Unclassified Renal Cell Carcinoma: Diagnostic and Molecular Updates [Review]
Unclassified renal cell carcinoma is a diagnostic category for renal cell tumors not fitting into one of the established subtypes in our current classification system and includes a heterogeneous group of tumors with variable clinicopathologic features and biological behaviors. Unclassified renal cell carcinoma with high-grade histologic features represents a particularly challenging group of tumors for diagnosis and management, given their complex pathologic features, aggressive clinical attributes, and a lack of standard therapy. Using an example case of high-grade unclassified renal cell carcinoma, this review discusses the diagnostic approaches to these tumors in the context of the World Health Organization 2016 classification system and provides updates on the molecular characteristics of these tumors.
Nitroxoline induces apoptosis and slows glioma growth in vivo
BACKGROUND:Nitroxoline is an FDA-approved antibiotic with potential antitumor activity. Here we evaluated whether nitroxoline has antiproliferative properties on glioma cell growth in vitro and in vivo using glioma cell lines and a genetically engineered PTEN/KRAS mouse glioma model. METHODS:The effect of nitroxoline treatment on U87 and/or U251 glioma cell proliferation, cell-cycle arrest, invasion, and ability to induce an apoptotic cascade was determined in vitro. Magnetic resonance imaging was used to measure glioma volumes in genetically engineered PTEN/KRAS mice prior to and after nitroxoline therapy. Induction of apoptosis by nitroxoline was evaluated at the end of treatment using terminal deoxyribonucleotidyl transferase (TDT)-mediated dUTP-digoxigenin nick end labeling (TUNEL). RESULTS:Nitroxoline inhibited the proliferation and invasion of glioblastoma cells in a time- and dose-dependent manner in vitro. Growth inhibition was associated with cell-cycle arrest in G1/G0 phase and induction of apoptosis via caspase 3 and cleaved poly(ADP-ribose) polymerase. In vivo, nitroxoline-treated mice had no increase in tumor volume after 14 days of treatment, whereas tumor volumes doubled in control mice. Histological examination revealed 15%-20% TUNEL-positive cells in nitroxoline-treated mice, compared with âˆ¼5% in the control group. CONCLUSION/CONCLUSIONS:Nitroxoline induces apoptosis and inhibits glioma growth in vivo and in vitro. As an already FDA-approved treatment for urinary tract infections with a known safety profile, nitroxoline could move quickly into clinical trials pending confirmatory studies.