+1 (800) 713-8519 ext 500
lfoundationusa@gmail.com
Research
Laterally placed expandable interbody spacers improve radiographic and clinical outcomes: A 1-year follow-up study
Laterally Placed Expandable Interbody Spacers With and Without Adjustable Lordosis Improve Radiographic and Clinical Outcomes: A Two-Year Follow-Up Study
Introduction Interbody spacers are necessary for achieving disc height restoration when surgical intervention is used for the treatment of severe degenerative disc disease. Minimally invasive lateral lumbar interbody fusion (MIS LLIF) is a popular surgical approach that historically uses large static interbody spacers through a lateral approach. However, static spacers have been associated with iatrogenic distraction and excessive impaction forces, which may increase the risk of subsidence and loss of lordosis, compromising stability. Expandable interbody spacers with or without adjustable lordosis may help address these concerns by maximizing segmental lordosis and aiding in sagittal balance correction.
Expandable Technology Improves Clinical and Radiographic Outcomes of Minimally Invasive Lateral Lumbar Interbody Fusion for Degenerative Disc Disease
Background: Static interbody spacers are standard of care for minimally invasive lateral lumbar interbody fusion (MIS LLIF). However, placement of large static interbody spacers typically requires multiple trialing, endplate preparation, and forceful impaction. A lateral expandable interbody spacer with adjustable lordosis can be inserted at a reduced height, to optimize the endplate-to-endplate fit. This study describes radiographic and clinical outcomes in patients treated using lateral titanium expandable interbody spacers with adjustable lordosis using MIS LLIF.
Comparative Effectiveness of Laterally Placed Expandable versus Static Interbody Spacers: A 1-Year Follow-Up Radiographic and Clinical Outcomes Study
Study design: Retrospective chart review. Purpose: This study compared the clinical and radiographic outcomes of patients treated with expandable and static interbody spacers following minimally invasive lateral lumbar interbody fusion (MIS-LLIF) with 12-month follow-up.
Descriptive Analysis of 1972 Cervical Corpectomy Patients and 30-Day Postoperative Outcomes
Background: There exists no large, multi-institutional analysis of patients undergoing cervical corpectomy for common degenerative spinal disease, including patient demographics and comorbidities as well as postoperative complications.
Sepsis and septic shock after craniotomy: Predicting a significant patient safety and quality outcome measure
Objectives: Sepsis and septic shock are important quality and patient safety metrics. This study examines incidence of Sepsis and/or septic shock (S/SS) after craniotomy for tumor resection, one of the most common neurosurgical operations.
Risk factors and associated complications with unplanned intubation in patients with craniotomy for brain tumor
Patients undergoing surgical resection of a brain tumor have the potential risk for beingintubated post-operatively, which may be associated with significant morbidity and/or mortality after surgery. This study was analyzed various preoperative patient characteristics, postoperative outcomes, and complications to identify risk factors for unplanned intubation (UI) in adult patients undergoing craniotomy for a brain tumor and created a risk score framework for that cohort.
Surgical Management and Adjuvant Therapy for Patients With Neurological Deficits From Vertebral Hemangiomas: A Meta-Analysis
Study design: Meta-analysis. Objective: To understand the benefits and limitations of surgical management and adjuvant therapies for patients presenting with neurological deficits from vertebral hemangiomas (VH).
Translational Brain Mapping at the University of Rochester Medical Center: Preserving the Mind Through Personalized Brain Mapping
The Translational Brain Mapping Program at the University of Rochester is an interdisciplinary effort that integrates cognitive science, neurophysiology, neuroanesthesia, and neurosurgery. Patients who have tumors or epileptogenic tissue in eloquent brain areas are studied preoperatively with functional and structural MRI, and intraoperatively with direct electrical stimulation mapping.
Laterally Placed Expandable Interbody Spacers With and Without Adjustable Lordosis Improve Radiographic and Clinical Outcomes: A Two-Year Follow-Up Study
Introduction Interbody spacers are necessary for achieving disc height restoration when surgical intervention is used for the treatment of severe degenerative disc disease. Minimally invasive lateral lumbar interbody fusion (MIS LLIF) is a popular surgical approach that historically uses large static interbody spacers through a lateral approach. However, static spacers have been associated with…
Laterally Placed Expandable Interbody Spacers With and Without Adjustable Lordosis Improve Radiographic and Clinical Outcomes: A Two-Year Follow-Up Study
Introduction Interbody spacers are necessary for achieving disc height restoration when surgical intervention is used for the treatment of severe degenerative disc disease. Minimally invasive lateral lumbar interbody fusion (MIS LLIF) is a popular surgical approach that historically uses large static interbody spacers through a lateral approach.
Nomogram for Individualized Prediction and Prognostic Factors for Survival in Patients with Primary Spinal Chordoma: A Population-Based Longitudinal Cohort Study
Background: Chordoma is a type of rare bone tumor and is a relatively slow-growing, low-grade malignancy that is locally invasive and aggressive. The nomogram is widely used in the field of cancer because it can provide a clear picture for clinicians to predict the survival rate, which can lead more accurate decisions in clinical treatment.
Surgical Management and Adjuvant Therapy for Patients With Neurological Deficits From Vertebral Hemangiomas: A Meta-Analysis
Study design: Meta-analysis. Objective: To understand the benefits and limitations of surgical management and adjuvant therapies for patients presenting with neurological deficits from vertebral hemangiomas (VH).
The correlation of fractional anisotropy parameters with Ki-67 index, and the clinical implication in grading of non-enhancing gliomas and neuronal-glial tumors
Purpose: To investigate the correlation between the FA parameters and Ki-67 labeling index, and their diagnostic performance in grading supratentorial non-enhancing gliomas and neuronal-glial tumors (GNGT).
Comparative Effectiveness of Laterally Placed Expandable versus Static Interbody Spacers: A 1-Year Follow-Up Radiographic and Clinical Outcomes Study
Study Design Retrospective chart review. Purpose This study compared the clinical and radiographic outcomes of patients treated with expandable and static interbody spacers following minimally invasive lateral lumbar interbody fusion (MIS-LLIF) with 12-month follow-up.
Translational Brain Mapping at the University of Rochester Medical Center: Preserving the Mind Through Personalized Brain Mapping
The Translational Brain Mapping Program at the University of Rochester is an interdisciplinary effort that integrates cognitive science, neurophysiology, neuroanesthesia, and neurosurgery. Patients who have tumors or epileptogenic tissue in eloquent brain areas are studied preoperatively with functional and structural MRI, and intraoperatively with direct electrical stimulation mapping. Post-operative neural and cognitive outcome…
Laterally Placed Expandable Interbody Spacers With and Without Adjustable Lordosis Improve Radiographic and Clinical Outcomes: A Two-Year Follow-Up Study
Introduction Interbody spacers are necessary for achieving disc height restoration when surgical intervention is used for the treatment of severe degenerative disc disease. Minimally invasive lateral lumbar interbody fusion (MIS LLIF) is a popular surgical approach that historically uses large static interbody spacers through a lateral approach.
Domain-Specific Diaschisis: Lesions to Parietal Action Areas Modulate Neural Responses to Tools in the Ventral Stream
Neural responses to small manipulable objects (“tools”) in high-level visual areas in ventral temporal cortex (VTC) provide an opportunity to test how anatomically remote regions modulate ventral stream processing in a domain-specific manner.
Nomogram for Individualized Prediction and Prognostic Factors for Survival in Patients with Primary Spinal Chordoma: A Population-Based Longitudinal Cohort Study
Background: Chordoma is a type of rare bone tumor and is a relatively slow-growing, low-grade malignancy that is locally invasive and aggressive. The nomogram is widely used in the field of cancer because it can provide a clear picture for clinicians to predict the survival rate, which can lead more accurate decisions in clinical treatment.
Comparative Analysis of Decompression Versus Decompression and Fusion for Surgical Management of Lumbar Spondylolisthesis
Objective: When lumbar stenosis involves spondylolisthesis, many surgeons include fixation. Two recent trials have shown no consensus to definitive treatment. We aimed to add to the discourse of fusion versus decompression in patients with lumbar spondylolisthesis by providing a large-scale generalizable study.
What is the advance of extent of resection in glioblastoma surgical treatment-a systematic review
Glioblastoma multiform (GBM) is the most common malignant brain tumor characterized by poor prognosis, increased invasiveness, and high relapse rates. The relative survival estimates are quite low in spite of the standard treatment for GBM in recent years. Now, it has been gradually accepted that the amount of tumor mass removed correlates with longer survival rates.
Risk Factors and Associated Complications of Symptomatic Venous Thromboembolism in Patients with Craniotomy for Meningioma
Objective: Patients undergoing surgical resection of meningioma are at increased risk for developing venous thromboembolism (VTE). The aim of this study was to assess occurrence of VTE in patients who underwent surgical resection of meningioma to determine risk factors and associated complications of VTE.
Current strategies of reduce the rate of dysphagia and dysphonia after anterior cervical spine surgery and role of corticosteroids
Conflict of interest statement Conflicts of interest: The authors have no conflicts of interest to declare
Use of image-guided bone scalpel for resection of spine tumors: technical note
In the literature, the use of navigation for spine tumor surgery has largely centered on implant placement. We describe the cases of two patients with spinal tumors on whom we utilized our resection technique of registering an ultrasonic bone scalpel (UBS) to a navigation system. In both cases, we achieved a satisfactory tumor resection with negative margins and excellent neurologic outcomes. We feel that using the navigation-registered UBS is a valuable tool to increase the operator’s ability to achieve desired resections while minimizing the neurologic deficits and operative morbidity associated with these challenging surgical cases.
Metastatic prostate cancer mimicking a subdural hematoma: A case report and literature review
Occurrences of metastatic prostate cancer imitating a subdural hematoma are limited to a small number of case reports, even though prostate cancer spreads to the dura more than other types of cancer. Here, we present the case of a 64 year-old male whose prostate carcinoma’s metastasis mimicked a subdural hematoma, and he suffered a middle cerebral artery stroke. Prostate cancer’s high rate of progression to the dura is disproportionate to its relatively low rate of brain metastasis. Furthermore, we explore the potential molecular implications of prostate cancer’s propensity to spread to the dura.
Chondrosarcoma of the Osseous Spine Treated by Surgery With or Without Radiotherapy: A Propensity Score Matched and Grade/Stage-stratified Study
Study design: This was a longitudinal cohort study. Objective: The main objective of this study was to investigate the outcomes of surgery with or without radiotherapy during treatment of patients with chondrosarcoma of the osseous spine.
The expression profile of PD-L1 and CD8+ lymphocyte in pituitary adenomas indicating for immunotherapy
Background: Pituitary adenomas (PAs) are the second most common brain tumors, and mostly are benign tumors. However, there exists subtypes of PAs refractory to common treatments, and need novel therapy. Programmed death 1 (PD-1) blockade has shown durable objective response in a variety of malignancies, and the key predictive markers for this immunotherapy were PD-L1 and CD8+ tumor-infiltrating lymphocyte (TILs) expression. To evaluate the potential immunotherapy for PAs, we investigated the expression of these two immune markers in PAs.
Molecular and clinical characterization of PTPN2 expression from RNA-seq data of 996 brain gliomas
Abstract Background: Immune checkpoint inhibitors have been shown to promote antitumor immunity and achieve durable tumor remissions. However, certain tumors are refractory to current immunotherapy. These negative results encouraged us to uncover other therapeutic targets and strategies. PTPN2 (protein tyrosine phosphatase, non-receptor type 2) has been newly identified as an immunotherapy target. Loss of PTPN2 sensitizes the tumor to immunotherapy via IFNγ signaling.
The compression of L5 nerve root, single or double sites?-radiographic graded signs, intra-operative detect technique and clinical outcomes
Background: The L5 nerve root could be compressed at both L4-5 and L5-S1 regions. If L5 nerve root has confirmed compression at L4-5 level and questionable compression at L5-S1 foramina, performing both surgeries at L4-5 and L5-S1 levels may induce unnecessary extra surgery on L5-S1; however, ignoring foraminal stenosis of L5/S1 may require re-exploration.
Risk Factors Associated with Readmission and Reoperation in Patients Undergoing Spine Surgery
Objective: Reoperation and readmission are often avoidable, costly, and difficult to predict. We sought to identify risk factors for readmission and reoperation after spine surgery and to use these factors to develop a scoring system predictive of readmission and reoperation.
Effect of Single-Level Transforaminal Lumbar Interbody Fusion on Segmental and Overall Lumbar Lordosis in Patients with Lumbar Degenerative Disease
Objective: To investigate the ability of transforaminal lumbar interbody fusion (TLIF) to improve lumbar lordosis (LL). Methods: In this retrospective study, 92 patients undergoing single-level TLIF to treat lumbar degenerative disease were divided into a low back pain, radiculopathy, and neurogenic claudication group according to their symptoms. Preoperative and postoperative measures, including segmental LL, whole LL, pelvic incidence (PI), pelvic tilt, thoracic kyphosis, sagittal vertical axis, visual analog scale for back and leg pain, and Oswestry Disability Index, were used to evaluate radiographic and clinical outcomes.
Mesenchymal stem cells deliver exogenous miR-21 via exosomes to inhibit nucleus pulposus cell apoptosis and reduce intervertebral disc degeneration
Although mesenchymal stem cells (MSCs) transplantation into the IVD (intervertebral disc) may be beneficial in inhibiting apoptosis of nucleus pulposus cells (NPCs) and alleviating IVD degeneration, the underlying mechanism of this therapeutic process has not been fully explained. The purpose of this study was to explore the protective effect of MSC-derived exosomes (MSC-exosomes) on NPC apoptosis and IVD degeneration and investigate the regulatory effect of miRNAs in MSC-exosomes and associated mechanisms for NPC apoptosis. MSC-exosomes were isolated from MSC medium, and its anti-apoptotic effect was assessed in a cell and rat model…
Risk factors associated with venous thromboembolism in patients undergoing spine surgery
OBJECTIVE Patients undergoing spinal surgery are at risk for developing venous thromboembolism (VTE). The authors sought to identify risk factors for VTE in these patients. METHODS The American College of Surgeons National Surgical Quality Improvement Project database for the years 2006-2010 was reviewed for patients who had undergone spinal surgery according to their primary Current Procedural Terminology code(s). Clinical factors were analyzed to identify associations with VTE. RESULTS Patients who…
Advanced Neuroimaging in the Evaluation of Spinal Cord Tumors and Tumor Mimics: Diffusion Tensor and Perfusion-Weighted Imaging
Spinal cord tumors are an important component of pathologic diseases involving the spinal cord. Conventional magnetic resonance (MR) imaging only provides anatomical information. MR diffusion tensor imaging (DTI) and MR perfusion-weighted imaging (PWI) may detect microstructure diffusion and hemodynamic changes in these tumors. We review recent application studies of MR DTI and PWI in spinal cord tumors. Overall, MR DTI and MR PWI are …
Association of the Extent of Resection With Survival in Glioblastoma: A Systematic Review and Meta-analysis
Importance: Glioblastoma multiforme (GBM) remains almost invariably fatal despite optimal surgical and medical therapy. The association between the extent of tumor resection (EOR) and outcome remains undefined, notwithstanding many relevant studies. Objective: To determine whether greater EOR is associated with improved 1- and 2-year overall survival and 6-month and 1-year progression-free survival in patients with GBM.
The influence of maximum safe resection of glioblastoma on survival in 1229 patients: Can we do better than gross-total resection?
Objective: Glioblastoma multiforme (GBM) is the most common and deadliest primary brain tumor. The value of extent of resection (EOR) in improving survival in patients with GBM has been repeatedly confirmed, with more extensive resections providing added advantages. The authors reviewed the survival of patients with significant EORs and assessed the relative benefit/risk of resecting 100% of the MRI region showing contrast-enhancement with or without additional resection of the surrounding FLAIR abnormality region, and they assessed the relative benefit/risk of performing this additional resection.
An update on the clinical diagnostic value of β-hCG and αFP for intracranial germ cell tumors
Background: Pathological examination combined with tumor markers has become a standard for the diagnosis of intracranial germ cell tumors (ICGCTs), but the current concept of ‘secreting germ cell tumors’ and three empirically highly specific diagnostic criteria (β-hCG ≥ 50 IU/L or αFP ≥ 10 ng/mL; β-hCG ≥ 100 IU/L or αFP ≥ 50 ng/mL; β-hCG > 50 IU/L or αFP > 25 ng/mL) are not based upon pathology examination or CSF cytology. Further investigation is needed to re-evaluate their value.
Intraventricular Hemangiopericytoma: A Case Report and Literature Review
Background: Hemangiopericytomas are rare intracranial neoplasms that generally occur in the fifth decade of life and are commonly dural-based, supratentorial tumors. They are classified as World Health Organization grade II or III because of their aggressive nature with high rates of local recurrence and distant metastasis. This case is of an intraventricular hemangiopericytoma in a 23-year-old man. Intraventricular locations are rare, with only 10 cases reported in the literature. Our patient is the youngest to be diagnosed with an intraventricular hemangiopericytoma outside a pediatric case discovered at autopsy
A novel brain metastasis xenograft model for convection enhanced delivery of targeted toxins via a micro osmotic pump system enabled for real time bioluminescence imaging
Brain metastasis is a common cause of mortality in patients with cancer, and is associated with poor prognosis. There is a current requirement for the identification of relevant brain metastasis tumor models, which may be used to test novel therapeutic agents and delivery systems in pre clinical studies. The present study aimed to investigate the development of a murine model of brain metastasis, and the application of bioluminescence imaging (BLI) for monitoring tumor growth and response to targeted toxins (TT). A luciferase modified human brain…
Xanthomatous hypophysitis
We present a 69-year-old woman who presented with chronic headaches and was found to have a pituitary mass on MRI, which was biopsied and said to be lymphocytic hypophysitis. The woman was placed on prednisone and followed with routine eye examinations. Two years later, the lesion gradually increased in size and the woman developed a decrease in peripheral vision in the right eye. An MRI showed abutment of the right optic nerve by the mass. A repeat endoscopic transsphenoidal biopsy/resection of …
Clinical Outcomes of 36 Sacral Chordoma Surgeries
Chordoma is the most frequent primary spine tumor, with the majority involved in the sacrococcygeal region. Because chordoma is rare, slowly growing and locally aggressive, it is difficult to evaluate the effectiveness of treatment protocols and prediction of outcome. En bloc resection of primary sacral tumors is the primary treatement modality. Rates of local recurrence and survival were dependent on negative surgical margins.
Diphtheria toxin-based targeted toxin therapy for brain tumors
Targeted toxins (TT) are molecules that bind cell surface antigens or receptors such as the transferrin or interleukin-13 receptor that are overexpressed in cancer. After internalization, the toxin component kills the cell. These recombinant proteins consist of an antibody or carrier ligand coupled to a modified plant or bacterial toxin such as diphtheria toxin (DT). These fusion proteins
A novel brain metastasis xenograft model for convection enhanced delivery of targeted toxins via a micro osmotic pump system enabled for real time bioluminescence imaging
Brain metastasis is a common cause of mortality in patients with cancer, and is associated with poor prognosis. There is a current requirement for the identification of relevant brain metastasis tumor models, which may be used to test novel therapeutic agents and delivery systems in pre clinical studies. The present study aimed to investigate the development of a murine model of brain metastasis, and the application of bioluminescence imaging (BLI) for monitoring tumor growth and response to targeted toxins (TT). A luciferase modified human brain…
Return to play after cervical spine injury in sports
Spinal cord injuries (SCIs) resulting from sports now represent 8.9% of the total causes of SCI. Regardless of cause, there are bound to be return-to-play decisions to be made for athletes. Since catastrophic cervical spine injuries are among the most devastating injuries in all of sports, returning from a cervical spine injury is one of the most difficult decisions in sports medicine. Axial loading is the primary mechanism for catastrophic cervical spine injuries. Axial loading occurs…
Shunt-Related Intracranial Abscess Caused by Staphylococcus lugdunensis in a Hydranencephalic Patient
Background Staphylococcus lugdunensis is a coagulase-negative staphylococcus with aggressive and rapidly progressive infectious behavior. This organism has emerged as an important pathogen implicated in both community-acquired and nosocomial infections, including meningitis, brain abscess, catheter-related bacteremia, and ventriculoperitoneal shunt infection.
Intracerebral infusion of the bispecific targeted toxin DTATEGF in a mouse xenograft model of a human metastatic non-small cell lung cancer
The aim of this study is to investigate the anti-cancer effect of the bispecific diphtheria toxin (DT) based immunotoxin DTATEGF, which targets both the epidermal growth factor (EGF) receptor (EGFR) and the urokinase-type plasminogen activator (uPA) receptor (uPAR) in vitro and in vivo when delivered by convection-enhanced delivery (CED) via an osmotic minipump in a human metastatic non-small cell lung cancer (NSCLC) brain tumor mouse xenograft model. The effects of the bispecific immunotoxin DTATEGF, and…
Structure-based discovery of a novel inhibitor targeting the β-catenin/Tcf4 interaction
Overactivation or overexpression of β-catenin in the Wnt (wingless) signaling pathway plays an important role in tumorigenesis. Interaction of β-catenin with T-cell factor (Tcf) DNA binding proteins is a key step in the activation of the proliferative genes in response to upstream signals of this Wnt/β-catenin pathway. Recently, we identified a new small molecule inhibitor, named BC21 (C(32)H(36)Cl(2)Cu(2)N(2)O(2)), which effectively…
Cell surface receptors in malignant glioma
Despite advances in surgery, radiation, and chemotherapy, malignant gliomas are still highly lethal tumors. Traditional treatments that rely on nonspecific, cytotoxic approaches have a marginal impact on patient survival. However, recent advances in the molecular cancer biology underlying glioma pathogenesis have revealed that abnormalities in common cell surface receptors, including receptor tyrosine kinase and other cytokines, mediate the abnormal cellular signal pathways and…
Familial Chiari malformation: case series
Chiari malformations (Types I-IV) are abnormalities of the posterior fossa that affect the cerebellum, brainstem, and the spinal cord with prevalence rates of 0.1%-0.5%. Case reports of familial aggregation of Chiari malformation, twin studies, cosegregation of Chiari malformation with known genetic conditions, and recent gene and genome-wide association studies provide strong evidence of the genetic underpinnings of familial Chiari malformation. The authors report …
Spontaneous acute subdural hematoma as the initial manifestation of chronic myeloid leukemia
Spontaneous acute subdural hematoma is rare and limited to sporadic case reports, associated with neoplasm, aneurysm, arteriovenous malformation and cocaine use. Subdural hematoma has also been reported in association with leukemic malignancies, either during therapy or after diagnosis. However, there are no reports of spontaneous acute subdural hematoma as the primary initial presenting manifestation of a chronic myeloid leukemia.
Targeted Toxins in Brain Tumor Therapy
Targeted toxins, also known as immunotoxins or cytotoxins, are recombinant molecules that specifically bind to cell surface receptors that are overexpressed in cancer and the toxin component kills the cell. These recombinant proteins consist of a specific antibody or ligand coupled to a protein toxin. The targeted toxins bind to a surface antigen or receptor overexpressed in tumors, such as the epidermal growth factor receptor or interleukin-13 receptor. The toxin part of…
Amplification of LAPTM4B and YWHAZ contributes to chemotherapy resistance and recurrence of breast cancer
Adjuvant chemotherapy for breast cancer after surgery has effectively lowered metastatic recurrence rates. However, a considerable proportion of women suffer recurrent cancer at distant metastatic sites despite adjuvant treatment. Identification of the genes crucial for tumor response to specific chemotherapy drugs is a challenge but is necessary to improve outcomes. By using integrated genomics, we identified a small number of overexpressed and amplified genes from chromosome 8q22 that were associated with early disease recurrence despite…
Inhibition of retinal neovascularization by gene transfer of small interfering RNA targeting HIF-1alpha and VEGF
Retinal neovascularization (NV) occurs in various ocular disorders including proliferative diabetic retinopathy, retinopathy of prematurity and secondary neovascular glaucoma, which often result in blindness. Vascular endothelial growth factor (VEGF) is an essential growth factor for angiogenesis, and is particularly regulated by hypoxia inducible factor-1alpha (HIF-1alpha) under hypoxic conditions. Therefore, HIF-1alpha and VEGF could provide targets for …
Suppression of retinal neovascularization by shRNA targeting HIF-1alpha
Purpose: To investigate whether vector-based HIF-1alpha -targeted shRNA expression system (pSUPER(siHIF-1alpha)) can inhibit HIF-1alpha and VEGF expression in vitro and suppress retinal neovascularization in the murine model of oxygen-induced retinopathy. Methods: pSUPER(siHIF-1alpha) from which siRNA targeting HIF-1alpha could be generated was constructed and transfected to human umbilical vein endothelial cell lines (HUVECs). Then…
A hypoxia-independent hypoxia-inducible factor-1 activation pathway induced by phosphatidylinositol-3 kinase/Akt in HER2 overexpressing cells
HER2 overexpression, a known prognostic factor in many human cancers, can activate phosphatidylinositol-3 kinase (PI-3K)/Akt pathways and plays an important role in mediating cell survival and tumor development. Hypoxia-inducible factors (HIFs) promote angiogenesis and energy metabolism and thereby enhance tumor growth and metastasis. HIFs, composed of alpha and beta subunits, are activated in most human cancers, including…
Erk associates with and primes GSK-3beta for its inactivation resulting in upregulation of beta-catenin
Beta-catenin is upregulated in many human cancers and considered to be an oncogene. Hepatocellular carcinoma (HCC) is one of the most prevalent human malignancies, and individuals who are chronic hepatitis B virus (HBV) carriers have a greater than 100-fold increased relative risk of developing HCC. Here we report a mechanism by which HBV-X protein (HBX) upregulates beta-catenin. Erk, which is activated by HBX, associates with…
Suppression of pancreatic tumor progression by systemic delivery of a pancreatic-cancer-specific promoter driven Bik mutant
Pancreatic cancer is highly aggressive with extremely poor prognosis. Developing a pancreatic cancer specific promoter (PCSP) is one approach for pancreatic cancer gene therapy. We have modified the promoter of cholecystokinin type A receptor (CCKAR), named CCK/Mpd, which possesses a relatively high activity in pancreatic cancer cells as compared with normal cells. The CCK/Mpd promoter-driven…
Upregulation of CXCR4 is essential for HER2-mediated tumor metastasis
The receptor tyrosine kinase HER2 enhances tumor metastasis; however, its role in homing to metastatic organs is poorly understood. The chemokine receptor CXCR4 has recently been shown to mediate the movement of malignant cancer cells to specific organs. Here, we show that HER2 enhances the expression of CXCR4, which is required for HER2-mediated invasion in …
Dual regulation of Snail by GSK-3beta-mediated phosphorylation in control of epithelial-mesenchymal transition
The phenotypic changes of increased motility and invasiveness of cancer cells are reminiscent of the epithelial-mesenchymal transition (EMT) that occurs during embryonic development. Snail, a zinc-finger transcription factor, triggers this process by repressing E-cadherin expression; however, the mechanisms that regulate Snail remain elusive. Here we find that Snail is highly unstable, with a short half-life about 25 min. We show that GSK-3beta binds to and phosphorylates Snail at two consensus motifs to dually regulate…
Cancer-specific activation of the survivin promoter and its potential use in gene therapy
Survivin is expressed in many cancers but not in normal adult tissues and is transcriptionally regulated. To test the feasibility of using the survivin promoter to induce cancer-specific transgene expression in lung cancer gene therapy, a vector expressing a luciferase gene driven by the survivin promoter was constructed and evaluated in vitro and in vivo. We found that the survivin promoter was generally more highly activated in cancer cell lines than…
Upregulation of IKKalpha/IKKbeta by integrin-linked kinase is required for HER2/neu-induced NF-kappaB antiapoptotic pathway
Constitutively active HER2/neu activates nuclear factor kappa-B (NF-kappaB) in cells and induces their resistance to apoptotic stimuli such as tumor necrosis factor-alpha (TNF-alpha). Here, we show that integrin-linked kinase (ILK), the crucial signal transducer in the integrin pathway, is involved in HER2/neu-mediated activation of NF-kappaB. Expression of…
Enhancement of Bik antitumor effect by Bik mutants
Bik was initially identified as a BH3-domain-only protein that interacts with E1B 19K. Although systemically administered wild-type Bik significantly inhibited tumor growth and metastasis in an orthotopic nude mouse model, the proapoptotic potency of Bik can be modulated by posttranslational phosphorylation. Here, we found that…
HER-2/Neu signaling and therapeutic approaches in breast cancer
Amplification or overexpression of HER-2/neu occurs in 30% of human breast and ovarian cancers and is associated with a poor clinical outcome, including short survival and time to relapse. Recent advances in our understanding of HER-2/neu signaling pathways have significantly increased our understanding of the tumorigenesis of breast cancer and …
The apoptosis and proliferation after photorefractive keratectomy
Objective: To search the correlation between the apoptosis and proliferation of keratocytes and investigate the influence of phototherapeutic keratectomy (PTK) and mechanical epithelial scrape (MES) on keratocyte apoptosis and proliferation. Methods: Rabbit corneas received photorefractive keratectomy (PRK, -9.9 diopters, 6 mm diameter). Animals were evaluated subsequently up to 6 months after surgery by in vivo confocal microscopy. Corneas were prepared for H.E. staining, corneal cell…
Artificial senescence of bovine retinal pigment epithelial cells induced by near-ultraviolet in vitro
RPE cells irradiated by near-ultraviolet (NUV) were characterized at cellular, biochemical and molecular levels in order to determine whether light-induced RPE changes contribute to the senescence of RPE cells in vitro. Biochemical and molecular parameters of cellular senescence were studied by using both bovine RPE cells at confluence repeatedly irradiated by NUV (peaking at 365 nm) and RPE cells at different levels of population doubling (PDL). After repeated NUV…