The BRD4 Inhibitor I-BET-762 Reduces HO-1 Expression in Macrophages and the Pancreas of Mice

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(18), P. 9985 - 9985

Published: Sept. 16, 2024

In pancreatic cancer, the tumor microenvironment (TME) accounts for up to 90% of mass. Pancreatitis, characterized by increased infiltration macrophages into pancreas, is a known risk factor cancer. The NRF2 (nuclear erythroid 2-related 2) transcription regulates responses oxidative stress and can promote cancer chemoresistance. also attenuates inflammation through regulation macrophage-specific genes. Heme oxygenase 1 (HO-1) expressed anti-inflammatory degrade heme, its expression dependent on translocation nucleus. stimulated with conditioned media from cells, HO-1 protein levels increased, which correlated higher in nuclear fraction. Significant differences macrophage were detected LSL-KrasG12D/+; Pdx-1-Cre (KC) mice, Nrf2 whole-body knockout (KO) mice wildtype pancreatitis. Since epigenetic modulation mechanism used tumors regulate TME, using small molecules as modulators activate immune recognition therapeutically desirable. When bromodomain inhibitor I-BET-762 was treat or pancreatitis, high reduced. This study shows that inhibitors be prevent physiological tumorigenesis.

Language: Английский

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The importance of stroma and stromal sma expression in pancreatic ductal adenocarcinoma

Turkish Journal of Pathology, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Pancreatic stellate cells (PSC) have been defined to be the key players in pancreatic fibrogenesis and carcinogenesis. They undergo myofibroblast-like differentiation, express α-smooth muscle actin (α-SMA), play a crucial role injury inflammation sites. This study aims evaluate relationship between α-SMA expression histopathological parameters of ductal adenocarcinoma (PDAC), investigate their association with prognosis.

Language: Английский

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Exosome-derived miR-21-5p promotes pancreatic cancer progression via ABCD2 gene

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 11, 2024

Pancreatic cancer is an aggressive malignancy with a dismal prognosis, and the underlying molecular mechanisms remain only partially understood. This study aimed to clarify role of microRNA-21-5p (miR-21-5p) in pancreatic progression investigate associated mechanisms. We found that miR-21-5p was significantly elevated tissues, its high expression correlated poorer patients’ prognosis. Functional assays revealed enhanced proliferation, migration, invasive capabilities cells. Through bioinformatics analysis experimental validation, we discovered ATP-binding cassette transporter D2 (ABCD2) as novel direct target gene miR-21-5p. ABCD2 downregulated low reduced patient survival. Mechanistically, inhibited transcription translation by directly targeting 3'UTR, process facilitated exosome delivery. Importantly, overexpression effectively reversed pro-oncogenic effects Our findings establish critical miR-21-5p/ABCD2 axis highlight tumor-suppressive function ABCD2. may represent promising therapeutic potential site for diagnosis treatment cancer.

Language: Английский

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The pros and cons of mechanical dissociation and enzymatic digestion in patient-derived organoid cultures for solid tumor

Cell organoid (Print), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Patient-derived organoids (PDOs) are revolutionizing cancer research, serving as invaluable models for tumor biology and therapeutic screening. The fidelity applicability of these fundamentally shaped by the tissue dissociation techniques employed, namely mechanical enzymatic digestion. This comprehensive review delves into nuances two methods, scrutinizing their effects on solid organoid properties, including stemness, heterogeneity, long-term culturing. We discuss advantages limitations each technique, with a focus impact microenvironment preservation, application in drug screening modeling. Moreover, we examine how recent technological breakthroughs have bolstered efficiency scalability production through methods. Our analysis is designed to assist researchers choosing optimal strategy research objectives fuel evolution organoid-based models.

Language: Английский

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Vitamin D and Pancreatic Ductal Adenocarcinoma—A Review of a Complicated Relationship

Nutrients, Journal Year: 2024, Volume and Issue: 16(23), P. 4085 - 4085

Published: Nov. 27, 2024

Introduction: From the observation of a negative relationship between UV-B exposure and cancer rates, we hypothesized that vitamin D (VD) may play protective role in oncogenesis. Moreover, repurposing well-known relatively safe drug for conditions with dismal prospects, such as pancreatic ductal adenocarcinoma (PDAC), is tempting idea. Thus, aimed to summarize current knowledge regarding VD prevention treatment PDAC. Methods: We conducted systematic review PDAC using Medline-indexed studies accessed through PubMed primary data source. This study identify articles focusing on risk prognostic factor PDAC, mechanistic evaluating effects or analogs (VDAs) models, clinical trials VDAs After screening, 97 were included final manuscript. Conclusion: Even though results from epidemiologic contradictory, basic research has demonstrated can act cells either directly, inhibiting proliferation, apoptosis, EMT, migration, invasion, stemness, indirectly, stromal remodeling. A better understanding consequences VD-induced tumor–stroma cross-talk alterations needed determine whether VD/VDAs be used our own advantage

Language: Английский

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