<div>AbstractPurpose:<p>This study aimed to assess the antitumor activity and safety of neoadjuvant chemotherapy combined with PD-1 inhibitor camrelizumab in patients with locally advanced head and neck squamous cell carcinoma (HNSCC).</p>Patients and Methods:<p>In this single-center, single-arm, phase 2 trial, patients with resectable stage III–IVB HNSCC received chemotherapy [albumin-bound paclitaxel 260 mg/m<sup>2</sup> (or docetaxel 75 mg/m<sup>2</sup>) plus cisplatin 75 mg/m<sup>2</sup>] and camrelizumab 200 mg on day 1 of each 21-day cycle for three cycles, followed by surgery, and adjuvant radiotherapy. Co-primary end points were pathological complete response (pCR) rate and safety.</p>Results:<p>Thirty patients were enrolled and completed the neoadjuvant therapy, with an objective response rate (ORR) of 96.7% (29/30). Twenty-seven patients underwent surgery without delay, with an R0 resection rate of 92.6% (25/27). The clinical to pathological downstaging rate was 100% (27/27). The pCR rate was 37.0% [95% confidence interval (CI), 19.4%–57.6%], and the major pathological response (MPR) rate was 74.1% (95% CI, 53.7%–88.9%). The median follow-up duration was 16.1 months (range, 8.3–28.5), and the disease-free survival rate at 12 months was 95.8% (95% CI, 73.9%–99.4%). Grade 3 neoadjuvant therapy–related adverse events included rash (1; 3.3%), pruritis (1; 3.3%), and thrombocytopenia (1; 3.3%), and no grade 4 or 5 treatment-related events occurred. The most common surgical complication was delayed wound healing (5; 18.5%).</p>Conclusions:<p>Neoadjuvant chemotherapy plus camrelizumab for locally advanced HNSCC showed high ORR, pCR, and MPR rates, with an acceptable safety profile. These data support further evaluation of neoadjuvant chemoimmunotherapy for the treatment of locally advanced HNSCC.</p></div>
Existing evidence has shown that circulating Epstein-Barr virus (EBV)-miR-BART13-3p is highly expressed in plasma of nasopharyngeal carcinoma (NPC) patients, especially among patients with advanced diseases. However, the exact role that EBV-miR-BART13-3p plays in the development of NPC remains poorly understood. Here we show that up-regulated expression of EBV-miR-BART13-3p leads to increased capacity in migration and invasion of NPC cells in vitro and causes tumor metastasis in vivo. Furthermore, we find that EBV-miR-BART13-3p directly targets ABI2, known as a tumor suppressor and a cell migration inhibitor, drives epithelial-mesenchymal transition (EMT) by activating c-JUN/SLUG signaling pathway. Silencing ABI2 shows similar effects to overexpression of EBV-miR-BART13-3p, whereas reconstitution of ABI2 resulted in a phenotypic reversion, highlighting the role of ABI2 in EBV-miR-BART13-3p-driven metastasis in NPC. Besides, expression levels of ABI2 in NPC tissue samples correlate with N stages of NPC patients. Taken together, these results suggest a novel mechanism by which ABI2 downregulation by EBV-miR-BART13-3p promotes EMT and metastasis of NPC via upregulating c-JUN/SLUG signaling pathway.
Abstract Due to the urgent demand for more anti-cancer methods, the new applications of metal ions in cancer have attracted increasing attention. Especially the three kinds of the new mode of cell death, including ferroptosis, calcicoptosis, and cuproptosis, are of great concern. Meanwhile, many metal ions have been found to induce cell death through different approaches, such as interfering with osmotic pressure, triggering biocatalysis, activating immune pathways, and generating the prooxidant effect. Therefore, varieties of new strategies based on the above approaches have been studied and applied for anti-cancer applications. Moreover, many contrast agents based on metal ions have gradually become the core components of the bioimaging technologies, such as MRI, CT, and fluorescence imaging, which exhibit guiding significance for cancer diagnosis. Besides, the new nano-theranostic platforms based on metal ions have experimentally shown efficient response to endogenous and exogenous stimuli, which realizes simultaneous cancer therapy and diagnosis through a more controlled nano-system. However, most metal-based agents have still been in the early stages, and controlled clinical trials are necessary to confirm or not the current expectations. This article will focus on these new explorations based on metal ions, hoping to provide some theoretical support for more anti-cancer ideas.
Abstract Cisplatin-based chemotherapy improves the control of distant metastases in patients with nasopharyngeal carcinoma (NPC); however, around 30% of patients fail treatment due to acquired drug resistance. Epigenetic regulation is known to contribute to cisplatin resistance; nevertheless, the underlying mechanisms remain poorly understood. Here, we showed that lysine-specific demethylase 5B (KDM5B) was overexpressed and correlates with tumor progression and cisplatin resistance in patients with NPC. We also showed that specific inhibition of KDM5B impaired the progression of NPC and reverses cisplatin resistance, both in vitro and in vivo. Moreover, we found that KDM5B inhibited the expression of ZBTB16 by directly reducing H3K4me3 at the ZBTB16 promoter, which subsequently increased the expression of Topoisomerase II- α (TOP2A) to confer cisplatin resistance in NPC. In addition, we showed that the deubiquitinase USP7 was critical for deubiquitinating and stabilizing KDM5B. More importantly, the deletion of USP7 increased sensitivity to cisplatin by disrupting the stability of KDM5B in NPC cells. Therefore, our findings demonstrated that USP7 stabilized KDM5B and promoted cisplatin resistance through the ZBTB16/TOP2A axis, suggesting that targeting KDM5B may be a promising cisplatin-sensitization strategy in the treatment of NPC.
Supplementary Data from Neoadjuvant Chemoimmunotherapy for the Treatment of Locally Advanced Head and Neck Squamous Cell Carcinoma: A Single-Arm Phase 2 Clinical Trial
Supplementary Data from Neoadjuvant Chemoimmunotherapy for the Treatment of Locally Advanced Head and Neck Squamous Cell Carcinoma: A Single-Arm Phase 2 Clinical Trial
Supplementary Data from Neoadjuvant Chemoimmunotherapy for the Treatment of Locally Advanced Head and Neck Squamous Cell Carcinoma: A Single-Arm Phase 2 Clinical Trial
Neural Radiance Fields (NeRF) has shown great success in novel view synthesis due to its state-of-the-art quality and flexibility. However, NeRF requires dense input views (tens to hundreds) and a long training time (hours to days) for a single scene to generate high-fidelity images. Although using the voxel grids to represent the radiance field can significantly accelerate the optimization process, we observe that for sparse inputs, the voxel grids are more prone to overfitting to the training views and will have holes and floaters, which leads to artifacts. In this paper, we propose VGOS, an approach for fast (3-5 minutes) radiance field reconstruction from sparse inputs (3-10 views) to address these issues. To improve the performance of voxel-based radiance field in sparse input scenarios, we propose two methods: (a) We introduce an incremental voxel training strategy, which prevents overfitting by suppressing the optimization of peripheral voxels in the early stage of reconstruction. (b) We use several regularization techniques to smooth the voxels, which avoids degenerate solutions. Experiments demonstrate that VGOS achieves state-of-the-art performance for sparse inputs with super-fast convergence. Code will be available at https://github.com/SJoJoK/VGOS.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)
'/%3e%3cuse xlink:href='%23a' transform='rotate(144 450 300)'/%3e%3cuse xlink:href='%23a' transform='rotate(216 450 300)'/%3e%3cuse xlink:href='%23a' transform='rotate(288 450 300)'/%3e%3c/svg%3e)