Non-coding RNA-related FCGBP downregulation in head and neck squamous cell carcinoma: a novel biomarker for predicting paclitaxel resistance and immunosuppressive microenvironment.

In head and neck squamous cell carcinoma (HNSC), chemoresistance is a major reason for poor prognosis. Nevertheless, there is a lack of validated biomarkers to screen for patients for categorical chemotherapy. Fc gamma binding protein (FCGBP) is a mucus protein associated with mucosal epithelial cells and has immunological functions that protect against tumors and metastasis. However, the effect of FCGBP on HNSC is unclear. In pan-cancer tissues, the expression of FCGBP and the survival status of patients were analyzed using information from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Correlation analysis and Cox regression analysis were conducted to confirm the relationship and survival outcome. Bioinformatics analysis was utilized to predict the probable upstream non-coding RNA. FCGBP functioned as a potential tumor suppressor gene in HNSC. Notably, FCGBP expression was negatively correlated with enriched tumor-infiltrating macrophages and paclitaxel resistance. Cox regression with gene, clinical, and immune factors showed that FCGBP was a risk factor acting in an independent manner. In HNSC, the utmost possibly upstream non-coding RNA-related pathway of FCGBP was also discovered to be the PART1/AC007728.2/LINC00885/hsa-miR-877-5p/FCGBP axis. According to the present study, non-coding RNA-related low levels of FCGBP are a prognostic indicator and are linked to an HNSC-related immunosuppressive state.

Early assessment of induction chemotherapy response of nasopharyngeal carcinoma by pretreatment diffusion-weighted magnetic resonance imaging.

OBJECTIVES: This study aimed to evaluate the feasibility of pretreatment diffusion-weighted imaging in predicting response after induction chemotherapy (IC) in nasopharyngeal carcinoma (NPC). METHODS: Fifty-four patients with stage III and IV NPC underwent MRI examination at baseline, after 2 cycles of chemotherapy, and at the end of chemoradiotherapy. Apparent diffusion coefficient (ADC) values were compared between effective and ineffective subjects after IC. RESULTS: Mean ADC in effective groups was significantly (P < 0.05) higher than that in the ineffective group. Average and minimum ADCs demonstrated higher sensitivity than maximum ADC for predicting IC response, with 68.4%, 71.1%, and 50.0%, respectively, at an equivalent 68.7% specificity. We observed negative correlations between pretreatment ADC and tumor regression after chemotherapy (γ = - 0.425, P = 0.001) and after chemoradiotherapy (γ = - 0.418, P = 0.003). CONCLUSIONS: Pretreatment ADC was a valuable biomarker for predicting IC response of NPC. Noninvasive diffusion-weighted imaging provides additional indicator in guiding optical therapeutic options for patients with NPC.

Single-atom Zr embedded Ti4O7 anode coupling with hierarchical CuFe2O4 particle electrodes toward efficient electrooxidation of actual pharmaceutical wastewater.

Electrocatalytic oxidation is commonly restricted by low degradation efficiency, slow mass transfer, and high energy consumption. Herein, a synergetic electrocatalysis system was developed for removal of various drugs, i.e., atenolol, florfenicol, and diclofenac sodium, as well as actual pharmaceutical wastewater, where the newly-designed single-atom Zr embedded Ti4O7 (Zr/Ti4O7) and hierarchical CuFe2O4 (CFO) microspheres were used as anode and microelectrodes, respectively. In the optimal reaction system, the degradation efficiencies of 40 mg L-1 atenolol, florfenicol, and diclofenac sodium could achieve up to 98.8%, 93.4%, and 85.5% in 120 min with 0.1 g L-1 CFO at current density of 25 mA cm-2. More importantly, in the flow-through reactor, the electrooxidation lasting for 150 min could reduce the COD of actual pharmaceutical wastewater from 432 to 88.6 mg L-1, with a lower energy consumption (25.67 kWh/m3). Meanwhile, the electrooxidation system maintained superior stability and environmental adaptability. DFT theory calculations revealed that the excellent performance of this electrooxidation system could be ascribed to the striking features of the reduced reaction energy barrier by single-atom Zr loading and abundant oxygen vacancies on the Zr/Ti4O7 surface. Moreover, the characterization and experimental results demonstrated that the CFO unique hierarchical structure and synergistic effect between electrodes were also the important factors that could improve the system performance. The findings shed light on the single-atom material design for boosting electrochemical oxidation performance.

Laser tweezer Raman spectroscopy combined with deep neural networks for identification of liver cancer cells.

Rapid identification of cancer cells is crucial for clinical treatment guidance. Laser tweezer Raman spectroscopy (LTRS) that provides biochemical characteristics of cells can be used to identify cell phenotypes through classification models in a non-invasive and label-free manner. However, traditional classification methods require extensive reference databases and clinical experience, which is challenging when sampling at inaccessible locations. Here, we describe a classification method combing LTRS with deep neural network (DNN) for differential and discriminative analysis of multiple liver cancer (LC) cells. By using LTRS, we obtained high-quality single-cell Raman spectra of normal hepatocytes (HL-7702) and liver cancer cell lines (SMMC-7721, Hep3B, HepG2, SK-Hep1 and Huh7). The tentative assignment of Raman peaks indicated that arginine content was elevated and phenylalanine, glutathione and glutamate content was decreased in liver cancer cells. Subsequently, we randomly selected 300 spectra from each cell line for DNN model analysis, achieving a mean accuracy of 99.2%, a mean sensitivity of 99.2% and a mean specificity of 99.8% for the identification and classification of multiple LC cells and hepatocyte cells. These results demonstrate the combination of LTRS and DNN is a promising method for rapid and accurate cancer cell identification at single cell level.

The immunogenicity of Alum+CpG adjuvant SARS-CoV-2 inactivated vaccine in mice.

The ongoing evolution and emergence of SARS-CoV-2 variants have raised concerns regarding the efficacy of existing vaccines and therapeutic agents. This study aimed to investigate the immunogenicity of an aluminum hydroxide (Alum) and CpG adjuvanted inactivated vaccine (IAV) candidate against SARS-CoV-2 in mice. A comparison was made between the immune response of mice vaccinated with the Alum+CpG adjuvant IAV and those vaccinated with the Alum adjuvant IAV. Mice immunized with Alum+CpG adjuvant IAV demonstrated high antibody titers and a durable humoral immune response, as well as a Th1-type cellular immune response. Notably, compared to Alum alone vaccine, the Alum+CpG adjuvant IAV induced significantly higher proportions of GC B cells in the splenocytes of immunized mice. Importantly, the changes in inflammatory cytokine levels in the sera of mice vaccinated with the Alum+CpG adjuvant IAV followed a similar trend to that of the Alum adjuvant IAV, which had been proven safe in clinical trials. Overall, our results demonstrate that Alum+CpG adjuvant has the potential to serve as a novel adjuvant, thereby providing valuable insights into the development of vaccine formulations.

Identifying the optimal candidates for locoregional radiation therapy in patients with de novo metastatic nasopharyngeal carcinoma.

BACKGROUND: To evaluate the value of locoregional radiation therapy (LRRT) in de novo metastatic nasopharyngeal carcinoma (mNPC) and identify suitable candidates for additional LRRT after palliative chemotherapy (PCT). METHODS: Patients with de novo mNPC received platinum-based chemotherapy for a minimum of four cycles with or without definitive LRRT via intensity-modulated radiation therapy (IMRT) were all candidates for this study. RESULTS: A total of 168 patients were included for this analysis. Additional LRRT was associated with significantly longer median OS (69.5 vs. 17.8 months, p < 0.001) when compared with PCT alone. However, this survival benefit of LRRT was only reflected in patients with oligometastatic diseases (90.8 vs. 17 months, p < 0.001), but not for those with polymetastatic disease (p = 0.86). CONCLUSIONS: Additional LRRT after PCT may only improve OS for oligometastatic patients. For patients with polymetastatic disease, intensive systemic treatment such as the combination of immunotherapy and adequate PCT might be necessary.

Long Noncoding RNA HOXA11-AS Modulates the Resistance of Nasopharyngeal Carcinoma Cells to Cisplatin via miR-454-3p/c-Met.

To elucidate the mechanism of action of HOXA11-AS in modulating the cisplatin resistance of nasopharyngeal carcinoma (NPC) cells. HOXA11-AS and miR-454-3p expression in NPC tissue and cisplatin-resistant NPC cells were measured via quantitative reverse transcriptase polymerase chain reaction. NPC parental cells (C666-1 and HNE1) and cisplatin-resistant cells (C666-1/DDP and HNE1/DDP) were transfected and divided into different groups, after which the MTT method was used to determine the inhibitory concentration 50 (IC50) of cells treated with different concentrations of cisplatin. Additionally, a clone formation assay, flow cytometry and Western blotting were used to detect DDP-induced changes. Thereafter, xenograft mouse models were constructed to verify the in vitro results. Obviously elevated HOXA11-AS and reduced miR-454-3p were found in NPC tissue and cisplatin-resistant NPC cells. Compared to the control cells, cells in the si-HOXA11-AS group showed sharp decreases in cell viability and IC50, and these results were reversed in the miR-454-3p inhibitor group. Furthermore, HOXA11-AS targeted miR-454-3p, which further targeted c-Met. In comparison with cells in the control group, HNE1/DDP and C666-1/DDP cells in the si-HOXA11-AS group demonstrated fewer colonies, with an increase in the apoptotic rate, while the expression levels of c-Met, p-Akt/Akt and p-mTOR/mTOR decreased. Moreover, the si-HOXA11-AS-induced enhancement in sensitivity to cisplatin was abolished by miR-454-3p inhibitor transfection. The in vivo experiment showed that DDP in combination with si-HOXA11-AS treatment could inhibit the growth of xenograft tumors. Silencing HOXA11-AS can inhibit the c-Met/AKT/mTOR pathway by specifically upregulating miR-454-3p, thus promoting cell apoptosis and enhancing the sensitivity of cisplatin-resistant NPC cells to cisplatin.

Novel polypyridyl ruthenium complexes acting as high affinity DNA intercalators, potent transcription inhibitors and antitumor reagents.

Six novel polypyridyl ruthenium complexes with (E)-2-styryl-1H- imidazo[4,5-f][1,10]phenanthroline ligand and its analogues have been designed to enhance the DNA intercalation ability of their model compound [Ru(bpy)2(pip)]2+ (bpy = 2,2'-bipyridine, pip = 2-phenyl-1H-imidazo[4,5-f][1,10]phenanthroline). As shown in the optimized geometry of the complexes, the introduction of styryl group not only extended the conjugated area of the intercalative ligand, but also retained the excellent planarity. These two merits have been proven to be beneficial for their DNA intercalation, thus greatly improved their inhibition activity towards DNA transcription by RNA polymerase and DNA topoisomerase, two enzymes closely related to both DNA and tumor cell growth. The relationships between the substituent group structures and the biological activities have also been investigated from energetic and electronic aspects by quantum chemistry calculations. Results from cell cytotoxicity and apoptosis assay testified that the styryl substituted ruthenium complexes possessed higher antitumor activity than [Ru(bpy)2(pip)]2+, as expected. As quantified in the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, the tumor cell death is caused mostly through apoptosis for Ru2 and Ru3, while non-apoptotic processes for Ru1, Ru4 and Ru5. In vitro fluorescence evaluation revealed that all complexes located mainly in cytoplasm, but the three complexes with high antiproliferative activity could enter nucleus. All complexes have shown apparent lower cytotoxicity towards normal human colon epithelial cell CCD-841-CON than the examined tumor cell lines.

Quantitative study of lung perfusion SPECT scanning and pulmonary function testing for early radiation-induced lung injury in patients with locally advanced non-small cell lung cancer.

Radiation lung injury is a common side-effect of pulmonary radiotherapy. The aim of this study was to quantitatively assess early changes in lung perfusion single photon emission computed tomography (SPECT) scanning and pulmonary function testing (PFT) prior to and after intensity modulated radiotherapy (IMRT) for patients suffering from locally advanced non-small cell lung cancer (LANSCLC). Twenty patients with LANSCLC received lung perfusion SPECT scanning and PFT prior to IMRT and immediately after IMRT. Lung perfusion index (LPI) was calculated after the quantification of perfusion SPECT images. The LPI of the two groups was analyzed by matched t-test. The radioactive count of each layer of single lung was added to obtain the sum of the irradiated area. The percentage of the irradiated area of single lung was calculated. Linear correlation analysis was carried out between the percentage of the irradiated area and LPI in order to verify the validity of LPI. In this study, LPI and the percentage of the irradiated area of single lung exhibited an excellent correlation either prior to or after IMRT (r=0.820 and r=0.823, respectively; p<0.001). There was no statistically significant difference between pre-IMRT LPI and post-IMRT LPI (p=0.135). LPI in the group receiving a radical dose had no statistically significant difference (p=0.993), however, it showed a statistically significant difference in the group receiving a non-radical dose (p=0.025). In the non-radical dose group, the post-IMRT LPI was larger compared to pre-IMRT. None of the parameters of PFT exhibited a statistically significant difference prior to and after IMRT (p>0.05). The quantitative method of lung perfusion SPECT scanning can be used to evaluate changes in perfusion early in patients receiving a non-radical dose (BED ≤126,500 cGy) IMRT. Evaluating early changes in global lung function using the current method of PFT is difficult, since time can be a contributing factor for radiation-induced lung injury.

[Clinical analysis of 60 cases with radiative nasopharyngeal necrosis in nasopharyngeal carcinoma].

OBJECTIVE: To study the clinical characteristics, diagnosis, treatment and prognostic factors of patients with postradiation nasopharyngeal necrosis (PRNN) in nasopharyngeal carcinoma (NPC). METHODS: Sixty patients with PRNN were studied retrospectively, 50 males and 10 females, age ranging from 30 - 70 years of (median 51.5 years). All patients were treated with endoscopic debridement and systemic or local anti-inflammatory treatment. Kruskal-Wallis H test was used to assess the interval time between irradiation completion and necrosis onset and related factors of treatment outcome. Multivariate Cox proportional hazards regression survival analysis was performed to analyze risk factors. RESULTS: The latent period between the last irradiation and the onset of the symptom ranged from 1 to 156 months, with a median of 5 months. The median interval time was 7.0 months in 1 course group and 4.5 months in ≥2 courses group (χ2=5.527, P=0.031), and 7.5 months in T2 group and 5.0 months in ≥T3 group (χ2=4.330, P=0.037), respectively. Forty-one patients of them had nasopharyngeal infection, and the difference in curative effect between infection group and non-infection group was significantly (χ2=14.775, P<0.001). Symptoms were alleviated in all patients after endoscopic debridement and systemic or local anti-inflammatory treatment. Follow-up for all patients ranged from 2 to 46 months (median 12.5 months). Seven patients with internal carotid artery exposure died of sudden nasopharyngeal massive bleeding and fifteen patients died of tumor or systemic exhaustion; five cases were lost, and the rest were all in survival. Inter carotid artery erosion was an independent prognostic risk factor according to multivariate Cox proportional hazards regression survival analysis (P<0.05). CONCLUSIONS: Endoscopic debridement is effective in treating irradiation-related nasopharyngeal necrosis. The occurrence of nasopharyngeal necrosis is related to infection, irradiation dose and course, and T stage. Internal carotid artery erosion is a severe situation and also an independent prognostic factor for the patients. The most common causes of death were nasopharyngeal bleeding and systemic exhaustion.