Treatment of nasopharyngeal carcinoma (NPC), though initially successful, can unfortunately be followed by the development of distant metastasis. Accordingly, it is essential to explore the underlying mechanisms of metastasis in order to generate novel therapeutic solutions. Human tumors have been directly linked to the activity of Nucleophosmin 1 (NPM1), which may exhibit both a tumor-suppressing and oncogenic potential. NPM1, though frequently overexpressed in diverse solid tumors, continues to hold its enigmatic function in the context of nasopharyngeal carcinoma pathogenesis. In a study exploring the impact of NPM1 in NPC, we found elevated NPM1 levels in clinical samples of NPC patients, which emerged as a marker for poor prognosis. The increased activity of NPM1 promoted the migration and the cancer stem cell properties of NPC cells, as observed in both laboratory studies and animal experiments. The mechanistic process by which p53 is degraded through ubiquitination and proteasomal action involves NPM1's recruitment of E3 ubiquitin ligase Mdm2, as revealed by analyses. By knocking down NPM1, the stemness and EMT signaling cascades were effectively suppressed. In summary, this study unveiled the part played by NPM1 and its underlying molecular mechanism in NPC, giving support to NPM1 as a therapeutic target for nasopharyngeal carcinoma treatment.
Prospective studies have identified allogeneic natural killer (NK) cell therapies as a promising strategy for cancer immunosurveillance and immunotherapy, yet a deficiency in thorough comparisons of NK cells across different sources, including umbilical cord blood (UCB) and bone marrow (BM), severely restricts their broad clinical use. Starting from mononuclear cells (MNC), we isolated resident NK cells (rUC-NK and rBM-NK), and the corresponding expanded populations (eUC-NK and eBM-NK) were subjected to analyses. The eUC-NK and eBM-NK cell lines were then explored through a comprehensive, multifaceted bioinformatics analysis, including gene expression profiling and genetic variations. Relative to the rUC-NK group, the rBM-NK group showed a near doubling of total and activated NK cell percentages. Conversely, the percentage of total natural killer (NK) cells in the eUC-NK group exceeded that observed in the eBM-NK group, notably within the CD25+ memory-like NK cell population. Moreover, eUC-NK and eBM-NK cells manifested a diverse yet overlapping gene expression pattern and genetic spectrum, while both exhibited outstanding tumor cytotoxicity. A comprehensive analysis of the cellular and transcriptomic profiles of NK cells derived from UC-MNCs and BM-MNCs yielded novel insights into their characteristics, paving the way for future advancements in cancer immunotherapy.
The overexpression of centromere protein H (CENPH) is a driver of cancer expansion and progression. Yet, the duties and the underlying processes are not comprehensively understood. To that end, we endeavor to explore the functions and underlying processes of CENPH in lung adenocarcinoma (LUAD) development, utilizing detailed data analysis and cellular experiments. This research investigated the relationship between CENPH expression, as obtained from the TCGA and GTEx databases, and the clinical characteristics and prognosis of LUAD patients, while assessing the diagnostic value of CENPH. CENPH-based risk models and nomograms, developed using Cox and LASSO regression, were used to assess the outlook of LUAD patients. To ascertain the roles and mechanisms of CENPH in LUAD cells, a multi-faceted approach was employed, encompassing CCK-8 assay, wound healing and migration tests, and western blotting. CC-930 Correlation analysis was used to determine the relationship among CENPH expression, RNA modifications, and the characteristics of the immune microenvironment. hepatic impairment In LUAD tissue samples, CENPH expression was elevated, notably in tumors larger than 3cm, with lymph node and distant metastasis, in late-stage disease, in male patients, and in deceased cancer patients. Elevated CENPH expression displayed a relationship with the diagnosis, survival rates (poor), disease-specific survival rates (low), and disease progression in patients with LUAD. Employing CENPH-related nomograms and risk models, estimations of survival rates for LUAD patients are possible. Dampening the expression of CENPH within LUAD cells demonstrably decreased cell migration, proliferation, and invasion, and boosted their sensitivity to cisplatin, a change correlated with reduced p-AKT, p-ERK, and p-P38 phosphorylation. Interestingly, neither AKT, ERK, nor P38 exhibited any response to the intervention. Marked increases in CENPH expression were significantly linked to immune scores, the presence of immune cells, cellular characteristics, and RNA modification profiles. Finally, CENPH exhibited robust expression within LUAD tissues, correlating with a less favorable prognosis, characteristics of the immune microenvironment, and RNA modification patterns. Overexpression of CENPH can augment cell proliferation, metastasis, and cisplatin resistance through the AKT and ERK/P38 pathways, suggesting its potential as a prognostic biomarker for lung adenocarcinoma (LUAD).
More recent years have seen a significant increase in the understanding of how neoadjuvant chemotherapy (NACT) in ovarian cancer patients is linked to the rate of venous thromboembolism (VTE). Preliminary findings from studies on NACT in ovarian cancer patients point towards a potential correlation with a heightened risk of VTE. In order to examine the incidence of VTE during NACT and its associated risk factors, a thorough meta-analysis and systematic review were conducted. We scoured PubMed, Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, meticulously searching for relevant studies. The International Standard Randomized Controlled Trial Number Register (ISRCTN), from its establishment until September 15, 2022, meticulously documented trial data. We determined the frequency of VTE as a percentage rate and employed logistic regression to examine combined VTE rates. Presented as odds ratios (ORs), risk factors for venous thromboembolism (VTE) were analyzed, and pooled ORs were calculated using the inverse variance method. Our report included a summary of pooled effect estimates, with 95% confidence intervals (CIs) provided. Seven cohort studies, totalling 1244 participants, formed part of our review. Analyzing multiple studies collectively revealed a pooled VTE incidence of 13% during neoadjuvant chemotherapy (NACT) among 1224 participants, with a 95% confidence interval (CI) of 9% to 17%. Body mass index (BMI) emerged as a risk factor for VTE during NACT in three of the included studies (633 participants), presenting an odds ratio (OR) of 176, and a 95% confidence interval (CI) of 113 to 276.
While aberrant TGF signaling is crucial for the progression of several cancers, the precise functional mechanisms of this signaling network within the infectious context of esophageal squamous cell carcinoma (ESCC) are still unknown. Employing global transcriptomic analysis, this study found that Porphyromonas gingivalis infection induced an increase in TGF secretion, promoting the activation of TGF/Smad signaling in cultured cells and in clinical ESCC samples. In addition, we pioneered the discovery that P. gingivalis boosted Glycoprotein A repetitions predominant (GARP) expression, consequently triggering TGF/Smad signaling. Significantly, the enhanced GARP expression and subsequent TGF activation were partially mediated by the fimbriae (FimA) of Porphyromonas gingivalis. Curiously, the elimination of P. gingivalis, the impediment of TGF, or the silencing of GARP led to decreased Smad2/3 phosphorylation, the key mediator in TGF signaling, and a reduced malignant presentation in ESCC cells, indicating that TGF signaling activation might be an adverse prognostic factor in ESCC. The poor prognosis of ESCC patients was consistently reflected in our clinical data by a positive correlation between Smad2/3 phosphorylation and the expression of GARP. Xenograft models revealed that P. gingivalis infection prominently activated TGF signaling, consequently contributing to augmented tumor growth and lung metastasis. The collective findings of our study reveal that TGF/Smad signaling facilitates the oncogenic action of P. gingivalis on esophageal squamous cell carcinoma (ESCC), a process that is strengthened by the presence of GARP. For this reason, a potential treatment for ESCC patients may lie in either the inhibition of P. gingivalis or the manipulation of the GARP-TGF signaling cascade.
Globally, pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death, with unfortunately limited effective treatment options. Trials combining immunotherapy with chemotherapy for PDAC have produced outcomes that are not considered promising. Accordingly, we examined the application of a novel combination approach, including disulfiram (DSF), to enhance the treatment outcome of pancreatic ductal adenocarcinoma (PDAC) and to investigate its associated molecular mechanisms. A mouse allograft tumor model was employed to compare the efficacy of single agents with combination therapies in terms of antitumor effects. The combination of DSF and chemoimmunotherapy significantly decreased the growth of subcutaneous pancreatic ductal adenocarcinoma (PDAC) allografts and prolonged the survival of the mice. In order to investigate the modifications in the tumor immune microenvironment associated with varying treatment protocols, we utilized flow cytometry and RNA sequencing to evaluate the infiltration of immune cells into the tumor and the levels of expression of diverse cytokines. Analysis of our results showed a marked increase in the percentage of CD8 T cells and a concurrent upregulation of various cytokines within the combined treatment group. genetic correlation Moreover, quantitative real-time polymerase chain reaction (qRT-PCR) findings revealed that DSF enhanced the mRNA expression of IFN and IFN, an effect counteracted by STING pathway inhibitors.