Decreased lactate concentration and glycolytic enzyme expression reflect inhibition of mTOR signal transduction pathway in B-cell lymphoma.

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Decreased lactate concentration and glycolytic enzyme expression reflect inhibition of mTOR signal transduction pathway in B-cell lymphoma. / Lee, Seung-Cheol; Marzec, Michal; Liu, Xiaobin; Wehrli, Suzanne; Kantekure, Kanchan; Ragunath, Puthiyaveettil N.; Nelson, David S.; Delikatny, Edward J.; Glickson, Jerry D.; Wasik, Mariusz A.

In: NMR in Biomedicine, Vol. 26, No. 1, 2013, p. 106-114.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Lee, S-C, Marzec, M, Liu, X, Wehrli, S, Kantekure, K, Ragunath, PN, Nelson, DS, Delikatny, EJ, Glickson, JD & Wasik, MA 2013, 'Decreased lactate concentration and glycolytic enzyme expression reflect inhibition of mTOR signal transduction pathway in B-cell lymphoma.', NMR in Biomedicine, vol. 26, no. 1, pp. 106-114. https://doi.org/10.1002/nbm.2825

APA

Lee, S-C., Marzec, M., Liu, X., Wehrli, S., Kantekure, K., Ragunath, P. N., Nelson, D. S., Delikatny, E. J., Glickson, J. D., & Wasik, M. A. (2013). Decreased lactate concentration and glycolytic enzyme expression reflect inhibition of mTOR signal transduction pathway in B-cell lymphoma. NMR in Biomedicine, 26(1), 106-114. https://doi.org/10.1002/nbm.2825

Vancouver

Lee S-C, Marzec M, Liu X, Wehrli S, Kantekure K, Ragunath PN et al. Decreased lactate concentration and glycolytic enzyme expression reflect inhibition of mTOR signal transduction pathway in B-cell lymphoma. NMR in Biomedicine. 2013;26(1):106-114. https://doi.org/10.1002/nbm.2825

Author

Lee, Seung-Cheol ; Marzec, Michal ; Liu, Xiaobin ; Wehrli, Suzanne ; Kantekure, Kanchan ; Ragunath, Puthiyaveettil N. ; Nelson, David S. ; Delikatny, Edward J. ; Glickson, Jerry D. ; Wasik, Mariusz A. / Decreased lactate concentration and glycolytic enzyme expression reflect inhibition of mTOR signal transduction pathway in B-cell lymphoma. In: NMR in Biomedicine. 2013 ; Vol. 26, No. 1. pp. 106-114.

Bibtex

@article{b8551949fedc4426aa04d670972202f8,

title = "Decreased lactate concentration and glycolytic enzyme expression reflect inhibition of mTOR signal transduction pathway in B-cell lymphoma.",

abstract = "The application of kinase inhibitors in cancer treatment is growing rapidly. However, methods for monitoring the effectiveness of the inhibitors are still poorly developed and currently rely mainly on the tracking of changes in the tumor vol., a rather late and relatively insensitive marker of the therapeutic response. In contrast, MRS can detect changes in cell metab. and has the potential to provide early and patient-specific markers of drug activity. Using human B-cell lymphoma models and MRS, we have demonstrated that the inhibition of the mTOR signaling pathway can be detected in malignant cells in vitro and noninvasively in vivo by the measurement of lactate levels. An mTOR inhibitor, rapamycin, suppressed lactic acid prodn. in lymphoma cell line cultures and also diminished steady-state lactate levels in xenotransplants. The inhibition was time dependent and was first detectable 8 h after drug administration in cell cultures. In xenotransplants, 2 days of rapamycin treatment produced significant changes in lactic acid concn. in the tumor measured in vivo, which were followed by tumor growth arrest and tumor vol. regression. The rapamycin-induced changes in lactate prodn. were strongly correlated with the inhibition of expression of hexokinase II, the key enzyme in the glycolytic pathway. These studies suggest that MRS or 18F-fluorodeoxyglucose positron emission tomog. (FDG PET) detection of changes in glucose metab. may represent effective noninvasive methods for the monitoring of mTOR targeting therapy in lymphomas and other malignancies. Furthermore, the measurement of glucose metabolic inhibition by MRS or FDG PET imaging may also prove to be effective in monitoring the efficacy of other kinase inhibitors given that the rapamycin-sensitive mTOR lies downstream of many oncogenic signaling pathways. [on SciFinder(R)]",

keywords = "rapamycin anticancer mTOR inhibitor lactate glycolysis B cell lymphoma",

author = "Seung-Cheol Lee and Michal Marzec and Xiaobin Liu and Suzanne Wehrli and Kanchan Kantekure and Ragunath, {Puthiyaveettil N.} and Nelson, {David S.} and Delikatny, {Edward J.} and Glickson, {Jerry D.} and Wasik, {Mariusz A.}",

year = "2013",

doi = "10.1002/nbm.2825",

language = "English",

volume = "26",

pages = "106--114",

journal = "NMR in Biomedicine",

issn = "0952-3480",

publisher = "Wiley",

number = "1",

}

RIS

TY - JOUR

T1 - Decreased lactate concentration and glycolytic enzyme expression reflect inhibition of mTOR signal transduction pathway in B-cell lymphoma.

AU - Lee, Seung-Cheol

AU - Marzec, Michal

AU - Liu, Xiaobin

AU - Wehrli, Suzanne

AU - Kantekure, Kanchan

AU - Ragunath, Puthiyaveettil N.

AU - Nelson, David S.

AU - Delikatny, Edward J.

AU - Glickson, Jerry D.

AU - Wasik, Mariusz A.

PY - 2013

Y1 - 2013

N2 - The application of kinase inhibitors in cancer treatment is growing rapidly. However, methods for monitoring the effectiveness of the inhibitors are still poorly developed and currently rely mainly on the tracking of changes in the tumor vol., a rather late and relatively insensitive marker of the therapeutic response. In contrast, MRS can detect changes in cell metab. and has the potential to provide early and patient-specific markers of drug activity. Using human B-cell lymphoma models and MRS, we have demonstrated that the inhibition of the mTOR signaling pathway can be detected in malignant cells in vitro and noninvasively in vivo by the measurement of lactate levels. An mTOR inhibitor, rapamycin, suppressed lactic acid prodn. in lymphoma cell line cultures and also diminished steady-state lactate levels in xenotransplants. The inhibition was time dependent and was first detectable 8 h after drug administration in cell cultures. In xenotransplants, 2 days of rapamycin treatment produced significant changes in lactic acid concn. in the tumor measured in vivo, which were followed by tumor growth arrest and tumor vol. regression. The rapamycin-induced changes in lactate prodn. were strongly correlated with the inhibition of expression of hexokinase II, the key enzyme in the glycolytic pathway. These studies suggest that MRS or 18F-fluorodeoxyglucose positron emission tomog. (FDG PET) detection of changes in glucose metab. may represent effective noninvasive methods for the monitoring of mTOR targeting therapy in lymphomas and other malignancies. Furthermore, the measurement of glucose metabolic inhibition by MRS or FDG PET imaging may also prove to be effective in monitoring the efficacy of other kinase inhibitors given that the rapamycin-sensitive mTOR lies downstream of many oncogenic signaling pathways. [on SciFinder(R)]

AB - The application of kinase inhibitors in cancer treatment is growing rapidly. However, methods for monitoring the effectiveness of the inhibitors are still poorly developed and currently rely mainly on the tracking of changes in the tumor vol., a rather late and relatively insensitive marker of the therapeutic response. In contrast, MRS can detect changes in cell metab. and has the potential to provide early and patient-specific markers of drug activity. Using human B-cell lymphoma models and MRS, we have demonstrated that the inhibition of the mTOR signaling pathway can be detected in malignant cells in vitro and noninvasively in vivo by the measurement of lactate levels. An mTOR inhibitor, rapamycin, suppressed lactic acid prodn. in lymphoma cell line cultures and also diminished steady-state lactate levels in xenotransplants. The inhibition was time dependent and was first detectable 8 h after drug administration in cell cultures. In xenotransplants, 2 days of rapamycin treatment produced significant changes in lactic acid concn. in the tumor measured in vivo, which were followed by tumor growth arrest and tumor vol. regression. The rapamycin-induced changes in lactate prodn. were strongly correlated with the inhibition of expression of hexokinase II, the key enzyme in the glycolytic pathway. These studies suggest that MRS or 18F-fluorodeoxyglucose positron emission tomog. (FDG PET) detection of changes in glucose metab. may represent effective noninvasive methods for the monitoring of mTOR targeting therapy in lymphomas and other malignancies. Furthermore, the measurement of glucose metabolic inhibition by MRS or FDG PET imaging may also prove to be effective in monitoring the efficacy of other kinase inhibitors given that the rapamycin-sensitive mTOR lies downstream of many oncogenic signaling pathways. [on SciFinder(R)]

KW - rapamycin anticancer mTOR inhibitor lactate glycolysis B cell lymphoma

U2 - 10.1002/nbm.2825

DO - 10.1002/nbm.2825

M3 - Journal article

VL - 26

SP - 106

EP - 114

JO - NMR in Biomedicine

JF - NMR in Biomedicine

SN - 0952-3480

IS - 1

ER -

ID: 202374751