Immune checkpoint blockade (ICB) has demonstrated curative potential in several types of cancer, but only for a small number of patients. Thus, the identification of reliable and noninvasive biomarkers for predicting ICB responsiveness is an urgent unmet need. Here, we show that ICB increased tumor vessel perfusion in treatment-sensitive EO771 and MMTV-PyVT breast tumor as well as CT26 and MCA38 colon tumor models, but not in treatment-resistant MCaP0008 and 4T1 breast tumor models. In the sensitive tumor models, the ability of anti-cytotoxic T lymphocyte-associated protein 4 or anti-programmed cell death 1 therapy to increase vessel perfusion strongly correlated with its antitumor efficacy. Moreover, globally enhanced tumor vessel perfusion could be detected by Doppler ultrasonography before changes in tumor size, which predicted final therapeutic efficacy with more than 90% sensitivity and specificity. Mechanistically, CD8+ T cell depletion, IFN-γ neutralization, or implantation of tumors in IFN-γ receptor knockout mice abrogated the vessel perfusion enhancement and antitumor effects of ICB. These results demonstrated that ICB increased vessel perfusion by promoting CD8+ T cell accumulation and IFN-γ production, indicating that increased vessel perfusion reflects the successful activation of antitumor T cell immunity by ICB. Our findings suggest that vessel perfusion can be used as a novel noninvasive indicator for predicting ICB responsiveness.

As(III) specifically interacts with an arsenic-binding aptamer to form an As(III)-aptamer complex, so that the following cationic polymer can aggregate gold nanoparticles (AuNPs) and cause a remarkable change in color, which enables the colorimetric detection of As(III) with high selectivity and a detection limit of 5.3 ppb.

Recently, traditional Chinese medicine and medicinal herbs have attracted more attentions worldwide for its anti-tumor efficacy. Celastrol and Triptolide, two active components extracted from the Chinese herb Tripterygium wilfordii Hook F (known as Lei Gong Teng or Thunder of God Vine), have shown anti-tumor effects. Celastrol was identified as a natural 26 s proteasome inhibitor which promotes cell apoptosis and inhibits tumor growth. The effect and mechanism of Triptolide on prostate cancer (PCa) is not well studied. Here we demonstrated that Triptolide, more potent than Celastrol, inhibited cell growth and induced cell death in LNCaP and PC-3 cell lines. Triptolide also significantly inhibited the xenografted PC-3 tumor growth in nude mice. Moreover, Triptolide induced PCa cell apoptosis through caspases activation and PARP cleavage. Unbalance between SUMOylation and deSUMOylation was reported to play an important role in PCa progression. SUMO-specific protease 1 (SENP1) was thought to be a potential marker and therapeutical target of PCa. Importantly, we observed that Triptolide down-regulated SENP1 expression in both mRNA and protein levels in dose-dependent and time-dependent manners, resulting in an enhanced cellular SUMOylation in PCa cells. Meanwhile, Triptolide decreased AR and c-Jun expression at similar manners, and suppressed AR and c-Jun transcription activity. Furthermore, knockdown or ectopic SENP1, c-Jun and AR expression in PCa cells inhibited the Triptolide anti-PCa effects. Taken together, our data suggest that Triptolide is a natural compound with potential therapeutic value for PCa. Its anti-tumor activity may be attributed to mechanisms involving down-regulation of SENP1 that restores SUMOylation and deSUMOyaltion balance and negative regulation of AR and c-Jun expression that inhibits the AR and c-Jun mediated transcription in PCa.

The demand for selection of aptamers against various small chemical molecules has substantially increased in recent years. To incubate and separate target-specific aptamers, the conventional SELEX procedures generally need to immobilize target molecules on a matrix, which may be impotent to screen aptamers toward small molecules without enough sites for immobilization. Herein we chose Cd(II) as a model of a small molecule with less sites, and proposed a novel SELEX strategy of immobilizing ssDNA libraries rather than target molecules on a matrix, for selection of aptamers with high affinity to Cd(II). After eleven rounds of positive and negative selection, twelve T and G-rich of nonrepeating ssDNA sequences were identified, of which the Cd-4 aptamer displayed the highest binding affinity to Cd(II). The secondary structures of these sequences revealed that a stem-loop structure folded by the domain of their 30-random sequence is critical for aptamers to bind targets. Then the interaction between the selected Cd-4 aptamer and Cd(II) was confirmed by CD analysis, and the binding specificity toward other competitive metal ions was also investigated. The dissociation constant (Kd) of Cd-4 aptamer was determined as 34.5 nM for Cd(II). Moreover, the Cd-4 aptamer was considered a recognition element for the colorimetric detection of Cd(II) based on the aggregation of AuNPs by cationic polymer. Through spectroscopic quantitative analysis, Cd(II) in aqueous solution can be detected as low as 4.6 nM. The selected Cd-4 aptamer will offer a new substitute for the detection of Cd(II) or other applications like recovery of cadmium from polluted samples.