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Eva Bezak - One of the best experts on this subject based on the ideXlab platform.
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The Potential Role of Radiomics and Radiogenomics in Patient Stratification by Tumor Hypoxia Status.
Journal of the American College of Radiology, 2019Co-Authors: Loredana G. Marcu, Jake C. Forster, Eva BezakAbstract:Absract Background Despite the clinical knowledge accumulated over a century about Tumor Hypoxia, this biologic parameter remains a major challenge in cancer treatment. Patients presenting with hypoxic Tumors are more resistant to radiotherapy and often poor responders to chemotherapy. Treatment failure because of Hypoxia is, therefore, very common. Several methods have been trialed to measure and quantify Tumor Hypoxia, with varied success. Over the last couple of decades, Hypoxia-specific functional imaging has started to play an important role in personalized treatment planning and delivery. Yet, there are no gold standards in place, owing to inter- and intrapatient phenotypic variations that further complicate the overall picture. The aim of the current article is to analyze, through the review of the literature, the potential role of radiomics and radiogenomics in patient stratification by Tumor Hypoxia status. Methods Search of literature published in English since 2000 was conducted using Medline. Additional articles were retrieved via pearling of identified literature. Publications were reviewed and summarized in text and in a tabulated format. Results Although still an immature area of science, radiomics has shown its potential in the quantification of Hypoxia within the heterogeneous Tumor, quantification of changes regarding the degree of Hypoxia after radiotherapy and drug delivery, monitoring Tumor response to anti-angiogenic therapy, and assisting with patient stratification and outcome prediction based on the hypoxic status. Conclusions The lack of technique standardization to measure and quantify Tumor Hypoxia presents an opportunity for data mining and machine learning in radiogenomics.
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The Potential Role of Radiomics and Radiogenomics in Patient Stratification by Tumor Hypoxia Status.
Journal of the American College of Radiology : JACR, 2019Co-Authors: Loredana G. Marcu, Jake C. Forster, Eva BezakAbstract:Despite the clinical knowledge accumulated over a century about Tumor Hypoxia, this biologic parameter remains a major challenge in cancer treatment. Patients presenting with hypoxic Tumors are more resistant to radiotherapy and often poor responders to chemotherapy. Treatment failure because of Hypoxia is, therefore, very common. Several methods have been trialed to measure and quantify Tumor Hypoxia, with varied success. Over the last couple of decades, Hypoxia-specific functional imaging has started to play an important role in personalized treatment planning and delivery. Yet, there are no gold standards in place, owing to inter- and intrapatient phenotypic variations that further complicate the overall picture. The aim of the current article is to analyze, through the review of the literature, the potential role of radiomics and radiogenomics in patient stratification by Tumor Hypoxia status. Search of literature published in English since 2000 was conducted using Medline. Additional articles were retrieved via pearling of identified literature. Publications were reviewed and summarized in text and in a tabulated format. Although still an immature area of science, radiomics has shown its potential in the quantification of Hypoxia within the heterogeneous Tumor, quantification of changes regarding the degree of Hypoxia after radiotherapy and drug delivery, monitoring Tumor response to anti-angiogenic therapy, and assisting with patient stratification and outcome prediction based on the hypoxic status. The lack of technique standardization to measure and quantify Tumor Hypoxia presents an opportunity for data mining and machine learning in radiogenomics. Copyright © 2019 American College of Radiology. All rights reserved.
Peter Vaupel - One of the best experts on this subject based on the ideXlab platform.
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Tumor Hypoxia: Causative Mechanisms, Microregional Heterogeneities, and the Role of Tissue-Based Hypoxia Markers.
Advances in experimental medicine and biology, 2016Co-Authors: Peter Vaupel, Arnulf MayerAbstract:Tumor Hypoxia is a hallmark of solid malignant Tumor growth, profoundly influences malignant progression and contributes to the development of therapeutic resistance. Pathogenesis of Tumor Hypoxia is multifactorial, with contributions from both acute and chronic factors. Spatial distribution of Hypoxia within Tumors is markedly heterogeneous and often changes over time, e.g., during a course of radiotherapy. Substantial changes in the oxygenation status can occur within the distance of a few cell layers, explaining the inability of currently used molecular imaging techniques to adequately assess this crucial trait. Due to the possible importance of Tumor Hypoxia for clinical decision-making, there is a great demand for molecular tools which may provide the necessary resolution down to the single cell level. Exogenous and endogenous markers of Tumor Hypoxia have been investigated for this purpose. Their potential use may be greatly enhanced by multiparametric in situ methods in experimental and human Tumor tissue.
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Tumor Hypoxia and malignant progression.
Experimental oncology, 2009Co-Authors: Osinsky S, Peter VaupelAbstract:Abstract The current problems of malignant growth biology, in particular the molecular background of the specific microenvironment of Tumor cells and their interaction with stromal cells, which mediates the behavior of Tumors and the Tumor-host interrelationship were the subject of the International Conference entitled "Tumor Hypoxia and Malignant Progression", a meeting held at the House of Scientists of the NAS of Ukraine in Kyiv, Ukraine, October 1 st to 4 th , 2008. The meeting was hosted by the R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of the NAS of Ukraine (IEPOR), and was dedicated to the 90 th Anniversary of the National Academy of Sciences of Ukraine. Over the last years, scientists have focused extensively on the problem of Tumor Hypoxia as a factor promoting Tumor progression. It is known that Hypoxia, as a constituent of the Tumor cell microenvironment as well as aerobic glycolysis, are important features of malignant Tumors. The direct correlation between high levels of Hypoxia and Tumor aggressiveness has been shown in numerous studies. Therefore, Hypoxia is regarded as a factor of unfavorable prognosis. There is a number of different methods available for the evaluation of the level of Hypoxia, some of which are being applied in the clinical setting. The stimulating impact of Hypoxia and Hypoxia-associated proteins on neoangiogenesis and vasculogenesis in Tumor tissue has been demonstrated. Several studies have focused on the development of agents capable of blocking Hypoxia-associated signaling pathways and vasculogenesis in Tumor. Recently, the direct association between Hypoxia-dependent signaling pathways and expression of factors that mediate inflammation in Tumor tissue, in particular Tumor-associated macrophages has been shown. To summarize, a better understanding of the relationships between Hypoxia-associated signaling pathways, metabolic peculiarities and inflammatory factors that positively influence Tumor progression may elucidate not only how the aggressive Tumor phenotype is formed but also may assist in the development of new approaches for the treatment of cancer patients.
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Tumor Hypoxia and therapeutic resistance
Recombinant Human Erythropoietin (rhEPO) in Clinical Oncology, 2008Co-Authors: Peter Vaupel, Michael HöckelAbstract:For many years, the identification of Tumor Hypoxia, its systematic characterization and the assessment of its clinical relevance were not possible due to the lack of methods suitable for the routine measurement of intraTumoral oxygen tensions in patients. In the late 1980s, a novel and clinically applicable standardized procedure was established enabling the determination of Tumor oxygenation in accessible primary Tumors, local recurrences, and metastatic lesions in patients using a computerized polarographic needle electrode system (Vaupel et al. 1991; Hockel et al. 1991). Within a relatively short period of time, the significance of Tumor oxygenation for therapy outcome became evident in numerous experimental and clinical studies (for a review see Vaupel and Kelleher 1999).
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detection and characterization of Tumor Hypoxia using po2 histography
Antioxidants & Redox Signaling, 2007Co-Authors: Peter Vaupel, Michael Höckel, Arnulf MayerAbstract:Data from 125 studies describing the pretreatment oxygenation status as measured in the clinical setting using the computerized Eppendorf pO2 histography system have been compiled in this article. Tumor oxygenation is heterogeneous and severely compromised as compared to normal tissue. Hypoxia results from inadequate perfusion and diffusion within Tumors and from a reduced O2 transport capacity in anemic patients. The development of Tumor Hypoxia is independent of a series of relevant Tumor characteristics (e.g., clinical size, stage, histology, and grade) and various patient demographics. Overall median pO2 in cancers of the uterine cervix, head and neck, and breast is 10 mm Hg with the overall hypoxic fraction (pO2
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Tumor Hypoxia: Causative Factors, Compensatory Mechanisms, and Cellular Response
The Oncologist, 2004Co-Authors: Peter Vaupel, Louis B. HarrisonAbstract:Hypoxia is a characteristic feature of locally advanced solid Tumors resulting from an imbalance between oxygen (O2) supply and consumption. Major causative factors of Tumor Hypoxia are abnormal structure and function of the microvessels supplying the Tumor, increased diffusion distances between the nutritive blood vessels and the Tumor cells, and reduced O2 transport capacity of the blood due to the presence of disease- or treatment-related anemia. Tumor Hypoxia is a therapeutic concern since it can reduce the effectiveness of radiotherapy, some O2-dependent cytotoxic agents, and photodynamic therapy. Tumor Hypoxia can also negatively impact therapeutic outcome by inducing changes in the proteome and genome of neoplastic cells that further survival and malignant progression by enabling the cells to overcome nutritive deprivation or to escape their hostile environment. The selection and clonal expansion of these favorably altered cells further aggravate Tumor Hypoxia and support a vicious circle of increasing Hypoxia and malignant progression while concurrently promoting the development of more treatmentresistant disease. This pattern of malignant progression, coupled with the demonstration of a relationship between falling hemoglobin level and worsening Tumor oxygenation, highlights the need for effective treatment of anemia as one approach for correcting anemic Hypoxia in Tumors, and in so doing, possibly improving therapeutic response. The Oncologist 2004;9(suppl 5):4-9
Xiaoyuan Chen - One of the best experts on this subject based on the ideXlab platform.
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Monitoring Tumor Hypoxia Using (18)F-FMISO PET and Pharmacokinetics Modeling after Photodynamic Therapy.
Scientific reports, 2016Co-Authors: Xiao Tong, Gang Niu, Avinash Srivatsan, Orit Jacobson, Yu Wang, Zhantong Wang, Xiangyu Yang, Dale O. Kiesewetter, Hairong Zheng, Xiaoyuan ChenAbstract:Photodynamic therapy (PDT) is an efficacious treatment for some types of cancers. However, PDT-induced Tumor Hypoxia as a result of oxygen consumption and vascular damage can reduce the efficacy of this therapy. Measuring and monitoring intrinsic and PDT-induced Tumor Hypoxia in vivo during PDT is of high interest for prognostic and treatment evaluation. In the present study, static and dynamic 18F-FMISO PET were performed with mice bearing either U87MG or MDA-MB-435 Tumor xenografts immediately before and after PDT at different time points. Significant difference in Tumor Hypoxia in response to PDT over time was found between the U87MG and MDA-MB-435 Tumors in both static and dynamic PET. Dynamic PET with pharmacokinetics modeling further monitored the kinetics of 18F-FMISO retention to hypoxic sites after treatment. The Ki and k3 parametric analysis provided information on Tumor Hypoxia by distinction of the specific tracer retention in hypoxic sites from its non-specific distribution in Tumor. Dynamic 18F-FMISO PET with pharmacokinetics modeling, complementary to static PET analysis, provides a potential imaging tool for more detailed and more accurate quantification of Tumor Hypoxia during PDT.
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Monitoring Tumor Hypoxia using [18F]-FMISO PET and Pharmacokinetics Modeling after Photodynamic Therapy
The Journal of Nuclear Medicine, 2016Co-Authors: Xiao Tong, Gang Niu, Avinash Srivatsan, Orit Jacobson, Yu Wang, Zhantong Wang, Xiangyu Yang, Dale O. Kiesewetter, Hairong Zheng, Xiaoyuan ChenAbstract:368 Objectives Photodynamic therapy (PDT) is an efficacious treatment for some types of cancers. Irradiation of intraTumoral photosensitizers leads to the conversion of tissue oxygen into singlet oxygen with subsequent generation of cytotoxic compounds. PDT-induced Tumor Hypoxia as a result of oxygen consumption and vascular damage can limit the efficacy of this therapy. Measuring and monitoring intrinsic and PDT-induced Tumor Hypoxia in vivo during PDT is of high interest for prognostic and treatment evaluation. Methods Static and dynamic 18F-FMISO PET were performed sequentially with mice bearing either U87MG or MDA-MB-435 Tumor xenografts immediately before and after PDT at different time points. The 18F-FMISO Tumor uptake was first calculated based on the static PET data. The 18F-FMISO transportation rate between plasma, diffusive and trapping compartments (K1, k2, k3) and the influx rate (Ki) were derived from dynamic PET using irreversible two-tissue compartmental modeling. The parametric mapping of k3 and Ki was further performed to assess heterogeneity of the Tumor Hypoxia. The above analyses were conducted for both Tumor types at different time points; the variation of different parameters over time was compared between the two Tumor types. Results A significant difference (P Conclusions With its ability to monitor the change of Tumor Hypoxia following PDT on voxels basis, pharmacokinetic modeling with parametric mapping of 18F-FMISO PET allowed quantitative identification of the hypoxic sub-volume of a Tumor in vivo. This technique provides a potentially improved imaging tool, relative to static images, to map and monitor Tumor Hypoxia in PDT and other anti-cancer therapies.
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Tumor Hypoxia Imaging
Molecular imaging and biology, 2010Co-Authors: Xilin Sun, Gang Niu, Nicholas K Chan, Baozhong Shen, Xiaoyuan ChenAbstract:There is a need to measure Tumor Hypoxia in assessing the aggressiveness of Tumor and predicting the outcome of therapy. A number of invasive and noninvasive techniques have been exploited to measure Tumor Hypoxia, including polarographic needle electrodes, immunohistochemical staining, radionuclide imaging (positron emission tomography [PET] and single-photon emission computed tomography [SPECT]), magnetic resonance imaging (MRI), optical imaging (bioluminescence and fluorescence), and so on. This review article summarizes and discusses the pros and cons of each currently available method for measuring tissue oxygenation. Special emphasis was placed on noninvasive imaging Hypoxia with emerging new agents and new imaging technologies to detect the molecular events that are relevant to Tumor Hypoxia.
Martin Pruschy - One of the best experts on this subject based on the ideXlab platform.
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Dynamics of Tumor Hypoxia in Response to Patupilone and Ionizing Radiation
PloS one, 2012Co-Authors: Katrin Orlowski, Carla Rohrer Bley, Martina Zimmermann, Van Vuong, Daniel Hug, Alex Soltermann, Angela Broggini-tenzer, Martin PruschyAbstract:Tumor Hypoxia is one of the most important parameters that determines treatment sensitivity and is mainly due to insufficient Tumor angiogenesis. However, the local oxygen concentration in a Tumor can also be shifted in response to different treatment modalities such as cytotoxic agents or ionizing radiation. Thus, combined treatment modalities including microtubule stabilizing agents could create an additional challenge for an effective treatment response due to treatment-induced shifts in Tumor oxygenation. Tumor Hypoxia was probed over a prolonged observation period in response to treatment with different cytotoxic agents, using a non-invasive bioluminescent ODD-Luc reporter system, in which part of the oxygen-dependent degradation (ODD) domain of HIF-1α is fused to luciferase. As demonstrated in vitro, this system not only detects Hypoxia at an ambient oxygen concentration of 1% O2, but also discriminates low oxygen concentrations in the range from 0.2 to 1% O2. Treatment of A549 lung adenocarcinoma-derived Tumor xenografts with the microtubule stabilizing agent patupilone resulted in a prolonged increase in Tumor Hypoxia, which could be used as marker for its antiTumoral treatment response, while irradiation did not induce detectable changes in Tumor Hypoxia. Furthermore, despite patupilone-induced Hypoxia, the potency of ionizing radiation (IR) was not reduced as part of a concomitant or adjuvant combined treatment modality.
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Ionizing radiation antagonizes Tumor Hypoxia induced by antiangiogenic treatment.
Clinical Cancer Research, 2006Co-Authors: Oliver Riesterer, Michael Honer, Wolfram Jochum, Christoph Oehler, Simon M. Ametamey, Martin PruschyAbstract:Purpose: The combined treatment modality of ionizing radiation with inhibitors of angiogenesis is effective despite the supposition that inhibition of angiogenesis might increase Tumor Hypoxia and thereby negatively affect radiation sensitivity. To directly assess this still controversial issue, we analyzed treatment-dependent alterations of Tumor oxygenation in response to inhibition of angiogenesis alone, ionizing radiation, and combined treatment. Experimental Design: Serial measurements with high-resolution [ 18 F]fluoromisonidazole positron emission tomography and immunohistochemical detection of the endogenous Hypoxia marker glucose transporter-1 were done to determine Tumor Hypoxia in a murine mammary carcinoma allograft model. Results: Inhibition of angiogenesis with the clinically relevant vascular endothelial growth factor receptor tyrosine kinase inhibitor PTK787/ZK222584 reduced microvessel density but had only minimal effects on Tumor growth, Tumor cell apoptosis, and proliferation. However, PTK787/ZK222584 treatment increased overall and local Tumor Hypoxia as revealed by extended expression of the Hypoxia marker glucose transporter-1 and increased uptake of [ 18 F]fluoromisonidazole. Fractionated irradiation induced a strong growth delay, which was associated with enhanced apoptosis and reduced proliferation of Tumor cells but only minor effects on microvessel density and allograft oxygenation. Combined treatment with fractionated irradiation resulted in extended Tumor growth delay and Tumor cell apoptosis but no increase in Tumor Hypoxia. Conclusions: These results show that irradiation antagonizes the increase of Hypoxia by vascular endothelial growth factor receptor tyrosine kinase inhibition and abrogates the potential negative effect on Tumor Hypoxia. Thus, the risk of treatment-induced Hypoxia by inhibitors of angiogenesis exists but is kept minimal when combined with a cytotoxic treatment modality.
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Ionizing radiation antagonizes Tumor Hypoxia induced by antiangiogenic treatment.
Clinical cancer research : an official journal of the American Association for Cancer Research, 2006Co-Authors: Oliver Riesterer, Michael Honer, Wolfram Jochum, Christoph Oehler, Simon M. Ametamey, Martin PruschyAbstract:The combined treatment modality of ionizing radiation with inhibitors of angiogenesis is effective despite the supposition that inhibition of angiogenesis might increase Tumor Hypoxia and thereby negatively affect radiation sensitivity. To directly assess this still controversial issue, we analyzed treatment-dependent alterations of Tumor oxygenation in response to inhibition of angiogenesis alone, ionizing radiation, and combined treatment. Serial measurements with high-resolution [18F]fluoromisonidazole positron emission tomography and immunohistochemical detection of the endogenous Hypoxia marker glucose transporter-1 were done to determine Tumor Hypoxia in a murine mammary carcinoma allograft model. Inhibition of angiogenesis with the clinically relevant vascular endothelial growth factor receptor tyrosine kinase inhibitor PTK787/ZK222584 reduced microvessel density but had only minimal effects on Tumor growth, Tumor cell apoptosis, and proliferation. However, PTK787/ZK222584 treatment increased overall and local Tumor Hypoxia as revealed by extended expression of the Hypoxia marker glucose transporter-1 and increased uptake of [18F]fluoromisonidazole. Fractionated irradiation induced a strong growth delay, which was associated with enhanced apoptosis and reduced proliferation of Tumor cells but only minor effects on microvessel density and allograft oxygenation. Combined treatment with fractionated irradiation resulted in extended Tumor growth delay and Tumor cell apoptosis but no increase in Tumor Hypoxia. These results show that irradiation antagonizes the increase of Hypoxia by vascular endothelial growth factor receptor tyrosine kinase inhibition and abrogates the potential negative effect on Tumor Hypoxia. Thus, the risk of treatment-induced Hypoxia by inhibitors of angiogenesis exists but is kept minimal when combined with a cytotoxic treatment modality.
Loredana G. Marcu - One of the best experts on this subject based on the ideXlab platform.
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The Potential Role of Radiomics and Radiogenomics in Patient Stratification by Tumor Hypoxia Status.
Journal of the American College of Radiology, 2019Co-Authors: Loredana G. Marcu, Jake C. Forster, Eva BezakAbstract:Absract Background Despite the clinical knowledge accumulated over a century about Tumor Hypoxia, this biologic parameter remains a major challenge in cancer treatment. Patients presenting with hypoxic Tumors are more resistant to radiotherapy and often poor responders to chemotherapy. Treatment failure because of Hypoxia is, therefore, very common. Several methods have been trialed to measure and quantify Tumor Hypoxia, with varied success. Over the last couple of decades, Hypoxia-specific functional imaging has started to play an important role in personalized treatment planning and delivery. Yet, there are no gold standards in place, owing to inter- and intrapatient phenotypic variations that further complicate the overall picture. The aim of the current article is to analyze, through the review of the literature, the potential role of radiomics and radiogenomics in patient stratification by Tumor Hypoxia status. Methods Search of literature published in English since 2000 was conducted using Medline. Additional articles were retrieved via pearling of identified literature. Publications were reviewed and summarized in text and in a tabulated format. Results Although still an immature area of science, radiomics has shown its potential in the quantification of Hypoxia within the heterogeneous Tumor, quantification of changes regarding the degree of Hypoxia after radiotherapy and drug delivery, monitoring Tumor response to anti-angiogenic therapy, and assisting with patient stratification and outcome prediction based on the hypoxic status. Conclusions The lack of technique standardization to measure and quantify Tumor Hypoxia presents an opportunity for data mining and machine learning in radiogenomics.
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The Potential Role of Radiomics and Radiogenomics in Patient Stratification by Tumor Hypoxia Status.
Journal of the American College of Radiology : JACR, 2019Co-Authors: Loredana G. Marcu, Jake C. Forster, Eva BezakAbstract:Despite the clinical knowledge accumulated over a century about Tumor Hypoxia, this biologic parameter remains a major challenge in cancer treatment. Patients presenting with hypoxic Tumors are more resistant to radiotherapy and often poor responders to chemotherapy. Treatment failure because of Hypoxia is, therefore, very common. Several methods have been trialed to measure and quantify Tumor Hypoxia, with varied success. Over the last couple of decades, Hypoxia-specific functional imaging has started to play an important role in personalized treatment planning and delivery. Yet, there are no gold standards in place, owing to inter- and intrapatient phenotypic variations that further complicate the overall picture. The aim of the current article is to analyze, through the review of the literature, the potential role of radiomics and radiogenomics in patient stratification by Tumor Hypoxia status. Search of literature published in English since 2000 was conducted using Medline. Additional articles were retrieved via pearling of identified literature. Publications were reviewed and summarized in text and in a tabulated format. Although still an immature area of science, radiomics has shown its potential in the quantification of Hypoxia within the heterogeneous Tumor, quantification of changes regarding the degree of Hypoxia after radiotherapy and drug delivery, monitoring Tumor response to anti-angiogenic therapy, and assisting with patient stratification and outcome prediction based on the hypoxic status. The lack of technique standardization to measure and quantify Tumor Hypoxia presents an opportunity for data mining and machine learning in radiogenomics. Copyright © 2019 American College of Radiology. All rights reserved.
