Generally, patients with pancreatic ductal adenocarcinoma, especially those with wide metastatic lesions, have a poor prognosis. Recently, a breakthrough in improving their survival has been achieved by using first-line chemotherapy, such as gemcitabine plus nab-paclitaxel or oxaliplatin plus irinotecan plus 5-fluorouracil plus calcium folinate. Unfortunately, regimens with high effectiveness are still absent in second- or later-line settings. In addition, although immunotherapy using checkpoint inhibitors definitively represents a novel method for metastatic cancers, monotherapy using checkpoint inhibitors is almost completely ineffective for pancreatic ductal adenocarcinomas largely due to the suppressive immune milieu in such tumors. Critically, the genomic alteration pattern is believed to impact cancer immune environment. Surprisingly, KRAS gene mutation is found in almost all pancreatic ductal adenocarcinomas. Moreover, KRAS mutation is indispensable for pancreatic carcinogenesis. On these bases, a relationship likely exists between this oncogene and immunosuppression in this cancer. During pancreatic carcinogenesis, KRAS mutation-driven events, such as metabolic reprogramming, cell autophagy, and persistent activation of the yes-associated protein pathway, converge to cause immune evasion. However, intriguingly, KRAS mutation can dictate a different immune environment in other types of adenocarcinoma, such as colorectal adenocarcinoma and lung adenocarcinoma. Overall, the KRAS mutation can drive an immunosuppression in pancreatic ductal adenocarcinomas or in colorectal carcinomas, but this mechanism is not true in KRAS-mutant lung adenocarcinomas, especially in the presence of TP53 inactivation. As a result, the response of these adenocarcinomas to checkpoint inhibitors will vary.

Gallic acid (GA) and lecithin showed important roles in antioxidant and drug delivery, respectively. A complex synthesized from GA and soybean lecithin (SL-GAC), significantly improved bioavailabil...

Currently, no available coherent management protocol exists for pediatric cancers associated with pleural effusion, ascites, and pericardial effusion. This study aimed to retrospectively present our experience in treating pediatric cancer patients with pleural effusion, ascites, and pericardial effusion using interleukin-2 (IL-2) and dexamethasone (DEX) intracavitary injections. Between January 1st, 2008 and December 31st, 2020, medical reports of patients diagnosed with solid tumors or lymphoma were checked to identify patients diagnosed with > 2 cm pleural effusion, and/or more than grade 1 ascites, and/or more than small pericardial effusion. Patients diagnosed with effusions and treated with IL-2 and DEX were identified as being in the effusion group. Meanwhile, patients with the same primary tumors and effusions but did not receive interleukin 2 and DEX injection were reviewed and classified as the control group. Forty patients with solid tumors and 66 patients with lymphoma were further diagnosed with pleural effusion, ascites, or pericardial effusion. A total of 85 patients received IL-2 and DEX injection while the remaining 21 did not. The Kaplan Meier analysis revealed a significant difference between the two groups, with p < 0.01 for event free survival (EFS) and p < 0.01 for overall survival (OS), both of which had p < 0.01. Hazard ratio was found to be 0.344 for OS and 0.352 for EFS. This retrospective study illustrates that thoracic, intraperitoneal, or pericardial intracavitary injection of DEX plus IL-2 can be an effective and safe treatment for pediatric cancers with pleural effusion, ascites, and pericardial effusion.

The RING finger protein 5 (RNF5), an E3 ubiquitin ligase, has demonstrated significant antiviral activity against various viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Kaposi’s sarcoma-associated herpesvirus (KSHV). However, its role in hepatitis B virus (HBV) replication has not been previously studied. In this study, we demonstrate that RNF5 effectively inhibits HBV replication by promoting the degradation of the HBV Core protein through a Caspase-3-dependent pathway. We first show that RNF5 expression is upregulated in HBV-infected cells and patient samples, suggesting a role in the host’s antiviral response. Subsequently, we investigate the mechanism by which RNF5 mediates its antiviral effect, finding that RNF5 targets the Core protein for degradation independently of its E3 ubiquitin ligase activity. The degradation of Core protein is mediated through a Caspase-3-dependent mechanism rather than the proteasomal pathway. Interestingly, RNF5’s antiviral function does not rely on ubiquitination, indicating an alternative pathway involving apoptosis-related processes. These findings highlight the multifunctional role of RNF5 and suggest that targeting RNF5 could serve as a novel therapeutic approach to control HBV replication, providing new insights into the development of antiviral therapies against HBV.