The radiologic criteria that should be used for assessment of RLN metastases in NPC patients are nodes with a minimal axial diameter 6 mm or larger, any node with central necrosis, groups of two or more RLNs, or any medial RLN; these criteria may be useful in tumor staging and treatment planning.
Programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) interaction plays a crucial role in tumor-associated immune escape. Here, we verify that triple-negative breast cancer (TNBC) has higher PD-L1 expression than other subtypes. We then discover that nucleophosmin (NPM1) binds to PD-L1 promoter specifically in TNBC cells and activates PD-L1 transcription, thus inhibiting T cell activity in vitro and in vivo. Furthermore, we demonstrate that PARP1 suppresses PD-L1 transcription through its interaction with the nucleic acid binding domain of NPM1, which is required for the binding of NPM1 at PD-L1 promoter. Consistently, the PARP1 inhibitor olaparib elevates PD-L1 expression in TNBC and exerts a better effect with anti-PD-L1 therapy. Together, our research has revealed NPM1 as a transcription regulator of PD-L1 in TNBC, which could lead to potential therapeutic strategies to enhance the efficacy of cancer immunotherapy.
The equivalent laminate assumption is a commonly-used method to model the random architecture of discontinuous composites, but which has never been validated experimentally. This study aims to verify the equivalent laminate assumption, focusing on tow-based discontinuous composites (TBDCs), which have higher fibre-content and thus improved modulus and strength, compared to conventional discontinuous-fibre composites. This verification was achieved by manufacturing and testing (i) actual TBDCs with randomly oriented tows and (ii) their equivalent laminates (ELs), at two different tow thicknesses. The results show that ELs exhibit the same failure mechanisms as TBDCs, and are similarly weakened by an increase in tow thickness. However, ELs lack the spatial variability in local fibre-content and local tow orientations, which makes ELs stronger than TBDCs. Therefore, the equivalent laminate assumption is suitable for predicting the modulus of discontinuous composites, but cannot predict their strength without considering the local variability in their microstructure.
Sirtuin 5 (SIRT5), a mitochondrial class III NAD-dependent deacetylase, plays controversial roles in tumorigenesis and chemoresistance. Accordingly, its role in ovarian cancer development and drug resistance is not fully understood. Here, we demonstrate that SIRT5 is increased in ovarian cancer tissues compared to its expression in normal tissues and this predicts a poor response to chemotherapy. SIRT5 levels were also found to be higher in cisplatin-resistant SKOV-3 and CAOV-3 ovarian cancer cells than in cisplatin-sensitive A2780 cells. Furthermore, this protein was revealed to facilitate ovarian cancer cell growth and cisplatin-resistance
in vitro
. Mechanistically, we show that SIRT5 contributes to cisplatin resistance in ovarian cancer by suppressing cisplatin-induced DNA damage in a reactive oxygen species (ROS)-dependent manner via regulation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway.
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