Taku Kimura

Muscle-invasive bladder cancer is molecularly heterogeneous, and the basal/squamous subtype frequently exhibits elevated EGFR expression and TP53 and RB1 alterations. Functional vulnerabilities associated with these alterations remain incompletely defined, while large-scale in vivo screening in mammalian models is experimentally demanding. Therefore, we developed a genotype-defined Drosophila melanogaster model combining Egfr overexpression, mutant p53, and Rbf suppression in Malpighian tubules. The resulting 3-hit model showed increased Malpighian tubule volume and reduced adult eclosion rate. A dominant modifier screen targeting 216 kinase genes identified 72 genes whose perturbation significantly increased the eclosion rate, and a complementary RNA interference screen identified eight kinases whose knockdown increased the eclosion rate. Among these hits, Pka-C3, which is a Drosophila ortholog of human PRKX, emerged as one of the strongest suppressors of the 3-hit phenotype. PRKX was prioritized for further study because public transcriptomic datasets showed higher PRKX expression in bladder tumors than in normal bladder tissue. PRKX knockdown reduced spheroid volume in four human bladder cancer cell lines with distinct EGFR, TP53, and RB1 profiles. Both small interfering RNAs produced significant reductions in two cell lines, whereas only one siRNA reached significance in the other two. These findings nominate PRKX as a candidate vulnerability in bladder cancer and highlight a cross-species approach that combines genotype-informed Drosophila screening with functional testing in human cancer cells to prioritize targets for further investigation.

Oral verruciform xanthoma (OVX) is a rare benign lesion of the oral mucosa that often mimics other oral diseases. We report three cases of OVX and describe their clinical and histopathological characteristics. All patients presented with asymptomatic, well‐demarcated verrucous lesions located on the attached gingiva. The patients ranged in age from 59 to 85 years, with a median age of 73 years. One patient had a history of umbilical cord blood transplantation and possible chronic graft‐versus‐host disease. Clinically, the lesions were suspected to represent papillary lesions. Excisional biopsy was performed in all cases. Histopathological examination demonstrated papillary epithelial architecture with elongated rete ridges and infiltration of foamy macrophages within the underlying connective tissue, thereby confirming the diagnosis of OVX. No recurrence was observed during the follow‐up period. These findings emphasize the importance of histopathological evaluation for the accurate diagnosis of OVX.