Introduction: Androgen receptor (AR)-targeted therapies are the first-line treatment for metastatic prostate cancer. However, resistance inevitably develops in most cases, resulting in castration-resistant prostate cancer (CRPC). CRPCs can be classified into 3 subtypes: AR-positive CRPC (ARPC), neuroendocrine prostate cancer (NEPC), and double-negative prostate cancer (DNPC), which lacks both AR and neuroendocrine markers. DNPC is associated with poor prognosis and limited therapeutic options, representing a significant clinical challenge. The aim of this study is to analyze the molecular characteristics of the 3 CRPC subtypes and to identify therapeutic targets for DNPC.

Methods: We characterized the molecular signature of diverse CRPC models using gene expression profiles from publicly available datasets. We then analyzed the effect of inhibiting potential therapeutic targets using LNCaP cells and DU145 cells as models for ARPC and DNPC, respectively.

Results: We classified 40 CRPC models, including human prostate cancer organoids, patient-derived xenografts, and cell lines, into ARPC, NEPC, and DNPC by Uniform Manifold Approximation and Projection (UMAP) analysis. Integrated analysis using weighted gene co-expression network analysis (WGCNA) and gene set enrichment analysis (GSEA) revealed specific signaling pathways characterizing each subtype. Although both WGCNA and GSEA suggested activation of transforming growth factor-beta (TGF-β) signaling in DNPC, inhibition of TGF-β signaling failed to suppress the migratory activity of DU145 cells. In contrast, inhibition of MEK/ERK signaling, another signaling pathway upregulated in DNPC, suppressed both the migration and proliferation of DU145 cells.

Conclusions: Inhibition of MEK/ERK signaling may represent a promising therapeutic strategy for DNPC.

Introduction: Acute appendicitis is generally managed either surgically by appendectomy or non-surgically with antibiotics. The therapeutic strategy is mainly determined by the presence of clinical or computed tomography (CT) findings suggestive of gangrenous appendicitis or perforation. Although several systematic reviews have evaluated the diagnostic utility of contrast-enhanced CT in complicated appendicitis, none have focused exclusively on plain CT. In this study, we aimed to assess the usefulness of 5 findings detectable on plain CT for determining surgical indications in adults with acute appendicitis.

Methods: A PubMed search identified studies published between 2015 and 2024 using the keywords "acute appendicitis," "diagnosis," and "CT." Case reports, pediatric and pregnant populations, low-dose CT studies, abstracts only, and studies with fewer than 100 participants were excluded. Seventeen articles (6 on CT diagnostic accuracy and 11 on appendiceal findings) were included.

Results: Regarding complicated appendicitis, pooled sensitivity, specificity, and accuracy were 94.2%, 88.9%, and 91.8% for contrast-enhanced CT, and 88.7%, 86.4%, and 87.6% for plain CT, respectively. The diagnostic accuracies of 5 detectable on plain CT were as follows: appendicolith (50.7%, 74.2%, 66.3%), periappendiceal fat stranding (91.6%, 30.3%, 54.2%), enlarged appendiceal diameter (54.3%, 66.9%, 61.7%), periappendiceal air (22.4%, 99.0%, 70.3%), and periappendiceal fluid collection (61.4%, 57.6%, 59.0%).

Conclusions: Each of the 5 findings detectable on plain CT is insufficient as a standalone criterion for determining surgical indication; however, the combined assessment of selected findings-particularly appendicolith characteristics, periappendiceal fat stranding, and periappendiceal air-might substantially improve identification of complicated appendicitis. These findings may be particularly useful when contrast-enhanced CT is contraindicated.