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Open Access Publications from the University of California

Scholarly Works (6 results)

  • Thesis
  • Peer Reviewed
UC Irvine Electronic Theses and Dissertations (2017)

Background: Glioblastoma is a highly aggressive brain cancer that leads to death within 15 months of diagnosis. Despite active research in the field, effective treatment options are currently limited to surgery, radiotherapy, and chemotherapy. Recently, there has been a push towards characterizing glioblastoma tumors genetically, epigenetically, transcriptionally, and proteomically in order to develop new, more targeted and individualized therapeutic approaches to glioblastoma.

Aims: The aim of this thesis is to develop a study proposal for the characterization of one of the genes believed to be over-expressed in glioblastoma, EMP2. The study proposed will evaluate EMP2 role’s in glioblastoma pathogenesis and evaluate the therapeutic potential of antibodies developed against EMP2 expressed on the glioblastoma surface membrane.

Methods: In-vitro and in-vivo background studies performed in our labs as well as those found in the literature are presented and discussed as the foundation and groundwork for the proposed study. The study proposal is then outlined in detail.

Results: The purpose of the proposed study is to demonstrate the efficacy of targeting EMP2 on glioblastoma tumor cells using an antibody against EMP2. A detailed description of the proposed study design is given followed by the dissemination and implementation potential of the results of this study. We hypothesize that the functional consequence of EMP2 up-regulation in glioblastoma cells is to orchestrate the membrane expression of proteins required for cell migration, invasion, and neoangiogenesis. Additionally, we predict that the expression of EMP2 can be therapeutically exploited as a novel treatment target using antibodies against EMP2.

Discussion: Our results from the background studies and the expected results from the study proposal suggest that EMP2 may be a promising molecular therapeutic target in glioblastoma. Additional work will be needed to determine whether anti-EMP2 antibodies can be combined with standard chemotherapy or molecularly-targeted treatments to treat glioblastoma in human patients.

    Cover page: Developing Epithelial Membrane Protein 2 as a Prognostic Marker for Glioblastoma Treatment Response and Outcomes: Study Proposal and Design
    • Article
    • Peer Reviewed
    UCLA Previously Published Works (2016)
    Surgeons need to visualize the facial nerve reliably in relation to the vestibular schwannoma (VS) in surgical planning. Diffusion tensor imaging (DTI) tractography has enabled unprecedented in vivo preoperative visualization. We collected data to measure the accuracy of DTI for an accurate location of the nerve in preoperative VS resection planning. A PubMed search for relevant studies was conducted. Inclusion criteria were gross total resection of VS, preoperative DTI identification of the facial nerve, and intraoperative cranial nerve localization by the surgeon. Exclusion criteria were tumors other than VS and unsuccessful preoperative location of the cranial nerve. Accuracy rate was calculated by comparing the intraoperative and preoperative locations detailed by DTI. The query identified 38 cases of VS that fit our inclusion criteria. Overall, 89% had surgical findings that agreed with the DTI location of the facial nerve. Of these cases, 32 patients had a postoperative House-Brackmann grade I or II. Our findings suggest that DTI is a reliable method for facial nerve imaging. Implementation of this technique may help decrease facial nerve injury during surgery. Limitations and further studies are needed to better understand what factors correlate with successful location of the facial nerve and DTI in patients with VS.
      Cover page: A Systematic Analysis of the Reliability of Diffusion Tensor Imaging Tractography for Facial Nerve Imaging in Patients with Vestibular Schwannoma
      • Article
      • Peer Reviewed
      UCLA Previously Published Works (2017)
      Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumor and is associated with an extremely poor clinical prognosis. One pathologic hallmark of GBM is excessive vascularization with abnormal blood vessels. Extensive investigation of anti-angiogenic therapy as a treatment for recurrent GBM has been performed. Bevacizumab, a monoclonal anti-vascular endothelial growth factor A (VEGF-A), suggests a progression-free survival benefit but no overall survival benefit. Developing novel anti-angiogenic therapies are urgently needed in controlling GBM growth. In this study, we demonstrate tumor expression of epithelial membrane protein-2 (EMP2) promotes angiogenesis both in vitro and in vivo using cell lines from human GBM. Mechanistically, this pro-angiogenic effect of EMP2 was partially through upregulating tumor VEGF-A levels. A potential therapeutic effect of a systemic administration of anti-EMP2 IgG1 on intracranial xenografts was observed resulting in both significant reduction of tumor load and decreased tumor vasculature. These results suggest the potential for anti-EMP2 IgG1 as a promising novel anti-angiogenic therapy for GBM. Further investigation is needed to fully understand the molecular mechanisms how EMP2 modulates GBM pathogenesis and progression and to further characterize anti-EMP2 therapy in GBM.
        Cover page: Epithelial membrane protein-2 (EMP2) promotes angiogenesis in glioblastoma multiforme
        • Article
        • Peer Reviewed
        UCLA Previously Published Works (2017)
        Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumor and is associated with an extremely poor clinical prognosis. One pathologic hallmark of GBM is excessive vascularization with abnormal blood vessels. Extensive investigation of anti-angiogenic therapy as a treatment for recurrent GBM has been performed. Bevacizumab, a monoclonal anti-vascular endothelial growth factor A (VEGF-A), suggests a progression-free survival benefit but no overall survival benefit. Developing novel anti-angiogenic therapies are urgently needed in controlling GBM growth. In this study, we demonstrate tumor expression of epithelial membrane protein-2 (EMP2) promotes angiogenesis both in vitro and in vivo using cell lines from human GBM. Mechanistically, this pro-angiogenic effect of EMP2 was partially through upregulating tumor VEGF-A levels. A potential therapeutic effect of a systemic administration of anti-EMP2 IgG1 on intracranial xenografts was observed resulting in both significant reduction of tumor load and decreased tumor vasculature. These results suggest the potential for anti-EMP2 IgG1 as a promising novel anti-angiogenic therapy for GBM. Further investigation is needed to fully understand the molecular mechanisms how EMP2 modulates GBM pathogenesis and progression and to further characterize anti-EMP2 therapy in GBM.
          Cover page: Epithelial membrane protein-2 (EMP2) promotes angiogenesis in glioblastoma multiforme.
          • Article
          • Peer Reviewed
          UC Irvine Previously Published Works (2017)
          Myeloid sarcoma, a rare consequence of myeloproliferative disorders, is rarely seen in the central nervous system, most commonly in the pediatric population. Although there are a handful of case reports detailing initial presentation of CNS myeloid sarcoma in the adult population, we have been unable to find any reports of CNS myeloid sarcoma presenting as a large mass lesion in a herniating patient. Here, we present the case of a patient transferred to our facility for a very large subdural hematoma. Based on imaging characteristics, it was felt to be a spontaneous hematoma secondary to coagulopathy. No coagulopathy was found. Interestingly, he did have a history of acute myeloid leukemia (AML) diagnosed 2 months previously, and intraoperatively he was found to have a confluent white mass invading both the subdural and subarachnoid spaces. There was minimal associated hemorrhage and final pathology showed myeloid sarcoma. This is the first report we are aware of in which CNS myeloid sarcoma presented as a subdural metastasis and also the first report in which we are aware of this etiology causing a herniation syndrome secondary to mass effect.
            Cover page: Intracranial Myeloid Sarcoma Metastasis Mimicking Acute Subdural HematomaCreative Commons 'BY' version 4.0 license
            • Article
            • Peer Reviewed
            UCLA Previously Published Works (2018)
            Epithelial membrane protein-2 (EMP2) expression is noted in many human cancers. We evaluated EMP2 as a biomarker in gliomas. A large tissue microarray of lower grade glioma (WHO grades II-III, n = 19 patients) and glioblastoma (GBM) (WHO grade IV, n = 50 patients) was stained for EMP2. EMP2 expression was dichotomized to low or high expression scores and correlated with clinical data. The mean EMP2 expression was 1.68 in lower grade gliomas versus 2.20 in GBMs (P = 0.01). The percentage of samples with high EMP2 expression was greater in GBMs than lower grade gliomas (90.0 vs. 52.6%, P = 0.001). No significant difference was found between median survival among patients with GBM tumors exhibiting high EMP2 expression and survival of those with low EMP2 expression (8.38 vs. 10.98 months, P = 0.39). However, EMP2 expression ≥2 correlated with decreased survival (r = -0.39, P = 0.001). The EMP2 expression level also correlated with Ki-67 positivity (r = 0.34, P = 0.008). The mortality hazard ratio for GBM patients with EMP2 score of 3 or higher was 1.92 (CI 0.69-5.30). Our findings suggest that elevated EMP2 expression is associated with GBM. With other biomarkers, EMP2 may have use as a molecular target for the diagnosis and treatment of gliomas.
              Cover page: Tissue microarray analysis for epithelial membrane protein-2 as a novel biomarker for gliomas
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