Glioblastoma multiform (GBM) continues to threaten people's lives due to the limited therapeutic strategies. As a new drug, Valerenic Acid suppresses the progression of GBM, however, the mechanism is largely unknown. Here, we found that Valerenic Acid can inhibit cell proliferation, migration and invasion of GBM cells by increasing innate immune signals such as enhancing ROS levels and activating the AMPK pathway. Inhibition of ROS by N-acetylcysteine (NAC) or attenuation of AMPK by Compound C could block Valerenic Acid-induced cell death. Additionally, the xenograft mouse model also confirmed that Valerenic Acid had anti-tumor effect. Together, our results provide compelling rational to develop Valerenic Acid as an anti-tumor agent against GBM patients.

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Basal cell carcinoma (BCC) is the most common skin cancer. While most of the basal cell carcinomas were localized lesion and can be easily managed, the treatment options to the advanced basal cell carcinomas are still remarkably limited. In recent years, proBDNF and its receptor p75NTR have been reported to play important roles in various diseases, including cancers and psychotic disorders. However, the role of p75NTR/proBDNF signaling in basal cell carcinoma remains unclear. Here, we found that the expression level of p75NTR/proBDNF was decreased in basal cell carcinoma patient samples and cell lines. In vitro study showed overexpression of p75NTR/proBDNF could significantly facilitate tumor cell death, including inflammatory-silent apoptosis and lytic inflammatory activated necroptosis. In vivo study showed overexpression of p75NTR/proBDNF dramatically promotes tumor-associated macrophage (M1) and T cell recruitment in a syngeneic mouse model of BCC. These results show a crucial role for p75NTR/proBDNF signaling in basal cell carcinoma immune microenvironment.

BackgroundKaposi sarcoma (KS) has features of both neoplastic growth and hyperplastic proliferation. It is the most common tumor seen in patients with HIV infection. Whether KS is a real tumor or a benign hyperplastic disease is not known.Material/MethodsTissues from KS and cutaneous hemangioma lesion DNA were extracted, and then digested with methylation-sensitive restriction endonuclease HpaII. Human androgen receptor gene (HUMARA) was amplified with PCR method and the product was separated on 10% denaturing polyacrylamide gels and stained with ethylene dibromide (EB) to show the polymorphism of HUMARA. Phosphoglycerate kinase (PGK) was amplified and the product was digested by BStXI, agarose gel and EB stained to show the polymorphism of PGK. Finally, we analyzed the clonality of KS.ResultsIn the 14 patients with KS, heterozygosity of the HUMARA gene was observed in 12 (85.7%) cases. Loss of heterozygosity of HUMARA gene on X-chromosome (without HpaII digestion there were 2 bands, after HpaII digestion there were just 1 of the bands), representing monoclonal origin, was present in 11 cases of Kaposi sarcoma. Heterozygosity of the PGK gene was observed in 5 (35.7%) cases, which all represent monoclonal origin. There was no significant difference according to country, stage, or HIV and HHV-8 (P>0.05).ConclusionsThe current findings suggest that Kaposi sarcoma is a clonal neoplasm, not a reactive proliferation.