Valerie S. Wong

Bio: Valerie S. Wong is an academic researcher from University of California, San Francisco. The author has contributed to research in topics: Lymphoma & Brain biopsy. The author has an hindex of 2, co-authored 3 publications receiving 187 citations.

Complement Activation and Intraventricular Rituximab Distribution in Recurrent Central Nervous System Lymphoma

Abstract: Purpose: To elucidate the mechanistic basis for efficacy of intrathecal rituximab. We evaluated complement activation as well as the pharmacokinetics of intraventricular rituximab in patients who participated in two phase 1 multicenter studies. Experimental Design: We evaluated complement activation as a candidate mediator of rituximab within the central nervous system (CNS). Complement C3 and C5b-9 were quantified by ELISA in serial cerebrospinal fluid (CSF) specimens after intraventricular rituximab administration. We determined rituximab concentration profiles in CSF and serum. A population three- compartment pharmacokinetic model was built to describe the disposition of rituximab following intraventricular administration. The model was derived from results of the first trial and validated with results of the second trial. Results: Complement C3 and C5b-9 were reproducibly activated in CSF after intraventricular rituximab. Ectopic expression of C3 mRNA and protein within CNS lymphoma lesions was localized to myeloid cells. Constitutive high C3 activation at baseline was associated with adverse prognosis. A pharmacokinetic model was built, which contains three distinct compartments, to describe the distribution of rituximab within the neuroaxis after intraventricular administration. Conclusions: We provide the first evidence of C3 activation within the neuroaxis with intraventricular immunotherapy and suggest that complement may contribute to immunotherapeutic responses of rituximab in CNS lymphoma. Penetration of rituximab into neural tissue is supported by this pharmacokinetic model and may contribute to efficacy. These findings have general implications for intraventricular immunotherapy. Our data highlight potential innovations to improve efficacy of intraventricular immunotherapy both via modulation of the innate immune response as well as innovations in drug delivery. Clin Cancer Res; 20(4); 1029–41. ©2013 AACR .

Abstract 2728: Multivariate analysis of cerebrospinal fluid protein biomarkers in central nervous system lymphoma patients and controls

Abstract: Establishing the diagnosis of primary central nervous system lymphoma (PCNSL) is often difficult as the clinical presentation and radiographic features are nonspecific. The gold standards for diagnosis are cytologic analysis of the CSF, which has poor sensitivity, or brain biopsy, which may be associated with significant morbidity and a high rate of diagnostic failure. We are testing the hypothesis that the cerebrospinal fluid (CSF) proteome contains information which may facilitate early and noninvasive diagnosis of CNS lymphoma as well as provide prognostic information. We evaluated the CSF concentrations of three candidate CNS lymphoma protein biomarkers: CXCL-13, a B-cell homing chemokine, Interleukin-10 (IL-10), an autocrine B-cell growth factor, and antithrombin-III (ATIII), a candidate tumor biomarker which we previously identified by mass spectrometric analysis of the CSF. Determinations were performed by ELISA of CSF diagnostic specimens from 228 patients: 75 specimens were from patients with a confirmed diagnosis of non-Hodgkin9s lymphoma of the brain and 153 controls including 15 specimens from patients with astrocytic neoplasms, 16 specimens from secondary brain tumors including metastases from breast and lung cancer, and 122 other controls including patients with established systemic lymphoma who staged negative for CNS involvement. Mean concentrations of CXCL-13, IL-10 and ATIII were each significantly elevated in the CSF of CNS lymphoma patients compared to the controls (p These preliminary data support a role for CXCL-13 and IL-10 in the pathogenesis of B-cell non-Hodgkin9s lymphoma involving the brain and support our hypothesis that molecular signals within the CSF may be rapidly evaluated in combination to facilitate early and relatively non-invasive diagnosis. This approach may also be applied with other diagnostic modalities such as neuroimaging and flow-cytometry. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2728.

Drug Delivery Systems, CNS Protection, and the Blood Brain Barrier

Abstract: Present review highlights various drug delivery systems used for delivery of pharmaceutical agents mainly antibiotics, antineoplastic agents, neuropeptides, and other therapeutic substances through the endothelial capillaries (BBB) for CNS therapeutics. In addition, the use of ultrasound in delivery of therapeutic agents/biomolecules such as proline rich peptides, prodrugs, radiopharmaceuticals, proteins, immunoglobulins, and chimeric peptides to the target sites in deep tissue locations inside tumor sites of brain has been explained. In addition, therapeutic applications of various types of nanoparticles such as chitosan based nanomers, dendrimers, carbon nanotubes, niosomes, beta cyclodextrin carriers, cholesterol mediated cationic solid lipid nanoparticles, colloidal drug carriers, liposomes, and micelles have been discussed with their recent advancements. Emphasis has been given on the need of physiological and therapeutic optimization of existing drug delivery methods and their carriers to deliver therapeutic amount of drug into the brain for treatment of various neurological diseases and disorders. Further, strong recommendations are being made to develop nanosized drug carriers/vehicles and noninvasive therapeutic alternatives of conventional methods for better therapeutics of CNS related diseases. Hence, there is an urgent need to design nontoxic biocompatible drugs and develop noninvasive delivery methods to check posttreatment clinical fatalities in neuropatients which occur due to existing highly toxic invasive drugs and treatment methods.

Lyme neuroborreliosis—epidemiology, diagnosis and management

Abstract: Lyme disease, caused by the Borrelia burgdorferi bacterium, is the most common vector-borne disease in the northern hemisphere. The clinical presentation varies with disease stage, and neurological manifestations (often referred to as Lyme neuroborreliosis) are reported in up to 12% of patients with Lyme disease. Most aspects of the epidemiology, clinical manifestation and treatment of Lyme neuroborreliosis are well known and accepted; only the management of so-called chronic Lyme disease is surrounded by considerable controversy. This term is used for disparate patient groups, including those who have untreated late-stage infection (for example, late neuroborreliosis), those with subjective symptoms that persist after treatment (termed 'post-treatment Lyme disease syndrome' [PTLDS]), and those with unexplained subjective complaints that may or may not be accompanied by positive test results for B. burgdorferi infection in serum (here called 'chronic Lyme disease'). The incidence of PTLDS is still a matter of debate, and its pathogenesis is unclear, but there is evidence that these patients do not have ongoing B. burgdorferi infection and, thus, do not benefit from additional antibiotic therapy. Chronic Lyme disease lacks an accepted clinical definition, and most patients who receive this diagnosis have other illnesses. Thus, a careful diagnostic work-up is needed to ensure proper treatment.