Feedback loop LINC00511-YTHDF2-SOX2 regulatory network drives cholangiocarcinoma progression and stemness.

Cholangiocarcinoma (CCA) was identified as a malignant tumor with rising incidence and mortality rates, and the roles of long noncoding RNA (lncRNA) in CCA remained not entirely clear. In this study, LINC00511 had high expression in CCA, which was closely related to poor prognosis. Knockdown of LINC00511 significantly inhibited cell malignant biological behaviors. It also affected the stemness of CCA, evidenced by decreased SOX2 protein expression. Moreover, the study revealed the interaction of LINC00511, YTHDF2, and SOX2 in CCA. Specifically, LINC00511 facilitated the formation of a complex with YTHDF2 on SOX2 mRNA, which uniquely enhances the mRNA's stability through m6A methylation sites. This stabilization appears crucial for maintaining malignant behaviors in CCA cells. Additionally, LINC00511 modulated SOX2 expression via the PI3K/AKT signaling pathway. Meanwhile, SOX2 can also promote LINC00511 expression as an upstream transcription factor, thereby confirming a positive feedback loop formed by LINC00511, YTHDF2, and SOX2, which plays a significant role in the occurrence and development of CCA. Finally, the study successfully constructed two patient-derived xenograft models, revealing the vital role of LINC00511 in CCA development. In summary, this research provides a comprehensive understanding of the role of LINC00511 in the pathogenesis of CCA.

Research progress and applications of epigenetic biomarkers in cancer.

Epigenetic changes are heritable changes in gene expression without changes in the nucleotide sequence of genes. Epigenetic changes play an important role in the development of cancer and in the process of malignancy metastasis. Previous studies have shown that abnormal epigenetic changes can be used as biomarkers for disease status and disease prediction. The reversibility and controllability of epigenetic modification changes also provide new strategies for early disease prevention and treatment. In addition, corresponding drug development has also reached the clinical stage. In this paper, we will discuss the recent progress and application status of tumor epigenetic biomarkers from three perspectives: DNA methylation, non-coding RNA, and histone modification, in order to provide new opportunities for additional tumor research and applications.

Advances in Drug Therapy for Metastatic Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a notably poor prognosis. A large number of patients with PDAC develop metastases before they are diagnosed with metastatic pancreatic cancer (mPDAC). For mPDAC, FOLFIRINOX or gemcitabine plus nab-paclitaxel are the current first-line treatments. It is important to note, however, that many patients will fail chemotherapy because of drug resistance. ​Heterogeneous tumors and complex tumor microenvironments are key factors. As a result, clinical researchers are exploring a variety of alternative treatment modalities. Current understanding of the molecular signature and immune landscape of PDAC has motivated the emergence of different targeted and immune-based therapeutic approaches, some of which have shown promising results. The purpose of this review is to discuss the new targets and new drugs for mPDAC in terms of specific pathogenic factors such as metabolic vulnerability, DNA damage repair system, tumor microenvironment and immune system, in order to identify potential vulnerabilities in mPDAC patients and hopefully improve the prognosis of mPDAC patients.

Utilization of 3D printing technology in hepatopancreatobiliary surgery. / 3D打印技术在肝胆胰外科中的应用进展.

The technology of three-dimensional (3D) printing emerged in the late 1970s and has since undergone considerable development to find numerous applications in mechanical engineering, industrial design, and biomedicine. In biomedical science, several studies have initially found that 3D printing technology can play an important role in the treatment of diseases in hepatopancreatobiliary surgery. For example, 3D printing technology has been applied to create detailed anatomical models of disease organs for preoperative personalized surgical strategies, surgical simulation, intraoperative navigation, medical training, and patient education. Moreover, cancer models have been created using 3D printing technology for the research and selection of chemotherapy drugs. With the aim to clarify the development and application of 3D printing technology in hepatopancreatobiliary surgery, we introduce seven common types of 3D printing technology and review the status of research and application of 3D printing technology in the field of hepatopancreatobiliary surgery.

Ferroptosis: New Strategies and Ideas for the Treatment of Pancreatic Ductal Adenocarcinoma.

Pancreatic cancer is a malignancy that affects the digestive tract and has a low 5-year survival rate of lower than 15%. Owing to its genetic mutation and metabolic complexity, pancreatic cancer is difficult to treat with surgical resection, radiotherapy, and chemotherapy. The predominant modality of pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC), primarily attributed to mutations in KRAS gene. Ferroptosis, an iron-mediated reactive oxygen species (ROS)-elevated nonapoptotic cell death caused by lipid peroxidation, is distinct from any other known type of cell death. Ferroptosis is closely related to the occurrence and progression of different types of cancers, including PDAC. Previous research has demonstrated that ferroptosis not only triggers cell death in PDAC and hampers tumor growth but also enhances the effectiveness of antitumor medications. In our review, we mainly focus on the core mechanism of ferroptosis, reveal its interrelationship with PDAC, and illustrate the progress of ferroptosis in different treatment methods of PDAC.

Circular RNAs in pancreatic cancer progression.

Pancreatic cancer (PC), typically diagnosed at relatively advanced stages with poor prognosis, is a dominant cause of cancer-related deaths worldwide. Accumulating evidence demonstrates that circular RNAs (circRNAs) are abnormally expressed in diverse tumors and affect tumorigenesis and progression. In this article, we examine the roles of circRNAs in regulation of PC progression. Additionally, circRNAs enriched in exosomes could be transferred among PC cells to modulate malignancy. Characterization of regulatory mechanisms involving circRNAs in general and PC specifically will enable earlier detection and potential development of therapeutic strategies.

Liver fibrosis and MAFLD: the exploration of multi-drug combination therapy strategies.

In recent years, the prevalence of metabolic-associated fatty liver disease (MAFLD) has reached pandemic proportions as a leading cause of liver fibrosis worldwide. However, the stage of liver fibrosis is associated with an increased risk of severe liver-related and cardiovascular events and is the strongest predictor of mortality in MAFLD patients. More and more people believe that MAFLD is a multifactorial disease with multiple pathways are involved in promoting the progression of liver fibrosis. Numerous drug targets and drugs have been explored for various anti-fibrosis pathways. The treatment of single medicines is brutal to obtain satisfactory results, so the strategies of multi-drug combination therapies have attracted increasing attention. In this review, we discuss the mechanism of MAFLD-related liver fibrosis and its regression, summarize the current intervention and treatment methods for this disease, and focus on the analysis of drug combination strategies for MAFLD and its subsequent liver fibrosis in recent years to explore safer and more effective multi-drug combination therapy strategies.