Three-dimensional topological defects and quasi-long-range order in biological liquid crystals.

Active nematic liquid crystals are the main structural phase of gliomas, promoting collective migration and aggression. We establish the existence of nematic order and topological defect lines and loops in 3D in vivo mouse and human glioma brain tumors. As predicted by theory, sections through the disclination lines in 3D appear as ±1/2 topological defects in 2D.

Targeting fatty acid synthase in preclinical models of TNBC brain metastases synergizes with SN-38 and impairs invasion.

Fatty acid synthesis (FAS) has been shown to play a key role in the survival of brain-metastatic (BM) breast cancer. We demonstrate that the fatty acid synthase inhibitor TVB-2640 synergizes with the topoisomerase inhibitor SN-38 in triple-negative breast cancer (TNBC) BM cell lines, upregulates FAS and downregulates cell cycle progression gene expression, and slows the motility of TNBC BM cell lines. The combination of SN-38 and TVB-2640 warrants further consideration as a potential therapeutic option in TNBC BMs.

Subclonal evolution and expansion of spatially distinct THY1-positive cells is associated with recurrence in glioblastoma.

Purpose: Glioblastoma(GBM) is a lethal disease characterized by inevitable recurrence. Here we investigate the molecular pathways mediating resistance, with the goal of identifying novel therapeutic opportunities.

Experimental Design: We developed a longitudinal in vivo recurrence model utilizing patient-derived explants to produce paired specimens(pre- and post-recurrence) following temozolomide(TMZ) and radiation(IR).

Association of Autologous Tumor Lysate-Loaded Dendritic Cell Vaccination With Extension of Survival Among Patients With Newly Diagnosed and Recurrent Glioblastoma: A Phase 3 Prospective Externally Controlled Cohort Trial.

Importance: Glioblastoma is the most lethal primary brain cancer. Clinical outcomes for glioblastoma remain poor, and new treatments are needed.

Objective: To investigate whether adding autologous tumor lysate-loaded dendritic cell vaccine (DCVax-L) to standard of care (SOC) extends survival among patients with glioblastoma.

Rapid Automated Analysis of Skull Base Tumor Specimens Using Intraoperative Optical Imaging and Artificial Intelligence.

Background: Accurate specimen analysis of skull base tumors is essential for providing personalized surgical treatment strategies. Intraoperative specimen interpretation can be challenging because of the wide range of skull base pathologies and lack of intraoperative pathology resources.

Objective: To develop an independent and parallel intraoperative workflow that can provide rapid and accurate skull base tumor specimen analysis using label-free optical imaging and artificial intelligence.

Correlation between brain tissue oxygen tension and regional cerebral oximetry in uninjured human brain under conditions of changing ventilation strategy.

Controversy surrounds regional cerebral oximetry (rSO) because extracranial contamination and unmeasured changes in cerebral arterial:venous ratio confound readings. Correlation of rSO with brain tissue oxygen (PbrO), a "gold standard" for cerebral oxygenation, could help resolve this controversy but PbrO measurement is highly invasive. This was a prospective cohort study.

A customized 3D implant to target laser interstitial thermal therapy ablation of a posterior fossa mass.

Laser interstitial thermal therapy (LITT) is a minimally invasive neurosurgical technique that has been demonstrated to successfully ablate intracranial tumors. While LITT for supratentorial lesions can often be straightforward, ablation of infratentorial lesions can be difficult with current targeting technologies and instrumentation. The anatomical difficulty of targeting posterior fossa masses can be further complicated in patients who have had a prior craniectomy or other procedure that removed the bone that is required to set the surgical trajectory.

Rapid, label-free detection of diffuse glioma recurrence using intraoperative stimulated Raman histology and deep neural networks.

Background: Detection of glioma recurrence remains a challenge in modern neuro-oncology. Noninvasive radiographic imaging is unable to definitively differentiate true recurrence versus pseudoprogression. Even in biopsied tissue, it can be challenging to differentiate recurrent tumor and treatment effect.

Near real-time intraoperative brain tumor diagnosis using stimulated Raman histology and deep neural networks.

Intraoperative diagnosis is essential for providing safe and effective care during cancer surgery. The existing workflow for intraoperative diagnosis based on hematoxylin and eosin staining of processed tissue is time, resource and labor intensive. Moreover, interpretation of intraoperative histologic images is dependent on a contracting, unevenly distributed, pathology workforce.

Thirty-Day Hospital Readmission and Surgical Complication Rates for Shunting in Normal Pressure Hydrocephalus: A Large National Database Analysis.

Background: Research on age-related complications secondary to shunts in normal pressure hydrocephalus (NPH) is primarily limited to single-center studies and small cohorts.

Objective: To determine the rates of hospital readmission and surgical complications, and factors that predict them, following shunt surgery for NPH in a large healthcare network.

Methods: Surgical procedures, complications, and readmissions for adults undergoing ventricular shunting for NPH were determined using de-identified claims from a privately insured United States healthcare network in years 2007-2014.

Correction to: First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma.

Following publication of the original article [1], the authors reported an error in the spelling of one of the author names. In this Correction the incorrect and correct author names are indicated and the author name has been updated in the original publication. The authors also reported an error in the Methods section of the original article.

First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma.

Background: Standard therapy for glioblastoma includes surgery, radiotherapy, and temozolomide. This Phase 3 trial evaluates the addition of an autologous tumor lysate-pulsed dendritic cell vaccine (DCVax-L) to standard therapy for newly diagnosed glioblastoma.

Methods: After surgery and chemoradiotherapy, patients were randomized (2:1) to receive temozolomide plus DCVax-L (n = 232) or temozolomide and placebo (n = 99).

Serious adverse events following Normal Pressure Hydrocephalus surgery.

Objective: Recent Normal Pressure Hydrocephalus (NPH) practice guidelines describe a serious adverse event (SAE) rate following surgery of 11%.

Patients & Methods: We conducted a retrospective review of 162 consecutive patients who have undergone work-up at our center's multidisciplinary NPH clinic over a 47 month time period (2/2014-12/2017). Of these, 22 ultimately underwent neurosurgical ventricular shunt surgery as treatment for NPH.

Rapid intraoperative histology of unprocessed surgical specimens via fibre-laser-based stimulated Raman scattering microscopy.

Conventional methods for intraoperative histopathologic diagnosis are labour- and time-intensive, and may delay decision-making during brain-tumour surgery. Stimulated Raman scattering (SRS) microscopy, a label-free optical process, has been shown to rapidly detect brain-tumour infiltration in fresh, unprocessed human tissues. Here, we demonstrate the first application of SRS microscopy in the operating room by using a portable fibre-laser-based microscope and unprocessed specimens from 101 neurosurgical patients.

Comparison of Diffusion Tensor Imaging and Magnetic Resonance Perfusion Imaging in Differentiating Recurrent Brain Neoplasm From Radiation Necrosis.

Rationale And Objectives: To compare differences in diffusion tensor imaging (DTI) and dynamic susceptibility-weighted contrast-enhanced (DSC) magnetic resonance (MR) perfusion imaging characteristics of recurrent neoplasm and radiation necrosis in patients with brain tumors previously treated with radiotherapy with or without surgery and chemotherapy.

Materials And Methods: Patients with a history of brain neoplasm previously treated with radiotherapy with or without chemotherapy and surgery who developed a new enhancing lesion on posttreatment surveillance MRI were enrolled. DSC perfusion MRI and DTI were performed.

Detection of human brain tumor infiltration with quantitative stimulated Raman scattering microscopy.

Differentiating tumor from normal brain is a major barrier to achieving optimal outcome in brain tumor surgery. New imaging techniques for visualizing tumor margins during surgery are needed to improve surgical results. We recently demonstrated the ability of stimulated Raman scattering (SRS) microscopy, a nondestructive, label-free optical method, to reveal glioma infiltration in animal models.

Lateral inhibition of Notch signaling in neoplastic cells.

During normal development, heterogeneous expression of Notch ligands can result in pathway suppression in the signal-sending cell, a process known as lateral inhibition. It is unclear if an analogous phenomenon occurs in malignant cells. We observed significant induction of Notch ligands in glioblastoma neurospheres and pancreatic carcinoma cells cultured in low oxygen, suggesting that this phenomenon could occur around hypoxic regions.

Silencing BMI1 eliminates tumor formation of pediatric glioma CD133+ cells not by affecting known targets but by down-regulating a novel set of core genes.

Clinical outcome of children with malignant glioma remains dismal. Here, we examined the role of over-expressed BMI1, a regulator of stem cell self-renewal, in sustaining tumor formation in pediatric glioma stem cells. Our investigation revealed BMI1 over-expression in 29 of 54 (53.

Tenascin-C: a novel candidate marker for cancer stem cells in glioblastoma identified by tissue microarrays.

Glioblastoma multiforme (GBM) is a highly aggressive brain tumor, with dismal survival outcomes. Recently, cancer stem cells (CSCs) have been demonstrated to play a role in therapeutic resistance and are considered to be the most likely cause of cancer relapse. The identification of CSCs is an important step toward finding new and effective ways to treat GBM.

Restoration of the orbital aesthetic subunit with the thoracodorsal artery system of flaps in patients undergoing radiation therapy.

Objectives To demonstrate the advantages of the thoracodorsal artery scapular tip autogenous transplant (Tdast) for patients requiring restoration of the orbital aesthetic subunit. Design Prospective case series. Setting Tertiary center.

Immunohistochemical staining, laser capture microdissection, and filter-aided sample preparation-assisted proteomic analysis of target cell populations within tissue samples.

An important problem involves isolating subpopulations of cells defined by protein markers in clinical tissue samples for proteomic studies. We describe a method termed Immunohistochemical staining, laser capture microdissection (LCM) and filter-aided sample preparation (FASP)-Assisted Proteomic analysis of Target cell populations within tissue samples (ILFAPT). The principle of ILFAPT is that a target cell population expressing a protein of interest can be lit up by immunohistochemical staining and isolated from tissue sections using LCM for FASP and proteomic analysis.

Neurosurgical aspects of central nervous system infections.

Infections of the central nervous system (CNS) can be severe, disabling, and potentially fatal. Infections of the central nervous system (CNS) can be severe, disabling, and potentially fatal. Appropriate recognition of symptoms facilitates expeditious evaluation, prompt diagnosis, and timely treatment.

Regression of a meningioma during paclitaxel and bevacizumab therapy for breast cancer.

Meningiomas often are not amenable to total resection, and subtotally resected meningiomas often recur. Recurrent meningiomas present a clinical dilemma, particularly when surgical and radiotherapy options are exhausted, as there are no chemotherapeutic options that demonstrate consistent, significant efficacy. We report a patient with the regression of a recurrent World Health Organization grade I meningioma during combination chemotherapy with bevacizumab and paclitaxel for breast cancer.

CD90 is identified as a candidate marker for cancer stem cells in primary high-grade gliomas using tissue microarrays.

Although CD90 has been identified as a marker for various kinds of stem cells including liver cancer stem cells (CSCs) that are responsible for tumorigenesis, the potential role of CD90 as a marker for CSCs in gliomas has not been characterized. To address the issue, we investigated the expression of CD90 in tissue microarrays containing 15 glioblastoma multiformes (GBMs), 19 WHO grade III astrocytomas, 13 WHO grade II astrocytomas, 3 WHO grade I astrocytomas and 8 normal brain tissues. Immunohistochemical analysis showed that CD90 was expressed at a medium to high level in all tested high-grade gliomas (grade III and GBM) whereas it was barely detectable in low-grade gliomas (grade I and grade II) and normal brains.