OSBPL3 modulates the immunosuppressive microenvironment and predicts therapeutic outcomes in pancreatic cancer.

Background: Pancreatic cancer is characterized by a complex tumor microenvironment that hinders effective immunotherapy. Identifying key factors that regulate the immunosuppressive landscape is crucial for improving treatment strategies.

Methods: We constructed a prognostic and risk assessment model for pancreatic cancer using 101 machine learning algorithms, identifying OSBPL3 as a key gene associated with disease progression and prognosis.

FOXM1-Cx31 Axis Drives Pancreatic Cancer Stem Cell-Like Properties and Chemoresistance.

Pancreatic cancer is a highly lethal malignancy with few effective treatment options. Connexin 31 (Cx31) is a membrane protein capable of forming hexameric channels to facilitate the exchange of metabolites and signaling molecules. Yet, the contribution of Cx31 to the onset and progression of pancreatic cancer remains to be understood.

Clinical Relevance and Drug Modulation of PPAR Signaling Pathway in Triple-Negative Breast Cancer: A Comprehensive Analysis.

Triple-negative breast cancer (TNBC) is highly heterogeneous and poses a significant medical challenge due to limited treatment options and poor outcomes. Peroxisome proliferator-activated receptors (PPARs) play a crucial role in regulating metabolism and cell fate. While the association between PPAR signal and human cancers has been a topic of concern, its specific relationship with TNBC remains unclear.

GATA6 in pancreatic cancer initiation and progression.

Pancreatic ductal adenocarcinoma (PDA) is a lethal malignancy characterized by insidious onset and lack of effective therapy. The molecular pathogenesis of PDA remains to be understood fully. Transcriptional factor GATA6 is an important transcriptional regulator in normal pancreas development, particularly in the initial specification and differentiation of the pancreas.

Exploring the oncogenic potential of Aiolos in lung cancer through OTUB1-mediated ubiquitination.

Aiolos (IKZF3), a zinc finger transcription factor, has been identified in various solid tumors. While most research on Aiolos focuses on its role in the hematopoietic system, its expression patterns, mechanisms of action, and biological impacts in lung cancer remain relatively unexplored. This study investigates Aiolos' role in the proliferation, migration, and invasion of lung cancer cells.

Plakophilin 1 in carcinogenesis.

Plakophilin 1 (PKP1) belongs to the desmosome family as an anchoring junction protein in cellular junctions. It localizes at the interface of the cell membrane and cytoplasm. Although PKP1 is a non-transmembrane protein, it may become associated with the cell membrane via transmembrane proteins such as desmocollins and desmogleins.

WNK1 Interaction with KEAP1 Promotes NRF2 Stabilization to Enhance the Oxidative Stress Response in Hepatocellular Carcinoma.

Cellular oxidative stress plays a key role in the development and progression of hepatocellular carcinoma (HCC). A better understanding of the processes that regulate reactive oxygen species (ROS) homeostasis could uncover improved strategies for treating HCC. Herein, we identified protein kinase with-no-lysine kinase 1 (WNK1) as an antioxidative factor and therapeutic target in HCC.

Cingulin family: Structure, function and clinical significance.

Cingulin and its paralog paracingulin are vital components of the apical junctional complex in vertebrate epithelial and endothelial cells. They are both found in tight junctions (TJ), and paracingulin is also detectable in adherens junctions (AJ) as TJ cytoplasmic plaque proteins. Cingulin and paracingulin interact with other proteins to perform functions.

Roles of PPAR activation in cancer therapeutic resistance: Implications for combination therapy and drug development.

Therapeutic resistance is a major obstacle to successful treatment or effective containment of cancer. Peroxisome proliferator-activated receptors (PPARs) play an essential role in regulating energy homeostasis and determining cell fate. Despite of the pleiotropic roles of PPARs in cancer, numerous studies have suggested their intricate relationship with therapeutic resistance in cancer.

Nuclear GRP78 Promotes Metabolic Reprogramming and Therapeutic Resistance in Pancreatic Ductal Adenocarcinoma.

Purpose: Stromal fibrosis limits nutritional supply and disarrays metabolism in pancreatic cancer (PDA, pancreatic ductal adenocarcinoma). Understanding of the molecular basis underlying metabolic cues would improve PDA management. The current study determined the interaction between glucose-regulated proteins 78 (GRP78) and hypoxia-inducible factor 1α (HIF-1α) and its mechanistic roles underlying PDA response to oxygen and glucose restrains.

Loss of GATA6-mediated up-regulation of UTX promotes pancreatic tumorigenesis and progression.

Ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX), also known as lysine (K)-specific demethylase 6A (KDM6A), functions as a tumor suppressor gene or oncogene depending on the tumor type and context. However, its tumor-suppressive mechanisms remain largely unknown. Here, we investigated the clinical significance and biological effects of UTX expression in pancreatic ductal adenocarcinoma (PDA) and determined the potential mechanisms of its dysregulation.

Low molecular weight heparin synergistically enhances the efficacy of adoptive and anti-PD-1-based immunotherapy by increasing lymphocyte infiltration in colorectal cancer.

Background: Immunotherapy, including adoptive cell therapy (ACT) and immune checkpoint inhibitors (ICIs), has a limited effect in most patients with colorectal cancer (CRC), and the efficacy is further limited in patients with liver metastasis. Lack of antitumor lymphocyte infiltration could be a major cause, and there remains an urgent need for more potent and safer therapies for CRC.

Methods: In this study, the antitumoral synergism of low molecular weight heparin (LMWH) combined with immunotherapy in the microsatellite stable (MSS) highly aggressive murine model of CRC was fully evaluated.

Senescence program and its reprogramming in pancreatic premalignancy.

Tumor is a representative of cell immortalization, while senescence irreversibly arrests cell proliferation. Although tumorigenesis and senescence seem contrary to each other, they have similar mechanisms in many aspects. Pancreatic ductal adenocarcinoma (PDA) is highly lethal disease, which occurs and progresses through a multi-step process.

Zonula Occludens Proteins Signaling in Inflammation and Tumorigenesis.

Tight junction (TJ) is the barrier of epithelial and endothelial cells to maintain paracellular substrate transport and cell polarity. As one of the TJ cytoplasmic adaptor proteins adjacent to cell membrane, zonula occludens (ZO) proteins are responsible for connecting transmembrane TJ proteins and cytoplasmic cytoskeleton, providing a binding platform for transmembrane TJ proteins to maintain the barrier function. In addition to the basic structural function, ZO proteins play important roles in signal regulation such as cell proliferation and motility, the latter including cell migration, invasion and metastasis, to influence embryonic development, tissue homeostasis, damage repair, inflammation, tumorigenesis, and cancer progression.

Acinar cells and the development of pancreatic fibrosis.

Pancreatic fibrosis is caused by excessive deposition of extracellular matrixes of collagen and fibronectin in the pancreatic tissue as a result of repeated injury often seen in patients with chronic pancreatic diseases. The most common causative conditions include inborn errors of metabolism, chemical toxicity and autoimmune disorders. Its pathophysiology is highly complex, including acinar cell injury, acinar stress response, duct dysfunction, pancreatic stellate cell activation, and persistent inflammatory response.

KLF4 transcription factor in tumorigenesis.

Krüppel-like transcriptional factor is important in maintaining cellular functions. Deletion of Krüppel-like transcriptional factor usually causes abnormal embryonic development and even embryonic death. KLF4 is a prominent member of this family, and embryonic deletion of KLF4 leads to alterations in skin permeability and postnatal death.

Epigenetic reprogramming in pancreatic premalignancy and clinical implications.

Pancreatic cancer (PC) is the most lethal human cancer, with less than 10% 5-year survival. Pancreatic premalignancy is a genetic and epigenomic disease and is linked to PC initiation. Pancreatic premalignant lesions include pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasm (IPMN), and mucinous cystic neoplasm (MCN), with pancreatic acinar-to-ductal metaplasia (ADM) as the major source of pancreatic premalignant lesions.

Anticoagulants Enhance Molecular and Cellular Immunotherapy of Cancer by Improving Tumor Microcirculation Structure and Function and Redistributing Tumor Infiltrates.

Purpose: Pancreatic ductal adenocarcinoma (PDA) resists immunotherapy of adoptive cell transfer (ACT) and immune checkpoint inhibitors. Understanding the mechanisms underlying this resistance will improve PDA immunotherapy. This study investigated therapeutic effects and underlying mechanisms of anticoagulants on immunotherapy in PDA.

The Preparation of High Saturation Magnetization and Low Coercivity Feco Soft Magnetic Thin Films via Controlling the Thickness and Deposition Temperature.

FeCo thin films with high saturation magnetization (4 π) can be applied in high-frequency electronic devices such as thin film inductors and microwave noise suppressors. However, due to its large magnetocrystalline anisotropy constant and magnetostrictive coefficient of FeCo, the coercivity () of FeCo films is generally high, which is detrimental to the soft magnetic properties. Meanwhile, the thickness and deposition temperature have significant effects on the coercivity and saturation magnetization of FeCo films.

Molecular signaling in pancreatic ductal metaplasia: emerging biomarkers for detection and intervention of early pancreatic cancer.

Pancreatic ductal metaplasia (PDM) is the transformation of potentially various types of cells in the pancreas into ductal or ductal-like cells, which eventually replace the existing differentiated somatic cell type(s). PDM is usually triggered by and manifests its ability to adapt to environmental stimuli and genetic insults. The development of PDM to atypical hyperplasia or dysplasia is an important risk factor for pancreatic intraepithelial neoplasia (PanIN) and pancreatic ductal adenocarcinoma (PDA).

Ductal metaplasia in pancreas.

Pancreatic ductal metaplasia (PDM) is the transformation of potentially many type of cells in pancreas into ductal or ductal-like cells, which eventually replace the existing differentiated somatic cell type(s). PDM is usually triggered by and manifests its ability to adapt to environmental and cellular stimuli and stresses. Acinar to ductal metaplasia (ADM) is the predominant form of ductal metaplasia in pancreas.

Clinical significance of pancreatic ductal metaplasia.

Pancreatic ductal metaplasia (PDM) is the stepwise replacement of differentiated somatic cells with ductal or ductal-like cells in the pancreas. PDM is usually triggered by cellular and environmental insults. PDM development may involve all cell lineages of the pancreas, and acinar cells with the highest plasticity are the major source of PDM.

Coupled liquid biopsy and bioinformatics for pancreatic cancer early detection and precision prognostication.

Early detection and diagnosis are the key to successful clinical management of pancreatic cancer and improve the patient outcome. However, due to the absence of early symptoms and the aggressiveness of pancreatic cancer, its 5-year survival rate remains below 5 %. Compared to tissue samples, liquid biopsies are of particular interest in clinical settings with respect to minimal invasiveness, repeated sampling, complete representation of the entire or multi-site tumor bulks.

Therapeutic resistance of pancreatic cancer: Roadmap to its reversal.

Pancreatic cancer is a lethal disease with limited opportunity for resectable surgery as the first choice for cure due to its late diagnosis and early metastasis. The desmoplastic stroma and cellular genetic or epigenetic alterations of pancreatic cancer impose physical and biological barriers to effective therapies, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy. Here, we review the current therapeutic options for pancreatic cancer, and underlying mechanisms and potential reversal of therapeutic resistance, a hallmark of this deadly disease.