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Background: Currently, there is no consensus on the treatment of recurrent hepatocellular carcinoma (HCC) after hepatectomy. It is necessary to assess the efficacy and safety of radiofrequency ablation (RFA) combined with iodine-125 seeds implantation (RFA-125I) in the treatment of recurrent HCC. Methods: This study retrospectively analyzed the clinical data of patients with postoperative recurrence of HCC receiving RFA-125I or RFA treatment from January 2013 to January 2023. Both RFA and 125I seeds implantation were performed under dual guidance of ultrasound and CT. Overall survival (OS), progression-free survival (PFS), recurrence, and complications were compared between the two groups. Results: A total of 210 patients with recurrent HCC were enrolled in this study, including 125 patients in the RFA-125I group and 85 patients in the RFA group. The RFA-125I group showed a significantly better survival benefit than RFA group (median OS: 37 months vs. 16 months, P < 0.001; median PFS: 15 months vs. 10 months, P = 0.001). The uni- and multivariate analysis showed that RFA-125I was a protective factor for OS and PFS. There were no procedure-related deaths and no grade 3 or higher adverse events in both groups. Conclusions: RFA combined with 125I seeds implantation under dual guidance of ultrasound and CT is effective and safe for the treatment of HCC patients with recurrence after hepatectomy. [ABSTRACT FROM AUTHOR]

The pharmacological effects of natural product therapy have received sigificant attention, among which terpenoids such as sesquiterpene lactones stand out due to their biological activity and pharmacological potential as anti-tumor drugs. Inula sesquiterpene lactones are a kind of sesquiterpene lactones extracted from Inula species. They have many pharmacological activities such as anti-inflammation, anti-asthma, anti-tumor, neuroprotective and anti-allergic. In recent years, more and more studies have proved that they are important candidate drugs for the treatment of a variety of cancers because of its good anti-tumor activity. In this paper, the structure, structure–activity relationship, antitumor activities, mechanisms and targets of Inula sesquiterpene lactones reported in recent years were reviewed in order to provide clues for the development of novel anticancer drugs. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies worldwide because of rapid progression and high incidence of metastasis or recurrence. Accumulating evidence shows that CD58-expressing tumor cell is implicated in development of various cancers. The present study aimed to reveal the functional significance of CD58 in HCC progression and the underlying mechanisms. Methods: Immunohistochemical staining (IHC), and western blotting were used to detect the expression of CD58 in HCC tissues and cells. The levels of sCD58 (a soluble form of CD58) in the cell supernatants and serum were assessed by ELISA. CCK-8, colony formation, and xenograft assays were used to detect the function of CD58 on proliferation in vitro and in vivo. Transwell assay and sphere formation assay were performed to evaluate the effect of CD58 and sCD58 on metastasis and self-renewal ability of HCC cells. Western blotting, immunofluorescence (IF), TOP/FOP Flash reporter assay, and subcellular fractionation assay were conducted to investigate the molecular regulation between CD58/sCD58 and AKT/GSK-3β/β-catenin axis in HCC cells. Results: CD58 was significantly upregulated in HCC tissues. Elevation of CD58 expression correlated with more satellite foci and vascular invasion, and poorer tumor-free and overall survival in HCC patients. Higher sCD58 levels were in HCC patients' serum compared to healthy individuals. Functionally, CD58 promotes the proliferation of HCC cells in vitro and in vivo. Meanwhile, CD58 and sCD58 induce metastasis, self-renewal and pluripotency in HCC cells in vitro. Mechanistically, CD58 activates the AKT/GSK-3β/β-catenin signaling pathway by increasing phosphorylation of AKT or GSK3β signaling, promoting expression of Wnt/β-catenin target proteins and TCF/LEF-mediated transcriptional activity. Furthermore, AKT activator SC-79 or inhibitor LY294002 abolished the inhibitory effect of CD58 silencing on the proliferation, metastasis, and stemness of HCC cells. Conclusions: Taken together, CD58 promotes HCC progression and metastasis via activating the AKT/GSK-3β/β-catenin pathway, suggesting that CD58 is a novel prognostic biomarker and therapeutic target for HCC. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the present study was to assess the efficacy and safety of transarterial chemoembolization (TACE) combined with atezolizumab and bevacizumab (hereafter, TACE-Atez/Bev) in the treatment of advanced hepatocellular carcinoma (HCC) patients. Materials and methods: Clinical information was collected from consecutive patients with advanced HCC who received treatment with TACE-Atez/Bev or Atez/Bev from April 2021 and October 2022. Treatment response, overall survival (OS), and progression-free survival (PFS) were the primary outcomes of this study. Adverse events (AEs) were the secondary outcomes. Propensity score matching (PSM) analysis was applied to reduce bias between two groups. Results: This study included 62 patients in the TACE-Atez/Bev group and 77 patients in the Atez/Bev group. The objective response rate (ORR) of the TACE-Atez/Bev group and the Atez/Bev group were 38.7% and 16.9% (P=0.004). However, there was no statistical difference in disease control rate between the two groups (69.4% vs 63.6%, P=0.479). Before PSM, the median OS was 14 months in the TACE-Atez/Bev group and 10 months in the Atez/Bev group (P=0.014). The median PFS in the TACE-Atez/Bev and Atez/Bev groups was 10 months and 6 months, respectively (P=0.001). After PSM, the median OS in the two groups was 14 months and 9 months, respectively (P=0.01). The median PFS was 7 months and 6 months, respectively (P=0.036). Multivariable analysis showed that treatment method was independent prognostic factors affecting OS. Conclusions: Compared with Atez/Bev treatment, TACE-Atez/Bev showed better OS, PFS, and ORR for Chinese patients with advanced HCC, with an acceptable safety profile. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies worldwide because of rapid progression and high incidence of metastasis or recurrence. Accumulating evidence shows that CD58-expressing tumor cell is implicated in development of various cancers. The present study aimed to reveal the functional significance of CD58 in HCC progression and the underlying mechanisms. Methods: Immunohistochemical staining (IHC), and western blotting were used to detect the expression of CD58 in HCC tissues and cells. The levels of sCD58 (a soluble form of CD58) in the cell supernatants and serum were assessed by ELISA. CCK-8, colony formation, and xenograft assays were used to detect the function of CD58 on proliferation in vitro and in vivo. Transwell assay and sphere formation assay were performed to evaluate the effect of CD58 and sCD58 on metastasis and self-renewal ability of HCC cells. Western blotting, immunofluorescence (IF), TOP/FOP Flash reporter assay, and subcellular fractionation assay were conducted to investigate the molecular regulation between CD58/sCD58 and AKT/GSK-3β/β-catenin axis in HCC cells. Results: CD58 was significantly upregulated in HCC tissues. Elevation of CD58 expression correlated with more satellite foci and vascular invasion, and poorer tumor-free and overall survival in HCC patients. Higher sCD58 levels were in HCC patients' serum compared to healthy individuals. Functionally, CD58 promotes the proliferation of HCC cells in vitro and in vivo. Meanwhile, CD58 and sCD58 induce metastasis, self-renewal and pluripotency in HCC cells in vitro. Mechanistically, CD58 activates the AKT/GSK-3β/β-catenin signaling pathway by increasing phosphorylation of AKT or GSK3β signaling, promoting expression of Wnt/β-catenin target proteins and TCF/LEF-mediated transcriptional activity. Furthermore, AKT activator SC-79 or inhibitor LY294002 abolished the inhibitory effect of CD58 silencing on the proliferation, metastasis, and stemness of HCC cells. Conclusions: Taken together, CD58 promotes HCC progression and metastasis via activating the AKT/GSK-3β/β-catenin pathway, suggesting that CD58 is a novel prognostic biomarker and therapeutic target for HCC. [ABSTRACT FROM AUTHOR]

Background: Probiotics have been reported to reduce total cholesterol levels in vitro, but more evidence is needed to determine the clinical relevance of this activity. Chinese traditional fermented pickles are a good source of lactic acid bacteria. Therefore, pickle samples were collected for screening lactic acid bacteria based on their ability to survive stresses encountered during gastrointestinal passage and cholesterol reducing potency. Results: Seventy five lactic acid bacteria strains were isolated from 22 fermented pickles. From these bacteria, Lactobacillus plantarum E680, showed the highest acid (85.25%) and bile tolerance (80.79%). It was sensitive to five of the eight antibiotics tested, inhibited the growth of four pathogenic bacteria, and reduced the total cholesterol level by 66.84% in broth culture. In vivo testing using hypercholesterolemic mice fed high-fat emulsion, independent of food intake, found that L. plantarum E680 suppressed body weight gain and reduced total cholesterol and low-density lipoprotein cholesterol levels, with no effect on high-density lipoprotein cholesterol. Conclusions: Chinese traditional fermented pickles are a good source for probiotics. L. plantarum E680, isolated from pickles, was acid and bile tolerant, sensitive to antibiotics, and reduced cholesterol levels both in vitro and in vivo. Based on these results, L. plantarum E680 may have potential as a novel probiotic for the development of cholesterol-lowering functional food. [ABSTRACT FROM AUTHOR]

Background: Secondary metabolites as natural products from endophytic fungi are important sources of pharmaceuticals. However, there is currently little understanding of endophytic fungi at the omics levels about their potential in secondary metabolites. Calcarisporium arbuscula, an endophytic fungus from the fruit bodies of Russulaceae, produces a variety of secondary metabolites with anti-cancer, anti-nematode and antibiotic activities. A comprehensive survey of the genome and transcriptome of this endophytic fungus will help to understand its capacity to biosynthesize secondary metabolites and will lay the foundation for the development of this precious resource. Results: In this study, we reported the high-quality genome sequence of C. arbuscula NRRL 3705 based on Single Molecule Real-Time sequencing technology. The genome of this fungus is over 45 Mb in size, larger than other typical filamentous fungi, and comprises 10,001 predicted genes, encoding at least 762 secretory-proteins, 386 carbohydrate-active enzymes and 177 P450 enzymes. 398 virulence factors and 228 genes related to pathogen-host interactions were also predicted in this fungus. Moreover, 65 secondary metabolite biosynthetic gene clusters were revealed, including the gene cluster for the mycotoxin aurovertins. In addition, several gene clusters were predicted to produce mycotoxins, including aflatoxin, alternariol, destruxin, citrinin and isoflavipucine. Notably, two independent gene clusters were shown that are potentially involved in the biosynthesis of alternariol. Furthermore, RNA-Seq assays showed that only expression of the aurovertin gene cluster is much stronger than expression of the housekeeping genes under laboratory conditions, consistent with the observation that aurovertins are the predominant metabolites. Gene expression of the remaining 64 gene clusters for compound backbone biosynthesis was all lower than expression of the housekeeping genes, which partially explained poor production of other secondary metabolites in this fungus. Conclusions: Our omics data, along with bioinformatics analysis, indicated that C. arbuscula NRRL 3705 contains a large number of biosynthetic gene clusters and has a huge potential to produce a profound number of secondary metabolites. This work also provides the basis for development of endophytic fungi as a new resource of natural products with promising biological activities. [ABSTRACT FROM AUTHOR]

Background: Using texture features derived from contrast-enhanced computed tomography (CT) combined with general imaging features as well as clinical information to predict treatment response and survival in patients with hepatocellular carcinoma (HCC) who received transarterial chemoembolization (TACE) treatment. Methods: From January 2014 to November 2022, 289 patients with HCC who underwent TACE were retrospectively reviewed. Their clinical information was documented. Their treatment-naïve contrast-enhanced CTs were retrieved and reviewed by two independent radiologists. Four general imaging features were evaluated. Texture features were extracted based on the regions of interest (ROIs) drawn on the slice with the largest axial diameter of all lesions using Pyradiomics v3.0.1. After excluding features with low reproducibility and low predictive value, the remaining features were selected for further analyses. The data were randomly divided in a ratio of 8:2 for model training and testing. Random forest classifiers were built to predict patient response to TACE treatment. Random survival forest models were constructed to predict overall survival (OS) and progress-free survival (PFS). Results: We retrospectively evaluated 289 patients (55.4 ± 12.4 years old) with HCC treated with TACE. Twenty features, including 2 clinical features (ALT and AFP levels), 1 general imaging feature (presence or absence of portal vein thrombus) and 17 texture features, were included in model construction. The random forest classifier achieved an area under the curve (AUC) of 0.947 with an accuracy of 89.5% for predicting treatment response. The random survival forest showed good predictive performance with out-of-bag error rate of 0.347 (0.374) and a continuous ranked probability score (CRPS) of 0.170 (0.067) for the prediction of OS (PFS). Conclusions: Random forest algorithm based on texture features combined with general imaging features and clinical information is a robust method for predicting prognosis in patients with HCC treated with TACE, which may help avoid additional examinations and assist in treatment planning. [ABSTRACT FROM AUTHOR]

Background: The association of hepatitis B virus (HBV) DNA levels and liver fibrosis in chronic hepatitis B (CHB) patients with immune-tolerant phase remains unclear. We explored the association between liver fibrosis and HBV DNA levels in HBeAg-positive CHB patients with normal alanine transaminase (ALT) with relatively high HBV DNA. Methods: Six hundred and twenty-two HBeAg-positive CHB patients with normal ALT were included. Patients were divided into three categories: low (6 log10 IU/mL ≤ HBV DNA < 7 log10 IU/mL), moderate (7 log10 IU/mL ≤ HBV DNA < 8 log10 IU/mL), and high (HBV DNA ≥ 8 log10 IU/mL). APRI, FIB-4, transient elastography, or liver biopsy were used to assess liver fibrosis. Results: The median age of patients was 33.0 years and 57.9% patients were male. 18.8%, 52.1%, and 29.1% of patients had low, moderate, and high HBV DNA levels, respectively. The APRI (0.33 vs. 0.26 vs. 0.26, P < 0.001), FIB-4 (1.03 vs. 0.71 vs. 0.68, P < 0.001), and LSM values (7.6 kPa vs. 5.6 kPa vs. 5.5 kPa, P = 0.086) were higher in low HBV DNA group than other two groups. Low HBV DNA group had higher proportions of significant fibrosis (24.8% vs. 9.9% vs. 3.3%, P < 0.001) and cirrhosis (7.7% vs. 2.5% vs. 1.1%, P = 0.004) than moderate and high HBV DNA groups. Moderate (OR 3.095, P = 0.023) and low (OR 4.968, P = 0.003) HBV DNA were independent risk factors of significant fibrosis. Conclusion: Lower HBV DNA level was associated with more severe liver fibrosis in HBeAg-positive CHB patients with ALT. [ABSTRACT FROM AUTHOR]

Background: Glioblastoma (GBM) is considered the most malignant and devastating intracranial tumor without effective treatment. Autophagy, apoptosis, and necrosis, three classically known cell death pathways, can provide novel clinical and immunological insights, which may assist in designing personalized therapeutics. In this study, we developed and validated an effective signature based on autophagy-, apoptosis- and necrosis-related genes for prognostic implications in GBM patients.Methods: Variations in the expression of genes involved in autophagy, apoptosis and necrosis were explored in 518 GBM patients from The Cancer Genome Atlas (TCGA) database. Univariate Cox analysis, least absolute shrinkage and selection operator (LASSO) analysis, and multivariate Cox analysis were performed to construct a combined prognostic signature. Kaplan-Meier survival, receiver-operating characteristic (ROC) curves and Cox regression analyses based on overall survival (OS) and progression-free survival (PFS) were conducted to estimate the independent prognostic performance of the gene signature. The Chinese Glioma Genome Atlas (CGGA) dataset was used for external validation. Finally, we investigated the differences in the immune microenvironment between different prognostic groups and predicted potential compounds targeting each group.Results: A 16-gene cell death index (CDI) was established. Patients were clustered into either the high risk or the low risk groups according to the CDI score, and those in the low risk group presented significantly longer OS and PFS than the high CDI group. ROC curves demonstrated outstanding performance of the gene signature in both the training and validation groups. Furthermore, immune cell analysis identified higher infiltration of neutrophils, macrophages, Treg, T helper cells, and aDCs, and lower infiltration of B cells in the high CDI group. Interestingly, this group also showed lower expression levels of immune checkpoint molecules PDCD1 and CD200, and higher expression levels of PDCD1LG2, CD86, CD48 and IDO1.Conclusion: Our study proposes that the CDI signature can be utilized as a prognostic predictor and may guide patients' selection for preferential use of immunotherapy in GBM. [ABSTRACT FROM AUTHOR]

Background: Glucoside natural products have been showing great medicinal values and potentials. However, the production of glucosides by plant extraction, chemical synthesis, and traditional biotransformation is insufficient to meet the fast-growing pharmaceutical demands. Microbial synthetic biology offers promising strategies for synthesis and diversification of plant glycosides. Results: In this study, the two efficient UDP-glucosyltransferases (UGTs) (UGT85A1 and RrUGT3) of plant origin, that are capable of recognizing phenolic aglycons, are characterized in vitro. The two UGTs show complementary regioselectivity towards the alcoholic and phenolic hydroxyl groups on phenolic substrates. By combining a developed alkylphenol bio-oxidation system and these UGTs, twenty-four phenolic glucosides are enzymatically synthesized from readily accessible alkylphenol substrates. Based on the bio-oxidation and glycosylation systems, a number of microbial cell factories are constructed and applied to biotransformation, giving rise to a variety of plant and plant-like O-glucosides. Remarkably, several unnatural O-glucosides prepared by the two UGTs demonstrate better prolyl endopeptidase inhibitory and/or anti-inflammatory activities than those of the clinically used glucosidic drugs including gastrodin, salidroside and helicid. Furthermore, the two UGTs are also able to catalyze the formation of N- and S-glucosidic bonds to produce N- and S-glucosides. Conclusions: Two highly efficient UGTs, UGT85A1 and RrUGT3, with distinct regioselectivity were characterized in this study. A group of plant and plant-like glucosides were efficiently synthesized by cell-based biotransformation using a developed alkylphenol bio-oxidation system and these two UGTs. Many of the O-glucosides exhibited better PEP inhibitory or anti-inflammatory activities than plant-origin glucoside drugs, showing significant potentials for new glucosidic drug development. [ABSTRACT FROM AUTHOR]

Background: Ferroptosis is associated with the development of many cancers; the molecular features of colorectal carcinoma (CRC) based on ferroptosis-related genes (FRGs) remain unknown. Herein, we aimed to identify ferroptosis-associated molecular subtypes of CRC based on the expression profiles of FRGs. Methods: To explore ferroptosis-associated subtypes of CRC, the gene expression data and clinical information of 682 patients were extracted from The Cancer Genome Atlas and Gene Expression Omnibus databases. We performed consensus clustering to identify robust clusters of patients. Then the distribution of the subtypes in terms of prognosis significance, transcriptome features, immune microenvironment, drug sensitivity, gene mutations, and copy number alternations (CNAs) were evaluated respectively. In addition, we analyzed the correlation of these ferroptosis-associated molecular subtypes with the distribution of conventional clinical indicators in CRC. Results: Four subtypes of CRC (C1, C2, C3, and C4) were identified in which the prognosis, immune cell infiltration, immune score, stromal score, and tumor purity were significantly different between the four subtypes. The C3 subtype had a higher infiltration of B cells, M2 macrophages, resting mast cells, monocytes, natural killer cells, plasma cells, and CD8 T cells. The C3 subtype had the highest immune and stromal scores and the lowest tumor purity. In contrast, the C4 subtype demonstrated the lowest immune and stromal scores and the highest tumor purity. Programmed cell death ligand 1 (PD-L1), an immune checkpoint protein, was differentially expressed in the four subtypes (P < 2e–16) and was significantly correlated with the expression of several FRGs in all subtypes. Significant differences in stem cell indices (P < 0.01) and drug sensitivity (P < 0.01) were observed in the four subtypes. Additionally, gene mutations analysis showed that FRGs such as TP53 had a high frequency of mutation in the four subtypes (49%, 62%, 61%, and 71%, respectively), and the CNAs showed significant difference among all subtypes (P < 0.001). Conclusion: In summary, the ferroptosis-associated subtypes could serve as an independent biomarker for estimating oncological outcomes in patients with CRC. Our results demonstrated that the high level of heterogeneity in the expression of FRGs might be useful for the stratification of patients with CRC and the implementation of individualized therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: The effect of comorbid hypertriglyceridemia (HTG) and abdominal obesity (AO) on acute pancreatitis (AP) remains unclear. The aim of this study was to explore the effect of comorbid HTG and AO and discuss which is the dominant disorder. Methods: In this study, 1219 AP patients who presented with HTG or AO were stratified into four groups: non-HTG + non-AO, HTG + non-AO, non-HTG + AO, and HTG + AO. Results: The 328 patients with comorbid HTG + AO were much younger (42.29 ± 11.77), mainly male (79.57%), and had higher TG levels, larger waist circumferences, and more past medical histories than the patients in the other three non-comorbid groups (P < 0.001). The comorbidity group developed more incidences of persistent organ failure and local complications (P < 0.05). Multivariate logistic regression analysis showed that AO (OR = 3.205, 95% CI = 1.570–6.544), mild HTG (OR = 2.746, 95% CI = 1.125–6.701), and moderate to very severe HTG (OR = 3.649, 95% CI = 1.403–9.493) were independent risk factors for persistent respiratory failure (P < 0.05). Age > 60 years (OR = 1.326, 95% CI = 1.047–1.679), AO (OR = 1.701, 95% CI = 1.308–2.212), diabetes mellitus (OR = 1.551, 95% CI = 1.063–2.261), mild HTG (OR = 1.549, 95% CI = 1.137–2.112), and moderate to very severe HTG (OR = 2.810, 95% CI = 1.926–4.100) were independent risk factors associated with local complications (P < 0.05). Moreover, HTG seemed to be more dangerous than AO. The higher the serum TG level was, the greater the likelihood of persistent respiratory failure and local complications. Conclusions: Comorbid HTG and AO will aggravate the severity and increase the incidence of local complications of AP. HTG may play a dominant role of risk in the condition of comorbidity. Chinese clinical trial registry: ChiCTR2100049566. Registered on 3rd August, 2021. Retrospectively registered, https://www.chictr.org.cn/edit.aspx?pid=127374&htm=4. [ABSTRACT FROM AUTHOR]

Background: Numerous studies have investigated the relationship between COX-2 8473 T > C polymorphism and cancer susceptibility, however, the results remain controversial. Therefore, we carried out the present meta-analysis to obtain a more accurate assessment of this potential association.Methods: In this meta-analysis, 79 case-control studies were included with a total of 38,634 cases and 55,206 controls. We searched all relevant articles published in PubMed, EMBASE, OVID, Web of Science, CNKI and Wanfang Data, till September 29, 2017. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of the association. We performed subgroup analysis according to ethnicity, source of controls, genotyping method and cancer type. Moreover, Trial sequential analysis (TSA) was implemented to decrease the risk of type I error and estimate whether the current evidence of the results was sufficient and conclusive.Results: Overall, our results indicated that 8473 T > C polymorphism was not associated with cancer susceptibility. However, stratified analysis showed that the polymorphism was associated with a statistically significant decreased risk for nasopharyngeal cancer and bladder cancer, but an increased risk for esophageal cancer and skin cancer. Interestingly, TSA demonstrated that the evidence of the result was sufficient in this study.Conclusion: No significant association between COX-2 8473 T > C polymorphism and cancer risk was detected. [ABSTRACT FROM AUTHOR]

Background: Glioblastoma is refractory to conventional treatment, which is combined of surgery, chemotherapy and radiotherapy. Recent studies have shown that glioma initiating cells (GICs) contribute to tumorigenesis and radioresistance. Recently, other studies showed that the GICs use the autophagy as the major pathway to survive. Chloroquine, an anti-malarial chemical, is an autophagic inhibitor which blocks autophagosome fusion with lysosome and slows down lysosomal acidification. The aim of this study was to explore the mechanisms of chloroquine on the radiosensitivity of GICs.Methods: Human glioblastoma cell lines U87 were investigated. MTT and clonogenic survival assay were used to evaluate the cell viability and survival from radiation. The formation of autophagosomes were evaluated by immunofluorescence. Annexin V-FITC/PI staining and flow cytometry were used to quantify the apoptotic cells. The expression levels of proteins were analyzed by Western blot. Cell cycle status was analyzed by checking DNA content after staining with PI. A comet assay was used to assess the DNA repair in the cells. Tumorsphere assay was used for evaluating GICs' renewal ability.Results: Treatment of U87 GICs with chloroquine (10-80 nmol/L) alone inhibited the cell growth in a dose-dependent manner. A dose of chloroquine (20 nmol/L) obviously enhanced the radiation sensitivity of U87 GICs., we found more punctate patterns of microtubule-associated protein LC3 immunoreactivity in radiation-treated U87 GICs, and the level of membrane-bound LC3-II was obviously enhanced. A combination of radiation and chloroquine obviously enhanced the U87 GICs' apoptosis, as demonstrated by the enhanced levels of caspase-3, and reduced level of Bcl-2. In additon, combination of radiation and chloroquine cause G1/G0 cell cycle arrest. what's more, Chloroquine obviously weakened the repair of radiation-induced DNA damage as reflected by the tail length of the comet. Combination treatment of irradiation and chloroquine has synergistic effects on decreasing the GICs' tumorsphere number and diameter.Conclusion: Chloroquine enhances the radiosensitivity of GICs in vitro, suggesting the feasibility of joint treatment with chloroquine with radiation for GBM. [ABSTRACT FROM AUTHOR]