A5017193459- Glioma Diagnosis and Treatment
- Cancer Research and Treatments
- Radiomics and Machine Learning in Medical Imaging
- Cancer, Hypoxia, and Metabolism
- Sphingolipid Metabolism and Signaling
- MicroRNA in disease regulation
- Nanoplatforms for cancer theranostics
- Acupuncture Treatment Research Studies
- Ferroptosis and cancer prognosis
- Pain Management and Placebo Effect
- Healthcare and Venom Research
- Histone Deacetylase Inhibitors Research
- MRI in cancer diagnosis
- Advanced Neuroimaging Techniques and Applications
- Nanoparticle-Based Drug Delivery
- RNA modifications and cancer
- Cancer Mechanisms and Therapy
- Metalloenzymes and iron-sulfur proteins
- Glycosylation and Glycoproteins Research
- Retinoids in leukemia and cellular processes
- Brain Tumor Detection and Classification
- Iron Metabolism and Disorders
- Pain Management and Opioid Use
- Chromatin Remodeling and Cancer
- Veterinary Pharmacology and Anesthesia
Medical College of Wisconsin
2014-2024
University of Minnesota
2004
Glioblastoma remains the most common, malignant primary cancer of central nervous system with a low life expectancy and an overall survival less than 1.5 years. The treatment options are limited there is no cure. Moreover, almost all patients develop recurrent tumors, which typically more aggressive. Therapeutically resistant glioblastoma or stem-like cells (GSCs) hypothesized to cause this inevitable recurrence. Identifying prognostic biomarkers will potentially advance knowledge about...
Gallium, a metal with antineoplastic activity, binds transferrin (Tf) and enters tumor cells via Tf receptor1 (TfR1); it disrupts iron homeostasis leading to cell death. We hypothesized that TfR1 on brain microvascular endothelial (BMEC) would facilitate Tf-Ga transport into the enabling target TfR-bearing glioblastoma. show U-87 MG D54 glioblastoma lines multiple stem (GSC) express TfRs, their growth is inhibited by gallium maltolate (GaM) in vitro After 24 hours of incubation GaM,...
Cancer is a complex disease; glioblastoma (GBM) no exception. Short survival, poor prognosis, and very limited treatment options make it imperative to unravel the disease pathophysiology. The critically important identification of proteins that mediate various cellular events during made possible with advancements in mass spectrometry (MS)-based proteomics. objective our study identify characterize are differentially expressed GBM better understand their interactions functions lead...
Glioblastoma multiforme (GBM) is the most common primary, intracranial malignancy of central nervous system. The standard treatment protocol, which involves surgical resection, and concurrent radiation with adjuvant temozolomide (TMZ), still imparts a grim prognosis. Ultimately, all GBMs exhibit recurrence or progression, developing resistance to treatment. This study demonstrates that acquire via upregulation acid ceramidase (ASAH1) sphingosine‑1-phosphate (Sph-1P). Moreover, inhibition...
Pediatric brain tumors are the most common solid in children and also a leading culprit of cancer-related fatalities children. remain hard to treat. In this study, we demonstrated that medulloblastoma, pediatric glioblastoma, atypical teratoid rhabdoid express significant levels acid ceramidase, where highest radioresistant tumors, suggesting ceramidase may confer radioresistance. More importantly, showed inhibitors highly effective at targeting these with low IC50 values (4.6-50 μM). This...
Background Treatment-resistant glioblastoma (trGBM) is an aggressive brain tumor with a dismal prognosis, underscoring the need for better treatment options. Emerging data indicate that trGBM iron metabolism attractive therapeutic target. The novel mimetic, gallium maltolate (GaM), inhibits mitochondrial function via iron-dependent and -independent pathways. Methods In vitro irradiated adult GBM U-87 MG cells were tested cell viability allowed to reach confluence prior stereotactic...
The absence of major progress in the treatment glioblastoma (GBM) is partly attributable to our poor understanding both GBM tumor biology and acquirement resistance recurrent GBMs. Recurrent GBMs are characterized by their radiation. In this study, we used an established stable U87 radioresistant model total RNA sequencing shed light on global mRNA expression changes following irradiation. We identified many genes, expressions which were altered model, that have never before been reported be...
Osteosarcoma is the most common malignant bone tumor found in children and adolescents associated with many complications including cancer pain metastasis. While patients often seek complementary alternative medicine (CAM) approaches to treat fatigue or side effects of chemotherapy treatment, there little known about effect acupuncture treatment on growth Here we evaluate six different electroacupuncture (EA) regimens osteosarcoma metastasis both male female mice. The significant positive...
Previous studies have shown that electroacupuncture (EA) is able to reduce hyperalgesia in rodent models of persistent pain, but very little known about the analgesic effects and potential sex differences different EA treatment regimens. In present study, we examined five treatments on tumor-induced male female mice. applied ST-36 acupoint either twice weekly (EA-2X/3) beginning postimplantation day (PID) 3 or prophylactically three times prior implantation produced most robust longest...
Background and Purpose: Gliomas have been found to alter iron metabolism transport in ways that result an expansion of their intracellular compartments support aggressive tumor growth. This study used deep neural network trained quantitative susceptibility mapping assess basal ganglia concentrations glioma patients. Materials Methods: Ninety-two patients with brain lesions were initially enrolled this fifty-nine met the inclusion criteria. Susceptibility-weighted images collected at 3.0 T...
Pediatric glioblastoma (GBM) is a relatively rare brain tumor in children that has dismal prognosis. Surgery followed by radiotherapy the main treatment protocol used for older patients. The benefit of adjuvant chemotherapy still limited due to poor understanding underlying molecular and genetic changes occur with irradiation tumor. In this study, we performed total RNA sequencing on an established stable radioresistant pediatric GBM cell line identify mRNA expression following radiation....
// Hisham S. Alhajala 1 , John L. Markley 2 Jin Hae Kim Mona M. Al-Gizawiy 3 Kathleen Schmainda Kuo 4 and Christopher R. Chitambar Division of Hematology Oncology, Department Medicine, Medical College Wisconsin, Milwaukee, USA Biochemistry, University Wisconsin-Madison, Madison, Biophysics, Neurosurgery Mulva Clinic for the Neurosciences, Dell School, Austin, Texas, Correspondence to: Chitambar, email: chitambr@mcw.edu Keywords: glioblastoma; iron; gallium; metformin; mitochondrial complex I...
Abstract BACKGROUND Glioblastoma (GBM) is an aggressive brain tumor with a dismal prognosis. New drugs that exploit previously underexplored cancer-related pathways are needed. We and others have shown GBM stem cells require significantly greater amounts of iron than normal to drive critical iron-dependent processes altered in malignancy. showed oral gallium maltolate (GaM), iron-targeting metal compound, has significant activity against vitro shrinks tumors prolongs survival rat model....
e15099 Background: Cancer Health Disparities (CHD), in the US is well documented. The significant evidence of CHD treatment related outcomes along ancestry lines. Africans and Hispanics generally have higher rates adverse drug reactions (ADR), poorer survival response when compared to Europeans Asians. causes are poorly understood but it plausible believe that has a genetic basis, given human genomic variations underlie both disease susceptibility outcomes. Our goal determine basis outcome,...
Glioblastoma cells have an increased requirement for iron relative to normal brain cells. This demand is support ribonucleotide reductase (RRM2) activity, mitochondrial function, and signaling through the mTOR WNT pathways which are altered in tumors. Given that GBM rapidly proliferating, whereas not, we examined expression of RRM2 effect a RR inhibitor on proliferation U87 D54 vitro. Human cell lines were incubated 96 hours with chelator deferoxamine (DFO) Didox combination at molar ratio...
Glioblastoma (GBM) is a devastating cancer of the central nervous system. The prognosis this most malignant form brain tumor remains poor, largely due to inherent resistance GBM therapy. Unfortunately, recurrent or progressive (rGBM) frequently has very different molecular characteristics from original tumor. Moreover, it exhibits vastly biological behavior. Thus, rGBM proven exceedingly difficult treat. Current preclinical models primarily reflect treated de novo tumor, and require either...
BACKGROUND: The Cancer Genome Atlas (TCGA) project previously identified genetic changes in the DNA sequence and copy number, methylation, gene expression of glioblastoma multiforme (GBM) tumors, leading to an enthused effort compile characterize genome, transcriptome, proteome human GBM so that aberrantly functioning molecular pathways tumor subtypes could be identified. METHODS: Agilent GeneSpring Mass Profiler Professional (MPP) software was used perform integrated multi-omics analysis...
BACKGROUND: Limited treatment options and an aggressive nature make glioblastoma multiforme (GBM) a highly deadly cancer associated with poor prognosis short survival. Gallium (Ga), iron-mimetic metal, disrupts tumor iron homeostasis, thus effecting potential antineoplastic activity. Here we present compelling evidence that gallium maltolate (GaM) has profound antitumor effect on GBM in vitro vivo. METHODS: The cytotoxic effects of GaM were measured by MTT assay human U87 D54 cells, cells...
BACKGROUND: Advanced MR imaging provides invaluable information on brain tumor biology and behavior, making it an important complement to standard histopathology. In light of mounting molecular evidence against the existence true mixed gliomas, we present use relative cerebral blood volume (rCBV) classify gliomas as a function glioma type grade. METHODS: Histopathological findings 145 tissue specimens from 42 consented adult patients were studied. diagnosis for each specimen was obtained...
Glioblastoma (GBM) remains the most common malignant cancer of central nervous system. Therapeutically resistant GBM or glioblastoma stem-like cells (GSC) are hypothesized to cause inevitable recurrence. Acid ceramidase (ASAH1), a lysosome cysteine amidase important in metabolism sphingolipids, plays significant role tumor progression many cancers. Here, acid promoting radioresistant was evaluated. levels were measured by Western blot. Liquid chromatography mass spectroscopy technique...
Acid ceramidase (ASAH1) plays an important role in the production of sphingosine-1-phosphate (S1P), a known tumor promotor. While S1P was shown to stimulate invasiveness glioblastoma (GBM) cells vitro, exact ASAH1 glioma biology still needs be established. To our knowledge, this is first use characterize gliomas by grade and type. All studies were conducted with IRB approval. Tissue specimens 19 consented adult patients who previously underwent therapeutic brain resection submitted for...