Bypassing cisplatin resistance in Nrf2 hyperactivated head and neck cancer through effective PI3Kinase targeting.

Background: For patients with head and neck squamous cell carcinoma (HNSCC), failure of definitive radiation combined with cisplatin nearly universally results in death. Although hyperactivation of the Nrf2 pathway can drive radiation and cisplatin resistance along with suppressed anti-tumor immunity, treatment-refractory HNSCC tumors may retain sensitivity to targeted agents secondary to synergistic lethality with other oncogenic drivers (e.g.

Woven Endobridge (WEB) augmented by Y-stent in a shallow basilar tip aneurysm.

The Woven Endobridge (WEB) device can be an effective and simple treatment modality for wide-neck bifurcation intracranial aneurysms. We present a case of a shallow basilar tip aneurysm treated with the WEB device that required stabilization with Y-stent through radial access.

Superior Sagittal Sinus Tumor Eroding through the Skull: An Unfamiliar Presentation of Hepatocellular Carcinoma and Literature Review.

Background: Hepatocellular carcinoma (HCC) most commonly develops in patients with liver cirrhosis caused by hepatitis C and B virus. HCC is the most common cause of death in people with cirrhosis. The lungs, bone, and lymph nodes are frequent sites of metastasis of HCC.

Spinal dural attachments to the vertebral column: An anatomic report and review of the literature.

Background: The spinal dura is anchored within the vertebral canal by connective tissue in the epidural space as well as the spinal roots. Inadvertent disruption of these dural attachments may lead to durotomy and cerebrospinal fluid (CSF) leaks. We observed well-developed connective tissue ligaments connecting the lumbar dura to the spinal column and examined these tissues microscopically.

Chordoma in the lateral medullary cistern in a patient with tuberous sclerosis: A case report and review of the literature.

Background: Chordomas are rare intracranial tumors. There are several reported cases of these tumors arising in patients with tuberous sclerosis (TSC), a neurocutaneous disorder inherited in autosomal dominant fashion that predisposes patients to hamartomatous and neoplastic lesions.

Case Description: A 38-year-old man with the diagnosis of TSC presented with the complaint of dizziness and near syncope.

The relationship between the zygomatic arch and the floor of the middle cranial fossa: a radiographic study.

Objective: Access to the floor of the middle cranial fossa (MCF) is often required for approaches to cranial base lesions. This study measures the craniocaudal distance between the zygomatic arch (ZA) and the floor of the MCF from a random sample of high-resolution computed tomography scans of the cranial base.

Methods: Forty computed tomography scans were imported into an OsiriX station and reconstructed in multiple planes.

Overexpression of dimethylarginine dimethylaminohydrolase protects against cerebral vascular effects of hyperhomocysteinemia.

Rationale: Hyperhomocysteinemia is a cardiovascular risk factor that is associated with elevation of the nitric oxide synthase inhibitor asymmetrical dimethylarginine (ADMA).

Objective: Using mice transgenic for overexpression of the ADMA-hydrolyzing enzyme dimethylarginine dimethylaminohydrolase-1 (DDAH1), we tested the hypothesis that overexpression of DDAH1 protects from adverse structural and functional changes in cerebral arterioles in hyperhomocysteinemia.

Methods And Results: Hyperhomocysteinemia was induced in DDAH1 transgenic (DDAH1 Tg) mice and wild-type littermates using a high methionine/low folate (HM/LF) diet.

Overexpression of dimethylarginine dimethylaminohydrolase inhibits asymmetric dimethylarginine-induced endothelial dysfunction in the cerebral circulation.

Background And Purpose: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase (NOS). An elevation of plasma ADMA levels is associated with cardiovascular disease. ADMA is hydrolyzed by dimethylarginine dimethylaminohydrolases (DDAHs).

Gene-based therapies for the induction of spinal fusion.

Numerous mesenchymal growth factors with osteogenic properties have now been identified. Although many of these proteins can induce bone formation when delivered on a carrier matrix, these approaches have not been fully developed in the laboratory or clinic. The expression of osteogenic proteins via direct or ex vivo gene therapy techniques is also compelling because high-level, long-term gene expression can now be achieved using novel viral and nonviral vectors.

Bone graft substitutes for the promotion of spinal arthrodesis.

In the prototypical method for inducing spinal fusion, autologous bone graft is harvested from the iliac crest or local bone removed during the spinal decompression. Although autologous bone remains the "gold standard" for stimulating bone repair and regeneration, modern molecular biology and bioengineering techniques have produced unique materials that have potent osteogenic activities. Recombinant human osteogenic growth factors, such as bone morphogenetic proteins, transforming growth factor-beta, and platelet-derived growth factor are now produced in highly concentrated and pure forms and have been shown to be extremely potent bone-inducing agents when delivered in vivo in rats, dogs, primates, and humans.

Emerging concepts in the treatment of intracranial aneurysms: stents, coated coils, and liquid embolic agents.

Endovascular techniques for the treatment of intracranial aneurysms are rapidly evolving. Modifications of more traditional coils have been introduced. Such modifications include newer coils coated with various polymers to increase both coil thrombogenicity and degree of aneurysm packing.

Overexpression of dimethylarginine dimethylaminohydrolase reduces tissue asymmetric dimethylarginine levels and enhances angiogenesis.

Background: This study was designed to determine whether overexpression of the enzyme dimethylarginine dimethylaminohydrolase (DDAH) could enhance angiogenesis by reducing levels of the endogenous nitric oxide synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA).

Methods And Results: In DDAH1 transgenic (TG) and wild-type mice (each n=42), the role of DDAH overexpression on angiogenesis was studied by use of the disk angiogenesis system and a murine model of hindlimb ischemia (each n=21). After surgery, animals were treated with either PBS or the NOS inhibitors ADMA or N(omega)-nitro-L-arginine methyl ester (L-NAME; each 250 micromol x kg(-1) x d(-1)) by use of osmotic minipumps (each n=7).

Dimethylarginine dimethylaminohydrolase regulates nitric oxide synthesis: genetic and physiological evidence.

Background: NO is a major regulator of cardiovascular physiology that reduces vascular and cardiac contractility. Accumulating evidence indicates that endogenous inhibitors may regulate NOS. The NOS inhibitors asymmetric dimethylarginine (ADMA) and N-monomethylarginine are metabolized by the enzyme dimethylarginine dimethylaminohydrolase (DDAH).

Human mesenchymal stem cells transduced with recombinant bone morphogenetic protein-9 adenovirus promote osteogenesis in rodents.

The present study was undertaken to determine whether ex vivo bone morphogenetic protein-9 (BMP-9) gene therapy using human mesenchymal stem cells (hMSCs) can induce endochondral bone formation in athymic nude rats. An in vitro study was initially performed on hMSCs to evaluate morphological changes and osteoblastic differentiation induced by replication-defective adenovirus type 5 with the cytomegalovirus promoter and either the BMP-9 (Ad-BMP-9) or beta-galactosidase (Ad-beta-gal) gene. In vivo, athymic nude rats received an injection (10(6) hMSCs transduced with recombinant adenovirus at 50 PFU/cell) into the anterior thigh musculature: Ad-BMP-9 on the left and Ad-beta-gal (control) on the right.

Ex vivo bone morphogenetic protein-9 gene therapy using human mesenchymal stem cells induces spinal fusion in rodents.

Objective: Ex vivo gene therapy with the use of human mesenchymal stem cells (hMSCs) and bone morphogenetic protein (BMP) genes provides a local supply of precursor cells and a supraphysiological dose of osteoinductive molecules that may promote bone formation in patients with inadequate hMSC populations because of age, osteoporosis, metastatic bone disease, iatrogenic depletion, or other metabolic derangements. This study was undertaken to evaluate the efficacy of ex vivo gene therapy with the use of hMSCs and the BMP-9 gene to promote spinal fusion in the rat.

Methods: Sixteen athymic nude rats were treated with hMSCs transduced with recombinant, replication-defective Type 5 adenovirus containing the cytomegalovirus promoter and either the BMP-9 (Ad-BMP-9) or the beta-galactosidase (Ad-beta-gal) gene.

Ectopic osteogenesis using adenoviral bone morphogenetic protein (BMP)-4 and BMP-6 gene transfer.

Bone morphogenetic proteins (BMPs) delivered on scaffolds can induce ectopic bone formation after subcutaneous injection. Adenoviral vectors (Ad) carrying BMP2, BMP7, and BMP9 cDNAs have been shown to produce bone through endochondral ossification. The present study was performed to elucidate the histological events leading to ectopic ossification for two novel first-generation adenoviral constructs encoding BMPs, AdBMP4 and AdBMP6.

Nicotine accelerates angiogenesis and wound healing in genetically diabetic mice.

Recently, we have discovered an endogenous cholinergic pathway for angiogenesis mediated by endothelial nicotinic acetylcholine receptors (nAChRs). Since angiogenesis plays a major role in wound repair, we hypothesized that activation of nAChRs with nicotine would accelerate wound healing in a murine excisional wound model. In genetically diabetic and control mice full-thickness skin wounds (0.