Characterization and verification of CD81 as a potential target in lung squamous cell carcinoma.

CD81 is a cell surface transmembrane protein of the tetraspanin family, which critically regulates signal transduction and immune response. Growing evidence has shown that CD81 plays important roles in tumorigenesis and influences immunotherapy response. Here, combining bio-informatics and functional analysis, we find that CD81 is a risk factor in lung squamous cell carcinoma (LUSC), whereas a protective factor in lung adenocarcinoma. In LUSC with high expression of CD81, the autophagy and JAK-STAT signaling pathway are activated. Meanwhile, the expression level of CD81 is negatively correlated with tumor mutational load (TMB), microsatellite instability (MSI), and neoantigen (NEO). Furthermore, patients with LUSC and high expression of CD81 do not respond to immunotherapy drugs, but can respond to chemotherapy drugs. Importantly, depletion of CD81 suppresses the proliferation of LUSC cell, and enhances the sensitivity to cisplatin. Our findings suggest that CD81 represents a potential target for cisplatin-based chemotherapy in patients with LUSC.

Highly Selective Synthesis of Monoclinic-Phased Platinum-Tellurium Nanotrepang for Direct Formic Acid Oxidation Catalysis.

Designing efficient formic acid oxidation reaction (FAOR) catalysts with remarkable membrane electrode assembly (MEA) performance in a direct formic acid fuel cell (DFAFC) medium is significant yet challenging. Herein, we report that the monoclinic-phased platinum-tellurium nanotrepang (m-PtTe NT) can be adopted as a highly active, selective, and stable FAOR catalyst with a desirable direct reaction pathway. The m-PtTe NT exhibits the high specific and mass activities of 6.78 mA cm-2 and 3.2 A mgPt-1, respectively, which are 35.7/22.9, 2.8/2.6, and 3.9/2.9 times higher than those of commercial Pt/C, rhombohedral-phased Pt2Te3 NT (r-Pt2Te3 NT), and trigonal-phased PtTe2 NT (t-PtTe2 NT), respectively. Simultaneously, the highest reaction tendency for the direct FAOR pathway and the best tolerance to poisonous CO intermediate can also be realized by m-PtTe NT. More importantly, even in a single-cell medium, the m-PtTe NT can display a much higher MEA power density (171.4 mW cm-2) and stability (53.2% voltage loss after 5660 s) than those of commercial Pt/C, demonstrating the great potential in operating DFAFC device. The in-situ Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy jointly demonstrate that the unique nanostructure of m-PtTe NT can effectively optimize dehydrogenation steps and inhibit the CO intermediate adsorption, as well as promote the oxidation of noxious CO intermediate, thus achieving the great improvement of FAOR activity, poisoning tolerance, and stability. Density functional theory calculations further reveal that the direct pathway is the most favorable on m-PtTe NT than r-Pt2Te3 NT and t-PtTe2 NT. The higher activation energy to produce CO and the relatively weaker binding with CO of m-PtTe NT result in the better CO tolerance. This work achieves remarkable FAOR and MEA performances of advanced Pt-based anodic catalysts for DFAFCs via a phase engineering strategy.

Multifunctionalized Gold Sub-Nanometer Particles for Sensitizing Radiotherapy against Glioblastoma.

Glioblastoma is the most common lethal malignant intracranial tumor with a low 5-year survival rate. Currently, the maximal safe surgical resection, followed by high-dose radiotherapy (RT), is a standard treatment for glioblastoma. However, high-dose radiation to the brain is associated with brain injury and results in a high fatality rate. Here, integrated pharmaceutics (named D-iGSNPs) composed of gold sub-nanometer particles (GSNPs), blood-brain barrier (BBB) penetration peptide iRGD, and cell cycle regulator α-difluoromethylornithine is designed. In both simulated BBB and orthotopic murine GL261 glioblastoma models, D-iGSNPs are proved to have a beneficial effect on the BBB penetration and tumor targeting. Meanwhile, data from cell and animal experiments reveal that D-iGSNPs are able to sensitize RT. More importantly, the synergy of D-iGSNPs with low-dose RT can exhibit an almost equal therapeutic effect with that of high-dose RT. This study demonstrates the therapeutic advantages of D-iGSNPs in boosting RT, and may provide a facile approach to update the current treatment of glioblastoma.

Exteriorization of the distal catheter for ventriculoperitoneal shunt protruding through the peritoneal space: experience with 1 case.

Ventriculoperitoneal (VP) shunting is the most widely used procedure for diverting cerebrospinal fluid (CSF) for hydrocephalus. Migration of the distal catheter of VP shunts has been reported but extrusion through the abdominal wall is rare. We report a case involving distal catheter extrusion. The catheter was exteriorized without compromising CSF flow while awaiting reoperation. This controlled hydrocephalus and allowed confirmation of CSF sterility prior to shunt replacement.

Comprehensive analysis of PSME3: from pan-cancer analysis to experimental validation.

PSME3 plays a significant role in tumor progression. However, the prognostic value of PSME3 in pan-cancer and its involvement in tumor immunity remain unclear. We conducted a comprehensive study utilizing extensive RNA sequencing data from the TCGA (The Cancer Genome Atlas) and GTEx (Genotype-Tissue Expression) databases. Our research revealed abnormal expression levels of PSME3 in various cancer types and unveiled a correlation between high PSME3 expression and adverse clinical outcomes, especially in cancers like liver cancer (LIHC) and lung adenocarcinoma (LUAD). Functional enrichment analysis highlighted multiple biological functions of PSME3, including its involvement in protein degradation, immune responses, and stem cell regulation. Moreover, PSME3 showed associations with immune infiltration and immune cells in the tumor microenvironment, indicating its potential role in shaping the cancer immune landscape. The study also unveiled connections between PSME3 and immune checkpoint expression, with experimental validation demonstrating that PSME3 positively regulates CD276. This suggests that PSME3 could be a potential therapeutic target in immunotherapy. Additionally, we predicted sensitive drugs targeting PSME3. Finally, we confirmed in both single-factor Cox and multiple-factor Cox regression analyses that PSME3 is an independent prognostic factor. We also conducted preliminary validations of the impact of PSME3 on cell proliferation and wound healing in liver cancer. In summary, our study reveals the multifaceted role of PSME3 in cancer biology, immune regulation, and clinical outcomes, providing crucial insights for personalized cancer treatment strategies and the development of immunotherapy.

The association between ferroptosis-related patterns and tumor microenvironment in colorectal cancer.

Ferroptosis, a form of regulated cell death (RCD), exhibits distinct characteristics such as iron-dependence and lipid peroxidation accumulation (ROS), setting it apart from other types of cell death like apoptosis and necrosis. Its role in cancer biology is increasingly recognized, particularly its potential interaction with tumor microenvironment (TME) and CD8 T cells in cancer immunotherapy. However, the impact of ferroptosis on TME cell infiltration remains unclear. In this study, we conducted unsupervised clustering analysis on patient data from public databases, identifying three ferroptosis patterns with distinct TME cell infiltration characteristics: immune-inflamed, immune-excluded, and immune-desert phenotypes. We developed a ferroptosis score based on differentially expressed genes (DEGs) among these patterns, which correlated with various biological features including chemotherapy-resistance and immune cells infiltration. Despite patients with high ferroptosis scores exhibiting worse prognosis, they showed increased likelihood of benefiting from immunotherapy. Our findings highlight the importance of ferroptosis-related patterns in understanding TME cell infiltration and suggest novel strategies for drug combinations and immune-related therapies.

Platinum-Tellurium Heterojunction Nanosheet Assemblies for Efficient Direct Formic Acid Electrooxidation Catalysis.

Two-dimensional (2D) heterojunction nanomaterials offer exceptional physicochemical and catalytic properties, thanks to their special spatial electronic structure. However, synthesizing morphologically uniform 2D platinum (Pt)-based metallic nanomaterials with diverse crystalline phases remains a formidable challenge. In this study, we have achieved the successful synthesis of advanced 2D platinum-tellurium heterojunction nanosheet assemblies (Ptx-PtTe2 HJNSAs, x = 0, 1, 2), seamlessly integrating both trigonal PtTe2 (t-PtTe2) and cubic Pt (c-Pt) phases. By enabling efficient electron transport and leveraging the specific electron density present at the heterojunction, the Pt2-PtTe2 HJNSAs/C demonstrated exceptional formic acid oxidation reaction (FAOR) activity and stability. Specifically, the specific and mass activities reached 8.4 mA cm-2 and 6.1 A mgPt-1, which are 46.7 and 50.8 times higher than those of commercial Pt/C, respectively. Impressively, aberration-corrected high-angle annular dark field scanning transmission electron microscopy (AC-HAADF-STEM) revealed a closely packed arrangement of atomic layers and a coherent intergrowth heterogeneous structure. Density functional theory (DFT) calculations further indicated that rearrangement of electronic structure occurred on the surface of Pt2-PtTe2 HJNSAs resulting in a more favorable dehydrogenation pathway and excellent CO tolerance, beneficial for performance improvement. This work inspires the targeted exploration of Pt-based nanomaterials through 2D heterostructure design, leading to an important impact on fuel cell catalysis and beyond.

IL4I1 in M2-like macrophage promotes glioma progression and is a promising target for immunotherapy.

Background: Glioma is the prevailing malignant intracranial tumor, characterized by an abundance of macrophages. Specifically, the infiltrating macrophages often display the M2 subtype and are known as tumor-associated macrophages (TAMs). They have a critical role in promoting the oncogenic properties of tumor cells. Interleukin-4-induced-1 (IL4I1) functions as an L-phenylalanine oxidase, playing a key part in regulating immune responses and the progression of various tumors. However, there is limited understanding of the IL4I1-mediated cross-talk function between TAMs and glioma cell in the glioma microenvironment. Methods: TCGA, GTEx, and HPA databases were applied to assess the IL4I1 expression, clinical characteristics, and prognostic value of pan-cancer. The link between IL4I1 levels and the prognosis, methylation, and immune checkpoints (ICs) in gliomas were explored through Kaplan-Meier curve, Cox regression, and Spearman correlation analyses. The IL4I1 levels and their distribution were investigated by single-cell analysis and the TIMER 2 database. Additionally, validation of IL4I1 expression was performed by WB, RT-qPCR, IHC, and IF. Co-culture models between glioma cells and M2-like macrophages were used to explore the IL4I1-mediated effects on tumor growth, invasion, and migration of glioma cells. Moreover, the function of IL4I1 on macrophage polarization was evaluated by ELISA, RT-qPCR, WB, and siRNA transfection. Results: Both transcriptome and protein levels of IL4I1 were increased obviously in various tumor types, and correlated with a dismal prognosis. Specifically, IL4I1 was implicated in aggressive progression and a dismal prognosis for patients with glioma. A negative association was noticed between the glioma grade and DNA promoter methylation of IL4I1. Enrichment analyses in glioma patients suggested that IL4I1 was linked to cytokine and immune responses, and was positively correlated with ICs. Single-cell analysis, molecular experiments, and in vitro assays showed that IL4I1 was significantly expressed in TAMs. Importantly, co-culture models proved that IL4I1 significantly promoted the invasion and migration of glioma cells, and induced the polarization of M2-like macrophages. Conclusion: IL4I1 could be a promising immunotherapy target for selective modulation of TAMs and stands as a novel macrophage-related prognostic biomarker in glioma.

Comprehensive analysis of disulfidptosis-related lncRNA features for prognosis and immune landscape prediction in colorectal cancer.

Disulfidptosis is a novel mechanism underlying actin-cytoskeleton-associated cell death, but its function in colorectal cancer (CRC) is still elusive. In this study, we investigated the potential role of Disulfidptosis-Related Long Non-Coding RNAs (DRLs) as prognostic indicators in CRC. Through transcriptome data from TCGA CRC cases, we identified 44 prognosis-correlated DRLs by Univariate Cox Regression Analysis and observed a differential expression pattern of these DRLs between CRC and normal tissues. Consensus clustering analysis based on DRL expression led to subgroup classification of CRC patients with distinct molecular fingerprints, accompanied by a superior survival outcome in cluster 2. We are encouraged to develop a score model incorporating 12 key DRLs to predict patient outcomes. Notably, this model displayed more reliable accuracy than other predictive indicators since DRLs are intimately related to tumor immune cell infiltration, suggesting a considerable potential of our DRL-score model for tumor therapy. Our data offered a valuable insight into the prognostic significance of DRLs in CRC and broke a new avenue for tumor prognosis prediction.

Alkylamine-Confined Thickness-Tunable Synthesis of Co(OH)2-CoO Nanosheets toward Oxygen Evolution Catalysis.

Thickness regulation of transition metal hydroxides/oxides nanosheets with superior catalytic properties represents a promising strategy to enhance catalytic performance, but it remains an enormous challenge to achieve precise control, especially when it comes to the ultrathin limit (several atomic layers). In this work, a facile strategy of alkylamine-confined growth is proposed for the synthesis of thickness-tunable metal hydroxide/oxide nanosheets. Specifically, ultrathin cobalt hydroxide and cobaltous oxide hybrid (Co(OH)2-CoO) nanosheets (Co-O NSs) with a thickness in the range of 2-6 nm (5-13 atomic layers) are synthesized by using alkylamines with different carbon chain lengths as the ligand to modulate vertical coordination ability. Co-O NSs with a thickness of 2 nm (Co-O NSs-2 nm) exhibit excellent oxygen evolution reaction (OER) performance with an overpotential of 278 mV at 10 mA/cm2. The maximized number of active sites including oxygen vacancies, optimal adsorption strength, and the highest electrical conductivity are considered as the potential factors contributing to the excellent OER performance of Co-O NSs-2 nm. This work holds great significance for the precise thickness-tunable synthesis of transition metal layered hydroxide nanosheets with modulated and improved catalytic performance.

Editorial for the Special Issue on Recent Advances in Thin Film Electronic Devices.

Thin film electronic devices have been attracting more and more attention because of their applications in many industry fields, such as in flat panel displays (FPDs), energy devices, sensors, memories, and so on [...].

Amorphous InGaZnO Thin-Film Transistors with Double-Stacked Channel Layers for Ultraviolet Light Detection.

Amorphous InGaZnO thin film transistors (a-IGZO TFTs) with double-stacked channel layers (DSCL) were quite fit for ultraviolet (UV) light detection, where the best DSCL was prepared by the depositions of oxygen-rich (OR) IGZO followed by the oxygen-deficient (OD) IGZO films. We investigated the influences of oxygen partial pressure (PO) for DSCL-TFTs on their sensing abilities by experiments as well as Technology Computer Aided Design (TCAD) simulations. With the increase in PO values for the DSCL depositions, the sensing parameters, including photogenerated current (Iphoto), sensitivity (S), responsivity (R), and detectivity (D*) of the corresponding TFTs, apparently degraded. Compared with PO variations for the OR-IGZO films, those for the OD-IGZO depositions more strongly influenced the sensing performances of the DSCL-TFT UV light detectors. The TCAD simulations showed that the variations of the electron concentrations (or oxygen vacancy (VO) density) with PO values under UV light illuminations might account for these experimental results. Finally, some design guidelines for DSCL-TFT UV light detectors were proposed, which might benefit the potential applications of these novel semiconductor devices.

Neisseria meningitidis Opca Protein/MnO2 Hybrid Nanoparticles for Overcoming the Blood-Brain Barrier to Treat Glioblastoma.

The major hurdle in glioblastoma therapy is the low efficacy of drugs crossing the blood-brain barrier (BBB). Neisseria meningitidis is known to specifically enrich in the central nervous system through the guidance of an outer membrane invasion protein named Opca. Here, by loading a chemotherapeutic drug methotrexate (MTX) in hollow manganese dioxide (MnO2 ) nanoparticles with surface modification of the Opca protein of Neisseria meningitidis, a bionic nanotherapeutic system (MTX@MnO2 -Opca) is demonstrated to effectively overcome the BBB. The presence of the Opca protein enables the drug to cross the BBB and penetrate into tumor tissues. After accumulating in glioblastoma, the nanotherapeutic system catalyzes the decomposition of excess H2 O2 in the tumor tissue and thereby generates O2 , which alleviates tumor hypoxia and enhances the effect of chemotherapy in the treatment of glioblastoma. This bionic nanotherapeutic system may exhibit great potential in the treatment of glioblastoma.

Atmosphere Effect in Post-Annealing Treatments for Amorphous InGaZnO Thin-Film Transistors with SiOx Passivation Layers.

We investigated the electrical performance and positive bias stress (PBS) stability of the amorphous InGaZnO thin-film transistors (a-IGZO TFTs) with SiOx passivation layers after the post-annealing treatments in different atmospheres (air, N2, O2 and vacuum). Both the chamber atmospheres and the device passivation layers proved important for the post-annealing effects on a-IGZO TFTs. For the heat treatments in O2 or air, the larger threshold voltage (VTH) and off current (IOFF), smaller field-effect mobility (µFE), and slightly better PBS stability of a-IGZO TFTs were obtained. The X-ray photoemission spectroscopy (XPS) and secondary ion mass spectroscopy (SIMS) measurement results indicated that the oxygen atoms from the ambience led to less oxygen vacancies (VO) and more oxygen-related defects in a-IGZO after the heat treatments in O2 or air. For the annealing processes in vacuum or N2, the electrical performance of the a-IGZO TFTs showed nearly no change, but their PBS stability evidently improved. After 4500 seconds' stressing at 40 V, the VTH shift decreased to nearly 1 V. In this situation, the SiOx passivation layers were assumed to effectively prevent the oxygen diffusion, keep the VO concentration unchanged and refuse the oxygen-related defects into the a-IGZO films.

Performance and multi-scale investigation on the phase miscibility of poly(lactic acid)/amided silica nanocomposites.

In this work, amino-functionalized nano-SiO2 (m@g-SiO2) was synthesized through coupling reaction on the surface of nano-SiO2. Moreover, the optimum preparation conditions of m@g-SiO2 were selected via orthogonal experiments as follows: reaction temperature of 80 °C, reaction time of 8 h, the mass ratio of stearic acid, N,N'­carbonyldiimidazole, imidazole hydrochloride and g-SiO2 of 0.5:0.7:0.7:1. Fourier transform infrared spectroscopy, static angle measurement and X-ray photoelectron spectroscopy unanimously confirmed the formation of m@g-SiO2. Furthermore, poly(lactic acid)(PLA)/m@g-SiO2 nanocomposites was prepared with m@g-SiO2 as fillers to improve the comprehensive performance of PLA. Then, the mechanical properties and crystallization behavior of PLA/m@g-SiO2 nanocomposites were studied, which showed that the impact strength and elongation-at-break of PLA/m@g-SiO2 (0.3 wt%) nanocomposites were increased by 78.05% and 1148%, respectively, and its crystallinity was increased by 26.46%. Simultaneously, thermal gravimetric analysis indicated that the thermal stability of PLA/m@g-SiO2 nanocomposites was improved. Eventually, the multi-scale investigation on the phase miscibility of PLA/m@g-SiO2 nanocomposites was probed by rheological behaviors analysis and the molecular dynamics simulations, which confirmed that surface modification of SiO2 greatly enhanced the interaction energy and miscibility between the filler and PLA bulk.

PBK as a Potential Biomarker Associated with Prognosis of Glioblastoma.

Glioblastoma (GBM) is the most aggressive intracranial tumors. Despite the comprehensive treatments, the median survival of GBM patients is still dismal. Consequently, it is critical to explore potential biomarkers and underlying molecular mechanisms of GBM. We integrated two datasets (GSE19728 and GSE 4290) to identify differentially expressed genes (DEGs) of GBM. Eighty-two GBM samples and 31 brain normal samples were screened by using GEO2R and Draw Venn Diagram. We carried out Database for Annotation, Visualization and Integrated Discovery (DAVID) to analyze gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) to analyze the DEGs. To further screen hub genes, protein-protein interaction (PPI) of these DEGs was visualized by Cytoscape with Search Tool for the Retrieval of Interacting Genes (STRING). GEPIA and UALCAN website were utilized to identify the hub genes expression and survival data. In total, 568 common DEGs were determined, including 141 upregulated genes and 427 downregulated genes. Thirty-five hub genes were identified in the highest module consisting of 35 nodes and 535 edges, which are mainly associated with cell cycle, p53 signaling pathway. According to the further analysis results of hub genes, we found that the PDZ-binding kinase (PBK) gene had a high expression and significantly worse survival in GBM contrasted to brain normal samples (P < 0.05). PBK could be a potential prognostic factor and therapeutic target for GBM treatment. In the future, the potential biomarkers for significant prognostic information can be preliminarily assessed using this method, although further experimentations are needed to verify the results.

IGFBP5 increases cell invasion and inhibits cell proliferation by EMT and Akt signaling pathway in Glioblastoma multiforme cells.

BACKGROUND: Recurrence of Glioblastoma multiforme (GBM) seems to be the rule despite combination therapies. Cell invasion and cell proliferation are major reasons for recurrence of GBM. And insulin-like growth factor binding protein 5 (IGFBP5) is the most conserved of the IGFBPs and is frequently dysregulated in cancers and metastatic tissues. RESULTS: By studying the human glioma tissues, we find that IGFBP5 expression associate to the histopathological classification and highly expressed in GBM. Using IGFBP5 mutants we demonstrate that knockdown of IGFBP5 inhibited cell invasion, whereas promoting cell proliferation in GBM cells. Mechanistically, we observed that promoting GBM cell proliferation by inhibiting IGFBP5 was associated with stimulating Akt (Protein kinase B) phosphorylation. However, IGFBP5 promote GBM cell invasion was related to the epithelial-to-mesenchymal transition (EMT). Furthermore, the Chinese Glioma Genome Altas (CGGA) database show that IGFBP5 is significantly increased in recurrent glioma and it predicted worse survival. CONCLUSIONS: The obtained results indicate that IGFBP5 has two sides in GBM-inhibiting cell proliferation but promoting cell invasion.

Self-assembly of oxidation-responsive polyethylene glycol-paclitaxel prodrug for cancer chemotherapy.

Amphiphilic drug conjugates can self-assemble into nanovehicles for cancer drug delivery, but the key is to design stable yet intracellular labile drug linkers for drug retention during blood circulation but fast intracellular drug release. The conjugation of paclitaxel (PTX) is generally via the ester of its 2'-hydroxyl group, but the ester is either too stable to release PTX in the cytosol or so labile that hydrolyzes during circulation. Herein, we report a p-(boronic ester)benzyl-based tumor-specifically cleavable linker for preparing PTX-conjugate with polyethylene glycol (PEG, Mw = 5000 Da) (PEG-B-PTX). The amphiphilic PEG-B-PTX self-assembled into micelle with an average size of ~50 nm and a PTX loading content of 13.3 wt%. The PEG-B-PTX micelles were very stable at the normal physiological environment and thus circulated long in the blood compartment, but fast dissociated and released PTX in response to the elevated reactive­oxygen species (ROS) level in tumors. The conjugate micelles showed significantly improved antitumor efficiency in vitro and in vivo against human glioma and breast cancer cells, and reduced toxicity compared to the clinically used Taxol. Thus, the PTX-conjugate micelles were characteristic of well-characterized chemical structure and nanostructure, precise and reproducible drug loading efficiency (i.e., 100%) and fixed loading content, high PTX loading content due to PTX itself as part of the carrier, no burst drug release, and easy and reproducible fabrication of the micelles, which are all essential for clinical translation.

The enhanced efficacy of herpes simplex virus by lentivirus mediated VP22 and cytosine deaminase gene therapy against glioma.

Despite the comprehensive treatment of surgery following by concurrent radiochemotherapy, the prognosis of malignant glioma remains unsatisfactory with an awful median survival time of only 12-18 months. This might be improved by the development of oncolytic herpes simplex virus. However, the biggest challenge of recombinant herpes simplex virus (rHSV) lies in their limited therapeutic efficiency in clinical trials. This study aims to enhance the efficacy of rHSV against glioma by a HSV-1 tegument protein VP22 modified cytosine deaminase/5-flurocytosine (CD/5-FC) suicide gene system. Stable glioma cell lines carrying CD or VP22-CD fusion gene were successfully obtained by lentiviral infection following Fluorescence-activated cell sorting. The lethal effect of the prodrug 5-FC was significantly increased in the transduced VP22-CD glioma cells compared to the transduced CD glioma cells. Interestingly, VP22 was found to elicit the enhanced efficacy of rHSV-1 against glioma. Furthermore, we detected a synergistic efficacy of rHSV-1 combined with lentivirus mediated VP22 and CD suicide gene therapy in the orthotopic glioma xenograft models. In conclusion, we successfully established the stable cell lines carrying VP22-CD fusion genes. The incorporation of VP22 further induced an enhanced efficacy of rHSV-1 as well as CD suicide gene therapy respectively and synthetically in vitro. Also, we demonstrated an increased therapeutic benefit of rHAV-1 by VP22 modified CD gene therapy against glioma in vivo.