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Clonogenic cell studies with human brain tumors: BCNU-resistance
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ANTIGLIOMA MONOCLONAL ANTIBODIES N. de Tribolet, V. Piguet, A.C. Diserens, M.F. Hamou, J.P. Mach, 5'. Carrel. Neurosurgical Service, CHUV, 1011 Lausanne, and Ludwig Institute for Cancer Resear‘,ii, 1066 Epalinqes, Switzerland Monoclonal antibodies (Mabs) are useful tools to identify tumor markers and differentiation markers expressed on cells from gliomas and other tumors derived from the neuroectoderm. 90 human qlioma and other neuroectoderm derived cell lines have been analysed using a panel of Mabs reacting with 3 different groups of markers. The first group, qlioma associated, is expressed by most gliomas in antibody binding radioimmunoassay, but also by normal astrocytes and cells from other normal tissues such as spleen, liver and kidney in immunoperoxydase staining of fresh frozen sections. The second group consists of differentiation markers expressed by fetal brain and tumors derived from the neuroectoderm such 3s qliomas, melanomas and neuroblastomas. These early differentiation markers do not seem to be expressed on normai adult cells and could be suitable for in viva tumor localization since they are operationally specific for the central nervous system. The third group comprises lymphoid differentiation markers. CALLA and HLA-DR, also expressed on certain tumor cells of neuroectodermal origin. HLA-DR antigens have also been identified on normaL reactive astrocytes, which raises the question of their possible functional role JS accessory cells.
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THE ROLE OF BLOOD-BRAIN TUMORS E.A. Neuwelt,
BARR:ER
MODIFICATION
IN CHEMOTHERAPY
OF MALIGANT
BRAIN
M.D.
Inadequate drug delivery to the brain, caused by an intact or partially intact blood-brain barrier (BBB), probably accounts for poor therapeutic responsiveness to cytoreductive drugs by malignant metastatic and primary brain tumors. Drug delivery can be enhanced in normal brains and brains with tumors by administering drugs into the carotid or vertebral circulation after osmotic opening of the The osmotic procedure in humans invclves infusion into the carotid or BBB. vertebral arteries of a 25% mannitol solution for 30 s. The procedure is reversible, can be accomplished without long-term neurological deficits, and can be monitored in dogs and humans by means of enhanced computerized tomography. Osmotic BBB disruption, when combined with multiple drug administraiton, has proved effective in treating brain tumors in a small number of clinical cases.
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Clonogenic cell studies with human brain turors: BCNU-resistance. Massimo A. Gerosa Istituto di Neurochirurgia - Universiti di Verona. Like all nitrosoureas of major clinical role, EXXJ - i.e. the sxosteffective chemotherapeutic agent for C.N.S. malignancies - biologically degrades into active alkylating/cross-linkingand carbasoylatingmoieties. Using a human brain tusrx stem cell assay we have analyzed a panel of human malignant glicmas characterized by different degrees of XNU-resistance. Early passage cultures fm these tars were treated in vitro with rode1 drugs for alkylation ( XNU, ENU, CHLZ ) , cross-linking ( XWJ, CHLZ ) and carbarfoylation (BIICNU) : dose-scheduleswere canpatible with clinically achievable levels. Results of the chgnosensitivitytesting indicate that KNU-resistance is closely related to the cross-linking activity of the alkylating moiety, whereas EWNU, the prely carbanqlating agent, was egually cytotoxic in all cell lines in vitro. Carbanqlating drugs might be useful in future attempts to overcellular resistance to nitrosoureas.
43
ANTIGLIOMA MONOCLONAL ANTIBODIES N. de Tribolet, V. Piguet, A.C. Diserens, M.F. Hamou, J.P. Mach, 5'. Carrel. Neurosurgical Service, CHUV, 1011 Lausanne, and Ludwig Institute for Cancer Resear‘,ii, 1066 Epalinqes, Switzerland Monoclonal antibodies (Mabs) are useful tools to identify tumor markers and differentiation markers expressed on cells from gliomas and other tumors derived from the neuroectoderm. 90 human qlioma and other neuroectoderm derived cell lines have been analysed using a panel of Mabs reacting with 3 different groups of markers. The first group, qlioma associated, is expressed by most gliomas in antibody binding radioimmunoassay, but also by normal astrocytes and cells from other normal tissues such as spleen, liver and kidney in immunoperoxydase staining of fresh frozen sections. The second group consists of differentiation markers expressed by fetal brain and tumors derived from the neuroectoderm such 3s qliomas, melanomas and neuroblastomas. These early differentiation markers do not seem to be expressed on normai adult cells and could be suitable for in viva tumor localization since they are operationally specific for the central nervous system. The third group comprises lymphoid differentiation markers. CALLA and HLA-DR, also expressed on certain tumor cells of neuroectodermal origin. HLA-DR antigens have also been identified on normaL reactive astrocytes, which raises the question of their possible functional role JS accessory cells.
44
THE ROLE OF BLOOD-BRAIN TUMORS E.A. Neuwelt,
BARR:ER
MODIFICATION
IN CHEMOTHERAPY
OF MALIGANT
BRAIN
M.D.
Inadequate drug delivery to the brain, caused by an intact or partially intact blood-brain barrier (BBB), probably accounts for poor therapeutic responsiveness to cytoreductive drugs by malignant metastatic and primary brain tumors. Drug delivery can be enhanced in normal brains and brains with tumors by administering drugs into the carotid or vertebral circulation after osmotic opening of the The osmotic procedure in humans invclves infusion into the carotid or BBB. vertebral arteries of a 25% mannitol solution for 30 s. The procedure is reversible, can be accomplished without long-term neurological deficits, and can be monitored in dogs and humans by means of enhanced computerized tomography. Osmotic BBB disruption, when combined with multiple drug administraiton, has proved effective in treating brain tumors in a small number of clinical cases.
45
Clonogenic cell studies with human brain turors: BCNU-resistance. Massimo A. Gerosa Istituto di Neurochirurgia - Universiti di Verona. Like all nitrosoureas of major clinical role, EXXJ - i.e. the sxosteffective chemotherapeutic agent for C.N.S. malignancies - biologically degrades into active alkylating/cross-linkingand carbasoylatingmoieties. Using a human brain tusrx stem cell assay we have analyzed a panel of human malignant glicmas characterized by different degrees of XNU-resistance. Early passage cultures fm these tars were treated in vitro with rode1 drugs for alkylation ( XNU, ENU, CHLZ ) , cross-linking ( XWJ, CHLZ ) and carbarfoylation (BIICNU) : dose-scheduleswere canpatible with clinically achievable levels. Results of the chgnosensitivitytesting indicate that KNU-resistance is closely related to the cross-linking activity of the alkylating moiety, whereas EWNU, the prely carbanqlating agent, was egually cytotoxic in all cell lines in vitro. Carbanqlating drugs might be useful in future attempts to overcellular resistance to nitrosoureas.