Synergistic Effects of Amine Functional Groups and Enriched-Atomic-Iron Sites in Carbon Dots for Industrial-Current-Density CO2 Electroreduction.

Metal phthalocyanine molecules with Me-N4 centers have shown promise in electrocatalytic CO2 reduction (eCO2R) for CO generation. However, iron phthalocyanine (FePc) is an exception, exhibiting negligible eCO2R activity due to a higher CO2 to *COOH conversion barrier and stronger *CO binding energy. Here, amine functional groups onto atomic-Fe-rich carbon dots (Af-Fe-CDs) are introduced via a one-step solvothermal molecule fusion approach. Af-Fe-CDs feature well-defined Fe-N4 active sites and an impressive Fe loading (up to 8.5 wt%). The synergistic effect between Fe-N4 active centers and electron-donating amine functional groups in Af-Fe-CDs yielded outstanding CO2-to-CO conversion performance. At industrial-relevant current densities exceeding 400 mA cm-2 in a flow cell, Af-Fe-CDs achieved >92% selectivity, surpassing state-of-the-art CO2-to-CO electrocatalysts. The in situ electrochemical FTIR characterization combined with theoretical calculations elucidated that Fe-N4 integration with amine functional groups in Af-Fe-CDs significantly reduced energy barriers for *COOH intermediate formation and *CO desorption, enhancing eCO2R efficiency. The proposed synergistic effect offers a promising avenue for high-efficiency catalysts with elevated atomic-metal loadings.

Risk prediction and treatment assessment in glioma patients using SEER database: a prospective observational study.

OBJECTIVES: To use a nomogram to predict the risk of mortality and estimate the impact of current treatment on the prognosis of glioma patients. METHODS: A total of 3798 cases were obtained from the Surveillance Epidemiology and End Results database according to the selection criteria. A nomogram was built on the independent clinical factors screened by the variance inflation factor, univariate analyses and a multivariate Cox regression model. Then, categorising the overall population into high-risk, medium-risk and low-risk groups using nomogram-derived risk scores, to study the impact of treatment on different subgroups' survival outcomes. Furthermore, based on the postmatch cohorts, the influences of treatment on survival outcomes were assessed by the log-rank test. RESULT: Age, race, stage of disease, histological type, histological grade, surgery, radiotherapy and chemotherapy were identified as the independent prognostic factors. A nomogram with good discrimination and consistency was built. Generally, the patients who underwent surgery, radiotherapy and chemotherapy were more likely to achieve better prognosis than those who did not, except for those who received radiotherapy in the low-risk cohort and those who underwent surgery in the high-risk cohort. Furthermore, the isocitrate dehydrogenase 1/2 (IDH1/2) wild-type patients with surgery, radiotherapy or chemotherapy tended to have higher survival probabilities, while some inconsistent results were observed in the IDH mutant-type cohort. CONCLUSION: Surgery, radiotherapy and chemotherapy improved the prognosis, while appropriate selection of topical treatment for the low-risk or high-risk patients deserves further consideration. IDH status gene might be a reliable indicator of therapeutic effectiveness.

Multimodal evaluation of the bloodstream alteration before and after combined revascularization for Moyamoya disease.

Objective: This study aimed to explore the hemodynamic changes before and after anastomosis in patients with Moyamoya disease (MMD) using multiple models. Methods: We prospectively enrolled 42 MMD patients who underwent combined revascularization. Intraoperative FLOW800 was performed before and after anastomosis, and parameters was collected, including maximum intensity, delay time, rise time, slope, blood flow index, and microvascular transit time (MVTT). Additionally, preoperative and postoperative hemodynamic parameters were measured using color Doppler ultrasonography (CDUS), including peak systolic velocity, end-diastolic velocity, resistance index (RI), pulsatility index (PI), and flow volume. Subsequently, the correlation between FLOW800 and CDUS parameters was explored. Results: A total of 42 participants took part with an average age of 46.5 years, consisting of 19 men and 23 women. The analysis of FLOW800 indicated that both the delay time and rise time experienced a substantial decrease in both the recipient artery and vein. Additionally, the MVTT was found to be significantly reduced after the surgery (5.7 ± 2.2 s vs. 4.9 ± 1.6, p = 0.021). However, no statistically significant differences were observed among the other parameters. Similarly, all postoperative parameters in CDUS hemodynamics exhibited significant alterations in comparison to the preoperative values. The correlation analysis between FLOW800 and CDUS parameters indicated a significant association between MVTT and RI and PI, no significant relationships were found among the other parameters in the two groups. Conclusion: The hemodynamic outcomes of the donor and recipient arteries demonstrated significant changes following bypass surgery. The parameter of time appears to be more precise and sensitive in assessing hemodynamics using FLOW800. Multiple evaluations of hemodynamics could offer substantial evidence for perioperative management.

Biosynthesized gold nanoparticles that activate Toll-like receptors and elicit localized light-converting hyperthermia for pleiotropic tumor immunoregulation.

Manipulating the tumor immune contexture towards a more active state can result in better therapeutic outcomes. Here we describe an easily accessible bacterial biomineralization-generated immunomodulator, which we name Ausome (Au + [exo]some). Ausome comprises a gold nanoparticle core covered by bacterial components; the former affords an inducible hyperthermia effect, while the latter mobilizes diverse immune responses. Multiple pattern recognition receptors actively participate in Ausome-initiated immune responses, which lead to the release of a broad spectrum of pro-inflammatory cytokines and the activation of effector immune cells. Upon laser irradiation, tumor-accumulated Ausome elicits a hyperthermic response, which improves tissue blood perfusion and contributes to enhanced infiltration of immunostimulatory modules, including cytokines and effector lymphocytes. This immune-modulating strategy mediated by Ausome ultimately brings about a comprehensive immune reaction and selectively amplifies the effects of local antitumor immunity, enhancing the efficacy of well-established chemo- or immuno-therapies in preclinical cancer models in female mice.

Environmental health risks induced by interaction between phthalic acid esters (PAEs) and biological macromolecules: A review.

As a kind of compounds abused in industry productions, phthalic acid esters (PAEs) cause serious problems in natural environment. PAEs pollution has penetrated into environmental media and human food chain. This review consolidates the updated information to assess the occurrence and distribution of PAEs in each transmission section. It is found that micrograms per kilogram of PAEs are exposed to humans through daily diets. After entering the human body, PAEs often undergo the metabolic process of hydrolysis to monoesters phthalates and conjugation process. Unfortunately, in the process of systemic circulation, PAEs will interact with biological macromolecules in vivo under the action of non-covalent binding, which is also the essence of biological toxicity. The interactions usually operate in the following pathways: (a) competitive binding; (b) functional interference; and (c) abnormal signal transduction. While the non-covalent binding forces mainly contain hydrophobic interaction, hydrogen bond, electrostatic interaction, and π interaction. As a typical endocrine disruptor, the health risks of PAEs often start with endocrine disorder, further leading to metabolic disruption, reproductive disorders, and nerve injury. Besides, genotoxicity and carcinogenicity are also attributed to the interaction between PAEs and genetic materials. This review also pointed out that the molecular mechanism study on biological toxicity of PAEs are deficient. Future toxicological research should pay more attention to the intermolecular interactions. This will be beneficial for evaluating and predicting the biological toxicity of pollutants at molecular scale.

Safety of benzophenone-type UV filters: A mini review focusing on carcinogenicity, reproductive and developmental toxicity.

Consumer products containing benzophenone-type ultraviolet (UV) filters (BPs) have been widely accepted by the public, resulting in the widely existence of various BPs in the human body and environment. In recent years, more and more evidences show that BPs are endocrine disruptors. In view of the continuous exposure risk of BPs and their endocrine disrupting characteristics, the carcinogenicity of BPs and their effects on reproduction and development are of particular concern. However, due to the wide varieties of BPs and the scattered toxicity studies on BPs, people have a limited understanding on the safety of BPs. Therefore, this paper systematically reviews the carcinogenicity, reproductive and developmental toxicity of BPs in order to expand people's knowledge on the health risks of BPs and screen for more safe BPs. Although existing toxicological studies are insufficient, it can be determined that BPs have different potentials for carcinogenicity, and reproductive and developmental toxicity. Among those BPs, 2-hydroxyl-4-methoxyl benzophenone needs to be used with caution due to its adverse effects on cancer cell proliferation and migration, reproductive ability, sex differentiation, neurodevelopment, and so on. It is worth noting that functional group substitutions significantly affect the interaction between BPs and biomolecules such as DNA, cancer cells, and seminal fluid, resulting in different levels of toxicity. In short, it is very necessary to evaluate the carcinogenicity, reproductive and developmental toxicity of BPs, which is of great significance for establishing reasonable BPs content standards in cosmetics, water quality treatment standards for BPs, and so on.

A predictive model for early death in elderly colorectal cancer patients: a population-based study.

Purpose: The purpose of this study is to determine what variables contribute to the early death of elderly colorectal cancer patients (ECRC) and to generate predictive nomograms for this population. Methods: This retrospective cohort analysis included elderly individuals (≥75 years old) diagnosed with colorectal cancer (CRC) from 2010-2015 in the Surveillance, Epidemiology, and End Result databases (SEER) databases. The external validation was conducted using a sample of the Chinese population obtained from the China-Japan Union Hospital of Jilin University. Logistic regression analyses were used to ascertain variables associated with early death and to develop nomograms. The nomograms were internally and externally validated with the help of the receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA). Results: The SEER cohort consisted of 28,111 individuals, while the Chinese cohort contained 315 cases. Logistic regression analyses shown that race, marital status, tumor size, Grade, T stage, N stage, M stage, brain metastasis, liver metastasis, bone metastasis, surgery, chemotherapy, and radiotherapy were independent prognostic factors for all-cause and cancer-specific early death in ECRC patients; The variable of sex was only related to an increased risk of all-cause early death, whereas the factor of insurance status was solely associated with an increased risk of cancer-specific early death. Subsequently, two nomograms were devised to estimate the likelihood of all-cause and cancer-specific early death among individuals with ECRC. The nomograms exhibited robust predictive accuracy for predicting early death of ECRC patients, as evidenced by both internal and external validation. Conclusion: We developed two easy-to-use nomograms to predicting the likelihood of early death in ECRC patients, which would contribute significantly to the improvement of clinical decision-making and the formulation of personalized treatment approaches for this particular population.

Predictive performance of different NTCP techniques for radiation-induced esophagitis in NSCLC patients receiving proton radiotherapy.

This study aimed to compare the predictive performance of different modeling methods in developing normal tissue complication probability (NTCP) models for predicting radiation-induced esophagitis (RE) in non-small cell lung cancer (NSCLC) patients receiving proton radiotherapy. The dataset was composed of 328 NSCLC patients receiving passive-scattering proton therapy and 41.6% of the patients experienced ≥ grade 2 RE. Five modeling methods were used to build NTCP models: standard Lyman-Kutcher-Burman (sLKB), generalized LKB (gLKB), multivariable logistic regression using two variable selection procedures-stepwise forward selection (Stepwise-MLR), and least absolute shrinkage and selection operator (LASSO-MLR), and support vector machines (SVM). Predictive performance was internally validated by a bootstrap approach for each modeling method. The overall performance, discriminative ability, and calibration were assessed using the Negelkerke R2, area under the receiver operator curve (AUC), and Hosmer-Lemeshow test, respectively. The LASSO-MLR model showed the best discriminative ability with an AUC value of 0.799 (95% confidence interval (CI): 0.763-0.854), and the best overall performance with a Negelkerke R2 value of 0.332 (95% CI: 0.266-0.486). Both of the optimism-corrected Negelkerke R2 values of the SVM and sLKB models were 0.301. The optimism-corrected AUC of the gLKB model (0.796) was higher than that of the SVM model (0.784). The sLKB model had the smallest optimism in the model variation and discriminative ability. In the context of classification and probability estimation for predicting the NTCP for radiation-induced esophagitis, the MLR model developed with LASSO provided the best predictive results. The simplest LKB modeling had similar or even better predictive performance than the most complex SVM modeling, and it was least likely to overfit the training data. The advanced machine learning approach might have limited applicability in clinical settings with a relatively small amount of data.

Near infrared light fluorescence imaging-guided biomimetic nanoparticles of extracellular vesicles deliver indocyanine green and paclitaxel for hyperthermia combined with chemotherapy against glioma.

BACKGROUND: We investigated the therapeutic effect of targeting extracellular vesicles (EVs) loaded with indocyanine green (ICG) and paclitaxel (PTX) on glioma. METHODS: Raw264.7 cells were harvested to extract EVs for the preparation of ICG/PTX@RGE-EV by electroporation and click chemistry. We evaluated the success of modifying Neuropilin-1 targeting peptide (RGE) on the EV membrane of ICG/PTX@RGE-EV using super-resolution fluorescence microscopy and flow cytometry. Spectrophotometry and high performance liquid chromatography (HPLC) were implemented for qualitative and quantitative analysis of the ICG and PTX loaded in EVs. Photothermal properties of the vesicles were evaluated by exposing to 808-nm laser light. Western blot analysis, cell counting kit 8 (CCK-8), Calcein Acetoxymethyl Ester/propidium iodide (Calcein-AM/PI) staining, and flow cytometry were utilized for assessing effects of vesicle treatment on cellular behaviors. A nude mouse model bearing glioma was established to test the targeting ability and anti-tumor action of ICG/PTX@RGE-EV in vivo. RESULTS: Under exposure to 808-nm laser light, ICG/PTX@RGE-EV showed good photothermal properties and promotion of PTX release from EVs. ICG/PTX@RGE-EV effectively targeted U251 cells, with activation of the Caspase-3 pathway and elevated apoptosis in U251 cells through chemotherapy combined with hyperthermia. The anti-tumor function of ICG/PTX@RGE-EV was confirmed in the glioma mice via increased accumulation of PTX in the ICG/PTX@RGE-EV group and an increased median survival of 48 days in the ICG/PTX@RGE-EV group as compared to 25 days in the PBS group. CONCLUSION: ICG/PTX@RGE-EV might actively target glioma to repress tumor growth by accelerating glioma cell apoptosis through combined chemotherapy-hyperthermia.

Clinical Features and Prognostic Factors of Pediatric Glioblastoma: Report of 38 Cases.

OBJECTIVE: To better characterize children with glioblastoma, assess outcomes, and identify prognostic factors associated with overall survival and progression-free survival in a relatively large cohort from a single institution. METHODS: For this retrospective review, 38 pediatric patients with a diagnosis of glioblastoma who were treated at The First Affiliated Hospital of Zhengzhou University between January 2015 and January 2020 were selected. Clinical and pathological characteristics, imaging, treatment, and survival variables were compared. RESULTS: There were 24 boys and 14 girls with a median age of 11.5 years (range, 3-18 years). All patients underwent surgery, with gross total resection in 16 and subtotal resection in 22. Of patients, 18 received radiation combined with chemotherapy, 6 received radiation or chemotherapy alone, and 14 did not receive any adjuvant therapy. Contrast-enhanced magnetic resonance imaging of 21 patients showed rim enhancement, while heterogeneous enhancement was shown on imaging of the other 17 patients. Tumors were observed in hemispheric locations in 19 cases and in central locations in the others. Median overall survival was 10.5 months with a median progression-free survival of 6 months. Extent of resection, adjuvant therapy, and original site of tumor were identified as independent predictors for progression-free survival and overall survival on multivariate analysis. There were significant differences in prognosis among different enhancement characteristics; patients with rim-enhancing tumors had a better prognosis. CONCLUSIONS: Pediatric glioblastoma carries a dismal prognosis. Maximum safe resection followed by adjuvant radiation with chemotherapy is considered standard treatment. Better outcomes are associated with hemispheric tumor locations and rim enhancement on magnetic resonance imaging.

Autophagy inhibition enhances anti-pituitary adenoma effect of tetrandrine.

Pituitary adenoma (PA) is a benign intracranial neoplasm originated from pituitary gland. Surgery is the first-line therapy for most of PAs, but lead to unsatisfactory prognosis in some cases. Tetrandrine (Tet) has anticancer effect on some cancers. However, growth inhibition effect on PA is unknown. To elucidate the inhibitory effect of Tet on the growth of PA and its potential mechanisms, we validated the in vitro and in vivo anti-PA effect of Tet and illustrated the cellular and molecular alterations by confocal microscopy observation, flow cytometry, and RNA interference. Tet inhibited PA cell growth in vitro and tumor progression in vivo. Tet induced autophagy and apoptosis in a dose-dependent manner. Low dosage (1.25 µM) of Tet induced PA cell autophagy by down-regulation of MAPK/STAT3 signal. While, higher dosage (5.0 µM) of Tet partially induced PA cell death through caspase-dependent apoptosis. Autophagy inhibitors enhanced Tet-induced caspase activity and apoptotic cell death. These findings demonstrated that Tet has anti-PA effect by inducing autophagy and apoptosis through MAPK/STAT3 signaling pathway attenuation and autophagy inhibition might enhance its anti-PA effect, indicating that Tet (or combined with autophagy inhibitor) is a potential therapeutic regimen for PAs.

HER2 Overexpression and Mismatch Repair Deficiency are Correlated with Malignancy in Colorectal Cancer.

PURPOSE: This study was designed to investigate the correlation between the expression of human epidermal growth factor receptor 2 (HER2), mismatch repair (MMR), and clinicopathological parameters and serum tumor markers in a total of 522 resection samples materials from colorectal cancer (CRC) patients. These data were also used to determine the links between HER2 and MMR expression and prognosis. METHODS: We conducted a retrospective analysis of the clinical data from 522 CRC patients. Immunohistochemistry (IHC) was used to detect HER2 overexpression and MMR deficiency (dMMR) in tumor specimens which were then correlated with various clinicopathological parameters. Prognostic value for HER2 and MMR expression was then evaluated using the data from 105 CRC patients. RESULTS: HER2 overexpression was identified in 35.63% of the samples evaluated in this study, while the total dMMR rate was 12.64%. Expression of HER2 and several, MMR proteins (MLH1, MSH-2, MSH-6, and PMS-2) were then correlated with tumor location. HER2 overexpression is significantly associated with increased depth of tumor invasion, lymph node metastasis, distant metastases, pTNM staging, vascular invasion, nerve infiltration, and serum carcinoembryonic antigen (CEA) levels. HER2 overexpression and dMMR increased with advancing clinical stage. In addition, deficiencies in MLH1 and PMS2 correlated with HER2 overexpression. Finally, the prognostic evaluations revealed that HER2 overexpression was closely associated with poorer clinical outcomes. CONCLUSION: HER2 overexpression is significantly correlated with multiple clinicopathological parameters resulting in a poorer prognosis. Moreover, the prognosis of patients with HER2 overexpression was worse, confirming its significance during disease assessment. In clinical practice, clinicians should pay close attention to the HER2 profile of patients as they may require more extensive clinical intervention. In addition, deficiencies in MLH1, MSH-2, MSH-6, or PMS-2 correlate with tumor location, and MLH1 and PMS2 expression is associated with lymph node metastasis and pTNM stage, suggesting that these may be additional markers in CRC risk assessments.

Short-term outcomes of medium-low rectal cancer treated by taTME and experience of 22 cases.

BACKGROUND AND METHODS: Transanal total mesorectal excision (taTME) is a novel radical resection technique that may address the unsatisfactory functional and oncological outcomes of medium-low rectal cancers. Although its oncological safety remains unclear, taTME has demonstrable value in surgery, complications, and oncological outcomes. Here, we explore the short-term outcomes of rectal cancer after taTME and discuss the surgical experience. Twenty-two patients with medium-low rectal cancer who underwent taTME were retrospectively evaluated. Comprehensive demographic, oncological, and clinical data were analyzed and the perioperative state and postoperative follow-up were evaluated. RESULTS: Over a median follow-up period of 24.4 (4-36) months, local recurrence occurred in one patient at 6 months postsurgery. Fecal incontinence was the most common postoperative complication, and 3-6 months of pelvic-floor-rehabilitation training greatly improved  anal function CONCLUSIONS: taTME achieved satisfactory short-term outcomes in oncological complications and postoperative functions. Accurate intraoperative anatomical location, identification of the rectovesical fascia, and neuroprotection are critical. However, this procedure has a steep learning curve, and large samples and multicenter studies are required to substantiate its effectiveness. DISCUSSION: We retrospectively analyzed the oncological and functional prognosis of 22 patients with colorectal cancer undergoing taTME surgery and preliminarily concluded taTME can be regarded as a safe and feasible treatment.

Risk factors and predictors for tumor site origin in metastatic adenocarcinoma of unknown primary site.

BACKGROUND: Metastatic adenocarcinoma of unknown primary site (MACUP) is the most common cancer of unknown primary site, and shows worse prognosis. Prediction of its tumor site origin attracts a growing attention. However, the site determined by gene expression profiling does not have a significant impact on the survival. Some other special method might need to be found out. METHODS: We reviewed 1011 MACUP patients diagnosed by pathological examination and immunohistochemistry based on the Surveillance, Epidemiology, and End Results (SEER) database during 2010-2016. Kaplan-Meier curves and Cox proportional hazard model were analyzed to compare the survival. Logistic regression models and relevant nomograms were performed to predicting the probability of the primary site which including digestive system, respiratory system, and female breast. The validation and clinical utility of models were measured with relevant statistical approaches. RESULTS: About 324 (32.1%), 299 (29.6%), and 203 (20.1%) of MACUP patients were identified as the primary sites of digestive system, respiratory system, and female breast, respectively. Patients derived from digestive system and respiratory system showed poorer survival than these with other sites. Digestive system was significantly associated with liver (Odds ratio =13.21 [95% confidence interval =8.48-21.02]) or lung (2.36 [1.40-3.97]) metastasis, while respiratory system was linked to brain (11.68 [6.68-21.26]) or lymph node (3.39 [2.26-5.13]) metastasis. Patients identified as female breast were prone to occur bone metastasis (5.85 [3.68-9.45]). Logistic regression nomograms were developed to help clinicians intuitively predict the probabilities of tumor site origin with 0.867, 0.824, and 0.753 of the C-index, respectively. Decision curve analysis and clinical impact curves both revealed the clinical effectiveness. CONCLUSIONS: We profiled different tumor site origin of MACUP patients and established prediction models. These features might be significant for clinicians to improve the probabilities of predicting the primary sites, and to decide subsequent treatment strategy.

Hyperprolactinemia in clinical non-functional pituitary macroadenomas: A STROBE-compliant study.

Hyperprolactinemia is a prevalent endocrine disorder presented in patients with non-functional pituitary adenomas (NFPAs). However, the mechanism involved in hyperprolactinemia in NFPA is not fully illustrated. The current study aims to investigate predictors for hyperprolactinemia in NFPA via analyzing relevant clinical features. Thus, in this study, a cohort of 214 cases with integrated medical records was retrospectively analyzed concerning clinical, pathological, and endocrinological studies before and after surgery.Hyperprolactinemia happened in 93 cases (43.5%). Women (adjust odds ratio [OR] = 3.093; P < .01), age of patients (adjust OR = 0.951; P < .01), and serum free tetraiodothyronine (FT4) level (adjust OR = 0.882; P = .02) were independent predictors for developing preoperative hyperprolactinemia. Tumor size and hypopituitarism had no impact on hyperprolactinemia. During a median follow-up of 43.5 (range, 22-80) months, 83.9% patients with preoperative hyperprolactinemia experienced prolactin (PRL) normalization. Preoperative PRL level (adjusted OR = 1.741, P = .03) was the exclusive predictor for PRL normalization after adjusting for tumor volume, preoperative serum FT4 concentration, and postoperative residual. The PRL normalization rate of patients with lower PRL level (<2.35-fold upper limit of normal range) was 95.2% and decreased to 65.5% for patients with higher PRL level.In conclusion, our results suggest existence of potentially alternative mechanisms underlying hyperprolactinemia in NFPAs, like the discrepancy of sex and age and the negative feedback of FT4. Preoperative PRL is a predictor for postoperative PRL normalization, which is of clinically relevant for postoperative management of NFPAs.

Glioma exosomal microRNA-148a-3p promotes tumor angiogenesis through activating the EGFR/MAPK signaling pathway via inhibiting ERRFI1.

BACKGROUND: Glioma is the most frequent and lethal primary brain malignancy. Amounting evidence has highlighted the importance of exosomal microRNAs (miRNAs or miRs) in this malignancy. This study aimed to investigate the regulatory role of exosomal miR-148a-3p in glioma. METHODS: Bioinformatics analysis was firstly used to predict the target genes of miR-148a-3p. Exosomes were then extracted from normal human astrocytes and glioma cells. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was applied to determine the expression patterns of miR-148a-3p and ERBB receptor feedback inhibitor 1 (ERRFI1). Dual-luciferase reporter gene assay was applied to verify the direct binding between miR-148a-3p and ERRFI1. Cell counting kit-8 and tube formation assays were further conducted to assess the proliferation and angiogenic properties of human umbilical vein endothelial cells (HUVECs) in the co-culture system with exosomes. Lastly, glioma tumor models were established in BALB/c nude mice to study the role of exosomal miR-148a-3p in vivo. RESULTS: miR-148a-3p was highly expressed, while ERRFI1 was poorly expressed in glioma. miR-148a-3p was found to be enriched in glioma cells-derived exosomes and could be transferred to HUVECs via exosomes to promote their proliferation and angiogenesis. ERRFI1 was identified as a target gene of miR-148a-3p. In addition, miR-148a-3p activated the epidermal growth factor receptor (EGFR)/mitogen-activated protein kinase (MAPK) signaling pathway by inhibiting ERRFI1. In the co-culture system, our data demonstrated that glioma cells-derived exosomal miR-148a-3p down-regulated ERRFI1 and activated the EGFR/MAPK signaling pathway, so as to promote cell proliferation and angiogenesis. In vivo experimentation further demonstrated that this mechanism was responsible for the promotive role of exosomal miR-148a-3p in tumorigenesis and angiogenesis. CONCLUSION: Taken together, glioma-derived exosomal miR-148a-3p promoted tumor angiogenesis through activation of the EGFR/MAPK signaling pathway by ERRFI1 inhibition.

Clinical significance and diagnostic value of serum NSE, CEA, CA19-9, CA125 and CA242 levels in colorectal cancer.

The present study investigated the value of combinations of five specific tumor biomarkers for the diagnosis of colorectal cancer (CRC): Neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), cancer antigen (CA)19-9, CA125 and CA242. Associations between these markers and clinicopathological characteristics (including the Tumor-Node-Metastasis stage) were also assessed. Serum levels of the 5 markers were compared between 358 patients with CRC and 298 healthy individuals (CRC and control group, respectively). The NSE concentration of the CRC group was significantly higher compared with the control. Furthermore, patients at clinical stage III+IV exhibited significantly higher NSE levels compared with those at stage I+II. The serum NSE level of N+ patients was significantly higher compared with the N- group, and the NSE level of M1 patients was significantly compared with the M0 group. NSE level was also significantly associated with tumor stage, lymph node metastasis, distant metastasis and hematochezia. The area under the receiver operating characteristic curve (AUC) for NSE in CRC was 0.766, which was significantly higher than that of the other four markers, which ranged from 0.560-0.682. The AUC of NSE, CEA, CA19-9, CA125, CA242 combined was significantly higher compared with any of the markers individually (range, 0.796-0.858). Therefore, serum NSE may be a good clinical tool for the auxiliary diagnosis of colorectal cancer. Besides, the combination of NSE, CEA, CA19-9, CA125 and CA242 was significantly more sensitive compared with NSE alone. Thus, the combined detection of the 5 tumor markers may be more useful for the diagnosis of CRC.

Proton and photon radiosensitization effects of niraparib, a PARP-1/-2 inhibitor, on human head and neck cancer cells.

BACKGROUND: Combining photon or proton radiotherapy with targeted therapy shows promise for head and neck cancer (HNSCC). The poly (adenosine diphosphate [ADP]-ribose) polymerase-1/2 inhibitor niraparib targets DNA damage repair (DDR). We evaluated the effects of niraparib in combination with photons or protons, and its effects on the relative biological effectiveness (RBE) of protons, in human HNSCC cell lines. METHODS: Radiosensitivity was assessed and RBE was calculated with clonogenic survival assays; unrepaired DNA double-strand breaks were evaluated using immunocytochemical analysis of 53BP1 foci. RESULTS: Niraparib reduced colony formation in two of the four cell lines tested (P < .05), enhanced radiosensitivity in all four cell lines, delayed DDR (P < .05), and increased proton vs photon RBE. CONCLUSION: Niraparib enhanced the sensitivity of four HNSCC cell lines to both photons and protons and increased the RBE of protons, possibly by inhibiting DDR. Niraparib may enhance the effectiveness of both photon and proton radiotherapy for patients with HNSCC.

Correlation study between serum neuro-specific enolase and gastric and colorectal cancers.

This study investigated the diagnostic value of preoperative serum neuro-specific enolase (NSE) in gastric cancer (GC) and colorectal cancer (CRC), and the diagnostic viability of combined serum NSE, carcinoembryonic antigen (CEA), cancer antigen (CA)19-9, and CA242.Patients with GC and CRC, and a healthy control group (n = 666 and 266, respectively) were compared with regard to NSE, CEA, CA19-9, and CA242 serum levels. NSE was analyzed for associations with clinicopathological parameters. To estimate the diagnostic potential of NSE, a receiver operating characteristic curve was constructed and the area under the curve (AUCs) was calculated for different patient subgroups.The median serum NSE level of the tumor group (20.925 ng/mL) was significantly higher than that of the control (15.190 ng/mL). Serum NSE was associated with pathological tumor-node-metastasis staging, lymph node metastasis, distant metastasis, vascular invasion, and nerve infiltration. The area under the receiver operating characteristic curve (AUC) for NSE in GC and CRC (0.769) was higher than for the other 3 markers (0.571-0.680). The AUC of the combined markers was higher than for any of the markers individually (0.778-0.810).The AUC for NSE alone suggests it may be an independent tumor marker, and useful for diagnosis of GC and CRC. However, the AUC for combined NSE, CEA, CA19-9, and CA242 was higher and thus potentially more diagnostic value.

Clinical significance of serum neuron-specific enolase in gastric adenocarcinoma.

As a biomarker, neuron-specific enolase (NSE) has been widely recognized in the diagnosis of benign diseases and malignant tumors. This study aimed to investigate the potential diagnostic value of NSE in patients with gastric adenocarcinoma.Serum levels of the NSE were compared between 219 patients with gastric adenocarcinoma and 298 healthy individuals, NSE and clinicopathological parameters were analyzed. Meanwhile, to evaluate the diagnostic capability of NSE, the receiver operating characteristic (ROC), and area under curve (AUC) was calculated.In the present study, the median serum NSE level of the patient group was 20.770 ng/mL, which was higher than that of the control group 15.625 ng/mL (P < .05). Serum NSE level in patients group compared with healthy control was statistically significant (P < .05). Serum NSE level was associated with pathological tumor-node-metastasis (pTNM) staging, lymph node metastasis, and distant metastasis in patients with gastric adenocarcinoma. Besides, the AUC of NSE in gastric adenocarcinoma was 0.742, which was higher than those of the other 3 markers (0.573-0.644). Besides, the AUC of the combined 4 markers was higher than any individual marker (0.778).Serum NSE detecting may have good value for diagnosis of gastric adenocarcinoma. Besides, the combination of NSE, CEA, CA19-9, and CA242 performed even better than any single marker. Thus, the combined detection of the 4 tumor markers may be more useful for the diagnosis of gastric adenocarcinoma.