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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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  3. Multidimensional LC-MS/MS enables simultaneous quantification of intact human insulin and five recombinant analogs in human plasma

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  4. Electrochemical reduction of disulfide-containing proteins for hydrogen/deuterium exchange monitored by mass spectrometry

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  5. Metabolic phenotype of the healthy rodent model using in-vial extraction of dried serum, urine, and cerebrospinal fluid spots

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  1. Epigenetic therapy in hematological cancers

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  2. Mother-child transmission of epigenetic information by tunable polymorphic imprinting

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  3. Enzyme-free digital counting of endogenous circular RNA molecules in B-cell malignancies

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  4. Epidemiology of chronic red-cell transfusion recipients in Sweden and Denmark-a 10 year follow-up study

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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.

Original languageEnglish
JournalAnalytical Chemistry
Volume90
Issue number24
Pages (from-to)14198-14206
Number of pages9
ISSN0003-2700
DOIs
Publication statusPublished - 18 Dec 2018

ID: 56423781