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Cells Nov 2020Pancreatic ductal adenocarcinoma (PDA) is characterized by an extensive fibroinflammatory microenvironment that accumulates from the onset of disease progression.... (Review)
Review
Pancreatic ductal adenocarcinoma (PDA) is characterized by an extensive fibroinflammatory microenvironment that accumulates from the onset of disease progression. Cancer-associated fibroblasts (CAFs) are a prominent cellular component of the stroma, but their role during carcinogenesis remains controversial, with both tumor-supporting and tumor-restraining functions reported in different studies. One explanation for these contradictory findings is the heterogeneous nature of the fibroblast populations, and the different roles each subset might play in carcinogenesis. Here, we review the current literature on the origin and function of pancreatic fibroblasts, from the developing organ to the healthy adult pancreas, and throughout the initiation and progression of PDA. We also discuss clinical approaches to targeting fibroblasts in PDA.
Topics: Animals; Cancer-Associated Fibroblasts; Embryonic Development; Fibroblasts; Humans; Mesoderm; Pancreas; Pancreatic Neoplasms
PubMed: 33198201
DOI: 10.3390/cells9112464 -
IUBMB Life Jan 2020There is an urgent need for the development of novel therapeutics options for diabetic patients given the high prevalence of diabetes worldwide and that, currently,... (Review)
Review
There is an urgent need for the development of novel therapeutics options for diabetic patients given the high prevalence of diabetes worldwide and that, currently, there is no cure for this disease. The transplantation of pancreatic islets that contain insulin-producing cells is a promising therapeutic alternative, particularly for type 1 diabetes. However, the shortage of organ donors constitutes a major limitation for this approach; thus, developing alternative sources of insulin-producing cells is of critical importance. In the last decade, our knowledge of the molecular mechanisms controlling embryonic pancreas development has significantly advanced. More importantly, this knowledge has provided the basis for the in vitro generation of insulin-producing cells from stem cells. Recent studies have revealed that GATA transcription factors are involved in various stages of pancreas formation and in the adult ß cell function. Here, we review the fundamental role of GATA transcription factors in pancreas morphogenesis and their association with congenital diseases associated with pancreas.
Topics: Animals; GATA Transcription Factors; Gene Expression Regulation, Developmental; Humans; Pancreas; Pancreatic Diseases; Signal Transduction
PubMed: 31580534
DOI: 10.1002/iub.2170 -
Abdominal Radiology (New York) Aug 2022Percutaneous pancreatic interventions performed by abdominal radiologists play important diagnostic and therapeutic roles in the management of a wide range of pancreatic... (Review)
Review
Percutaneous pancreatic interventions performed by abdominal radiologists play important diagnostic and therapeutic roles in the management of a wide range of pancreatic pathology. While often performed with endoscopy, pancreatic mass biopsy obtained via a percutaneous approach may serve as the only feasible option for diagnosis in patients with post-surgical anatomy, severe cardiopulmonary conditions, or prior non-diagnostic endoscopic attempts. Biopsy of pancreatic transplants are commonly performed percutaneously due to inaccessible location of the allograft by endoscopy, usually in the right lower quadrant or pelvis. Percutaneous drainage of collections in acute pancreatitis is primarily indicated for infection with clinical deterioration and may be performed alone or in combination with endoscopic drainage. Post-surgical pancreatic collections related to pancreatic duct fistula or leak also often warrant therapeutic percutaneous drainage. Knowledge of appropriate indications, strategies of approach, technique, and complications associated with these procedures is critical for a successful clinical practice.
Topics: Acute Disease; Biopsy; Drainage; Endoscopy, Gastrointestinal; Humans; Pancreas; Pancreatic Ducts; Pancreatitis; Treatment Outcome
PubMed: 34410433
DOI: 10.1007/s00261-021-03244-z -
Frontiers in Endocrinology 2021Vitamin A (VA), which is stored in several forms in most tissues, is required to maintain metabolite homeostasis and other processes, including the visual cycle, energy... (Review)
Review
Vitamin A (VA), which is stored in several forms in most tissues, is required to maintain metabolite homeostasis and other processes, including the visual cycle, energy balance, epithelial cell integrity, and infection resistance. In recent years, VA molecules, also known as retinoids, have been extensively explored and used in the treatment of skin disorders and immune-related tumors. To date, several observational and interventional studies have explored the relationship between VA status and the pathogenesis of diabetes. In particular, VA micronutrients have been shown to regulate pancreatic development, β-cell function, pancreatic innate immune responses, and pancreatic stellate cells phenotypes through multiple mechanisms. However, there are still many problems to be proven or resolved. In this review, we summarize and discuss recent and available evidence on VA biological metabolism in the pancreas. Analysis of the effects of VA on metabolism in the pancreas will contribute to our understanding of the supportive physiological roles of VA in pancreas protection.
Topics: Animals; Glucose; Homeostasis; Humans; Lipid Metabolism; Pancreas; Vitamin A
PubMed: 33679618
DOI: 10.3389/fendo.2021.620941 -
ELife Jan 2024The secretion of insulin from the pancreas relies on both gap junctions and subpopulations of beta cells with specific intrinsic properties.
The secretion of insulin from the pancreas relies on both gap junctions and subpopulations of beta cells with specific intrinsic properties.
Topics: Pancreas; Gap Junctions; Insulin; Insulin-Secreting Cells
PubMed: 38270512
DOI: 10.7554/eLife.95103 -
Scientific Reports Apr 2023In slowly progressive type 1 diabetes mellitus (SPIDDM), the pancreas shows sustained islet inflammation, pancreatitis, pancreatic acinar cell metaplasia/dysplasia...
In slowly progressive type 1 diabetes mellitus (SPIDDM), the pancreas shows sustained islet inflammation, pancreatitis, pancreatic acinar cell metaplasia/dysplasia (ADM), and intraepithelial neoplasia (PanIN), a precancerous lesion. The mechanisms underlying these changes remain unclear. The presence of enterovirus (EV) encoded-capsid protein 1 (VP1) and -2A protease (2A) and the innate immune responses of the pancreas were studied using immunohistochemistry and in situ hybridization in 12 SPIDDM and 19 non-diabetic control pancreases. VP1, 2A, and EV-RNA were detected in islets and the exocrine pancreas in all SPIDDM pancreases. Innate immune receptor, melanoma differentiation-associated gene 5 (MDA5), and interferon (IFN)-beta1 were intensified in the islets of SPIDDM patients with short disease duration. However, expressions of MDA5 and IFN-beta1were suppressed in those with longer disease duration. CD3 T cell infiltration was observed in the VP1- and insulin-positive islets (insulitis) and exocrine acinar cells. CD11c dendritic cells (DCs) in islets were scarce in long-term SPIDDM. This study showed the consistent presence of EV, suggesting an association with inflammatory changes in the endocrine and exocrine pancreas in SPIDDM. Suppressed expressions of MDA5 and IFN-beta1, as well as decreased numbers of DCs in the host cells, may contribute to persistent EV infection and induction of ADM/PanIN lesions, which may potentially provide a scaffold for pancreatic neoplasms.
Topics: Humans; Enterovirus; Diabetes Mellitus, Type 1; Pancreas; Enterovirus Infections; Pancreas, Exocrine; Antigens, Viral; Islets of Langerhans
PubMed: 37117225
DOI: 10.1038/s41598-023-33011-7 -
Current Diabetes Reports Dec 2019Novel 3D organoid culture techniques have enabled long-term expansion of pancreatic tissue. This review comprehensively summarizes and evaluates the applications of... (Review)
Review
PURPOSE OF REVIEW
Novel 3D organoid culture techniques have enabled long-term expansion of pancreatic tissue. This review comprehensively summarizes and evaluates the applications of primary tissue-derived pancreatic organoids in regenerative studies, disease modelling, and personalized medicine.
RECENT FINDINGS
Organoids derived from human fetal and adult pancreatic tissue have been used to study pancreas development and repair. Generated adult human pancreatic organoids harbor the capacity for clonal expansion and endocrine cell formation. In addition, organoids have been generated from human pancreatic ductal adenocarcinoma in order to study tumor behavior and assess drug responses. Pancreatic organoids constitute an important translational bridge between in vitro and in vivo models, enhancing our understanding of pancreatic cell biology. Current applications for pancreatic organoid technology include studies on tissue regeneration, disease modelling, and drug screening.
Topics: Adult; Animals; Cell Culture Techniques; Fetus; Humans; Models, Biological; Organoids; Pancreas; Precision Medicine; Regenerative Medicine
PubMed: 31828551
DOI: 10.1007/s11892-019-1261-z -
The British Journal of Radiology Jul 2019MRI plays an important role in the clinical management of pancreatic disorders and interpretation is reliant on qualitative assessment of anatomy. Conventional sequences... (Review)
Review
MRI plays an important role in the clinical management of pancreatic disorders and interpretation is reliant on qualitative assessment of anatomy. Conventional sequences capturing pancreatic structure can however be adapted to yield quantitative measures which provide more diagnostic information, with a view to increasing diagnostic accuracy, improving patient stratification, providing robust non-invasive outcome measures for therapeutic trials and ultimately personalizing patient care. In this review, we evaluate the use of established techniques such as secretin-enhanced MR cholangiopancreatography, diffusion-weighted imaging, , * and fat fraction mapping, but also more experimental methods such as MR elastography and arterial spin labelling, and their application to the assessment of diffuse pancreatic disease (including chronic, acute and autoimmune pancreatitis/IgG4 disease, metabolic disease and iron deposition disorders) and cystic/solid focal pancreatic masses. Finally, we explore some of the broader challenges to their implementation and future directions in this promising area.
Topics: Humans; Magnetic Resonance Imaging; Pancreas; Pancreatic Diseases
PubMed: 30982337
DOI: 10.1259/bjr.20180941 -
International Journal of Molecular... Oct 2019Aquaporins are a family of transmembrane proteins permeable to water. In mammals, they are subdivided into classical aquaporins that are permeable to water;... (Review)
Review
Aquaporins are a family of transmembrane proteins permeable to water. In mammals, they are subdivided into classical aquaporins that are permeable to water; aquaglyceroporins that are permeable to water, glycerol and urea; peroxiporins that facilitate the diffusion of HO through cell membranes; and so called unorthodox aquaporins. Aquaporins ensure important physiological functions in both exocrine and endocrine pancreas. Indeed, they are involved in pancreatic fluid secretion and insulin secretion. Modification of aquaporin expression and/or subcellular localization may be involved in the pathogenesis of pancreatic insufficiencies, diabetes and pancreatic cancer. Aquaporins may represent useful drug targets for the treatment of pathophysiological conditions affecting pancreatic function, and/or diagnostic/predictive biomarker for pancreatic cancer. This review summarizes the current knowledge related to the involvement of aquaporins in the pancreas physiology and physiopathology.
Topics: Aquaporins; Humans; Insulin; Islets of Langerhans; Pancreas; Pancreas, Exocrine; Pancreatic Diseases
PubMed: 31614661
DOI: 10.3390/ijms20205052 -
Frontiers in Endocrinology 2021Although first described over a hundred years ago, tissue optical clearing is undergoing renewed interest due to numerous advances in optical clearing methods,... (Review)
Review
Although first described over a hundred years ago, tissue optical clearing is undergoing renewed interest due to numerous advances in optical clearing methods, microscopy systems, and three-dimensional (3-D) image analysis programs. These advances are advantageous for intact mouse tissues or pieces of human tissues because samples sized several millimeters can be studied. Optical clearing methods are particularly useful for studies of the neuroanatomy of the central and peripheral nervous systems and tissue vasculature or lymphatic system. Using examples from solvent- and aqueous-based optical clearing methods, the mouse and human pancreatic structures and networks will be reviewed in 3-D for neuro-insular complexes, parasympathetic ganglia, and adipocyte infiltration as well as lymphatics in diabetes. Optical clearing with multiplex immunofluorescence microscopy provides new opportunities to examine the role of the nervous and circulatory systems in pancreatic and islet functions by defining their neurovascular anatomy in health and diabetes.
Topics: Adipocytes; Animals; Autonomic Nervous System; Diabetes Mellitus; Ganglia; Humans; Image Processing, Computer-Assisted; Imaging, Three-Dimensional; In Vitro Techniques; Islets of Langerhans; Mice; Mice, Inbred C57BL; Microscopy, Fluorescence; Neuroanatomy; Pancreas; Schwann Cells
PubMed: 33981285
DOI: 10.3389/fendo.2021.644826