application-laparoscopic-programmatic-neurolymphatic-radical

Application of Laparoscopic Programmatic Neurolymphatic Radical Pancreaticoduodenectomy in Pancreatic Head Cancer

Laparoscopic pancreaticoduodenectomy (LPD) has become a widely adopted surgical approach for treating pancreatic head cancer. Traditional open ...

Southern Medical University

Perineural invasion (PNI) is a biological characteristic commonly observed in pancreatic cancer. Although PNI plays a key role in pancreatic cancer metastasis, recurrence, and poor postoperative survival, its mechanism is largely unclarified. Clinical sample analysis and endoscopic ultrasonographic elasticity scoring indicated that cancer-associated fibroblasts (CAFs) were closely related to the occurrence of PNI. Furthermore, CAF-derived extracellular vesicles (EVs) were involved in PNI in dorsal root ganglion coculture and mouse sciatic nerve models. Next, we demonstrated that CAFs promoted PNI through extracellular vesicle transmission of PNI-associated transcript (PIAT). Mechanistically, PIAT specifically bound to YBX1 and blocked the YBX1-Nedd4l interaction to inhibit YBX1 ubiquitination and degradation. Furthermore, PIAT enhanced the binding of YBX1 and PNI-associated mRNAs in a 5-methylcytosine (m5C)-dependent manner. Mutation of m5C recognition motifs in YBX1 or m5C sites in downstream target genes reversed PIAT-mediated PNI. Consistent with these findings, analyses using a KPC mouse model demonstrated that the PIAT/YBX1 axis enhanced PNI through m5C modification. Clinical data suggested that the PIAT expression in the serum EVs of patients with pancreatic cancer was associated with the degree of neural invasion and prognosis. Our study revealed the important role of the PIAT/YBX1 signaling axis in the tumor microenvironment (TME) in promoting tumor cell PNI and provided a new target for precise interference with CAFs and RNA methylation in the TME to suppress PNI in pancreatic cancer.

Extracellular vesicle-packaged PIAT from cancer-associated fibroblasts drives neural remodeling by mediating m5C modification in pancreatic cancer mouse models.

Hydrogel drug-delivery system that can effectively load antibacterial drugs, realize the in-situ drug release in the microenvironment of wound infection to promote wound healing. In this study, a multifunctional hydrogel drug delivery system (HA@TA-Okra) was constructed through the integration of hyaluronic acid methacrylate (HAMA) matrix with tannic acid (TA) and okra extract. The composition and structural characteristics of HA@TA-Okra system and its unique advantages in the treatment of diverse wounds were systematically evaluated. TA, due to its unique chemical structure, is able to anchor within the HAMA network through interactions and cross-linking, conferring exceptional mechanical strength and stability to the hydrogel. Both TA and okra extract possess antioxidant and antibacterial properties, and when they two acts synergistically they can effectively scavenge free radicals, enhance antibacterial action, diminishing the risk of wound infection. In vitro experiments revealed that HA@TA-Okra system has superior properties, such as rapid gel response, remarkable swelling regulation, and potent antioxidant ability. Furthermore, the HA@TA-Okra system significantly outperformed conventional dressings in terms of hemostatic performance in a rat hemorrhage model. We further evaluated the repair role of HA@TA-Okra system in vivo by establishing an animal model of full-thickness skin defects and a model of infected total skin defects. The results confirmed its positive effects in fighting bacterial infection, reducing inflammation and promoting wound healing. In summary, the HA@TA-Okra system exhibits comprehensive properties such as antibacterial, antioxidant and hemostatic properties, which has a potential application in the field of tissue repair medicine.

An antibacterial, antioxidant and hemostatic hydrogel accelerates infectious wound healing.

Cancer-associated fibroblasts (CAFs) play a key role in oxaliplatin resistance in pancreatic ductal adenocarcinoma (PDAC). However, the potential mechanisms by which CAFs promote chemotherapy resistance have not yet been explored. In this study, we found that circABCC4 (hsa_circ_0030582) was positively correlated with poor platinum-chemotherapeutic response and a shorter progression-free survival (PFS) time in late-stage PDAC patients. CircABCC4 enhanced the ability of CAFs to induce oxaliplatin resistance in pancreatic cancer cells through glycolysis reprogramming. Mechanistically, circABCC4 enhanced the interaction between PKM2 and KPNA2 to promote PKM2 nuclear translocation in CAFs, leading to the transcription of glycolysis-related genes. The glycolytic reprogramming of CAFs promoted the secretion of IL-8, which in turn enhanced DNA damage repair in pancreatic cancer. Blocking PKM2 nuclear translocation abolished circABCC4-driven oxaliplatin resistance of pancreatic cancer in vivo. Collectively, our study reveals a circRNA-mediated glycolysis reprogramming of CAFs to induce oxaliplatin resistance and highlights circABCC4 as a potential therapeutic target.

Glycolysis reprogramming in CAFs promotes oxaliplatin resistance in pancreatic cancer through circABCC4 mediated PKM2 nuclear translocation.

Perineural invasion (PNI) is a pivotal prognostic factor in pancreatic cancer, associated with aggressive tumor behavior and adverse patient outcomes. The recognized clinical impact of PNI highlights the need to better understand the molecular mechanisms underlying PNI-induced phenotypes. In this study, we isolated PNI-associated cancer-associated fibroblasts (pCAF), which demonstrated a markedly enhanced capacity to promote neural invasion in pancreatic cancer compared with non-PNI-associated CAFs. Single-cell, high-throughput sequencing and metabolomics data showed a significant upregulation of glycolysis in pCAFs, fostering a high-lactate tumor microenvironment conducive to cancer progression. pCAF-derived lactate was absorbed by tumor cells, facilitating histone H3K18 lactylation. The lactate-induced epigenetic modification activated the transcription of neural invasion-associated genes, such as L1CAM and SLIT1, thereby driving PNI in pancreatic cancer. Further exploration of metabolic reprogramming in pCAFs revealed enhanced acetylation of the glycolytic enzyme GAPDH, which correlated with increased enzymatic activity and glycolytic flux. Targeting GAPDH and lactylation modifications significantly inhibited neural invasion in a genetically engineered mouse model. Clinical data suggested that high levels of H3K18 lactylation correlate with severe PNI and poorer patient prognosis. Together, these findings provide critical insights into the role of CAFs in promoting PNI of pancreatic cancer, highlighting glycolytic reprogramming and lactate-driven histone modifications as potential therapeutic targets for PDAC.

Cancer-Associated Fibroblasts Foster a High-Lactate Microenvironment to Drive Perineural Invasion in Pancreatic Cancer.

Liver diseases are established risk factors for hepatobiliary and pancreatic cancers. This study explores the relationship between liver disease and hepatobiliary-pancreatic cancers, focusing on transaminase levels and genetic susceptibility.

Article	Year
Extracellular vesicle-packaged PIAT from cancer-associated fibroblasts drives neural remodeling by mediating m5C modification in pancreatic cancer mouse models. Science translational medicine\| PubMed ID: 39018369	2024
An antibacterial, antioxidant and hemostatic hydrogel accelerates infectious wound healing. Journal of nanobiotechnology\| PubMed ID: 39871272	2025
Glycolysis reprogramming in CAFs promotes oxaliplatin resistance in pancreatic cancer through circABCC4 mediated PKM2 nuclear translocation. Cell death & disease\| PubMed ID: 39988592	2025
Cancer-Associated Fibroblasts Foster a High-Lactate Microenvironment to Drive Perineural Invasion in Pancreatic Cancer. Cancer research\| PubMed ID: 40138590	2025
Liver diseases, transaminases, and hepatobiliary-pancreatic cancer risk: a cohort and Mendelian randomisation study using data from UK Biobank. BMJ open gastroenterology\| PubMed ID: 40645641	2025

Tianhao Huang

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