Apoptosis plays a crucial role in the normal development, homeostasis of multicellular organisms,... more Apoptosis plays a crucial role in the normal development, homeostasis of multicellular organisms, carcinogenic process, and response of cancer cells to anticancer drugs. It is a genetically strictly regulated process, controlled by the balance between pro- and antiapoptotic proteins. Resistance to standard chemotherapeutics also seems to be an apoptosis-related process due to failure to activate the apoptotic machinery. Hence, the molecular pathways (extrinsic and intrinsic) regulating the apoptotic process are attractive targets for potential therapeutic intervention. The goal of proapoptotic drugs is to selectively induce apoptosis in the tumor cell while leaving healthy cells unharmed. Several proapoptotic receptor agonists have recently been developed, activating selectively the extrinsic pathway, and give promising results. Targets for the intrinsic pathway include the Bcl-2 family proteins, the inhibitor of apoptosis proteins, the p53 pathway, and many others. However, several...
The aim of this study was to assess the expression pattern and prognostic value of the high affin... more The aim of this study was to assess the expression pattern and prognostic value of the high affinity glucose transporters GLUT-1, 3, 4, 8 and 9, SGLT-1 and of hexokinases (HK) I, II and III in squamous cell carcinoma of the tonsil and mobile tongue (TTSCC) by means of immunohistochemistry. Seventy-one consecutive patients suffering from TTSCC were included. The intensity and amount of positive tumour cells in the immunoreaction (histology score (H-score)) for GLUT-1, 3, 4, 8 and 9 as well as for HK-I, II and III were assessed independently by two experienced observers, blinded to the clinical results. H-scores as well as clinical variables were related to patient outcome. Median follow-up time was 49 months (range 1-123 months). Mean H-scores for GLUT expression in decreasing order of magnitude were respectively 10.99 for GLUT-1 (sd 3.9), 5.7 for GLUT-8 (sd 4.0), 5.4 for GLUT-3 (sd 3.7), 1.0 for GLUT-4 (sd 2.0), 1.1 (sd 1.3) for SGLT-1, and 0.4 for GLUT-9 (sd 0.6); GLUT-1 > GLUT-...
European Journal of Nuclear Medicine and Molecular Imaging, 2009
Tissue hypoxia results from an inadequate supply of oxygen (O2) that compromises biological funct... more Tissue hypoxia results from an inadequate supply of oxygen (O2) that compromises biological functions. Structural and functional abnormalities of the tumour vasculature together with altered diffusion conditions inside the tumour seem to be the main causes of tumour hypoxia. Evidence from experimental and clinical studies points to a role for tumour hypoxia in tumour propagation, resistance to therapy and malignant
Apoptosis plays a crucial role in the normal development, homeostasis of multicellular organisms,... more Apoptosis plays a crucial role in the normal development, homeostasis of multicellular organisms, carcinogenic process, and response of cancer cells to anticancer drugs. It is a genetically strictly regulated process, controlled by the balance between pro- and antiapoptotic proteins. Resistance to standard chemotherapeutics also seems to be an apoptosis-related process due to failure to activate the apoptotic machinery. Hence, the molecular pathways (extrinsic and intrinsic) regulating the apoptotic process are attractive targets for potential therapeutic intervention. The goal of proapoptotic drugs is to selectively induce apoptosis in the tumor cell while leaving healthy cells unharmed. Several proapoptotic receptor agonists have recently been developed, activating selectively the extrinsic pathway, and give promising results. Targets for the intrinsic pathway include the Bcl-2 family proteins, the inhibitor of apoptosis proteins, the p53 pathway, and many others. However, several studies have implicated that using monotherapy will probably not be sufficient to sensitize or induce apoptosis in all tumor cells. Most promising results, in terms of killing the tumor cell, will be achieved by the combination of various therapeutic strategies. In this review, promising apoptosis-inducing anticancer therapies are summarized.
In this review, data on noninvasive imaging of apoptosis in oncology are reviewed. Imaging data a... more In this review, data on noninvasive imaging of apoptosis in oncology are reviewed. Imaging data available are presented in order of occurrence in time of enzymatic and morphologic events occurring during apoptosis. Available studies suggest that various radiopharmaceutical probes bear great potential for apoptosis imaging by means of positron emission tomography and single-photon emission computed tomography (SPECT). However, for several of these probes, thorough toxicologic studies are required before they can be applied in clinical studies. Both preclinical and clinical studies support the notion that 99mTc-hydrazinonicotinamide-annexin A5 and SPECT allow for noninvasive, repetitive, quantitative apoptosis imaging and for assessing tumor response as early as 24 hours following treatment instigation. Bioluminescence imaging and near-infrared fluorescence imaging have shown great potential in small-animal imaging, but their usefulness for in vivo imaging in humans is limited to stru...
Apoptosis plays a crucial role in the normal development, homeostasis of multicellular organisms,... more Apoptosis plays a crucial role in the normal development, homeostasis of multicellular organisms, carcinogenic process, and response of cancer cells to anticancer drugs. It is a genetically strictly regulated process, controlled by the balance between pro- and antiapoptotic proteins. Resistance to standard chemotherapeutics also seems to be an apoptosis-related process due to failure to activate the apoptotic machinery. Hence, the molecular pathways (extrinsic and intrinsic) regulating the apoptotic process are attractive targets for potential therapeutic intervention. The goal of proapoptotic drugs is to selectively induce apoptosis in the tumor cell while leaving healthy cells unharmed. Several proapoptotic receptor agonists have recently been developed, activating selectively the extrinsic pathway, and give promising results. Targets for the intrinsic pathway include the Bcl-2 family proteins, the inhibitor of apoptosis proteins, the p53 pathway, and many others. However, several...
The aim of this study was to assess the expression pattern and prognostic value of the high affin... more The aim of this study was to assess the expression pattern and prognostic value of the high affinity glucose transporters GLUT-1, 3, 4, 8 and 9, SGLT-1 and of hexokinases (HK) I, II and III in squamous cell carcinoma of the tonsil and mobile tongue (TTSCC) by means of immunohistochemistry. Seventy-one consecutive patients suffering from TTSCC were included. The intensity and amount of positive tumour cells in the immunoreaction (histology score (H-score)) for GLUT-1, 3, 4, 8 and 9 as well as for HK-I, II and III were assessed independently by two experienced observers, blinded to the clinical results. H-scores as well as clinical variables were related to patient outcome. Median follow-up time was 49 months (range 1-123 months). Mean H-scores for GLUT expression in decreasing order of magnitude were respectively 10.99 for GLUT-1 (sd 3.9), 5.7 for GLUT-8 (sd 4.0), 5.4 for GLUT-3 (sd 3.7), 1.0 for GLUT-4 (sd 2.0), 1.1 (sd 1.3) for SGLT-1, and 0.4 for GLUT-9 (sd 0.6); GLUT-1 > GLUT-...
European Journal of Nuclear Medicine and Molecular Imaging, 2009
Tissue hypoxia results from an inadequate supply of oxygen (O2) that compromises biological funct... more Tissue hypoxia results from an inadequate supply of oxygen (O2) that compromises biological functions. Structural and functional abnormalities of the tumour vasculature together with altered diffusion conditions inside the tumour seem to be the main causes of tumour hypoxia. Evidence from experimental and clinical studies points to a role for tumour hypoxia in tumour propagation, resistance to therapy and malignant
Apoptosis plays a crucial role in the normal development, homeostasis of multicellular organisms,... more Apoptosis plays a crucial role in the normal development, homeostasis of multicellular organisms, carcinogenic process, and response of cancer cells to anticancer drugs. It is a genetically strictly regulated process, controlled by the balance between pro- and antiapoptotic proteins. Resistance to standard chemotherapeutics also seems to be an apoptosis-related process due to failure to activate the apoptotic machinery. Hence, the molecular pathways (extrinsic and intrinsic) regulating the apoptotic process are attractive targets for potential therapeutic intervention. The goal of proapoptotic drugs is to selectively induce apoptosis in the tumor cell while leaving healthy cells unharmed. Several proapoptotic receptor agonists have recently been developed, activating selectively the extrinsic pathway, and give promising results. Targets for the intrinsic pathway include the Bcl-2 family proteins, the inhibitor of apoptosis proteins, the p53 pathway, and many others. However, several studies have implicated that using monotherapy will probably not be sufficient to sensitize or induce apoptosis in all tumor cells. Most promising results, in terms of killing the tumor cell, will be achieved by the combination of various therapeutic strategies. In this review, promising apoptosis-inducing anticancer therapies are summarized.
In this review, data on noninvasive imaging of apoptosis in oncology are reviewed. Imaging data a... more In this review, data on noninvasive imaging of apoptosis in oncology are reviewed. Imaging data available are presented in order of occurrence in time of enzymatic and morphologic events occurring during apoptosis. Available studies suggest that various radiopharmaceutical probes bear great potential for apoptosis imaging by means of positron emission tomography and single-photon emission computed tomography (SPECT). However, for several of these probes, thorough toxicologic studies are required before they can be applied in clinical studies. Both preclinical and clinical studies support the notion that 99mTc-hydrazinonicotinamide-annexin A5 and SPECT allow for noninvasive, repetitive, quantitative apoptosis imaging and for assessing tumor response as early as 24 hours following treatment instigation. Bioluminescence imaging and near-infrared fluorescence imaging have shown great potential in small-animal imaging, but their usefulness for in vivo imaging in humans is limited to stru...
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Papers by Christel Vangestel