A major challenge in chemotherapy is chemotherapy resistance in cells lacking p53. Here we demonstrate that NIP30, an inhibitor of the oncogenic REGγ-proteasome, attenuates cancer cell growth and sensitizes p53-compromised cells to chemotherapeutic agents. NIP30 acts by binding to REGγ via an evolutionarily-conserved serine-rich domain with 4-serine phosphorylation. We find the cyclin-dependent phosphatase CDC25A is a key regulator for NIP30 phosphorylation and modulation of REGγ activity during the cell cycle or after DNA damage. We validate CDC25A-NIP30-REGγ mediated regulation of the REGγ target protein p21 in vivo using p53−/− and p53/REGγ double-deficient mice. Moreover, Phosphor-NIP30 mimetics significantly increase the growth inhibitory effect of chemotherapeutic agents in vitro and in vivo. Given that NIP30 is frequently mutated in the TCGA cancer database, our results provide insight into the regulatory pathway controlling the REGγ-proteasome in carcinogenesis and offer a novel approach to drug-resistant cancer therapy.

Introduction: Metabolic dysfunction-associated steatohepatitis (MASH) is increasingly becoming a prevalent cause of hepatocellular carcinoma (HCC). Our study examines the burden of MASH-related HCC globally, regionally, and nationally, along with associated risk factors from 1990 to 2019, considering variables such as age, sex, and socioeconomic status.Objective: We aimed to report the global, regional, and national burden of liver cancer due to MASH and its attributable risk factors between 1990 and 2019, by age, sex, and sociodemographic index (SDI).Methods: Utilizing the Global Burden of Disease 2019 project, we analyzed data on prevalence, mortality, and disability-adjusted life years (DALYs) for liver cancer attributable to MASH across 204 countries. We provided counts and rates per 100,000 population, including 95% uncertainty intervals.Results: In 2019, there were 46.8 thousand cases of MASH-related HCC, leading to 34.7 thousand deaths, and 795.8 thousand DALYs globally. While the prevalence increased by 19.8% since 1990, the death and DALY rates decreased by 5.3% and 15.1%, respectively. The highest prevalence was in High-income Asia Pacific, with the greatest increases observed in Australasia, Central Asia, and High-income North America. Southern Sub-Saharan Africa reported the highest death rate, while the lowest rates were in parts of Latin America, Central Sub-Saharan Africa, and Eastern Europe. DALY rates were the highest in Southern Sub-Saharan Africa and the lowest in Tropical Latin America.Discussion: The burden of MASH-related HCC is expected to rise slightly over the next decade. This disease, which is not associated with the SDI, remains a major public health problem. In addition, the escalating rates of obesity, demographic shifts, and an aging population could position MASH as a leading factor in liver cancer cases, surpassing viral hepatitis. It is imperative, therefore, that the forthcoming years see the implementation of strategic interventions aimed at the early detection and prevention of liver cancer associated with MASH.

Background: Studies focused on surgical interventions of spinal metastases of nasopharyngeal carcinoma (SMNPC) are blank. Methods: Patients with SMNPC who received surgical treatment in our center between 2005 and 2017 were included. Univariate and multivariate analysis of various clinical characteristics and operation-related data were analyzed to identify the independent factors that affected prognosis. Factors with P values of 0.1 or less were subjected to multivariate Cox regression analysis. P values of 0.05 or less were considered statistically significant. Results: A total of 30 patients with SMNPC treated with surgery were included. The thoracic spine was the most frequently involved site. The patients in this series achieved good overall survival (OS, 20.26 months) with limited perioperative complications. The univariate analysis suggested that preoperative Karnofsky performance scale, number of spinal metastases, number of visceral metastases, preoperative Frankel score, surgical resection mode and Ki 67 were potential prognostic factors. In the multivariate analyses, number of visceral metastases, preoperative Frankel score and resection mode were found to be independent prognostic factors. Conclusion: This is the first study focusing on surgical outcomes in SMNPC. The thoracic spine was the most frequently involved site of SMNPC. Preoperative Frankel score, number of visceral metastasis and surgical resection mode were independent prognostic factors for SMNPC. Combined with adjuvant therapies, surgical interventions should be recommended early when necessary.

AIM: To investigate the clinical characteristics and prognostic factors that may influence outcomes of patients undergoing benign-appearing intraspinal malignant peripheral nerve sheath tumors (MPNSTs). MATERIAL and METHODS: This study included a total of 14 consecutive patients who were diagnosed with benign intraspinal tumors firstly and confirmed as intraspinal MPNSTs by pathology. The univariate analyses of various clinical factors were performed to identify variables that could predict prognosis. Endpoints were mortality and local recurrence. The survival rate was estimated using the Kaplan-Meier method, and differences were analyzed by carrying out the log-rank test. In addition, factors with p values of <= 0.05 were considered statistically significant. RESULTS: Benign-appearing intraspinal MPNSTs showed some different clinical features compared with spinal MPNSTs and intraspinal benign tumors. The present study found that age at diagnosis, Neurofibromatosis type 1 (NF-1) history, tumor sites, malignant grade, Ki-67 and tumor resection method might be factors closely associated with recurrence and survival of intraspinal MPNSTs patients. CONCLUSION: Benign-appearing intraspinal MPNSTs are relatively rare tumors with a better overall prognosis compared with common spinal MPNSTs. A lot of factors can affect patients' survival and local recurrence. These prognostic factors still require further confirmation with further studies including more patients.

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