Topical Capsaicin in Poly(lactic-co-glycolic)acid (PLGA) Nanoparticles Decreases Acute Itch and Heat Pain.

BACKGROUND: Capsaicin, the hot pepper agent, produces burning followed by desensitization. To treat localized itch or pain with minimal burning, low capsaicin concentrations can be repeatedly applied. We hypothesized that alternatively controlled release of capsaicin from poly(lactic-co-glycolic acid) (PLGA) nanoparticles desensitizes superficially terminating nociceptors, reducing burning. METHODS: Capsaicin-loaded PLGA nanoparticles were prepared (single-emulsion solvent evaporation) and characterized (size, morphology, capsaicin loading, encapsulation efficiency, in vitro release profile). Capsaicin-PLGA nanoparticles were applied to murine skin and evaluated in healthy human participants (n = 21) for 4 days under blinded conditions, and itch and nociceptive sensations evoked by mechanical, heat stimuli and pruritogens cowhage, ß-alanine, BAM8-22 and histamine were evaluated. RESULTS: Nanoparticles (loading: 58 µg capsaicin/mg) released in vitro 23% capsaicin within the first hour and had complete release at 72 h. In mice, 24 h post-application Capsaicin-PLGA nanoparticles penetrated the dermis and led to decreased nociceptive behavioral responses to heat and mechanical stimulation (desensitization). Application in humans produced a weak to moderate burning, dissipating after 3 h. A loss of heat pain up to 2 weeks was observed. After capsaicin nanoparticles, itch and nociceptive sensations were reduced in response to pruritogens cowhage, ß-alanine or BAM8-22, but were normal to histamine. CONCLUSIONS: Capsaicin nanoparticles could be useful in reducing pain and itch associated with pruritic diseases that are histamine-independent.

Autocatalytic Delivery of Brain Tumor-targeting, Size-shrinkable Nanoparticles for Treatment of Breast Cancer Brain Metastases.

Breast cancer brain metastases (BCBMs) represent a major cause of morbidity and mortality among patients with breast cancer. Chemotherapy, which is widely used to treat tumors outside of the brain, is often ineffective on BCBMs due to its inability to efficiently cross the blood-brain barrier (BBB). Although the BBB is partially disrupted in tumor lesions, it remains intact enough to prevent most therapeutics from entering the brain. Here, we report a nanotechnology approach that can overcome the BBB through synthesis of lexiscan-loaded, AMD3100-conjugated, shrinkable NPs, or LANPs. LANPs respond to neutrophil elastase-enriched tumor microenvironment by shrinking in size and disrupt the BBB in tumors through lexiscan-mediated modulation. LANPs recognize tumor cells through the interaction between AMD3100 and CXCR4, which are expressed in metastatic tumor cells. We demonstrate that the integration of tumor responsiveness, tumor targeting, and BBB penetration enables LANPs to penetrate metastatic lesions in the brain with high efficiency, and, when doxorubicin was encapsulated, LANPs effectively inhibited tumor growth and prolonged the survival of tumor-bearing mice. Due to their high efficiency in penetrating the BBB for BCBMs treatment, LANPs have the potential to be translated into clinical applications for improved treatment of patients with BCBMs.

kmcEx: memory-frugal and retrieval-efficient encoding of counted k-mers.

MOTIVATION: K-mers along with their frequency have served as an elementary building block for error correction, repeat detection, multiple sequence alignment, genome assembly, etc., attracting intensive studies in k-mer counting. However, the output of k-mer counters itself is large; very often, it is too large to fit into main memory, leading to highly narrowed usability. RESULTS: We introduce a novel idea of encoding k-mers as well as their frequency, achieving good memory saving and retrieval efficiency. Specifically, we propose a Bloom filter-like data structure to encode counted k-mers by coupled-bit arrays-one for k-mer representation and the other for frequency encoding. Experiments on five real datasets show that the average memory-saving ratio on all 31-mers is as high as 13.81 as compared with raw input, with 7 hash functions. At the same time, the retrieval time complexity is well controlled (effectively constant), and the false-positive rate is decreased by two orders of magnitude. AVAILABILITY AND IMPLEMENTATION: The source codes of our algorithm are available at github.com/lzhLab/kmcEx. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

In vitro and in vivo evaluation of functionalized chitosan-Pluronic micelles loaded with myricetin on glioblastoma cancer.

This study aimed to develop a novel polymeric carrier based on chitosan-functionalized Pluronic P123/F68 micelles loaded with myricetin (MYR) to improve the therapeutic index of chemotherapy for glioblastoma cancer. Following characterization and assessment of the cellular uptake and antitumor effects of MYR-loaded micelles (MYR-MCs) in vitro, the acute toxicity, blood-brain barrier (BBB) translocation, brain uptake and biodistribution in vivo were assessed. The results demonstrated that MYR-MCs exhibited improved cellular uptake and antitumor activity compared to free MYR in vitro, with a significantly enhanced anticancer effect in vivo following efficient transport across the BBB. However, MYR-MCs did not affect the brain endothelial, barrier function, the liver, heart or kidneys. Furthermore, MYR-MCs altered the expression of apoptotic proteins, such as Bcl-2, BAD and BAX, in mice. In conclusion, MYR-MCs may be considered an effective and promising drug delivery system for glioblastoma treatment.

Intravital biobank and personalized cancer therapy: the correlation with omics.

Biobanks have played a decisive role in all aspects of the field of cancer, including pathogenesis, diagnosis, prognosis and treatment. The significance of cancer biobanks is epitomized through the appropriate application of various "-omic" techniques (omics). The mutually motivated relationship between biobanks and omics has intensified the development of cancer research. Human cancer tissues that are maintained in intravital biobanks (or living tissue banks) retain native tumor microenvironment, tissue architecture, hormone responsiveness and cell-to-cell signalling properties. Intravital biobanks replicate the structural complexity and heterogeneity of human cancers, making them an ideal platform for preclinical studies. The application of omics with intravital biobanks renders them more active, which makes it possible for the cancer-related evaluations to be dynamically monitored on a real-time basis. Integrating intravital biobank and modern omics will provide a useful tool for the discovery and development of new drugs or novel therapeutic strategies. More importantly, intravital biobanks may play an essential role in the creation of meaningful patient-tailored therapies as for personalized medicine.

New grading scale based on early factors for predicting delayed cerebral ischemia in patients with aneurysmal subarachnoid hemorrhage: a multicenter retrospective study.

Delayed cerebral ischemia (DCI) could lead to poor clinical outcome(s). The aim of the present study was to establish and validate a predictive model for DCI after aneurysmal subarachnoid hemorrhage (aSAH) based on clinical data. Data from a series of 217 consecutive patients with aSAH were reviewed and analyzed. Related risk factors within 72 h after aSAH were analyzed depending on whether DCI recurred. Least absolute shrinkage and selection operator (LASSO) analysis was performed to reduce data dimensions and screen for optimal predictors. Multivariable logistic regression was used to establish a predictive model and construct a nomogram. Receiver operating characteristic (ROC) and calibration curves were generated to assess the discriminative ability and goodness of fit of the model. Decision curve analysis was applied to evaluated the clinical applicability of the predictive model. LASSO regression identified 4 independent predictors, including Subarachnoid Hemorrhage Early Brain Edema Score (i.e., "SEBES"), World Federation of Neurosurgical Societies scale score (i.e., "WFNS"), modified Fisher Scale score, and intraventricular hemorrhage (IVH), which were incorporated into logistic regression to develop a nomogram. After verification, the area under the ROC curve for the model was 0.860. The calibration curve indicated that the predictive probability of the new model was in good agreement with the actual probability, and decision curve analysis demonstrated the clinical applicability of the model within a specified range. The prediction model could precisely calculate the probability of DCI after aSAH, and may contribute to better clinical decision-making and personalized treatment to achieve better outcomes.

Cross-platform analysis reveals cellular and molecular landscape of glioblastoma invasion.

BACKGROUND: Improved treatment of glioblastoma (GBM) needs to address tumor invasion, a hallmark of the disease that remains poorly understood. In this study, we profiled GBM invasion through integrative analysis of histological and single-cell RNA sequencing (scRNA-seq) data from 10 patients. METHODS: Human histology samples, patient-derived xenograft mouse histology samples, and scRNA-seq data were collected from 10 GBM patients. Tumor invasion was characterized and quantified at the phenotypic level using hematoxylin and eosin and Ki-67 histology stains. Crystallin alpha B (CRYAB) and CD44 were identified as regulators of tumor invasion from scRNA-seq transcriptomic data and validated in vitro, in vivo, and in a mouse GBM resection model. RESULTS: At the cellular level, we found that invasive GBM are less dense and proliferative than their non-invasive counterparts. At the molecular level, we identified unique transcriptomic features that significantly contribute to GBM invasion. Specifically, we found that CRYAB significantly contributes to postoperative recurrence and is highly co-expressed with CD44 in invasive GBM samples. CONCLUSIONS: Collectively, our analysis identifies differentially expressed features between invasive and nodular GBM, and describes a novel relationship between CRYAB and CD44 that contributes to tumor invasiveness, establishing a cellular and molecular landscape of GBM invasion.

Intracranial delivery of synthetic mRNA to suppress glioblastoma.

Owing to messenger RNA's unique biological advantages, it has received increasing attention to be used as a therapeutic, known as mRNA-based gene therapy. It is critical to have an ideal strategy of mRNA gene therapy for glioma, which grows in a special environment. In the present study, we screened out a safe and efficient transfection reagent for intracranial delivery of synthetic mRNA in mouse brain. First, in order to analyze the effect of different transfection reagents on the intracranial delivery of mRNA, the synthetic luciferase mRNA was wrapped with two different transfection reagents and microinjected into the brain at the fixed point. The expression status of delivered mRNA was monitored by a small animal imaging system. The possible reagent-induced biological toxicity was evaluated by behavioral and blood biochemical measurements. Then, to test the therapeutic effect of our intracranial delivery mRNA model on glioma, synthetic modified tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mRNA was used as an example of therapeutic application. This model demonstrated that synthetic mRNA could be successfully delivered into the brain using commercially available transfection reagents, and TransIT-mRNA showed better results than in vivo-jetPEI kit. This model can be applied in precise targeting and personalized gene therapy of glioma.

Synthetic mRNA-based gene therapy for glioblastoma: TRAIL-mRNA synergistically enhances PTEN-mRNA-based therapy.

Glioblastoma (GBM) is characterized as having high molecular heterogeneity and complexity, which can be well revealed by genomic study. A truly effective treatment for GBM should flexibly address its heterogeneities, complexity, and strong drug resistance. This study was performed to explore the effectiveness of an mRNA-based therapeutic strategy using in vitro synthesized PTEN-mRNA and TRAIL-mRNA in tumor cells derived from PTEN-deletion patients. The PTEN gene alterations were revealed by whole-exome sequencing of three paired clinical GBMs and selected as the therapy target. Patient-derived primary glioblastoma stem cells (GBM2) and a DBTRG-cell-derived xenograft were used to detect mRNA's cytotoxicity in vitro and tumor suppression in vivo. Following the successful in vitro synthesis of PTEN-mRNA and TRAIL-mRNA, the combinational treatment of PTEN-mRNA and TRAIL-mRNA significantly suppressed tumor growth compared with treatment with PBS (96.4%), PTEN-mRNA (89.7%), and TRAIL-mRNA (84.5%). The combinational application of PTEN-mRNA and TRAIL-mRNA showed synergistic inhibition of tumor growth, and the JNK pathway might be the major mechanism involved. This study provided a basis for an mRNA-based therapeutic strategy to be developed into an effective patient-tailored treatment for GBM.

Recombinant human bone morphogenetic protein 2 and 7 inhibit the degeneration of intervertebral discs by blocking the Puma-dependent apoptotic signaling.

Recombinant human bone morphogenetic proteins (rhBMPs) can stimulate bone formation and growth in the treatment of spinal fusions and nonunions. However, it is still unclear whether rhBMPs function in the prevention of intervertebral disc degeneration (IDD). Here, we discovered that BMP levels were decreased in IDD patients, which impaired the BMP/Smad (Mothers against decapentaplegic homologs) signaling. Conducting a microarray assay in Smad4-knockdown cells, we found that expression of PUMA (p53-upregulated modulator of apoptosis) was significantly induced. The molecular analysis revealed that Smad4 recruited HDAC1 (histone deacetylase 1) and the phosphorylated Smad1/5/8 to dock on the promoter of PUMA to repress its expression. The impairment of BMP/Smad signaling in IDD patients caused the significant induction of Puma-dependent apoptosis and resulted in the pathogenesis of IDD. In vitro knockdown of BMP receptors (BMPR1a and BMPR2) in nucleus pulposus (NP) cells could mimic the molecular changes of BMP/Smad signaling and Puma-dependent apoptotic signaling that were observed in IDD patients. Exposing NP cells to RITA (reactivating p53 and inducing tumor apoptosis) small molecule and rhBMP2 (or rhBMP7), we observed that rhBMP2/7 could significantly decrease protein levels of Puma and its downstream proapoptotic molecules, blocking cell apoptosis. Importantly, administration of rhBMPs in aged rats could inhibit the occurrence of IDD. Our results provide a link between BMP/Smad signaling and Puma-dependent apoptotic signaling, revealing a new mechanism of how BMPs contribute to IDD pathogenesis and providing evidence that rhBMPs may decrease apoptosis and improve the outcome of IDD.

Case Report: Primary Pulmonary Angiosarcoma With Brain Metastasis.

Primary pulmonary angiosarcoma (PPA) is a rare malignant vascular tumor, of which early diagnosis is challenging due to lack of specific clinical manifestations and a low level of suspicion. Here, we report a case of PPA presented with advanced brain metastasis. A 21-year-old patient with 1 week history of headache and mild cough was hospitalized for a head injury. Head MRI showed multiple intracranial lesions with brain edema. Chest CT displayed bilateral pulmonary infiltrates with mediastinal lymph node enlargement. After 2 months of anti-tuberculosis treatment, the patient was readmitted for persistent headache and cough with occasional hemosputum along with worsening pulmonary and intracranial lesions. Despite seizure prophylaxis and control of intracranial pressure and brain edema, his symptoms progressively aggravated, accompanied by cough with bloody sputum, frequent epileptic seizures, and hypotension. He eventually developed coma and died within 3 months of onset of symptoms. An autopsy confirmed PPA with brain metastasis.

Prognostic and Predictive Value of an Immunoscore Signature in Glioblastoma Multiform.

BACKGROUND: Although increasing evidence shows that immune infiltration plays an essential role in glioblastoma (GBM), current prognostic indicators do not accurately represent the risk of immune cells infiltration in patients. It is therefore critical to identify new prognostic markers for GBM. Here, we investigated the effectiveness of using immunoscore to improve risk stratification and prediction of prognosis in GBM patients receiving chemotherapy. METHODS: Using mRNA microarrays and CIBERSORT, we analyzed 22 types of immune cell fractions in 517 GBM samples and characterized an immunoscore using the least absolute shrinkage and selection operator (LASSO) Cox regression model based on the fraction of immune cell types and patients' overall survival. The prognostic and predictive accuracy of immunoscore was verified in the validation cohort and the entire cohort. RESULTS: Using the LASSO model, an immunoscore was developed to classify patients into High and Low immunoscore groups in the training cohort (P < 0.0001) based on the fraction of eight immune cell types. The immunoscore performance was validated in the validation cohort (P < 0.0001) and the entire cohort (P < 0.0001). Furthermore, a nomogram comprising age, IDH1 status, and immunoscore was generated to predict one- and three-year survival rates in the training cohort. The predictive value of the immunoscore was also confirmed in the validation cohort and the entire cohort (C-index: 0.66, 0.67, and 0.68, respectively). In addition, we concluded that patients in the low-immunoscore group may benefit from adjuvant chemotherapy for GBM. CONCLUSION: Immunoscore, an immune-infiltration-based signature, is a reliable prognostic and predictive tool for GBM.

PI3K/mTORC1/2 inhibitor PQR309 inhibits proliferation and induces apoptosis in human glioblastoma cells.

Glioblastoma (GBM) is the most common type of primary central nervous system tumor in adults, which has high mortality and morbidity rates, and short survival time, namely <15 months after the diagnosis and application of standard therapy, which includes surgery, radiation therapy and chemotherapy; thus, novel therapeutic strategies are imperative. The activation of the PI3K/AKT signaling pathway plays an important role in GBM. In the present study, U87 and U251 GBM cells were treated with the PI3K/mTORC1/2 inhibitor PQR309, and its effect on glioma cells was investigated. Cell Counting Kit­8 assay, 5­ethynyl­2'­deoxyuridine and colony formation assays revealed dose­ and time­dependent cytotoxicity in glioma cells that were treated with PQR309. Flow cytometry and western blotting revealed that PQR309 can significantly induce tumor cell apoptosis and arrest the cell cycle in the G1 phase. Furthermore, the expression levels of AKT, phosphorylated (p)­AKT, Bcl­2, Bcl­xL, Bad, Bax, cyclin D1, cleaved caspase­3, MMP­9 and MMP­2 were altered. In addition, the migration and invasion of glioma cells, as detected by wound healing, migration and Transwell invasion assays, exhibited a marked suppression after treating the cells with PQR309. These results indicated that PQR309 exerts an antitumor effect by inhibiting proliferation, inducing apoptosis, inducing G1 cell cycle arrest, and inhibiting invasion and migration in human glioma cells. The present study provides evidence supportive of further development of PQR309 for adjuvant therapy of GBM.

Therapeutic Prospects of mRNA-Based Gene Therapy for Glioblastoma.

The treatment of glioblastoma has been a big challenge for decades in the oncological field mainly owing to its unique biological characteristics, such as high heterogeneity, diffusing invasiveness, and capacity to resist conventional therapies. The mRNA-based therapeutic modality holds many superior features, including easy manipulation, rapid and transient expression, and adaptive convertibility without mutagenesis, which are suitable for dealing with glioblastoma's complexity and variability. Synthetic anticancer mRNAs carried by various vehicles act as the ultimate attackers of the tumor across biological barriers. In this modality, specifically targeted glioblastoma treatment can be guaranteed by adding targeting molecules at certain levels. The choice of mRNA-bearing vehicle and administration method is a fully patient-tailored selection. This review covers the advantages and possible limitations of mRNA-based gene therapy, the in vitro synthesis of mRNA, the feasible methods for synthetic mRNA delivery and clinical therapeutic prospects of mRNA-based gene therapy for glioblastoma.

Identification of a Specific Gene Module for Predicting Prognosis in Glioblastoma Patients.

Introduction: Glioblastoma (GBM) is the most common and malignant variant of intrinsic glial brain tumors. The poor prognosis of GBM has not significantly improved despite the development of innovative diagnostic methods and new therapies. Therefore, further understanding the molecular mechanism that underlies the aggressive behavior of GBM and the identification of appropriate prognostic markers and therapeutic targets is necessary to allow early diagnosis, to develop appropriate therapies and to improve prognoses. Methods: We used a weighted gene co-expression network analysis (WGCNA) to construct a gene co-expression network with 524 glioblastoma samples from The Cancer Genome Atlas (TCGA). A risk score was then constructed based on four module genes and the patients' overall survival (OS) rate. The prognostic and predictive accuracy of the risk score were verified in the GSE16011 cohort and the REMBRANDT cohort. Results: We identified a gene module (the green module) related to prognosis. Then, multivariate Cox analysis was performed on 4 hub genes to construct a Cox proportional hazards regression model from 524 glioblastoma patients. A risk score for predicting survival time was calculated with the following formula based on the top four genes in the green module: risk score = (0.00889 × EXPCLEC5A) + (0.0681 × EXPFMOD) + (0.1724 × EXPFKBP9) + (0.1557 × EXPLGALS8). The 5-year survival rate of the high-risk group (survival rate: 2.7%, 95% CI: 1.2-6.3%) was significantly lower than that of the low-risk group (survival rate: 8.8%, 95% CI: 5.5-14.1%). Conclusions: This study demonstrated the potential application of a WGCNA-based gene prognostic model for predicting the survival outcome of glioblastoma patients.

Novel Strategies to Discover Effective Drug Targets in Metabolic and Immune Therapy for Glioblastoma.

Glioblastoma multiforme is a common primary brain tumor, which exhibits an imbalance between glioma cell growth and glucose metabolism. Recent discoveries have found that the multiple pathways and downstream genes involved in the dysregulated metabolic pathway allow tumor to manifest and progress, which is critical to patients with glioblastoma associated with significant systemic and immunosuppression. Moreover, immune microenvironment is considered a major obstacle to generating an effective antitumor immune response. Therefore, identification of patient-specific tumor antigens through highly personalized approach, and effective combination with other therapeutic modalities such as molecular agents targeting tumor metabolic oncogene addiction and potent host immune modulators, may provide targets for more effective therapeutic strategies for glioblastoma. In this review, we aim to highlight the most recent findings regarding glucose uptake and proliferation, cell mobility and to expand our investigations and more comprehensively examine different aspects of glucose metabolism in glioblastoma, such as pentose phosphate pathway (PPP) and its enzymes, metabolic modulation of genetics and epigenetics and key metabolic regulators, importantly, tumor cell-induced glucose deprivation inhibits T-cell glycolysis and immunogenic functions. Furthermore, this review will concentrate on how to discover effective drug targets to regulate glucose metabolism in tumor and T cell growth for future glioblastoma therapies, and the challenges faced by the field of metabolism in tumor immune microenviroment.

Pluronic-based micelle encapsulation potentiates myricetin-induced cytotoxicity in human glioblastoma cells.

As one of the natural herbal flavonoids, myricetin has attracted much research interest, mainly owing to its remarkable anticancer properties and negligible side effects. It holds great potential to be developed as an ideal anticancer drug through improving its bioavailability. This study was performed to investigate the effects of Pluronic-based micelle encapsulation on myricetin-induced cytotoxicity and the mechanisms underlying its anticancer properties in human glioblastoma cells. Cell viability was assessed using a methylthiazol tetrazolium assay and a real-time cell analyzer. Immunoblotting and quantitative reverse transcriptase polymerase chain reaction techniques were used for determining the expression levels of related molecules in protein and mRNA. The results indicated that myricetin-induced cytotoxicity was highly potentiated by the encapsulation of myricetin. Mitochondrial apoptotic pathway was demonstrated to be involved in myricetin-induced glioblastoma cell death. The epidermal growth factor receptor (EGFR)/PI3K/Akt pathway located in the plasma membrane and cytosol and the RAS-ERK pathway located in mitochondria served as upstream and downstream targets, respectively, in myricetin-induced apoptosis. MiR-21 inhibitors interrupted the expression of EGFR, p-Akt, and K-Ras in the same fashion as myricetin-loaded mixed micelles (MYR-MCs) and miR-21 expression were dose-dependently inhibited by MYR-MCs, indicating the interaction of miR-21 with MYR-MCs. This study provided evidence supportive of further development of MYR-MC formulation for preferentially targeting mitochondria of glioblastoma cells.

Protective effect of microRNA-138 against cerebral ischemia/reperfusion injury in rats.

MicroRNAs (miRs) serve a regulatory function in oxidative radical-mediated inflammation and apoptosis during ischemia/reperfusion (IR) injury. Lipocalin 2 (Lcn-2), a target protein of miR-138, is widely involved in the systemic response to IR injury. The aim of the present study was to investigate the association between miR-138 and Lcn-2 in a rat model of cerebral ischemia/reperfusion (CIR) injury and to verify the interaction between miR-138 and Lcn-2 in a PC12 cell model of hypoxia/reoxygenation injury. Reverse transcription-quantitative polymerase chain reaction and western blot analysis were used to detect the mRNA and protein expression levels of miR-138 and Lcn-2. Cell proliferation was determined by MTT assay. The results suggested that the expression of miR-138 was inversely correlated with the expression of Lcn-2 in the CIR rat model and the PC12 cells subjected to hypoxia and reoxygenation. The expression of Lcn-2 was inhibited by miR-138 mimics and enhanced by miR-138 inhibitors, thereby indicating that miR-138 functions as a negative regulator for Lcn-2 expression. This study provides an experimental basis for the further study of miR-138-based therapy for CIR injury.

The application of mRNA-based gene transfer in mesenchymal stem cell-mediated cytotoxicity of glioma cells.

Since the tumor-oriented homing capacity of mesenchymal stem cells (MSCs) was discovered, MSCs have attracted great interest in the research field of cancer therapy mainly focused on their use as carries for anticancer agents. Differing from DNA-based vectors, the use of mRNA-based antituor gene delivery benefits from readily transfection and mutagenesis-free. However, it is essential to verify if mRNA transfection interferes with MSCs' tropism and their antitumor properties. TRAIL- and PTEN-mRNAs were synthesized and studied in an in vitro model of MSC-mediated indirect co-culture with DBTRG human glioma cells. The expression of TRAIL and PTEN in transfected MSCs was verified by immunoblotting analysis, and the migration ability of MSCs after anticancer gene transfection was demonstrated using transwell co-cultures. The viability of DBTRG cells was determined with bioluminescence, live/dead staining and real time cell analyzer. An in vivo model of DBTRG cell-derived xenografted tumors was used to verify the antitumor effects of TRAIL- and PTEN-engineered MSCs. With regard to the effect of mRNA transfection on MSCs' migration toward glioma cells, an enhanced migration rate was observed with MSCs transfected with all tested mRNAs compared to non-transfected MSCs (p<0.05). TRAIL- and PTEN-mRNA-induced cytotoxicity of DBTRG glioma cells was proportionally correlated with the ratio of conditioned medium from transfected MSCs. A synergistic action of TRAIL and PTEN was demonstrated in the current co-culture model. The immunoblotting analysis revealed the apoptotic nature of the cells death in the present study. The growth of the xenografted tumors was significantly inhibited by the application of MSCPTEN or MSCTRAIL/PTEN on day 14 and MSCTRAIL on day 28 (p<0.05). The results suggested that anticancer gene-bearing mRNAs synthesized in vitro are capable of being applied for MSC-mediated anticancer modality. This study provides an experimental base for further clinical anticancer studies using synthesized mRNAs.