Pancreatic ductal adenocarcinoma (PDAC) is one of the cancers with the highest incidence of perineural invasion (PNI), which often indicates a poor prognosis. Aggressive tumor cells invade nerves, causing neurogenic inflammation; the tumor microenvironment also induces nerves to undergo a series of structural and functional reprogramming. In turn, neurons and the surrounding glial cells promote the development of pancreatic cancer through autocrine and/or paracrine signaling. In addition, hyperalgesia in PDAC patients implies alterations of pain transmission in the peripheral and central nervous systems. Currently, the studies on this topic are relatively limited. This review will elaborate on the mechanisms of tumor–neural interactions and its possible relationship with pain from several aspects that have been focused on in recent years.

The effects of ISG15 or ISGylation on tumor progression have been widely revealed; however, its roles in glioma progression are largely unknown. This study aims to explore the roles and underlying mechanisms of ISG15 in glioma progression. Here, ISG15 level was found to be upregulated in glioma tissues compared to the paired/ unpaired normal tissues, and positively correlated with the level of stemness markers in glioma tissues. Loss of functional experiments indicated that ISG15 positively regulated glioma cell stemness, as evident by the increase of sphere formation ability, ALDH activity, stemness marker expression, and tumor-initiating ability. Further mechanistic studies revealed that ISG15 directly interacted with Oct4 protein, a critical stemness promoter, induced the ISGylation of Oct4 protein, and thus enhanced Oct4 protein stability. Additionally, it was found that Oct4 was ISGylated at lysine 284 (K284), which has been confirmed to be the ubiquitination site of Oct4 protein, and ISG15 knockdown did not degrade K284R mutant Oct4. Furthermore, ISG15 knockdown-induced downregulation of glioma cell stemness was rescued by Oct4 overexpression, but not by K284R mutant Oct4. Altogether, we suggest that ISG15-induced ISGylation of Oct4 protein is essential for glioma cell stemness.

Although photodynamic immunotherapy has been promoted in the clinical practice of cholangiocarcinoma, the insensitivity to photodynamic immunotherapy remains to be a great problem. This can be largely attributed to an immune‐suppressive tumor microenvironment (TME) manifested as immature myeloid cells and exhausted cytotoxic T lymphocytes. Here, a three‐in‐one oncolytic adenovirus system PEG‐PEI‐Adv‐Catalase‐KillerRed (p‐Adv‐CAT‐KR) has been constructed to multiply, initiate, and enhance immune responses in photodynamic immunotherapy, using genetically‐engineered KillerRed as photosensitizer, catalase as in situ oxygen‐supplying mediator, and adenovirus as immunostimulatory bio‐reproducible carrier. Meanwhile, PEG‐PEI is applied to protect adenovirus from circulating immune attack. The administration of p‐Adv‐CAT‐KR induces increased antigen presenting cells, elevated T cell infiltrations, and reduced tumor burden. Further investigation into underlying mechanism indicates that hypoxia inducible factor 1 subunit alpha (Hif‐1α) and its downstream PD‐1/PD‐L1 pathway contribute to the transformation of immune‐suppressive TME in cholangiocarcinoma. Collectively, the combination of KillerRed, catalase, and adenovirus brings about multi‐amplified antitumor photo‐immunity and has the potential to be an effective immunotherapeutic strategy for cholangiocarcinoma.

The molecular mechanism that promotes pancreatic cancer remains unclear, so it is important to find the molecular network of important genes related to pancreatic cancer. To find the key molecule of pancreatic cancer, differential gene expression analyses were analyzed by the Deseq2 package, edgeR package, and limma-voom package, respectively. Pancreatic cancer survival-related genes were analyzed by COX survival analysis. Finally, we integrated the results to obtain the significantly differentially expressed gene, MYEOV (myeloma overexpressed gene), most strongly related to survival in pancreatic cancer. Experimental verification by qRT-PCR confirmed that transcription levels of MYEOV mRNA markedly increased in pancreatic cancer cells relative to normal human pancreatic ductal epithelial cells (HPDE). Through the comprehensive analysis of multiple databases, we constructed a molecular network centered on MYEOV and found specific links between molecules in this network and tumor-associated immune cells. It was noted that MYEOV could serve as a ceRNA by producing molecular sponging effects on hsa-miR-103a-3p and hsa-miR-107, thus affecting the role of GPRC5A, SERPINB5, EGFR, KRAS, EIF4G2, and PDCD4 on pancreatic cancer progression. Besides, we also identified that infiltrated immune cells are potential mediators for the molecules in the MYEOV-related network to promote pancreatic cancer progression. It is the first report to focus on the possibility that MYEOV may act as a competing endogenous RNA (ceRNA) to form an interactive network with some pancreatic cancer-related genes such as KRAS and serve as a key therapeutic target of pancreatic cancer treatment.

Background: Transcatheter arterial chemoembolization (TACE) is extensively used in the treatment of advanced hepatocellular carcinoma (HCC). However, the efficacy of TACE is usually limited to secondary tumor hypoxia and hypoxia-related tumor angiogenesis. Methods: In this study, poly(lactic-co-glycolic acid) (PLGA) microspheres ( SO R-CAT-PLGA MSs) encapsulating sorafenib (SOR) and catalase (CAT) were prepared by double-emulsion solvent diffusion method. Sorafenib inhibits tumor angiogenesis, and catalase decomposes hydrogen peroxide (H 2 O 2 ) to generate oxygen in the tumor. Results: In vitro and in vivo , SOR -CAT-PLGA MSs could significantly improve the efficacy of hepatic artery embolization in the treatment of rabbit VX2 liver tumors, regulate tumor hypoxia and immunosuppressive microenvironment, then achieved near-complete and rapid necrosis of liver tumors. Conclusions: The application of new SOR -CAT-PLGA MSs in hepatic artery chemoembolization of rabbit VX2 liver tumor is a promising approach to improve the therapeutic effect of liver tumors and has a broad clinical application prospect.