Spontaneous Resolution of an Aggressive Direct Carotid Cavernous Fistula Following Partial Transvenous Embolization Treatment: A Case Report and Review of Literatures.

Traumatic direct type carotid cavernous fistula (CCF) is an acquired arteriovenous shunt between the carotid artery and the cavernous sinus post severe craniofacial trauma or iatrogenic injury. We reported a 46-year-old woman who had developed a traumatic direct type CCF after severe head trauma with a skull base fracture and brain contusion hemorrhage. The clinical manifestations of the patient included pulsatile exophthalmos, proptosis, bruits, chemosis, and a decline in consciousness.

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).

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 hyperthermia produced by a magnetic field.

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.

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.

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 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 outweigh its therapeutic benefits.

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--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.

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--glycolide acid) (PLGA) microparticles in the treatment of brain abscess. The vancomycin embedded microparticles (VMPs) were stereotactically introduced into the cerebral parenchyma in bacteria- induced brain abscess-bearing rats.

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 O-methylguanine-DNA methyltransferase (MGMT) in tumors.

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

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. 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.

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.

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.

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 O-alkylguanine-DNA alkyltransferase (AGT). O-benzylguanine (O-BG) can irreversibly inactivate AGT by competing with O-methylguanine and has been confirmed to increase the therapeutic activity of alkylators.

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.

Targeted concurrent and sequential delivery of chemotherapeutic and antiangiogenic agents to the brain by using drug-loaded nanofibrous membranes.

Glioblastoma is the most frequent and devastating primary brain tumor. Surgery followed by radiotherapy with concomitant and adjuvant chemotherapy is the standard of care for patients with glioblastoma. Chemotherapy is ineffective, because of the low therapeutic levels of pharmaceuticals in tumor tissues and the well-known tumor-cell resistance to chemotherapy.

Blockade of Inhibitors of Apoptosis Proteins in Combination with Conventional Chemotherapy Leads to Synergistic Antitumor Activity in Medulloblastoma and Cancer Stem-Like Cells.

Background: Medulloblastoma (MB) is the most common pediatric primary malignant brain tumor. Approximately one-third of MB patients succumb to treatment failure and some survivors suffer detrimental side effects. Hence, the purpose of this study is to explore new therapeutic regimens to overcome chemotherapeutic agent resistance or reduce chemotherapy-induced toxicity.

Advanced interstitial chemotherapy combined with targeted treatment of malignant glioma in rats by using drug-loaded nanofibrous membranes.

Glioblastoma multiforme (GBM), the most prevalent and malignant form of a primary brain tumour, is resistant to chemotherapy. In this study, we concurrently loaded three chemotherapeutic agents [bis-chloroethylnitrosourea, irinotecan, and cisplatin; BIC] into 50:50 poly[(d,l)-lactide-co-glycolide] (PLGA) nanofibres and an antiangiogenic agent (combretastatin) into 75:25 PLGA nanofibres [BIC and combretastatin (BICC)/PLGA]. The BICC/PLGA nanofibrous membranes were surgically implanted onto the brain surfaces of healthy rats for conducting pharmacodynamic studies and onto C6 glioma-bearing rats for estimating the therapeutic efficacy.

Advanced interstitial chemotherapy for treating malignant glioma.

Glioblastoma multiforme (GBM) is the most prevalent primary neoplasm of the brain. Moreover, the prognosis of patients with GBM has been poor, with almost uniform progressive neurological impairment and rapid death. Despite the availability of multimodal treatments through surgery, focal radiation, and chemotherapy, no major progress has been reported until recently.

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.

Concurrent delivery of carmustine, irinotecan, and cisplatin to the cerebral cavity using biodegradable nanofibers: In vitro and in vivo studies.

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor, and the prognosis of patients afflicted with GBM has been dismal, exhibiting progressive neurologic impairment and imminent death. Even with the most active regimens currently available, chemotherapy achieves only modest improvement in the overall survival. New chemotherapeutic agents and novel approaches to therapy are required for improving clinical outcomes.

Nanofibers used for the delivery of analgesics.

Nanofibers are extremely advantageous for drug delivery because of their high surface area-to-volume ratios, high porosities and 3D open porous structures. Local delivery of analgesics by using nanofibers allows site-specificity and requires a lower overall drug dosage with lower adverse side effects. Different analgesics have been loaded onto various nanofibers, including those that are natural, synthetic and copolymer, for various medical applications.