Biomedical subjects

Andrew T Parsa

Publications and source records attributed to Andrew T Parsa.

26 records · Page 2Linked to original sources

PubMed2004

Unique astrocyte ribbon in adult human brain contains neural stem cells but lacks chain migration.

The subventricular zone (SVZ) is a principal source of adult neural stem cells in the rodent brain, generating thousands of olfactory bulb neurons every day. If the adult human brain contains a comparable germinal region, this could have considerable implications for future neuroregenerative therapy. Stem cells have been isolated from the human brain, but the identity, organization and function of adult neural stem cells in the human SVZ are unknown. Here we describe a ribbon of SVZ astrocytes lining the lateral ventricles of the adult human brain that proliferate in vivo and behave as multipotent progenitor cells in vitro. This astrocytic ribbon has not been observed in other vertebrates studied. Unexpectedly, we find no evidence of chains of migrating neuroblasts in the SVZ or in the pathway to the olfactory bulb. Our work identifies SVZ astrocytes as neural stem cells in a niche of unique organization in the adult human brain.

Adult↗

PubMed2004

Cooperative translational control of gene expression by Ras and Akt in cancer.

Ras and Akt are signaling proteins that mediate fundamental aspects of normal growth and development in many organisms. When the Ras and Akt pathways become overly active, malignant transformation of normal tissue can occur. The combined activity of these two proteins has generated the transformation of human cell cultures and tumor formation in mice. In this review we highlight malignant glioma as a tumor type in which Ras and Akt pathways cooperate to cause tumorigenesis and regulate translation. The downstream components of these pathways have provided therapeutic targets that are currently being tested in clinical trials.

Animals↗

PubMed2004

Neuromonitoring during surgery for metastatic tumors to the spine: intraoperative interpretation and management strategies.

Resection of metastatic tumors of the spine poses great technical challenges, with the potential of creating severe neurologic deficits. Several modalities of electrophysiologic monitoring, including SSEPs and MEPs, have evolved to aid in resection of these tumors. This review has presented additional techniques-such as mapping of the dorsal columns with antidromic-elicited SSEPs to plan the myelotomy and direct intra-medullary stimulation-that help to identify the extent of the tumor margin at its interface with functional tracts. Neuromonitoring can potentially minimize the sensory and motor damage that can occur during resection of metastatic tumors of the spine. Further experience with these techniques should allow improved results follow-ing surgical procedures in functionally eloquent are as of the spinal cord during the surgical management of metastatic tumors.

Electric Stimulation↗

PubMed2003

Intraventricular neurocytomas.

The literature to date on the treatment of CNC reflects an evolution of clinical practice in neurooncology. The advent of sophisticated tools, such as MRS and molecular pathology, has facilitated more efficient diagnosis of CNC. Decreased morbidity associated with surgical intervention has resulted in better outcomes in patients undergoing resection of CNC. Prospective monitoring of treated patients with MRI coupled with judicious use of radiosurgery will likely further decrease treatment-related morbidity.

Brain↗

PubMed2002

Changes in the immunologic phenotype of human malignant glioma cells after passaging in vitro.

Although immunotherapeutic strategies against glioblastomas have been promising both in vitro and in animal models, similar successes have not been realized in human clinical trials. One reason may be that immunotherapeutic strategies are based on prior studies that primarily have used human glioblastoma cell lines passaged in vitro, which may not accurately reflect the in vivo properties of glioblastoma cells. In this report, we used flow cytometry to quantify the expression of immunological cell surface molecules on human glioblastomas directly ex vivo (prior to any in vitro culturing) and after varying passages in vitro. Furthermore, we used ELISA to quantitate cytokine secretion after various passages in vitro. We demonstrate that in vitro culturing of established cell lines led to increases in the cell surface expression of MHC class I and ICAM-1 and secretion of IL-6 and TGF-beta(2). Furthermore, there were significant changes in the expression of MHC class I, MHC class II, B7-2, ICAM-1, and FasL when comparing ex vivo tumor cells to those after a single passage in vitro. After passaging once in vitro, there were also significant changes in the secretion of TGF-beta(2) and IL-10. This report indicates that in vitro culturing leads to significant changes in both cell surface molecules and secreted cytokines, which are known to affect the ability of immune cells to initiate an anti-tumor immune response. These changes in the immunological phenotype of glioblastomas after in vitro culturing may in part explain the limited success of immunotherapeutic strategies against glioblastomas in human clinical trials.

Antigens, CD↗

PubMedDate not supplied

Autologous adjuvant linked fibroblasts induce anti-glioma immunity: implications for development of a glioma vaccine.

OBJECTIVES: Adjuvant-linked vaccines have been shown to induce anti-tumor immunity in patients with a variety of solid tumors. In this study we describe an in vitro model of active immunotherapy using autologous fibroblasts as immunogen. Correlative results from glioma patients immunized with autologous fibroblasts are also described. METHODS: Peripheral blood lymphocytes (PBLs) from normal subjects were immunized in vitro against autologous skin fibroblasts coupled to the adjuvant muramyl dipeptide. The lymphocytes developed cell-mediated cytotoxicity that was measured with a short-term chromium release assay. Results of in vitro experiments were compared to data derived from glioma patients immunized with subcutaneous injection of an autologous adjuvant-linked fibroblast vaccine. Glioma target cells and fibroblast immunogens were derived from early passage primary tissue culture. RESULTS: A comparison of autologous vs. homologous immunogen indicated that major histocompatibility complex matching was required at the sensitization stage of immunity (17.2 +/- 3.4% specific lysis vs. 0.4 +/- 3.1%, P < 0.01). Pre-treatment of fibroblast immunogen cells with interferon gamma (IFN-gamma) was found to significantly increase immunity (42.2 +/- 10.0%, P < 0.01), as did IFN-gamma pre-treatment of tumor target cells (35.8 +/- 9.0%, P < 0.01). The positive effect of IFN-gamma was diminished by treatment of cells with IFN-alpha. These in vitro results correlated well with in vivo data derived from glioma patients immunized with an autologous adjuvant-linked fibroblast vaccine. PBLs from patients developed direct cell-mediated cytotoxicity against autologous tumor cells. Lysis of tumor targets after in vivo immunization increased over a three-week interval (from 1.2 +/- 3.0% to 21.0 +/- 3.4%, P < 0.01) while lysis of a non-MHC matched control cell line remained essentially unchanged. CONCLUSIONS: Specific lysis of glioma targets in vitro was achieved after in vivo sensitization with autologous adjuvant-linked fibroblasts. Collectively, the data indicate that biochemically modified autologous cells can stimulate anti-glioma immunity in humans. The degree of specific immunity seen in our patients compares favorably with other published series using glioma cells as an antigenic source. Accordingly, fibroblasts may represent a practical alternative to glioma cells for vaccine construction.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMedDate not supplied

Stereotactic radiosurgery and interstitial brachytherapy for glial neoplasms.

The application of focal radiation therapies in the management of malignant gliomas has gone through a number of stages. Earlier efforts to improve local control of malignant gliomas involved the use of brachytherapy. Despite some early encouraging results, Phase 3 studies did not prove a significant survival benefit for the addition of brachytherapy for newly diagnosed glioblastoma. Most recently radiosurgery has been employed using the same rationale in that improved local control may improve survival. Results of the RTOG Phase 3 study are pending final publication, but early abstracted reports are negative. While radiosurgery and brachytherapy continue to be used as a form of therapy for selected patients with recurrent gliomas, new information from metabolic imaging studies suggests our problem with these techniques in part may be related to targeting. This paper reviews the recent literature and results of the use of brachytherapy and radiosurgery in the management of newly diagnosed and recurrent malignant gliomas.

Brachytherapy↗

PubMedDate not supplied

Spinal cord and intradural-extraparenchymal spinal tumors: current best care practices and strategies.

The management of patients with intradural spinal tumors differs in many respects from approaches taken for patients with intracranial tumors. Intramedullary lesions are often completely surrounded by normal spinal cord, displacing vital functional tracts eccentrically. Extramedullary lesions can drastically compress the spinal cord and nerve roots, reducing normal tissue to a ribbon-like consistency. The small amount of normal tissue relative to tumor has implications for surgery and postoperative adjuvant therapy. In addition, operative intervention must take spinal stability into consideration. In this report, we describe the current best care practices and strategies for patients with a diagnosis of spinal astrocytoma, ependymoma, hemangioblastoma, schwannoma, and meningioma. Treatment of patients with intradural tumors of the spinal cord and adjoining structures has changed over the past 20 years. Advances in many disciplines including neuroradiology, neurosurgery, neurooncology, and neuropathology have contributed to expediting diagnosis and improving outcomes.

Humans↗