A5015891058- Glioma Diagnosis and Treatment
- Cancer-related cognitive impairment studies
- Brain Metastases and Treatment
- Neurogenesis and neuroplasticity mechanisms
- Cancer, Stress, Anesthesia, and Immune Response
- Neuroscience and Neuropharmacology Research
- Mitochondrial Function and Pathology
- Anesthesia and Neurotoxicity Research
- MicroRNA in disease regulation
- Pluripotent Stem Cells Research
- Extracellular vesicles in disease
- Neuroinflammation and Neurodegeneration Mechanisms
- Cancer Cells and Metastasis
- Tryptophan and brain disorders
- Lung Cancer Research Studies
- Ubiquitin and proteasome pathways
- Nerve injury and regeneration
- Axon Guidance and Neuronal Signaling
- Sirtuins and Resveratrol in Medicine
- Head and Neck Surgical Oncology
- ATP Synthase and ATPases Research
- Protein Tyrosine Phosphatases
- Effects of Radiation Exposure
- Metabolism and Genetic Disorders
- Hydrogen's biological and therapeutic effects
University of California, Los Angeles
2024
Neurological Surgery
2015-2023
University of Southern California
2015-2023
LAC+USC Medical Center
2017-2022
Health First
2021
University of California, Irvine
2012-2019
University of California, San Diego
2014
A substantial proportion of breast cancer survivors report significant, long-lasting impairments in cognitive function, often referred to as "chemobrain." Advances detection and treatment mean that many more patients are surviving long-term following diagnosis invasive cancer. Thus, it is important define the types, extent, persistence with cytotoxic drugs.We examined effects chronic two agents commonly used cancer, cyclophosphamide doxorubicin (Adriamycin). Athymic nude rats were given 50...
Cancer survivors face a variety of challenges as they cope with disease recurrence and myriad normal tissue complications brought on by radio- chemotherapeutic treatment regimens. For patients subjected to cranial irradiation for the control CNS malignancy, progressive debilitating cognitive dysfunction remains pressing unmet medical need. Although this problem has been recognized decades, few if any satisfactory long-term solutions exist resolve serious unintended side effect radiotherapy....
Aims: Radiation-induced disruption of mitochondrial function can elevate oxidative stress and contribute to the metabolic perturbations believed compromise functionality central nervous system. To clarify role in mediating adverse effects radiation brain, we analyzed transgenic (mitochondrial catalase [MCAT]) mice that overexpress human localized mitochondria. Results: Compared with wild-type (WT) controls, overexpression MCAT transgene significantly decreased cognitive dysfunction after...
Abstract The frequent use of chemotherapy to combat a range malignancies can elicit severe cognitive dysfunction often referred as “chemobrain,” condition that persist long after the cessation treatment in many 75% survivors. Although health is critical determinant therapeutic outcome, chemobrain remains an unmet medical need adversely affects quality life pediatric and adult cancer Using rodent model chemobrain, we showed chronic cyclophosphamide induced significant performance-based...
Abstract Cranial radiotherapy, although beneficial for the treatment of brain tumors, inevitably leads to normal tissue damage that can induce unintended neurocognitive complications are progressive and debilitating. Ionizing radiation exposure has also been shown compromise structural integrity mature neurons throughout brain, an effect believed be at least in part responsible deterioration cognitive health. Past work cranially transplanted human neural stem cells (hNSCs) or their...
Medulloblastoma (MB) is a malignant pediatric brain tumor arising in the cerebellum.Although abnormal GABAergic receptor activation has been described MB, studies have not yet elucidated contribution of receptor-independent GABA metabolism to MB pathogenesis.We find primary tumors globally display decreased expression transaminase (ABAT), protein responsible for metabolism, compared with normal cerebellum.However, less aggressive WNT and SHH subtypes express higher ABAT levels metastatic G3...
Abstract Past preclinical studies have demonstrated the capability of using human stem cell transplantation in irradiated brain to ameliorate radiation-induced cognitive dysfunction. Intrahippocampal embryonic cells and neural (hNSCs) was found functionally restore cognition rats 1 4 months after cranial irradiation. To optimize potential therapeutic benefits transplantation, we further defined optimal windows for maximizing irradiation used induced pluripotent cell-derived hNSCs...
Radiotherapy remains a primary treatment modality for the majority of central nervous system tumors, but frequently leads to debilitating cognitive dysfunction. Given absence satisfactory solutions this serious problem, we have used human stem cell therapies ameliorate radiation-induced impairment. Here, past studies been extended determine whether engrafted cells provide even longer-term benefits cognition.Athymic nude rats were cranially irradiated (10 Gy) and subjected intrahippocampal...
Brain metastases (BM) are responsible for neurological decline and poor overall survival. Although the pro-metastatic roles of glial cells, acquisition neuronal attributes in established BM tumors have been described, there no studies that investigate initial interplay between neurons brain-seeking tumor cells. The aim this study was to characterize early tumor-neuron interactions induced CNS-adaptive changes cells prior macro-colonization.Utilizing pure cultures brain-naïve patient-derived...
Abstract Background Effective control of brain metastasis remains an urgent clinical need due a limited understanding the mechanisms driving it. Although gain neuro-adaptive attributes in breast-to-brain metastases (BBMs) has been described, that govern this neural acclimation and resulting competency are poorly understood. Herein, we define role neural-specific splicing factor Serine/Arginine Repetitive Matrix Protein 4 (SRRM4) regulating microenvironmental adaptation colonization breast...
Abstract The mitochondrial genome (mtDNA) is an important source of inherited extranuclear variation. Clonal increases in mtDNA mutation heteroplasmy have been implicated aging and disease, although the impact this shift on cell function challenging to assess. Reprogramming pluripotency affects heteroplasmy. We reprogrammed three human fibroblast lines with known for deleterious point or deletion mutations. Quantification resulting 76 induced pluripotent stem (iPSC) clones yielded a bimodal...
Elevated basal cortisol levels are present in women with primary and metastatic breast cancer. Although cortisol's potential role breast-to-brain metastasis has yet to be sufficiently studied, prior evidence indicates that it functions as a double-edged sword-cortisol induces cancer vivo, but strengthens the blood-brain-barrier (BBB) protect brain from microbes peripheral immune cells.In this study, we provide novel examination on whether tumor invasiveness eclipses its supporting...
Abstract A population of neural stem cells exists in the adult mammalian central nervous system. Purification and characterization neurospheres provide valuable tools to study regulation differentiation both vitro vivo . Successful stimulation production can ultimately be used for therapeutic purposes. The currently available methods are limited by their poor yield large number animals required compensate that. Here, we describe a procedure purify from mouse whole brain. We detailed steps on...
Abstract Control of breast‐to‐brain metastasis remains an urgent unmet clinical need. While chemotherapies are essential in reducing systemic tumor burden, they have been shown to promote non‐brain metastatic invasiveness and drug‐driven neurocognitive deficits through the formation neurofibrillary tangles (NFT), independently. Now, this study, we investigated effect chemotherapy on brain progression promoting tumor‐mediated NFT. Results show increase brain‐barrier permeability facilitate...
Abstract Background Medulloblastoma (MB) is a pediatric brain tumor occurring in the posterior fossa. MB highly heterogeneous tumor, which can be grouped into four main subgroups: WNT, SHH, Group 3, and 4. Each subgroup different both its implicated pathways pathology, as well how they are treated clinic. Recent Findings Standard protocol for treatment consists of maximal safe resection, followed by craniospinal radiation (in patients 3 years older) adjuvant chemotherapy. Advances clinical...
Abstract Background Meningiomas are the most common primary brain tumor. Though typically benign with a low mutational burden, tumors histology may behave aggressively and there no proven chemotherapies. Although DNA methylation patterns distinguish subgroups of meningiomas have higher predictive value for tumor behavior than histologic classification, little is known about differences in between surrounding normal dura tissue. Methods Whole-exome sequencing array profiling were performed on...
Abstract Patient‐derived cells from surgical resections are of paramount importance to brain tumor research. It is well known that there cellular and microenvironmental heterogeneity within a single mass. Thus, current established protocols for propagating in vitro limiting because obtained conventional singular samples limit the diversity cell populations do not accurately model heterogeneous tumor. Utilization discarded tissue cavitron ultrasonic aspirator (CUSA) whole mass allows...
Brain tumors are the most common cause of childhood oncological death, and medulloblastoma (originating in cerebellum) is malignant pediatric brain tumor. Current therapy including surgical resection, whole-brain spinal cord radiation, aggressive chemotherapy supplemented by bone marrow transplant yields five-year survival rates 60–70%. DUSPs (dual-specificity phosphatases) a heterogeneous group protein phosphatases that can dephosphorylate both phosphotyrosine phosphoserine/phosphothreonine...