Treatment of Ethmoidal Dural Arteriovenous Fistulae Using Supraorbital Keyhole Subfrontal Approach.

Due to a unique cortical venous drainage pattern without sinus drainage, ethmoidal dural arteriovenous fistula (DAVF) are uncommon cerebral vascular lesions that carry a high risk of brain bleeding and neurologic deficit. Surgical intervention has been found to have a lower complication rate and a more satisfactory obliteration rate than endovascular treatment among the various DAVF treatment options. The supraorbital keyhole subfrontal approach is one of the least invasive and appropriate surgical techniques for addressing the anterior fossa vascular lesion in eDAVFs. We describe two men, ages 60 and 71, who underwent this surgical intervention to treat asymptomatic Cognard type IV eDAVFs. Complete obliteration with a detached fistulous point and skeletonization was accomplished with the aid of intraoperative neuronavigation. Thus, we suggest that a suitable surgical method for the treatment of eDAVFs would be to use a supraorbital keyhole subfrontal approach.

Angiopep-2-conjugated FeTi@Au core-shell nanoparticles for tumor targeted dual-mode magnetic resonance imaging and hyperthermic glioma therapy.

Herein, we fabricated gold surface-coated iron titanium core-shell (FeTi@Au) nanoparticles (NPs) with conjugation of angiopep-2 (ANG) (FeTi@Au-ANG) NPs for targeted delivery and improved NPs penetration by receptor-mediated endocytosis to achieve hyperthermic treatment of gliomas. The synthesized "core-shell" FeTi@Au-ANG NPs exhibited spherical in shape with around 16 nm particle size and increased temperature upon alternating magnetic field (AMF) stimulation, rendering them effective for localized hyperthermic therapy of cancer cells. Effective targeted delivery of FeTi@Au-ANG NPs was demonstrated in vitro by improved transport and cellular uptake, and increased apoptosis in glioma cells (C6) compared with normal fibroblast cells (L929). FeTi@Au-ANG NPs exhibited higher deposition in brain tissues and a superior therapeutic effect in an orthotopic intracranial xenograft mouse model. Taken together, our data indicate that FeTi@Au-ANG NPs hold significant promise as a targeted delivery strategy for glioma treatment using hyperthermia.

Enhanced Anti-Tumor Activity in Mice with Temozolomide-Resistant Human Glioblastoma Cell Line-Derived Xenograft Using SN-38-Incorporated Polymeric Microparticle.

Glioblastoma multiforme (GBM) has remained one of the most lethal and challenging cancers to treat. Previous studies have shown encouraging results when irinotecan was used in combination with temozolomide (TMZ) for treating GBM. However, irinotecan has a narrow therapeutic index: a slight dose increase in irinotecan can induce toxicities that outweigh its therapeutic benefits. SN-38 is the active metabolite of irinotecan that accounts for both its anti-tumor efficacy and toxicity. In our previous paper, we showed that SN-38 embedded into 50:50 biodegradable poly[(d,l)-lactide-co-glycolide] (PLGA) microparticles (SMPs) provides an efficient delivery and sustained release of SN-38 from SMPs in the brain tissues of rats. These properties of SMPs give them potential for therapeutic application due to their high efficacy and low toxicity. In this study, we tested the anti-tumor activity of SMP-based interstitial chemotherapy combined with TMZ using TMZ-resistant human glioblastoma cell line-derived xenograft models. Our data suggest that treatment in which SMPs are combined with TMZ reduces tumor growth and extends survival in mice bearing xenograft tumors derived from both TMZ-resistant and TMZ-sensitive human glioblastoma cell lines. Our findings demonstrate that combining SMPs with TMZ may have potential as a promising strategy for the treatment of GBM.

Spinal metastasis of glioblastoma multiforme before gliosarcomatous transformation: a case report.

BACKGROUND: Glioblastoma multiforme (GBM) is one of the most aggressive malignant brain tumors. Intracranial GBM metastases to the spine are rarely detected clinically. Secondary gliosarcomas after treatment of primary GBM are rarely described. CASE PRESENTATION: Herein, we report the case of a 53-year-old woman who presented to our emergency room with progressive headache and weakness on the left side. Plain computed tomography and contrast magnetic resonance imaging of the brain revealed an approximately 6.8 cm × 4.5 cm right temporoparietooccipital intraaxial cystic tumor with surrounding diffuse perifocal edema that caused midline shift toward the left. Emergency craniotomy was performed to remove the tumor, and pathological examination revealed GBM. The patient received proton beam therapy, Gliadel implantation, and oral temozolomide chemotherapy as well as targeted therapy with bevacizumab. Approximately 15 months after diagnosis, she underwent surgical resection of the right temporal recurrent tumor and was newly diagnosed as having a metastatic spinal tumor. Pathologically, the right temporal and metastatic spinal tumors were gliosarcoma and GBM, respectively. CONCLUSIONS: Concurrent spinal metastasis and gliosarcomatous transformation, which are two types of GBM complications, are rare. To our knowledge, this is the first report of a case of recurrent GBM with gliosarcoma after proton bean therapy.

Sustained local delivery of high-concentration vancomycin from a hybrid biodegradable, antibiotic-eluting, nanofiber-loaded endovascular prosthesis for treatment of mycotic aortic aneurysms.

BACKGROUND: Endovascular repair for mycotic aortic aneurysm (MAA) is a less invasive alternative to open surgery, although the placement of a stent graft in an infected environment remains controversial. In this study, we developed hybrid biodegradable, vancomycin-eluting, nanofiber-loaded endovascular prostheses and evaluated antibiotic release from the endovascular prostheses both in vitro and in vivo. METHODS: Poly(D,L)-lactide-co-glycolide and vancomycin were dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol. This solution was electrospun into nanofibrous tubes, which were mounted onto commercial vascular stents and endovascular aortic stent grafts. In vitro antibiotic release from the nanofibers was characterized using an elution method and high-performance liquid chromatography. Antibiotic release from the hybrid stent graft was analyzed in a three-dimensional-printed model of a circulating MAA. The in vivo drug release characteristics were examined by implanting the antibiotic-eluting stents in the abdominal aorta of New Zealand white rabbits (n = 15). RESULTS: The in vitro study demonstrated that the biodegradable nanofibers and the nanofiber-loaded stent graft provided sustained release of high concentrations of vancomycin for up to 30 days. The in vivo study showed that the nanofiber-loaded stent exhibited excellent biocompatibility and released high concentrations of vancomycin into the local aortic wall for 8 weeks. CONCLUSIONS: The proposed biodegradable vancomycin-eluting nanofibers significantly contribute to the achievement of local and sustainable delivery of antibiotics to the aneurysm sac and the aortic wall, and these nanofibers may have therapeutic applications for MAAs.

Honokiol induces autophagic cell death in malignant glioma through reactive oxygen species-mediated regulation of the p53/PI3K/Akt/mTOR signaling pathway.

Honokiol, an active constituent extracted from the bark of Magnolia officinalis, possesses anticancer effects. Apoptosis is classified as type I programmed cell death, while autophagy is type II programmed cell death. We previously proved that honokiol induces cell cycle arrest and apoptosis of U87 MG glioma cells. Subsequently in this study, we evaluated the effect of honokiol on autophagy of glioma cells and examined the molecular mechanisms. Administration of honokiol to mice with an intracranial glioma increased expressions of cleaved caspase 3 and light chain 3 (LC3)-II. Exposure of U87 MG cells to honokiol also induced autophagy in concentration- and time-dependent manners. Results from the addition of 3-methyladenine, an autophagy inhibitor, and rapamycin, an autophagy inducer confirmed that honokiol-induced autophagy contributed to cell death. Honokiol decreased protein levels of PI3K, phosphorylated (p)-Akt, and p-mammalian target of rapamycin (mTOR) in vitro and in vivo. Pretreatment with a p53 inhibitor or transfection with p53 small interfering (si)RNA suppressed honokiol-induced autophagy by reversing downregulation of p-Akt and p-mTOR expressions. In addition, honokiol caused generation of reactive oxygen species (ROS), which was suppressed by the antioxidant, vitamin C. Vitamin C also inhibited honokiol-induced autophagic and apoptotic cell death. Concurrently, honokiol-induced alterations in levels of p-p53, p53, p-Akt, and p-mTOR were attenuated following vitamin C administration. Taken together, our data indicated that honokiol induced ROS-mediated autophagic cell death through regulating the p53/PI3K/Akt/mTOR signaling pathway.

Comparison of the therapeutic effect of teriparatide with that of combined vertebroplasty with antiresorptive agents for the treatment of new-onset adjacent vertebral compression fracture after percutaneous vertebroplasty.

STUDY DESIGN: Comparing a prospective group of 32 patients, who underwent percutaneous vertebroplasty (PVP) and who were treated with teriparatide for at least 18 months after a new-onset adjacent vertebral compression fracture (VCF), and compared it with a retrospective group of 33 patients, who received antiresorptive agents combined with repeated PVPs for post-PVP new-onset adjacent VCFs. OBJECTIVE: This comparative study aimed to assess the immediate and mid-term efficacy and safety of teriparatide for treating new adjacent VCFs after vertebroplasty. SUMMARY OF BACKGROUND DATA: Vertebroplasty may provoke fractures in adjacent, nonaugmented vertebrae. Subsequent VCFs can occur much sooner and more frequently after PVPs. Antiresorptive agents do not effectively prevent new-onset VCFs or prompt pain relief. Treatment with teriparatide is effective and rapid in increasing spinal bone mineral density (BMD) and in decreasing vertebral fracture risk in patients with osteoporosis. METHODS: Relevant clinical data were compared between a prospective group of patients who received teriparatide and a retrospective group of patients who received antiresorptive agents and repeated PVPs for new-onset adjacent VCFs after PVP. RESULTS: Data in prospective group, including visual analogue scale scores and BMD were compared with those in a retrospective group. In group A, only 1 new-onset VCF occurred during the mean follow-up period of 22.56 months. In group B, 5 patients (6 vertebrae) developed new-onset VCFs after the second PVP, and 2 of these 5 patients had additional new VCFs after the third PVP. Teriparatide significantly reduced the risk of new VCFs after vertebroplasty (odds ratio=0.18; 95% confidence interval, 0.02-1.64). The increase of lumbar spine BMD was 26.32% after 18 months of treatment with teriparatide and 4.62% after 18 months of treatment with antiresorptive agents. In addition, at the 18-month follow-up, mean visual analogue scale scores had decreased from 8.03±1.97-1.37±0.52 in the teriparatide group and from 7.91±1.95-4.23±1.21 in the antiresorptive group. CONCLUSIONS: For the treatment of new-onset adjacent VCF after PVPs, the therapeutic effects of teriparatide is better than that of the combined vertebroplasty and an antiresorptive agent in fracture prevention, BMD change, and sustained pain relief.

Angiopep-2-decorated titanium-alloy core-shell magnetic nanoparticles for nanotheranostics and medical imaging.

The poor permeability of therapeutic agents across the blood-brain barrier and blood-tumor barrier is a significant barrier in glioma treatment. Low-density lipoprotein receptor-related protein (LRP-1) recognises a dual-targeting ligand, angiopep-2, which is overexpressed in the BBB and gliomas. Here, we have synthesized Ti@FeAu core-shell nanoparticles conjugated with angiopep-2 (Ti@FeAu-Ang nanoparticles) to target glioma cells and treat brain cancer via hyperthermia produced by a magnetic field. Our results confirmed that Ti@FeAu core-shell nanoparticles were superparamagnetic, improved the negative contrast effect on glioma, and exhibited a temperature elevation of 12° C upon magnetic stimulation, which implies potential applications in magnetic resonance imaging (MRI) and hyperthermia-based cancer therapy. Angiopep-2-decorated nanoparticles exhibited higher cellular uptake by C6 glioma cells than by L929 fibroblasts, demonstrating selective glioma targeting and improved cytotoxicity up to 85% owing to hyperthermia produced by a magnetic field. The in vivo findings demonstrated that intravenous injection of Ti@FeAu-Ang nanoparticles exhibited a 10-fold decrement in tumor volume compared to the control group. Furthermore, immunohistochemical analysis of Ti@FeAu-Ang nanoparticles showed that coagulative necrosis of tumor tissues and preliminary safety analysis highlighted no toxicity to the haematological system, after Ti@FeAu-Ang nanoparticle-induced hyperthermia treatment.

Role of Polymeric Local Drug Delivery in Multimodal Treatment of Malignant Glioma: A Review.

Malignant gliomas (MGs) are the most common and devastating primary brain tumor. At present, surgical interventions, radiotherapy, and chemotherapy are only marginally effective in prolonging the life expectancy of patients with MGs. Inherent heterogeneity, aggressive invasion and infiltration, intact physical barriers, and the numerous mechanisms underlying chemotherapy and radiotherapy resistance contribute to the poor prognosis for patients with MGs. Various studies have investigated methods to overcome these obstacles in MG treatment. In this review, we address difficulties in MG treatment and focus on promising polymeric local drug delivery systems. In contrast to most local delivery systems, which are directly implanted into the residual cavity after intratumoral injection or the surgical removal of a tumor, some rapidly developing and promising nanotechnological methods-including surface-decorated nanoparticles, magnetic nanoparticles, and focused ultrasound assist transport-are administered through (systemic) intravascular injection. We also discuss further synergistic and multimodal strategies for heightening therapeutic efficacy. Finally, we outline the challenges and therapeutic potential of these polymeric drug delivery systems.

Assessment of Antimicrobial Agents, Analgesics, and Epidermal Growth Factors-Embedded Anti-Adhesive Poly(Lactic-Co-Glycolic Acid) Nanofibrous Membranes: In vitro and in vivo Studies.

BACKGROUND: Postoperative tissue adhesion is a major concern for most surgeons and is a nearly unpreventable complication after abdominal or pelvic surgeries. This study explored the use of sandwich-structured antimicrobial agents, analgesics, and human epidermal growth factor (hEGF)-incorporated anti-adhesive poly(lactic-co-glycolic acid) nanofibrous membranes for surgical wounds. MATERIALS AND METHODS: Electrospinning and co-axial electrospinning techniques were utilized in fabricating the membranes. After spinning, the properties of the prepared membranes were assessed. Additionally, high-performance liquid chromatography and enzyme-linked immunosorbent assays were utilized in assessing the in vitro and in vivo liberation profiles of the pharmaceuticals and the hEGF from the membranes. RESULTS: The measured data suggest that the degradable anti-adhesive membranes discharged high levels of vancomycin/ceftazidime, ketorolac, and hEGF in vitro for more than 30, 24, and 27 days, respectively. The in vivo assessment in a rat laparotomy model indicated no adhesion in the peritoneal cavity at 14 days post-operation, demonstrating the anti-adhesive capability of the sandwich-structured nanofibrous membranes. The nanofibers also released effective levels of vancomycin, ceftazidime, and ketorolac for more than 28 days in vivo. Histological examination revealed no adverse effects. CONCLUSION: The outcomes of this study implied that the anti-adhesive nanofibers with sustained release of antimicrobial agents, analgesics, and growth factors might offer postoperative pain relief and infection control, as well as promote postoperative healing of surgical wounds.

Injectable SN-38-embedded Polymeric Microparticles Promote Antitumor Efficacy against Malignant Glioma in an Animal Model.

Malignant glioma (MG) is extremely aggressive and highly resistant to chemotherapeutic agents. Using electrospraying, the potent chemotherapeutic agent 7-ethyl-10-hydroxycamptothecia (SN-38) was embedded into 50:50 biodegradable poly[(d,l)-lactide-co-glycolide] (PLGA) microparticles (SMPs). The SMPs were stereotactically injected into the brain parenchyma of healthy rats and intratumorally injected into F98 glioma-bearing rats for estimating the pharmacodynamics and therapeutic efficacy. SN-38 was rapidly released after injection and its local (brain tissue) concentration remained much higher than that in the blood for more than 8 weeks. Glioma-bearing rats were divided into three groups-group A (n = 13; stereotactically injected pure PLGA microparticles), group B (n = 12; stereotactically injected Gliadel wafer and oral temozolomide), and group C (n = 13; stereotactic and intratumoral introduction of SMPs). The SMPs exhibited significant therapeutic efficacy, with prolonged survival, retarded tumor growth, and attenuated malignancy. The experimental results demonstrated that SMPs provide an effective and potential strategy for the treatment of MG.

Treating Intracranial Abscesses in Rats with Stereotactic Injection of Biodegradable Vancomycin-Embedded Microparticles.

Brain abscesses are emergent and life-threating despite advances in modern neurosurgical techniques and antibiotics. The present study explores the efficacy of vancomycin embedded to 50:50 poly(lactic-co-glycolide acid) (PLGA) microparticles in the treatment of brain abscess. The vancomycin embedded microparticles (VMPs) were stereotactically introduced into the cerebral parenchyma in Staphylococcus aureus bacteria- induced brain abscess-bearing rats. Experimental rats were divided into three groups: group A (n = 13; no treatment), group B (n = 14; daily vancomycin injection (5 mg intraperitoneally), and group C (n = 12; stereotactic introduction of VMPs into the abscess cavity). Group C exhibited no inflammatory response and significantly increased survival and reduced mean abscess volumes (p <0.001) at the eighth week, compared with other groups. Vancomycin delivery via a biodegradable PLGA vehicle can easily attain Area Under the Curve (AUC)/minimum inhibitory concentration (MIC) ratios of ≥400, and strengthens the therapeutic efficacy of antibiotics without provoking any potential toxicity. Biodegradable VMPs are a safe and sustainable drug delivery vehicle for the treatment of brain abscess.

Study on strontium doped tricalcium silicate synthesized through sol-gel process.

We successfully synthesized a strontium-doped tricalcium silicate (SrxCa3-xSiO5, Sr = 0 to 2 mol%) bone cement using the sol-gel process. The material properties including crystallinity, setting time, mechanical strength, and hydration products were characterized. Release of ions and pH values of simulated body fluid soaked with the bone cement were measured. In vitro biocompatibility of different concentrations of the material was evaluated by the viability of L929 cells. The setting times of as-prepared slurries were all <70 min. Doping with 0.5 mol% Sr reduced the final setting time by 20 min. After 14 days curing, 0.25 mol% Sr-doped SrxCa3-xSiO5 possessed the highest compressive strength of 45 MPa among all the Sr-doped groups with no statistical difference to Ca3SiO5. The bioactivity of the materials was confirmed with the formation of an apatite layer on the surface of the materials after immersion in simulated body fluid. In addition, the proliferation of L929 cells exposed to 1 mol% Sr was significantly promoted as compared to no Sr doping. SrxCa3-xSiO5 is a novel and advanced material that has the potential to serve as a bone cement in bone restoration with appropriate mechanical strength and favorable biocompatibility.

Novel multi-drugs incorporating hybrid-structured nanofibers enhance alkylating agent activity in malignant gliomas.

BACKGROUND: Malignant gliomas (MGs) are highly chemotherapy-resistant. Temozolomide (TMZ) and carmustine (BiCNU) are alkylating agents clinically used for treating MGs. However, their effectiveness is restrained by overexpression of the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) in tumors. O6-benzylguanine (O6-BG) is a nonreversible inhibitor of MGMT, it promotes the cytotoxicity of alkylating chemotherapy. The authors have developed a hybrid-structured nanofibrous membrane (HSNM) that sequentially delivers high concentrations of O6-BG, BiCNU, and TMZ in an attempt to provide an alternative to the current therapeutic options for MGs. METHODS: The HSNMs were implanted onto the cerebral surface of pathogen-free rats following surgical craniectomy, while the in vivo release behaviors of O6-BG, TMZ, and BiCNU from the HSNMs were explored. Subsequently, the HSNMs were surgically implanted onto the brain surface of two types of tumor-bearing rats. The survival rate, tumor volume, malignancy of tumor, and apoptotic cell death were evaluated and compared with other treatment regimens. RESULTS: The biodegradable HSNMs sequentially and sustainably delivered high concentrations of O6-BG, BiCNU, and TMZ for more than 14 weeks. The tumor-bearing rats treated with HSNMs demonstrated therapeutic advantages in terms of retarded and restricted tumor growth, prolonged survival time, and attenuated malignancy. CONCLUSION: The results demonstrated that O6-BG potentiates the effects of interstitially transported BiCNU and TMZ. Therefore, O6-BG may be required for alkylating agents to offer maximum therapeutic benefits for the treatment of MGMT-expressing tumors. In addition, the HSNM-supported chemoprotective gene therapy enhanced chemotherapy tolerance and efficacy. It can, therefore, potentially provide an improved therapeutic alternative for MGs.

Anesthetics and human epidermal growth factor incorporated into anti-adhesive nanofibers provide sustained pain relief and promote healing of surgical wounds.

Background: This study exploited sheath-core-structured lidocaine/human EGF (hEGF)-loaded anti-adhesive poly[(d,l)-lactide-co-glycolide] (PLGA) nanofibrous films for surgical wounds via a co-axial electrospinning technique. Materials and methods: After spinning, the properties of the co-axially spun membranes were characterized by scanning electron microscopy, laser-scanning confocal microscopy, Fourier Transform Infrared spectrometry, water contact angle measurements, and tensile tests. Furthermore, a HPLC analysis and an ELISA evaluated the in vitro and in vivo release curves of lidocaine and hEGF from the films. Results: PLGA anti-adhesion nanofibers eluted high levels of lidocaine and hEGF for over 32 and 27 days, respectively, in vitro. The in vivo evaluation of post-surgery recovery in a rat model demonstrated that no adhesion was noticed in tissues at 2 weeks after surgery illustrating the anti-adhesive performance of the sheath-core-structured nanofibers. Nanofibrous films effectively released lidocaine and hEGF for >2 weeks in vivo. In addition, rats implanted with the lidocaine/hEGF nanofibrous membranes exhibited greater activities than the control demonstrating the pain relief efficacy of the films. Conclusion: The empirical outcomes suggested that the anti-adhesive nanofibrous films with extended release of lidocaine and hEGF offer post-operative pain relief and wound healing.

Honokiol Induces Autophagic Apoptosis in Neuroblastoma Cells through a P53-Dependent Pathway.

In children, neuroblastomas are the most common and deadly solid tumor. Our previous studies showed that honokiol can cross the blood-brain barrier and kill neuroblastoma cells. In this study, we further evaluated if exposure to honokiol for short periods could induce autophagy and subsequent apoptosis of neuroblastoma cells and possible mechanisms. Exposure of neuroblastoma neuro-2a cells to honokiol for 24 h induced morphological shrinkage and cell death. As to the mechanisms, honokiol consecutively induced cytochrome c release from mitochondria, caspase-3 activation, DNA fragmentation and cell apoptosis. Separately, honokiol time-dependently augmented the proportion of autophagic cells and the ratio of light chain 3 (LC3)-II/LC3-I. Pretreatment of neuro-2a cells with 3-methyladenine, an inhibitor of autophagy, attenuated honokiol-induced cell autophagy, caspase-3 activation, DNA damage and cell apoptosis. In contrast, stimulation of autophagy by rapamycin, an inducer of autophagy, significantly enhanced honokiol-induced cell apoptosis. Furthermore, honokiol-induced autophagic apoptosis was confirmed in neuroblastoma NB41A3 cells. Knocking down translation of p53 using RNA interference attenuated honokiol-induced autophagy and apoptosis in neuro-2a and NB41A3 cells. Taken together, this study showed that at early periods, honokiol can induce autophagic apoptosis of neuroblastoma cells through activating a p53-dependent mechanism. Consequently, honokiol has the potential to be a therapeutic option for neuroblastomas.

Percutaneous polymethylmethacrylate vertebroplasty in the treatment of pain induced by metastatic spine tumor.

BACKGROUND: Metastases to the spine are a common problem in the large oncology center and represent a challenging problem in oncology practice. Patients with osteolytic metastases often experience intractable local and/or radicular pain. Therapeutic intervention can alleviate pain, preserve or improve neurologic function, achieve mechanical stability, and improve quality of life. Percutaneous polymethylmethacrylate vertebroplasty is an effective and relatively easy method of relieving patients' pain. METHOD: Between January 2002 and December 2006, 57 patients (78 vertebrae) with spinal metastatic tumor treated with PMMA vertebroplasty were enrolled in this study. The main indication for treatment was pain. RESULT: The mean value of VAS was 8.1+/-0.67 preoperatively, and it significantly decreased to 3.8+/-1.9 (1-8, P<.015) 1 day after vertebroplasty. The mean VAS value 6 months after vertebroplasty was 2.8+/-2.0 (P<.001). The mean amounts of preoperative nonnarcotic analgesic and narcotic analgesic were 1.98+/-1.4 and 1.19+/-0.73, respectively. Postoperatively, the mean amounts of nonnarcotic and narcotic analgesic decreased to 1.35+/-0.70 (P<.05) and 0.65+/-0.53 (P<.05). A statistically significant reduction of nonnarcotic analgesic use was noticed in our study. CONCLUSIONS: Percutaneous vertebroplasty is a minimally invasive procedure that offers a remarkable advantage of effective and immediate pain relief with few complications.

Biodegradable hybrid-structured nanofibrous membrane supported chemoprotective gene therapy enhances chemotherapy tolerance and efficacy in malignant glioma rats.

Chemotherapy is ineffective for treating malignant glioma (MG) because of the low therapeutic levels of pharmaceuticals in tumour tissues and the well-known tumour resistance. The resistance to alkylators is modulated by the DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT). O6-benzylguanine (O6-BG) can irreversibly inactivate AGT by competing with O6-methylguanine and has been confirmed to increase the therapeutic activity of alkylators. We developed hybrid-structured poly[(d,l)-lactide-co-glycolide] nanofibrous membranes (HSNMs) that enable the sequential and sustained release of O6-BG and two alkylators (carmustine and temozolomide [TMZ]). HSNMs were surgically instilled into the cerebral cavity of pathogen-free rats and F98 glioma-bearing rats. The release behaviours of loaded drugs were quantified by using high-performance liquid chromatography. The treatment results were compared with the rats treated with intraperitoneal injection of O6-BG combined with surgical implantation of carmustine wafer and oral TMZ. The HSNMs revealed a sequential drug release behaviour with the elution of high drug concentrations of O6-BG in the early phase, followed by high levels of two alkylators. All drug concentrations remained high for over 14 weeks. Tumour growth was slower and the mean survival time was significantly prolonged in the HSNM-treated group. Biodegradable HSNMs can enhance therapeutic efficacy and prevent toxic systemic effects.

Targeting inhibitors of apoptosis proteins suppresses medulloblastoma cell proliferation via G2/M phase arrest and attenuated neddylation of p21.

Medulloblastoma (MB) is the most common type of malignant childhood brain tumor. We previously showed that inhibitors of apoptosis proteins (IAP) small-molecule inhibitors (LCL161 or LBW242) combined with chemotherapy have synergistic antiproliferative effects on MB cells. The synergistic antitumor effects of combination treatments happen through induction of autophagy and caspase-3/7-activated apoptosis. Here, we investigated the effects of IAP inhibitors or silencing IAP on cell cycle regulation. We discovered that treatment with IAP inhibitors or their combination with conventional chemotherapy (vincristine or cisplatin), as well as RNAi knockdown of cIAP1/2 or XIAP arrested MB cells in the G2/M phase through downregulation of cyclin B1-CDK1 and cyclin A-CDK1/2. Among these three IAPs, only silencing cIAP1 expression enhanced p21 dependent-G2/M phase accumulation. IAP inhibitors reduced cIAP1 expression and increased p21 expression in time course experiments. Furthermore, cIAP1 can govern p21 proteasomal degradation via neddylation in lieu of ubiquitination. Inhibition of IAPs significantly abrogated cIAP1-mediated p21 degradation. We also observed an inverse correlation between nuclear cIAP1 and nuclear p21 expressions in MB tumor tissues. These findings provide new mechanistic evidence of the influence of IAP inhibitors on MB cell proliferation through disruption of the cell cycle.

Transarterial embolization for intractable oronasal hemorrhage associated with craniofacial trauma: evaluation of prognostic factors.

BACKGROUND: This study analyzed the outcomes for clinical application of transarterial embolization (TAE) to treat intractable posttraumatic oronasal hemorrhage in patients who suffered from craniofacial injuries. METHODS: The charts and radiologic and operative records of 34 patients from January 2002 to December 2007 were retrospectively reviewed. Inclusion criteria focused on the patients whose intractable posttraumatic oronasal hemorrhage associated with craniofacial trauma required TAE treatment. The patients' survival was correlated with prognostic factors with Spearman's rank correlation coefficients. Wilcoxon signed ranks test was used to analyze the differences between the severity of shock before and after TAE, and Fisher's exact test was used to analyze unvaried factors. RESULTS: TAE successfully stopped the posttraumatic oronasal hemorrhage in 27 of 34 patients (79.4%). The internal maxillary artery was the most common hemorrhaging vessel requiring embolization. Successful hemostasis by TAE significantly contributed to patient survival (p = 0.001). In addition, higher Glasgow Coma Scale score (>/=8) at presentation, lower shock index (calculated as heart rate/systolic blood pressure;