The value of PET, CT and in-line PET/CT in patients with gastrointestinal stromal tumours: long-term outcome of treatment with imatinib mesylate

Goerres, Gerhard W.; Stupp, Roger; Barghouth, Ghassan; Hany, Thomas F.; Paulweber, Bernhard; Dizendorf, Elena; Schnyder, P.; Lüthi, François; Schulthess, Gustav K. von; Leyvraz, Serge

doi:10.1007/s00259-004-1633-7

Cited by 206 publications

(126 citation statements)

References 19 publications

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“…The active utilization of glucose by tumor cells constitutes the basis for 18 FDG-PET imaging for cancer diagnosis, and positive FDG-PET signals in the tumor sites after treatment predict poor prognosis. [21][22][23][24] Because CSCs are resistant to conventional chemotherapeutic agents, it is possible that the tumor cells in the residual lesions after chemotherapy might represent CSCs with elevated glycolytic activity. This prompted us to compare glucose metabolic activity in SP and non-SP cells.…”

Section: Resultsmentioning

confidence: 99%

Metabolic regulation of cancer cell side population by glucose through activation of the Akt pathway

et al. 2013

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Side population (SP) cells within tumors are a small fraction of cancer cells with stem-like properties that can be identified by flow cytometry analysis based on their high ability to export certain compounds such as Hoechst 33342 and chemotherapeutic agents. The existence of stem-like SP cells in tumors is considered as a key factor contributing to drug resistance, and presents a major challenge in cancer treatment. Although it has been recognized for some time that tumor tissue niches may significantly affect cancer stem cells (CSCs), the role of key nutrients such as glucose in the microenvironment in affecting stem-like cancer cells and their metabolism largely remains elusive. Here we report that SP cells isolated from human cancer cells exhibit higher glycolytic activity compared to non-SP cells. Glucose in the culture environment exerts a profound effect on SP cells as evidenced by its ability to induce a significant increase in the percentage of SP cells in the overall cancer cell population, and glucose starvation causes a rapid depletion of SP cells. Mechanistically, glucose upregulates the SP fraction through ATP-mediated suppression of AMPK and activation of the Akt pathway, leading to elevated expression of the ATP-dependent efflux pump ABCG2. Importantly, inhibition of glycolysis by 3-BrOP significantly reduces SP cells in vitro and impairs their ability to form tumors in vivo. Our data suggest that glucose is an essential regulator of SP cells mediated by the Akt pathway, and targeting glycolysis may eliminate the drug-resistant SP cells with potentially significant benefits in cancer treatment. Accumulating evidence suggests that tumors of various tissue origins, including the brain, breast, and lung, contain a small subpopulation of special cells with stem-like properties, often referred to as cancer stem cells (CSCs) or tumor-initiating cells. [1][2][3][4][5][6][7] In addition to the ability of CSCs to self-renew and initiate tumor formation, one important biochemical feature of CSCs is their ability to export certain toxic compounds and resistance to many chemotherapeutic agents due in part to their high expression of ATP-dependent efflux pump ABCG2, their increased DNA repair capacity, and activation of survival pathways. [8][9][10] The increase in expression of ABCG2 also confers CSCs the ability to effectively export the DNA-binding dye Hoechst 33342 out of the cells, leading to a low retention of the fluorescent signal in these cells, which appear at the low-left corner in flow cytometry analysis and thus are known as 'side population' or SP cells. 2,11 As SP cells can be readily identified by flow cytometry in a quantitative manner, the measurement of SP cells has been widely used as a quantitative assay for the relative number (%) of stem-like cancer cells in the bulk of the overall cancer cell population. Importantly, as this assay is functionally based on the ability of SP cells to export Hoechst 33342 and certain toxic compounds, it is also a quantitative analysis of the subpopulatio...

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Section: Resultsmentioning

confidence: 99%

Metabolic regulation of cancer cell side population by glucose through activation of the Akt pathway

et al. 2013

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“…Positron emission tomography (PET) using [ 18 (4,5), high-grade soft tissue sarcomas (3), metastatic breast cancer (6), lung cancer (7), and adenocarcinoma of the esophagogastric junction (8).…”

mentioning

confidence: 99%

Noninvasive prediction of tumor responses to gemcitabine using positron emission tomography

Laing

Walter²,

Campbell³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Gemcitabine (2 ,2 -difluorodeoxycytidine, dFdC) and cytosine arabinoside (cytarabine, ara-C) represent a class of nucleoside analogs used in cancer chemotherapy. Administered as prodrugs, dFdC and ara-C are transported across cell membranes and are converted to cytotoxic derivatives through consecutive phosphorylation steps catalyzed by endogenous nucleoside kinases. Deoxycytidine kinase (DCK) controls the rate-limiting step in the activation cascade of dFdC and ara-C. DCK activity varies significantly among individuals and across different tumor types and is a critical determinant of tumor responses to these prodrugs. Current assays to measure DCK expression and activity require biopsy samples and are prone to sampling errors. Noninvasive methods that can detect DCK activity in tumor lesions throughout the body could circumvent these limitations. Here, we demonstrate an approach to detecting DCK activity in vivo by using positron emission tomography (PET) and 18

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“…Recently, FDG-PET has been shown to be highly sensitive in detecting early responses in patients with GISTs; it has also been shown to be useful in the prediction of long-term responses to imatinib mesylate (1)(2)(3)(4)(5)(6)8). However, FDG-PET has been rarely used to report liver metastases in gastric adenocarcinoma.…”

Section: Hepatic Metastases Of Gastric Adenocarcinoma Showing Metabolmentioning

confidence: 99%

Hepatic Metastases of Gastric Adenocarcinoma Showing Metabolic Remission on FDG-PET Despite an Increase in Size on CT

et al. 2009

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The value of PET, CT and in-line PET/CT in patients with gastrointestinal stromal tumours: long-term outcome of treatment with imatinib mesylate

Cited by 206 publications

References 19 publications

Metabolic regulation of cancer cell side population by glucose through activation of the Akt pathway

Metabolic regulation of cancer cell side population by glucose through activation of the Akt pathway

Noninvasive prediction of tumor responses to gemcitabine using positron emission tomography

Hepatic Metastases of Gastric Adenocarcinoma Showing Metabolic Remission on FDG-PET Despite an Increase in Size on CT

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