New insights and options into the mechanisms and effects of combined targeted therapy and immunotherapy in prostate cancer

Chronic inflammation is believed to drive prostate carcinogenesis by producing reactive oxygen species or reactive nitrogen species to induce DNA damage. This effect might subsequently cause epigenetic and genomic alterations, leading to malignant transformation. Although established therapeutic advances have extended overall survival, tumors in patients with advanced prostate cancer are prone to metastasis, transformation into metastatic castration-resistant prostate cancer, and therapeutic resistance. The tumor microenvironment (TME) of prostate cancer is involved in carcinogenesis, invasion and drug resistance. A plethora of preclinical studies have focused on immune-based therapies. Understanding the intricate TME system in prostate cancer may hold much promise for developing novel therapies, designing combinational therapeutic strategies, and further overcoming resistance to established treatments to improve the lives of prostate cancer patients. In this review, we discuss nonimmune components and various immune cells within the TME and their putative roles during prostate cancer initiation, progression, and metastasis. We also outline the updated fundamental research focusing on therapeutic advances of targeted therapy as well as combinational options for prostate cancer

Study on the Hydrogen Effect and Interface/Border Traps of a Depletion-Mode AlGaN/GaN High-Electron-Mobility Transistor with a SiN_x Gate Dielectric at Different Temperatures

In this study, the electrical characteristics of depletion-mode AlGaN/GaN high-electron-mobility transistors (HEMTs) with a SiNx gate dielectric were tested under hydrogen exposure conditions. The experimental results are as follows: (1) After hydrogen treatment at room temperature, the threshold voltage VTH of the original device was positively shifted from −16.98 V to −11.53 V, and the positive bias of threshold was 5.45 V. When the VDS was swept from 0 to 1 V with VGS of 0 V, the IDS was reduced by 25% from 9.45 A to 7.08 A. (2) Another group of original devices with identical electrical performance, after the same duration of hydrogen treatment at 100 °C, exhibited a reverse shift in threshold voltage with a negative threshold shift of −0.91 V. The output characteristics were enhanced, and the saturation leakage current was increased. (3) The C-V method and the low-frequency noise method were used to investigate the effect of hydrogen effect on the device interface trap and border trap, respectively. It was found that high-temperature hydrogen conditions can passivate the interface/border traps of SiNx/AlGaN, reducing the density of interface/border traps and mitigating the trap capture effect. However, in the room-temperature hydrogen experiment, the concentration of interface/border traps increased. The research findings in this paper provide valuable references for the design and application of depletion-mode AlGaN/GaN HEMT devices

TET2 is required to suppress mTORC1 signaling through urea cycle with therapeutic potential

Abstract Tumor development, involving both cell growth (mass accumulation) and cell proliferation, is a complex process governed by the interplay of multiple signaling pathways. TET2 mainly functions as a DNA dioxygenase, which modulates gene expression and biological functions via oxidation of 5mC in DNA, yet whether it plays a role in regulating cell growth remains unknown. Here we show that TET2 suppresses mTORC1 signaling, a major growth controller, to inhibit cell growth and promote autophagy. Mechanistically, TET2 functions as a 5mC “eraser” by mRNA oxidation, abolishes YBX1–HuR binding and promotes decay of urea cycle enzyme mRNAs, thus negatively regulating urea cycle and arginine production, which suppresses mTORC1 signaling. Therefore, TET2-deficient tumor cells are more sensitive to mTORC1 inhibition. Our results uncover a novel function for TET2 in suppressing mTORC1 signaling and inhibiting cell growth, linking TET2-mediated mRNA oxidation to cell metabolism and cell growth control. These findings demonstrate the potential of mTORC1 inhibition as a possible treatment for TET2-deficient tumors