John H. Rossmeisl, Jr.

John H. Rossmeisl, Jr.
Virginia Polytechnic Institute and State University | VT · Department of Small Animal Clinical Sciences

DVM, MS, DACVIM

About

199
Publications
40,821
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3,229
Citations
Introduction
My research focus is on the development of novel therapeutics for brain tumors, and the use of dogs with spontaneous brain tumors as translational disease models. I have particular interests in biomedical devices that facilitate drug delivery to the central nervous system, and identification of the molecular and genetic signatures of malignant gliomas.
Additional affiliations
June 2012 - October 2020
Wake Forest University
Position
  • Principal Investigator
August 2003 - present
Virginia Polytechnic Institute and State University
Position
  • Professor
Education
August 1993 - June 1997
Auburn University
Field of study
  • Veterinary Medicine

Publications

Publications (199)
Article
Magnetic resonance imaging (MRI) diffusion tensor imaging (DTI) measures have been described as methods for quantifying spinal cord injury and predicting outcome in dogs with intervertebral disc herniation (IVDH); however, studies comparing methods for selecting regions of interest (ROIs) are currently lacking. The aims of this retrospective, metho...
Article
Full-text available
Glioblastoma is the deadliest malignant brain tumor. Its location behind the blood-brain barrier (BBB) presents a therapeutic challenge by preventing effective delivery of most chemother-apeutics. H-FIRE is a novel tumor ablation method that transiently disrupts the BBB through currently unknown mechanisms. We hypothesized that H-FIRE mediated BBB...
Article
Introduction: Convection-enhanced delivery (CED) has been extensively studied for drug delivery to the brain due to its inherent ability to bypass the blood-brain barrier. Unfortunately, CED has also been shown to inadequately distribute therapeutic agents over a large enough targeted tissue volume to be clinically beneficial. In this study, we exp...
Article
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Three juvenile dogs presented with an acute onset of paraspinal hyperesthesia and/or neurologic deficits. These dogs underwent anesthesia for MRI and additional diagnostics. The thoracolumbar MRI in Dog 1 revealed an accumulation of T2-weighted (T2W) hyperintense, T1-weighted (T1W) iso- to hyperintense, contrast enhancing extradural material. The d...
Article
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Background: Brain tumor therapeutic responses can be quantified from magnetic resonance images (MRI) using 1- (1D) and 2-dimensional (2D) linear and volumetric methods, but few studies in dogs compare these techniques. Hypotheses: Linear methods will be obtained faster, but have less agreement than volumetric measurements. Therapeutic response agre...
Article
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Background: Seizures in the early postoperative period after intracranial surgery may affect outcome in dogs. Objectives: To determine the incidence of early postoperative seizures (EPS) in dogs with brain tumors, identify specific risk factors for EPS, and determine if EPS affects outcome. Animals: Eighty-eight dogs that underwent 125 intracranial...
Article
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Background: Orthostatic tremor (OT) is a rare movement disorder characterized by high-frequency (>12 Hz) involuntary, rhythmic, sinusoidal movements affecting predominantly the limbs while standing. Objective: To describe the signalment, presenting complaints, phenotype, diagnostic findings, treatment, and outcome of a large sample of dogs with OT....
Article
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The treatment of CNS disorders suffers from the inability to deliver large therapeutic agents to the brain parenchyma due to protection from the blood-brain barrier (BBB). Herein, we investigated high-frequency pulsed electric field (HF-PEF) therapy of various pulse widths and interphase delays for BBB disruption while selectively minimizing cell a...
Article
The fiberoptic microneedle device (FMD) is a fused-silica microcatheter capable of co-delivery of fluids and light that has been developed for convection-enhanced delivery and photothermal treatments of glioblastoma. Here we investigate the biocompatibility of FMD fragments chronically implanted in the rat brain in the context of evaluating potenti...
Chapter
In veterinary medicine, irreversible electroporation (IRE) applications have been evaluated in several early phase clinical trials evaluating the safety and feasibility of treatment of solid tumors located within different organ systems. These clinical trials support the use of IRE as a safe and effective alternative treatment option for tumors tha...
Article
Improved therapeutics for malignant brain tumors are urgently needed. High-frequency irreversible electroporation (H-FIRE) is a minimally invasive, nonthermal tissue ablation technique, which utilizes high-frequency, bipolar electric pulses to precisely kill tumor cells. The mechanisms of H-FIRE-induced tumor cell death and potential for cellular r...
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Full-text available
New therapeutic strategies are direly needed in the fight against cancer. Over the last decade, several tumor ablation strategies have emerged as stand-alone or combination therapies. Histotripsy is the first completely non-invasive, non-thermal, and non-ionizing tumor ablation method. Histotripsy can produce consistent and rapid ablations, even ne...
Article
Background: High-grade meningioma is an aggressive type of brain cancer that is often recalcitrant to surgery and radiotherapy, leading to poor overall survival. Currently, there are no FDA-approved drugs for meningioma, highlighting the need for new therapeutic options, but development is challenging due to the lack of predictive preclinical mode...
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Objective Design 3D printed skull contoured brain biopsy guides (3D‐SCGs) from computed tomography (CT) or T1‐weighted magnetic resonance imaging (T1W MRI). Study Design Feasibility study. Sample Population Five beagle dog cadavers and two client‐owned dogs with brain tumors. Methods Helical CT and T1W MRI were performed on cadavers. Planned tar...
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Dissemination of glioma in humans can occur as leptomeningeal nodules, diffuse leptomeningeal lesions, or ependymal lesions. Cerebrospinal fluid (CSF) drop metastasis of glioma is not well-recognized in dogs. Ten dogs with at least two anatomically distinct and histologically confirmed foci of glioma were included in this study. The 10 dogs underwe...
Article
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The updated VCOG‐CTCAE v2 guidelines contain several important updates and additions since the last update (v1.1) was released in 2011 and published within Veterinary and Comparative Oncology in 2016. As the Veterinary Cooperative Oncology Group (VCOG) is no longer an active entity, the original authors and contributors to the VCOG‐CTCAE v1.0 and v...
Article
Full-text available
OBJECTIVE Treatment of CNS disorders suffer from the inability to deliver large therapeutic agents to the brain parenchyma due to protection from the blood-brain barrier (BBB). High-frequency electroporation (HFE) employs a series of high voltage pulsed electric fields to disrupt the BBB and/or ablate tumor tissue while sparring proteinaceous struc...
Article
Glioblastoma (GBM) complexity and heterogeneity requires treatment that addresses those pathobiological features. We have been developing selective cytotoxic agents able to target at the same time several GBM-associated factors. The chosen targets are responsible for the disease progression and/or recurrence as well as for resistance to the existin...
Article
The interleukin 13 receptor alpha 2 (IL13RA2) and ephrin type-A receptor 2 (EPHA2) receptors are attractive therapeutic targets, being expressed in ~90% of canine and human gliomas, and absent in normal brain. Clinical trials using an earlier generation IL-13 based cytotoxin showed encouraging clinical effects in human glioma, but met with technica...
Article
Standard treatment for glioblastoma is non-curative and only partially effective. Convection enhanced delivery (CED) was developed as an alternative approach for effective loco-regional delivery of drug via a small catheter inserted into the diseased brain. However, previous CED clinical trials revealed the need for improved catheters for controlle...
Article
Full-text available
Background: Quantitative magnetic resonance imaging (QMRI) techniques of magne-tization transfer ratio (MTR) and diffusion tensor imaging (DTI) provide microstruc-tural information about the spinal cord. Objective: Compare neurologic grades using the modified Frankel scale with MTR and DTI measurements in dogs with thoracolumbar intervertebral disk...
Article
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Background: Stereotactic brain biopsy (SBB) allows for histopathologic diagnosis of brain tumors. Adverse events (AE) occur in 5 to 29% of dogs after SBB, but risk factors associated with developing AE are poorly described. Objective: Identify clinicopathologic, diagnostic imaging, or procedural variables that are associated with AE in dogs after S...
Article
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Background Treatment for glioblastoma (GBM) remains an unmet need in medicine. Novel therapies that address GBM complexity and heterogeneity in particular are warranted. To this end, we target four tumor-associated receptors at a time that span virtually all of the GBM microenvironment including bulk tumor cells, infiltrating tumor cells, neovascul...
Article
Full-text available
Background: The interleukin 13 receptor alpha 2 (IL13RA2) and ephrin type-A receptor 2 (EPHA2) receptors are attractive therapeutic targets, being expressed in ~90% of canine and human gliomas, and absent in normal brain. Clinical trials using an earlier generation IL-13 based cytotoxin showed encouraging clinical effects in human glioma, but met...
Article
Full-text available
In veterinary medicine, quality of life (QOL) assessment instruments, which are important components of the holistic evaluation of treatment success, have largely not included organ-specific concerns that may be broadly relevant to caregivers of dogs with intracranial disease. The objective of this study was to identify core questionnaire items and...
Article
Full-text available
BACKGROUND: The interleukin 13 receptor alpha 2 (IL13RA2) and ephrin type-A receptor 2 (EPHA2) receptors are attractive therapeutic targets, being expressed in ~90% of canine and human gliomas, and absent in normal brain. Clinical trials using an earlier generation IL-13 based cytotoxin showed encouraging clinical effects in human glioma, but met w...
Article
Full-text available
Background Intracranial hypertension (ICH) is often presumptively diagnosed based on clinical or imaging findings. Clinical or imaging surrogates of ICH are not usually validated with reference standard direct intracranial pressure (dICP) recordings. Hypotheses Dogs with brain magnetic resonance imaging (MRI) or clinical features of presumed ICH w...
Article
Full-text available
Background: Seizures are a common presenting sign in dogs with brain tumors. Hypothesis/objectives: To investigate the effect of radiotherapy on freedom from brain tumor-associated seizures and survival time in dogs. Animals: Thirty-two client-owned dogs with brain tumor-associated seizures; 18 received medical treatment and radiotherapy, 14 r...
Article
Sporadic gliomas in companion dogs provide a window on the interaction between tumorigenic mechanisms and host environment. We compared the molecular profiles of canine gliomas with those of human pediatric and adult gliomas to characterize evolutionarily conserved mammalian mutational processes in gliomagenesis. Employing whole-genome, exome, tran...
Article
Primary brain tumors are among the deadliest cancers that remain highly incurable. A need exists for new approaches to tumor therapy that can circumvent the blood brain barrier (BBB), target highly resistant tumors and cancer stem-like cells (CSCs) as well create an anti-cancer immunomodulatory environment. Successful treatments may also require a...
Article
Full-text available
Background: Histiocytic sarcoma affecting the central nervous system (CNS HS) in dogs may present as primary or disseminated disease, often characterized by inflammation. Prognosis is poor, and imaging differentiation from other CNS tumors can be problematic. Objective: To characterize the clinicopathological inflammatory features, breed predisp...
Article
Full-text available
Treatment of intracranial disorders suffers from the inability to accumulate therapeutic drug concentrations due to protection from the blood–brain barrier (BBB). Electroporation-based therapies have demonstrated the capability of permeating the BBB, but knowledge of the longevity of BBB disruption (BBBD) is limited. In this study, we quantify the...
Article
A heterogeneous and infiltrating tumor like glioblastoma (GBM) cannot be effectively treated with a single-targeted therapy. Hence, targeting several GBM-associated factors that are responsible for the disease progression and/or recurrence at once is a way to address the issue of tumor heterogeneity. Building on a Phase I clinical trial of a cytoto...
Article
Diffuse gliomas are the commonest of malignant brain tumors with high-grade tumors carrying dismal prognosis. Preclinical models have proven themselves as poor predictors of clinical efficacy, attributed to the lack of a comparable tumor microenvironment. Comparative genomics of canine and human gliomas provide an attractive alternative modality to...
Article
Full-text available
In the dog, primary intracranial neoplasia represents ~2–5% of all cancers and is especially common in certain breeds including English and French bulldogs and Boxers. The most common types of primary intracranial cancer in the dog are meningioma, glioma, and choroid plexus tumors, generally occurring in middle aged to older dogs. Much work has rec...
Article
Full-text available
Clinical translation of novel therapeutics that improve the survival and quality of life of patients with neurological disease remains a challenge, with many investigational drug and device candidates failing in advanced stage clinical trials. Naturally occurring inherited and acquired neurological diseases, such as epilepsy, inborn errors of metab...
Article
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Background: The intranasal (IN) route for rapid drug administration in patients with brain disorders, including status epilepticus, has been investigated. Status epilepticus is an emergency, and the IN route offers a valuable alternative to other routes, especially when these fail. Objectives: To compare IN versus IV midazolam (MDZ) at the same...
Article
Full-text available
Granulomas can “mimic” gliomas on magnetic resonance imaging (MRI) in human patients. The goal of this retrospective study was to report canine brain granulomas that were consistent with glioma based upon MRI, report their histologic diagnosis, and identify MRI criteria that might be useful to distinguish granuloma from glioma. Ten granulomas, init...
Article
Full-text available
Intramedullary signal change (ISC) is a non-specific finding that is frequently observed on magnetic resonance imaging (MRI) examinations of the canine spinal cord. ISC can represent a variety of primary pathological processes such as neoplasms or myelitides or secondary changes such as edema, cysts, gliosis, or myelomalacia. An unusual phenotype o...
Article
Full-text available
Intramedullary signal change (ISC) is a non-specific finding that is frequently observed on magnetic resonance imaging (MRI) examinations of the canine spinal cord. ISC can represent a variety of primary pathological processes such as neoplasms or myelitides or secondary changes such as edema, cysts, gliosis, or myelomalacia. An unusual phenotype of...
Preprint
Full-text available
Sporadic gliomas in companion dogs provide a window on the interaction between tumorigenic mechanisms and host environment. We compared the molecular profiles of canine gliomas with those of human pediatric and adult gliomas to characterize evolutionarily conserved mammalian mutational processes in gliomagenesis. Employing whole genome-, exome-, tr...
Article
Vertebral osteosarcoma (OSA) is the most common primary vertebral tumor in dogs, however studies examining the survival time after surgical decompression of these tumors are limited. There is also limited information regarding the benefit of adjunctive treatments such as radiation therapy or chemotherapy in these patients. The goal of this study wa...
Article
Full-text available
Background: Despite promising treatments for breast cancer, mortality rates remain high and treatments for metastatic disease are limited. High-frequency irreversible electroporation (H-FIRE) is a novel tumor ablation technique that utilizes high-frequency bipolar electric pulses to destabilize cancer cell membranes and induce cell death. However,...
Article
Full-text available
Background Stereotactic brain biopsy (SBB) is a technique that allows for definitive diagnosis of brain lesions. Little information is available regarding the diagnostic utility of SBB in dogs with intracranial diseases. Objective To investigate the diagnostic accuracy (DA) of SBB in dogs with brain tumors. Animals Thirty‐one client‐owned dogs th...
Patent
Full-text available
The present invention relates to the field of optical imaging and therapeutics. More particularly, embodiments of the present invention provide minimally-invasive Fiberoptic Microneedle Devices (FMDs) for light-based therapeutics, which physically penetrate tissue and deliver light directly into the target area below the skin surface. Embodiments o...
Article
Malignant gliomas are incurable tumors and canine spontaneous gliomas are the closest model to human disease. In our Phase I canine clinical trial we are delivering a cocktail targeting IL-13RA2 and EphA2 receptors containing modified bacterial cytotoxins using convection enhanced delivery (CED). Dogs with forebrain gliomas demonstrating IL-13RA2 a...
Article
Glioblastoma is a heterogeneous tumor for which all single-targeted agents failed. Being that a cytotoxic cocktail targeting IL-13RA2 and EphA2 receptors is effective in the treatment of spontaneous gliomas in dogs, we have been further pursuing molecular resection by targeting four tumor-specific/associated receptors at once: IL-13RA2, EphA2, EphA...
Article
Sporadic glioma occurs in companion dogs at frequencies comparable to humans. Genomic characterization of canine glioma has a distinct merit, in that age distribution at the time of diagnosis implies a pediatric disease while the animals are in the adult stage of life. This creates an opportunity to compare relative timing of driver events to that...
Article
Full-text available
In dogs diagnosed with solid tumors, regional lymph node involvement or evidence of distant metastasis can predict worse prognoses and significantly decreased survival. Lymph node size alone has been shown to be insufficient as a predictor for the accurate clinical staging of some canine neoplasia. However, certain regional lymph nodes (including t...
Article
Full-text available
High-frequency irreversible electroporation is a nonthermal method of tissue ablation that uses bursts of 0.5-to 2.0-microsecond bipolar electric pulses to permeabilize cell membranes and induce cell death. High-frequency irreversible electroporation has potential advantages for use in neurosurgery, including the ability to deliver pulses without i...
Article
Sporadic glioma occurs in companion dogs at frequencies comparable to humans, despite differences in environmental exposures and age at time of diagnosis. Despite advances in molecular and phenotypic characterization of adult gliomas, accurate prognostication and curative treatment modalities are often limited by lack of animal translational models...
Article
Full-text available
A variety of inflammatory conditions of unknown cause (meningoencephalomyelitis of unknown etiology-MUE) and neoplastic diseases can affect the central nervous system (CNS) of dogs. MUE can mimic intracranial neoplasia both clinically, radiologically and even in some cases, histologically. Serum immunosignature protein microarray assays have been u...
Article
The National Cancer Institute Comparative Brain Tumor Consortium, Patient Outcomes Working Group, propose a consensus document in support of standardized magnetic resonance imaging protocols for canine brain tumor clinical trials. The intent of this manuscript is to address the widely acknowledged need to ensure canine brain tumor imaging protocols...
Article
Full-text available
Glioma is a unique neoplastic disease that develops exclusively in the central nervous system (CNS) and rarely metastasizes to other tissues. This feature strongly implicates the tumor-host CNS microenvironment in gliomagenesis and tumor progression. We investigated the differences and similarities in glioma biology as conveyed by transcriptomic pa...
Article
Full-text available
High-frequency irreversible electroporation is a nonthermal method of tissue ablation that uses bursts of 0.5- to 2.0-microsecond bipolar electric pulses to permeabilize cell membranes and induce cell death. High-frequency irreversible electroporation has potential advantages for use in neurosurgery, including the ability to deliver pulses without...