Targeted delivery of CEBPA-saRNA for the treatment of pancreatic ductal adenocarcinoma by transferrin receptor aptamer decorated tetrahedral framework nucleic acid.

Pancreatic cancer, predominantly pancreatic ductal adenocarcinoma (PDAC), remains a highly lethal malignancy with limited therapeutic options and a dismal prognosis. By targeting the underlying molecular abnormalities responsible for PDAC development and progression, gene therapy offers a promising strategy to overcome the challenges posed by conventional radiotherapy and chemotherapy. This study sought to explore the therapeutic potential of small activating RNAs (saRNAs) specifically targeting the CCAAT/enhancer-binding protein alpha (CEBPA) gene in PDAC. To overcome the challenges associated with saRNA delivery, tetrahedral framework nucleic acids (tFNAs) were rationally engineered as nanocarriers. These tFNAs were further functionalized with a truncated transferrin receptor aptamer (tTR14) to enhance targeting specificity for PDAC cells. The constructed tFNA-based saRNA formulation demonstrated exceptional stability, efficient saRNA release ability, substantial cellular uptake, biocompatibility, and nontoxicity. In vitro experiments revealed successful intracellular delivery of CEBPA-saRNA utilizing tTR14-decorated tFNA nanocarriers, resulting in significant activation of tumor suppressor genes, namely, CEBPA and its downstream effector P21, leading to notable inhibition of PDAC cell proliferation. Moreover, in a mouse model of PDAC, the tTR14-decorated tFNA-mediated delivery of CEBPA-saRNA effectively upregulated the expression of the CEBPA and P21 genes, consequently suppressing tumor growth. These compelling findings highlight the potential utility of saRNA delivered via a designed tFNA nanocarrier to induce the activation of tumor suppressor genes as an innovative therapeutic approach for PDAC.

Association between anxiety, depression, and symptom burden in patients with advanced colorectal cancer: A multicenter cross-sectional study.

OBJECTIVES: Patients with advanced colorectal cancer (CRC) have multiple concurrent physical and psychological symptoms. This study aimed to explore the relationship between anxiety, depression, and symptom burden in advanced CRC. METHODS: A multicenter cross-sectional study was conducted in 10 cancer centers from geographically and economically diverse sites in China. A total of 454 patients with advanced CRC completed the Hospital Anxiety and Depression Scale and the MD Anderson Symptom Inventory. Multiple regression analysis was applied to explore the relationship between anxiety, depression and symptom burden. RESULTS: About one-third of the patients showed symptoms of anxiety or depression. Patients with anxiety or depression reported significantly higher symptom burden than those without (p < 0.001). Patients with anxiety or depression reported a higher proportion of moderate-to-severe (MS) symptom number than those without (p < 0.001). About 52% of the patients with anxiety or depression reported at least three MS symptoms. The prevalence of MS symptoms was ranging from 7.3% (shortness of breath) to 22% (disturbed sleep), and in patients with anxiety or depression was 2-10 times higher than in those without (p < 0.001). Disease stage (ß = -2.55, p = 0.003), anxiety (ß = 15.33, p < 0.001), and depression (ß = 13.63, p < 0.001) were associated with higher symptom burden. CONCLUSIONS: Anxiety and depression in patients with advanced cancer correlated with higher symptom burden. Findings may lead oncology professionals to pay more attention to unrecognized and untreated psychological symptoms in symptom management for advanced cancer patients.

Development of a prediction model for suicidal ideation in patients with advanced cancer: A multicenter, real-world, pan-cancer study in China.

BACKGROUND: Patients diagnosed with advanced stage cancer face an elevated risk of suicide. We aimed to develop a suicidal ideation (SI) risk prediction model in patients with advanced cancer for early warning of their SI and facilitate suicide prevention in this population. PATIENTS AND METHODS: We consecutively enrolled patients with multiple types of advanced cancers from 10 cancer institutes in China from August 2019 to December 2020. Demographic characteristics, clinicopathological data, and clinical treatment history were extracted from medical records. Symptom burden, psychological status, and SI were assessed using the MD Anderson Symptom Inventory (MDASI), Hospital Anxiety and Depression Scale (HADS), and Patient Health Questionnaire-9 (PHQ-9), respectively. A multivariable logistic regression model was employed to establish the model structure. RESULTS: In total, 2814 participants were included in the final analysis. Nine predictors including age, sex, number of household members, history of previous chemotherapy, history of previous surgery, MDASI score, HADS-A score, HADS-D score, and life satisfaction were retained in the final SI prediction model. The model achieved an area under the curve (AUC) of 0.85 (95% confidential interval: 0.82-0.87), with AUCs ranging from 0.75 to 0.95 across 10 hospitals and higher than 0.83 for all cancer types. CONCLUSION: This study built an easy-to-use, good-performance predictive model for SI. Implementation of this model could facilitate the incorporation of psychosocial support for suicide prevention into the standard care of patients with advanced cancer.

Unraveling the efficacy of verbascoside in thwarting MRSA pathogenicity by targeting sortase A.

In the fight against hospital-acquired infections, the challenge posed by methicillin-resistant Staphylococcus aureus (MRSA) necessitates the development of novel treatment methods. This study focused on undermining the virulence of S. aureus, especially by targeting surface proteins crucial for bacterial adherence and evasion of the immune system. A primary aspect of our approach involves inhibiting sortase A (SrtA), a vital enzyme for attaching microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) to the bacterial cell wall, thereby reducing the pathogenicity of S. aureus. Verbascoside, a phenylethanoid glycoside, was found to be an effective SrtA inhibitor in our research. Advanced fluorescence quenching and molecular docking studies revealed a specific interaction between verbascoside and SrtA, pinpointing the critical active sites involved in this interaction. This molecular interaction significantly impedes the SrtA-mediated attachment of MSCRAMMs, resulting in a substantial reduction in bacterial adhesion, invasion, and biofilm formation. The effectiveness of verbascoside has also been demonstrated in vivo, as shown by its considerable protective effects on pneumonia and Galleria mellonella (wax moth) infection models. These findings underscore the potential of verbascoside as a promising component in new antivirulence therapies for S. aureus infections. By targeting crucial virulence factors such as SrtA, agents such as verbascoside constitute a strategic and potent approach for tackling antibiotic resistance worldwide. KEY POINTS: • Verbascoside inhibits SrtA, reducing S. aureus adhesion and biofilm formation. • In vivo studies demonstrated the efficacy of verbascoside against S. aureus infections. • Targeting virulence factors such as SrtA offers new avenues against antibiotic resistance.

Suicidal ideation in Chinese patients with advanced breast cancer: a multi-center mediation model study.

PURPOSE: The pathways underpinning suicide ideation (SI) and certain physical and psychological factors in patients with advanced breast cancer remain unclear. This study develops and validates a mediation model that delineates the associations between several multidimensional variables and SI in Chinese patients with advanced breast cancer. METHODS: Patients with advanced breast cancer (n = 509) were recruited as study participants from 10 regional cancer centers across China from August 2019 to December 2020. Participants were required to complete five questionnaires using an electronic patient-reported outcomes (ePRO) system: 9 item- Patient Health Questionnaire (PHQ-9), Hospital Anxiety and Depression Scale (HADS), Insomnia Severity Index (ISI), 5-level EQ-5D (EQ-5D-5L), and MD Anderson Symptom Inventory (MDASI). Risk factors for SI were identified using multivariable logistic regression, and inputted into serial multiple mediation models to elucidate the pathways linking the risk factors to SI. RESULTS: SI prevalence was 22.8% (116/509). After adjusting for covariates, depression (odds ratio [OR] = 1.384), emotional distress (OR = 1.107), upset (OR = 0.842), and forgetfulness (OR = 1.236) were identified as significant independent risk factors (all p < 0.05). The ORs indicate that depression and distress have the strongest associations with SI. Health status has a significant indirect effect (OR=-0.044, p = 0.005) and a strong total effect (OR=-0.485, p < 0.001) on SI, mediated by insomnia severity and emotional distress. CONCLUSIONS: There is a high SI prevalence among Chinese patients with advanced breast cancer. Our analysis revealed predictive pathways from poor health to heightened SI, mediated by emotional distress and insomnia. Regular management of distress and insomnia can decrease suicide risk in this vulnerable population.

Physical symptoms and anxiety and depression in older patients with advanced cancer in China: a network analysis.

BACKGROUND: Little is understood about the association between psychosomatic symptoms and advanced cancer among older Chinese patients. METHODS: This secondary analysis was part of a multicenter cross-sectional study based on an electronic patient-reported outcome platform. Patients with advanced cancer were included between August 2019 and December 2020 in China. Participants (over 60 years) completed the MD Anderson Symptom Inventory (MDASI) and Hospital Anxiety and Depression Scale (HADS) to measure symptom burden. Network analysis was also conducted to investigate the network structure, centrality indices (strength, closeness, and betweenness) and network stability. RESULTS: A total of 1022 patients with a mean age of 66 (60-88) years were included; 727 (71.1%) were males, and 295 (28.9%) were females. A total of 64.9% of older patients with advanced cancer had one or more symptoms, and up to 80% had anxiety and depression. The generated network indicated that the physical symptoms, anxiety and depression symptom communities were well connected with each other. Based on an evaluation of the centrality indices, 'distress/feeling upset' (MDASI 5) appears to be a structurally important node in all three networks, and 'I lost interest in my own appearance' (HADS-D4) had the lowest centrality indices. The network stability was relatively high (> 0.7). CONCLUSION: The symptom burden remains high in older patients with advanced cancer in China. Psychosomatic symptoms are highly interactive and often present as comorbidities. This network can be used to provide targeted interventions to optimize symptom management in older patients with advanced cancer in China. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR1900024957), registered on 06/12/2020.

Echinacoside, a promising sortase A inhibitor, combined with vancomycin against murine models of MRSA-induced pneumonia.

Methicillin-resistant Staphylococcus aureus (MRSA) is a pathogenic bacterium responsible for a range of severe infections, such as skin infections, bacteremia, and pneumonia. Due to its antibiotic-resistant nature, current research focuses on targeting its virulence factors. Sortase A (SrtA) is a transpeptidase that anchors surface proteins to the bacterial cell wall and is involved in adhesion and invasion to host cells. Through fluorescence resonance energy transfer (FRET), we identified echinacoside (ECH), a natural polyphenol, as a potential SrtA inhibitor with an IC50 of 38.42 µM in vitro. It was demonstrated that ECH inhibited SrtA-mediated S. aureus fibrinogen binding, surface protein A anchoring, and biofilm formation. The fluorescence quenching assay determined the binding mode of ECH to SrtA and calculated the KA-binding constant of 3.09 × 105 L/mol, demonstrating the direct interaction between the two molecules. Molecular dynamics simulations revealed that ECH-SrtA interactions occurred primarily at the binding sites of A92G, A104G, V168A, G192A, and R197A. Importantly, the combination of ECH and vancomycin offered protection against murine models of MRSA-induced pneumonia. Therefore, ECH may serve as a potential antivirulence agent against S. aureus infections, either alone or in combination with vancomycin.

Loganin reduces diabetic kidney injury by inhibiting the activation of NLRP3 inflammasome-mediated pyroptosis.

Diabetic kidney disease (DKD) is an essential cause of end-stage renal disease. The ongoing inflammatory response in the proximal tubule promotes the progression of DKD. Timely and effective blockade of the inflammatory process to protect the kidney during DKD progression is a proven strategy. The purpose of this study was to investigate the protective effect of loganin on diabetic nephropathy in vivo and in vitro and whether this effect was related to the inhibition of pyroptosis. The results indicated that loganin reduced fasting blood glucose, blood urea nitrogen and serum creatinine concentrations, and alleviated renal pathological changes in DKD mice. In parallel, loganin downregulated the expression of pyroptosis related proteins in the renal tubules of DKD mice and decreased serum levels of interleukin-1beta (IL-1ß) and interleukin-18 (IL-18). Furthermore, in vitro experiments showed that loganin attenuated high glucose-induced HK-2 cell injury by reducing the expression of pyroptosis-related proteins, and cytokine levels were also decreased. These fundings were also confirmed in the polyphyllin VI (PPVI) -induced HK-2 cell pyroptosis model. Loganin reduces high glucose induced HK-2 cells pyroptosis by inhibiting reactive oxygen species (ROS) production and NOD-like receptor protein 3 (NLRP3) inflammasome activation. In conclusion, the inhibition of pyroptosis via inhibition of the NLRP3/Caspase-1/Gasdermin D (GSDMD) pathway might be an essential mechanism for loganin treatment of DKD.

Changes in Patient-Reported Health Status in Advanced Cancer Patients from a Symptom Management Clinic: A Longitudinal Study Conducted in China.

Objectives: The integration of patient-reported health status has been increasingly emphasised for delivering high-quality care to advanced cancer patients. This research is designed to track health status changes over time in Chinese advanced cancer patients to explore the risk factors affecting their health status. Methods: Advanced cancer patients were recruited from Peking University Cancer Hospital. An electronic patient-reported outcome (ePRO) system with validated measurements was used to collect the data. ANOVA, the chi-square test, the nonparametric Kruskal-Wallis H test, and generalized estimating equation (GEE) analysis were used for the data analysis. Results: One hundred and three patients completed a baseline survey (T = 0) and two follow-up surveys (T1 = 14 days, T2 = 28 days). Chi-square test results indicate a significant decrease in the percentage of patients reporting moderate or severe difficulty experienced by patients in terms of mobility, pain/discomfort, and anxiety/depression. However, there is a significant increase in the percentage of patients reporting moderate or severe difficulty in self-care and usual activities. Scores on the visual analogue scale in the EQ-5D-5L instrument (EQ-VAS) are associated with patients' income, and the degree of moderate or severe anxiety/depression is found to be associated with employment status. The GEE results show that pain, loss of appetite, poor walking status effected by symptoms, depression, and anxiety has worsened the health status. Conclusions: The health status of Chinese advanced cancer patients under ePRO follow-up in China significantly improves in the physical and psychological dimensions, accompanied by a decrease in usual activities and self-care. Routine screening and rational supportive care are recommended in oncology for cancer care. Based on the rational application of ePRO, longitudinal studies exploring the potential mechanisms of health status changing would provide more beneficial guidance for improving the quality of life in patients with advanced cancer.

Suicidal ideation in advanced cancer patients without major depressive disorder.

INTRODUCTION: Major depressive disorder (MDD) is associated with an increased risk of suicide and suicide attempt among cancer patients. However, we do not know how many cancer patients without MDD have suicidal ideation (SI). OBJECTIVES: This study aimed to investigate the prevalence, characteristics and correlated factors of SI among advanced cancer patients without MDD. METHODS: This is a multi-center, cross-sectional study based on an electronic patient-reported outcome systems in patients who were diagnosed with advanced lung, liver, gastric, esophageal, colorectal or breast cancer, the top six prevalent cancers in China. A total of 2930 advanced cancer patients were recruited from 10 regional representative cancer centers across China from August 2019 to December 2020. Patients completed the Patient Health Questionnaire-9 regarding if they had thoughts of being better off dead or of hurting themselves in some way in the previous 2 weeks. Patients also completed the symptom inventory and quality of life assessment. Generalized estimating equation model was performed to explore the correlated factors associated with SI among the patients without MDD. RESULTS: The overall prevalence of SI among advanced cancer patients without MDD was 13.1%. The prevalence was higher in older patients. After adjusted for existing conditions, patients with vomiting symptom (p < 0.001), poorer life quality (p < 0.001), and middle education level (p = 0.031) were correlated factors of SI. CONCLUSIONS: The suicidal ideation is common in advanced cancer patients without MDD. Patients with vomiting, poor quality of life, and middle education level should be screened and monitored for suicidal ideation even without MDD. CLINICAL TRIAL INFORMATION: ChiCTR1900024957.

Hibifolin, a Natural Sortase A Inhibitor, Attenuates the Pathogenicity of Staphylococcus aureus and Enhances the Antibacterial Activity of Cefotaxime.

This study aimed to identify hibifolin as a sortase A (SrtA) inhibitor and to determine whether it could attenuate the virulence of methicillin-resistant Staphylococcus aureus (MRSA). We employed a fluorescence resonance energy transfer (FRET) assay to screen a library of natural molecules to identify compounds that inhibit SrtA activity. Fluorescence quenching assay and molecular docking were performed to verify the direct binding interaction between SrtA and hibifolin. The pneumonia model was established using C57BL/6J mice by MRAS nasal administration for evaluating the effect of hibifolin on the pathogenicity of MRSA. Herein, we found that hibifolin was able to inhibit SrtA activity with an IC50 of 31.20 µg/mL. Further assays showed that the capacity of adhesion of bacteria to the host cells and biofilm formation was decreased in hibifolin-treated USA300. Results obtained from fluorescence quenching assay and molecular docking indicated that hibifolin was capable of targeting SrtA protein directly. This interaction was further confirmed by the finding that the inhibition activities of hibifolin on mutant SrtA were substantially reduced after mutating the binding sites (TRP-194, ALA-104, THR-180, ARG-197, ASN-114). The in vivo study showed that hibifolin in combination with cefotaxime protected mice from USA300 infection-induced pneumonia, which was more potent than cefotaxime alone, and no significant cytotoxicity of hibifolin was observed. Taken together, we identified that hibifolin attenuated the pathogenicity of S. aureus by directly targeting SrtA, which may be utilized in the future as adjuvant therapy for S. aureus infections. IMPORTANCE We identified hibifolin as a sortase A (SrtA) inhibitor by screening the natural compounds library, which effectively inhibited the activity of SrtA with an IC50 value of 31.20 µg/mL. Hibifolin attenuated the pathogenic behavior of Staphylococcus aureus, including adhesion, invasion, and biofilm formation. Binding assays showed that hibifolin bound to SrtA protein directly. Hibifolin improved the survival of pneumonia induced by S. aureus USA300 in mice and alleviated the pathological damage. Moreover, hibifolin showed a synergistic antibacterial effect with cefotaxime in USA300-infected mice.

Solamargine Inhibits the Development of Hypopharyngeal Squamous Cell Carcinoma by Decreasing LncRNA HOXA11-As Expression.

Hypopharyngeal squamous cell carcinoma (HSCC) is one of the high mortality cancers with a poor prognosis, which is driving the development of new chemotherapeutic agents. We identified the anticancer effects of a natural compound, solamargine (SM), on FaDU cells and explored its mechanism in terms of non-coding RNA. It was observed that SM inhibited the proliferation of FaDU cells with an IC50 of 5.17 µM. High-throughput sequencing data revealed that lncRNA HOXA11-AS was significantly downregulated in cells co-incubated with SM. Further assays demonstrated that SM-induced downregulation of lncRNA HOXA11-AS showed important implications for apoptosis. Given the properties of HOXA11-AS as a miR-155 sponge, we further confirmed that SM upregulated the expression of miR-155 in FaDU cells. C-Myc is a transcription factor that regulates cell differentiation and apoptosis, whose mRNA is considered to be targeted by miR-155. We showed that c-Myc expression was downregulated by SM and accompanied by increased apoptosis, which was consistent with the findings of transcriptome sequencing. Furthermore, SM administration suppressed xenograft tumor growth in a xenograft mouse model in vivo. In the light of the aforementioned findings, our results suggested that SM downregulated the expression of HOXA11-AS, which in turn induces apoptosis by downregulating c-Myc in FaDU, providing evidence for the anticancer effect of SM on HSCC and uncovering the effect of SM on non-coding RNAs as, at least partly, a mechanism of action.

Implementing Symptom Management Follow-up Using an Electronic Patient-Reported Outcome Platform in Outpatients With Advanced Cancer: Longitudinal Single-Center Prospective Study.

BACKGROUND: Patients with cancer experience multiple symptoms related to cancer, cancer treatment, and the procedures involved in cancer care; however, many patients with pain, depression, and fatigue, especially those outside the hospital, receive inadequate treatment for their symptoms. Using an electronic patient-reported outcome (ePRO) platform to conduct symptom management follow-up in outpatients with advanced cancer could be a novel and potentially effective approach. However, empirical evidence describing in detail the preparation and implementation courses in a real setting is needed. OBJECTIVE: The purpose of this paper was to describe the implementation process and evaluation of an ePRO platform that facilitates symptom management for patients with cancer, share our experiences and the problems we encountered during the process of implementation, and share the solutions we identified for those problems. Moreover, we tested the feasibility, safety, and efficacy of the ePRO platform. METHODS: This was a real-world, ongoing, longitudinal, single-center, prospective study with a total of 7 follow-ups conducted within 4 weeks after the first visit to the symptom management clinic (on days 1, 3, 7, 10, 14, 21, and 28). Participants were encouraged to complete scales for physical symptoms (pain, fatigue, and shortness of breath), cognitive symptoms (memory problems and impaired concentration), and affective symptoms (especially depression and anxiety) during follow-up. The design and function of the ePRO-doctor client and ePRO-patient client, the patient-reported outcome (PRO) scales used in the study, and the strategies to promote symptom tracking have been described. Moreover, the training and evaluation for research assistants have been presented. The efficacy of the ePRO platform was assessed with a comparison of the baseline and 4-week outcomes on the MD Anderson Symptom Inventory. RESULTS: Using the ePRO platform for symptom management follow-ups in advanced cancer patients was associated with a high completion rate (72.7%-86.4%) and a low drop-off rate (23.6%). The ePRO platform sent 293 alert notifications to both patients and doctors, which promoted patient security. The short and sharp PRO tool selection, user-friendly interface, automatic reminder notifications and alerts, and multiple dimensional training were essential components for the preparation and implementation of the ePRO system. The results showed significant improvements in the mean scores of pain, fatigue, and numbness from baseline to day 28 (P=.02, P=.02, and P<.001, respectively). CONCLUSIONS: The use of an ePRO platform for symptom management follow-ups in advanced cancer patients is time-saving, energy-saving, and effective. PRO tool selection, platform design, and training of research assistants are important aspects for implementation. Future research should validate the ePRO platform in a larger randomized controlled study.

Scutellarin potentiates vancomycin against lethal pneumonia caused by methicillin-resistant Staphylococcus aureus through dual inhibition of sortase A and caseinolytic peptidase P.

The strategy of targeting virulence factor has received great attention as it barely develops bacterial resistance. Sortase A (SrtA) and caseinolytic peptidase P (ClpP), as important virulence factors, are considered to be ideal pharmacological targets for methicillin-resistant Staphylococcus aureus (MRSA) infection. Through screening hundreds of compounds, we found scutellarin, a natural flavonoid, markedly inhibited SrtA and ClpP activities of MRSA strain USA300 with an IC50 of 53.64 µg/mL and 107.00 µg/mL, respectively. Subsequently, we observed that scutellarin could inhibit the SrtA-related virulence of MRSA. To demonstrate whether scutellarin directly binding to SrtA, fluorescence quenching assay and molecular docking were performed and the results indicated that scutellarin directly bonded to SrtA molecule with a KA value of 7.58 × 104 L/mol. In addition to direct SrtA inhibition, scutellarin could also inhibit hemolytic activity of S. aureus by inhibiting the expression of Hla in a SrtA-independent manner. Further assays confirmed that scutellarin inhibited hemolysis by inhibiting ClpP. The combination of scutellarin and vancomycin showed enhancing inhibition of USA300 in vitro and in vivo, evidenced by decreased MIC from 3 µg/mL to 0.5 µg/mL and increased survival and improvement of lung pathology in pneumonia mice. Taken together, these results suggest that scutellarin exhibited di-inhibitory effects on SrtA and ClpP of USA300. The di-inhibition of virulence factors by scutellarin combined with vancomycin to prevent MRSA invasion of A549 cells and pneumonia in mice, indicating that scutellarin is expected to be a potential adjuvant against MRSA in the future.

Functions of lncRNA DUXAP8 in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) poses a serious threat to public health due to its significant morbidity and mortality rates. The processes of NSCLC formation and development are quite complex and involve numerous regulatory biomolecules. Long non-coding RNAs (lncRNAs) have attracted attention since they have been found to play critical roles in the tumorigenesis of various human malignancies. Recently, double homeobox A pseudogene 8 (DUXAP8) was identified as an oncogenic lncRNA that is overexpressed in different tumor types. In NSCLC, high expression of DUXAP8 is associated with poor prognosis in patients. The regulatory mechanism underlying the oncogenic effects of DUXAP8 can be divided into transcriptional level and post-transcriptional level. DUXAP8 promotes proliferation, epithelial-mesenchymal transition, and aerobic glycolysis in NSCLC cells. Moreover, DUXAP8 shows potential for the diagnosis and treatment of NSCLC. Herein, we review the molecular mechanisms underlying the DUXAP8-mediated phenotypes of NSCLC as well as its potential clinical applications.

Analysis of Long Noncoding RNAs in Aila-Induced Non-Small Cell Lung Cancer Inhibition.

Non-small cell lung cancer (NSCLC) has the highest morbidity and mortality among all carcinomas. However, it is difficult to diagnose in the early stage, and current therapeutic efficacy is not ideal. Although numerous studies have revealed that Ailanthone (Aila), a natural product, can inhibit multiple cancers by reducing cell proliferation and invasion and inducing apoptosis, the mechanism by which Aila represses NSCLC progression in a time-dependent manner remains unclear. In this study, we observed that most long noncoding RNAs (lncRNAs) were either notably up- or downregulated in NSCLC cells after treatment with Aila. Moreover, alterations in lncRNA expression induced by Aila were crucial for the initiation and metastasis of NSCLC. Furthermore, in our research, expression of DUXAP8 was significantly downregulated in NSCLC cells after treatment with Aila and regulated expression levels of EGR1. In conclusion, our findings demonstrate that Aila is a potent natural suppressor of NSCLC by modulating expression of DUXAP8 and EGR1.

Estimation of associations between 10 common gene polymorphisms and gastric cancer: evidence from a meta-analysis.

AIMS: Associations between polymorphisms in cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4)/mannose-binding lectin (MBL)/interleukin-4 (IL-4)/interleukin-6 (IL-6)/phospholipase C ε-1 (PLCE1) and gastric cancer (GC) were already reported by many studies, yet the conclusions of these studies were somehow controversial. The aim of this meta-analysis was to better clarify associations between polymorphisms in CTLA-4/MBL/IL-4/IL-6/PLCE1 and GC by combing the results of all relevant studies. METHODS: Eligible studies were searched from PubMed, Embase, WOS and CNKI. We used Review Manager to combine the results of individual studies. RESULTS: Forty-three studies were included in this meta-analysis. Combined results revealed that CTLA-4 rs5742909 (dominant comparison: OR: 1.58, 95 % CI: 1.01 to 2.48; allele comparison: OR: 1.69, 95 % CI: 1.12 to 2.56) and PLCE1 rs2274223 (dominant comparison: OR: 0.84, 95 % CI: 0.72 to 0.98; recessive comparison: OR: 1.23, 95 % CI: 1.08 to 1.40; over-dominant comparison: OR: 1.16, 95 % CI: 1.00 to 1.34; allele comparison: OR 0.88, 95 % CI 0.78 to 0.99) polymorphisms were significantly associated with GC in the general population. We also obtained similar significant associations with GC for rs5742909 and rs2274223 polymorphisms in East Asians. Nevertheless, no positive results were observed for the other eight investigated polymorphisms. CONCLUSION: Collectively, this meta-analysis demonstrated that CTLA-4 rs5742909 and PLCE1 rs2274223 polymorphisms may confer susceptibility to GC, especially for East Asians.

Longitudinal study of symptom burden in outpatients with advanced cancers based on electronic Patient-Reported Outcome (ePRO) platform: a single institution, prospective study protocol.

INTRODUCTION: An electronic Patient-Reported Outcome (ePRO) platform is needed for implementing evidence-based symptom management in outpatients with advanced cancer. We describe the overall protocol and the methodology for measuring symptom burden, to provide critical parameters needed to implement symptom management on the ePRO platform. METHODS AND ANALYSIS: The study focusses on patients with advanced lung cancer, stomach cancer, oesophagus cancer, liver cancer, colorectal cancer or breast cancer. The primary outcome is the change of symptom burden. MD Anderson Symptom Inventory, and other PRO instruments (Insomnia Severity Index, Hospital Anxiety and Depression Scale, 9-item Patient Health Questionnaire and EuroQol-5 dimensions-5 levels version) were used. The secondary outcomes include feasibility of using ePRO, symptom-related quality of life, reasons for no improvement of symptoms, defining frequency of PRO assessments and cut-points, items for screening and management of comorbidity and satisfaction with ePRO platform in patients and health providers. After initial outpatient visit for baseline assessment, ePRO system will automatically send follow-up notification seven times over 4 weeks to patients. The characteristics and changing trajectory of symptoms of patients will be described. Parameters for using PROs, such as optimal time points for follow-up and cut-off point for alert will be determined. The feasibility of ePRO platform to track the changes of target symptoms in outpatients will be evaluated. ETHICS AND DISSEMINATION: The study protocol and related documents were approved by the Institutional Research Board (IRB) of Peking University Cancer Hospital on 13 February 2019 (2019YJZ07). The results of this study will be disseminated through academic workshops, peer-reviewed publications and conferences. TRIAL REGISTRATION NUMBER: ChiCTR1900023560.

The Small Glutathione Peroxidase Mimic 5P May Represent a New Strategy for the Treatment of Liver Cancer.

Glutathione peroxidase (GPx) is an antioxidant protein containing selenium. Owing to the limitations of native GPx, considerable efforts have been made to develop GPx mimics. Here, a short 5-mer peptides (5P) was synthesized and characterized using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Enzyme coupled assays were used to evaluate GPx activity. The cell viability and apoptosis of H22 cells were tested, and mice bearing H22 cell-derived tumors were used to determine the effects of 5P on tumor inhibition. In comparison with other enzyme models, 5P provided a suitable substrate with proper catalytic site positions, resulting in enhanced catalytic activity. In our mouse model, 5P showed excellent inhibition of tumor growth and improved immunity. In summary, our findings demonstrated the design and synthesis of the small 5P molecule, which inhibited tumor growth and improved immunity. Notably, 5P could inhibit tumor growth without affecting normal growth. Based on these advantages, the novel mimic may have several clinical applications.

Medical training fails to prepare providers to care for patients with chronic hepatitis B infection.

AIM: To investigate physicians' knowledge including chronic hepatitis B (CHB) diagnosis, screening, and management in various stages of their training. METHODS: A voluntary 20-question survey was administered in Santa Clara County, CA where Asian and Pacific Islanders (API) account for a third of the population. Among the 219 physician participants, there were 63 interns, 60 second-year residents, 26 chief residents and 70 attending physicians. The survey asked questions regarding respondents' demographics, general hepatitis B virus knowledge questions (i.e., transmission, prevalence, diagnostic testing, prevention, and treatment options), as well as, self-reported practice behavior and confidence in knowledge. RESULTS: Knowledge about screening and managing patients with CHB was poor: only 24% identified the correct tests to screen for CHB, 13% knew the next steps for patients testing positive for CHB, 18% knew the high prevalence rate among API, and 31% knew how to screen for liver cancer. Wald chi-square analysis determined the effect of training level on knowledge; in all cases except for knowledge of liver cancer screening (P = 0.0032), knowledge did not significantly increase with length in residency training or completion of residency. CONCLUSION: Even in a high-risk region, both medical school and residency training have not adequately prepared physicians in the screening and management of CHB.