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Specific Lipid and Metabolic Profiles of R-CHOP-Resistant Diffuse Large B-Cell Lymphoma Elucidated by Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging and in Vivo Imaging

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Barré, Florian P Y ; Claes, Britt S R ; Dewez, Frédéric ; Peutz-Kootstra, Carine ; Munch-Petersen, Helga F ; Grønbæk, Kirsten ; Lund, Anders H ; Heeren, Ron M A ; Côme, Christophe ; Cillero-Pastor, Berta. / Specific Lipid and Metabolic Profiles of R-CHOP-Resistant Diffuse Large B-Cell Lymphoma Elucidated by Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging and in Vivo Imaging. I: Analytical Chemistry. 2018 ; Bind 90, Nr. 24. s. 14198-14206.

Bibtex

@article{87a0b45982e2410eb56ccdd55c44d154,
title = "Specific Lipid and Metabolic Profiles of R-CHOP-Resistant Diffuse Large B-Cell Lymphoma Elucidated by Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging and in Vivo Imaging",
abstract = "Diffuse large B-cell lymphoma (DLBCL) is the most common B-cell non-Hodgkin lymphoma. To treat this aggressive disease, R-CHOP, a combination of immunotherapy (R; rituximab) and chemotherapy (CHOP; cyclophosphamide, doxorubicin, vincristine, and prednisone), remains the most commonly used regimen for newly diagnosed DLBCLs. However, up to one-third of patients ultimately becomes refractory to initial therapy or relapses after treatment, and the high mortality rate highlights the urgent need for novel therapeutic approaches based upon selective molecular targets. In order to understand the molecular mechanisms underlying relapsed DLBCL, we studied differences in the lipid and metabolic composition of nontreated and R-CHOP-resistant tumors, using a combination of in vivo DLBCL xenograft models and mass spectrometry imaging. Together, these techniques provide information regarding analyte composition and molecular distributions of therapy-resistant and sensitive areas. We found specific lipid and metabolic profiles for R-CHOP-resistant tumors, such as a higher presence of phosphatidylinositol and sphingomyelin fragments. In addition, we investigated intratumor heterogeneity and identified specific lipid markers of viable and necrotic areas. Furthermore, we could monitor metabolic changes and found reduced adenosine triphosphate and increased adenosine monophosphate in the R-CHOP-resistant tumors. This work highlights the power of combining in vivo imaging and MSI to track molecular signatures in DLBCL, which has potential application for other diseases.",
author = "Barr{\'e}, {Florian P Y} and Claes, {Britt S R} and Fr{\'e}d{\'e}ric Dewez and Carine Peutz-Kootstra and Munch-Petersen, {Helga F} and Kirsten Gr{\o}nb{\ae}k and Lund, {Anders H} and Heeren, {Ron M A} and Christophe C{\^o}me and Berta Cillero-Pastor",
year = "2018",
month = "12",
day = "18",
doi = "10.1021/acs.analchem.8b02910",
language = "English",
volume = "90",
pages = "14198--14206",
journal = "Analytical Chemistry",
issn = "0003-2700",
publisher = "American Chemical Society",
number = "24",

}

RIS

TY - JOUR

T1 - Specific Lipid and Metabolic Profiles of R-CHOP-Resistant Diffuse Large B-Cell Lymphoma Elucidated by Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging and in Vivo Imaging

AU - Barré, Florian P Y

AU - Claes, Britt S R

AU - Dewez, Frédéric

AU - Peutz-Kootstra, Carine

AU - Munch-Petersen, Helga F

AU - Grønbæk, Kirsten

AU - Lund, Anders H

AU - Heeren, Ron M A

AU - Côme, Christophe

AU - Cillero-Pastor, Berta

PY - 2018/12/18

Y1 - 2018/12/18

N2 - Diffuse large B-cell lymphoma (DLBCL) is the most common B-cell non-Hodgkin lymphoma. To treat this aggressive disease, R-CHOP, a combination of immunotherapy (R; rituximab) and chemotherapy (CHOP; cyclophosphamide, doxorubicin, vincristine, and prednisone), remains the most commonly used regimen for newly diagnosed DLBCLs. However, up to one-third of patients ultimately becomes refractory to initial therapy or relapses after treatment, and the high mortality rate highlights the urgent need for novel therapeutic approaches based upon selective molecular targets. In order to understand the molecular mechanisms underlying relapsed DLBCL, we studied differences in the lipid and metabolic composition of nontreated and R-CHOP-resistant tumors, using a combination of in vivo DLBCL xenograft models and mass spectrometry imaging. Together, these techniques provide information regarding analyte composition and molecular distributions of therapy-resistant and sensitive areas. We found specific lipid and metabolic profiles for R-CHOP-resistant tumors, such as a higher presence of phosphatidylinositol and sphingomyelin fragments. In addition, we investigated intratumor heterogeneity and identified specific lipid markers of viable and necrotic areas. Furthermore, we could monitor metabolic changes and found reduced adenosine triphosphate and increased adenosine monophosphate in the R-CHOP-resistant tumors. This work highlights the power of combining in vivo imaging and MSI to track molecular signatures in DLBCL, which has potential application for other diseases.

AB - Diffuse large B-cell lymphoma (DLBCL) is the most common B-cell non-Hodgkin lymphoma. To treat this aggressive disease, R-CHOP, a combination of immunotherapy (R; rituximab) and chemotherapy (CHOP; cyclophosphamide, doxorubicin, vincristine, and prednisone), remains the most commonly used regimen for newly diagnosed DLBCLs. However, up to one-third of patients ultimately becomes refractory to initial therapy or relapses after treatment, and the high mortality rate highlights the urgent need for novel therapeutic approaches based upon selective molecular targets. In order to understand the molecular mechanisms underlying relapsed DLBCL, we studied differences in the lipid and metabolic composition of nontreated and R-CHOP-resistant tumors, using a combination of in vivo DLBCL xenograft models and mass spectrometry imaging. Together, these techniques provide information regarding analyte composition and molecular distributions of therapy-resistant and sensitive areas. We found specific lipid and metabolic profiles for R-CHOP-resistant tumors, such as a higher presence of phosphatidylinositol and sphingomyelin fragments. In addition, we investigated intratumor heterogeneity and identified specific lipid markers of viable and necrotic areas. Furthermore, we could monitor metabolic changes and found reduced adenosine triphosphate and increased adenosine monophosphate in the R-CHOP-resistant tumors. This work highlights the power of combining in vivo imaging and MSI to track molecular signatures in DLBCL, which has potential application for other diseases.

U2 - 10.1021/acs.analchem.8b02910

DO - 10.1021/acs.analchem.8b02910

M3 - Journal article

VL - 90

SP - 14198

EP - 14206

JO - Analytical Chemistry

JF - Analytical Chemistry

SN - 0003-2700

IS - 24

ER -

ID: 56423781