified TAM2-driven genes using the WGCNA algorithm. Molecular subtypes based on TAM2-driven genes were clustered using the ConsensusClusterPlus algorithm. The study constructed a prognostic model based on TAM2-driven genes through Lasso-COX regression analysis. A total of 178 samples obtained by accessing TCGA were accurately categorized into two molecular subtypes, including the high-TAM2 infiltration (HMI) cluster and the low-TAM2 infiltration (LMI) cluster. The HMI cluster exhibits a poor prognosis, a malignant tumor phenotype, immune-suppressive immune cell infiltration, resistance to immunotherapy, and a high number of genetic mutations, while the LMI cluster is the opposite. The prognostic model composed of six hub genes from TAM2-driven genes exhibits a high degree of accuracy in predicting the prognosis of patients with PC and serves as an independent risk factor. The induction of TAM2 was employed as a means of verifying these six gene expressions, revealing the significant up-regulation of BCAT1, BST2, and MERTK in TAM2 cells. In summary, the immunophenotype and prognostic model based on TAM2-driven genes offers a foundation for the clinical management of PC. The core TAM2-driven genes, including BCAT1, BST2, and MERTK, are involved in regulating tumor progression and TAM2 polarization, which are potential targets for PC therapy. Full article
(This article belongs to the Special Issue Therapeutic Targets in Pancreatic Cancer)
►▼ Show Figures

Figure 1

9 pages, 1003 KiB  
Communication
Galanin 2 Receptor: A Novel Target for a Subset of Pancreatic Ductal Adenocarcinoma
by Pawel Namsolleck, Barbara Kofler and Gert N. Moll
Int. J. Mol. Sci. 2023, 24(12), 10193; https://doi.org/10.3390/ijms241210193 - 15 Jun 2023
Cited by 1 | Viewed by 1160
Abstract
Galanin is a 30 amino acid peptide that stimulates three subtype receptors (GAL1–3R). M89b is a lanthionine-stabilized, C-terminally truncated galanin analog that specifically stimulates GAL2R. We investigated the potential of M89b as a therapeutic for pancreatic ductal adenocarcinoma (PDAC) [...] Read more.
Galanin is a 30 amino acid peptide that stimulates three subtype receptors (GAL1–3R). M89b is a lanthionine-stabilized, C-terminally truncated galanin analog that specifically stimulates GAL2R. We investigated the potential of M89b as a therapeutic for pancreatic ductal adenocarcinoma (PDAC) and assessed its safety. The anti-tumor activity of subcutaneously injected M89b on the growth of patient-derived xenografts of PDAC (PDAC–PDX) in mice was investigated. In addition, the safety of M89b was assessed in vitro using a multi-target panel to measure the off-target binding and modulation of enzyme activities. In a PDAC–PDX with a high GAL2R expression, M89b completely inhibited the growth of the tumor (p < 0.001), while in two PDAC–PDXs with low GAL2R expression, low or negligeable inhibition of tumor growth was measured, and in the PDX without GAL2R expression no influence on the tumor growth was observed. The M89b treatment of the GAL2R high-PDAC–PDX-bearing mice led to a reduction in the expression of RacGap1 (p < 0.05), PCNA (p < 0.01), and MMP13 (p < 0.05). In vitro studies involving a multi-target panel of pharmacologically relevant targets revealedexcellent safety of M89b. Our data indicated that GAL2R is a safe and valuable target for treating PDACs with high GAL2R expression. Full article
(This article belongs to the Special Issue Therapeutic Targets in Pancreatic Cancer)
►▼ Show Figures

Figure 1

Review

Jump to: Research, Other

29 pages, 1551 KiB  
Review
Clinical and Preclinical Targeting of Oncogenic Pathways in PDAC: Targeted Therapeutic Approaches for the Deadliest Cancer
by Diego J. Jiménez, Aadil Javed, Teresa Rubio-Tomás, Ndioba Seye-Loum and Carles Barceló
Int. J. Mol. Sci. 2024, 25(5), 2860; https://doi.org/10.3390/ijms25052860 - 01 Mar 2024
Viewed by 855
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related death worldwide. It is commonly diagnosed in advanced stages and therapeutic interventions are typically constrained to systemic chemotherapy, which yields only modest clinical outcomes. In this review, we examine recent developments [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related death worldwide. It is commonly diagnosed in advanced stages and therapeutic interventions are typically constrained to systemic chemotherapy, which yields only modest clinical outcomes. In this review, we examine recent developments in targeted therapy tailored to address distinct molecular pathway alteration required for PDAC. Our review delineates the principal signaling pathways and molecular mechanisms implicated in the initiation and progression of PDAC. Subsequently, we provide an overview of prevailing guidelines, ongoing investigations, and prospective research trajectories related to targeted therapeutic interventions, drawing insights from randomized clinical trials and other pertinent studies. This review focus on a comprehensive examination of preclinical and clinical data substantiating the efficacy of these therapeutic modalities, emphasizing the potential of combinatorial regimens and novel therapies to enhance the quality of life for individuals afflicted with PDAC. Lastly, the review delves into the contemporary application and ongoing research endeavors concerning targeted therapy for PDAC. This synthesis serves to bridge the molecular elucidation of PDAC with its clinical implications, the evolution of innovative therapeutic strategies, and the changing landscape of treatment approaches. Full article
(This article belongs to the Special Issue Therapeutic Targets in Pancreatic Cancer)
►▼ Show Figures

Figure 1

35 pages, 749 KiB  
Review
Pancreatic Neuroendocrine Tumors: Signaling Pathways and Epigenetic Regulation
by Zena Saleh, Matthew C. Moccia, Zachary Ladd, Upasana Joneja, Yahui Li, Francis Spitz, Young Ki Hong and Tao Gao
Int. J. Mol. Sci. 2024, 25(2), 1331; https://doi.org/10.3390/ijms25021331 - 22 Jan 2024
Viewed by 1240
Abstract
Pancreatic neuroendocrine tumors (PNETs) are characterized by dysregulated signaling pathways that are crucial for tumor formation and progression. The efficacy of traditional therapies is limited, particularly in the treatment of PNETs at an advanced stage. Epigenetic alterations profoundly impact the activity of signaling [...] Read more.
Pancreatic neuroendocrine tumors (PNETs) are characterized by dysregulated signaling pathways that are crucial for tumor formation and progression. The efficacy of traditional therapies is limited, particularly in the treatment of PNETs at an advanced stage. Epigenetic alterations profoundly impact the activity of signaling pathways in cancer development, offering potential opportunities for drug development. There is currently a lack of extensive research on epigenetic regulation in PNETs. To fill this gap, we first summarize major signaling events that are involved in PNET development. Then, we discuss the epigenetic regulation of these signaling pathways in the context of both PNETs and commonly occurring—and therefore more extensively studied—malignancies. Finally, we will offer a perspective on the future research direction of the PNET epigenome and its potential applications in patient care. Full article
(This article belongs to the Special Issue Therapeutic Targets in Pancreatic Cancer)
►▼ Show Figures

Figure 1

41 pages, 4075 KiB  
Review
Graphene Oxide Nanoparticles and Organoids: A Prospective Advanced Model for Pancreatic Cancer Research
by Shaoshan Mai and Iwona Inkielewicz-Stepniak
Int. J. Mol. Sci. 2024, 25(2), 1066; https://doi.org/10.3390/ijms25021066 - 15 Jan 2024
Cited by 1 | Viewed by 1845
Abstract
Pancreatic cancer, notorious for its grim 10% five-year survival rate, poses significant clinical challenges, largely due to late-stage diagnosis and limited therapeutic options. This review delves into the generation of organoids, including those derived from resected tissues, biopsies, pluripotent stem cells, and adult [...] Read more.
Pancreatic cancer, notorious for its grim 10% five-year survival rate, poses significant clinical challenges, largely due to late-stage diagnosis and limited therapeutic options. This review delves into the generation of organoids, including those derived from resected tissues, biopsies, pluripotent stem cells, and adult stem cells, as well as the advancements in 3D printing. It explores the complexities of the tumor microenvironment, emphasizing culture media, the integration of non-neoplastic cells, and angiogenesis. Additionally, the review examines the multifaceted properties of graphene oxide (GO), such as its mechanical, thermal, electrical, chemical, and optical attributes, and their implications in cancer diagnostics and therapeutics. GO’s unique properties facilitate its interaction with tumors, allowing targeted drug delivery and enhanced imaging for early detection and treatment. The integration of GO with 3D cultured organoid systems, particularly in pancreatic cancer research, is critically analyzed, highlighting current limitations and future potential. This innovative approach has the promise to transform personalized medicine, improve drug screening efficiency, and aid biomarker discovery in this aggressive disease. Through this review, we offer a balanced perspective on the advancements and future prospects in pancreatic cancer research, harnessing the potential of organoids and GO. Full article
(This article belongs to the Special Issue Therapeutic Targets in Pancreatic Cancer)
►▼ Show Figures

Figure 1

21 pages, 4429 KiB  
Review
Iron-Dependent Cell Death: A New Treatment Approach against Pancreatic Ductal Adenocarcinoma
by Carlos Lopez-Blazquez, Carlos Lacalle-Gonzalez, Lara Sanz-Criado, Michael Ochieng’ Otieno, Jesus Garcia-Foncillas and Javier Martinez-Useros
Int. J. Mol. Sci. 2023, 24(19), 14979; https://doi.org/10.3390/ijms241914979 - 07 Oct 2023
Viewed by 1475
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a devastating tumor type where a very high proportion of people diagnosed end up dying from cancer. Surgical resection is an option for only about 20% of patients, where the 5-year survival increase ranges from 10 to 25%. [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) is a devastating tumor type where a very high proportion of people diagnosed end up dying from cancer. Surgical resection is an option for only about 20% of patients, where the 5-year survival increase ranges from 10 to 25%. In addition to surgical resection, there are adjuvant chemotherapy schemes, such as FOLFIRINOX (a mix of Irinotecan, oxaliplatin, 5-Fluorouraci and leucovorin) or gemcitabine-based treatment. These last two drugs have been compared in the NAPOLI-3 clinical trial, and the NALIRIFOX arm was found to have a higher overall survival (OS) (11.1 months vs. 9.2 months). Despite these exciting improvements, PDAC still has no effective treatment. An interesting approach would be to drive ferroptosis in PDAC cells. A non-apoptotic reactive oxygen species (ROS)-dependent cell death, ferroptosis was first described by Dixon et al. in 2012. ROS are constantly produced in the tumor cell due to high cell metabolism, which is even higher when exposed to chemotherapy. Tumor cells have detoxifying mechanisms, such as Mn-SOD or the GSH-GPX system. However, when a threshold of ROS is exceeded in the tumor cell, the cell’s antioxidant systems are overwhelmed, resulting in lipid peroxidation and, ultimately, ferroptosis. In this review, we point out ferroptosis as an approach to consider in PDAC and propose that altering the cellular ROS balance by combining oxidizing agents or with inhibitors of the main cellular detoxifiers triggers ferroptosis in PDAC. Full article
(This article belongs to the Special Issue Therapeutic Targets in Pancreatic Cancer)
►▼ Show Figures

Figure 1

22 pages, 4181 KiB  
Review
Microfluidics and Organoids, the Power Couple of Developmental Biology and Oncology Studies
by Laura Ann Hetzel, Ahmed Ali, Vincenzo Corbo and Thomas Hankemeier
Int. J. Mol. Sci. 2023, 24(13), 10882; https://doi.org/10.3390/ijms241310882 - 29 Jun 2023
Viewed by 1438
Abstract
Organoids are an advanced cell model that hold the key to unlocking a deeper understanding of in vivo cellular processes. This model can be used in understanding organ development, disease progression, and treatment efficacy. As the scientific world embraces the model, it must [...] Read more.
Organoids are an advanced cell model that hold the key to unlocking a deeper understanding of in vivo cellular processes. This model can be used in understanding organ development, disease progression, and treatment efficacy. As the scientific world embraces the model, it must also establish the best practices for cultivating organoids and utilizing them to the greatest potential in assays. Microfluidic devices are emerging as a solution to overcome the challenges of organoids and adapt assays. Unfortunately, the various applications of organoids often depend on specific features in a device. In this review, we discuss the options and considerations for features and materials depending on the application and development of the organoid. Full article
(This article belongs to the Special Issue Therapeutic Targets in Pancreatic Cancer)
►▼ Show Figures

Figure 1

14 pages, 1778 KiB  
Review
Predictive Value of MUC5AC Signature in Pancreatic Ductal Adenocarcinoma: A Hypothesis Based on Preclinical Evidence
by Ashish Manne, Anup Kasi, Ashwini Kumar Esnakula and Ravi Kumar Paluri
Int. J. Mol. Sci. 2023, 24(9), 8087; https://doi.org/10.3390/ijms24098087 - 30 Apr 2023
Cited by 3 | Viewed by 1970
Abstract
Mucin 5AC (MUC5AC) glycoprotein plays a crucial role in carcinogenesis and drug sensitivity in pancreatic ductal adenocarcinoma (PDAC), both individually and in combination with other mucins. Its function and localization are glycoform-specific. The immature isoform (detected by the CLH2 monoclonal antibody, or mab) [...] Read more.
Mucin 5AC (MUC5AC) glycoprotein plays a crucial role in carcinogenesis and drug sensitivity in pancreatic ductal adenocarcinoma (PDAC), both individually and in combination with other mucins. Its function and localization are glycoform-specific. The immature isoform (detected by the CLH2 monoclonal antibody, or mab) is usually in the perinuclear (cytoplasmic) region, while the mature (45 M1, 2-11, Nd2) variants are in apical and extracellular regions. There is preclinical evidence suggesting that mature MUC5AC has prognostic and predictive (response to treatment) value. However, these findings were not validated in clinical studies. We propose a MUC5AC signature with three components of MUC5AC—localization, variant composition, and intensity—suggesting a reliable marker in combination of variants than with individual MUC5AC variants alone. We also postulate a theory to explain the occurrence of different MUC5AC variants in abnormal pancreatic lesions (benign, precancerous, and cancerous). We also analyzed the effect of mature MUC5AC on sensitivity to drugs often used in PDAC management, such as gemcitabine, 5-fluorouracil, oxaliplatin, irinotecan, cisplatin, and paclitaxel. We found preliminary evidence of its predictive value, but there is a need for large-scale studies to validate them. Full article
(This article belongs to the Special Issue Therapeutic Targets in Pancreatic Cancer)
►▼ Show Figures

Figure 1

Other

Jump to: Research, Review

13 pages, 7299 KiB  
Case Report
Novel Ultrastructural Insights into the Clear-Cell Carcinoma of the Pancreas: A Case Report
by Valentina Giansante, Luca Di Angelo, Chiara Calabrese, Paolo De Sanctis, Paolo Regi, Filippo Maria Martelli, Gianmarco Stati, Rossano Lattanzio, Saverio Alberti, Emanuela Guerra and Roberta Di Pietro
Int. J. Mol. Sci. 2024, 25(8), 4313; https://doi.org/10.3390/ijms25084313 - 13 Apr 2024
Viewed by 500
Abstract
Pancreatic cancer, most frequently as ductal adenocarcinoma (PDAC), is the third leading cause of cancer death. Clear-cell primary adenocarcinoma of the pancreas (CCCP) is a rare, aggressive, still poorly characterized subtype of PDAC. We report here a case of a 65-year-old male presenting [...] Read more.
Pancreatic cancer, most frequently as ductal adenocarcinoma (PDAC), is the third leading cause of cancer death. Clear-cell primary adenocarcinoma of the pancreas (CCCP) is a rare, aggressive, still poorly characterized subtype of PDAC. We report here a case of a 65-year-old male presenting with pancreatic neoplasia. A histochemical examination of the tumor showed large cells with clear and abundant intracytoplasmic vacuoles. The clear-cell foamy appearance was not related to the hyperproduction of mucins. Ultrastructural characterization with transmission electron microscopy revealed the massive presence of mitochondria in the clear-cell cytoplasm. The mitochondria showed disordered cristae and various degrees of loss of structural integrity. Immunohistochemistry staining for NADH dehydrogenase [ubiquinone] 1 alpha subcomplex, 4-like 2 (NDUFA4L2) proved specifically negative for the clear-cell tumor. Our ultrastructural and molecular data indicate that the clear-cell nature in CCCP is linked to the accumulation of disrupted mitochondria. We propose that this may impact on the origin and progression of this PDAC subtype. Full article
(This article belongs to the Special Issue Therapeutic Targets in Pancreatic Cancer)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-12
Back to TopTop