Retrospective study of the correlation between the DNA repair protein alkyltransferase and survival of brain tumor patients treated with carmustine

Michael Belanich, Monica Pastor, Terri Randall, Denise Guerra, Jeannie Kibitel, Lori Alas, Ben Li, Marc Citron, Patricia Wasserman, Agnes White, Harmon Eyre, Kurt Jaeckle, Susan Schulman, Dori Rector, Michael Prados, Stephen Coons, William Shapiro, Daniel Yarosh

Research output: Contribution to journalArticle

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Abstract

We tested the hypothesis that the level of the DNA repair protein O6- alkylguanine-DNA alkyltransferase in brain tumors was correlated with resistance to carmustine (BCNU) chemotherapy. Alkyltransferase levels in individual cells in sections from 167 primary brain tumors treated with BCNU were quantitated with an immunofluorescence assay using monoclonal antibodies against human alkyltransferase. Patients with high levels of alkyltransferase had shorter time to treatment failure (P = 0.05) and death (P = 0.004) and a death rate 1.7 times greater than patients with low alkyltransferase levels. Furthermore, the size of the subpopulation of cells with high levels of alkyltransferase was correlated directly with drug resistance. For all tumors the variables most closely correlated with survival, in order of importance, were age, tumor grade, and alkyltransferase levels. For glioblastoma multiforme, survival was more strongly correlated with alkyltransferase levels than with age. These results should encourage prospective studies to evaluate alkyltransferase levels as a method for identifying brain tumor patients with the best likelihood of response to BCNU chemotherapy.

Original languageEnglish (US)
Pages (from-to)783-788
Number of pages6
JournalCancer Research
Volume56
Issue number4
StatePublished - Feb 15 1996

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Alkyl and Aryl Transferases
Carmustine
Brain Neoplasms
DNA Repair
Retrospective Studies
Survival
Proteins
Drug Therapy
Glioblastoma
Treatment Failure
Cell Size
Drug Resistance
Fluorescent Antibody Technique
Neoplasms
Monoclonal Antibodies
Prospective Studies

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Belanich, M., Pastor, M., Randall, T., Guerra, D., Kibitel, J., Alas, L., ... Yarosh, D. (1996). Retrospective study of the correlation between the DNA repair protein alkyltransferase and survival of brain tumor patients treated with carmustine. Cancer Research, 56(4), 783-788.
Belanich, Michael ; Pastor, Monica ; Randall, Terri ; Guerra, Denise ; Kibitel, Jeannie ; Alas, Lori ; Li, Ben ; Citron, Marc ; Wasserman, Patricia ; White, Agnes ; Eyre, Harmon ; Jaeckle, Kurt ; Schulman, Susan ; Rector, Dori ; Prados, Michael ; Coons, Stephen ; Shapiro, William ; Yarosh, Daniel. / Retrospective study of the correlation between the DNA repair protein alkyltransferase and survival of brain tumor patients treated with carmustine. In: Cancer Research. 1996 ; Vol. 56, No. 4. pp. 783-788.
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abstract = "We tested the hypothesis that the level of the DNA repair protein O6- alkylguanine-DNA alkyltransferase in brain tumors was correlated with resistance to carmustine (BCNU) chemotherapy. Alkyltransferase levels in individual cells in sections from 167 primary brain tumors treated with BCNU were quantitated with an immunofluorescence assay using monoclonal antibodies against human alkyltransferase. Patients with high levels of alkyltransferase had shorter time to treatment failure (P = 0.05) and death (P = 0.004) and a death rate 1.7 times greater than patients with low alkyltransferase levels. Furthermore, the size of the subpopulation of cells with high levels of alkyltransferase was correlated directly with drug resistance. For all tumors the variables most closely correlated with survival, in order of importance, were age, tumor grade, and alkyltransferase levels. For glioblastoma multiforme, survival was more strongly correlated with alkyltransferase levels than with age. These results should encourage prospective studies to evaluate alkyltransferase levels as a method for identifying brain tumor patients with the best likelihood of response to BCNU chemotherapy.",
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Belanich, M, Pastor, M, Randall, T, Guerra, D, Kibitel, J, Alas, L, Li, B, Citron, M, Wasserman, P, White, A, Eyre, H, Jaeckle, K, Schulman, S, Rector, D, Prados, M, Coons, S, Shapiro, W & Yarosh, D 1996, 'Retrospective study of the correlation between the DNA repair protein alkyltransferase and survival of brain tumor patients treated with carmustine', Cancer Research, vol. 56, no. 4, pp. 783-788.

Retrospective study of the correlation between the DNA repair protein alkyltransferase and survival of brain tumor patients treated with carmustine. / Belanich, Michael; Pastor, Monica; Randall, Terri; Guerra, Denise; Kibitel, Jeannie; Alas, Lori; Li, Ben; Citron, Marc; Wasserman, Patricia; White, Agnes; Eyre, Harmon; Jaeckle, Kurt; Schulman, Susan; Rector, Dori; Prados, Michael; Coons, Stephen; Shapiro, William; Yarosh, Daniel.

In: Cancer Research, Vol. 56, No. 4, 15.02.1996, p. 783-788.

Research output: Contribution to journalArticle

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T1 - Retrospective study of the correlation between the DNA repair protein alkyltransferase and survival of brain tumor patients treated with carmustine

AU - Belanich, Michael

AU - Pastor, Monica

AU - Randall, Terri

AU - Guerra, Denise

AU - Kibitel, Jeannie

AU - Alas, Lori

AU - Li, Ben

AU - Citron, Marc

AU - Wasserman, Patricia

AU - White, Agnes

AU - Eyre, Harmon

AU - Jaeckle, Kurt

AU - Schulman, Susan

AU - Rector, Dori

AU - Prados, Michael

AU - Coons, Stephen

AU - Shapiro, William

AU - Yarosh, Daniel

PY - 1996/2/15

Y1 - 1996/2/15

N2 - We tested the hypothesis that the level of the DNA repair protein O6- alkylguanine-DNA alkyltransferase in brain tumors was correlated with resistance to carmustine (BCNU) chemotherapy. Alkyltransferase levels in individual cells in sections from 167 primary brain tumors treated with BCNU were quantitated with an immunofluorescence assay using monoclonal antibodies against human alkyltransferase. Patients with high levels of alkyltransferase had shorter time to treatment failure (P = 0.05) and death (P = 0.004) and a death rate 1.7 times greater than patients with low alkyltransferase levels. Furthermore, the size of the subpopulation of cells with high levels of alkyltransferase was correlated directly with drug resistance. For all tumors the variables most closely correlated with survival, in order of importance, were age, tumor grade, and alkyltransferase levels. For glioblastoma multiforme, survival was more strongly correlated with alkyltransferase levels than with age. These results should encourage prospective studies to evaluate alkyltransferase levels as a method for identifying brain tumor patients with the best likelihood of response to BCNU chemotherapy.

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