GPR120 promotes metastasis but inhibits tumor growth in pancreatic ductal adenocarcinoma.

OBJECTIVES: G-protein-coupled receptor 120 (GPR120) is a long-chain unsaturated fatty acid receptor, which regulates glucose metabolism and lipid. To date, there are disputes on the roles of GPR120 in the pathogenesis of cancer. Besides, little is known about its roles in the pathogenesis of pancreatic ductal adenocarcinoma (PDAC). This study was designed to investigate the roles of GPR120 in the pathogenesis of PDAC. METHODS: Immunohistochemical staining (IHC) was used for detecting the level of GPR120, epithelial-mesenchymal transformation (EMT) markers, Ki-67 and CD31 in ninety-one PDAC patients. Western blot, CCK8, flow cytometry and transwell assays were performed to determine proliferation, apoptosis, and motility in vitro. Subcutaneous tumor model was established to validate the roles of GPR120 in vivo. RESULTS: GPR120 was highly expressed in PDAC tissues, which was associated with free fatty acids (FFAs), lymph node metastasis (LNM), and poor prognosis. Moreover, GPR120 activation led to down-regulation of E-cadherin and up-regulation of Snail, Vimentin, N-cadherin, MMP2, MMP9, and CD31. Additionally, GPR120 decreased the expression of P-PI3K, P-AKT and CMYC and increased the level of P-JAK2, P-STAT3, Wnt5a, total ß-catenin and ß-catenin in nucleus. CONCLUSIONS: GPR120 promoted proliferation inhibition and apoptosis of PDAC, and contributed to PDAC metastasis via inducing EMT and angiogenesis. GPR120 served as a double-edged sword in the pathogenesis of PDAC.

Validity and reliability of the simplified Chinese patient-reported outcomes version of the common terminology criteria for adverse events.

BACKGROUND: The psychometric properties of the simplified Chinese version of the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) have not been assessed. Therefore, we aimed to assess its validity, reliability, and responsiveness. PATIENTS AND METHODS: A Chinese version of the PRO-CTCAE and the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (QLQ-C30) were distributed to 1580 patients from four cancer hospitals in China. Validity assessments included construct validity, measured by Pearson's correlations and confirmatory factor analysis (CFA), and known-groups validity, measured by t-tests. The assessment of reliability included internal consistency, measured by Cronbach's ɑ, and test-retest reliability, measured by the intraclass correlation (ICC). Responsiveness was assessed by standardized response means (SRMs). RESULTS: Data from 1555 patients who completed the instruments were analyzed. The correlations were high between PRO-CTCAE items and parallel QLQ-C30 symptom scales (r > 0.60, p < 0.001), except for fatigue (severity: r = 0.49). Moreover, CFA showed the PRO-CTCAE structure was a good fit with the data (Root Mean Square Error of Approximation = 0.046). Known-groups validity was also confirmed. Cronbach's ɑ of all item clusters were greater than 0.9 and the median test-retest reliability coefficients of the 38 items were 0.85 (range = 0.71-0.91). In addition, the SRMs of PRO-CTCAE items were greater than 0.8, indicating strong responsiveness. CONCLUSION: The simplified Chinese version of the PRO-CTCAE showed good reliability, validity, and responsiveness.

TRIM23 overexpression is a poor prognostic factor and contributes to carcinogenesis in colorectal cancer.

The tripartite motif (TRIM) family proteins play a great role in carcinogenesis. However, the expression pattern, prognostic value and biological functions of tripartite motif containing 23 (TRIM23) in colorectal cancer (CRC) are poorly understood. Here, we found that TRIM23 is up-regulated and associated with tumour size, lymph node metastasis, American Joint Committee on Cancer (AJCC) stage and poor prognosis in CRC. Multivariate Cox regression analyses revealed that TRIM23 overexpression could be identified as an independent prognostic factor for CRC. TRIM23 could promote the proliferation of CRC cell in vitro and in vivo; additionally, TRIM23 depletion induced G1-phase arrest. Gene set enrichment analysis (GSEA) revealed that P53 and cell cycle signalling pathway-related genes were enriched in patients with high TRIM23 expression levels. We show in this study that TRIM23 physically binds to P53 and enhances the ubiquitination of P53, thereby promoting tumour proliferation. Thus, our data indicated that TRIM23 acts as an oncogene in colorectal carcinogenesis and may provide a novel therapeutic target for CRC management.

Quercetin radiosensitizes non-small cell lung cancer cells through the regulation of miR-16-5p/WEE1 axis.

BACKGROUND: Quercetin, a widely distributed bioflavonoid, plays a role in combating diverse human cancers including non-small cell lung cancer (NSCLC). However, the role of quercetin in reversing the radioresistance of NSCLC cells and its underlying mechanism are far from being elucidated. METHOD: Radiation-resistant NSCLC cell lines were established. Quantitative real-time PCR (qRT-PCR) was used to detect the expression of miR-16-5p and WEE1 G2 checkpoint kinase (WEE1) mRNA in radiation-resistant cells. After being treated with different concentrations of quercetin and different doses of X-ray, cell proliferation and apoptosis were monitored by CCK-8 assay, colony formation assay, and flow cytometry, respectively. Ultimately, the targeting relationship between miR-16-5p and WEE1 was verified via a dual fluorescent reporter gene assay. RESULTS: The expression of miR-16-5p was down-regulated in radiation-resistant cells, while the expression of WEE1 was up-regulated. Quercetin enhanced the radiosensitivity of NSCLC cells in a dose- and time-dependent manner. Furthermore, quercetin treatment increased the expression of miR-16-5p and decreased the expression of WEE1. The function of quercetin was reversed by miR-16-5p inhibitors or the transfection of WEE1 overexpressing plasmids. CONCLUSION: In conclusion, quercetin enhanced the radiosensitivity of NSCLC cells via modulating the expression of miR-16-5p and WEE1.

Hyaluronidase Enzyme-responsive Targeted Nanoparticles for Effective Delivery of 5-Fluorouracil in Colon Cancer.

PURPOSE: In this study, we have successfully prepared the hyaluronic acid (HA)-conjugated mesoporous silica nanoparticles loaded with 5-fluorouracil (5-FU) to increase the anticancer efficacy in colon cancers. METHODS: The particles were nanosized and perfectly spherical. In vitro release kinetics clearly showed the enzyme-sensitive release of 5-FU from HA-conjugated 5-FU loaded mesoporous silica nanoparticles (HA/FMSN). RESULTS: The presence of HA on the surface of nanoparticles targeted the CD44 receptors overexpressed in the colon cancer cells In vitro cell viability and apoptosis assay clearly showed the superior anticancer effect of HA/FMSN in HT29 colon cancer cells. HA/FMSN exhibited a remarkably higher 43% of cells in early apoptosis phase and 55% of cells in late apoptosis phase indicating the superior anticancer effect of HA/FMSN. HA/FMSN exhibited a significant reduction in the tumor burden compared to that of any group. HA/FMSN was 3-fold more effective than free drug and 2-fold more effective than -FU loaded mesoporous silica nanoparticles (FMSN). CONCLUSIONS: Overall, results suggest that the novel delivery strategy could hold enormous potential in colon cancer targeting.

Design synthesis of a controllable flower-like Pt-graphene oxide architecture through electrostatic self-assembly for DNA damage biomarker 8-hydroxy-2'-deoxyguanosine biosensing research.

A controllable flower-like Pt-graphene oxide (PtNF-GO) architecture was synthesized through layer-by-layer electrostatic self-assembly. Hexadecyltrimethylammonium chloride (CTAC) micelles were employed as the template and Pt nanoflowers with different sizes were selectively synthesized by controlling the dissolved K2PtCl4 precursor and CTAC amounts in the reaction system. The prepared PtNF-GO was applied for DNA damage biomarker 8-hydroxy-2'-deoxyguanosine (8-OHdG) biosensing research. With the distinctive flower-like morphology of PtNFs and high electrical conductivity of GO, the PtNF-GO architecture shows excellent electrochemical biosensing performance towards the oxidation of 8-OHdG. A very low detection limit of 0.025 nM is obtained. Moreover, the fabricated PtNF-GO was used for the detection of 8-OHdG generated from the damaged DNA sample, which can be used to evaluate and confirm the mechanism of DNA damage, and it is of great importance in gene diagnosis, clinical and life sciences.

microRNA-577 suppresses tumor growth and enhances chemosensitivity in colorectal cancer.

In this work, we aimed to determine the expression and biological functions of microRNA (miR)-577 in colorectal cancer (CRC). The results showed that miR-577 was downregulated in CRC specimens and cell lines. Restoration of miR-577 significantly suppressed the proliferation and colony formation and induced a G0/G1 cell cycle arrest in CRC cells. 5-Fluorouracil (5-FU)-resistant SW480 cells (SW480/5-FU) were found to have elevated levels of miR-577. Ectopic expression of miR-577 enhanced 5-FU sensitivity in SW480/5-FU cells. Heat shock protein 27 (HSP27) was identified as a target gene of miR-577. Enforced expression of HSP27 reversed the effects of miR-577 on CRC cell growth and 5-FU sensitivity. Xenograft tumors derived from miR-577-overexpressing SW480 cells exhibited significantly slower growth than control tumors. In conclusion, our results support that miR-577 acts as a tumor suppressor in CRC likely through targeting HSP27. Therefore, miR-577 may have therapeutic potential in the treatment of CRC.

Silk Biomaterials with Vascularization Capacity.

Functional vascularization is critical for the clinical regeneration of complex tissues such as kidney, liver or bone. The immobilization or delivery of growth factors has been explored to improve vascularization capacity of tissue engineered constructs, however, the use of growth factors has inherent problems such as the loss of signaling capability and the risk of complications such as immunological responses and cancer. Here, a new method of preparing water-insoluble silk protein scaffolds with vascularization capacity using an all aqueous process is reported. Acid was added temporally to tune the self-assembly of silk in lyophilization process, resulting in water insoluble scaffold formation directly. These biomaterials are mainly noncrystalline, offering improved cell proliferation than previously reported silk materials. These systems also have appropriate softer mechanical property that could provide physical cues to promote cell differentiation into endothelial cells, and enhance neovascularization and tissue ingrowth in vivo without the addition of growth factors. Therefore, silk-based degradable scaffolds represent an exciting biomaterial option, with vascularization capacity for soft tissue engineering and regenerative medicine.

Preparation, Structure and Properties of Epoxy/Carbonyl Iron Powder Wave-Absorbing Foam for Electromagnetic Shielding.

The application of absorbing materials for electromagnetic shielding is becoming extensive, and the use of absorbents is one of the most important points of preparing absorbing foam materials. In this work, epoxy resin was used as the matrix and carbonyl iron powder (CIP) was used as the absorbent, and the structural absorbing foam materials were prepared by the ball mill dispersion method. Scanning electron microscopy showed that the CIP was evenly dispersed in the resin matrix. The foam structures formed at pre-polymerization times of 10 min, 30 min and 50 min were analyzed, and it was found that the cell diameter decreased from 0.47 mm to 0.31 mm with the increase in the pre-polymerization time. The reflectivity of the frontal and reverse sides of the foam gradually tends to be unified at frequencies of 2-18 GHz. When the CIP content increased from 30 wt% to 70 wt%, the cell diameter increased from 0.32 mm to 0.4 mm, and the uniformity of CIP distribution deteriorated. However, with the increase in the CIP content, the absorption properties of the composite materials were enhanced, and the absorption frequency band broadened. When the CIP content reached 70 wt%, the compression strength and modulus of the foam increased to 1.32 MPa and 139.0 MPa, respectively, indicating a strong ability to resist deformation.

The Preparation and Performance of Epoxy/Acetylene Carbon Black Wave-Absorbing Foam.

The epoxy foam material filled with an absorbing agent effectively absorbs electromagnetic waves. In this study, epoxy resin was used as the matrix, and acetylene carbon black was used as the magnetic absorbing agent to prepare an absorbing foam material (epoxy/CB). The microstructure of acetylene carbon black (CB) and its distribution in epoxy resin, as well as the effects of pre-polymerization time and CB content on the foam structure, were systematically characterized. Additionally, two dispersion methods, the hot-melt in situ stirring dispersion method and the three-roll milling dispersion method, were studied for their effects on the foaming process and absorbing properties of epoxy/CB. The results showed that with the prolongation of pre-polymerization time, the pore size decreased from 1.02 mm to 0.4 mm, leading to a more uniform pore distribution. Compared to the hot-melt in situ stirring dispersion method, the three-roll milling dispersion method effectively improved the dispersion of CB in epoxy resin, reducing the aggregate size from 300-400 nm to 70-80 nm. The pore diameter also decreased from 0.453 mm to 0.311 mm, improving the uniformity of particle size distribution. However, the absorbing material prepared with the three-roll milling dispersion method exhibited unsatisfactory absorption performance, with values close to 0 dB at mid-low frequencies and around -1 dB at high frequencies. In contrast, the absorbing material prepared with the hot-melt in situ stirring dispersion method showed better absorption performance at high frequencies, reaching around -9 dB.

Polyene phosphatidylcholine enhances the therapeutic response of oxaliplatin in gastric cancer through Nrf2/HMOX1 mediated ferroptosis.

Oxaliplatin (OXA)-based chemotherapy is one of the first-line treatments for advanced gastric cancer. However, the potential risk for chemotherapy-induced hepatic injury can hinder its effectiveness. Polyene phosphatidylcholine (PPC) is often used as a hepatoprotective agent to counter OXA-induced hepatic injury; however, its impact on the antitumour effectiveness of OXA remains uncertain. Our retrospective study examined 98 patients with stage IV gastric cancer to assess the impact of PPC on progression-free survival (PFS) and disease control rate (DCR). Furthermore, in vitro and in vivo assays were conducted to elucidate the combined biological effects of OXA and PPC (OXA+PPC) on gastric cancer. RNA sequencing, luciferase reporter assays, live/dead cell assays, immunofluorescence, and western blotting were used to identify the activated signalling pathways and downstream factors post OXA+PPC treatment. The findings indicated that PPC served as an independent prognostic factor, correlating with prolonged PFS and improved DCR in patients with gastric cancer. The combination of OXA and PPC significantly inhibited tumour cell growth both in vitro and in vivo. RNA sequencing revealed that OXA+PPC treatment amplified reactive oxygen species and ferroptosis signalling pathways. Mechanistically, OXA+PPC upregulated the expression of haem oxygenase-1 by promoting the nuclear migration of nuclear factor erythroid 2-related factor (Nrf2), thereby enhancing its transcriptional activity. Drug-molecule docking analysis demonstrated that PPC competitively bound to the peptide structural domains of both Nrf2 and Kelch-like ECH-associated protein 1 (KEAP1), accounting for the increased translocation of Nrf2. In conclusion, our study reveals the synergistic antitumour potential of PPC and OXA while protecting patients against hepatic injury. This suggests a promising combined treatment approach for patients with advanced gastric cancer.

High-fidelity intracellular imaging of multiple miRNAs via stimulus-responsive nanocarriers and catalytic hairpin assembly.

An advanced nanoplatform was developed by integrating catalytic hairpin assembly (CHA) with glutathione-responsive nanocarriers, enabling superior imaging of dual cancer-related miRNAs. Two distinct CHA circuits for the sensing of miRNA-21 and miRNA-155 were functionalized on biodegraded MnO2. In the presence of GSH and the corresponding miRNAs, the degraded MnO2 released the DNA cargos, activating the CHA circuits and recovering the fluorescence. This approach offers a reliable sensing performance with highly selective cell-identification capacity, positioning it as a pivotal tool for imaging multiple biomarkers in living cells.

PiR-hsa-23533 promotes malignancy in head and neck squamous cell carcinoma via USP7.

BACKGROUND: With regard to head and neck squamous cell carcinoma (HNSCC), its occurrence and advancement are controlled by genetic and epigenetic anomalies. PIWI-interacting RNAs (piRNAs) are recognized with significance in tumor, but the precise molecular mechanisms of piRNAs in HNSCC largely remain undisclosed. METHODS: Differentially expressed piRNAs were identified by RNA sequencing. The expression of piR-hsa-23533 was evaluated using quantitative real-time PCR and RNA in situ hybridization. The impacts of piR-hsa-23533 on the proliferation and apoptosis of HNSCC cells were investigated by a series of in vitro and in vivo assays. RESULTS: piR-hsa-23533 exhibits upregulation within HNSCC cells and tissues. Besides, piR-hsa-23533 overexpression promotes proliferation while inhibiting apoptosis in vitro and in vivo, while piR-hsa-23533 silencing has an opposite function. From the mechanistic perspective, piR-hsa-23533 can bind to Ubiquitin-specific protease 7 (USP7), as shown through RNA pull-down and RNA immunoprecipitation assays, promoting USP7 mRNA and protein expression. CONCLUSIONS: These findings highlight the functional importance of piR-hsa-23533 in HNSCC and may assist in the development of anti-HNSCC therapeutic target.

The impact of bolus on clinical outcomes for post-mastectomy breast cancer patients treated with IMRT: data from China.

PURPOSE: This study aims to investigate the effects of chest wall bolus in intensity-modulated radiotherapy (IMRT) technology on clinical outcomes for post-mastectomy breast cancer patients. MATERIALS AND METHODS: This retrospective study included patients with invasive carcinoma ((y)pT0-4, (y)pN0-3) who received photon IMRT after mastectomy at the Affiliated Hospital of Qingdao University from 2014 to 2019. The patients were divided into two groups based on whether they received daily bolus application or not, and the baseline characteristics were matched using propensity score matching (PSM). Cumulative incidence (CI) of local recurrence (LR), locoregional recurrence (LRR), overall survival (OS) and disease-free survival (DFS) were evaluated with a log-rank test. Acute skin toxicity and late radiation pneumonia was analyzed using chi-square test. RESULTS: A total of 529 patients were included in this study, among whom 254 (48%) patients received bolus application. The median follow-up time was 60 months. After matching, 175 well-paired patients were selected. The adjusted 5-year outcomes (95% confidence interval) in patients treated with and without bolus were, respectively: CI of LR 2.42% (0.04-4.74) versus 2.38% (0.05-4.65), CI of LRR 2.42% (0.04-4.74) versus 3.59% (0.73-6.37), DFS 88.12% (83.35-93.18) versus 84.69% (79.42-90.30), OS 94.21% (90.79-97.76) versus 95.86% (92.91-98.91). No correlation between bolus application and skin toxicity (P = 0.555) and late pneumonia (P = 0.333) was observed. CONCLUSIONS: The study revealed a low recurrence rate using IMRT technology. The daily used 5 mm chest wall bolus was not associated with improved clinical outcomes.

Observation of the delineation of the target volume of radiotherapy in adult-type diffuse gliomas after temozolomide-based chemoradiotherapy: analysis of recurrence patterns and predictive factors.

BACKGROUND: Radiation therapy is the cornerstone of treatment for adult-type diffuse gliomas, but recurrences are inevitable. Our study assessed the prognosis and recurrence pattern of different radiotherapy volumes after temozolomide-based chemoradiation in our institution. METHODS: The treatment plans were classified into two groups, the plan 1 intentionally involved the entire edema area while plan 2 did not. Retrospectively investigate the differences in outcomes of 118 adult-type diffuse gliomas patients between these two treatment plans. Then, patients who underwent relapse were selected to analyze their recurrence patterns. Continuous dynamic magnetic resonance images (MRI) were collected to categorized the recurrence patterns into central, in-field, marginal, distant, and cerebrospinal fluid dissemination (CSF-d) recurrence. Finally, the clinical and molecular characteristics which influenced progression were analyzed. RESULTS: Plan 1 (n = 63) showed a median progression-free survival (PFS) and overall survival (OS) of 9.5 and 26.4 months while plan 2 (n = 55) showed a median PFS and OS of 9.4 and 36.5 months (p = 0.418; p = 0.388). Treatment target volume had no effect on the outcome in patients with adult-type diffuse gliomas. And there was no difference in radiation toxicity (p = 0.388). Among the 90 relapsed patients, a total of 58 (64.4%) patients had central recurrence, 10 (11.1%) patients had in-field recurrence, 3 (3.3%) patients had marginal recurrence, 11 (12.2.%) patients had distant recurrence, and 8 (8.9%) patients had CSF-d recurrence. By treatment plans, the recurrence patterns were similar and there was no significant difference in survival. Reclassifying the progression pattern into local and non-local groups, we observed that oligodendroglioma (n = 10) all relapsed in local and no difference in PFS and OS between the two groups (p > 0.05). Multivariable analysis showed that subventricular zone (SVZ) involvement was the independent risk factor for non-local recurrence in patients with GBM (p < 0.05). CONCLUSION: In our study, deliberately including or not the entire edema had no impact on prognosis and recurrence. Patients with varied recurrence patterns had diverse clinical and genetic features.

Development and validation of a nomogram to predict cervical lymph node metastasis in head and neck squamous cell carcinoma.

Background: Head and neck cancers are a heterogeneous, aggressive, and genetically complex collection of malignancies of the oral cavity, nasopharynx, oropharynx, hypopharynx, larynx, paranasal sinuses and salivary glands, which are difficult to treat. Regional lymph nodes metastasis is a significant poor prognosis factor for head and neck squamous cell carcinoma. Metastasis to the regional lymph nodes reduces the 5-year survival rate by 50% compared with that of patients with early-stage disease. Accurate evaluation of cervical lymph node is a vital component in the overall treatment plan for patients with squamous cell carcinoma of the head and neck. However, current models are struggle to accurately to predict cervical lymph node metastasis. Here, we analyzed the clinical, imaging, and pathological data of 272 patients with HNSCC confirmed by postoperative pathology and sought to develop and validate a nomogram for prediction of lymph node metastasis in patients with head and neck squamous cell carcinoma. Methods: We retrospectively analyzed the clinical, imaging, and pathological data of 272 patients with head and neck squamous cell carcinoma (HNSCC) confirmed by postoperative pathology at the Affiliated Hospital of Qingdao University from June 2017 to June 2021. Patients were randomly divided into the training and validation cohorts in a 3:1 ratio, and after screening risk factors by logistic regression, nomogram was developed for predicting lymph nodes metastasis, then the prediction model was verified by C-index, area under curve (AUC), and calibration curve. Results: Of the 272 patients, seven variables were screened to establish the predictive model, including the differentiation degree of the tumor [95% confidence interval(CI):1.224~6.735, P=0.015], long-to-short axis ratio of the lymph nodes (95%CI: 0.019~0.217, P<0.001), uneven/circular enhancement (95%CI: 1.476~16.715, P=0.010), aggregation of lymph nodes (95%CI:1.373~10.849, P=0.010), inhomogeneous echo (95%CI: 1.337~23.389, P=0.018), unclear/absent medulla of lymph nodes (95%CI: 2.514~43.989, P=0.001), and rich blood flow (95%CI: 1.952~85.632, P=0.008). The C-index was 0.910, areas under the curve of training cohort and verification cohort were 0.953 and 0.938 respectively, indicating the discriminative ability of this nomogram. The calibration curve showed a favorable compliance between the prediction of the model and actual observations. The clinical decision curve showed this model is clinically useful and had better discriminative ability between 0.25 and 0.9 for the probability of cervical LNs metastasis. Conclusions: We established a good prediction model for cervical lymph node metastasis in head and neck squamous cell carcinoma patients which can provide reference value and auxiliary diagnosis for clinicians in making neck management decisions of HNSCC patients.

New advances into cisplatin resistance in head and neck squamous carcinoma: Mechanisms and therapeutic aspects.

Head and neck squamous cell carcinoma (HNSCC) arises from the interplay of multiple factors, such as smoking, alcohol consumption, and viral infections. Cisplatin-based concurrent radiotherapy regimens represent the first-line treatment for advanced HNSCC cases. However, cisplatin resistance significantly contributes to poor prognoses in HNSCC patients, making it crucial to unravel the underlying mechanisms to overcome this resistance. The complexity of cisplatin resistance in HNSCC involves cancer stem cells, autophagy, epithelial-mesenchymal transition, drug efflux, and metabolic reprogramming. Recent advances in nanodrug delivery systems, combined with existing small-molecule inhibitors and innovative genetic technologies, have opened new therapeutic avenues for addressing cisplatin resistance in HNSCC. This review systematically summarizes research progress from the past five years on cisplatin resistance in HNSCC, with a particular focus on the roles of cancer stem cells and autophagy. Additionally, potential future treatment strategies to overcome cisplatin resistance are discussed, including the targeting of cancer stem cells or autophagy through nanoparticle-based drug delivery systems. Furthermore, the review highlights the prospects and challenges associated with nanodelivery platforms in addressing cisplatin resistance in HNSCC.

ER predicts poor prognosis in male lung squamous cell cancer of stage IIIA-N2 disease after sequential adjuvant chemoradiotherapy.

Introduction: The efficacy of postoperative radiotherapy (PORT) is still unclear in non-small cell lung cancer (NSCLC) patients with pIIIA-N2 disease. Estrogen receptor (ER) was proven significantly associated with poor clinical outcome of male lung squamous cell cancer (LUSC) after R0 resection in our previous study. Methods: A total of 124 male pIIIA-N2 LUSC patients who completed four cycles of adjuvant chemotherapy and PORT after complete resection were eligible for enrollment in this study from October 2016 to December 2021. ER expression was evaluated using immunohistochemistry assay. Results: The median follow-up was 29.7 months. Among 124 patients, 46 (37.1%) were ER positive (stained tumor cells≥1%), and the rest 78 (62.9%) were ER negative. Eleven clinical factors considered in this study were well balanced between ER+ and ER- groups. ER expression significantly predicted a poor prognosis in disease-free survival (DFS, HR=2.507; 95% CI: 1.629-3.857; log-rank p=1.60×10-5). The 3-year DFS rates were 37.8% with ER- vs. 5.7% with ER+, with median DFS 25.9 vs. 12.6 months, respectively. The significant prognostic advantage in ER- patients was also observed in overall survival (OS), local recurrence free survival (LRFS), and distant metastasis free survival (DMFS). The 3-year OS rates were 59.7% with ER- vs. 48.2% with ER+ (HR, 1.859; 95% CI: 1.132-3.053; log-rank p=0.013), the 3-year LRFS rates were 44.1% vs. 15.3% (HR=2.616; 95% CI: 1.685-4.061; log-rank p=8.80×10-6), and the 3-year DMFS rates were 45.3% vs. 31.8% (HR=1.628; 95% CI: 1.019-2.601; log-rank p=0.039). Cox regression analyses indicated that ER status was the only significant factor for DFS (p=2.940×10-5), OS (p=0.014), LRFS (p=1.825×10-5) and DMFS (p=0.041) among other 11 clinical factors. Conclusions: PORT might be more beneficial for ER negative LUSCs in male, and the examination of ER status might be helpful in identifying patients suitable for PORT.

Immunotherapy in SMARCB1 (INI-1)-deficient sinonasal carcinoma: Two case reports.

BACKGROUND: SMARCB1/INI-1 deficient sinonasal carcinoma (SDSC) is a rare subset of sinonasal undifferentiated carcinoma with a poor prognosis. Here, we present two case reports of SDSC patients. We also review the literature on this tumor. This is the first published report of SDSC treatment with immunotherapy. CASE SUMMARY: Here we present two patient cases of SDSC in which initial consultation and diagnosis were complicated but SDSC was ultimately diagnosed. One patient received a traditional treatment of surgery and adjuvant chemoradiotherapy, while the other patient received additional immunotherapy; the prognoses of these two patients differed. We review previous diagnostic literature reports and SDSC treatments and provide a unique perspective on this rare type of tumor. CONCLUSION: SDSC is a rare, diagnostically challenging carcinoma with a consistently poor prognosis, early distant metastases, and frequent recurrence. Timely diagnosis and intervention are critical for treatment, for which the standard of care is surgery followed by adjuvant chemoradiotherapy, though immunotherapy may be an effective new treatment for SDSC.

DNA-modulated single-atom nanozymes with enhanced enzyme-like activity for ultrasensitive detection of dopamine.

Despite the current progress in optimizing and tailoring the performance of nanozymes through structural and synthetic adaptation, there is still a lack of dynamic modulation approaches to alter their catalytic activity. Here, we demonstrate that DNA can act as an auxiliary regulator via a straightforward incubation method with Fe-N-C single-atom nanozymes (SAzymes), causing a leap in the enzyme-like activity of Fe-N-C from moderate to a higher level. The DNA-assisted enhancement is attributed to the increased substrate affinity of Fe-N-C nanozymes through electrostatic attraction between the substrate and DNA. Based on the prepared DNA/Fe-N-C system, colorimetric sensors for dopamine (DA) detection were constructed. Surprisingly, the incorporation of DNA not only enabled the detection of DA in a low concentration range, but also greatly improved the sensitivity with a 436-fold decrease in detection limit. The quantitative determination of DA was achieved in two-segment linear ranges of 0.01-4 µM and 5-100 µM with an ultralow detection limit of 9.56 nM. The DNA/Fe-N-C system shows superior performance compared to the original Fe-N-C system, making it an ideal choice for nanozyme-based biosensors. This simple design approach has paved the way for enhancing nanozyme activity and is expected to serve as a general strategy for optimizing biosensor performance.