Progress in the treatment of drug-loaded nanomaterials in renal cell carcinoma.

Renal cell carcinoma (RCC) is a common urinary tract tumor that arises from the highly heterogeneous epithelium of the renal tubules. The incidence of kidney cancer is second only to the incidence of bladder cancer, and has shown an upward trend over time. Although surgery is the preferred treatment for localized RCC, treatment decisions should be customized to individual patients considering their overall health status and the risk of developing or worsening chronic kidney disease postoperatively. Anticancer drugs are preferred to prevent perioperative and long-term postoperative complications; however, resistance to chemotherapy remains a considerable problem during the treatment process. To overcome this challenge, nanocarriers have emerged as a promising strategy for targeted drug delivery for cancer treatment. Nanocarriers can transport anticancer agents, achieving several-fold higher cytotoxic concentrations in tumors and minimizing toxicity to the remaining parts of the body. This article reviews the use of nanomaterials, such as liposomes, polymeric nanoparticles, nanocomposites, carbon nanomaterials, nanobubbles, nanomicelles, and mesoporous silica nanoparticles, for RCC treatment, and discusses their advantages and disadvantages.

Nanoparticle-mediated therapeutic management in cholangiocarcinoma drug targeting: Current progress and future prospects.

Patients with cholangiocarcinoma (CCA) often have an unfavorable prognosis because of its insidious nature, low resectability rate, and poor response to anticancer drugs and radiotherapy, which makes early detection and treatment difficult. At present, CCA has a five-year overall survival rate (OS) of only 5%, despite advances in therapies. New an increasing number of evidence suggests that nanoplatforms may play a crucial role in enhancing the pharmacological effects and in reducing both short- and long-term side effects of cancer treatment. This document reviews the advantages and shortcomings of nanoparticles such as liposomes, polymeric nanoparticle，inorganic nanoparticle, nano-metals and nano-alloys, carbon dots, nano-micelles, dendrimer, nano-capsule, bio-Nanomaterials in the diagnosis and treatment of CCA and discuss the current challenges in of nanoplatforms for CCA.

Nanoparticles for Chemoimmunotherapy Against Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) exhibits high recurrence and mortality rates because of the lack of effective treatment targets. Surgery and traditional chemotherapy are the primary treatment options. Immunotherapy shows high potential for treating various cancers but exhibits limited efficacy against TNBC as a monotherapy. Chemoimmunotherapy has broad prospects for applications for cancer treatment conferred through the synergistic immunomodulatory and anti-tumor effects of chemotherapy and immunotherapeutic strategies. However, improving the efficacy of synergistic therapy and reducing the side effects of multiple drugs remain to be the main challenges in chemoimmunotherapy against TNBC. Nanocarriers can target both cancer and immune cells, promote drug accumulation, and show minimal toxicity, making them ideal delivery systems for chemotherapeutic and immunotherapeutic agents. In this review, we introduce the immunomodulatory effects of chemotherapy and combined mechanisms of chemoimmunotherapy, followed by a summary of nanoparticle-mediated chemoimmunotherapeutic strategies used for treating TNBC. This up-to-date synthesis of relevant findings in the field merits contemplation, while considering avenues of investigation to enable advances in the field.

Correction to "Novel long non-coding RNA LINC02532 promotes gastric cancer cell proliferation, migration, and invasion in vitro".

[This corrects the article on p. 91 in vol. 11, PMID: 30788037.].

Current Strategies and Potential Prospects for Nanoparticle-Mediated Treatment of Diabetic Nephropathy.

Diabetic nephropathy (DN), a severe microvascular complication of diabetes mellitus (DM), is the most common form of chronic kidney disease (CKD) and a leading cause of renal failure in end-stage renal disease. No currently available treatment can achieve complete cure. Traditional treatments have many limitations, such as painful subcutaneous insulin injections, nephrotoxicity and hepatotoxicity with oral medication, and poor patient compliance with continual medication intake. Given the known drawbacks, recent research has suggested that nanoparticle-based drug delivery platforms as therapeutics may provide a promising strategy for treating debilitating diseases such as DN in the future. This administration method provides multiple advantages, such as delivering the loaded drug to the precise target of action and enabling early prevention of CKD progression. This article discusses the development of the main currently used nanoplatforms, such as liposomes, polymeric NPs, and inorganic NPs, as well as the prospects and drawbacks of nanoplatform application in the treatment of CKD.

Recent Advances in Nanoplatforms for the Treatment of Osteosarcoma.

Osteosarcoma (OS) is the most common primary bone tumor in children and young people. Traditional surgical excision combined with chemotherapy presents many limitations, such as resistance and systemic side effects of chemotherapy drugs, postoperative recurrence, and bone defects. Given these limitations, novel therapeutic modalities for OS treatment using nanometer-sized platform-based chemotherapeutic delivery have emerged as a promising alternative therapy. This form of therapy offers multiple advantages, such as accurate delivery of the drug to the tumor site and repair of limited bone defects after tumor resection. In this review, we briefly summarize nanoplatforms, including liposomes, polymeric nanoparticles, inorganic nanoparticles, nanomicelles, dendrimers, nanocapsules, and exosomes. The essential shortcomings involved in these nanoplatforms, such as poor stability, immunogenicity, insufficient circulation, and drug leakage are also discussed, and related solutions are briefly proposed. Finally, the application prospects of nanoplatforms in the treatment of OS are discussed.

Recent advances in nanoplatforms for the treatment of neuropathic pain.

STUDY DESIGN: Narrative review. OBJECTIVES: The objective was to summarize the literature on nanoplatforms in spinal cord injury (SCI) and describe their effect in facilitating experiments for SCI. Currently, the primary clinical treatment for neuropathic pain (NP) is drug therapy, but these traditional drugs have many disadvantages, such as high dose, rapid clearance from the circulatory system, off-target side effects, and cytotoxicity. Moreover, the treatment for NP is complicated by the existence of blood-brain barrier. In recent years, nanomedicine has been receiving increased attention; this novel modality could help deliver drugs to treat NP via nanoplatforms, making it a promising alternative therapy. The use of nanoplatforms can enhance pharmaceutic effectiveness by either avoiding rapid clearance from the blood or ensuring adequate concentration in the lesion. METHODS: A literature review was conducted, with a focus on nanoplatforms that have been described in the experimental studies of neuropathic pain. RESULTS: We provide a brief description of the roles of liposomes, polymeric nanoparticles, metal nanoparticles, micelles, and dendrimers in the treatment of NP and discuss the prospective development of the nanoplatform system for NP. CONCLUSION: The emergence of various nanoplatform drug delivery systems can provide an advantageous resource tool for real-time diagnosis and effective treatment of SCI-related NP.

The novel role and function of LINC01235 in metastasis of gastric cancer cells by inducing epithelial-mesenchymal transition.

LncRNAs play a vital role in the tumorigenesis of gastric cancer (GC). This study determined that LINC01235 expression has greater fold changes by analyzing TCGA RNA-Seq data. The qRT-PCR assay confirmed that LINC01235 is significantly over-expressed in GC cells and tissues. Additionally, the overall survival analysis showed that patients with a higher LINC01235 expression had a poorer prognosis than those with a lower LINC01235 expression. Univariate Cox regression analysis indicated that high LINC01235 expression is positively correlated with poor prognosis. Moreover, LINC01235 was an independent poor prognostic marker for GC in multivariate Cox analysis. Invitro assays suggested that LINC01235 knockdown suppresses GC cell migration and invasion. GSEA revealed that high LINC01235 expression is strongly enriched in the EMT pathway. Western blotting results revealed that LINC01235 silencing decreases the expression of EMT-induced proteins. In conclusion, LINC01235 can promote GC cell metastasis via EMT and function as a prognostic biomarker.

A Modified Pathological N Stage Including Status of Tumor Deposits in Colorectal Cancer With Nodal Metastasis.

BACKGROUND: The American Joint Committee on Cancer 8th classification states that colorectal cancer (CRC) is classified as N1c stage when regional lymph nodes (LNs) are negative and tumor deposits (TDs) are positive. However, how to classify TDs when regional LNs are positive remains unclear. The current study aimed to investigate the possibility of combining positive LNs and positive TDs to develop a modified pathological N (mpN) stage for CRC. METHODS: We retrospectively analyzed 9,198 patients with stage III CRC from the Surveillance, Epidemiology, and End Results program who underwent surgery (6,440 in the training cohort and 2,758 the validation cohort). The combination of positive LNs and TD status was defined as mpN stage. Overall survival (OS) according to mpN and pathological N (pN) stages was analyzed by the Kaplan-Meier method. The area under the curves (AUCs) and Akaike's information criterion (AIC) were applied to assess the predictive discrimination abilities and goodness-of-fit of the model. The clinical benefits were measured using decision curve analyses. The validation cohort was used to validate the results. RESULTS: AUC analysis showed that the prognostic discrimination of mpN stage (AUC = 0.628, 95% confidence interval (CI), 0.616-0.640) was better than that of pN stage (AUC = 0.618, 95% CI, 0.606-0.630, p = 0.006) for OS. The AIC demonstrated that mpN stage (AIC = 30,217) also showed superior model-fitting compared with pN stage (AIC = 30,257) and decision curve analyses revealed that mpN stage had better clinical benefits than pN stage. Similar results were found in the validation cohort. CONCLUSIONS: Among patients with CRC and LN metastasis, mpN stage might be superior to pN stage for assessing prognosis and survival, suggesting that TD status should be included in the pN stage.

Identification of a nine-gene prognostic signature for gastric carcinoma using integrated bioinformatics analyses.

BACKGROUND: Gastric carcinoma (GC) is one of the most aggressive primary digestive cancers. It has unsatisfactory therapeutic outcomes and is difficult to diagnose early. AIM: To identify prognostic biomarkers for GC patients using comprehensive bioinformatics analyses. METHODS: Differentially expressed genes (DEGs) were screened using gene expression data from The Cancer Genome Atlas and Gene Expression Omnibus databases for GC. Overlapping DEGs were analyzed using univariate and multivariate Cox regression analyses. A risk score model was then constructed and its prognostic value was validated utilizing an independent Gene Expression Omnibus dataset (GSE15459). Multiple databases were used to analyze each gene in the risk score model. High-risk score-associated pathways and therapeutic small molecule drugs were analyzed and predicted, respectively. RESULTS: A total of 95 overlapping DEGs were found and a nine-gene signature (COL8A1, CTHRC1, COL5A2, AADAC, MAMDC2, SERPINE1, MAOA, COL1A2, and FNDC1) was constructed for the GC prognosis prediction. Receiver operating characteristic curve performance in the training dataset (The Cancer Genome Atlas-stomach adenocarcinoma) and validation dataset (GSE15459) demonstrated a robust prognostic value of the risk score model. Multiple database analyses for each gene provided evidence to further understand the nine-gene signature. Gene set enrichment analysis showed that the high-risk group was enriched in multiple cancer-related pathways. Moreover, several new small molecule drugs for potential treatment of GC were identified. CONCLUSION: The nine-gene signature-derived risk score allows to predict GC prognosis and might prove useful for guiding therapeutic strategies for GC patients.

miR-665 Suppresses the Epithelial-Mesenchymal Transition and Progression of Gastric Cancer by Targeting CRIM1.

BACKGROUND: Gastric cancer (GC) is one of the most common aggressive cancers and is characterized by high mortality. Increasing evidence has shown that microRNA-665 (miRNA-665) serves as inhibiting-miRNA in cancers. However, the role of miR-665 in GC is yet unclear. METHODS: miR-665 was first analyzed using bioinformatics. Subsequent quantitative real-time PCR was used to detect miR-665 expression levels in different GC cell lines and tissues. The function of miR-665 in GC cells was determined via Cell Counting Kit 8, colony formation, wound healing, and transwell assays. Furthermore, Western blotting was utilized to measure the expression level of epithelial-mesenchymal transition (EMT)-related proteins. The target prediction and luciferase reporter assays were performed to confirm the binding between miR-665 and 3'-UTR of the CRIM1 gene. In addition, rescue assays were used to determine whether CRIM1 upregulation abolished the inhibitory effect of miR-665. RESULTS: The expression of miR-665 was significantly decreased in GC patients and GC cell lines. Clinical and pathological analyses showed that the low expression of miR-665 was significantly associated with high TNM stage (P = 0.007), distant metastasis (P = 0.031), and poor differentiation (P = 0.029). Endogenic mimics of miR-665 remarkably suppressed GC cell proliferation, migration, invasion, and EMT in in vitro experiments. Inhibition of miR-665 expression induced the opposite effects. The results of the bioinformatics analysis and dual-luciferase assay showed that miR-665 targeted the 3'-UTR of the CRIM1 gene. Rescue assays revealed that overexpression of CRIM1 attenuated the inhibitory effects of miR-665 in GC progression and EMT. CONCLUSION: The overall study results demonstrated that miR-665 inhibits tumor progression and EMT in GC by targeting CRIM1, indicating that miR-665 might be a potential therapeutic target in the treatment of GC patients.

The comprehensive upstream transcription and downstream targeting regulation network of miRNAs reveal potential diagnostic roles in gastric cancer.

Evidence has shown that miRNAs can be regulated by multiple mechanisms and can participate in tumorigenesis and progression through binding to 3'-UTRs of target mRNAs. The present study identified differentially expressed miRNAs, mRNAs, and TFs by analyzing miRNA-Seq and mRNA-Seq data to construct a TFs/miRNAs/mRNAs regulation network for GC. We found five miRNAs (miR-18a-5p, miR-21-5p, miR-96-5p, miR-182-5p, and miR-196b-5p) that were significantly overexpressed in GC tissues. Clinical analyses indicated that higher miR-21-5p expression was associated with T3 + T4 and stage III + IV. The expression of miR-96-5p, miR-182-5p, and miR-196b-5p were positively correlated with the patients' ages. The five miRNAs had diagnostic efficacy in distinguishing GC from normal tissues. The gene interaction network showed that the five miRNAs were transcriptionally regulated by 11 TFs and negatively regulated 53 mRNA expressions through binding to the 3'-UTRs. Biological pathway analysis suggested that these TFs and target genes were involved in the p53 pathway, epithelial-to-mesenchymal transition, ErbB receptor, mTOR, VEGF, and VEGFR signaling networks. KEGG pathway analysis indicated that these genes were enriched in some cancer-associated pathways, including in GC. The five miRNAs may act as potential diagnostic markers and the TFs/miRNAs/mRNAs network could suggest a regulation mechanism of miRNAs.

Effects of epidural combined with general anesthesia versus general anesthesia alone in gastric cancer surgery: a propensity score matching analysis.

BACKGROUND: This study was conducted retrospectively to investigate the survival of patients undergoing gastric cancer surgery with epidural combined with general anesthesia (EGA) and general anesthesia alone (GA). METHODS: We retrospectively analyzed 596 patients with gastric cancer who were scheduled for radical resection. Propensity score matching was performed at a 1:1 ratio between GA (n=97) and EGA (n=97) to reduce selection bias. Univariate and multivariate analyses were used to identify factors significantly correlated with recurrence and/or metastasis and prognosis. The 5-year overall survival rates of patients receiving EGA and GA alone were compared. RESULTS: After the propensity scores were matched, there were 97 patients who underwent EGA and 97 patients who underwent GA. For the entire population, reconstruction type, pN stage, and complications were significantly correlated with prognosis based on multivariate analyses. For patients with a recurrence and/or metastasis, lymphadenectomy and pN stage were shown to be independent prognostic factors by multivariate analysis. CONCLUSIONS: In summary, patients might benefit from EGA as a result of better analgesic and anti-inflammatory effects, fewer postoperative complications, higher safety, and a lower rate of metastasis and recurrence is conducive to postoperative recovery in patients with gastric cancer.

Novel Nomograms Individually Predicting Overall Survival of Non-metastatic Colon Cancer Patients.

Background: This study aimed to develop an effective prognostic nomogram for predicting non-metastatic colon cancer. Methods: The Surveillance, Epidemiology, and End Results program was utilized to analyze patients who underwent surgical therapy (25,350 for training, 10,860 for validation). Nomograms were created depending upon multivariate analysis in the training cohort and were compared to current American Joint Committee on Cancer (AJCC) classifications. Areas under the receiver-operating characteristic curves (AUCs), Akaike's information criterions (AICs), and calibration curves were used. The clinical benefit was measured using decision curve analyses (DCAs). The validation cohort was used to validate the results. Results: Nomogram 1 included age, gender, histological grade, T stage, number of retrieved lymph nodes, tumor size, and N stage. Nomogram 2 included age, gender, histological grade, T stage, number of retrieved lymph nodes, tumor size, and number of positive lymph nodes. The prognostic discrimination of nomogram 1 (AUC, 0.729, 95% CI, 0.723-0.736) was better than that of nomogram 2 (AUC, 0.704, 95% CI, 0.698-0.710, p < 0.001) in five-year overall survival in the training cohort. Nomogram 1 (AIC, 137,319) also showed superior model-fitting compared to nomogram 2 (AIC, 137,453). Similarity, nomogram 1 was better than the AJCC 6th and 8th TNM classifications. DCA revealed that nomogram 1 had a superior net benefit than other models. These findings were validated using the validation cohort. Conclusions: The proposed nomogram 1 was a better prognostic prediction model with better discrimination and superior model-fitting for patients with non-metastatic colon cancer, which might prove to be clinically helpful.

A Novel Three-miRNA Signature Identified Using Bioinformatics Predicts Survival in Esophageal Carcinoma.

OBJECTIVE: We identified differentially expressed microRNAs (DEMs) between esophageal carcinoma (ESCA) tissues and normal esophageal tissues. We then constructed a novel three-miRNA signature to predict the prognosis of ESCA patients using bioinformatics analysis. Materials and Methods. We combined two microarray profiling datasets from the Gene Expression Omnibus (GEO) database and RNA-seq datasets from the Cancer Genome Atlas (TCGA) database to analyze DEMs in ESCA. The clinical data from 168 ESCA patients were selected from the TCGA database to assess the prognostic role of the DEMs. The TargetScan, miRDB, miRWalk, and DIANA websites were used to predict the miRNA target genes. Functional enrichment analysis was conducted using the Database for Annotation, Visualization, and Integrated Discovery (David), and protein-protein interaction (PPI) networks were obtained using the Search Tool for the Retrieval of Interacting Genes database (STRING). RESULTS: With cut-off criteria of P < 0.05 and |log2FC| > 1.0, 33 overlapping DEMs, including 27 upregulated and 6 downregulated miRNAs, were identified from GEO microarray datasets and TCGA RNA-seq count datasets. The Kaplan-Meier survival analysis indicated that a three-miRNA signature (miR-1301-3p, miR-431-5p, and miR-769-5p) was significantly associated with the overall survival of ESCA patients. The results of univariate and multivariate Cox regression analysis showed that the three-miRNA signature was a potential prognostic factor in ESCA. Furthermore, the gene functional enrichment analysis revealed that the target genes of the three miRNAs participate in various cancer-related pathways, including viral carcinogenesis, forkhead box O (FoxO), vascular endothelial growth factor (VEGF), human epidermal growth factor receptor 2 (ErbB2), and mammalian target of rapamycin (mTOR) signaling pathways. In the PPI network, three target genes (MAPK1, RB1, and CLTC) with a high degree of connectivity were selected as hub genes. CONCLUSIONS: Our results revealed that a three-miRNA signature (miR-1301-3p, miR-431-5p, and miR-769-5p) is a potential novel prognostic biomarker for ESCA.

Novel long non-coding RNA LINC02532 promotes gastric cancer cell proliferation, migration, and invasion in vitro.

BACKGROUND: Long non-coding RNAs (lncRNAs) are a kind of single-stranded RNA of more than 200 nucleotides in length and have no protein-coding function. Amounting studies have indicated that lncRNAs could play a vital role in the initiation and development of cancers, including gastric cancer (GC). Considering the crucial functions of lncRNAs, the identification and exploration of novel lncRNAs in GC is necessary. AIM: To explore the role of novel lncRNA LINC02532 in GC. METHODS: The upregulated LINC02532 was identified by processing the GC RNA-Seq data from The Cancer Genome Atlas. The qRT-PCR assay was performed to confirm the expression levels in GC cell lines and tissues. Cell proliferation, migration, and invasion were evaluated by the cell counting kit-8, colony formation, wound healing, and Transwell assays. The miRNAs downregulated in GC and sponged by LINC02532 were identified from and predicted by the data from the Firehose and RNA22 software programs, respectively. The miRNA downstream target genes were obtained from the TargetScan, miRDB, and DIANA online tools. Gene functional enrichment analysis was carried out using the Database for Annotation, Visualization, and Integrated Discovery software in the categories of cellular components, biological processes, molecular functions, and KEGG pathways. RESULTS: The qRT-PCR assay demonstrated that the LINC02532 expression level was significantly upregulated in the GC cell lines and 52 paired tissues. Kaplan-Meier survival analysis based on The Cancer Genome Atlas data showed that patients with higher LINC02532 expression had poorer prognosis than those with lower LINC02532 expression. The correlation analysis between expression and clinicopathological features revealed that high expression of LINC02532 was associated with a high TNM stage (P = 0.008) and poor differentiation grade (P = 0.023). Functional experiments showed that LINC02532 promoted GC cell proliferation, migration, and invasion. According to the bioinformatics analysis, LINC02532 may act as a ceRNA by sponging downregulated miR-129-5p and miR-490-5p. Target genes of the two miRNAs were selected for further functional enrichment analysis. Importantly, KEGG pathway analysis showed that the genes were mainly involved in transcriptional misregulation in cancer, cell cycle, and TGF-beta, mTOR, and p53 signaling pathways. CONCLUSION: The present study suggested that LINC02532 acted as an oncogene in GC and may be a promising target for therapy and prognosis management of GC.

KRT15, INHBA, MATN3, and AGT are aberrantly methylated and differentially expressed in gastric cancer and associated with prognosis.

AIM: The present study aims to identify aberrantly methylated and differentially expressed genes (DEGs) in gastric cancer (GC) and explore their potential role in the carcinogenesis and development of GC. METHODS: The original RNA-Seq, clinical information and Illumina Human Methylation 27 Chip data associated with GC were downloaded from The Cancer Genome Atlas (TCGA) database using the gdc-client tool. The DEGs and aberrantly methylated genes (AMGs) were screened with edgeR and limma package in R, respectively. The cut-off criteria for DEG identification were P < 0.05 and fold change (FC) >2.0, and for AMG identification were P < 0.05 and |t|>2.0. Genes which were both DEGs and AMGs were considered to be regulated by aberrant DNA methylation in GC. The common genes were used for further functional enrichment analysis in the categories of cellular component, molecular function, biological process and biological pathway. RESULTS: In total 465 genes including 336 down-regulated genes with hyper-methylation (DGs-Hyper) and 129 up-regulated genes with hypo-methylation (UGs-Hypo) were identified. Cellular component analysis showed that these genes were mainly expressed in the cytoplasm and plasma membrane. Molecular function and biological process analysis indicated that the genes primarily participate in cell communication, signal transduction, cell growth/maintenance and function as transcription factors, receptor, cell adhesion molecules, and transmembrane receptor protein tyrosine kinases. Biological pathway analysis revealed that the genes are involved in some crucial pathways including epithelial-to-mesenchymal transition, IL3-mediated signaling, mTOR signaling, VEGF/VEGFR and c-Met signaling. KRT15, INHBA, MATN3, and AGT are significantly associated with the prognosis of GC patients. CONCLUSION: Our study identified several DEGs regulated by aberrant DNA methylation in GC. The mechanism of DNA methylation in the carcinogenesis and development of GC could be further explored in these genes, especially KRT15, INHBA, MATN3, and AGT.

Downregulation of microRNA-376a in Gastric Cancer and Association with Poor Prognosis.

BACKGROUND/AIMS: MicroRNAs have a significant role in the tumorigenesis and progression of cancers, including gastric cancer (GC). Our study aimed to identify a novel biomarker to predict the prognosis of patients with GC. METHODS: The GC microarray dataset, GSE28700, was downloaded from the Gene Expression Omnibus (GEO) database and screened for differentially expressed miRNAs (DEMs). The downregulation of miR-376a expression was verified in GC cell lines and 82 paired GC tissues by performing RT-qPCR and the correlation between its expression and clinicopathological characteristics was also explored. The target genes of miR-376a were predicted using TargetScan7.1, miRDB, and DIANA website tools. A functional enrichment analysis was performed to explore the biological role of the common target genes. RESULTS: Bioinformatics analysis found that miR-376a was downregulated in GC tissues. Compared with the control group, RT-qPCR results showed that the expression of miR-376a in GC cell lines and tissues were also significantly decreased. The expression of miR-376a was statistically associated with T and N stage. Survival analysis with Kaplan-Meier showed that GC patients in the low expression group had a poorer prognosis than those in the high expression group (median survival of 26.4 and 46.9 months, respectively). Univariate and multivariate analysis demonstrated that low miR-376a expression was an independent prognostic marker for poor survival. Functional enrichment analysis indicated that the common targets genes were involved in cell-cell communication, VEGF and mTOR1-mediated signaling, and epithelial-to-mesenchymal transition (EMT). CONCLUSION: The results suggest that miR-376a could play an important role in the tumorigenesis and progression of GC and act as a novel therapeutic target and prognostic indicator in patients with GC.

Citrus aurantium Naringenin Prevents Osteosarcoma Progression and Recurrence in the Patients Who Underwent Osteosarcoma Surgery by Improving Antioxidant Capability.

Citrus aurantium is rich in flavonoids, which may prevent osteosarcoma progression, but its related molecular mechanism remains unclear. Flavonoids were extracted from C. aurantium and purified by reparative HPLC. Each fraction was identified by using electrospray ionisation mass spectrometry (ESI-MS). Three main components (naringin, naringenin, and hesperetin) were isolated from C. aurantium. Naringenin inhibited the growth of MG-63 cells, whereas naringin and hesperetin had no inhibitory function on cell growth. ROS production was increased in naringin- and hesperetin-treated groups after one day of culture while the level was always lowest in the naringenin-treated group after three days of culture. 95 osteosarcoma patients who underwent surgery were assigned into two groups: naringenin group (NG, received 20 mg naringenin daily, n = 47) and control group (CG, received 20 mg placebo daily, n = 48). After an average of two-year follow-up, osteosarcoma volumes were smaller in the NG group than in the CG group (P > 0.01). The rate of osteosarcoma recurrence was also lower in the NG group than in CG group. ROS levels were lower in the NG group than in the CG group. Thus, naringenin from Citrus aurantium inhibits osteosarcoma progression and local recurrence in the patients who underwent osteosarcoma surgery by improving antioxidant capability.