Targeting heterogeneous tumor microenvironments in pancreatic cancer mouse models of metastasis by TGF-β depletion.

The dual tumor-suppressive and -promoting functions of TGF-β signaling has made its targeting challenging. We examined the effects of TGF-β depletion by AVID200/BMS-986416 (TGF-β-TRAP), a TGF-β ligand trap, on the tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC) murine models with different organ-specific metastasis. Our study demonstrated that TGF-β-TRAP potentiates the efficacy of anti-programmed cell death 1 (anti-PD-1) in a PDAC orthotopic murine model with liver metastasis tropism, significantly reducing liver metastases.

Substrate stiffness modulates the emergence and magnitude of senescence phenotypes in dermal fibroblasts.

Cellular senescence is a major driver of aging and disease. Here we show that substrate stiffness modulates the emergence and magnitude of senescence phenotypes after exposure to senescence inducers. Using a primary dermal fibroblast model, we show that decreased substrate stiffness accelerates senescence-associated cell-cycle arrest and regulates the expression of conventional protein-based biomarkers of senescence.

DNA damage repair mutations in pancreatic cancer- prognostic or predictive?

Objective: The efficacy of platinum-based chemotherapy (PtCh) for pancreatic cancer (PC) patients with DNA damage repair gene mutations (DDRm) compared to those without DDRm remains uncertain.

Methods: After a thorough database searching in PubMed, Embase, and Web of Science, a total of 19 studies that met all the inclusion criteria were identified. The primary outcomes were overall survival (OS) and progression-free survival (PFS) for PC patients with DDRm versus those without DDRm after PtCh.

Engineered TCR T-cell therapy targeting mass spectrometry-identified natural epitope in PDAC.

Tumor antigens are crucial targets for T-cell-based therapy to induce tumor-specific rejection. However, identifying pancreatic ductal adenocarcinoma (PDAC)-specific T-cell epitopes has been challenging. Using advanced mass spectrometry (MS) analysis, we previously identified cancer-associated, class I MHC-bound epitopes shared by multiple PDAC patients with different HLA-A types.

Organoids: The current status and biomedical applications.

Organoids are three-dimensional (3D) miniaturized versions of organs or tissues that are derived from cells with stem potential and can self-organize and differentiate into 3D cell masses, recapitulating the morphology and functions of their in vivo counterparts. Organoid culture is an emerging 3D culture technology, and organoids derived from various organs and tissues, such as the brain, lung, heart, liver, and kidney, have been generated. Compared with traditional bidimensional culture, organoid culture systems have the unique advantage of conserving parental gene expression and mutation characteristics, as well as long-term maintenance of the function and biological characteristics of the parental cells in vitro.

Targeted therapy for pancreatic ductal adenocarcinoma: Mechanisms and clinical study.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and lethal malignancy with a high rate of recurrence and a dismal 5-year survival rate. Contributing to the poor prognosis of PDAC is the lack of early detection, a complex network of signaling pathways and molecular mechanisms, a dense and desmoplastic stroma, and an immunosuppressive tumor microenvironment. A recent shift toward a neoadjuvant approach to treating PDAC has been sparked by the numerous benefits neoadjuvant therapy (NAT) has to offer compared with upfront surgery.

Oxidative Stress, Mitochondrial Dysfunction, and Neuroprotection of Polyphenols with Respect to Resveratrol in Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease and is characterized by dopaminergic neuronal loss. The exact pathogenesis of PD is complex and not yet completely understood, but research has established the critical role mitochondrial dysfunction plays in the development of PD. As the main producer of cytosolic reactive oxygen species (ROS), mitochondria are particularly susceptible to oxidative stress once an imbalance between ROS generation and the organelle's antioxidative system occurs.