A Novel Multi-Effect Photosensitizer for Tumor Destruction via Multimodal Imaging Guided Synergistic Cancer Phototherapy.

Background: How to ingeniously design multi-effect photosensitizers (PSs), including multimodal imaging and multi-channel therapy, is of great significance for highly spatiotemporal controllable precise phototherapy of malignant tumors. Methods: Herein, a novel multifunctional zinc(II) phthalocyanine-based planar micromolecule amphiphile (ZnPc 1) was successfully designed and synthesized, in which N atom with photoinduced electron transfer effect was introduced to enhance the near-infrared absorbance and nonradiative heat generation. After simple self-assembling into nanoparticles (NPs), ZnPc 1 NPs would exhibit enhanced multimodal imaging properties including fluorescence (FL) imaging (FLI) /photoacoustic (PA) imaging (PAI) /infrared (IR) thermal imaging, which was further used to guide the combined photodynamic therapy (PDT) and photothermal therapy (PTT). Results: It was that under the self-guidance of the multimodal imaging, ZnPc 1 NPs could precisely pinpoint the tumor from the vertical and horizontal boundaries achieving highly efficient and accurate treatment of cancer. Conclusion: Accordingly, the integration of FL/PA/IR multimodal imaging and PDT/PTT synergistic therapy pathway into one ZnPc 1 could provide a blueprint for the next generation of phototherapy, which offered a new paradigm for the integration of diagnosis and treatment in tumor and a promising prospect for precise cancer therapy.

Efficacy and safety of metronomic oral vinorelbine and its combination therapy as second- and later-line regimens for advanced non-small-cell lung cancer: a retrospective analysis.

OBJECTIVE: This retrospective analysis aimed to evaluate the efficacy and adverse reactions of metronomic oral vinorelbine and its combination therapy as second- and later-line regimens for advanced non-small-cell lung cancer (NSCLC). METHODS: NSCLC patients undergoing metronomic oral vinorelbine as second- and later-line regimens in Fujian Cancer Hospital from October 2018 to October 2022 were enrolled, and patients' demographic and clinical characteristics were collected. The efficacy and safety of metronomic oral vinorelbine monotherapy and its combination therapy regimens were compared. RESULTS: Of 57 study subjects, 63.2% received third- and later-line therapy, with median progression-free survival (mPFS) of 4 months, overall response rate (ORR) of 10.5%, and disease control rate (DCR) of 80.7%. The incidence of therapy-related adverse events was 42.1%, and there was only one case presenting grades 3 and 4 adverse events (1.8%). Among driver gene-negative participants, vinorelbine combination therapy regimens achieved longer mPFS (4.6 vs. 1.2 months, hazards ratio = 0.11, P < 0.0001) and comparable toxicity in relative to metronomic oral vinorelbine, and metronomic oral vinorelbine combined with immune checkpoint inhibitors showed the highest response, with mPFS of 5.6 months (95% CI 4.8 to 6.4 months), ORR of 25%, and DCR of 81.3%. Among participants with gradual resistance to osimertinib, continuing osimertinib in combination with metronomic oral vinorelbine achieved mPFS of 6.3 months (95% CI 0.1 to 12.5 months) and DCR of 86.7%. CONCLUSION: Metronomic oral vinorelbine and its combination therapy regimens are favorable options as second- and later-line therapy for advanced NSCLC patients, with acceptable efficacy and tolerable toxicity. Vinorelbine combination therapy regimens show higher efficacy and comparable toxicity in relative to metronomic oral vinorelbine, and metronomic oral vinorelbine may have a synergistic effect with immunotherapy and EGFR-TKI targeted therapy.

[A new cucurbitane glycoside from Picrorhiza scrophulariiflora].

Chemical constituents from the ethanol extract of Picrorhiza scrophulariiflora were isolated and purified by column chromatography. Their structures were identified by HR-MS, 1D and 2D-NMR, and their cytotoxicity was assessed by CCK-8 assay. Four compounds were isolated and identified as follows: 2ß-D-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosterol-5,25-diene-22-one(1), 2ß-D-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5,24-diene-22-one(2), 25-acetoxy-2ß-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5-ene-22-one(3) and 25-acetoxy-2ß-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5,23-(E)-diene-22-one(4). Compound 1 represents a new cucurbitane glycoside. The half inhibitory concentrations of the 4 compounds exceeded 100 µmol·L~(-1) against four tumor cell lines, indicating no significant cytotoxicity.

Analysis of cuproptosis-related genes in prognosis and immune infiltration in grade 4 diffuse gliomas.

Background: Grade 4 diffuse gliomas are highly malignant tumours with poor prognosis. Cuproptosis is a novel form of cell death. Cuproptosis genes are associated with various tumours and affect the prognosis of patients with these tumours. However, the relationship between cuproptosis and grade 4 diffuse gliomas remains unclear. Methods: Differentially expressed genes associated with cuproptosis in grade 4 diffuse gliomas were identified. Second, the prognostic model was established by univariate and multivariate COX regression analyses, and the genes (p < 0.05) were selected for subsequent analysis. The endpoint of the study was death. Single-gene analysis was performed in accordance with the expression levels of SLC31A1. Third, based on the expression levels of SLC31A1, gene function enrichment, drug sensitivity, and immune cell infiltration analyses were performed. Finally, the expression and biological functions of SLC31A1 in grade 4 diffuse gliomas were identified using immunohistochemical staining, qRT-PCR, and related biological experiments. Results: We identified six coproptosis genes in the grade 4 diffuse gliomas dataset (SLC31A1, PDHA1, GLS, FDX1, LIPT1, and ATP7B). The six key cuproptosis genes of grade 4 diffuse gliomas were analysed using univariate COX analysis. Basic patient data, including age, race, year of diagnosis, sex, and treatment, were included in the univariate COX analysis. Then, multivariate COX analysis was performed for the factors with p < 0.2 in the univariate COX analysis. Age, year of diagnosis, and SLC31A1, PDHA1, and FDX1 levels were found to be independent prognostic factors. A nomogram was constructed using these 5 factors. Through experiments, we found that SLC31A1 had a higher expression level in cancer tissue than that near cancer among the three genes, SLC31A1, PDHA1, and FDX1; therefore, we focused on SLC31A1. According on the expression level of SLC31A1, we performed gene function enrichment, drug sensitivity, and immune cell infiltration analyses. Navitoclax was the most sensitive drug. Differential gene function enrichment was observed for metalloendopeptidase activity. SLC31A1 is expressed in dendritic cells, macrophages, neutrophils, and CD8+T cells. SLC31A1 is highly expressed in grade 4 diffuse gliomas, whereas SLC31A1 knockdown significantly reduces cell proliferation and mobility. Conclusions: Age, year of diagnosis, and SLC31A1, PDHA1, and FDX1 expression were independent prognostic factors. A nomogram was constructed based on age, year of diagnosis, and SLC31A1, PDHA1, and FDX1 levels. Through analysis and experimental verification, SLC31A1 was found to affect the prognosis and progression of patients with grade 4 diffuse gliomas and was associated with immune cell infiltration.

Prognostic and immunological implications of glutathione metabolism genes in lung adenocarcinoma: A focus on the core gene SMS and its impact on M2 macrophage polarization.

Glutathione metabolism (GM) is a crucial part of various metabolic and pathophysiological processes. However, its role in lung adenocarcinoma (LUAD) has not been comprehensively studied. This study aimed to explore the potential relationship between GM genes, the prognosis, and the immune microenvironment of patients with LUAD. We constructed a risk signature model containing seven GM genes using Lasso combined Cox regression and validated it using six GEO datasets. Our analysis showed that it is an independent prognostic factor. Functional enrichment analysis revealed that the GM genes were significantly enriched in cell proliferation, cell cycle regulation, and metabolic pathways. Clinical and gene expression data of patients with LUAD were obtained from the TCGA database and patients were divided into high- and low-risk groups. The high-risk patient group had a poor prognosis, reduced immune cell infiltration, poor response to immunotherapy, high sensitivity to chemotherapy, and low sensitivity to targeted therapy. Subsequently, single-cell transcriptome analysis using the GSE143423 and GSE127465 datasets revealed that the core SMS gene was highly enriched in M2 Macrophages. Finally, nine GEO datasets and multiple fluorescence staining revealed a correlation between the SMS expression and M2 macrophage polarization. Our prognostic model in which the core SMS gene is closely related to M2 macrophage polarization is expected to become a novel target and strategy for tumor therapy.

Impact of plasma Epstein-Barr virus DNA in posttreatment nasopharyngeal carcinoma patients after SARS-CoV-2 infection.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is prevalent in southern China. EBV DNA is the most useful biomarker in NPC. However, the value of EBV DNA in posttreatment NPC patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains unclear. METHODS: Sixty-four eligible NPC patients were enrolled between December 2022 and February 2023. Patients who met the following criteria were included: had non-metastatic NPC, completed radical treatment, were first firstly infected with SARS-CoV-2 and their EBV DNA changed from undetectable to detectable. RESULTS: At the end of follow-up, 81.25% (52/64) of patients were confirmed not to relapse with undetectable EBV DNA (no-relapse). In addition, 18.75% (12/64) of patients experienced relapse with consistent detection of EBV DNA (yes-relapse). For all 64 patients, the average time from diagnosis of coronavirus disease 2019 (COVID-19) to detection of detectable EBV DNA was 35.41 days (2 to 139 days). For 52 no-relapse patients, the average time from EBV DNA changing from detectable to undetectable was 63.12 days (6 to 147 days). The levels of EBV DNA were greater in yes-relapse patients than that in no-relapse patients, and the average of EBV DNA levels were 1216 copies/ml and 53.18 copies/ml, respectively. Using 62.3 copies/mL as the threshold, the area under the curve for EBV DNA was 0.88 for distinguishing yes-relapse patients from no-relapse patients. The sensitivity and specificity were 81.97% (95% CI 0.71-0.95) and 86.67% (95% CI 0.70-0.95), respectively. CONCLUSION: For NPC patients infected with SARS-CoV-2, EBV DNA alone is insufficient for monitoring relapse after radical therapy. Long-term follow-up and underlying mechanistic investigations of EBV DNA changes are urgently needed.

Targeting PARP14 with lomitapide suppresses drug resistance through the activation of DRP1-induced mitophagy in multiple myeloma.

Multiple myeloma (MM) is a hematological malignancy that remains incurable, primarily due to the high likelihood of relapse or development of resistance to current treatments. To explore and discover new medications capable of overcoming drug resistance in MM, we conducted cell viability inhibition screens of 1504 FDA-approved drugs. Lomitapide, a cholesterol-lowering agent, was found to exhibit effective inhibition on bortezomib-resistant MM cells in vitro and in vivo. Our data also indicated that lomitapide decreases the permeability of the mitochondrial outer membrane and induces mitochondrial dysfunction in MM cells. Next, lomitapide treatment upregulated DRP1 and PINK1 expression levels, coupled with the mitochondrial translocation of Parkin, leading to MM cell mitophagy. Excessive mitophagy caused mitochondrial damage and dysfunction induced by lomitapide. Meanwhile, PARP14 was identified as a direct target of lomitapide by SPR-HPLC-MS, and we showed that DRP1-induced mitophagy was crucial in the anti-MM activity mediated by PARP14. Furthermore, PARP14 is overexpressed in MM patients, implying that it is a novel therapeutic target in MM. Collectively, our results demonstrate that DRP1-mediated mitophagy induced by PARP14 may be the cause for mitochondrial dysfunction and damage in response to lomitapide treatment.

Plasma Epstein-Barr virus microRNA BART8-3p as a potential biomarker for detection and prognostic prediction in early nasopharyngeal carcinoma.

Epstein-Barr virus (EBV) encoded microRNA BART8-3p (miR-BART8-3p) was significantly associated with the metastasis in nasopharyngeal carcinoma (NPC). To explore the clinical values of plasma miR-BART8-3p in patients with early NPC. We retrospectively analyzed 126 patients with stage I and II NPC. A receiver operating characteristic curve was used to examine the diagnostic performance. Kaplan‒Meier analysis was applied to determine survival differences. Cox regression was used for univariate and multivariate analyses. Compared to healthy subjects, plasma EBV miR-BART8-3p was highly expressed in early NPC patients. The sensitivity, specificity, and area under the curve value of plasma miR-BART8-3p combined with plasma EBV DNA was up to 88.9%, 94.4%, and 0.931. Compared to patients with low expression of miR-BART8-3p, patients with high expression of miR-BART8-3p had poorer 5-year overall survival (OS) (98.9% vs. 91.1%, P = 0.025), locoregional recurrence-free survival (LRRFS) (100% vs. 83.9%, P < 0.001) and distant metastasis-free survival (DMFS) (98.9% vs. 88.0%, P = 0.006). Risk stratification analysis revealed that high-risk patients (with high levels of EBV DNA and miR-BART8-3p) had inferior OS, LRRFS, and DMFS than low-risk patients (without high levels of EBV DNA and miR-BART8-3p). Multivariate analysis verified that the high-risk group was an unfavorable factor for OS, LRRFS, and DMFS. A combination of plasma EBV miR-BART8-3p and EBV DNA could be a potential biomarker for the diagnosis and prognosis in early NPC.

A deep learning-based automatic image quality assessment method for respiratory phase on computed tomography chest images.

Background: Computed tomography (CT) chest scans have become commonly used in clinical diagnosis. Image quality assessment (IQA) for CT images plays an important role in CT examination. It is worth noting that IQA is still a manual and subjective process, and even experienced radiologists make mistakes due to human limitations (fatigue, perceptual biases, and cognitive biases). There are also kinds of biases because of poor consensus among radiologists. Excellent IQA methods can reliably give an objective evaluation result and also reduce the workload of radiologists. This study proposes a deep learning (DL)-based automatic IQA method, to assess whether the image quality of respiratory phase on CT chest images are optimal or not, so that the CT chest images can be used in the patient's physical condition assessment. Methods: This retrospective study analysed 212 patients' chest CT images, with 188 patients allocated to a training set (150 patients), validation set (18 patients), and a test set (20 patients). The remaining 24 patients were used for the observer study. Data augmentation methods were applied to address the problem of insufficient data. The DL-based IQA method combines image selection, tracheal carina segmentation, and bronchial beam detection. To automatically select the CT image containing the tracheal carina, an image selection model was employed. Afterward, the area-based approach and score-based approach were proposed and used to further optimize the tracheal carina segmentation and bronchial beam detection results, respectively. Finally, the score about the image quality of the patient's respiratory phase images given by the DL-based automatic IQA method was compared with the mean opinion score (MOS) given in the observer study, in which four blinded experienced radiologists took part. Results: The DL-based automatic IQA method achieved good performance in assessing the image quality of the respiratory phase images. For the CT sequence of the same patient, the DL-based IQA method had an accuracy of 92% in the assessment score, while the radiologists had an accuracy of 88%. The Kappa value of the assessment score between the DL-based IQA method and radiologists was 0.75, with a sensitivity of 85%, specificity of 91%, positive predictive value (PPV) of 92%, negative predictive value (NPV) of 93%, and accuracy of 88%. Conclusions: This study develops and validates a DL-based automatic IQA method for the respiratory phase on CT chest images. The performance of this method surpassed that of the experienced radiologists on the independent test set used in this study. In clinical practice, it is possible to reduce the workload of radiologists and minimize errors caused by human limitations.

In-depth analysis of prognostic markers associated with the tumor immune microenvironment and genetic mutations in breast cancer based on an NK cell-related risk model.

The natural killer (NK) cell population is unique because it consists of innate lymphocytes capable of detecting and eliminating tumors and virus-infected cells. This research aims to identify a new prognostic signal in breast cancer (BRCA) based on NK-cell-related genes (NKRGs). A variety of sequencing and gene mutation data, along with clinical information, were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Database (GEO). COX regression and least absolute shrinkage and selection operator (LASSO) Cox regression analyses were conducted to identify prognostic genes. In addition, the immune-related analysis was performed to evaluate the association between the immune microenvironment and clusters and risk model. The Edu assay, colony assay, wound healing assay, and transwell assay were performed to evaluate the cell proliferative and invasive abilities. A 4-NKRG-based prognostic model was constructed. Patients in high-risk groups were associated with poorer OS in TCGA and GSE42568. Further, a nomogram was constructed for better prediction of the prognosis of patients with BRCA. Finally, it was discovered that the over-expression of IFNE could suppress the proliferative and invasive abilities of BRCA cells, which might be a promising biomarker for patients with BRCA. As a result, we developed a novel 4-NKRG signal and nomogram capable of predicting the prognosis of patients with BRCA. Additionally, this model was closely associated with the immune microenvironment, which opened new therapeutic avenues for the treatment of cancer in the future.

Identification of SLC12A8 as a valuable prognostic biomarker and immunotherapeutic target by comprehensive pan-cancer analysis.

Solute carrier family 12 member 8 (SLC12A8) is a nicotinamide mononucleotide transporter. Despite emerging evidence supporting its potential involvement in oncogenesis, a systematic pan-cancer analysis of SLC12A8 has not been performed. Thus, this research aimed to explore the prognostic implications of SLC12A8 and assess its possible immune-related functions across 33 different tumor types. And multiple datasets were retrieved from the databases of TCGA, GTEx, Broad Institute CCLE, TISCH, HPA, and GDSC2. After this data acquisition, bioinformatics analyses were conducted to assess the potential involvement of SLC12A8 in cancer pathogenesis. These analyses focused on examining the relationship between SLC12A8 and prognosis, drug sensitivity, chemotherapy response, immune checkpoints (ICPs), immune cell infiltration, and immunotherapy efficacy across various tumor types. Furthermore, experimental methods such as EdU assay, wound healing assay, and transwell assay were conducted to evaluate the cell proliferative and invasive abilities. Finally, the data analysis demonstrated that SLC12A8 was differentially expressed and predicted unfavorable survival outcomes in the majority of the tumor types in the TCGA dataset. Furthermore, a notable upregulation in the expression of SLC12A8 mRNA and protein was observed in cancer tissues compared to normal tissues. Additionally, the SLC12A8 levels demonstrated a strong association with ICPs, chemokines, immune-activating genes, immune-suppressive genes, chemokine receptors, chemotherapy response, and immunotherapy efficacy. In vitro experiments substantiated that knockdown of SLC12A8 restricted the malignant phenotypes of MDA-MB-231 and BT-549 cells. So SLC12A8 holds promise as a cancer biomarker with the capacity to interact with other ICPs to synergistically regulate the immune microenvironment. Thus, the identification of SLC12A8 contributes to the development of novel therapeutic strategies for enhancing the efficacy of immunotherapy.

Three new metabolites from the endophyte Fusarium proliferatum T2-10.

One new cyclopeptide, cyclo-(L-Trp-L-Phe-L-Phe) (1), one new 2-pyridone derivative, fusarone A (3), and one new natural indole derivative, ethyl 3-indoleacetate (4), along with six known compounds were isolated from the endophytic fungus Fusarium proliferatum T2-10. The planar structures of three new compounds were identified by spectral methods including 1D and 2D NMR techniques, and the absolute configuration of compound 1 was elucidated by Marfey-MS method. In addition, all compounds were evaluated for their cytotoxic and antibacterial activities in vitro. Compound 2 showed remarkable cytotoxic activities against two human hepatoma cell lines SMMC7721 and HepG2 with IC50 values of 5.89 ± 0.74 and 6.16 ± 0.52 µM, and showed moderate antibacterial activities against Staphylococcus aureus and Enterococcus faecalis with MIC values of 7.81 and 15.62 µg/mL, respectively.

Enhanced tumor immunotherapy by polyfunctional CD19-CAR T cells engineered to secrete anti-CD47 single-chain variable fragment.

A high recurrence rate of non-Hodgkin's lymphoma (NHL) following chimeric antigen receptor T (CAR T) cell treatment remains a bottleneck, and immunosuppressive tumor microenvironment (TME) compromising CAR T cell efficacy in NHL is the primary cause of relapse. Accordingly, modifying the structure of CAR T cells to attenuate the inhibitory effect of TME thus reducing recurrence rate is a valuable research topic. CD47 has been proved to be a promising therapeutic target and is crucial in regulating macrophage function. Herein, we engineered CD19-CAR T cells to secrete an anti-CD47 single-chain variable fragment (scFv) and validated their function in enhancing antitumor efficacy, regulating T cells differentiation, modifying phagocytosis and polarization of macrophages by in vitro and in vivo researches. The efficacy was analogous or preferable to the combination of CAR T cells and CD47 antibody. Of note, anti-CD47 scFv secreting CAR T cells exert a more potent immune response following specific antigen stimulation compared with parental CAR T cells, characterized by more efficient degranulation and cytokine production with polyfunctionality. Furthermore, locally delivering anti-CD47 by CAR T cells potentially limits toxicities relevant to systemic antibody treatment. Collectively, our research provides a more effective and safer CAR T cell transformation method for enhancing tumor immunotherapy.

Multiple uremic tumoral calcinosis in periarticular soft tissues with chronic renal failure: a case report.

Uremic tumoral calcinosis (UTC) is an uncommon and severe complication of hemodialysis therapy. The most important pathogenic factor involved in UTC is an increase in calcium-phosphorus products. We report here a patient undergoing hemodialysis for renal failure caused by hypertensive nephropathy who presented multiple UTCs in the right shoulder, left elbow and wrist. After surgical excision, they all recurred, with a similar UTC in the left shoulder. By observing the imaging features of various imaging examinations during the whole period of this case, including X-ray, computed tomography (CT), magnetic resonance imaging (MRI), and single-photon emission computed tomography (SPECT), we highlight the importance of imaging for evaluating the state of UTC regarding treatment options, further deepening our understanding of the imaging manifestations for this disease and their clinical significance.

Efficacy of Osimertinib Continuation Plus Metronomic Oral Vinorelbine for EGFRmutant Advanced NSCLC Beyond Limited Progression on Osimertinib.

BACKGROUND: Treatment options for advanced non-small-cell lung cancer (NSCLC) after osimertinib failure are limited, and osimertinib continuation is recommended for selected patients. Metronomic oral vinorelbine is an effective treatment with less toxicity for advanced NSCLC. OBJECTIVE: The objective of the study was to investigate the effects of osimertinib plus metronomic oral vinorelbine on epidermal growth factor receptor (EGFR)-mutant advanced NSCLC beyond limited progression on osimertinib. METHODS: We have reviewed the medical records of 28 patients with EGFR-mutant advanced NSCLC who had received osimertinib continuation plus metronomic oral vinorelbine beyond limited progression on osimertinib. We also evaluated the clinicopathological characteristics of enrolled patients, as well as the efficacy and toxicity of the treatment. RESULTS: After a median follow-up period of 14.1 months, 57.1% (16/28) of cases showed NSCLC progression. The median progression-free survival (PFS) period under osimertinib plus metronomic oral vinorelbine was 9.4 months (95% confidence interval, 1.562-17.238 months), with a disease control rate of 89.3% and objective response rate of 17.9%. PFS did not differ between patients who had previously received osimertinib as first- (n = 16) and second-line (n = 12) therapy (median, 11.4 and 4.7 months, P = 0.391). In addition, the median PFS duration did not differ according to the efficacy (PFS2 ≥ 6 months vs. <6 months) of previous osimertinib monotherapy (median, 5.8 and 9.4 months, P = 0.677). CONCLUSIONS: Osimertinib continuation in conjunction with metronomic oral vinorelbine may enable overcoming TKI resistance and prolong the survival of patients with EGFR-mutant advanced NSCLC beyond limited progression on osimertinib treatment.

Histone acetylation by HBO1 (KAT7) activates Wnt/ß-catenin signaling to promote leukemogenesis in B-cell acute lymphoblastic leukemia.

B-cell acute lymphoblastic leukemia (B-ALL) is an aggressive hematological disorder with a dismal prognosis. The dysregulation of histone acetylation is of great significance in the pathogenesis and progression of B-ALL. Regarded as a fundamental acetyltransferase gene, the role of HBO1 (lysine acetyltransferase 7/KAT7) in B-ALL has not been investigated. Herein, we found that HBO1 expression was elevated in human B-ALL cells and associated with poor disease-free survival. Strikingly, HBO1 knockdown inhibited viability, proliferation, and G1-S cycle progression in B-ALL cells, while provoking apoptosis. In contrast, ectopic overexpression of HBO1 enhanced cell viability and proliferation but inhibited apoptotic activation. The results of in vivo experiments also certificated the inhibitory effect of HBO1 knockdown on tumor growth. Mechanistically, HBO1 acetylated histone H3K14, H4K8, and H4K12, followed by upregulating CTNNB1 expression, resulting in activation of the Wnt/ß-catenin signaling pathway. Moreover, a novel small molecule inhibitor of HBO1, WM-3835, potently inhibited the progression of B-ALL. Our data identified HBO1 as an efficacious regulator of CTNNB1 with therapeutic potential in B-ALL.

Radiofrequency ablation-induced superior vena cava stenosis in a 5-year-old boy with congenital left atrial appendage deformity: a case report and literature review.

Superior vena cava (SVC) stenosis is rarely caused by iatrogenic trauma. Herein, the case of a 5-year-old boy who underwent radiofrequency ablation for paroxysmal supraventricular tachycardia but developed SVC stenosis and related syndromes is reported. Notably, the child exhibited an enlarged left atrial appendage that had partially breached the pericardium. Subsequent interventions involved successful removal of the stenosis, artificial vascular reconstruction, and comprehensive radiofrequency ablation of the entire right atrium, along with ligation of the left atrial appendage under direct vision. As a result, the child experienced relief from symptoms.

Notch1 promotes resistance to cisplatin by up-regulating Ecto-5'-nucleotidase (CD73) in triple-negative breast cancer cells.

Triple-negative breast cancer (TNBC) is an aggressive molecular subtype that due to lack of druggable targets is treated with chemotherapy as standard of care. However, TNBC is prone to chemoresistance and associates with poor survival. The aim of this study was to explore the molecular mechanisms of chemoresistance in TNBC. Firstly, we found that the mRNA expression of Notch1 and CD73 in cisplatin-treated patient material associated with poor clinical outcome. Further, both were upregulated at the protein level in cisplatin-resistant TNBC cell lines. Overexpression of Notch1 intracellular domain (termed N1ICD) increased expression of CD73, whereas knockdown of Notch1 decreased CD73 expression. Using chromatin immunoprecipitation and Dual-Luciferase assay it was identified that N1ICD directly bound the CD73 promoter and activated transcription. Taken together, these findings suggest CD73 as a direct downstream target of Notch1, providing an additional layer to the mechanisms underlying Notch1-mediated cisplatin resistance in TNBC.

Identification of an individualized therapy prognostic signature for head and neck squamous cell carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) are the most common cancers in the head and neck. Therapeutic response-related genes (TRRGs) are closely associated with carcinogenesis and prognosis in HNSCC. However, the clinical value and prognostic significance of TRRGs are still unclear. We aimed to construct a prognostic risk model to predict therapy response and prognosis in TRRGs-defined subgroups of HNSCC. METHODS: The multiomics data and clinical information of HNSCC patients were downloaded from The Cancer Genome Atlas (TCGA). The profile data GSE65858 and GSE67614 chip was downloaded from public functional genomics data Gene Expression Omnibus (GEO). Based on TCGA-HNSC database, patients were divided into a remission group and a non-remission group according to therapy response, and differentially expressed TRRGs between those two groups were screened. Using Cox regression analysis and Least absolute shrinkage and selection operator (LASSO) analysis, candidate TRRGs that can predict the prognosis of HNSCC were identified and used to construct a TRRGs-based signature and a prognostic nomogram. RESULT: A total of 1896 differentially expressed TRRGs were screened, including 1530 upregulated genes and 366 downregulated genes. Then, 206 differently expressed TRRGs that was significantly associated with the survival were chosen using univariate Cox regression analysis. Finally, a total of 20 candidate TRRGs genes were identified by LASSO analysis to establish a signature for risk prediction, and the risk score of each patient was calculated. Patients were divided into a high-risk group (Risk-H) and a low-risk group (Risk-L) based on the risk score. Results showed that the Risk-L patients had better overall survival (OS) than Risk-H patients. Receiver operating characteristic (ROC) curve analysis revealed great predictive performance for 1-, 3-, and 5-year OS in TCGA-HNSC and GEO databases. Moreover, for patients treated with post-operative radiotherapy, Risk-L patients had longer OS and lower recurrence than Risk-H patients. The nomogram involves risk score and other clinical factors had good performance in predicting survival probability. CONCLUSIONS: The proposed risk prognostic signature and Nomogram based on TRRGs are novel promising tools for predicting therapy response and overall survival in HNSCC patients.